physio exam 3

electrocardiogram ECG

what are P, QRS,T

eletrical view of 3D heart

sum of total electrical activities

represents sum of multiple action potentials

ECG v cardiac AP

1887 first ECG

3 major components:

* P wave: atrial depolarization/ contraction
* QRS complex: ventricular depolarization/ contraction
* T wave: ventricular repolarization

extracellular, whole heart: distinct PQRST peaks/troughs

intracellular, one cardiac muscle fiber: no P, combined QRS, and downwards T

what ECG tells us 4

1. heart rate: tachycardia vs bradycardia
2. Does a QRS complex follow each P wave, and is the P-R semgent constant in length? if not, there might be problems of signaling conduction through AV node, action potentials from SA may fail to be sent to AV node
3. Normal wave form: is it present
4. Abnormal recordings, irregular rhythm?

ECG: normal v abnormal

3rd degree block, atrial fibrillation, ventricular fibrillation

describe/draw

normal: typical P, QRS, T waves

third degree block: ventricles are not contracting

atrial fib: HB faster, p-wave gone, atria not contracting

ventricular fib: ventricles are fluttering, SA/AV node control is gone, receives local signals instead

depolarization of heart and the wave type

P, PQ, Q, R, S, ST, T, end

cardiac cycle: diastole, systole, which phases

diastole: relaxation/filling, 70% of the cycle, phases 1/2/5

systole: contraction, 30%, phases 3/4

5 phases of the cycle:


1. mid/late diastole:
2. atrial systole
3. iso-volumic contraction
4. ventricular ejection
5. iso-volumic relaxation

cardiac cycle

1. late diastole: heart at rest, atrial and ventricle diastole, atria filling with blood, ventricle just finished a contraction, ventricles passively fill with blood \~80%
* Pvc > Pa > Pv
2. atrial systole: completion of ventricular filling: atrial systole\~20% of blood fills, some goes into ventricles, small amount of blood forced backward into veins because there are no one-way valves to block backflow
* Pa > Pv
* EDV: maximum amount of blood in ventricles occurs at the end of ventricular relaxation 135mL
3. early ventricular contraction and the first heart sound: atria contracting, depolarization moving towards heart apex, ventricle systole = blood pushed to AV valves, forces them closed so blood cannot flow into atria, closure of AV valve = LUB
* isovolumic ventricular contraction: AV and semilunar valves are closed, V blood has no where to go, V continues to contract, high pressure, no change in volume
* Paorta > Pv > Pa
4. ventricular ejection: heart pumps, ventricles contract to generate enough pressure to open semilunar valve and push blood into the arteries, atria continues to fill
* Pv > Paorta
* ESV: minimum amount of blood in ventricles 65mL
5. isovolumic ventricular relaxation and second heart sound: ventricles repolarize and relax, V pressure decreases below A pressure = blood flows backward into the heart against semilunar valve forcing them closed = dub sound
* Paorta > Pv > Pa

Wiggers Diagram: L26S3-4

SL valves open/close

AV valves open/close

ventricular ejection/filling

isovolumetric contraction/relaxation

SL = pulmonary

SL: ventricular volume decreases, ventricular pressure systole increases

AV: ventricular volume diastole increases

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SL valves open? 3

SL valves close? 4

AV valves open? 6

AV valves close? 1

Ventricular ejection? 7

Ventricular filling? 8

Isovolumetric contraction? 2

Isovolumetric relaxation? 5

pressure-volume loop

draw and label

change in volume and pressure

Pressure/volume loop = P x V = area = work, 1 ml = 1 cm^3, area tells us how much work is done by heart,

A: mitral valve opens

B: mitral valve closes, EDV

C: aortic valve opens

D: aortic valve closes, ESV

A → B: passive filling and atrial contraction, steps 1+2 cardiac cycle

B → C: isovolumic contraction, step 3

C → D: ejection of blood into aorta. step 4

D → A: isovolumic relaxation, step 5

work performed by the heart

work = g x cm = P x V = (force/area) \* V

area of pressure-volume loop = work of 1 cycle

right ventricle has smaller pressure than left ventricle

Work of LV > RV why? RV pressure is less than LV pressure, volume is the same for both, right ventricle works less than LV, RV only covers pulmonary but LV covers the rest of of system

2 factors affecting the work done by the heart

* increases EDV: preload, good for heart, pressure stays the same and volume increases
* increasing afterload: bad for cardiovascular system, volume stays the same but pressure increases

cardiac output

CO = HR x SV

measure of cardiac performance

Flow Q = /\\P / R = arterial pressure / Rtotal peripheral

MAP = CO x TPR

mean arterial pressure = cardiac output x total peripheral resistance

MAP: baroreceptors, can be easily monitored?, used to change cardiac function, too high? ejecting too much blood, must decrease CO to decrease MAP

