Physiology Learning Objectives PDF

✏️ Learning Objectives Created @December 14, 2024 12:06 AM Class Physiology Type Notes L15 learning objectives L16 learning objectives L17 learning objectives L18 learning...

✏️ Learning Objectives Created @December 14, 2024 12:06 AM Class Physiology Type Notes L15 learning objectives L16 learning objectives L17 learning objectives L18 learning objectives L19 learning objectives L20 learning objectives L21 learning objectives L22 learning objectives L15 learning objectives Explain how the ribs and diaphragm thoracic generates the negative pressure required for inhalation During inhalation, the diaphragm contracts and flattens, and the ribs move upward and outward. This increases thoracic volume, decreasing intrathoracic pressure and causing air to flow into the lungs (negative pressure). intercoastal muscles - moves the ribs up and out outercoastal muscles - moves ribs down and in Learning Objectives 1  Characterize the impact of anatomical dead space on alveolar ventilation Dead space refers to areas in the respiratory system where gas exchange doesn’t occur (e.g., trachea, bronchi). It reduces the efficiency of ventilation, as not all inspired air reaches the alveoli for gas exchange. Learning Objectives 2  Calculate the impact of varying the rate and depth of breathing on alveolar ventilation Increased depth (tidal volume) or rate (respiratory rate) of breathing improves alveolar ventilation, while shallow or rapid breathing leads to less effective ventilation. pulmonary is total amount of air coming in alveoli is the total amount of fresh air Patient A is breathing 12 breaths/min with a tidal volume (VT) of 500 mL. Patient B is breathing 20 breaths/min with V, of 300 mL. If both patients have anatomical dead space of 200 mL, who has better alveolar ventilation? Patient A A (500 - 200) x 12 B (300 - 200) x 20 Describe how several common pulmonary pathologies cause hypoxia Learning Objectives 3  Describe the mechanisms by which blood transports CO2 and O2 Explain how cooperative binding determines the shape of the oxygen dissociation curve Learning Objectives 4  Hemoglobin: The binding of O2 to one hemoglobin subunit increases the affinity of the other subunits for O2, leading to a sigmoidal-shaped oxygen dissociation curve. each hemoglobin has 4 chains The curve is flat at low pO₂ (hemoglobin is reluctant to bind O₂), steepens at intermediate pO₂ (affinity increases), and flattens again at high pO₂ (hemoglobin becomes saturated). Draw graphs (with accurate units and numbers along the axes) illustrating how the oxygen dissociation curve is altered by fetal development, pH, CO2, temperature and 2,3-DPG levels in RBCs oxyhemoglobin saturation chart more oxygen, more hemoglobin saturation low curve - more receptive after the first subunits bind high curve - starts to level off at 100% saturation because run out of binding sites maternal and fetal hemoglobin chart fetal hemoglobin has a high affinity fetal hemoglobin would pull oxygen from the maternal hemoglobin Learning Objectives 5  How and why do these curves differ? myoglobin has a higher affinity myoglobin has one binding site so no cooperative binding hemoglobin has 4 sites and cooperative binding (O binds to one then becomes more receptive) Changes in blood pH can cause a “Bohr Shift” in the O2 dissociation curve for hemoglobin The Bohr shift describes how increased CO₂ and decreased Learning Objectives 6  pH (more acidic conditions) reduce hemoglobin's affinity for oxygen, facilitating oxygen release in tissues that need it. It is an essential mechanism that enhances oxygen delivery to metabolically active tissues. What causes changes in blood pH? if we have extra CO2 waste → get extra protons → more acidic blood lactic acid buildup → running hard → anaerobic What is the functional significance of the difference between these curves? more basic → more binding between oxygen and hemoglobin more acidic → oxygen unbinds from oxygen and goes into tissues in the skeletal muscles and tissues Learning Objectives 7  gets more acidic there when exercising Changes in blood temperature can shift the O2 dissociation curve for hemoglobin Change in temperature is caused mainly by exercise, which increases metabolic heat production in active tissues like muscles. The functional significance of the rightward shift in the oxygen dissociation curve at higher temperatures is that it enhances oxygen release to tissues, particularly during exercise when tissues (like muscles) need more oxygen. Temperature changes in the blood occur in active tissues during exercise, and this facilitates efficient oxygen delivery to metabolically demanding areas of the body. Learning Objectives 8  Changes in 2,3 diphospho- glycerate (2,3-DPG) can shift the O2 dissociationcurve for hemoglobin 2,3-DPG decreases hemoglobin’s affinity for oxygen, which helps release oxygen more readily to tissues. When 2,3-DPG levels are high, it shifts the oxygen dissociation curve to the right, meaning more oxygen is releasedat a given partial pressure of oxygen. This mechanism is particularly important in hypoxic conditions (e.g., high altitudes, anemia, lung disease) where oxygen delivery to tissues is vital, and it allows the body to adapt to low oxygen environments. Explain how the brainstem coordinates output to the somatic motor neurons for breathing Central and peripheral chemoreceptors monitor blood gasses and pH Control networks in the brainstem regulate activity in somatic motor neurons, leading to respiratory muscles Learning Objectives 9  Describe how the upper respiratory system conditions/clean inhaled air The nose, pharynx, and sinuses warm, humidify, and filter incoming air to prevent damage to the lungs. L16 learning objectives List the sources of glucose and fatty acids for a muscle during exercise Learning Objectives 10  glucose can used for aerobic and anaerobic reactions fatty acids have to be for aerobic metabolism, not anaerobic conditions What is the main source of ATP during the 100-meter dash? a. carbohydrates b. fats c. phosphocreatine d. muscle ATP e. C and D Short, intense activities - During activities like throwing, jumping, or sprinting, ATP comes from the breakdown of phosphocreatine (PCr) and glycogen to lactate. This is known as the phosphagen system. Longer activities - For activities lasting 15 seconds to three minutes, the primary energy system is glycolysis, which uses glucose stored in muscles to form ATP. Sustained activities - For activities lasting more than six seconds, anaerobic glycolysis becomes the dominant source of ATP. Explain oxygen deficit and excess postexercise oxygen consumption (EPOC) Oxygen supply to exercising cells lags behind energy use, creating an oxygen deficit Excess postexercise oxygen consumption compensates for the oxygen deficits feed forward response - breath faster when exercising before you actually run low on oxygen Why isn’t oxygen demand met at the start of exercise? When exercise begins, oxygen demand isn't immediately met because the body's physiological systems, like the heart and lungs, take time to ramp up and deliver oxygen to the working muscles quickly enough, resulting in an "oxygen deficit" where the muscles Learning Objectives 11  initially rely on anaerobic energy production to meet the sudden demand for energy at the start of exercise At the start of an exercise bout, however, some of the energy must be supplied through anaerobic mechanisms because the aerobic system responds slowly to the initial increase in the demand for energy At the start of exercise ATP comes from metabolism and phosphocreatine Explain how exercise impacts the hemoglobin oxygen saturation curve Exercise causes a rightward shift in the oxygen dissociation curve, promoting oxygen release to tissues due to increased CO2, H+, and temperature. Sympathetic activation→increased CO = HR x SV→increased BP Learning Objectives 12  Vasodilation decreases peripheral resistance the harder we exercise so why does blood pressure increase? A lot more blood flowing through tat area Sympathetic activation→increased CO = HR x SV→increased BP Explain why strength increases with muscle cross-sectional area and discuss the factors that stimulate muscle hypertrophy Muscle hypertrophy increases cross-sectional area (CSA) of the muscle, which enables it to generate more force The primary stimuli for hypertrophy during strength-training are 1) the tearing of myofibrils, stimulates the repair and growth of muscle fibers, leading to an increase in CSA and muscle size. 2) mechanical tension, and from lifting heavy weights triggers molecular signaling that activates protein synthesis pathways, leading to muscle growth. 