Cardiovascular System
Heart, blood vessels and blood
Lymphatic system
Lymph vessels, lymph, lymphoid organs and nodules
Function of the cardiovascular system
Transport or supply system for cells in multicellular organisms: of oxygen, nutrients, wastes, hormonesHomeostasis: the plasma levels of physiological paremeters are what is regulated: pH, temperature, salts, water, fuel molecules, oxygen and BProtection: clotting mechanism and part of immune systemAlso used to transport heat and to transmit force-ultrafiltration in the kidney, erection
Function of lymphatic system
Circulatory part=vessels and lymph, return filtered plasma to CV, transport fats from villiImmune part=lymphoid tissue in nodes, spleen, nodules help to protect from microbes and cancer
Blood
a complex connective tissue, cosists of fluid and cells
Heart
Main propulsive organ, forces blood around body
Vessels-arteries
Distribute blood to cells, pressure reservoirArteriesArteriolesCapillariesVenulesVeins
arterioles
main site of regulation of blood flow and pressure
Capillaries
Where transfer of materials occurs between blood and tissues
Venules
bring blood to veins
veins
return blood to heart, volume reservoir
lymphatics
blind end tubes, drain extracellular fluid, return fluid to blood
Interstitial fluid
plasma filtered from capillary beds (no cells, proteins) tissue fluid, bathes cells
cytosol
tissue fluid that crosses cell membranes
lymph
interstitial fluid taken up by lympahtic capillaries
pericardium
fibrous sac enclosing the heart
atria
chambers that connect veins and ventricles
ventricles
chambers whose contractions drive the blood
valves
atrioventricular, pulmonary, aortic
myocardium
heart muscle, has 2 functions, carried out by 2 different cell types:contractile: produces forceconducting: initiates and spreads heart beat
Coronary arteries
feed the heart tissue
Heart Beat
Rythmic contraction of whole muscle massLike skeletal muscle contraction except beat is initiated by APs in pacemaker cells these are capable of spontaneous activityAP spreads to the whole heart via the electrical coupling (gap junctions) between cells
cardiac cycle
refers to the repeating pattern of contraction and relaxation of the heart
systole
ventricular contraction and blood ejection
diastole
ventricular relaxation and blood filling; followed by atrial contraction
Cardiac Cycle steps
1. atria and ventricles relax2. atria contract3. isometric ventricle contraction, AV valves closed4. Isotonic ventricle contraction, semilunar valves open, blood ejection5. isometric ventricular relaxation
2 kinds of cardiac cells and APs
pacemaker cellsmyocardial cells
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.
myocardial cells
have delayed repolarization mechanism: depolarization is due to opening of Na channelsSlow voltage gated Ca channelsPurpose: the long duration of the cardiac AP prevents summation and tetanus. Ensures that the heart beats in single twitches
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 fibersSA node serves as pacemaker because it has the fastest rate of spontaneous depolarization
P wave
depolarization of the atria
QRS wave
depolarization of ventricles (repolarization of atria in QRS)
T wave
repolarization of ventricles
Venous System
return blood to heart. volume reservoirPressure 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
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 capillaryCapillaries have pre-capillary sphincters which control blood distributionBlood can be shunted away from capillary beds, goes from arteriole to metarteriole to venuleThere 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!
