Midterm 3 Physio

  1. Cardiovascular System
    Heart, blood vessels and blood
  2. Lymphatic system
    Lymph vessels, lymph, lymphoid organs and nodules
  3. Function of the cardiovascular system
    • Transport or supply system for cells in multicellular organisms: of oxygen, nutrients, wastes, hormones
    • Homeostasis: the plasma levels of physiological paremeters are what is regulated: pH, temperature, salts, water, fuel molecules, oxygen and B
    • Protection: clotting mechanism and part of immune system
    • Also used to transport heat and to transmit force-ultrafiltration in the kidney, erection
  4. Function of lymphatic system
    • Circulatory part=vessels and lymph, return filtered plasma to CV, transport fats from villi
    • Immune part=lymphoid tissue in nodes, spleen, nodules help to protect from microbes and cancer
  5. Blood
    a complex connective tissue, cosists of fluid and cells
  6. Heart
    Main propulsive organ, forces blood around body
  7. Vessels-arteries
    • Distribute blood to cells, pressure reservoir
    • Arteries
    • Arterioles
    • Capillaries
    • Venules
    • Veins
  8. arterioles
    main site of regulation of blood flow and pressure
  9. Capillaries
    Where transfer of materials occurs between blood and tissues
  10. Venules
    bring blood to veins
  11. veins
    return blood to heart, volume reservoir
  12. lymphatics
    blind end tubes, drain extracellular fluid, return fluid to blood
  13. Interstitial fluid
    plasma filtered from capillary beds (no cells, proteins) tissue fluid, bathes cells
  14. cytosol
    tissue fluid that crosses cell membranes
  15. lymph
    interstitial fluid taken up by lympahtic capillaries
  16. pericardium
    fibrous sac enclosing the heart
  17. atria
    chambers that connect veins and ventricles
  18. ventricles
    chambers whose contractions drive the blood
  19. valves
    atrioventricular, pulmonary, aortic
  20. myocardium
    • heart muscle, has 2 functions, carried out by 2 different cell types:
    • contractile: produces force
    • conducting: initiates and spreads heart beat
  21. Coronary arteries
    feed the heart tissue
  22. Heart Beat
    • Rythmic contraction of whole muscle mass
    • Like skeletal muscle contraction except beat is initiated by APs in pacemaker cells these are capable of spontaneous activity
    • AP spreads to the whole heart via the electrical coupling (gap junctions) between cells
  23. cardiac cycle
    refers to the repeating pattern of contraction and relaxation of the heart
  24. systole
    ventricular contraction and blood ejection
  25. diastole
    ventricular relaxation and blood filling; followed by atrial contraction
  26. Cardiac Cycle steps
    • 1. atria and ventricles relax
    • 2. atria contract
    • 3. isometric ventricle contraction, AV valves closed
    • 4. Isotonic ventricle contraction, semilunar valves open, blood ejection
    • 5. isometric ventricular relaxation
  27. 2 kinds of cardiac cells and APs
    • pacemaker cells
    • myocardial cells
  28. Pacemaker cells
    • Have a slow, spontaneous depolarization. Due to fast Ca channels
    • Purpose-cardiac muscle can stimulate its own contraction, independent of nerve signals, which are used to effect changes in rate of heart beat.
  29. myocardial cells
    • have delayed repolarization mechanism: depolarization is due to opening of Na channels
    • Slow voltage gated Ca channels
    • Purpose: the long duration of the cardiac AP prevents summation and tetanus. Ensures that the heart beats in single twitches
  30. Transmission of cardiac AP
    • Effected by special conducting system which transmits APs initiated by pacemaker cells to entire organ: SA node --> AV node --> bundle fibers --> purkinje fibers
    • SA node serves as pacemaker because it has the fastest rate of spontaneous depolarization
  31. P wave
    depolarization of the atria
  32. QRS wave
    depolarization of ventricles (repolarization of atria in QRS)
  33. T wave
    repolarization of ventricles
  34. Venous System
    • return blood to heart. volume reservoir
    • Pressure is much lower in veins, return to heart is aided by; smooth muscle in vein walls, valves, skeletal muscle contractions, AV CT wrapping, the decrease in thoracic pressure caused by inspiration
  35. Capillaries
    • composed of only a single layer of endothelium which allows water and solutes to diffuse into ECF.
