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identify the major airways of the lungs and indicate where gas exchange can first occur in the lungs.
the major airways in the lungs can be divided into the upper respiratory tract (mouth, nasal cavity, pharynx, and larynx) and the lower respiratory tract (trachea, two primary bronchi, their branches, and the lungs). Gas exchange can first occur in the alveoli
why is the alveolus considered as the functional unit of the lungs
the alveolus is considered the functional unit of the lungs because that is where gas exchange (breathing) occurs
describe the effects that sympathetic or parasympathetic stimulation has on smooth muscle tissue surrounding the bronchioles and what that does to airway resistance
parasympathetic stimulation on the bronchioles causes bronchoconstriction (reflex protecting the lower respiratory tract from inhaled irritants) which increases resistance. There is no significant sympathetic stimulation of the bronchioles, however smooth muscle in the bronchioles is well supplied with beta-2 receptors that respond to circulating epinephrine, which relaxes airway smooth muscle and results in bronchodilation
differentiate between the following types of cells found in the alveolus: alveolar type I, alveolar type II, alveolar macrophages.
alveolar type 1- simple squamous epithelial cells, where gas exchange occurs
alveolar type 2 - septal cells, produce surfactant; decrease surface tension in the air/water interface and prevent the collapse of alveoli
alveolar macrophages - phagocytosis of particulate matter, non-specific defense; get attracted to chemicals, prevents stuff from getting in your lungs
describe the function of surfactant in alveoli.
mixes with the thin fluid lining of the alveoli to aid lungs as they expand during breathing (material that allows gases to move through better) Surfactant equalizes surface tension between large and small alveoli.
list the 3 major components of the respiratory membrane through which external respiration occurs
alveolar epithelium - thin layer of cells that makes up the walls of the alveoli; very thin, allowing for easy diffusion of gases, type 1 alveolar cells are the main cells involved in gas exchange, and they’re extremely thin to facilitate the rapid exchange of oxygen and carbon dioxide
capillary endothelium - the walls are thin (single layer of endothelial cells), and are close proximity to the alveolar epithelium, separated by the basement membrane, this proximity facilitates the diffusion of gases between the air in the alveoli and the blood in the capillaries
basement membrane - a thin layer of connective tissue that lies between the alveolar epithelium and the capillary endothelium, provides structural support and helps maintain the close proximity of the alveoli and capillaries, permeable to gases, allowing for efficient gas exchange
provide average values for the following pressures during normal inhalation and exhalation: intra-alveolar (intra-pulmonary) pressure and intrapleural pressure
normal inhalation (-1 mmHg) and normal exhalation (+1 mmHg), normal inhalation and exhalation averages -4 mmHg
why is it that weightlifters need to exhale while lifting very heavy weights (or alternatively, what is the alveolar pressure during a Valsalva maneuver and what harm can that cause)?
the alveolar pressure during a Valsalva maneuver (straining with the glottis closed) is +100 mmHg. During the Valsalva maneuver, alveolar pressure increases due to breath-holding and straining and increases the pressure within the chest, there is reduced venous return decreasing cardiac output and blood to the brain, which can cause dizziness, fainting, or other cardiovascular complications.
describe what the term compliance of the lung indicates and how lung function can be affected by either increased or decreased compliance
the “stretchiness” of the lung tissue. increased compliance makes the lung tissue very flimsy.
list the different lung volumes and be able to provide an accurate definition and average value for each volume as presented in lecture
total lung capacity - the amount of air that the lung holds (6 L for males, 4.2 L for females)
tidal volume - the amount of air exchanged each breath (about 500 mL)
respiratory minute volume (VE) - the amount of air moved each minute; respiration rate x (VT) (about 500 mL x 12 breaths/minute = 6L/minute)
alveolar ventilation (VA) - the amount of air moving in/out of the alveoli; respiration rate x VT - VD, VD is anatomic dead space, 150mL does not get to the area for gas exchange (500 mL - 150 mL) x 12 = 4.2 L/min
inspiratory reserve volume (IRV) - the amount of air above tidal volume that can forcibly be inhaled
expiratory reserve capacity (EV) - the amount of air that can be forcibly expelled
vital capacity - the maximum amount of air that can be exchanged/breath; VC = VT + ERV + IRV
residual volume - the amount of air that remains after exhalation
write the formula to determine minute volume.
tidal volume x respiratory rate (number of breaths per minute)
write the formula for alveolar ventilation: how is it calculated?
respiration rate x (VT - VD)
describe the significance of the FEV1.0/FVC ratio by comparing normal values with those altered when airway resistance is increased
FEV₁.₀ / FVC ratio is 85% for normal individuals, while asthmatics have reduced ratios; and can have reduced FVC (40%)
name a condition that increases airway resistance and indicate a possible cause.
asthma can increase airway resistance due to having a reduced forced vital capacity (FVC)- slower FVC, more resistance
describe the structure and function of hemoglobin. Include the sites where gas molecules bind to the hemoglobin
hemoglobin (Hb) is a tetramer with four globular protein chains, each centered around an iron-containing heme group. The central iron atom of each heme group can bind reversibly with one oxygen molecule- the iron-oxygen interaction is a weak bond that can easily be broken without altering either Hb or O₂. Hemoglobin bound to oxygen is known as oxyhemoglobin. Hb transports oxygen from the lungs to the tissues and organs throughout the body
name the molecules discussed in lecture that bind to hemoglobin and which ones bind tighter than others
the two primary molecules that hemoglobin can bind to are oxygen and carbon dioxide. Oxygen generally binds more tightly to hemoglobin than carbon dioxide. The binding of oxygen is cooperative, meaning that as one oxygen molecule binds to a hemoglobin subunit, it increases the affinity of the remaining subunits for oxygen
define what is meant by partial pressure of a gas (i.e., PO2). For instance, if air is 20% oxygen and the barometric pressure is 760 mmHg, then what is the partial pressure of oxygen?
partial pressure is the pressure of a single gas in a mixture, O2= 20% would have a 152 mmHg partial pressure (0.20 x 760 mmHg)
provide the average partial pressures for both oxygen and CO2 in the following places in the pulmonary circulatory system: alveoli, venous blood, and arterial blood
alveolus: PO₂ = 100, PCO₂ = 40
arterial Blood: PO₂ = 40, PCO₂ = 46
venous Blood: PO₂ = 100, PCO₂ = 40
provide the average partial pressures for both oxygen and CO2 in the following places in the systemic circulatory system: interstitial fluid, venous blood, and arterial blood
interstitial fluid: PO₂ = 40 mmHg, PCO₂ = 45 mmHg
venous blood: PO₂ = 40 mmHg, PCO₂ = 45 mmHg
arterial blood: PO₂ = 95 mmHg, 40 mmHg
describe how changes in hemoglobin structure or the pH of the solution affects the affinity of hemoglobin for oxygen. What is meant by a shift to the ‘right’ or to the 'left’?
changes in the structure of hemoglobin also change its oxygen-binding affinity- fetal hemoglobin, HbF, has two gamma protein chains instead of two beta chains in adults, causing them to have a higher affinity for oxygen-binding. As pH lowers, hemoglobin affinity for oxygen decreases (the “Bohr effect”), and CO₂ causes this. The graph will shift right as a result of decreased affinity of Hb for oxygen and will shift left as a result of increased affinity of Hb to oxygen
distinguish between internal and external respiration. where does each occur?