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
Capillary anatomy
what moves and how is a function of capillary anatomy-capillary walls are specialized for different degrees of permeability in different organsContinuousFenestratedSinusoidal
Continuous Capillary
caps in CNS, muscle, lung
Fenestrated
In kidney, intestine, endocrine glands
Sinusoidal
DiscontinuousIn marrow, liver, spleenCells and proteins can cross these cap wallsHydrophobic substances cross cell membranes, hydrophillic use channels, large molecules use pores
Mechanism for bulk flow/filtration
(Starling's Law of the Capillary)Hydrostatic pressure drives fluid out of the capillaryProteins stay in and constitute an osmotic force; exceeds the blood pressure at end of a capillary bedFluid is sucked back into capillary at venous enddue to high BP in mammals/birds-fluid remains in interstitial space and must be returned to heart ny lymphatic vessels
Cardiac Output
volume of blood pumped/unit time by each ventricle
Stroke volume
volume of blood pumped out per beat
CO=HR x SV
Control of heart rate
1. parasympathetic nerves (ACh) descrease HR2. sympathetic nerves and adrenalin increase HRAutonomic control of HR is mediated by cardiovascular center in medulla; emotions, stress, exercise, pH changesMechanism is change in speed of pacemaker cell depolarization
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 out2. 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)
Calciums role in cardiac physiology
Accounts in part for pacemaker potential in pacemaker cellsaccounts for upswing of AP in pacemaker cellssustains long depolarization of contractile cellscan effect increased strength of contraction-->increased SV
Hemodynamics
Relationship between pressure and flow and resistance F=P/R or P= FxRF=flow=volume/unit timeP=hydrostatic pressure, mm Hg, generated by the heartR=resistance, a result of blood viscocity and vessel diameterBlood 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
Intrinsic Control
Local control of arterioles --> tissue/blood exchange of nutrients and wastesPurpose: the most active tissue gets the most blood flowMechanism 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 relaxationMore blood delivered to active tissues: heat, cold, histamine also act locally to influence blood flowMechanism 2: myogenic mechanism. If blood flow is low, arterioles dilate, constrict if stretched
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 timeMechanism: arterioles are constricted or dilated by arteriole smooth muscle
Hormone regulation of arteriole smooth muscle
Epinephrine-primary effect is via beta blockers --> dilation in skeletal muscle arteriolesAngiotensin II-constricts most arteriolesADH (vasopressin) vasoconstricts and increases blood volume
Blood Pressure
Controlled because this is the force that delivers nutrients to cells a homeostatically regulated parameterHighest in arteries, decreased arterioles and is low in capillaries and veins. Pressure varies with phases of cardiac cycle
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
Equation for Cardiovascular Physiology
BP=CO (HR x SV) x AR
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 stretchIntegrator: Medullary cardiovascular center in medula. This center receives other input, integrates and regulates to a set pointEffector: Heart and arteriole muscle
Other Effectors of Blood Pressure
Chemoreceptors for oxygen and CO2 primarily influence respirationCertain behaviors and emotionsExercise and the anticipation of exerciseTemperature feedback loops integrated by hypothalamus will dilate blood vessel in skin for cooling; can override baroreceptor dictated vasoconstriction orders
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
Long Term Relation-Regulation of body fluid volume by kidney
Decrease in body fluid will lower blood pressure, an increase will raise BPKidney senses BP via juxtaglomerular apparatus, effects adjustments:Aldosterone-stiumulates Na retention and concomitant water retentionAngiotensin-stimulates vasoconstriction and thirstADH-released reflexly via osmoreceptors in hypothalamus, acts on kidney to promote water retention. Is also a vasoconstrictor (other name is vasopressin)
Respiration
Entire sequence of events in exchange of oxygen and CO2 between environment and cells, where oxygen is used for internal or cellular respiration.
Events with Respiration
1. Breathing or ventilation-moving air in and out of lungs2. Exchange of gases-between air and lungs and blood in pulmonary capillaries by process of diffusion3. Transport of gases in blood to/from cells4. Exchange of gases between blood and cells, by process of diffusionRespiratory sys. performs events 1 and 2. Circulatory sys. performs events 3 and 4.
Other functions of respiratory system
pH regulation, defense vs. invaders, site of water and heat loss, vocalization, enhances venous return.
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
Lungs
Hollow invaginated respiratory surface, consist of branched airways, elastic tissue, capillaries, alveoli.
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.
Ventilation
exchange of air between atmosphere and alveoliAir flow=pressure/resistance
Mechanism of Air Flow
Pressure GradientsAir 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 intercoastalsExpiration is usually passive relaxation, can be active using abdominals and internal intercostals.