    • Every cell is no more than 3-4 cells away from a capillary
    • Capillaries have pre-capillary sphincters which control blood distribution
    • Blood can be shunted away from capillary beds, goes from arteriole to metarteriole to venule
    • There must be a shunting of blood between capillary beds, no more than 30-50% can be open at one time, because there is not enough blood!
  36. Capillaries
    They are the site of nutrient and waste exchange between blood and individual cells (via intersitial fluid) movement of substances across capillary walls is driven by BP and concentration
  37. Capillary anatomy
    • what moves and how is a function of capillary anatomy-capillary walls are specialized for different degrees of permeability in different organs
    • Continuous
    • Fenestrated
    • Sinusoidal
  38. Continuous Capillary
    caps in CNS, muscle, lung
  39. Fenestrated
    In kidney, intestine, endocrine glands
  40. Sinusoidal
    • Discontinuous
    • In marrow, liver, spleen
    • Cells and proteins can cross these cap walls
    • Hydrophobic substances cross cell membranes, hydrophillic use channels, large molecules use pores
  41. Mechanism for bulk flow/filtration
    • (Starling's Law of the Capillary)
    • Hydrostatic pressure drives fluid out of the capillary
    • Proteins stay in and constitute an osmotic force; exceeds the blood pressure at end of a capillary bed
    • Fluid is sucked back into capillary at venous end
    • due to high BP in mammals/birds-fluid remains in interstitial space and must be returned to heart ny lymphatic vessels
  42. Cardiac Output
    volume of blood pumped/unit time by each ventricle
  43. Stroke volume
    volume of blood pumped out per beat
  44. CO=HR x SV
  45. Control of heart rate
    • 1. parasympathetic nerves (ACh) descrease HR
    • 2. sympathetic nerves and adrenalin increase HR
    • Autonomic control of HR is mediated by cardiovascular center in medulla; emotions, stress, exercise, pH changes
    • Mechanism is change in speed of pacemaker cell depolarization
  46. Control of stroke volume
    • SV is increased by more forceful contractions acheived two ways:
    • 1. Increase in venous return or end diastolic volume (intrinsic control) Heart contracts more forcefully when stretched (starlings law)
    • Result is that all blood coming in gets pumped out
    • 2. Increase in force of contraction-Sympathetic nerves and adrenalin act on contractile cells (as well as pacemaker cells) and cause an increase in force of contraction-more Ca channels are opened which increases number of active crossbridges --> greater contractile force, stimulates Ca uptake pump --> shortens relaxation time (extrinsic control)
  47. Calciums role in cardiac physiology
    • Accounts in part for pacemaker potential in pacemaker cells
    • accounts for upswing of AP in pacemaker cells
    • sustains long depolarization of contractile cells
    • can effect increased strength of contraction-->increased SV
  48. Hemodynamics
    • Relationship between pressure and flow and resistance F=P/R or P= FxR
    • F=flow=volume/unit time
    • P=hydrostatic pressure, mm Hg, generated by the heart
    • R=resistance, a result of blood viscocity and vessel diameter
    • Blood flow is directly proportional to BP, inversely proportional to resistance=vessel diameter arterioles offer greatest resitance to flow and their diameter can be changed=main way flow is controlled
  49. Intrinsic Control
    • Local control of arterioles --> tissue/blood exchange of nutrients and wastes
    • Purpose: the most active tissue gets the most blood flow
    • Mechanism 1: there are chemical changes in ECF associated with active tissues: Increase in CO2, temp and decrease in oxygen and pH: these act locally on precapillary sphincters causing relaxation
    • More blood delivered to active tissues: heat, cold, histamine also act locally to influence blood flow
    • Mechanism 2: myogenic mechanism. If blood flow is low, arterioles dilate, constrict if stretched
  50. Extrinsic Control
    • Nervous and Hormonal control of arterioles --> control of blood flow and distribution
    • Purpose: control BP, adjust flow for temp regulation; exercise need; blood flow must be allocated, only 30-50% of capillary beds can be perfused at one time
    • Mechanism: arterioles are constricted or dilated by arteriole smooth muscle
  51. Hormone regulation of arteriole smooth muscle
    • Epinephrine-primary effect is via beta blockers --> dilation in skeletal muscle arterioles
    • Angiotensin II-constricts most arterioles
    • ADH (vasopressin) vasoconstricts and increases blood volume
  52. Blood Pressure
    • Controlled because this is the force that delivers nutrients to cells a homeostatically regulated parameter
    • Highest in arteries, decreased arterioles and is low in capillaries and veins. Pressure varies with phases of cardiac cycle
  53. Measurement of Blood Pressure
    Done with pressure cuff, stethescope and sphygmomanometer; listen to arterial blood sounds. Measure systolic and diastolic pressure. Normal is 120/80
  54. Equation for Cardiovascular Physiology
    BP=CO (HR x SV) x AR
  55. NFL for BP
    • Sensor: baroreceptors, 2 primary ones are aortic and carotid baroreceptors. These are finely branched nerve endings in part of artery wall, sense stretch. Firing rate increases in response to stretch
    • Integrator: Medullary cardiovascular center in medula. This center receives other input, integrates and regulates to a set point
    • Effector: Heart and arteriole muscle
  56. Other Effectors of Blood Pressure
    • Chemoreceptors for oxygen and CO2 primarily influence respiration
    • Certain behaviors and emotions
    • Exercise and the anticipation of exercise
    • Temperature feedback loops integrated by hypothalamus will dilate blood vessel in skin for cooling; can override baroreceptor dictated vasoconstriction orders
  57. Intermediate regulation of Blood Pressure
    • Fluid Shift-fluid can be shifted between blood and interstitial space through capillaries.