internal respiration is gas exchange in systemic circulation between blood and the body’s tissues. It occurs in the systemic capillaries throughout the body where oxygen is delivered from the blood to the cells. External respiration is gas exchange in the pulmonary circulation and is the movement of gases between the environment (usually air in the lungs) and the body’s cells. Occurs in the lungs (alveoli) and the inhaled air diffuses into the blood and carbon dioxide from the blood diffuses into the air to be exhaled
why is CO2 produced by body tissue cells and released from blood in the pulmonary capillaries
CO₂ is produced by body tissues because the removal of CO₂ is necessary to maintain the pH balance of the blood and is released from the blood into the pulmonary capillaries to be transported to the lungs to be exhaled out
how is carbon dioxide transported in blood from body tissue cells to the lungs? Include all forms of CO2
CO₂ is transported in the blood from body tissue cells to the lungs by… a small fraction of CO₂ dissolves directly in the plasma of the blood, this can move freely across cell membranes and is in equilibrium with CO₂ in the tissues. Then majority of CO₂ is converted to bicarbonate ions in a series of chemical reactions known as the bicarbonate buffer system. This system takes place in red blood cells, this reaction is facilitated by an enzyme called carbonic anhydrase. Then CO₂ can bind to hemoglobin, forming carbaminohemoglobin and this form of CO₂ transport occurs in the peripheral tissues which releases CO₂ when it reaches the pulmonary capillaries in the lungs
write the equation describing the interaction of carbon dioxide with water. include all intermediate products. what enzyme is present in RBC membranes that catalyze this reaction?
CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻ . carbonic anhydrase enzyme catalyzes this reaction and H⁺ binds to hemoglobin in RBC
what is the ‘principle of mass action’ and how does it relate to CO2 transport?
the principle of mass action states that the concentration of products can determine the overall direction of a completely reversible process. It relates to CO₂ transport by reacting with water to create H⁺ and HCO₃⁻
indicate how the following conditions affect local control mechanisms regulate where blood flow is directed in the alveolar capillaries: high PO2 in alveoli; low PO2 in alveoli; high PCO2 in pulmonary capillaries
low alveolar PO₂ causes pulmonary capillaries to constrict, high alveolar PO₂ causes pulmonary capillaries to dilate (blood flow towards alveoli). High PCO₂ causes vasodilation in vessels
indicate what a condition of high alveolar and bronchiolar PCO2 would do to airway resistance
high PCO₂ levels will stimulate bronchodilation, reducing airway resistance. High PCO₂ levels would also decrease blood pH (high PCO₂ levels are associated with H₂CO₃)
list the brain centers in the pons and the medulla that are responsible for regulating (1) normal and (2) forced breathing patterns
the medulla oblangatas dorsal respiratory group is inspiratory muscles and ventral respiratory group is forced inspiratory, forced exhalation muscles. The pons has the pontine respiratory group that sets the rhythm of breathing (both rate and intensity)
describe the role of the dorsal respiratory group in stimulation of respiratory muscles. What role does the pontine respiratory group play in the regulation of breathing?
the pontine respiratory group sets the rhythm of breathing, both the rate and intensity. The dorsal respiratory group is skeletal muscle (you can consciously inhale), which include inspiratory muscles and motor neurons
describe the changes in ventilation upon activation of each of the following: higher brain centers, Hering-Bruer reflex, irritant receptors, central chemoreceptors, peripheral chemoreceptors
the higher brain centers can voluntarily influence ventilation- when activated, these centers and consciously increase or decrease the rate and depth of breathing. For example, when someone is upset, they breath heavier or when someone is exercising, the brain may signal for increased ventilation to meet the higher oxygen demand.
the Hering-Breuer reflex is triggered by stretch receptors in the lung tissue. When the lungs are inflated, stretch receptors send inhibitory signals to the respiratory centers in the brainstem, preventing overinflation of the lungs and regulates the duration of each breath.
irritant receptors are located in the airways and are sensitive to noxious stimuli, like smoke, dust, or irritating gases. This reflex leads to bronchoconstriction and increased ventilation. The goal is to protect the respiratory system from harmful substances by reducing airflow and promoting coughing.
central chemoreceptors are in the medulla oblongata and are sensitive to changes in PCO₂. An increase in PCO₂ stimulates them, leading to an increase in ventilation, helping to remove excess CO₂ and maintain acid-base balance.
peripheral chemoreceptors are in carotid bodies and aortic bodies, and are sensitive to changes in PO₂, PCO₂, and pH. Low PO₂, high PCO₂, or low pH can stimulate these receptors, leading to an increase in ventilation
how can CO2 in the blood stimulate chemoreceptors in the brain that respond to pH changes?
the primary role of central chemoreceptors is to regulate ventilation in response to changes in the partial rpessure of PCO₂ to maintain acid-base balance. First, CO₂ dissolves in the blood and undergoes a chemical reaction with water, then the formation of bicarbonate ion (HCO₃⁻) is formed, central chemoreceptors in the brainstem are sensitive to changes in the concentration of H⁺ ions. An increase in CO₂ results in an increase in H⁺ ions, which stimulates the central chemoreceptors, leading to an increase in the rate and depth of ventilation
how does minute volume change during exercise? why does this change occur?
minute volume (or total pulmonary ventilation) is the total volume of air that moves in and out of the lungs in one minute. Minute volume increases during exercise to meet the increased oxygen demand of the active muscles and to remove additional CO₂ produced during increased metabolism
define the terms hypercapnia and hypocapnia. What are the causes of these conditions? How does the body react to these conditions?
hypercapnia is elevated PCO₂ in the blood, which causes the pH disturbance known as acidosis. This can interfere with hydrogen bonding of molecules, denature proteins, and can depress the central nervous system function, causing confusion, coma, or even death. To prevent this, the body removes CO₂ to maintain homeostasis. Hypocapnia is a reduced level of PCO₂ which can be caused by hyperventilation (a decrease in plasma PCO₂) and can occur from emotional factors like anxiety, stress, or panic attacks. Central chemoreceptors become less sensitive to changes in PCO₂ leading to a decrease in the respiratory drive, helping to reduce the elimination of CO₂ in the blood
list several functions of the kidney in addition to the fact that “it filters the blood”
major functions of the kidney include the regulation blood volume and blood pressure (water loss, erythropoietin, renin), regulation of ion concentrations in plasma (controlling the amount of ions lost), stabilizing pH, conserving nutrients/excreting waste products, assisting the liver in detoxification of waste/metabolites
name the functional unit of the kidney
the nephron!
where are the following vascular components in the kidney and what functions do they perform in the kidney: afferent arteriole, efferent arteriole, glomerulus, peritubular capillaries, collecting ducts, and vasa recta
afferent arteriole - part of Bowman’s capsule, blood flows from renal arteries into this
efferent arteriole - part of Bowman’s capsule, blood leaving the glomerulus goes into this
glomerulus - part of Bowman’s capsule, the site of filtration, a ball-like network of capillary
peritubular capillaries - surround the tubule
collecting ducts - variable water and ion reabsorption, readjusts renal system for what our body needs
vasa recta - long peritubular capillaries that dip into the medulla
differentiate between the following basic kidney functions and identify where in the kidney these functions occur: filtration, reabsorption, secretion, and excretion
filtration - into the nephron tubes, occurs at Bowman’s capsule (can’t go through filter, go to blood), and it is a non-selective process
reabsorption - of solutes/fluids into ECF, occurs throughout nephron tubules and is a selective process.
secretion - of solutes/fluid into nephron tubule lumen and occurs throughout nephron tubules
list and describe all the fluid forces involved in glomerular filtration. Include the average values for each force
glomerular filtration fluid forces: movement of fluid across the filtration membrane; movement of fluid is caused by net filtration pressure (about 10 mmHg), glomerular hydrostatic pressure (GHP, or PH) is higher than capillary pressures and the afferent arteriole is larger in diameter than the efferent arteriole which causes higher pressure (about 55 mmHg, capillary is about 45 mmHg), capsular hydrostatic pressure (CsHP, or Pfluid) is the force working against glomerular filtration pressure (averages about 55 mmHg), net hydrostatic pressure (NHP) is: GFP (or PH) - CsHP (or Pfluid) = NHP which averages at about 40 mmHg (55 mmHg - 15 mmHg = 40 mmHg), blood colloidal osmotic pressure (BCOP or ℼ) is the force that opposes hydrostatic pressure (about 30 mmHg), net filtration pressure (FP= NHP-BCOP) is the force acting to move filtrate out of the plasma (40 mmHg - 30 mmHg = 10 mmHg), and glomerular filtration rate (GFR) is the main function of the kidney which is just your filtration rate
what is the glomerular filtration rate for 1 day?