3) metabolic stress via buildup of lactate, hydrogen ions, etc. from the accumulation of metabolites (such as lactate and hydrogen ions) leads to muscle fatigue, signaling pathways, and an Learning Objectives 13  increase in muscle volume. All these factors work synergistically to stimulate muscle hypertrophy, which increases the muscle's cross-sectional area (CSA) and, in turn, its strength capacity. The more muscle fibers you have (because of hypertrophy), the greater the force your muscles can produce, leading to increased strength. Succinate dehydrogenase (SDH) → Mitochondrial enzyme so saying you have a lot of Succinate dehydrogenase (SDH) means you have a lot of mitochondria - have more with more exercise Describe why peripheral resistance decreases, but blood pressure increases during exercise Peripheral resistance is the resistance to blood flow in the small arteries and arterioles. During exercise, muscles experience vasodilation (widening of blood vessels) to increase blood flow, which decreases peripheral resistance in active muscle groups. This allows more oxygen and nutrients to be delivered to the muscles. While peripheral resistance decreases in the active muscles, cardiac output (the volume of blood the heart pumps per minute) increases during exercise to meet the demands of the body. This increase in cardiac output, combined with vasoconstriction in non-essential organs (e.g., digestive system), leads to an overall increase in systemic blood pressureduring exercise. Explain how the following training-induced changes enhance endurance: increase vascularization of the heart; hypertrophy of the heart; and increases in mitochondrial density, resting ATP levels and aerobic enzyme concentrations Vascularization: Endurance training increases the number of capillaries surrounding muscle fibers, enhancing oxygen delivery to tissues. Capillary density increases, improving the ability to exchange oxygen and carbon dioxide between the blood and muscles. Hypertrophy of the Heart: Learning Objectives 14  The left ventricle of the heart undergoes hypertrophy during endurance training, allowing it to pump a greater volume of blood per beat (increased stroke volume). This results in a lower resting heart rate, as the heart becomes more efficient at pumping blood. Mitochondrial Density: Mitochondria are the energy powerhouses of the cells. Endurance training increases the number and size of mitochondria, enhancing the ability of muscles to use aerobic energy from fats and carbohydrates. This leads to improved endurance performance and a higher capacity for aerobic metabolism. Aerobic Enzyme Concentrations: Training increases the concentration of enzymes involved in the Krebs cycle and oxidative phosphorylation, leading to better ATP production through aerobic pathways, which is key for prolonged activity. Describe how skeletal muscle disuse impacts muscle Detraining or injury can lead to skeletal muscle atrophy Disuse (e.g., bed rest, sedentary lifestyle) leads to a reduction in muscle mass and muscle strength. Muscle fibers decrease in size (atrophy), and the capacity for oxidative metabolism (e.g., mitochondrial density) decreases. This process can be accelerated by immobilization or prolonged lack of exercise, leading to significant reductions in functional capacity. Disuse Age Nerve damage Unloading Learning Objectives 15  Define the lactate threshold and explain why lactate accumulates in the blood during exercise Lactate Threshold: The lactate threshold refers to the exercise intensity at which lactate begins to accumulate in the bloodstream. Up to this point, lactate is produced at a rate that matches its clearance, primarily by being converted back into glucose (via the Cori cycle) or used as a fuel by other tissues. When the exercise intensity exceeds this threshold, the rate of lactate production outpaces its clearance, leading to an increase in lactate in the blood. This signals a shift from predominantly aerobic to anaerobic metabolism. Lactate Accumulation: Accumulation of lactate is associated with the onset of fatigue and the burning sensation in muscles. However, lactate is also a useful fuel source when cleared effectively from the blood. Explain the following effects of endurance training: lower resting HR, lower increase in HR during exercise, and quicker return of HR to normal after exercise Heart Rate Adaptations: Resting Heart Rate: Endurance training results in a lower resting heart rate because of increased stroke volumeand cardiac efficiency. HR Response to Exercise: Trained individuals have a more gradual increase in heart rate during exercise, as their cardiovascular system is more efficient. Return to Normal: After exercise, a trained athlete’s heart rate returns to baseline levels more quickly than that of an untrained individual. This is due to improvements in parasympathetic nervous system tone and overall cardiovascular efficiency. Learning Objectives 16  Explain why endurance training increases an athlete’s lactate threshold Endurance training shifts the lactate threshold to a higher intensity, meaning athletes can sustain higher intensities of exercise before lactate accumulation occurs. This is due to: Improved mitochondrial density for better aerobic metabolism. Increased capillary density, enhancing oxygen delivery to muscles. Improved lactate clearance mechanisms, which reduce the buildup of lactate in the blood. Explain how changes in ventilation, pulmonary diffusion, cardiac output, capillary density and mitochondrial diffusion all contribute to training-induced increases in the lactate threshold Pulmonary Diffusion: Training enhances the efficiency of oxygen exchange in the lungs (pulmonary diffusion), which helps deliver more oxygen to the bloodstream during exercise. Capillary Density: Increased capillary density enhances oxygen delivery and nutrient exchange in the muscles, improving the capacity for aerobic metabolism. Mitochondrial Function: More mitochondria mean greater ability to use fatty acids and glucose for energy in the presence of oxygen, delaying the shift to anaerobic metabolism. Cardiac Output: Endurance training increases cardiac output (the volume of blood pumped per minute) during exercise, which helps supply more oxygen to muscles, increasing endurance capacity and raising the lactate threshold. Learning Objectives 17  L17 learning objectives (come back to for anatomy of kidney, glomerulus, and nephrons) List the 4 distinct functions of the nephron Filtration: Blood is filtered through the glomerulus, where water, small molecules, and waste products are separated from larger components like proteins and blood cells. Reabsorption: Once the filtrate enters the tubules, essential substances (like water, ions, glucose, amino acids) are reabsorbed back