    • Mechanism: Starling's law of capillary. Increase BP drives fluid out of capillaries, lowers return and CO --> lower BP
  58. Long Term Relation-Regulation of body fluid volume by kidney
    • Decrease in body fluid will lower blood pressure, an increase will raise BP
    • Kidney senses BP via juxtaglomerular apparatus, effects adjustments:
    • Aldosterone-stiumulates Na retention and concomitant water retention
    • Angiotensin-stimulates vasoconstriction and thirst
    • ADH-released reflexly via osmoreceptors in hypothalamus, acts on kidney to promote water retention. Is also a vasoconstrictor (other name is vasopressin)
  59. Respiration
    Entire sequence of events in exchange of oxygen and CO2 between environment and cells, where oxygen is used for internal or cellular respiration.
  60. Events with Respiration
    • 1. Breathing or ventilation-moving air in and out of lungs
    • 2. Exchange of gases-between air and lungs and blood in pulmonary capillaries by process of diffusion
    • 3. Transport of gases in blood to/from cells
    • 4. Exchange of gases between blood and cells, by process of diffusion
    • Respiratory sys. performs events 1 and 2. Circulatory sys. performs events 3 and 4.
  61. Other functions of respiratory system
    pH regulation, defense vs. invaders, site of water and heat loss, vocalization, enhances venous return.
  62. Respiratory airways
    Tubes that carry air from atmosphere to alveoli: nasal passages, trachea, larynx, bronchi, bronchioles. The airways are the conducting zone of respiratory sys., serve to warm, humidify, purify air
  63. Lungs
    Hollow invaginated respiratory surface, consist of branched airways, elastic tissue, capillaries, alveoli.
  64. Alveoli
    small, thin walled sacs encircled by pulmonary capillaries; these are the actual site of gas exchange, gas must cross 2 cells: alveolar type I cell and pulmonary capillary endothelial cell. This respiratory epithelium must be thin, moist and lined with surfactant which reduces surface tension. Also must have very large surface area.
  65. Ventilation
    • exchange of air between atmosphere and alveoli
    • Air flow=pressure/resistance
  66. Mechanism of Air Flow
    • Pressure Gradients
    • Air moves into and out of the lungs down pressure gradients; 2 pressure differences are important (Atmopsheric pressure is 760 mm/Hg)
    • Alveolar (intrapulmonary) pressure (inside lungs) can equilibrate with atmopsheric pressure. Changes in alveolar pressure are achieved by respiratory muscles that expand thoracic cavity: this expands volume which reduces pressure (Boyle's Law) and air flows in.
    • Respiratory muscles=inspiration = diaphragm and external intercoastals
    • Expiration is usually passive relaxation, can be active using abdominals and internal intercostals.
  67. Pneumothorax
    If chest is punctured, lungs collapse
  68. Airway Resistance
    • Normally not a significant determinant of flow, although smooth muscles in bronchioles are innervated by S/PS system.