80 L/day (50 gal)
describe the local autoregulatory mechanisms that adjust glomerular filtration rate
the myogenic response is the intrinsic ability of vascular smooth muscle to respond to pressure changes, the tubuloglomerular feedback is a paracrine signaling mechanism through which changes in fluid flow through the loop of Henle influence GFR
name two conditions (or diseases) that can cause alterations in glomerular filtration rate. how do these conditions alter filtration rate?
chronic kidney disease (CKD) is a disease that is characterized by a gradual and progressive loss of kidney function over time. The structural integrity of the glomeruli is compromised, leading to a reduced surface area available for filtration.
diabetic nephropathy is a complication of diabetes affecting the kidneys, it is a leading cause of CKD. High levels of blood glucose over an extended period can damage the small blood vessels, including the glomeruli. This damage impairs the filtration process and can lead to an increase/decrease in GFR depending on the stage
what is trans-epithelial transport? list the major steps in this process during the process of Na+ reabsorption in the proximal convoluted tubule
a step-wise movement of solutes across cells. Na⁺ is reabsorbed by active transport, then the electrochemical gradient drives anion reabsorption, then water moves by osmosis, following solute reabsorption. Concentrations of other solutes increase as fluid volume in the lumen decreases, and permeable solutes are then reabsorbed by diffusion through membrane transporters or by the paracellular pathway
where else in the body does trans-epithelial transport occur?
in the intestinal epithelium (absorption of nutrients, ions, and water), the respiratory epithelium (respiratory tract- airways and alveoli, movement of O₂ and CO₂), and the blood-brain barrier (salivary glands, sweat glands, and mammary glands)
why can glucose be filtered from the blood but normally is not found in urine excreted?
glucose is typically filtered from the blood by the renal glomerulus and glucose is efficiently reabsorbed by the renal tubules, preventing it from being excreted in the urine, which is essential to maintaining glucose homeostasis in the body
describe the permeability of kidney tubules to water and how that differs in the proximal convoluted tubule, descending and ascending loop of Henle, distal convoluted tubule, and collecting duct. Indicate whether the water permeability in each area is obligatory, facultative, or both
proximal convoluted tubule (PCT) - highly permeable to water, water reabsorption. As solutes are reabsorbed in the PCT, water flows into tubule cell and moves from the tubule cell into the peritubular capillary- moves 108 L/day (of the 180 filtrate/day)
descending loop of Henle - permeable to water and reabsorbs roughly 45 L/day of H₂O. It is impermeable to solutes, the deeper into the medulla you go, peritubular osmolarity increases, and as filtrate moves downward, the more water is reabsorbed.
ascending loop of Henle - impermeable to water but permeable to solutes- transport of Na⁺ and Cl⁻ into peritubular space, Na⁺, K⁺/2Cl⁻ carrier at the apical surface, K⁺ -Cl cotransport and Na⁺ -K⁺ exchange pump at the basolateral surface; K⁺ and Cl⁻ leak channels, it removes ⅔ of all Na⁺ and Cl⁻ from the filtrate. No net loss of K⁺ from the lumen, the more ions are removed at the beginning of the ascending limb- it is the cause of the osmotic gradient in the medulla and contributes to roughly 750 mOsm/L to the medullary osmotic gradient.
distal convoluted tubule - reabsorption of Na⁺ and Cl⁻; Na⁺-K⁺ exchange pump is enhanced by the presence of aldosterone (steroid hormone, slow acting, increases the number of Na⁺ channels and Na⁺/K⁺ pumps, reduces the amount of Na⁺ ions lost in urine) reabsorption of Ca²⁺; primary site for Ca²⁺ reabsorption, reabsorption stimulated by parathyroid hormone (Ca²⁺ homeostasis), stimulating calcitriol synthesis by the kidneys
collecting Tubule - aldosterone sensitive Na⁺/K⁺ exchange pump, bicarbonate reabsorption, urea reabsorption (passive reabsorption in the papillary duct), and water reabsorption
identify the approximate osmolarity of tubule filtrate in all major portions of the nephron
in the PCT, osmolarity is isotonic to plasma (300 mOsm/L) and it reabsorbs water and solutes in a nearly proportional manner, maintaining isotonicity with plasma. In the descending limb of the loop of Henle, becomes progressive the more concentrated as it descends into the medulla, and water is reabsorbed passively, concentrating the tubule fluid as it descends- the solutes (Na⁺ and Cl⁻) are left behind, increasing osmolarity. The ascending limb of the loop of Henle decreases as it ascends, the thick ascending limb actively reabsorbs solutes (Na⁺ and Cl⁻) but is impermeable to water, leading to a dilution of the tubule fluid. The distal convoluted tubule is variable and depends on the hormonal influence, limited water reabsorption, and solute transport. Osmolarity can vary based on the pressure of the antidiuretic hormone. The collecting duct is also variable and depends on hormonal influence
how does Na+ and Cl- reabsorption occur in the ascending loop of Henle? what special transport mechanisms are involved and where are they located in the tubule cell?
sodium reabsorption uses the Sodium-Potassium-Chloride cotransporter (Na⁺K⁺-2Cl⁻ cotransporter, NKCC2) in the apical (luminal) membrane of the tubule cell in the thick ascending limb. NKCC2 actively transports one sodium ion, one potassium ion, and two chloride ions from the tubular fluid into the tubule cell, creating a high concentration of sodium, potassium, and chloride ions within the tubule cell. Chloride reabsorption uses the chloride channel (CIC-Kb) in the apical (luminal) membrane of the tubule cell in the thick ascending limb. The chloride ions that enter the tubule cell via NKCC2 are transported across the apical membrane into the cell’s cytoplasm through chloride channels (CIC-Kb), contributing to the buildup of chloride ions inside the tubule cell
where is sodium reabsorption the greatest in the kidney tubule?
proximal convoluted tubule (PCT)
where is water reabsorption the greatest in the kidney tubule?
collecting ducts
what role does aldosterone play in kidney function?
aldosterone increases the number of Na⁺ channels and Na⁺/K⁺ pumps and reduces the amount of Na⁺ ions lost in the urine
how is aldosterone production stimulated? indicate two different mechanisms that act to stimulate aldosterone production
elevated potassium levels in the blood directly stimulate the adrenal cortex to release aldosterone and the release of renin by the juxtaglomerular cells in the kidneys is triggered by factors such as low blood pressure, low sodium concentration, or low blood volume, then renin acts on angiotensinogen which is converted into angiotensin 1 by an inactive precursor in the liver, then angiotensin 1 is converted into angiotensin 2 by the ACE enzyme, and angiotensin 2 stimulates the adrenal cortex to release aldosterone
describe the renin-angiotensin pathway. Indicate the signals that stimulate the pathway, and include all intermediates and effects on all systems discussed
it begins when juxtaglomerular granular cells in the afferent arterioles of a nephron secrete an enzyme called renin. Renin converts an inactive plasma protein, angiotensinogen, into angiotensin I. When ANG I in the blood encounters an enzyme called angiotensin-converting enzyme (ACE), ANG I is converted into ANG II. It occurs on the endothelium of blood vessels throughout the body. When ANG II in the blood reaches the adrenal gland, it causes synthesis and release of aldosterone. Finally, at the distal nephron, aldosterone initiates the intracellular reactions that cause the tubule to reabsorb Na⁺
what do cells in the juxtaglomerular complex produce and how does that alter renal function?