EDV and ESV and SV

SV = EDV - ESV

SV: volume of blood pumped per ventricle per contraction, directly related tp force generated by cardiac muscle during contraction

EDV: preload is affected by:

* elasticity of ventricle wall, filling time, more space for blood to fill = longer filling time
* venous return → filling pressure = Pa-Pv, Pa is affected by venous return

ESV: affected by

* afterload: arterial or aortic resistance (cannot eject blood as much)
* inotropy: contractility, increase inotropy? ESV decreases - like squeezing a water bottle, high contractility is bad because there will be less leftover blood in the heart

these factors dictate work done by the heart

preload

Frank-Starling

initial stretching of the cardiac myocytes prior to contraction

aka the degree of myocardial stretch before contraction

muscle length → preload → EDV

Frank-Starling mechanism: optimal filling pressure and stroke volume curve, length-tension relationship, stroke volume is proportional to EDV

factors determining R ventricular preload - 11

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LVP determined by same but with central venous pressure than pulmondary

positively impacted by

* atrial contractility
* ventricular compliance: ventricle relaxes more = more blood
* venous pressure: more blood returning, negatively impacted by venous compliance, increased by venous volume

negatively impacted by

* heart rate: filling time is decreased when heart rate increases
* inflow resistance: high? less blood can flow through

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venous return + total blood volume:??

* muscle contraction increases preload
* respiration deep breaths increases preload
* high gravity decreases preload
* vasoconstriction increases preload

afterload

the combined load of EDV and arterial resistance during ventricular contraction

the resistance to ventricular ejection

the load that the heart must eject the blood against

aortic pressure: increased in hypertension

positive inotropy

starlings law of the heart

starlings law of the heart:

* as EDV increases, pressure generated increases

positive inotropes: anything that affects contractility

* NE
* increases pressure without a change in volume
* increases contractility
* positively influence stroke volume
* squeezing more? ESV decreases, SV increases

effects on SV - flow chart

preload, afterload, inotropy

overall goal of the CV system

flow chart of what things affect MAP = CO x TPR

maintain mean arterial pressure

respiration: gases kinds

properties of gases 2

convection

properties of gases: partial pressure, solubility

respiration dependent on gas exchange

convection: gases traveling in liquid + air, like conduction

pH regulation, breathing air, breathing water, physical properties of gases

respiratory gases: O2 + CO2

* O2 simple diffusion, convective gas transport
* convective gas transport = transport by bulk flow: occurs when a gas or aqueous solution flows and they are carried by the fluid flow
* CO2 both^ + active transport: related to pH regulation which is important with active transport and rapid movement

fractional composition of Air

facts about the composition and can it change?

doesn’t change with altitude

Patm changes with altitude

can change in confined spaces, due to biological processes like decay and respiration

example: gopher burrow - confined area, limited air, O2 down CO2 up

O2 \~ 20.95%

CO2 \~ 0.03%

nitrogen \~ 78.09%

argon \~ 0.93%

Daltons Law of Partial Pressures

Ptotal sea level + mt everest

P total = 760mmHg @ sea level = pO2 + pCO2 + pN2

P total = (0.209)(760) + (0.0003)(760) + (0.78)(760) = 760mmHg

pO2 = Patm \* %comp = 158.8mmHg @sea level

pO2 @ Mt. Everest = 0.209 \* 250 = 52.3mmHg

3 times less partial pressure of O2 = 3x harder to breath

water vapor pressure

Pgas not affected much by temperature

Ph2o = water vapor pressure IS affected by temperature

increase temp = increase ph2o

humid day = harder to breath

calculating Pgas

MUST take into consideration Ph2o

Ptotal: (0.209)(Patm-Ph2o) + (0.0003)(Patm-Ph2o) + (0.78)(Patm-Ph2o)

@ 37°C, PH2O = 47 mm Hg

Henry’s Law

def, dep on 3, equation

determine the amount of gas dissolved in fluids (solubility)

dependent on temperature, ionic strength of fluid, and type of gas

\[gas\] = alpha(gas) x Pgas

alpha = solubility coefficient

CO2 in water

CO2 much more soluble in water than O2

CO2 dissolved in water determined by: gas solubility and CO2 partial pressure

gas solubility depends on temp

solubilities of gases in water @ 15C @ 1 atm

* Oxygen: 34.1 ml / L h2o
* Nitrogen: 16.9 ml / L h2o
* CO2: 1019 ml / L h2o

difference between O2 and CO2 concentration 21% to 0.03%, there is 700x difference in their concentrations

difference between O2 and CO2 solubility is 34.1 to 1019, there is a 30x difference in their solubilities