    • Epinephrine is poweful bronchiodilator
    • Disease have major impact-chronic obstructive pulmonary diseases: bronchitis, asthma, emphysema
  69. Lung Anatomy
    • Lung tissue must be stretchable and elastic
    • Lung compliance=the stretchability of lungs, how much they expand for any given pressure change. If lungs are stretchy, it is easier to breath; a function of elasticity of tissue and reduction of surface tension in water lined alveolar sacs.
    • Surface tension aids in elastic recoil of lungs, but can cause collapse of lungs. This is prevented by surfactant, a phospholipid and protein mixture (missing in premature infants)
  70. Lung Volumes
    • Measured with spirometer
    • Lungs never completely empty-would be hard to re-expand and not all air gets to alveoli, there is a respiratory dead space
  71. Tidal Volume
    • Volume air entering/leaving in one breath.
    • Normal breathing. Tides go in and out
  72. Inspiratory reserve volume (IRV)
    Extra for maximum inspiration
  73. Inspiratory Capacity (IC)
    Total inspiration (TV + IRV)
  74. Expiratory Reserve Volume (ERV)
    Extra for maximum expiration
  75. Residual Volume (RV)
    What can't be blown out
  76. Vital Capacity (VC)
    • TV + IRV + ERV
    • Maximum volume of air in one breath. Deepest breath in and deepest breath out.
  77. FEV1
    Forced expiratory volume, amount of air that can be forcibly exhaled in 1 second.
  78. Total Lung Capacity
    VC + RV
  79. Restrictive Diseases of Lungs
    Due to lung damage. Will have poor vital capacity
  80. Obstructive diseases of Lungs
    Due to block in airway, will have poor expiratory volume (FEV1)
  81. Partial Pressure Gradients
    • Oxygen in alveoli is 100 mm/Hg (Less atmospheric conditions due to humidification, low gas turnover in alveoli)
    • Oxygen in venous blood is 40 mm/Hg. The difference of 60 is the driving force to load blood with oxygen
    • CO2 in venous blood is 46 mm/Hg 40 in alveoli. CO2 leaves blood.
  82. Surface area and Thickness of respiratory epithelium are also important
    • Can be varied due to exercise-open more pulmonary capillaries and stretch alveoli with deeper breathing.
    • And in various disease states:
    • Emphysema-many alveolar walls are lost
    • Pulmonary edema-increased interstitial fluid due to conjestive heart failure
    • Pulmonary Fibrosis-Replacement og alveolar wall with thick fibrous tissue in response to chronic irritation
    • Pneumonia-fluid accumulation in alveoli, due to bacterial or viral infection of lungs, aspiration of fluids
  83. Partial Pressures-Exchange at tissue level
    • also occurs by passive diffusion, driven by partial pressure gradients
    • P of oxygen in arterial blood is 100, is 40 40 or below in systemic tissues. P of carbon dioxide is 46 in tissues and 40 in blood
    • With increased cellular respiration, P values for oxygen fall, carbon dioxide rise and an even greater gradient is created
  84. Pulmonary Circulation-Low Pressure System
    • The pul. circulation has the same cardiac output as systemic, but much less resistance therefore much lower pressure
    • When cardiac output increases (exercise) more pulmonary vessels open and the arteries expand because they are compliant. No change in pressure and increase in functional lung surface area.
    • The low pressure protects delicate lung tissue and favors fluid reabsorption at the end of capillary beds which protects lungs from edema
  85. Pulmonary Circulation-Ventilation
    • Perfusion matching: local control
    • It is important to match airflow and blood flow in lungs for efficient exchange.
    • There can be variations in both due to gravity and some disease states
    • Mechanisms for change:
    • Recruit additional capillary beds when BP rises. Capillaries can collapse if pulmonary BP is too low.
    • Both bronchioles and arterioles have smooth muscle which is responsive to local concentration of oxygen and carbon dioxide.
    • Low oxygen/high CO2 causes pulmonary arteriole constriction-bronchiole relaxation.
  86. Gas Transport-Oxygen
    • Some oxygen is delivered in blood but most is carried in hemoglobin.
    • Necessary because of low oxygen solubility in plasma and high oxygen needs of body
    • Hb is a tetramer protein (globin) and 4 iron containing heme groups
    • Oxygen binds loosely with iron portion of Hb; other substances can bind also
  87. Role of Hemoglobin
    • Increases carrying capacity of the blood.
    • Carries a maximum of 4 molecules of oxygen.