Pneumothorax
If chest is punctured, lungs collapse
Airway Resistance
Normally not a significant determinant of flow, although smooth muscles in bronchioles are innervated by S/PS system. Epinephrine is poweful bronchiodilatorDisease have major impact-chronic obstructive pulmonary diseases: bronchitis, asthma, emphysema
Lung Anatomy
Lung tissue must be stretchable and elasticLung 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)
Lung Volumes
Measured with spirometerLungs never completely empty-would be hard to re-expand and not all air gets to alveoli, there is a respiratory dead space
Tidal Volume
Volume air entering/leaving in one breath.Normal breathing. Tides go in and out
Inspiratory reserve volume (IRV)
Extra for maximum inspiration
Inspiratory Capacity (IC)
Total inspiration (TV + IRV)
Expiratory Reserve Volume (ERV)
Extra for maximum expiration
Residual Volume (RV)
What can't be blown out
Vital Capacity (VC)
TV + IRV + ERVMaximum volume of air in one breath. Deepest breath in and deepest breath out.
FEV1
Forced expiratory volume, amount of air that can be forcibly exhaled in 1 second.
Total Lung Capacity
VC + RV
Restrictive Diseases of Lungs
Due to lung damage. Will have poor vital capacity
Obstructive diseases of Lungs
Due to block in airway, will have poor expiratory volume (FEV1)
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 oxygenCO2 in venous blood is 46 mm/Hg 40 in alveoli. CO2 leaves blood.
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 lostPulmonary edema-increased interstitial fluid due to conjestive heart failurePulmonary Fibrosis-Replacement og alveolar wall with thick fibrous tissue in response to chronic irritationPneumonia-fluid accumulation in alveoli, due to bacterial or viral infection of lungs, aspiration of fluids
Partial Pressures-Exchange at tissue level
also occurs by passive diffusion, driven by partial pressure gradientsP 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 bloodWith increased cellular respiration, P values for oxygen fall, carbon dioxide rise and an even greater gradient is created
Pulmonary Circulation-Low Pressure System
The pul. circulation has the same cardiac output as systemic, but much less resistance therefore much lower pressureWhen 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
Pulmonary Circulation-Ventilation
Perfusion matching: local controlIt 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 statesMechanisms 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.
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 bodyHb is a tetramer protein (globin) and 4 iron containing heme groupsOxygen binds loosely with iron portion of Hb; other substances can bind also
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 occupiedLocated in RBCs-little or no osmotic effect in blood; maintains pressure diffusion gradient by storing oxygen
Factors determining % Hb saturation
Oxygen dissociation curveAt high P O2, oxygen is loaded and at low P O2, oxygen is unloadedCurve 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.
Oxygen Dissociation Curve
The affinity of Hb for oxygen changes with its state of oxygen saturationFlat portion-P O2 found in pulmonary capillaries: change here (altitude) will not affect oxygen loading in lungsSteep 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
What is carbon dioxide carried in the blood? 3 Ways
1. Dissolved-about 10% of the load is physically dissolved in plasma2. Bound to hemoglobin-carbamino hemoglobin, carries about 20%3. Transported as bicarbonate-about 70% Equation: Carbon Dioxide + water <--> H2CO3 <--> HCO3- + H+
What is happening in this equation:
Carbon Dioxide + water <--> H2CO3 <--> HCO3- + H+
The first reaction is catalyzed by carbonic anhydrase, an enzyme found in RBCsThe 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 effectThe fact that the unloading of oxygen facilitates carrying of CO2 and H+ is called the Haldane effectThese reactions are reversed in the lungs: Oxygen is loaded and CO2 is unloaded.
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 neurons2. Stretch receptors: located in smooth muscles of bronchioles and bronchi, when activated help to terminate inspiration3. Chemoreceptors: part of the NFL for control of oxygen. Sensors-chemoreceptorsIntegrator-medullary respiratory centerEffectors-Muscles (Diaphragm)
Control Neurons in the Pons
Pneumotaxic Center-helps to switch off inspirationApneustic center-prevents inspiratory neurons from being shut off.
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 bodiesResponse 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 curveHigh 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)
Central Chemoreceptors
Are located in the medulla and respond to plasma carbon dioxide in brain CSFThis is dominant control of respirationNote: 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.