700 difference / 30 difference = 23x

oxygen solubility is 30 times lower than CO2, but the concentration is significantly greater 700x more

even though CO2 is more soluble, O2 concentration in water will be higher than CO2

O2 is 23 times more dissolved in water bc partial pressure > solubility

water as respiratory medium

increase Patm, increase \[gases\] dissolved in water

\[O2\] air: 209 (700x more than CO2), water 4.7 (23 times more than CO2)

\[CO2\] air: 0.3 , water: 0.16

ratio of 44:1

44X harder to extract O2 from water than air

gill’s are more energy efficient than lungs - use mass movement to move water across gills

air is better respiratory medium because oxygen concentration has greater concentration of O2 than water

comparison of air v water as a respiratory medium 5

1. \[O2\] 44x greater in air
2. viscosity: H2O 50x greater than air
3. diffusion rate
* flux
* J = K A/\\C / /\\x
* K = diffusion coefficient in air = cm^2/atm\*min
* K is 8000x lower in H2O vs air
4. thermal conductivity: H2O 25x greater than air
5. heat capacity: H2O 3000x greater than air

respiration in water

\[O2\] 44x lower in water → higher ventilation rate

density and viscosity is greater than air

unidirectional flow

humans breath tidally in and out

energy demanding to breath tidally in water, so its unidirectionally

structure of fish’s gill

teleost: bony fish

gills: typically 4 arches, water from mouth flows over gills

lamella: singular gills? used to increase SA?

* alveola = lamella, similar functions
* H2O flows across well-vascularized lamellae in opposite direction of blood

operculum: flap that covers the gills

sheet flow: water passing in between gill lamella

* countercurrent flow: water goes one way and blood flows the opposite direction so oxygen can get into blood
* increase Pblood
* decrease thickness of sheet
* when thickness is wide = water can pass through easier
* when gap is smaller = better O2 exchange
* increasing thickness of sheet decreases the gap?
* LECTURE 29 SLIDE 2

gill surface area also varies among fish taxa

thickness of the membrane

larger gill SA = extract more oxygen

greater O2 extraction = more active

skipjack tuna: very active: 13.2cm^2/g

plaice: active: 4.33

oyster toadfish: sluggish: 2.14

climbing perch: very sluggish: 1.50

thickness of membrane:

* too thin? gills can collapse out of water
* thin is good
* too thick? more difficult to breath

concurrent design

water and blood flow in the same direction

water pressure decreases, blood pressure increases = the water and blood will eventually have the same pressure = no exchange of O2

when first in contact with water, pressure gradient is high but after long exposure, pressure gradient decreases to 0

no continuous pressure gradient/ O2 exchange

diffusion = K \* A (PO2water - PO2 tissue) / distance

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countercurrent design

allows for greater transfer of O2 from water to blood

pressure gradient is constant because

better for transfer of O2 bc gradient is maintained

O2 uptake efficiency

def, increase by 3, equation

O2 uptake efficiency: % removed from medium

U = (PO2 in - PO2 out) \* 100 / PO2 in

oxygen uptake efficiencies vary among species, physiological states: active and high

surface area and thickness effect O2 uptake efficiency

increase O2 uptake efficiency? 1) increase SA 2) thickness thinner 3) ventilation/perfusion ratio

uptake efficiency determined by 2

capacity and flow

gas transfer capacity: a composite value determined by thickness, conductance of tissue, mucus layers, Krogn’s coefficient of fas molecules in the relevant fluids

gas transfer capacity C = O2 uptake rate (flux) / partial pressure difference

flux = K \* A \* /\\P / x

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flow Q: of blood and water across diffusion surface

if water flow is very high relative to blood flow, there is little change in its PO2 as it flows across gills (going too fast for maximum diffusion)

diffusion distance (water-blood) varies among fish taxa

3\~8 um diff distance in fish,

diff distance in humans is 0.4um

the slower the fish the greater the diff distance

two measures that underlie ventilation: perfusion ratio

ventilation rate / blood perfusion rate = Vg/Q = ratio

if blood or water moves too fast = efficiency decreases

1:1 ratio is best

most fish have 10:1 ratio, more water must be perfused to get the same amount of oxygen as air (since water PO2 is low, the capacity rate values are low)

ventilating air is easier than water

2 disadvantages of fish: 1) oxygen content in water is LOW 2) water movement requires more energy x10 more

how do water-breathers ventilate

1. buccal pumping:

* floor of mouth is raised/lowered
* water flows into mouth through gills and out the operculum


* water flows through pressure gradient
* P external > Pbuccal + mouth opens (volume increase) = water enters the mouth
* mouth closes (volume decreases) + Pbuccal > P external = water leaves the gills/operculum to external


2. ram ventilation:

* mouth opens, swimming motion forces continuous flow across gils
* as swimming speed increases = faster ventilation = more oxygen
* gape: wide gape = more water = more oxygen
* smaller gapes not as good
* only used for faster swimming, will not work if fish swims too slowly

3 organs, respiration of air

1. gills
* terrestrial arthropods
* rigid
* evaginated
* breath air
2. trachea
* insects
* passive diffusion
* open circulatory system
* have another system to supply oxygen - tracheal
* there is a little bit of fluid in tracheole tips
* fluid levels in tracheole tips drops during high metabolic demand = increases gas diffusion rates
3. lung
* invaginated
* diffusion lungs:
* molluscs
* air coming in and out is passive
* not very invaginated - like a simple bag
* lower SA
* can explain why snail is slow
* ventilation lungs:
* tidal flow
* unidirectional flow
* bidirectional flow = less efficient
* crosscurrent efficiency: in between concurrent and countercurrent

structure of mammalian lung

develops as a diverticulum of gut

right lung: 3 lobes, upper, middle, lower

left lung: 2 lobes, upper + lower

functionally the same LL and RL

diaphragm: membrane of muscles, designed to recoil, when it contracts it pushes down, when it relaxes it recoils up

pleural space: space covers the ribs, surrounded by membrane and fluid, fluid has negative pressure, no negative pressure = lungs collapse?

trachea: divides bronchi into L and R

highly subdivided in mammals

much simpler in amphibians and reptiles

conducting airways v respiratory airways

trachea, main bronchi, bronchiole, terminal bronchiole = conducting airways, dead space, not designed for gas diffusion

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respiratory bronchiole, alveolar duct, alveolus, alveolar sac = respiratory airways, involved in gas exchange

* alveolus = exchange surface

pressure and volume change in the lung

pneumothorax

how does lung remain expanded

inhalation: diaphragm contracts/ lowers, Patm > Plung, volume increases, active part of breathing, easy to breath in because of pressure difference

exhalation: diaphragm relaxes/raises, Plung > Patm, volume decreases, easy to breath out because of pressure difference, passive because muscle relaxing

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lung membrane-encased and remain expanded because of negative pressure of fluid filled pleural cavity

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pneumothorax: if pleural cavity is punctured and negative pressure destroyed (aka replaced with air) lung often collapses

volume changes in the lung

residual volume

during high activity, tidal volume _?

vital capacity

inhalation is active, exhalation is passive, recoil from intercostal muscles

during high activity: tidal volume increases and utilizes inspiratory/ expiratory reserves

residual volume: lungs never empty completely

vital capacity: maximum breathing in and out, cannot maintain this maximum, typically 6L which almost matches blood volume \~5L (but lung never fully empties so approx 1:1 ratio)

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alveolar ventilation volume

alveolar ventilation rate

if tidal V = dead V

low ventilation rate vs high

total volume of air

alveolar ventilation volume (Va) = tidal - dead

Va = Vt-Vd

alveolar ventilation rate = Va \* frequency of breath

dead = anatomical dead space = conducting airways \~ 150ml

dead space never changes (with age yes but not important)

air must travel through the dead space before it can reach the respiratory airways

if tidal volume = dead volume … then = 0 ventilation volume

breathing

breathing shallow and quick = low ventilation rate

deep long slow breaths = high ventilation rate

total volume of air 6000mL

as tidal increases frequency of breath decreases

bicarbonate and pH

what happens when ventilation rate too low, too high,

if ventilation rate is too low, alveolar CO2 builds up and results in hypercapnia = high blood pCO2 = respiratory acidosis = drop in plasma pH due to the release of H

if ventilation rate too rapid, CO2 is eliminated too quickly and can result in respiratory alkalosis

metabolic pathways consume O2 and produce CO2 which have consequences in the blood

CO2 high = proton concentration high = pH low

CO2 + H2O

regulation of ventilation - water and air breathers

phrenic nerve

water breathers: respond to O2 decrease in blood and tissues

air breathers: chemoreceptors respond to increase CO2/H

* chemoreceptors:


1. carotid and aortic bodies: detect increased CO2 and/or low pH
2. cerebrospinal fluid chemoreceptors: has poor buffering ability, very sensitive to pH, medullary receptors respond to high CO2 and low pH
3. peripheral chemoreceptors
* pulmonary stretch receptors: prevents overexpansion, help regulate inflation of lungs
* phrenic nerve: diaphragm relays inspiratory signal from medulla respiratory center (nerve > medulla > signal to diaphragm), inflation of lung inhibits inspiratory activity in medulla = reduces the frequency of breathing
* increase activity? increase phrenic nerve activity, increase in discharge rate drops lung pressure
* discharge rate is enhanced by high PaCO2 (rapid rise results in deeper inspiration)

air breathers pathway to remove CO2

regulated by

how everything work together - draw flow chart

respiration regulated by brain, medulla respiratory center

lung expansion + phrenic nerve = breathing bigger to get rid of CO2

respiratory pigments

funx 3

in absence of resp pigments, O2 in solution in blood would be 0.3ml O2/ 100ml blood, but should be 20+ml O2 / 100ml blood \~70x greater

function:


1. increase carrying capacity (x70 more)
2. maintain PO2 gradient (air > blood > tissue)
3. transport (air > lung > blood > tissue)

types of respiratory pigments

hemoglobin and myoglobin: heme Fe2+, vertebrates, myoglobin mostly in muscle and stores O2 rather than transport O2

hemocyanin: copper, invertebrates, not in cells, bluish color = oxygenated

hemerythrin: no heme, annelids and brachiopods, iron directly binds to protein

structure of vertebrate hemoglobin and myoglobin

4 types hb

Hb is tetrameric, 4 subunits, 2 alpha + 2 beta, each with heme

myoglobin has 1 subunit looks like alpha, 1 heme

oxy Hb: O2 bound

deoxy Hb: no O2

carboxy Hb: CO bound

carbamino Hb: CO2 bound

CO competes with O2, CO2 doesn’t compete with O2

binding affinity of CO is 200x greater than O2 = very bad

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hemoglobin in red blood cells erythrocytes

matured RBC contain what?

hematocrit

erythropoiesis

intracellular v extracellular Hb

mammalian RBC: 4-10um

matured RBC: no nucleus, no mito, no ribosome, no energy use, carries hemoglobin

hematocrit: percentage of total blood volume occupied by RBC

erythropoiesis: making RBC, bone marrow, hormone erythropoetin secreted from kidney stimulate synthesis of RBC, stimulated in low O2 conditions

in some invertebrates, Hb can be found in the blood plasma = extracellular Hb

hemoglobin in RBC = intracellular Hb

oxygen dissociated curve of hemoglobin is sigmoidal

P50

subunit cooperativity: oxygenation of first subunit enhances binding affinity of the other subunits

myoglobin curve NOT cooperative, hyperbolic, has higher O2 affinity, lower P50, only has 1 binding site so cannot be cooperative

the greater P50 = O2 binding affinity is lower

hemoglobin has lower affinity for O2 than myoglobin

it only takes \~4mmHg PO2 to saturated myoglobin 50%

it takes 32mmHg PO2 to saturate hemoglobin 50%

lower affinity means that O2 comes off more easily

myoglobin used for O2 storage and isn’t used until O2 saturation of Hb is very low

factors that influence O2 binding affinity of Hb - 3

temperature:

* Hb has greater affinity for O2 at cooler temps
* temp high PO2 increases, binding affinity lower
* temp low, PO2 decreases, binding affinity higher
* slide 2 lect 30b

acidity:

* Bohr effect: reduction in binding affinity of Hb for oxygen as pH drops, effects of proton concentration on respiratory pigments
* significant because changes in blood PCO2 can indirectly affect O2 binding by changing blood pH
* high pCO2 at tissues enhances offloading of O2
* lower pH = lower O2 binding affinity
* atrial system O2 binding: high, more important because O2 is going to lung
* venous system O2 binding: lower, not as important because O2 is going to other tissues
* close to muscles/tissues: CO2 level is higher, pH low, binding affinity low, hemoglobin offloads more O2
* high PCO2 = more offloading
* average pH 7.2 < 7.4 < 7.6, death @6.8 + 7.8

organic phosphates:

* DPG: 2,3 diphosphoglycerate - naturally produced by erythrocytes by anaerobic glycolysis
* reduces binding affinity
* enhances O2 release
* binds near O2 binding site
* produced in response to low blood PO2
* improves offloading in tissues, not onloading in lung capillaries
* tries to provide more O2 to tissues
* inositol triphosphate - birds
* ATP - fish