    • Saturation depends on the number of Hb Oxygen sites occupied
    • Located in RBCs-little or no osmotic effect in blood; maintains pressure diffusion gradient by storing oxygen
  88. Factors determining % Hb saturation
    • Oxygen dissociation curve
    • At high P O2, oxygen is loaded and at low P O2, oxygen is unloaded
    • Curve is sigmoid shape due to coopertivity (Oxygen on #1 heme facilitates binding of #2-People getting in row boat)
    • An increase in carbon dioxide, H+, temperature or DPG will shift curve to right, therefore at any P O2, Hb has lower affinity for oxygen.
  89. Oxygen Dissociation Curve
    • The affinity of Hb for oxygen changes with its state of oxygen saturation
    • Flat portion-P O2 found in pulmonary capillaries: change here (altitude) will not affect oxygen loading in lungs
    • Steep portion-P O2 found in systemic capillaries: a small change here will unload significantly more oxygen.
    • At lower levels of P O2, such as are foudn in systemic capillaries, there is a greater change in % Hb saturation got a given drop in P O2 than is found at high P O2 levels
  90. What is carbon dioxide carried in the blood? 3 Ways
    • 1. Dissolved-about 10% of the load is physically dissolved in plasma
    • 2. Bound to hemoglobin-carbamino hemoglobin, carries about 20%
    • 3. Transported as bicarbonate-about 70%
    • Equation:
    • Carbon Dioxide + water <--> H2CO3 <--> HCO3- + H+
  91. What is happening in this equation:
    Carbon Dioxide + water <--> H2CO3 <--> HCO3- + H+
    • The first reaction is catalyzed by carbonic anhydrase, an enzyme found in RBCs
    • The bicarbonate diffuses from RBCs to plasma (Cl enters cells to balance charge, called the chloride shift)
    • The H+ binds to Hb and helps unload oxygen (binding of CO2 also unloads oxygen)
    • The affinity of Hb for oxygen is lower when pH is lower and when pH is higher-called the Bohr effect
    • The fact that the unloading of oxygen facilitates carrying of CO2 and H+ is called the Haldane effect
    • These reactions are reversed in the lungs: Oxygen is loaded and CO2 is unloaded.
  92. What are three ways to control respiration?
    • 1. Respiratory centers in brain-generate the normal breathing pattern. The primary control center is the medulla respiratory center. This generates cyclical signaling via motor nerves to respiratory skeletal muscles.
    • There are groups of inspiratoy and expriatory neurons, these are pacemaker neurons.
    • -->Note the difference relative to heart which has intrinsic pacemaker neurons
    • 2. Stretch receptors: located in smooth muscles of bronchioles and bronchi, when activated help to terminate inspiration
    • 3. Chemoreceptors: part of the NFL for control of oxygen.
    • Sensors-chemoreceptors
    • Integrator-medullary respiratory center
    • Effectors-Muscles (Diaphragm)
  93. Control Neurons in the Pons
    • Pneumotaxic Center-helps to switch off inspiration
    • Apneustic center-prevents inspiratory neurons from being shut off.
  94. Peripheral Chemoreceptors
    • These contain specialized cells (glomous cells) that detect oxygen, carbon dioxide, and H+ levels in blood, synapse with nerves that go to medullary resp. center; located in carotid and aortic bodies
    • Response to each parameter varies:
    • Low oxygen-response of increased ventilation only if P O2 is very low=emergency protection for severe oxygen depletion which depresses medulla respiratory center; not normally useful because of safety margin in Hb saturation curve
    • High H+-this is most important response, important in acid/base balance of blood; respiration changes can compensate for non-respiratory induced abnormalities in H+ such as certain foods or lactic acid from exercise (Kidneys are critical for pH regulation-only place to excrete H+, compensate for respiratory acidosis, alkalosis)
  95. Central Chemoreceptors
    • Are located in the medulla and respond to plasma carbon dioxide in brain CSF
    • This is dominant control of respiration
    • Note: they actually measure H+ but only derived from CO2 via carbonic anhydrase conversion; they cannot respond to arterial H+ changes since H+ does not cross blood brain barrier.
    • Collectively the chemoreceptors maintain the arterial blood gas composition with very precise regulation; acheived exclusively by varying magintude of respiration.