they are granular cells that secrete the enzyme renin. The release of renin by juxtaglomerular cells initiates the RAAS, which has effects on the cardiovascular system, aldosterone release, and water/sodium reabsorption in the kidneys
explain the regulatory mechanisms for controlling the release of renin
the SNS activation of renin is due to low blood pressure or reduced perfusion of the kidneys that triggers the activation of the sympathetic nervous system, increasing NE which binds to beta-1 adrenergic receptors on juxtaglomerular cells, stimulating the release of renin. Decreased blood pressure and perfusion to the kidneys are sensed by juxtaglomerular cells, reduced stretch of the afferent arterioles, leading to decreased perfusion of the glomerulus, in which juxtaglomerular cells respond to decreased stretch by releasing renin. The baroreceptors in the carotid sinus and aortic arch sense changes in blood pressure, decreased blood pressure triggers baroreceptors to send signals to the central nervous system, and the CNS can influence the release of renin through neural pathways, helping to maintain blood pressure
why is sodium reabsorption linked to high blood pressure?
through its involvement in the renin-angiotensin-aldosterone system (RAAS) and the regulation of blood volume. The sodium pulls water into your bloodstream, but if there is too much sodium, it pulls in too much water. The increase in water increases the blood volume, which increases blood pressure
how can high ECF [K+ ] lead to the production of aldosterone? What effect does Na+ reabsorption have on regulating [K+ ] in the ECF?
if K⁺ intake exceeds excretion and plasma K⁺ goes up, homeostatic mechanisms kick in to get rid of the excess K⁺. Elevated K⁺ levels act directly on adrenal cortex cells to promote the secretion of aldosterone. The reabsorption of Na⁺ in the distal tubules and collecting ducts of the kidney are regulated by aldosterone. The more aldosterone, the more Na⁺ reabsorption, and because one target of aldosterone is increased activity of the Na⁺-K⁺-ATPase, aldosterone causes K⁺ secretion
what are the specific mechanisms (exchange pumps, ion channels, co-transporters, active transporters) that are used in the proximal convoluted tubule to mediate the following substances in the filtrate: Na+ , glucose, H+ ion
the PCT reabsorbs sodium by using the sodium-glucose cotransporter (SGLT) in the apical membrane of the PCT cells. SGLT actively transports sodium ions and glucose molecules together from the filtrate into the tubule cells. The active transporter used is the Na⁺/K⁺-ATPase on the basolateral membrane of the PCT cells. Na⁺/K⁺-ATPase actively transports sodium out of the tubule cells into the interstitial fluid, maintaining a low intracellular sodium concentration and creating a sodium concentration gradient. The PCT reabsorbs glucose by using the sodium-glucose cotransporter (SGLT) on the apical membrane of the PCT cells. SGLT not only transports sodium but also facilitates the cotransport of glucose along with sodium from the filtrate into the tubule cells. It also uses facilitated diffusion with the glucose transporters (GLUT) on the basolateral membrane of the PCT cells. GLUT transporters facilitate the passive diffusion of glucose from the tubule cells into interstitial fluid and then into the peritubular capillaries. The reabsorption of hydrogen ions uses the hydrogen-ion ATPase (H⁺-ATPase) at the apical membrane of the PCT cells. H⁺-ATPase actively pumps hydrogen ions from the tubule cells into the filtrate, promoting the excretion of excess H⁺ ions. It also uses passive diffusion of hydrogen ion exchange on the basolateral membrane of the PCT cells and some hydrogen ions diffuse passively from the tubule cells into the interstitial fluid, maintaining a balance
how is Na+ and Cl- reabsorption mediated in the ascending loop of Henle?
the ascending limp of the loop of Henle uses the Na+-K+-2Cl- Cotransporter (NKCC2) at the apical membrane of cells in the thick ascending limb. The Na+-K+-2Cl- Cotransporter actively transports one sodium ion, one potassium ion, and 2 chloride ions from the tubular fluid into the tubule cells. The energy for this cotransport is derived from the downhill movement of sodium and potassium ions along their respective electrochemical gradients. It also uses the passive diffusion of ions- the thick ascending limb is relatively impermeable to water. As sodium, potassium, and chloride ions are actively transported into the tubule cells via the NKCC2 cotransporter, the ions create a high osmotic concentration in the interstitial fluid. This high osmolarity creates an osmotic gradient that facilitates the passive diffusion of sodium, potassium, and chloride ions through the tight junctions (paracellular pathway) between the tubule cells. The ascending limb also uses the Na+-K+ pump (Na+/K+-ATPase) on the basolateral membrane of cells. The Na+-K+ pump actively pumps sodium out of the tubule cells into the interstitial fluid while transporting potassium ions into the cells. This pump maintains a low intracellular sodium concentration, helping to sustain the active transport of ions from the tubular fluid into the tubule cells
how is the high osmolarity in the kidney medullary region (proximal region) maintained at 1200 mOsm? in other words, what contributes to this high osmolarity?
the concentration is maintained due to the active transport and reabsorption of solutes, particularly sodium, potassium, and chloride ions. This concentrated medullary interstitium is essential for the kidney’s ability to produce concentrated urine
what role does the vasa recta play in maintenance of the osmotic gradient in the kidney medullary region?
the vasa recta uses countercurrent exchange. Running parallel to the loop of Henle, it carries blood in a counterflow to the flow of tubular fluid in the loop of Henle. As the blood flows in the vasa recta, it exchanges solutes with the intersitial fluid surrounding the loop of Henle. Water moves in and out of the vasa recta based on the osmotic gradients created by the exchange of solutes. The countercurrent exchange in the vasa recta prevents the rapid washout of solutes from the meduallary interstitium. The vasa recta helps maintain the high osmolarity in the medullary interstitium, prevent dilution of the osmotic gradient created by the active transport of solutes in the loop of Henle. The slow movement of blood in the vasa recta allows for prolonged contact between the blood and the meduallary interstitium, preventing rapid equilibration of solutes, allowing the osmotic gradient to be maintained over a more extended period
what is the role of ADH in renal function? what cells are responsible for its production, and where does ADH act in the kidney. name specific processes that lead to the effect of ADH
ADH (vasopressin) is used to induce the expression of aquaporin-2 (water channels), which makes the nephron tubules more water permeable (water reabsorption), and by doing this helps concentrate urine. Granular cells respond in the afferent arteriole. Reduced blood volume/ decreased blood pressure is detected by baroreceptors, which triggers the release of ADH to conserve water
name 2 different renal diseases that affect the kidney. explain the mechanism that is altered and what effect the condition has on renal function
gout is a metabolic disease characterized by high blood concentrations of uric acid, monosodium urate precipitates out of solution and forms crystals in peripheral joints, causing periodic attacks of excruciating pain. Uric acid crystals may also form kidney stones in the renal pelvis. polycystic kidney disease is a genetic disorder characterized by the formation of fluid-filled cysts in the kidneys. The cysts gradually enlarge and replace normal kidney tissue, leading to a loss of functional nephrons. Compression of surrounding tissues by the cysts disrupts the normal renal architecture, reduced filtration surface area and impaired tubular function result in a decline in renal function, and can eventually lead to chronic kidney disease and end-stage renal disease, requiring renal replacement therapy like dialysis or transplatation
how does the kidney regulate excess H+ ions in the blood as well as in filtrate? where does this occur, and what types of other molecules and processes are needed in order for this to occur?