CO2 binding affinity of Hb and total CO2 content in blood

how is CO2 in body as

Haldane effect

venous vs atrial

oxygenated vs deoxygenated Hb

CO2 in body as


1. dissolved gas (molecular) 5%>
2. bicarbonate (+ carbonate) \~90%
3. carbamino Hb \~5-10%

Haldane effect: deoxygenated blood in venous system contains more CO2 than arterial blood

venous system: has MORE CO2

atrial system: has LESS CO2

CO2 unloads rapidly in lungs where pCO2 is low

Hb that are fully oxygenated can carry less CO2 than deoxygenated Hb

CO2 transport in tissue capillaries

CO2 produced in tissues → lungs


1. tissues: CO2 made
2. interstitial fluid: dissolved CO2
3. capillary wall
4. plasma: some CO2 remains dissolved
5. RBC: some remains dissolved, dissolved CO2 + Hb → HbCO2, dissolved CO2 + H2O + carbonic anhydrase = H2CO3 = H + HCO3
6. plasma: HCO3 passed from RBC to plasma, plasma \[Cl-\] sent to RBC, neutral cell charge

carbonic anhydrase in RBC not plasma

chloride shift: anion exchange, co-transport of Cl ion into RBC while bicarbonate moves into plasma, maintains electroneutrality, antiporter

consequence of chloride shift: Bohr effect

Bohr effect: transfer of bicarbonate out of the RBC to plasma raises H in RBC, decreases pH, helps offload O2 from Hb by reducing binding affinity

CO2 transport in pulmonary capillaries

RBC → plasma → capillary wall → alveoli → atmosphere


1. RBC: HbCO2 → dissolved CO2 + Hb, HCO3 + H = H2CO3 = dissolved CO2 + H2O, Cl- moved to plasma
2. Plasma: HCO3 goes back to RBC to make dissolved CO2, Cl reenters plasma, dissolved CO2 from RBC enters,
3. lung capillary wall: dissolved CO2 passes, contain carbonic anhydrase which converts HCO3 → CO2
4. alveoli: CO2 released as gas to atmosphere
5. atmosphere: expired CO2

chloride shift: H2CO3 back to RBC, Cl back to plasma

lung capillaries are continuous and unique because they have carbonic anhydrase in endothelium which speeds up bicarbonate conversion

CO2 bound to Hb

CO2 bound to Hb in RBC = carbamino Hb

hemoglobins affinity for CO2 is lower when O2 is bound = haldane effect

pulmonary capillaries uptake of O2 facilitation offloading of CO2

when HCO3 + H → CO2 + H2O, pH rises = O2 binding affinity rises

how does the Haldane and Bohr effect work together with CO2

Bohr effect: pH drops, O2 binding affinity drops

Haldane effect: deoxygenated blood contains more CO2 than arterial blood

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when bicarb converted to CO2, pH increases, which increases O2 binding affinity =Bohr effect

better O2 binding affinity = more oxygenated blood (contains less CO2 than arterial blood) = Haldane effect

acidification and Hb and O2 and H

cycle of HHb, HbO2, tissues, blood, environment

acidification is offset by the fact that H can bind directly to Hb and is displaced by O2

Hb acts as pH buffer in blood

O2 binding to Hb at respiratory surface facilitates formation of CO2

release of O2 from Hb in tissues facilitates formation of HCO3

regulation of body pH

3 major influences on body pH (easy)

alkaline tide

gas exchange is inherently linked to acid-base balance

major influences on body pH:


1. CO2 \*most important
2. ingested food: meats result in net uptake of acid, plant material net uptake of base
3. anaerobic metabolism: net acid production, metabolic acidosis

also can see changes in blood pH due to acid movement across fluid compartments: alkaline tide → acid transferred from blood to stomach after a large meal

respiratory disturbance

metabolic disturbances

an abnormal alteration of the rate of CO2 elimination by lung/gill

respiratory acidosis: impaired exhalation of CO2

respiratory alkalosis: increased exhalation of CO2

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metabolic disturbance: 1) altered blood bicarbonate concentration 2) numerous possible causes

* metabolic acidosis: loss of HCO3, increase H, in GI fluids or in saliva, anaerobic metabolism = lactic acid accumulation
* metabolic alkalosis: alkaline tide

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pH can change based on respiration and metabolism

alkaline tide: after big meal, normal stomach pH acidic, meal increases pH, lots of protons pumped into stomach to maintain low stomach pH = metabolic alkalosis because protons are removed from the rest of the body

summary of O2 binding affinity, CO2 transport, body pH

lung vs tissue levels of HCO3 and Cl in plasma (table)