into the bloodstream through the peritubular capillaries. Secretion: Some substances (e.g., drugs, excess ions, and waste products like urea) are actively secreted from the blood into the tubular fluid for excretion. Excretion: The final product, urine, is formed from the waste products and excess substances that are not reabsorbed, and is ultimately excreted from the body. Learning Objectives 18  Indicate the roles of the different segments of the nephron Each part of the nephron has specific roles in the filtration, reabsorption, secretion, and excretion of substances. Here's a breakdown: Bowman’s Capsule: The Bowman’s capsule surrounds the glomerulus and collects the filtrate that is filtered out of the blood. It’s the starting point for urine formation. Proximal Convoluted Tubule (PCT): The PCT is responsible for the bulk reabsorption of water, sodium, chloride, potassium, glucose, amino acids, and bicarbonate. It also participates in secretion of certain substances like organic acids and drugs. Loop of Henle: The loop has two main segments: Learning Objectives 19  Descending Limb: Permeable to water but not solutes; water is reabsorbed here. Ascending Limb: Impermeable to water, but actively transports sodium, potassium, and chloride ions into the interstitial fluid, which contributes to the countercurrent multiplier system (important for concentrating urine). Distal Convoluted Tubule (DCT): The DCT is involved in the fine-tuning of reabsorption of sodium, chloride, calcium, and water. It also plays a role in the secretion of potassium, hydrogen ions, and certain drugs. Collecting Duct: The collecting duct receives filtrate from multiple nephrons and is responsible for further reabsorption of water(under the influence of vasopressin/ADH) and ion regulation (sodium and potassium). It also plays a role in acid-base balance by secreting hydrogen ions. Indicate what can and cannot fit through a healthy glomerular filter The glomerular filter (found in the glomerulus) is a semi-permeable membrane that separates the blood from the filtrate. The filter is selective and depends on size, charge, and shape of the molecules: Can Fit (Filtered): Nutrients (salts, sugars, amino acids), urea and other small molecules in the plasma Water Small solutes: glucose, amino acids, electrolytes (Na+, K+, Cl-), urea, creatinine Waste products: urea, uric acid, metabolites of drugs Cannot Fit (Not Filtered): Large molecules: proteins (e.g., albumin), red blood cells, white blood cells, platelets Large particles (like lipids and large aggregates) Learning Objectives 20  This selectivity is due to the size of the pores in the glomerular capillaries and the negatively charged basement membrane, which repels negatively charged molecules (e.g., albumin). Describe the fate of the plasma as it enters the Bowman’s capsule—e.g., the % filtered and the % reabsorbed into the peritubular capillaries Only 20% of the plasma that passes through the glomerulus is filtered Total plasma volume: ~ 3 L Kidneys filter entire plasma volume ~ 60 times/day or 2.5 times/hr Note: if majority of filtrate was not reabsorbed, we would run out of plasma in < 30 min!! 99% of what was filtered in the bowman’s capsule gets reabsorbed into the capillaries Calculate the net filtration pressure in the glomerulus, based on P(H), P(fluid) and π Learning Objectives 21  The net filtration pressure (NFP) in the glomerulus is the force that drives filtration from the glomerular capillaries into the Bowman’s capsule. It is determined by the following equation: NFP=P(H)−P(fluid)−π P(H) = Hydrostatic pressure of the glomerular capillaries (approximately 55 mmHg, pushing fluid into the Bowman’s capsule). P(fluid) = Hydrostatic pressure in the Bowman’s capsule (approximately 15 mmHg, opposing filtration). π = Osmotic pressure due to proteins in the blood (approximately 30 mmHg, opposing filtration). Net filtration pressure is usually around 10 mmHg, which is sufficient to drive filtration into the nephron. Describe the local and auto-regulation of glomerular filtration rate (GFR) As long as mean is between 80 and 180, can be done locally What central (i.e., CNS) mechanisms can regulate GFR? Learning Objectives 22  1. Sympathetic Nervous System (SNS): SNS activation causes vasoconstriction (afferent and efferent arterioles), reducing renal blood flow and GFR, but efferent arteriole constriction can sometimes help maintain glomerular pressure and GFR. Increased renin release due to SNS activity stimulates RAAS, leading to further effects on GFR. 2. Renin-Angiotensin-Aldosterone System (RAAS): Angiotensin II constricts arterioles and helps maintain GFR during periods of low blood pressure. Acts in response to sympathetic stimulation, activating the feedback loop. 3. Baroreceptor Reflex: Low blood pressure stimulates sympathetic activation, leading to vasoconstriction and decreased GFR, and stimulates RAAS for long-term blood pressure regulation. 4. Antidiuretic Hormone (ADH): Released during low blood volume or high osmolality, promotes vasoconstriction and water reabsorption, influencing renal function and GFR. Overall, CNS-mediated mechanisms work in concert to maintain blood pressure, blood volume, and kidney function under conditions of stress, exercise, dehydration, or blood loss by adjusting GFR and renal blood flow. Why is it important to regulate GFR? An optimal GFR helps control blood volume (and hence, BP), and increases the efficiency of kidney filtration increase efficiency of kidneys Learning Objectives 23  Modulation of GFR GFR is auto-regulated by the juxtaglomerular apparatus (macula densa and granular cells) Learning Objectives 24  The nephron loops back on itself so that the ascending limb of the loop of Henle passes between the afferent and efferent arterioles High GFR increases Na+ uptake by the macula densa cells. These cells release paracrines, which cause the afferent arteriole to constrict. This lowers glomerular hydrostatic pressure and helps return GFR to normal Low blood pressure (BP) causes GFR to drop below normal. This low BP triggers renin release from granular cells. Renin causes a variety of effects. One is to constrict the efferent arteriole, which raises glomerular hydrostatic pressure and helps GFR return to normal Tubuloglomerular feedback via the juxtaglomerular apparatus help with GFR autoregulation Learning Objectives 25  The glomerular filtration rate (GFR) is the rate at which blood is filtered through the glomeruli of the kidneys. It is critical for kidney function and is tightly regulated to maintain homeostasis. Intrinsic (Autoregulation): The kidney has mechanisms to maintain GFR despite changes in blood pressure. This is achieved through two main mechanisms: Myogenic Mechanism: When blood pressure increases, the afferent arterioles constrict to reduce blood flow into the glomerulus, thereby maintaining a stable GFR. Conversely, when blood pressure decreases, the afferent arterioles dilate to increase blood flow. Tubuloglomerular Feedback (TGF): This mechanism involves the macula densa (a group of cells in the DCT) sensing sodium chloride concentration in the filtrate. If the concentration is too high (indicating high GFR), the macula densa signals the afferent arteriole to constrict, reducing GFR. If sodium chloride concentration is low, the afferent arteriole dilates to increase GFR. Extrinsic Regulation: The sympathetic nervous system can influence GFR through the constriction of afferent arterioles, particularly during stress or low blood volume (e.g., during hemorrhage or dehydration). Additionally, hormones such as renin (via the renin-angiotensin system) can help regulate blood flow to the kidneys and influence GFR. Indicate how the functions of the nephron and