The kidneys regulate excess H⁺ in the blood and filtrate to maintain acid-base balance. Filtration begins in the glomerulus, producing a filtrate containing H⁺. In the proximal tubule, bicarbonate ions (HCO₃⁻) are reabsorbed, serving as a buffer by combining with H⁺ to form carbonic acid. The distal tubule and collecting ducts actively secrete H⁺ ions into the filtrate which is influenced by aldosterone. Concurrently, remaining bicarbonate ions are reabsorbed, and ammonia is generated, combining with H⁺ to form ammonium ions. The kidneys also contribute to maintaining other buffer systems, such as the phosphate buffer system. The renin-angiotensin-aldosterone system indirectly influences H⁺ regulation by affecting aldosterone secretion. This intricate interplay of ion transporters, buffer systems, and hormonal regulation ensures the blood pH remains within a narrow range, crucial for cellular function and metabolic processes. The kidneys adjust H⁺ excretion based on blood pH, preventing both acidity and alkalinity extremes.
what is the total distribution of water in the ICF and the ECF of the human body?
The ICF accounts for roughly 28L, while the ECF makes up 14L (25% plasma, 75% interstitial fluid)
how does the body lose water? Indicate all possible mechanisms and their relative contributions to water loss.
urination (renal excretion), sweating, respiration (water vapor is expelled during breathing), fecal excretion, and saliva and digestive secretions
describe the general function of the kidney and thirst centers in terms of fluid regulation.
the primary function of the kidney is to filter and regulate the composition of blood, removing waste products and excess substances while retaining essential components. In terms of fluid regulation, the kidneys maintain water balance by adjusting the excretion or retention of water and electrolytes. This is achieved through processes such as filtration, reabsorption, and secretion in the renal tubules. Filtration - blood is filtered in the glomerulus, forming a filtrate that contains water and various solutes, including electrolytes. Reabsorption - essential substances like water, sodium, and other electrolytes are reabsorbed back into the bloodstream in the renal tubules, preventing their excessive loss in urine. Secretion - unwanted substances, including excess ions and drugs, are actively secreted into the filtrate for eventual excretion in urine. Thirst is the sensation that prompts an individual to seek and consume fluids. The thirst center in the brain, the hypothalamus, plays a crucial role in regulating fluid intake. When the body experiences dehydration or an increase in blood osmolarity (concentration of solutes), osmoreceptors in the hypothalamus are stimulated, triggering the release of antidiuretic hormone (ADH) from the pituitary gland, which acts on the kidneys to retain water.
how does osmolarity and body water volumes change in the ECF and the ICF when ingesting the following: plain water, isotonic saline, salt without water.
Drinking plain water results in an increase in total body water without a proportional increase in solute concentration, resulting in the osmolarity of both the ECF and ICF to decrease. For body water volumes, the ECF and ICF volumes increase, but the increase is more pronounced in the ICF because water moves into cells to equalize osmotic pressure. Isotonic saline has a concentration of solutes similar to that of normal body fluids. Ingesting isotonic saline does not cause a significant change in overall osmolarity. For the body water volumes, isotonic saline is distributed between the ECF and ICF without causing a major shift in water between compartments. Both the ECF and ICF volumes increase, maintaining the balance of osmotic pressures. Ingesting salt without water leads to an increase in solute concentration in the ECF. This results in higher osmolarity in the ECF, drawing water from the ICF to the ECF to equalize osmotic pressure. For body water volumes, the increase in solutes in the ECF causes water to move out of cells, leading to a decrease in ICF volume. While the ECF volume may increase due to the added salt, the overall effect is a reduction in total body water
describe the body’s reflexive homeostatic mechanisms in response to dehydration, low ECF volume, or low blood pressure. Indicate all systems that are affected and how they react to maintain homeostasis. Include details concerning substances and/or receptors that are expressed in response to these changes that mediate these reflexive changes
The renin-angiotensin-aldosterone system (RAAS) - low blood pressure or decreased blood flow to the kidneys stimulates the release of renin from specialized cells in the kidneys called juxtaglomerular cells. Renin acts on angiotensinogen (released by the liver) to produce angiotensin I, which is converted to angiotensin II by the angiotensin-converting enzyme (ACE). Angiotensin II stimulates the release of aldosterone, a hormone that acts on the kidneys to increase sodium reabsorption, leading to water retention and increased blood volume.
Cardiovascular system - low blood pressure activates the sympathetic nervous system, leading to the release of norepinephrine and epinephrine (adrenaline). These hormones act on the heart to increase heart rate (positive chronotropic effect) and contractility (positive inotropic effect), leading to an increase in cardiac output.
Endocrine system - as part of the RAAS response, aldosterone increases sodium reabsorption in the kidneys, leading to water retention and an increase in blood volume. ADH (vasopressin), in addition to its effects on the kidneys, can also cause vasoconstriction, contributing to the maintenance of blood pressure.
Baroreceptor reflex - specialized pressure receptors called baroreceptors are present in the walls of certain blood vessels, such as the carotid sinuses and aortic arch. When these receptors sense a decrease in blood pressure, they send signals to the cardiovascular control center in the brainstem, triggering the sympathetic nervous system to increase heart rate and vasoconstriction
where is aldosterone produced, how is its’ production stimulated, and what is its’ specific action in the human renal system?
aldosterone is a hormone produced by the adrenal glands, in the outer layer called the adrenal cortex, on the top of each kidney. The production of aldosterone is primarily stimulated by the RAAS, which is activated in response to low blood pressure, low blood volume, or low sodium levels. Specialized cells in the kidneys called juxtaglomerular cells release renin into the bloodstream in response to decreased blood flow, low sodium levels, or sympathetic nervous system stimulation. Renin acts on angiotensinogen, a protein produced by the liver, converting it into angiotensin I. Angiotensin II stimulates the adrenal cortex to release aldosterone. Aldosterone enhances the reabsorption of sodium ions from the urine in the distal tubules and collecting ducts. This results in an increased retention of sodium in the body. As sodium is reabsorbed, potassium ions and hydrogen ions are excreted into the urine. This is due to the exchange mechanism in the distal tubules, where sodium is reabsorbed in exchange for potassium and hydrogen ions. The reabsorption of sodium, accompanied by the osmotic movement of water, leads to increased water retention. This contributes to an increase in blood volume and blood pressure.
what is the average pH range for blood?
7.2-7.4
how do the respiratory system, renal system, and chemical buffers function to help maintain homeostatic levels of pH
the respiratory system regulates the levels of carbon dioxide in the blood. Carbon dioxide can combine with water to form carbonic acid (H2CO3). When blood with high levels of CO2 reaches the lungs, CO2 is expelled during exhalation. This reduces the concentration of carbonic acid in the blood. The overall effect is that an increase in CO2 leads to an increase in carbonic acid and H+ ions, making the blood more acidic. By eliminating CO2 through respiration, the respiratory system helps to decrease acidity and raise the pH. The renal system - the kidneys play a crucial role in regulating hydrogen ion concentration and bicarbonate levels. Excess hydrogen ions are excreted in the urine, and bicarbonate ions are reabsorbed back into the blood. The kidneys can also produce ammonia, which combines with hydrogen ions to form ammonium ions (NH4+), facilitating their excretion in the urine. The renal system's actions contribute to maintaining a proper balance of acids and bases in the body, helping to regulate blood pH. Chemical buffer system - bicarbonate ions act as a buffer, readily accepting or donating hydrogen ions to maintain a stable pH. This buffer system is present in both the extracellular and intracellular. The protein buffer system, particularly hemoglobin in red blood cells, can act as a buffer by binding and releasing hydrogen ions. Phosphate ions can also act as buffers to regulate hydrogen ion concentration. Chemical buffer systems act quickly to resist changes in pH by absorbing or releasing hydrogen ions as needed
indicate major buffers used by the human body and their location (ICF, ECF, urine).