Respiratory Problems/Diseases
Hypoxia-Low levels of oxygen at tissue levelHypercapnia-excess CO2 from hypoventilation, leads to respiratory acidosisHypoventilation-respiration rate is low, CO2 builds upHyperventilation-respiration rate exceeds metabolic needs-->low CO2 (hypocapnia) -->alkalosisHyperpnea-increased rate of respiration (Ex: in exercise, but matches use so blood CO2 is normal)
Obstructive Chronic Pulmonary Dysfunction
Airways are blocked, patient can't move the airDue to smooth muscle constriction, inflammation and edema, bronchiolar secretionPatient will have poor FEV1 (may have normal VC)Causes include: emphysema, bronchitis, asthma
Restrictive Chronic Pulmonary Dysfunction
Patient can't take in/hold normal amount of airDue to actual damage to lung tissuePatient has poor VC (but normal ratio of FEV1 to VC)Causes include: pulmonary fibrosis, emphysema
COPD
Chronic Obstructive Pulmonary DiseaseUsually refers to both bronchitis and emphysemaPatients 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 levelsAdministering too much oxygen can shut respiration off!
Kidney Function
Primary excretory and osmoregulatory organsPrinciple function is formation of urineRest of urinary system is ductwork to carry urine to outside (ureter, bladder, urethra)
Major Functions of Kidneys
Excretion:Removal of metabolic wastes, especially nitrogenRemoval of foreign substancesRegulation:Maintenance of solute concentrationsMaintenance of body fluid volume and osmolarity (ie water content)Assist in pH balanceEndocrine cells produce renin and erythropoietin
Excretion
Removal of metabolic waste products, nitrogen, excess salts and waterMechanism: filter the blood, reabsorb needed chemicals, secrete some substances, remove the concentrated metabolic wastes and foreign compounds
Osmoregulation
maintenance of internal osmolarity vs the environment; concerned with the homeostatic regulation of water and saltsProblems 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 environment2. have an impermeable skin and make regulatory adjustments in extracellular fluid in order to protect intracellular fluids
Kidneys must help compensate for salt and water deficits and excesses
1. feeding-salts and water come in with food2. temperature, exercise, respiration-water is essential for cooling and is lost during respiration3. Metabolic factors-water is essential for removal of toxic nitrogenous wastes4. Emergencies: diarrhea, vomiting, hemorrhage
Kidney
The urine forming organ; cortex, medulla, pelvis
Nephron
the functional unit of the kidney (1 million/kidney)See Picture
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
Urine Formation
Glomerular FiltrationTubular ReabsorptionSecretionConcentration
Urine Formation
Step 1
Glomerular Filtration
Occurs in glomerulusA passive bulk flow process, driven by BP-opposed by osmotic pressure in glomerulus and hydrostatic pressure in capsuleAllowed by 100x normal permeability of glomerular capillaries and high arterial pressurePlasma passes through capillary pores and capsular filtration slitsProduct is called filtrate=plasma minus proteins and cellsRate of production is very high: 125ml/min
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
Nephron-Descending Limb
no salt transportpermeable to water
Nephron-ascending, thin limb
No salt transportPermeable to saltImpermeable to water
Nephron-ascending, thick limb
Active Na transportimpermeable to water
Nephron-Distal Tubule
NaK pump presentregulated Na channels on lumen side
Nephron-collecting duct
Hormone regulated water permeability
Urine Formation
Step 3
Secretion
Transport of substances from plasma to lumenThere are specialized mechanisms for secretion of K+, H+ and organic acidsorganic acids the liver modifies "exotics" by conjugating them with glucuronic acid so they can be excreted by organic acid mechanismK+ and H+ see specifics in separate card
Secretion of K+
Filtered and reabsorbed in proximal tubule but not regulated thereCan be secreted in distal tubule if there is an excess in bloodMechanism is NAK pump on serosal surface, pumps Na into blood and K into urineRegulated by aldosterone secreted in response to high plasma K+
Secretion of H+
kidney and lungs regulate acid/base balance of bodyProximal tubule-primary event here is reabsorbing bicarbonate ion from filtrateDistal 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
Urine Formation
Step 4
Concentration
Water is regulated by kidneys, can be saved or peed out as necessaryRequires establishment of a concentration gradient in the interstitial fluid surrounding nephron
Loop of Henle
Countercurrent multiplier-created the gradientRequires:1. Ascending limb with Na pumps that can make a 200 mOsm difference-impermeable to water2. 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
Vasa Recta