O2 binding affinity: temp, pH (Bohr), DPG, other gases

CO2 transport: bicarbonate and chloride levels, affinity of Hb for CO2 (Haldane effect), intracellular pH of RBC (Bohr)

body pH: CO2, HCO3, H+

around lung: CO2 removed, O2 onload high

around tissue: CO2 made, O2 offload high

water and osmotic regulation

osmoregulators

conformeres

organs

osmoregulators: maintain constant blood osmotic pressure regardless of ambient osmotic pressure

conformers: permit their blood osmotic pressure to match ambient osmotic pressure

osmoregulatory organs: kidney, extra-renal

nitrogeneous wastes

challenges in osmoregulation 2

3 types water - what is in each

electrolyte vs non

1. retaining H2O - 3 types of water


1. intracellular fluid: majority of water in body, 28kg
2. interstitial fluid
3. blood plasma: 3kg
2. maintaining appropriate concentrations of solutes in extra/intra cellular compartments

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major electrolyte: compound that dissociates into charged ions

plasma: Na, Cl

interstitial: Na, Cl

intracellular: K, HPO4, proteins

non electrolytes: glucose lipids

these influence osmolarity

factors affecting ion/water exchange 5

1. animal-environment gradient
* fresh water v salt water
2. surface-volume ratio
* smaller organisms desiccate more easily because small animal surface-area is larger
3. integument permeability
* integument = barrier = skin, insect cuticle
4. metabolic factors
* feeding and excretion rates and water (using O2 and making Co2 + H2O)
5. respiration
* loosing water as breathing in all air breathers
* nose temp is lower but higher than air
* warm air holds more water than cold air
* water vapor pressure in lungs is high
* breathing out: holding onto water vapor
* nose system holds water vapor good
* breathing through mouth = more water loss

water uptake

water output

food 30%, drinking 60%, and metabolic water 10%

output per day: 60% urine, skin + lungs 28%, feces 4%, sweat 8%

metabolic water: C6H12O6 + 6O2 = 6CO2 + 6H2O

metabolic H2O production: lipids (most water produced - like migratory birds) > carb > protein w uric acid production > protein w urea production

marine animals: seals?

* eat invertebrates: skinner, more salts compared to fish, seals have to remove excess salt meaning it removes water too
* eat fish

osmolarity + osmolars

measure of effective osmotic pressure of solutes in fluids, largely correlates with number of solute particles

non dissociable solutes: 1M = 1 Osm

dissociable solutes: must consider # charges when calculating

* NaCl (0.05M) → Na + Cl (2 x 0.05) = 0.1 Osm
* MgCl2 (0.05M) → Mg + 2Cl (3 x 0.05) = 0.15 Osm

water and salt physiology: cell-volume regulation

how hypertonic and hypotonic solutions affect cell volume

how to regulate cell-volume?

how to decrease osmolarity 2

problems: need to maintain cell volume, hypotonic solution (solutes leave cell to maintain volume) and hypertonic solution (increase solutes in cell to maintain volume)

answer: organic solutes for cell-volume regulation

* increase organic solutes to maintain volume, will also increase Osm

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crab - how to decrease osmolarity?


1. accelerating oxidation - AA can be metabolized (decreasing \[organic solutes\] decreases osm
2. transport of AA out of cells - removing organic compounds

adjustment of intracellular osmotic pressure among animal groups ???? what is going on

all 4 groups are about the same in concentrations of inorganic ions in their intracellular fluids due to the contribution of organic solutes

group A: marine invertebrates and hagfish \~1000 mOsm each

* plasma = only inorganic ion - Na, Cl
* interstitial fluid = organic solutes, K, Na,Cl

group B: marine sharks, skates, rays, coelacanth \~1000 mOsm each

* blood plasma = organic solutes + Na Cl
* interstitial fluid = organic solutes and K, Na, Cl

group C: freshwater and terrestrial invertebrates \~300 mOsm each

* plasma: Na Cl > organic solutes
* interstitial fluid: K Na Cl > organic
* osmolarity is changing based on organic solutes

group D: freshwater and terrestrial vertebrates \~300 mOsm each

* plasma: Na Cl > organic solutes
* interstitial fluid: K Na Cl > organic
* osmolarity is changing based on organic solutes

osmoconformers - types of animals

osmoregulators

euryhaline

stenohaline

osmoconformers: marine invertebrates, follows isomotic line?

osmoregulators: teleosts, vertebrates, remains constant regardless of isosmotic line

some animals (green crab) can use both conformers and regulators depending on ambient osmotic pressure

euryhaline: wide range of osmolarity tolerated (green crab)

stenohaline: narrow range of osmolarity tolerated (shrimp, mussel)

osmoconformers

elasmobranchs - how isotonic

hagfish osmotic concentration similar to sea water \~1000

lamprey osmotic concentration 300 much lower than sea water

elasmobranchs (sharks, rays, dogfish) blood salt is 1/3 that of sea water, but still isotonic due to TMAO and urea

extraosmolytes: Urea and TMAO, organic compounds

why both TMAO and Urea?