HCO₃⁻ in ECF; proteins, hemoglobin, phosphates in ICF; phosphates, ammonia in urine
how does hyperventilation causes alkalosis and hypoventilation cause acidosis?
Hyperventilation (in alkalosis) refers to rapid and deep breathing, leading to an excessive loss of CO2 through the respiratory system. As more CO2 is expelled from the body during hyperventilation, the concentration of carbonic acid in the blood decreases. The decrease in carbonic acid results in a shift in the bicarbonate-carbonic acid equilibrium towards excess bicarbonate ions (HCO3-) in the blood, making it more alkaline (basic). The condition where hyperventilation causes an increase in blood pH is known as respiratory alkalosis. Hypoventilation (and acidosis) hypoventilation is characterized by slow and shallow breathing, leading to inadequate removal of CO2 from the body. As less CO2 is eliminated through respiration, the concentration of carbonic acid in the blood increases. The increase in carbonic acid results in a shit in the bicarbonate-carbonic acid equilibrium towards excess hydrogen (H+) in the blood, making it more acidic. The condition where hypoventilation causes a decrease in blood pH is known as respiratory acidosis.
indicate a metabolic condition that can lead to acidosis and one that can lead to alkalosis. how does the body respond to these changes to maintain homeostasis?
Metabolic acidosis - ex. Diabetic ketoacidosis (DKA) is an example of metabolic acidosis. In DKA, the body produces excessive ketone bodies due to uncontrolled diabetes, leading to an accumulation of acids in the blood. The respiratory system responds by increasing the rate and depth of breathing. This helps expel more CO2, reducing the concentration of carbonic acid (H2CO3) in the blood.The kidneys retain and regenerate bicarbonate ions (HCO3-) to counteract the excess hydrogen ions and maintain a more alkaline environment. The renal response is a slower but more sustained mechanism.
Metabolic alkalosis - ex. Prolonged vomiting, excessive use of certain antacids, or excessive aldosterone production can lead to metabolic alkalosis. These conditions result in an excess of bicarbonate ions (HCO3-) in the blood. The respiratory system responds by decreasing the rate and depth of breathing. This leads to an increase in carbon dioxide (CO2) retention, contributing to the formation of carbonic acid (H2CO3) and promoting a shift towards acidity. The kidneys excrete excess bicarbonate ions (HCO3-) in the urine, further assisting in restoring acid-base balance.
how does the kidney work to retain bicarbonate ions and release hydrogen ions in the urine?
in the renal tubules, especially the distal tubules and collecting ducts, specialized cells actively secrete hydrogen ions into the urine, this is facilitated by proton pumps on the apical membrane of these tubular cells. In the proximal tubule of the nephron, bicarbonate ions (HCO3-) are filtered from the blood into the tubular fluid during the glomerular filtration process. To prevent the loss bicarbonate, the majority of filtered bicarbonate ions are reabsorbed back into blood. In addition to directly secreting hydrogen ions, the kidneys can also generate ammonium ions (NH4+) from ammonia (NH3), ammonia is produced in the tubular cells from the breakdown of amino acids, ammonia combines with hydrogen ions to form ammonium ions, which can be excreted in the urine. The hydrogen ions that are actively secreted into the tubular fluid, along with those formed through the combination of ammonia and hydrogen, contribute to the acidity of the urine. The hydrogen ions are eventually excreted in the urine, helping eliminate excess acid form the body.
how does the kidney produce ammonia (and ammonium) to serve a buffer in urine? Why is this necessary?
the kidneys produce ammonia and its ionized form, ammonium, as part of a complex process to serve as a buffer in urine- this helps the kidneys regulate the acidity of the urine and contributes to the overall acid-base balance of the body: when the body has excess hydrogen ions, the kidneys excrete these ions into the urine. The combination of hydrogen ions with ammonia forms ammonium, which can be excreted in the urine, helping to eliminate excess acid from the body. By excreting hydrogen as ammonium the kidneys contribute to maintaining overall pH balance. Ammonia is produced in the tubular cells of the nephron, particularly in the proximal tubule, as a byproduct of the metabolism of amino acids- amino acids can be broken down in the tubular cells, leading to the production of ammonia. In the tubular lumen, ammonia can combine with excess hydrogen ions to form ammonium ions which are excreted in the urine, contributing to the urine's buffering capacity.
what are the various sources of H+ in the body?
During cellular respiration, cells generate energy by breaking down glucose and other substrates, producing CO₂ and water. Carbon dioxide can combine with water to form carbonic acid (H₂CO₃) which dissociates into bicarbonate ions (HCO₃-) and hydrogen ions
In the kidneys, hydrogen ions can be actively secreted into the renal tubules as part of the urine-forming process: the kidneys can produce ammonia (NH₃) from amino acid metabolism. Ammonia can then combine with hydrogen ions to form ammonium ions, which are excreted in the urine.
(respiratory processes) Carbon dioxide produced during cellular respiration can combine with water in the blood to form carbonic acid. This reaction is reversible, leading to the release of hydrogen ions and bicarbonate ions
how can cells communicate with each other? provide examples from the entire semester to serve as examples of each type of communication.
Gap junctions - specialized channels that directly connect the cytoplasm of adjacent cells. These channels allow for the direct exchange of ions, small molecules, and signaling molecules between cells. They’re common in tissues that require rapid and synchronized responses, such as cardiac and smooth muscle tissues.
Receptor-mediated signaling - signaling molecules, like hormones or growth factors, bind to specific receptors on the surface of target cells. This interaction triggers intracellular signaling cascades that lead to a cellular response.
Intracellular signaling - within a cell, various signaling pathways involve the transmission of signals from the cell membrane to the nucleus or other cellular compartments. This can involve second messengers, like cAMP or calcium ions, and activation of protein kinases or transcription factors.
Paracrine communication - paracrine factors (cytokines) - produced locally by cells, ex. Thromboxane’s, histamine, tissue factors
Synaptic communication - chemicals that bind to receptors onto another cell, travel short distances
what is the function of the hypothalamus with respect to the endocrine system? what are the three ways that the hypothalamus regulates endocrine function?
Secretion of pituitary regulatory hormones (releasing hormones/factors, inhibitory hormones/factors, affects pituitary control of many endocrine organs), sympathetic control over the adrenal medulla (epinephrine, norepinephrine release), directly releases hormones (antidiuretic hormone (ADH)).
where are osmoreceptors located in the human body and how do they function (what do they release and how)?
Osmoreceptors are in the hypothalamus and they release ANP (atrial natriuretic peptide, by cells in the atria of the heart in response to stretch caused by increased blood volume/pressure), ADH release (activation of osmoreceptors stimulates the release of antidiuretic hormone from the posterior pituitary gland), and thirst sensation (when plasma osmolarity increases, indicating higher solute concentration, osmoreceptors signal the brain to initiate the feeling of thirst).
what is the difference between the anterior and posterior pituitary gland?
the anterior pituitary gland regulates the production of the “trophic” hormones, and the posterior pituitary has hypothalamic neurons that release different hormones
list 7 hormones that are released from the anterior pituitary and their target organ/cells.
thyroid-stimulating hormone (helps stimulate production/release of the thyroid hormone), follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone (helps release cortisol), prolactin (helps mammary glands produce milk), growth hormone, and melanocyte-stimulating hormone (if the sun is out, this helps you release/generate melanin).
what hormones are released by the posterior pituitary? where are these substances synthesized and what are their targets in the body?