Countercurrent Exchanger-maintains the gradientThis gradient is not removed by blood because blood vessels and tubule form a countercurrent exchangerSalt enters descending limbof vasa recta, leaves ascending limb, remains in ISFWater leaves descending limb of vasa recta but enters ascending limb and is removed from ISFFiltrate 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
Collecting Duct
Uses the gradientConcentration of urine actually occurs in collecting ductWater leaves duct (reabsorbed into blood) and urine becomes hyperosmotic under influence of ADHIn ADH absence collecting duct membrane becomes impermeable to water and diuresis occursUnder these conditions urine is hypoosmotic!Note: Without loop of Henle urine would be isoosmotic, with loop it can be hypo or hyperosmotic
Glomerular Filtration Rate (GFR)
3 variables must be considered:Systemic blood pressure, renal blood flow and GFRGFR 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
2 arteriole control mechanisms
goal 1: maintain constant GFR for efficient nephron functionMechanisms: myogenic and tubulo-glomerularfeedback; autoregulationgoal 2: kidney adjusts GFR in order to contribute to regulation of arterial blood pressureMechanism: 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
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 BPThe reverse relaxation response also occurs, allows more flow, higher GFR despite lowered BPThis mechanism keeps GFR constant while systemic BP changes from 80-180 mm Hg
Tubulo-glomerular feedback mechanism
Arteriole control
Macula densa cells sense NaCl, indicative of filtrate flow, and trigger release of vasoactive chemicalsIf flow is high, effect is vasoconstriction; if low, vasodilation occursThus, each nephron regulates GFR through its own glomerulus!
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 reabsorptionUrine can be concentrated as it passes through collecting duct; due to gradient created by Loop of HenlePermeability of epithelium here is regulated by ADH (vasopressin)ADH increases permeability, water leaves lumen and enters blood; water is conserved, urine is hypertonic
Diuresis
Copious urine productionWithout ADH
ADH
Secretion is regulated by osmotically sensitive cells in hypothalamusThese osmoreceptors monitor osmolarity of immediate ECFIf it is high they stimulate nearby ADH cells and thirst center which results in water retention, dilutes ECFAngiotensin II also directly stimulates ADH release and thirstBaroreceptor 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
Control of Sodium Balance
And ECF volume and therefore BPMost Na is reabsorbed without control in proximal tubuleReabsorption of 8% of filtered Na is controlled, this occurs in distal tubule
RAAS
Renin-Angiotensin Aldosterone SystemGranular cells (JG Cells) of juxtaglomerular apparatus are baroreceptors, sense a decrease in BP secrete an enzyme, renin, which converts angiotensinogen into angiotensin ILungs convert angiotensin I to angiotensin II via angiotensinconverting enzyme (ACE) which stimulates aldosterone release from adrenal cortex and arteriolar vasoconstrictionAldosterone stimulates sodium retention, acts on distal convoluted tubule cells called principal cellsAll of this retains and/or adds water and salt and thereby increases BPMechanism: aldosterone, a steroid, stimulates synthesis of new proteinsNa channels and NaK pumps which are added to apical and basolateral membranes of tubule cells
Na Excreting System
When ECF is expanded atrial natriuretic hormone is released from atriaANH inhibits Na reabsorption in distal tubule; inhibits renin and aldosterone secretion
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
Hyperkalemia
Causes more K to stay in cells and depolarizes themInitially cells are more excitable, but then can't repolarize fully and become less excitable Primary effect is life threatening cardiac arrhythmias
Potassium Regulation
K secretion is regulated wheras Na and water reabsorption are regulatedK is reabsorbed in PCT despite presence of NaK pumps because of K channels in serosal membranesK can be secreted into DCT-elevated plasma K levels stimulate aldosterone secretionAldosterone stimulates addition of NaK pimps which save Na and secrete KK secretion is inversely linked to H+ secretionIn acidosis H+ secretion increases-K+ secretion decreasesIn alkalosis H+ secretion decreases and K+ secretion increases
Osmoregulation
ICF is a fluid compartment that needs to be controlled; plasma is compartment that can be controlledFluid balance includes ECF Volume and osmolarity; both are dependent on body load of water and NaCl
ECF Volume
must be regulated to control BPMaintenance of salt balance is key to long term regulation of ECF volumeAldosterone
ECF Osmolarity
Must be regulated to prevent cell shrinking/swellingMaintenance of water balance is key to ECF osmolarityADH