collecting ducts change along their length Proximal Convoluted Tubule (PCT): Reabsorption of about 65% of sodium, water, glucose, amino acids, and bicarbonate. Secretion of hydrogen ions and organic anions. Loop of Henle: Descending limb: Reabsorption of water. Ascending limb: Active transport of sodium, chloride, and potassium to create a concentration gradient for water reabsorption later in the Learning Objectives 26  nephron. Distal Convoluted Tubule (DCT): Fine-tuning of ion balance (reabsorption of sodium and calcium, secretion of potassium and hydrogen ions). Acid-base regulation (secretion of hydrogen and bicarbonate). Collecting Duct: Final water reabsorption (regulated by antidiuretic hormone, ADH). Potassium and hydrogen ion secretion for maintaining electrolyte balance and acid-base homeostasis. Learning Objectives 27  Explain and draw the mechanism by which organic anions are secreted into the proximal tubule Alpha ketoglutarate is one example of a dicarboxylate, it is not necessarily this one that is always used in this system OAT family of transporters can secrete various anions such as: bile salts, food preservatives (benzoate), artificial sweeteners (saccharine), medicines (penicillin & asprin), etc. Penicillin is an effective antibiotic, but OAT transporters are so effective at secreting it that after only 3-4 hours 80% of it is excreted in urine. Learning Objectives 28  Propose a solution to this problem to maintain higher levels of penicillin in the blood. temporary inhibitor of the OAT transporter so penicillin can remain longer Organic anions (e.g., urate, penicillin, bile acids) are secreted into the proximal tubule primarily via organic anion transporters (OATs). Here's a simplified version of the process: OATs located in the basolateral membrane of the proximal tubule cells transport organic anions from the blood into the tubule cells. Inside the tubule cell, the organic anions are then transported across the apical membrane into the filtrate (lumen) via other transport proteins, such as multidrug resistance proteins (MRPs) or anion exchangers. This process is important for the elimination of many drugs, toxins, and metabolic byproducts. L18 learning objectives Describe the osmolarity changes as fluid flows through the nephron Bowman’s Capsule: The filtrate entering the Bowman’s capsule has an osmolarity similar to blood plasma (about 300 mOsm/L) because water and solutes are filtered from the blood in a similar concentration. Proximal Convoluted Tubule (PCT): Learning Objectives 29  Isotonic reabsorption: The majority of water and solutes (like glucose, sodium, and bicarbonate) are reabsorbed here, so the osmolarity remains about the same (around 300 mOsm/L). Loop of Henle: The loop plays a key role in establishing the concentration gradient of the kidney's medulla. Descending limb: It is permeable to water but not solutes, so water is reabsorbed, making the filtrate more concentrated (osmolarity increases to about 1200 mOsm/L at the bottom of the loop). Ascending limb: It is impermeable to water but actively reabsorbs sodium, potassium, and chloride (via the Na+/K+/2Cl− symporter), decreasing the osmolarity of the filtrate as it moves upward (osmolarity drops back to 100 mOsm/L at the thick ascending limb). Distal Convoluted Tubule (DCT): Osmolarity of the filtrate is further reduced here due to the reabsorption of ions (especially sodium) but without water, leaving the filtrate at about 100 mOsm/L. Collecting Duct: The osmolarity of the filtrate can vary dramatically depending on the presence of vasopressin (ADH). In the presence of ADH: The collecting duct becomes permeable to water, so water is reabsorbed, and the osmolarity increases to up to 1200 mOsm/L in the deep medulla. In the absence of ADH, the collecting duct remains impermeable to water, resulting in a dilute urine with an osmolarity as low as 50 mOsm/L. Learning Objectives 30  List the factors that stimulate vasopressin release High osmolarity or low blood pressure causes vasopressin (ADH) release Vasopressin (also called antidiuretic hormone, ADH) is released from the posterior pituitary in response to the following stimuli: Increased plasma osmolarity (detected by osmoreceptors in the hypothalamus). Decreased blood volume (detected by baroreceptors in the atria and large veins). Decreased blood pressure (detected by baroreceptors in the aortic arch and carotid sinus). Other stimuli include stress and certain drugs (e.g., nicotine, morphine) which can also trigger ADH release. Learning Objectives 31  Describe the mechanism of action of vasopressin in the walls of the collecting duct Vasopressin acts on the collecting duct by binding to V2 receptors on the basolateral membrane of the principal cells in the collecting duct. This binding initiates a signaling cascade: V2 receptor activation leads to an increase in cyclic AMP (cAMP) levels. This activates protein kinase A (PKA), which promotes the insertion of aquaporin-2 channels (water channels) into the apical membrane of the collecting duct cells. Aquaporin-2 channels increase water permeability in the collecting duct, allowing water to move from the tubular fluid into the surrounding hypertonic interstitial fluid. This process leads to water reabsorption and concentrated urine (increased urine osmolality). Learning Objectives 32  Water does move out of the collecting duct in the presence of vasopressin Water does not leave the collecting duct in the absence of vasopressin Explain how the counter-current mechanism facilitates water re-uptake in the loop of Henle and collecting duct and draw an example of countercurrent Learning Objectives 33  exchange The countercurrent mechanism refers to the parallel flow of filtrate in the ascending and descending limbs of the Loop of Henle, and it plays a key role in creating a concentration gradient in the kidney medulla that facilitates water reabsorption in the collecting duct. Descending limb of the Loop of Henle: Water is reabsorbed due to the high osmolarity of the surrounding interstitial fluid (hypertonic environment). The filtrate becomes more concentrated as water moves out. Ascending limb of the Loop of Henle: The thick ascending limb actively pumps Na+, K+, and Cl− into the interstitial space via the Na+/K+/2Cl− symporter, but it is impermeable to water. This dilutes the filtrate as sodium and other solutes are removed, creating a concentration gradient in the medullary interstitium. The result of this countercurrent multiplier system is a high osmolarity in the renal medulla, which facilitates the reabsorption of water from the collecting duct when vasopressin is present. Countercurrent exchange occurs in the vasa recta (blood vessels surrounding the Loop of Henle), which run parallel to the nephron’s loop. The vasa recta carries away reabsorbed water and solutes, maintaining the osmotic gradient without dissipating it. Diagram of countercurrent exchange: 1. Filtrate flows down the descending limb (losing water, gaining solute). 2. Filtrate moves up the ascending limb (losing solute, no water loss). 