Osmoreceptive cells release ADH (when osmolarity rises above 280 mOsm, and in high concentration, causes vasoconstriction or ‘vasopressin’) and oxytocin (stimulates smooth muscle contraction: women - uterine contractions, milk let-down response, men - stimulates smooth muscle contraction in sperm duct during ejaculation).
how do peptide hormones cause a cell to respond? what does a peptide hormone directly interact with? provide 2 examples of such a hormone
peptide hormones bind to extracellular receptors on the cell surface (G protein-coupled receptors or tyrosine kinases). Upon binding of the peptide hormone, conformational changes occur in the receptor to activate intracellular signaling pathways. In many cases, second messenger systems such as cAMP. Receptor tyrosine kinases typically activate pathways involving phosphorylation cascades. The activation of second messengers leads to the activation of downstream signaling molecules within the cell, initiating a cascade of intracellular events, often involving the activation/inhibition of enzymes, changes in ion channel activity, and modulation of gene expression. Ex. atrial natriuretic peptide (ANP), erythropoietin (EPO), and angiotensin II.
how do lipid soluble hormones stimulate a cell? indicate one example from the semester that demonstrates this method of cell stimulation.
diffuse through cell membranes, bind to intracellular receptor proteins (cytoplasmic or nuclear location), causes changes in gene expression (ex. aldosterone: increases expression of Na+/K+ pumps, calcitriol: increases expression of calcium) - absorption mechanisms in the distal convoluted tubule.
how do peptide hormones cause a cell to respond? What does a peptide hormone directly interact with? Provide 2 examples of such a hormone.
they bind to specific receptors on the outer surface of the target cell, which activate intracellular signaling pathways through second messenger systems, then the activation of second messengers leads to the activation of intracellular signaling cascades involving protein kinases and other signaling molecules, and the intracellular signaling cascades results in cellular response. Ex. insulin and adrenocorticotropic hormone (ACTH)
what endocrine gland responds when serum Ca++ levels are too high? indicate the hormones involved, the location of synthesis and release, and the actions of the hormone to bring down Ca++ plasma levels.
calcitonin is released by parafollicular (‘C’) cells in thyroid stimulates calcium deposition in bone (osteoblast stimulation), and is released as blood calcium levels rise, with minimal impact in adults- Ca2+ is also filtered and excreted when in excess
what endocrine gland responds when serum Ca++ levels are too low? Indicate the hormones involved, the location of synthesis and release, and the actions of the hormone to bring down Ca++ plasma levels.
the parathyroid hormone is released by the parathyroid gland and increases Ca2+ reabsorption in the kidney and intestine (stimulates calcitriol (D3) release by tubule cells), stimulates degradation of bone matrix (osteoclasts stimulated), and release as blood calcium levels fall.
what endocrine gland(s) and cell type respond when serum levels of glucose are rising and what does the released hormone do to cells that respond to it?
insulin; made by beta cells - works to lower blood glucose, increases the rate of glucose transport into cells, rate of glucose utilization in ATP synthesis, rate of glucose to glycogen, amino acid uptake and protein synthesis, and triglyceride synthesis in adipocytes.
what endocrine gland(s) and cell type respond when serum levels of glucose are low and what does the released hormone do to cells that respond to it?
glucagon; made by alpha cells - works to raise blood glucose levels, increases the rate of glycogen breakdown in the liver/muscle, rate of fats to fatty acids (adipocytes), and rate of glucose synthesis in the liver (“gluconeogenesis”)
what does the release of insulin do to a cell that typically responds to it? what receptor does it interact with and what does that receptor activation do?
the release of insulin works to lower blood glucose and it is made by beta cells and plays a role in glucose homeostasis. It interacts with the insulin receptor leading to the autophosphorlation of tyrosine on the receptor itself.
what is the functional difference between ionotropic and metabotropic receptors?
ionotropic receptors are ligand=gated ion channels that directly allow ions to pass through the cell membrane when they bind to their respective ligands (neurotransmitters or other signaling molecules). These lead to rapid changes in the membrane potential. Metabotropic receptors are coupled to intracellular signaling pathways through G proteins that don’t have an intrinsic ion channel but instead activate second messenger systems inside the cell. These are slower and have a more prolonged response.
indicate the main ways that G-protein mediated signal transduction can cause responses in the cells which have G-protein coupled receptors. what causes some of the pathways to be ‘inhibitory’ while others ‘excitatory’?
cAMP - activation of certain GPCRs (G-protein coupled receptors) leads to the stimulation of adenylate cyclase, an enzyme that produces cyclic adenosine monophosphate (cAMP) from ATP- increased levels activate protein kinase which phosphorylates target proteins, leading to changes in cellular activity
Phospholipase C (PLC) pathway - activation of other GPCRs stimulates phospholipase C (PLC) which cleaves phosphatidylinositol into inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 releases calcium from intracellular stores, leading to various cellular responses, while DAG activates protein kinase, contributing to further downstream signaling.
Inhibitory pathways - lead to decreased cAMP levels, decreased PKA activity, and modulation of ion channel activity.
The determination of whether a GPCR-mediated pathway is excitatory or inhibitory is primarily dictated by the specific G protein subtype involved - G proteins are classified into different subtypes based on their alpha subunit (Gs, Gi, Gq) Gs proteins stimulate adenylate cyclase, leading to excitatory responses, Gi proteins inhibit adenylate cyclase, leading to inhibitory responses, and Gq proteins activate PLC, leading to excitatory responses.
what are the major types of hormones that are produced in the human body? provide an example of each
peptide hormones (insulin, produced by beta cells in the pancreas), steroid hormones (testosterone, produced by testes and in smaller amounts by the ovaries and adrenal glands), amino acid-derived hormones (thyroxine, made by the thyroid gland), monoamine hormones (epinephrine, secreted by the adrenal medulla), eicosanoids (prostaglandins, produced by various cells in the body), gaseous hormones (NO, synthesized in various tissues, including blood vessels)
what generally do lipid-soluble hormones do to cells and how do they cause these effects? Provide one example of this mechanism that has been mentioned in this course.
these hormones are able to diffuse through the cell membrane due to their hydrophobic nature, once inside they bind to a specific intracellular receptor, and the hormone-receptor complex then modulates gene transcription and subsequent protein synthesis: first, lipid-solluble hormones are able to pass through the cell membrane because they can dissolve in the lipid bilayer, once inside the cell these hormones bind to specific receptors located int he cytoplasm or nucleus, then the hormone-receptor complex is formed upon binding, leading to a conformational change in the receptor. The hormone-receptor complex translocated into the nucleus if the receptor is initially located in the cytoplasm, within the nucleus the hormone-receptor complex binds to specific DNA sequences, located in the regulatory regions of target genes. The binding initiates/enhances the transcription of these target genes, leading to the synthesis of messenger RNA and the mRNA exits the nucleus and enters the cytoplasm, where it directs the synthesis of new proteins by the cellular machinery. Ex. thyroid hormones - triiodothyronine (T3) and thyroxine (T4).
discuss the similarities/differences between the three major types of muscles and how they function in the body. Focus primarily on the mechanisms of contraction and relaxation
Skeletal muscle - skeletal muscles are attached to bones by tendons and are under voluntary control, having a striated appearance under a microscope due to the organization of sarcomeres. Contraction - initiated by nerve impulses (action potentials) from the somatic nervous system, the AP travels along the sarcolemma (muscle cel membrane) and into the t-tubules, calcium ions are released from the sarcoplasmic reticulum in response to the AP, calcium binds to troponin, leading to a conformational change that exposes the myosin-binding sites on actin, myosin heads bind to actin and form cross=bridges and ATP is hydrolyzed to provide energy for the power stroke, then the sarcomere shortens as myosin pulls actin filaments toward the center, causing muscle contraction. Relaxation - nerve impulses cease, and calcium ions are actively pumped back into the SR, troponin-tropomyosin complex covers the myosin-binding sites on actin, preventing further cross-bridge formation, ATP is required for the detachment of myosin heads from actin, allowing the muscle to relax.