  96. Respiratory Problems/Diseases
    • Hypoxia-Low levels of oxygen at tissue level
    • Hypercapnia-excess CO2 from hypoventilation, leads to respiratory acidosis
    • Hypoventilation-respiration rate is low, CO2 builds up
    • Hyperventilation-respiration rate exceeds metabolic needs-->low CO2 (hypocapnia) -->alkalosis
    • Hyperpnea-increased rate of respiration (Ex: in exercise, but matches use so blood CO2 is normal)
  97. Obstructive Chronic Pulmonary Dysfunction
    • Airways are blocked, patient can't move the air
    • Due to smooth muscle constriction, inflammation and edema, bronchiolar secretion
    • Patient will have poor FEV1 (may have normal VC)
    • Causes include: emphysema, bronchitis, asthma
  98. Restrictive Chronic Pulmonary Dysfunction
    • Patient can't take in/hold normal amount of air
    • Due to actual damage to lung tissue
    • Patient has poor VC (but normal ratio of FEV1 to VC)
    • Causes include: pulmonary fibrosis, emphysema
  99. COPD
    • Chronic Obstructive Pulmonary Disease
    • Usually refers to both bronchitis and emphysema
    • Patients have both obstructive (excess mucus in airways) and restricetive problems (lung tissue damage)
    • Patients with COPD have chronically high CO2 and low oxygen, the central chemoreceptors adapt. The peripheral chemoreceptors are then driving respiration based on low oxygen levels
    • Administering too much oxygen can shut respiration off!
  100. Kidney Function
    • Primary excretory and osmoregulatory organs
    • Principle function is formation of urine
    • Rest of urinary system is ductwork to carry urine to outside (ureter, bladder, urethra)
  101. Major Functions of Kidneys
    • Excretion:
    • Removal of metabolic wastes, especially nitrogen
    • Removal of foreign substances
    • Regulation:
    • Maintenance of solute concentrations
    • Maintenance of body fluid volume and osmolarity (ie water content)
    • Assist in pH balance
    • Endocrine cells produce renin and erythropoietin
  102. Excretion
    • Removal of metabolic waste products, nitrogen, excess salts and water
    • Mechanism: filter the blood, reabsorb needed chemicals, secrete some substances, remove the concentrated metabolic wastes and foreign compounds
  103. Osmoregulation
    • maintenance of internal osmolarity vs the environment; concerned with the homeostatic regulation of water and salts
    • Problems stem from teh fact that life processes depend on water and correct/unique concentrations of salts; internal concentration of body fluids may be different from the environment.
    • A variety of strategies (and organs) have evolved to meet these challenges; the principle ones are:
    • 1. match the environment
    • 2. have an impermeable skin and make regulatory adjustments in extracellular fluid in order to protect intracellular fluids
  104. Kidneys must help compensate for salt and water deficits and excesses
    • 1. feeding-salts and water come in with food
    • 2. temperature, exercise, respiration-water is essential for cooling and is lost during respiration
    • 3. Metabolic factors-water is essential for removal of toxic nitrogenous wastes
    • 4. Emergencies: diarrhea, vomiting, hemorrhage
  105. Kidney
    The urine forming organ; cortex, medulla, pelvis
  106. Nephron
    • the functional unit of the kidney (1 million/kidney)
    • See Picture
  107. Transport Epithelia
    • Nephron is lined by a single cell layer of regionally specialized cells which are anatomically and functionally specialized, having an apical or mucousal side which faces tje environment (lumen) and a basal or serosal side which faces the inside, interstitial fluid, blood.