3. Blood in the vasa recta flows in the opposite direction, which allows it to pick up water and solutes from the interstitial fluid. Learning Objectives 34  Describe the stimuli that elicit ANP release and its mode of action Increased blood volume causes myocardial cells to secrete atrial natriuretic peptide (ANP) Atrial Natriuretic Peptide (ANP) is released from the atria of the heart in response to: Increased blood volume or increased venous return, which stretches the atrial walls. Increased blood pressure. ANP's Mode of Action: It causes vasodilation, lowering systemic vascular resistance. Learning Objectives 35  Inhibition of aldosterone secretion reduces sodium reabsorption in the kidneys, promoting sodium and water excretion, which lowers blood volume and pressure. Inhibition of renin release reduces activation of the renin-angiotensin- aldosterone system (RAAS), leading to decreased sodium retention and further lowering of blood pressure. It increases glomerular filtration rate (GFR) by dilating afferent arterioles, promoting sodium excretion (natriuresis), and increasing urine production (diuresis). Discuss the relationship between sodium intake and aldosterone release Learning Objectives 36  more sodium, high blood pressure, decrease plasma aldosterone less sodium, low blood pressure, increased plasma aldosterone Low sodium levels: Aldosterone promotes sodium reabsorption in the distal convoluted tubule (DCT) and collecting duct, leading to increased sodium retention and water reabsorption to raise blood volume and pressure. High sodium intake: If sodium intake increases, less aldosterone is released to prevent excessive sodium retention. Indicate where aldosterone exerts its effects on the nephron Aldosterone primarily acts on the distal convoluted tubule (DCT) and collecting duct by stimulating the following processes: Sodium reabsorption: Aldosterone activates sodium channels (ENaC) on the apical membrane of principal cells, increasing sodium reabsorption into the bloodstream. Learning Objectives 37  Potassium secretion: Aldosterone stimulates the Na+/K+ ATPase pump on the basolateral membrane, increasing potassium secretion into the urine. Water reabsorption: By reabsorbing sodium, aldosterone indirectly promotes water retention, as water follows sodium by osmosis. Explain how the body would respond to ingestion of salty foods Ingestion of salty foods increases the osmolarity of the blood, which can lead to the following responses: Vasopressin release: The hypothalamus detects the increase in osmolarity and triggers the release of vasopressin (ADH) from the posterior pituitary to conserve water by increasing water reabsorption in the collecting duct. Aldosterone release: High sodium intake may lead to decreased renin release and lower aldosterone levelsbecause the body is trying to prevent excessive sodium retention and to avoid raising blood pressure. Learning Objectives 38  Increased thirst: The increase in blood osmolarity also stimulates thirst, prompting the individual to drink more water, which helps dilute the excess sodium. Explain how the renin-angiotensin system is activated and the effects it has on blood pressure Steps in RAAS Activation: 1. Release of Renin: Renin is an enzyme secreted by the juxtaglomerular cells of the kidneys, which are located near the glomerulus. The release of renin is triggered by several factors: Low blood pressure: Reduced perfusion of the kidneys, such as from low blood volume or systemic hypotension, is sensed by baroreceptors in the kidneys. Low sodium levels: If the macula densa (a part of the distal convoluted tubule) detects decreased sodium chloride (NaCl) in the tubular fluid (indicating low sodium levels), it signals the juxtaglomerular cells to release renin. Sympathetic nervous system (SNS): Increased sympathetic activity (such as during stress) stimulates beta-1 adrenergic receptors on juxtaglomerular cells, promoting renin release. 2. Conversion of Angiotensinogen to Angiotensin I: Once released, renin converts a plasma protein called angiotensinogen (produced by the liver) into angiotensin I. 3. Conversion of Angiotensin I to Angiotensin II: Angiotensin I is an inactive precursor that is converted to the active form, angiotensin II (ANG II), by the enzyme angiotensin-converting enzyme (ACE), which is primarily found in the lungs but also in endothelial cells throughout the body. Effects of Angiotensin II on Blood Pressure: Learning Objectives 39  Angiotensin II is a potent vasoconstrictor that plays several important roles in increasing blood pressure: 1. Vasoconstriction: ANG II causes vasoconstriction of arterioles, particularly the afferent arterioles in the kidneys and systemic vasculature. This increases systemic vascular resistance (SVR) and raises blood pressure quickly. The vasoconstriction reduces the diameter of blood vessels, making it harder for blood to flow, thus increasing the pressure inside the arteries. 2. Increased Heart Rate and Contractility: ANG II can increase heart rate (chronotropy) and the force of contraction (inotropy), which enhances cardiac output and further raises blood pressure. 3. Release of Aldosterone: ANG II stimulates the release of aldosterone from the adrenal glands. Aldosterone promotes sodium and water retention in the kidneys, leading to an increase in blood volume, which also increases blood pressure. 4. Release of Antidiuretic Hormone (ADH): ANG II stimulates the release of vasopressin (ADH) from the posterior pituitary, which promotes water retention by the kidneys, further increasing blood volume and blood pressure. 5. Sympathetic Nervous System Activation: ANG II also activates the sympathetic nervous system, causing further vasoconstriction and stimulating renin release, which perpetuates the cycle of blood pressure regulation. Draw and describe the effects of aldosterone in the nephron Aldosterone is a steroid hormone that is released by the adrenal cortex in response to angiotensin II (or increased potassium levels). It acts on Learning Objectives 40  the distal convoluted tubule (DCT) and collecting ducts of the nephron to increase sodium and water retention, which leads to increased blood volume and, therefore, higher blood pressure. Mechanism of Action in the Nephron: 1. Binding to Mineralocorticoid Receptors: Aldosterone binds to mineralocorticoid receptors (MR) in the cytoplasm of cells in the distal convoluted tubule and collecting duct of the nephron. 2. Activation of Sodium-Potassium ATPase Pump: Once bound to its receptor, aldosterone activates transcription of genes that produce sodium-potassium ATPase pumps on the basolateral side of the epithelial cells in the DCT and collecting duct. These pumps actively transport sodium (Na⁺) from the tubular fluid into the bloodstream in exchange for potassium (K⁺), which is excreted into the urine. 3. Increased Sodium and Water Reabsorption: The reabsorption of sodium increases the osmolarity of the blood. This creates an osmotic gradient that promotes water retention through osmosis (water follows sodium), further increasing blood volume. 4. Excretion of Potassium: As sodium is reabsorbed, potassium is excreted into the urine. This helps to maintain electrolyte balance. Overall Effect: By increasing sodium and water retention, aldosterone increases blood volume, which in turn increases blood pressure. Describe the integrated responses to changes in blood volume and pressure The RAAS is activated in response to low blood pressure or low blood volume and leads to vasoconstriction, aldosterone release, and water Learning Objectives 41  retention, all of which work to increase blood pressure and volume. Aldosterone acts on the nephron to increase sodium and water reabsorption, increasing blood volume. In response to high blood pressure or blood volume, ANP is released, which promotes vasodilation, inhibits aldosterone and renin release, and encourages sodium excretion to lower blood volume and pressure. L19 learning objectives Describe the functions of the mouth, saliva, stomach, pancreas, and small and large intestine in digestion mouth > oral cavity > esophagus > stomach > small intestine > large intestine > rectum > anus Mouth: Mechanical digestion: grinding food with teeth or muscular layers of the stomach Chemical digestion: Salivary amylase begins breaking down carbohydrates (starch) into simpler sugars (maltose). breaking chemical bonds