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Cardiovascular System
Heart, blood vessels and blood
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Lymphatic system
Lymph vessels, lymph, lymphoid organs and nodules
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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
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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
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Blood
a complex connective tissue, cosists of fluid and cells
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Heart
Main propulsive organ, forces blood around body
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Vessels-arteries
- Distribute blood to cells, pressure reservoir
- Arteries
- Arterioles
- Capillaries
- Venules
- Veins
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arterioles
main site of regulation of blood flow and pressure
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Capillaries
Where transfer of materials occurs between blood and tissues
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Venules
bring blood to veins
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veins
return blood to heart, volume reservoir
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lymphatics
blind end tubes, drain extracellular fluid, return fluid to blood
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Interstitial fluid
plasma filtered from capillary beds (no cells, proteins) tissue fluid, bathes cells
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cytosol
tissue fluid that crosses cell membranes
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lymph
interstitial fluid taken up by lympahtic capillaries
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pericardium
fibrous sac enclosing the heart
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atria
chambers that connect veins and ventricles
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ventricles
chambers whose contractions drive the blood
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valves
atrioventricular, pulmonary, aortic
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myocardium
- heart muscle, has 2 functions, carried out by 2 different cell types:
- contractile: produces force
- conducting: initiates and spreads heart beat
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Coronary arteries
feed the heart tissue
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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
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cardiac cycle
refers to the repeating pattern of contraction and relaxation of the heart
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systole
ventricular contraction and blood ejection
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diastole
ventricular relaxation and blood filling; followed by atrial contraction
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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
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2 kinds of cardiac cells and APs
- pacemaker cells
- myocardial cells
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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.
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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
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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
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P wave
depolarization of the atria
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QRS wave
depolarization of ventricles (repolarization of atria in QRS)
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T wave
repolarization of ventricles
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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
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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!
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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
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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
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Continuous Capillary
caps in CNS, muscle, lung
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Fenestrated
In kidney, intestine, endocrine glands
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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
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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
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Cardiac Output
volume of blood pumped/unit time by each ventricle
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Stroke volume
volume of blood pumped out per beat
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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
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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)
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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
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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
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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
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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
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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
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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
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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
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Equation for Cardiovascular Physiology
BP=CO (HR x SV) x AR
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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
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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
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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
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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)
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Respiration
Entire sequence of events in exchange of oxygen and CO2 between environment and cells, where oxygen is used for internal or cellular respiration.
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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.
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Other functions of respiratory system
pH regulation, defense vs. invaders, site of water and heat loss, vocalization, enhances venous return.
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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
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Lungs
Hollow invaginated respiratory surface, consist of branched airways, elastic tissue, capillaries, alveoli.
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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.
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Ventilation
- exchange of air between atmosphere and alveoli
- Air flow=pressure/resistance
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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 intercoastalsExpiration is usually passive relaxation, can be active using abdominals and internal intercostals.
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Pneumothorax
If chest is punctured, lungs collapse
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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
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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)
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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
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Tidal Volume
- Volume air entering/leaving in one breath.
- Normal breathing. Tides go in and out
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Inspiratory reserve volume (IRV)
Extra for maximum inspiration
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Inspiratory Capacity (IC)
Total inspiration (TV + IRV)
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Expiratory Reserve Volume (ERV)
Extra for maximum expiration
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Residual Volume (RV)
What can't be blown out
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Vital Capacity (VC)
- TV + IRV + ERV
- Maximum volume of air in one breath. Deepest breath in and deepest breath out.
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FEV1
Forced expiratory volume, amount of air that can be forcibly exhaled in 1 second.
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Total Lung Capacity
VC + RV
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Restrictive Diseases of Lungs
Due to lung damage. Will have poor vital capacity
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Obstructive diseases of Lungs
Due to block in airway, will have poor expiratory volume (FEV1)
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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.
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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
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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
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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
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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.
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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
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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
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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.
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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
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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+
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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 effectThe 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.
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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)
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Control Neurons in the Pons
- Pneumotaxic Center-helps to switch off inspiration
- Apneustic center-prevents inspiratory neurons from being shut off.
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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 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)
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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.
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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)
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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
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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
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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!
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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)
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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
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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
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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
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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
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Kidney
The urine forming organ; cortex, medulla, pelvis
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Nephron
- the functional unit of the kidney (1 million/kidney)
- See Picture
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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
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Urine Formation
- Glomerular Filtration
- Tubular Reabsorption
- Secretion
- Concentration
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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
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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
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Nephron-Descending Limb
- no salt transport
- permeable to water
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Nephron-ascending, thin limb
- No salt transport
- Permeable to salt
- Impermeable to water
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Nephron-ascending, thick limb
- Active Na transport
- impermeable to water
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Nephron-Distal Tubule
- NaK pump present
- regulated Na channels on lumen side
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Nephron-collecting duct
Hormone regulated water permeability
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Urine Formation
Step 3
Secretion
- 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
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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+
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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
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Urine Formation
Step 4
Concentration
- 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
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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
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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
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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 ADHIn 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
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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
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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
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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
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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!
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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
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Diuresis
- Copious urine production
- Without ADH
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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
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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
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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
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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
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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
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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
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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
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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
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ECF Volume
- must be regulated to control BP
- Maintenance of salt balance is key to long term regulation of ECF volume
- Aldosterone
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ECF Osmolarity
- Must be regulated to prevent cell shrinking/swelling
- Maintenance of water balance is key to ECF osmolarity
- ADH
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