    • This specialized tissue serves as a barrier and site of osmoregulation, maintains correct fluid/electrolyte concentration in the ECF
  108. Urine Formation
    • Glomerular Filtration
    • Tubular Reabsorption
    • Secretion
    • Concentration
  109. Urine Formation
    Step 1
    Glomerular Filtration
    • Occurs in glomerulus
    • A passive bulk flow process, driven by BP-opposed by osmotic pressure in glomerulus and hydrostatic pressure in capsule
    • Allowed by 100x normal permeability of glomerular capillaries and high arterial pressure
    • Plasma passes through capillary pores and capsular filtration slits
    • Product is called filtrate=plasma minus proteins and cells
    • Rate of production is very high: 125ml/min
  110. Urine Formation
    Step 2
    Tubular Reabsorption
    • Retrieval of water, salts, sugars, amino acids occurs primarily in proximal tubule, requires asymmetric transport epithelial cells (substances bound to proteins are not filters-fatty acids and steroids)
    • Na/K pump on serosal side is prime mover for all transport-drives co-transport of sugars and amino acids (carriers are on mucosal side) and osmotic movement of water carriers have transport maxima, can be exceeded by high blood levels of sugar (diabetes)
    • The rest of the nephron is involved in reabsorption also, but 75% of filtrate is reabsorbed in proximal tubule and the primary goal of reabsorption in long loops of Henle is concentration
  111. Nephron-Descending Limb
    • no salt transport
    • permeable to water
  112. Nephron-ascending, thin limb
    • No salt transport
    • Permeable to salt
    • Impermeable to water
  113. Nephron-ascending, thick limb
    • Active Na transport
    • impermeable to water
  114. Nephron-Distal Tubule
    • NaK pump present
    • regulated Na channels on lumen side
  115. Nephron-collecting duct
    Hormone regulated water permeability
  116. Urine Formation
    Step 3
    • Transport of substances from plasma to lumen
    • There are specialized mechanisms for secretion of K+, H+ and organic acids
    • organic acids the liver modifies "exotics" by conjugating them with glucuronic acid so they can be excreted by organic acid mechanism
    • K+ and H+ see specifics in separate card
  117. Secretion of K+
    • Filtered and reabsorbed in proximal tubule but not regulated there
    • Can be secreted in distal tubule if there is an excess in blood
    • Mechanism is NAK pump on serosal surface, pumps Na into blood and K into urine
    • Regulated by aldosterone secreted in response to high plasma K+
  118. Secretion of H+
    • kidney and lungs regulate acid/base balance of body
    • Proximal tubule-primary event here is reabsorbing bicarbonate ion from filtrate
    • Distal tubule-H+ must be trapped in lumen in impermeant form to be removed (only kidney can remove H+ from the body, lungs only shift HCO3 equation)
    • In these cells Na/H+ exchanger works; H+ joins HPO4 and NH3 and is excreted
  119. Urine Formation
    Step 4
    • Water is regulated by kidneys, can be saved or peed out as necessary
    • Requires establishment of a concentration gradient in the interstitial fluid surrounding nephron
  120. Loop of Henle
    • Countercurrent multiplier-created the gradient
    • Requires:
    • 1. Ascending limb with Na pumps that can make a 200 mOsm difference-impermeable to water
    • 2. Descending limb must be impermeable to salt and permeable to water, water is drawn out, leaves via capillaries (vasa recta)
    • 3. Constantly moving supply of filtrate; result is production of a salt gradient in interstitial fluid
  121. Vasa Recta
    • Countercurrent Exchanger-maintains the gradient
    • This gradient is not removed by blood because blood vessels and tubule form a countercurrent exchanger
    • Salt enters descending limbof vasa recta, leaves ascending limb, remains in ISF
    • Water leaves descending limb of vasa recta but enters ascending limb and is removed from ISF
    • Filtrate enters loop of Henle isomotic, becomes hyperosmotic and concentrated in the loop, but leaves loop as hyposmotic, enters distal tubule-->is reduced in volume, not hypertonic
  122. Collecting Duct
    • Uses the gradient
    • Concentration of urine actually occurs in collecting duct
    • Water leaves duct (reabsorbed into blood) and urine becomes hyperosmotic under influence of ADH
    • In ADH absence collecting duct membrane becomes impermeable to water and diuresis occurs
    • Under these conditions urine is hypoosmotic!
    • Note: Without loop of Henle urine would be isoosmotic, with loop it can be hypo or hyperosmotic
  123. Glomerular Filtration Rate (GFR)
    • 3 variables must be considered:
    • Systemic blood pressure, renal blood flow and GFR
    • GFR is proportional to renal blood flow and renal blood flow is kept relatively constant even when systemic blod pressure changes; regulation of flow is achieved by changes in afferent arteriole diameter
  124. 2 arteriole control mechanisms
    • goal 1: maintain constant GFR for efficient nephron function
    • Mechanisms: myogenic and tubulo-glomerularfeedback; autoregulation
    • goal 2: kidney adjusts GFR in order to contribute to regulation of arterial blood pressure
    • Mechanism: extrinsic sympathetic control-Low BP is sensed by baroreceptors--> a sympathetic discharge. Most arterioles including renal vasoconstrict -->decrease in GFR -->decrease in urine output -->increase plasma volume and BP.