with enzymes Lubrication: Saliva, produced by the salivary glands, moistens food, forming the bolus that is easier to swallow. Saliva: Saliva initiates starch and fat digestion, and delivers chemical stimuli to taste cells Contains salivary amylase (for carbohydrate digestion) and lysozyme (which has antimicrobial properties). Bicarbonate ions in saliva help to buffer acidic food and maintain a neutral pH for enzyme function. Stomach: Learning Objectives 42  Mechanical digestion: The stomach churns food, mixing it with gastric juices to form chyme. Chemical digestion: Gastric juices contain hydrochloric acid (HCl) and the enzyme pepsin, which begins the digestion of proteins. proteolytic (breaks down proteins) enzyme is secreted into the stomach - Pepsin Pepsin is initially secreted as a zymogen (i.e., an inactive form) called pepsinogen Protection: The stomach mucosa is protected by a mucus-bicarbonate barrier - protects it from the acidic environment and digestive enzymes. digests protein - physically breaks down food absorbs small amounts of lipophilic coumpods (ex. ethanol) - destroys ingested pathogens carefully regulates the rate at which chyme enters the small intestine - stores undigested food to permit discontinuous feeding bicarbonate is moved into the blood and the proteins are moved into the stomach Pancreas: Exocrine function: Secretes digestive enzymes into the small intestine, including amylase (for carbohydrates), lipase (for fats), and proteases (such as trypsin and chymotrypsin for proteins). Bicarbonate secretion: Neutralizes the acidic chyme entering the small intestine from the stomach, creating an optimal environment for digestive enzymes. Small Intestine: Duodenum: senses specific nutrients in the chyme and triggers release of appropriate enzymes; produces a mucus-rich bicarbonate secretion Jejunum: absorbs sugars, amino acids, and fatty acids Learning Objectives 43  Ileum: absorbs vitamin B12, bile acids, and any remaining nutrients; regulates gastric emptying The primary site for nutrient digestion and absorption. Enzymes from the pancreas and brush border enzymes (like lactase and sucrase) break down carbohydrates, proteins, and fats. The villi increase surface area for absorption. Nutrients are absorbed into the bloodstream (via capillaries) or lymphatic system (via lacteals for fats). Large Intestine: Water and electrolyte reabsorption: Absorbs most of the remaining water and electrolytes from the undigested food material. Fermentation: Some undigested carbohydrates are fermented by gut bacteria, producing gases and short-chain fatty acids (SCFAs). Formation of feces: Remaining undigested material is compacted into feces for elimination. Characterize the mechanism that elicits swallowing Swallowing (or deglutition) is a coordinated process that involves: Voluntary phase: The tongue pushes the food bolus to the back of the mouth (pharynx), triggering the reflex. Involuntary phase: The bolus is propelled down the pharynx and into the esophagus: The epiglottis closes over the trachea to prevent food from entering the airway. Peristalsis (a wave of muscular contractions) pushes the bolus down the esophagus. The lower esophageal sphincter (LES) relaxes to allow food to enter the stomach. Explain how food is both propelled through and mixed with enzymes in the intestine Learning Objectives 44  The small and large intestine exhibit 2 types of contractions Peristalsis propels bolus forward Segmental contractions (segmentation) mix the intestinal contents with bile, pancreatic juice and intestinal secretions. Discuss the mechanisms by which the stomach avoids digesting itself Mucus layer: The stomach lining is protected by a thick mucus layer that acts as a physical barrier, preventing HCl and digestive enzymes like pepsin from damaging the epithelial cells of the stomach lining. Bicarbonate secretion: Cells in the stomach wall secrete bicarbonate ions into the mucus, neutralizing any acid that comes in contact with the stomach lining. Cell turnover: The stomach lining undergoes rapid turnover (about every 3-5 days) to replace cells that are exposed to the harsh acidic environment. Prostaglandins: These molecules promote mucus and bicarbonate secretion, helping to protect the stomach lining from ulcers. Define zymogens, and discuss their relevance to digestion To digest proteins, the acinar cells of the pancreas secrete multiple zymogens into the lumen of the duodenum through two ducts Learning Objectives 45  Hormone CCK stimulates release of substances from pancreas and gallbladder Trypsinogen is converted to trypsin by enzymes in the brush border of the duodenum The other zymogens are converted to active proteolytic enzymes (endo- and exopepsidases) by trypsin in the lumen of the duodenum Learning Objectives 46  Summary Zymogens (or proenzymes) are inactive precursor enzymes that are activated only when needed to prevent the breakdown of proteins within the cells that produce them. pepsinogen, the zymogen form of pepsin, is secreted by chief cells in the stomach. It is activated to pepsin in the acidic environment, where it can begin breaking down proteins. In the pancreas, enzymes like trypsinogen are secreted as zymogens and activated in the small intestine by enterokinase, protecting the pancreas from self-digestion. Describe the mechanisms for digesting protein, carbohydrates and fats Proteins: In the stomach, pepsin starts breaking proteins into smaller polypeptides. In the small intestine, pancreatic proteases (like trypsin and chymotrypsin) further break down proteins into peptides and amino acids, which are absorbed by intestinal epithelial cells. Carbohydrates: Salivary amylase starts the breakdown of starches in the mouth. Learning Objectives 47  Pancreatic amylase continues carbohydrate digestion in the small intestine, breaking starches into disaccharides (like maltose). Brush border enzymes (such as lactase, sucrase, and maltase) break disaccharides into monosaccharides (like glucose, fructose, and galactose), which are absorbed by the enterocytes. Fats: In the small intestine, bile salts from the liver emulsify fats, breaking them into smaller droplets. Pancreatic lipase further breaks down triglycerides into fatty acids and monoglycerides, which are absorbed into the intestinal cells and reassembled into triglycerides before entering the lymphatic system. Proteolytic enzymes in the small The breakdown of complex intestine sequentially reduce carbohydrates in the small intestine proteins into absorbable involves a number of different constituents, which are then enzymes, which work in a transported into the body complementary manner brush border membrane enzyme: an enzyme located on the microvilli of the brush border, a specialized surface lining the small intestine, which plays a crucial role in the final stages of digestion by breaking down complex molecules like Learning Objectives 48  carbohydrates and proteins into smaller, absorbable units like monosaccharides and amino acids endo will cleave it in the middle - cleave on the inside exo cleaves the ends - cleaves in the outside both breaks down chains Explain the mechanisms for absorbing monosaccharides, amino acids, small peptides, fatty acids and glycerol Monosaccharides (glucose, fructose, and galactose): Absorbed through active transport (glucose and galactose via the SGLT1 transporter) or facilitated diffusion(fructose via GLUT5). Once inside the enterocytes, monosaccharides are transported to the bloodstream via GLUT2 transporters. Amino Acids and Small Peptides: Learning Objectives 49  Amino acids are absorbed via active transport (using specific transporters like Sodium-dependent amino acid transporters). Small peptides are absorbed via PepT1 transporter (a proton-coupled oligopeptide transporter), where they are further broken down into amino acids within the enterocyte. Fatty Acids and Glycerol: After digestion by pancreatic lipase, fatty acids and monoglycerides enter the enterocytes via simple diffusion. Inside the cells, they are re-esterified into triglycerides and packaged into chylomicrons, which enter the lacteals(lymphatic vessels) and eventually reach the bloodstream. Indicate where the different types of nutrients are absorbed in the gastrointestinal tract Carbohydrates: Absorbed mainly in the duodenum and jejunum as monosaccharides. Proteins: Absorbed mainly in the jejunum as amino acids and small peptides. Fats: Absorbed in the jejunum as fatty acids and monoglycerides. Water and Electrolytes: Most water and electrolytes are absorbed in the small intestine, but the large intestine also plays a significant role in absorbing water. /////// The duodenum is mainly responsible for the digestion and neutralization of stomach acid, preparing the chyme for nutrient absorption. It acts as the initial processing stage. The jejunum follows and is specialized for the absorption of nutrients into the bloodstream, utilizing its extensive surface area and blood supply to facilitate this process. Describe the importance of the hepatic portal system The hepatic portal vein carries all nutrients, except fats, to the liver Learning Objectives 50  The hepatic portal system transports absorbed nutrients from the gastrointestinal tract to the liver. The system ensures: Nutrient processing: The liver processes, stores, and detoxifies nutrients absorbed from the gut. Metabolism regulation: The liver regulates blood glucose, amino acid metabolism, and fat storage. Detoxification: It helps detoxify harmful substances (such as alcohol, drugs, and ammonia) before they enter the general circulation. Learning Objectives 51  hapato - anything related to the liver List the functions of the liver Metabolism: Learning Objectives 52  Glycogen storage and release: The liver stores glucose as glycogen and releases it into the bloodstream when blood glucose levels are low. Fat metabolism: It synthesizes cholesterol and lipoproteins, and converts excess glucose into fat for storage. Protein synthesis: It produces plasma proteins like albumin and clotting factors. Detoxification: The liver detoxifies substances like drugs, alcohol, and metabolic waste products (such as ammonia, which is converted to urea). Bile production: The liver produces bile, which is important for fat digestion and absorption in the small intestine. Storage: The liver stores fat-soluble vitamins (A, D, E, K) and minerals (iron and copper). L20 learning objectives Describe the importance of the hepatic portal system Nutrient Transport: The system carries blood from the gastrointestinal tract (GI) and spleen to the liver. This allows absorbed nutrients like glucose, amino acids, and fats (in the form of chylomicrons) to be processed by the liver before reaching the general circulation. Detoxification: The liver can filter toxins, drugs, and other harmful substances absorbed through the digestive system. For example, alcohol is metabolized by the liver before it enters the systemic circulation. Metabolic Regulation: The liver adjusts blood levels of nutrients (e.g., glucose) and stores excess nutrients (e.g., glycogen) for later use, ensuring homeostasis. Learning Objectives 53  List the functions of the liver glucose and fat metabolism protein synthesis hormone synthesis urea production detoxification storage Learning Objectives 54  Explain some reasons why we feel hungry or full Learning Objectives 55  Ghrelin - the hunger hormone - from the stomach AgRP - co-expressed in hypothalamus CCK - releases enzymes from pancreas and gall bladder recognizes for present in the small intestine triggers a feeling a fullness leptin - released from adipose cells increase in nutrient adsorption releases it and triggers a sense of fullness GLP - 1 - from the intestines released when food moves from the stomach to the intestine increase glucagon secretion close movement of food from stomach to intestine taking a shot of it increase satielty Learning Objectives 56  decrease appetite decrease gastric mitility decrease gastric emphtying increase insulin decrease in glucagon Hunger: Gherlin Satiety: Leptin, CCK, GLP-1 Discuss the transport and fate of chylomicrons, fatty acids, HDLs and LDLs Chylomicrons: After absorption in the small intestine, chylomicrons (lipoprotein particles) transport dietary lipids (mainly triglycerides) via the lymphatic system to the bloodstream. They are then delivered to peripheral tissues (e.g., muscle, adipose tissue) for energy or storage. Fatty Acids: Fatty acids are transported in the blood bound to albumin (a protein in the blood plasma). They can be used by tissues like muscle for beta-oxidation to produce energy, or stored in adipose tissue for later use. HDL (High-Density Lipoprotein): HDL is known as "good cholesterol" because it helps remove excess cholesterol from the bloodstream and transport it to the liver for excretion or recycling. Higher HDL levels are generally associated with a lower risk of cardiovascular diseases. LDL (Low-Density Lipoprotein): LDL is often referred to as "bad cholesterol" because it carries cholesterol from the liver to peripheral tissues. If there is excess LDL, it Learning Objectives 57  can deposit cholesterol in the arterial walls, contributing to the development of atherosclerosis and cardiovascular diseases. Indicate which tissues can use glucose, fatty acids and ketones for energy Muscles (and most other cells) can use glucose, fatty acids, amino acids, glycerol and ketones as a source of energy; the brain can only use glucose and ketones Learning Objectives 58  Explain the physiological responses to elevated plasma glucose and amino acids during and after a meal Elevated Plasma Glucose: After a meal, plasma glucose levels rise, triggering the release of insulin from the pancreas. Insulin facilitates the uptake of glucose into muscle, fat, and liver cells, where it can be used for energy or stored as glycogen. The increase in insulin also inhibits the release of glucagon, a hormone that typically raises blood glucose. Elevated Amino Acids: Amino acids, absorbed from protein in the meal, stimulate the release of insulin and promote protein synthesis in muscle and other tissues. Elevated amino acids also trigger the release of glucagon, which helps maintain normal blood glucose levels by stimulating gluconeogenesis in the liver. Learning Objectives 59  Describe the role of glucagon in blood glucose homeostasis Glucagon is a hormone secreted by alpha cells in the pancreas in response to low blood glucose levels (hypoglycemia). It stimulates glycogenolysis in the liver, breaking down glycogen into glucose and releasing it into the bloodstream. Learning Objectives 60  It promotes gluconeogenesis, the production of glucose from non- carbohydrate sources like amino acids and glycerol. Glucagon also inhibits the release of insulin to prevent excessive glucose storage during periods of low blood sugar. Glucagon's primary function is to raise blood glucose levels during fasting or between meals to provide energy for tissues like the brain. Learning Objectives 61  Explain how glucose vs fat utilization changes as a function of exercise intensity Low-Intensity Exercise (e.g., walking): Fat is the primary energy source because fat oxidation is efficient at low intensities when oxygen availability is sufficient. The body utilizes more fatty acids from stored fat for energy. Moderate-Intensity Exercise (e.g., jogging): Both fat and glucose are used for energy. The body starts to rely more on glycogen stores as exercise intensity increases. High-Intensity Exercise (e.g., sprinting): Glucose (in the form of glycogen) becomes the primary energy source due to the limited oxygen availability and the fast energy demands. Anaerobic metabolism (glycolysis) dominates, and the body relies on glucose for quick ATP production. Learning Objectives 62  Explain the inverse relationship of running velocity to duration of a race High velocity requires more energy, and the body can only sustain this intense effort for a short duration due to limited energy stores (mainly glycogen). As the velocity increases, the duration of the race decreases because glycogen stores deplete faster, and lactic acid builds up, leading to fatigue. Conversely, slower velocities (e.g., in long-distance running) allow for greater endurance, as the body can rely more on fat metabolism for sustained energy production, which does not deplete as quickly as glycogen. 