Smooth muscle - smooth muscles are found in the walls of organs, blood vessels, etc. They lack striations and are under involuntary control. Contraction - initiated by stimuli like hormones, stretch, or nerve impulses, calcium ions enter the cell from the ECF and are released from the SR, calcium binds to calmodulin and activates the enzyme myosin light-chain kinase (MLCK), MLCK phosphorylates myosin, allowing it to bind to actin and form cross bridges, the myosin heads undergo a power stroke, causing contraction. Relaxation - calcium is actively pumped out of the cell or back into the SR, dephosphorylation of myosin by myosin light-chain phosphatase leads to the detachment of myosin from actin, resulting in relaxation.
Cardiac muscle - found in the heart, striated, and under involuntary control. Contraction - initiated by a spontaneous AP is generated in pacemaker cells, calcium influx during the AP triggers the release of additional calcium from the SR, and calcium binds to troponin, initiating the contraction, cardiac muscles are interconnected by intercalated discs, allowing for coordinated contraction. Relaxation - calcium is actively pumped out of the cell or back into the SR, troponin-tropomyosin complex covers the myosin-binding sites on actin, preventing further cross-bridge formation, ATP is required for the detachment of myosin heads from actin, allowing the muscle to relax.
discuss what role Ca++ plays in at least 3 different physiological processes that have been covered this semester.
calcium is needed for smooth and skeletal muscle contraction - it binds to troponin causing the necessary change in the troponin-tropomyosin complex to expose the myosin binding sites. It’s needed for neurotransmitter release at the synapse - when an AP reaches the axon terminal of a neuron, voltage-gated calcium channels open, allowing for the influx of calcium ions into the terminal which triggers the fusion of synaptic vesicles with the presynaptic membrane, releasing neurotransmitter into the synaptic cleft. It’s needed for cardiac contraction and rhythm - calcium influx during the AP in cardiac muscle cells triggers the release of additional calcium from the sarcoplasmic reticulum which initiates the contraction of cardiac muscles, leading to systole.
indicate how renal, respiratory, cardiac, muscle, and nerve function can be altered by high [K+ ]out(hyperkalemia). answer in terms of effects on membrane potential, ion regulation, and functional consequences, including the various homeostatic control mechanisms that may be triggered to respond to these changes.
Renal function - in renal tubular cells, an elevated extracellular potassium concentration can lead to depolarization of the cell membrane, and hyperkalemia can impair the ability of the kidneys to excrete potassium into the urine, reduced potassium excretion contributes to elevated plasma potassium levels, which could result in renal failure. Respiratory function - can affect the resting membrane potential of respiratory muscles and neurons, the respiratory system does not directly regulate potassium levels, but alterations in membrane potential can impact neural control of respiratory muscles, hyperkalemia-induced changes in neural control may contribute to respiratory muscle weakness or paralysis, affecting ventilation.
Cardiac function - elevated extracellular potassium levels can lead to depolarization of cardiac cell membranes, can interfere with the normal repolarization phase of the cardiac AP affecting ion channels involved in repolarization, severe hyperkalemia can lead to cardiac arrhythmias, including ventricular fibrillation and cardiac arrest.
Muscle function - can lead to membrane depolarization in skeletal and smooth muscle cells, disruption of potassium homeostasis can impair the normal function of potassium channels, impacting muscle cell excitability, may result in muscle weakness or in severe cases, muscle paralysis.
Nerve function - elevated potassium levels can depolarize neuronal membranes, altered potassium gradients can affect the resting membrane potential and excitability of neurons, and may lead to neurological symptoms such as paresthesia’s, weakness, or neurological dysfunction.
Homeostatic control mechanisms - The kidneys may increase the excretion of potassium in the urine to combat this. Insulin facilitates the movement of potassium from the ECF into cells, contributing to the temporary lowering of plasma potassium levels. In conditions associated with metabolic acidosis (which can accompany hyperkalemia), respiratory compensation may occur, altering ventilation to help correct acid-base imbalances.
how does homeostatic regulation occur? provide an example from 3 systems studied where homeostatic regulation occurred, and indicate (1) what is being regulated and (2) how it functions as a negative feedback mechanism.
Thermoregulation - regulates body temperature; when the body temperature rises above the set point, thermoreceptors in the skin and hypothalamus detect change, the hypothalamus sends signals to initiate cooling mechanisms, such as sweating and vasodilation of blood vessels, allowing heat dissipation. If the body loses heat, the temperature needs to return to the set point, thermoreceptors signal the hypothalamus to activate warming mechanisms, such as vasoconstriction and shivering. This negative feedback loop helps maintain the body temperature within a narrow rage, despite external environmental changes.
Blood glucose regulation - blood glucose is being regulated; after consuming a meal, blood glucose levels rise, the pancreas detects the increase and releases insulin into the bloodstream, insulin stimulates cells to take up glucose for energy or storage, and the liver converts glucose into glycogen. As a result, blood glucose levels decrease. Between meals, when blood glucose levels drop, the pancreas releases glucagon which signals the liver to convert glycogen into glucose and release it into the bloodstream.
Blood pressure regulation - blood pressure is being regulated; when blood pressure increases above the set point, baroreceptors in the walls of blood vessels detect changes, the baroreceptors send signals to the cardiovascular center in the brain, which send signals to decrease the heart rate and cause vasoconstriction. These actions reduce cardiac output and peripheral resistance, leading to a decrease in blood pressure. If blood pressure drops below the set point, the baroreceptors signal the cardiovascular center to increase heart rate and vasoconstriction.
provide examples from the semester that indicate the ways that the nervous system can regulate the function of all other systems studied this semester in maintaining homeostasis. be able to provide an example of a “reflex control mechanism” that supports this role of the nervous system.
Cardiovascular system - the autonomic nervous system regulates heart rate and blood vessel diameter to control blood pressure; (baroreceptor reflex) when blood pressure increases, baroreceptors in the walls of the blood vessels detect the change, and sensory information is transmitted to the cardiovascular center in the brain via the glossopharyngeal nerve, the brain initiates responses, such as decreasing heart rate and vasodilation through the parasympathetic branch of the ANS.
Respiratory system - the respiratory centers in the brainstem control breathing rate and depth to maintain appropriate oxygen and carbon dioxide levels; (chemoreceptor reflex) peripheral chemoreceptors, located in the carotid and aortic bodies, detect changes in blood oxygen and carbon dioxide levels, the sensory information is transmitted to the respiratory centers in the brainstem via the glossopharyngeal and vagus nerves, the brainstem adjusts respiratory rate and depth to restore normal blood gas levels.
Sensory system - the nervous system processes sensory input from various sensory receptors to perceive and respond to the environment; (withdrawal reflex) when a person touches a hot surface, pain receptors (nociceptors) in the skin detect the stimulus, sensory neurons transmit the pain signal to the spinal cord, the spinal cord generates a rapid motor response, causing muscles to contract and move the body part away from the painful stimulus.
Muscular system - motor neurons from the nervous system control skeletal muscle contraction, allowing for voluntary movement and maintaining muscle tone; (stretch reflex) when a muscle is stretched, muscle spindles detect the change in muscle length, the sensory information is transmitted to the spinal cord via the dorsal root of the spinal nerve, the spinal cord responds by activating motor neurons that cause the muscle to contract, preventing overstretching.