    • High BP has opposite effect
  125. Myogenic Mechanism
    Arteriole Control
    • High BP increases GFR and stretches arteriole wall; arteriole muscle contracts in response to stretch, this reduced GFR to normal despite the elevated BP
    • The reverse relaxation response also occurs, allows more flow, higher GFR despite lowered BP
    • This mechanism keeps GFR constant while systemic BP changes from 80-180 mm Hg
  126. Tubulo-glomerular feedback mechanism
    Arteriole control
    • Macula densa cells sense NaCl, indicative of filtrate flow, and trigger release of vasoactive chemicals
    • If flow is high, effect is vasoconstriction; if low, vasodilation occurs
    • Thus, each nephron regulates GFR through its own glomerulus!
  127. Control of Water Balance
    • There is an obligatory reabsorption of water in proximal tubule, 20% of filtered load enters collecting duct for variable, hormone controlled reabsorption
    • Urine can be concentrated as it passes through collecting duct; due to gradient created by Loop of Henle
    • Permeability of epithelium here is regulated by ADH (vasopressin)
    • ADH increases permeability, water leaves lumen and enters blood; water is conserved, urine is hypertonic
  128. Diuresis
    • Copious urine production
    • Without ADH
  129. ADH
    • Secretion is regulated by osmotically sensitive cells in hypothalamus
    • These osmoreceptors monitor osmolarity of immediate ECF
    • If it is high they stimulate nearby ADH cells and thirst center which results in water retention, dilutes ECF
    • Angiotensin II also directly stimulates ADH release and thirst
    • Baroreceptor refelx also stimulates ADH release (hemorrhage)
    • ADH secretion is inhibited by ethanol (drinking-->peeing)
    • ADH also causes vasoconstriction, is one of 3 hormones that do this, to regulate BP
  130. Control of Sodium Balance
    • And ECF volume and therefore BP
    • Most Na is reabsorbed without control in proximal tubule
    • Reabsorption of 8% of filtered Na is controlled, this occurs in distal tubule
  131. RAAS
    • Renin-Angiotensin Aldosterone System
    • Granular cells (JG Cells) of juxtaglomerular apparatus are baroreceptors, sense a decrease in BP secrete an enzyme, renin, which converts angiotensinogen into angiotensin I
    • Lungs convert angiotensin I to angiotensin II via angiotensinconverting enzyme (ACE) which stimulates aldosterone release from adrenal cortex and arteriolar vasoconstriction
    • Aldosterone stimulates sodium retention, acts on distal convoluted tubule cells called principal cells
    • All of this retains and/or adds water and salt and thereby increases BP
    • Mechanism: aldosterone, a steroid, stimulates synthesis of new proteins
    • Na channels and NaK pumps which are added to apical and basolateral membranes of tubule cells
  132. Na Excreting System
    • When ECF is expanded atrial natriuretic hormone is released from atria
    • ANH inhibits Na reabsorption in distal tubule; inhibits renin and aldosterone secretion
  133. Hypokalemia
    Causes K to leave cells and resting membrane potential becomes more negative (hyperpolarized) muscle weakness or paralysis occurs because it is difficult for hyperpolarized neurons and muscles to fire APs
  134. Hyperkalemia
    • Causes more K to stay in cells and depolarizes them
    • Initially cells are more excitable, but then can't repolarize fully and become less excitable
    • Primary effect is life threatening cardiac arrhythmias
  135. Potassium Regulation
    • K secretion is regulated wheras Na and water reabsorption are regulated
    • K is reabsorbed in PCT despite presence of NaK pumps because of K channels in serosal membranes
    • K can be secreted into DCT-elevated plasma K levels stimulate aldosterone secretion
    • Aldosterone stimulates addition of NaK pimps which save Na and secrete K
    • K secretion is inversely linked to H+ secretion
    • In acidosis H+ secretion increases-K+ secretion decreases
    • In alkalosis H+ secretion decreases and K+ secretion increases
  136. Osmoregulation
    • ICF is a fluid compartment that needs to be controlled; plasma is compartment that can be controlled
    • Fluid balance includes ECF Volume and osmolarity; both are dependent on body load of water and NaCl
  137. ECF Volume
    • must be regulated to control BP
    • Maintenance of salt balance is key to long term regulation of ECF volume
    • Aldosterone
  138. ECF Osmolarity
    • Must be regulated to prevent cell shrinking/swelling
    • Maintenance of water balance is key to ECF osmolarity
    • ADH
Card Set
Midterm 3 Physio
Wilson Midterm 3 SRJC