100-meter sprint Requires an athlete to run as fast as possible(~ 10 m/s) This speed can only be maintained for 5 to 6 s the winner is the one who slows down the least What happens over the course of the race? ATP level in muscle drops from ~5.2 to 3.7 mM Creatine phosphate level decreases from ~9.1 to 2.6 mM Blood-lactate level increases from ~1.6 to 8.3 mM Learning Objectives 63  L21 learning objectives Distinguish innate and acquired immunity Innate immunity provides immediate, nonspecific responses to pathogens Acquired immunity provides specific (but delayed) responses to novel pathogens because it retains a memory of that pathogen, it can react more quickly in the future mediated by B and T lymphocytes specific to antigens (on the surface of pathogens) Outline the anatomy of the immune system Primary lymphoid organs: Bone marrow (produces all blood cells, including immune cells). Learning Objectives 64  Thymus (where T cells mature). Secondary lymphoid organs: Lymph nodes (filter lymph and house immune cells). Spleen (filters blood and stores immune cells). Mucosa-associated lymphoid tissues (MALT) (e.g., tonsils, Peyer’s patches in the intestines). Immune cells: Macrophages, neutrophils, dendritic cells (innate immune cells). T cells and B cells (adaptive immune cells). Learning Objectives 65  Describe the nature of the local inflammatory response and the specific effects of cytokines splinter (break in skin) allows a pathway for pathogens injury will activate mast cells which will release histamines macrophages release cytokines cytokines when bind to their receptors, increase permeability of the capillaries → leaky capillary makes the walls sticky so that neutrophlilis and monocytes stick so white blood cells move out of the capillary and into the space Learning Objectives 66  when in the space becomes macrophages histamine will also dilate the blood vessels causing more blood flow to the area which brings even more of the white blood cells to the site Cytokines alter local vasculature and ECF volume Why would cytokines would cause edema (i.e. accumulation of ECF and puffiness)? get a cut, blood goes to the site and it gets hot and painful Increased PH Increased capillary leakiness Reduced colloid osmotic pressure Lower protein concentration in blood Input to ECF > output from ECF Increased hydrostatic pressure Learning Objectives 67  Describe the functional significance of the local inflammatory response Protective function: Inflammation helps to contain the infection, recruit immune cells, and eliminate pathogens through phagocytosis. Tissue repair: It facilitates the healing of damaged tissues and the regeneration of cells. Activation of adaptive immunity: The inflammatory response enhances the recruitment of dendritic cells, which present antigens to T cells, initiating the adaptive immune response. Discuss the function of macrophages in the innate immune response Macrophages (innate immunity agents) are attracted to pathogens. They squeeze through capillaries and accumulate at damage sites, causing puss. They can recognize (via surface receptors), engulf and digest many common pathogens Learning Objectives 68  Some bacteria are coated with a polysaccharide capsule, and thus must be coated with specific types of antibodies before macrophages can grab and then engulf them Outline the nature and functions of antibodies Antibodies are central players in the innate and acquired immune responses. They are molecules keyed to a particular pathogens, which help target it for destruction by binding to proteins on their surface A sizeable fraction of your plasma proteins are gamma globulins (i.e., antibodies). They are divided into 5 classes: IgG: 75% of total; cross placental membrane; prevalent in secondary immune response in the mother can pass to the developing fetus IgA: in body secretions like saliva, tears, breast milk (highly concentrated in colostrum) IgE: associated with allergic response IgM: antibodies that react to blood type; also prevalent in primary immune response IgD: help some immune cells (T cells) trap antigens phagocytes can recognize the chains and engulf the pathogen Learning Objectives 69  Distinguish B and T cells Two main classes of lymphocytes mediate acquired immunity b-lymphocytes become differentiates in the bone and t- lymphocytes differentiated in the thymus Learning Objectives 70  The responses of the B and T lymphocytes to infection are characterized by specificity diversity memory capacity to distinguish self from non-self to not destroy oneself B cells: Humoral immunity: Produce antibodies to neutralize pathogens in the bloodstream. Activated by helper T cells: They differentiate into plasma cells that secrete antibodies. T cells: Cell-mediated immunity: Target infected or cancerous cells directly. Helper T cells (CD4+): Activate B cells and cytotoxic T cells. Cytotoxic T cells (CD8+): Kill infected cells by inducing apoptosis. List the four factors that distinguish the responses of lymphocytes to infection Specificity: Each lymphocyte responds to a unique antigen. Diversity: Lymphocytes generate a vast array of receptors to recognize many different pathogens. Memory: After an infection, memory cells are formed to mount a faster and stronger response upon re-exposure. Self-tolerance: Lymphocytes learn to distinguish between self and non- self, preventing attacks on the body’s own tissues. Explain how lymphocyte clones provide both specificity and diversity to the immune response Clonal selection: During an infection, specific lymphocytes (B or T cells) with receptors matching the pathogen’s antigen are selected for activation. Learning Objectives 71  Clonal expansion: These selected lymphocytes proliferate to produce a clone of cells capable of combating the infection. Diversity: The immune system generates millions of different receptors through genetic recombination in B cells and T cells, allowing it to recognize virtually any pathogen. Describe the process and functional significance of clonal selection in B cells “Clonal selection” is a mechanism by which the immune system selectively enhances production of one B cell clone so as to combat an infection Primary immune response involves producing effector (plasma) cells that secrete pathogen-specific antibodies, and memory cells that will combat the same pathogen more effectively during future infections Alternative illustration of “clonal selection” Learning Objectives 72  all of the clones are random changes to the binding site when the site binds to the antigen then it multiples and a small subset becomes a memory cell Clonal selection: When a B cell encounters its specific antigen, it becomes activated and begins to divide rapidly. This creates a clone of identical plasma cells, which secrete large amounts of antibodies that target the