1. Urea in high concentrations can denature proteins, TMAO will stabilize them
2. often both made together

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osmoregulators

organs of osmotic reguation 3

osmotic concentration closely regulated

teleosts live in marine/fresh water but all maintain similar blood osmolarity 300-400mOsm → regulated at organs

organs of osmotic regulation


1. gills: fish, aquatic
2. salt glands: marine reptiles, birds
3. kidneys: mammals, fish, birds

osmotic regulation depends on U/P ratio

ratio when isosmotic

effects on water excretion, solute excretion, composition of blood plasma

U/P ratio = urine concentration / plasma concentration

U/P = 1 isosmotic urine

U/P < 1 = diluted urine

U/P > 1 = concentrated urine

range human: 0.1-4 (40x difference)

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effects on water excretion:

* diluted: water in urine > water in plasma
* concentrated: water in plasma > water in urine

effects on solute excretion:

* diluted: solutes in plasma > solutes in urine
* concentrated: solutes in urine > solutes in plasma

effects on composition of blood plasma:

* diluted: osmotic pressure of plasma increases
* concentrated: osmotic pressure of plasma decreases

freshwater animals / teleost

2 different ways to regulate water and osmotic balance

how to avoid excess water

how to replace salts lost

1. hyperosmotic body fluids
2. gain H2O by osmosis, ionic loss by diffusion (via gills)

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problem + solution

* to avoid excess water - dilute urine, no drink
* to replace salts lost - active uptake by chloride cells and pavement cells found in the fish gill epithelium

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chloride cell: active Cl transport, Cl is anitported with HCO3, Cl in HCO3 out

pavement cell: antiported H with Na, active Na transport, Na in H out

ocean animals marine teleost

3 ways to replace water loss

how to remove uptaken salts

1. hyposmotic body fluids
2. loss of H2O by osmosis, ionic gain by diffusion

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3 to replace water loss: drinking, H2O absorption in gut, concentrated urine

to remove up-taken salts: active secretion

marine reptiles and birds

idk how to do this

how to maintain hyposmotic blood to seawater

confront problems of water loss (skin) and salt loading (by drinking and food uptake)

no concentrated urine

blood osmotic pressure much less than sea water

problem: maintaining hyposmotic blood to seawater?

solution: salt glands for osmotic and ionic regulation, salt glands found in head? ducts well arranged with capillaries, blood flow through capillaries, Na/K pump, Na and Cl pumped into secretory tubules

kidney structure picture - definitions

cortex: surrounds inner body of medulla, consists of Bowmans caupsules, beginning of collecting ducts, some tubule?

medulla: loops of Henle, collecting ducts

renal pyramid: lots of nephrons

renal pelvis

ureter: caries fluid from kidney to bladder

renal artery, vein

functional unit of kidney = nephron, makes urine

nephron

glomerulus + tubule

glomerulus: capillary clump surrounded by bowmans capsule, center of filtration

kidney tubule: 4 tubules

* proximal tubule
* loop of henle: thick and thin parts, long,
* distal tubule: collected to collecting duct
* collecting duct: where urine is found
* renal pelvis

cortical nephron: ??

renal vasculature flow through

renal artery →

afferent arteriole

glomerular capillaries:

efferent arteriole

vasa recta

venules

renal vein

3 processed contribute to urine formation

amount secreted equation

filtration: ultrafiltration, large molecules unable to pass through, primary urine, through tubule

reabsorption: solutes and water

secretion

amount excreted = filtered + secreted - reabsorbed

fenestrated capillary

filtration

where is it

what is filtered, how much

filtration barriers

glomerulus

all constitutes of the blood except blood cells and proteins

15-25% of water and solutes (glucose + ions) in the plasma filtered

kidney filters 180L per day, 7.5 L per hour, blood is 5-6L, only 3L is plasma which is the true thing being filtered because RBC cannot be filtered

filtration barrier: 3 layers


1. glomerular fenestrated capillary endothelium
2. basement membrane
3. podocytes: filtration slits, control the amount filtered, regulated by AND, can “open and close”

Flux across the glomerular capillaries formula

why pi bowman space = 0?

when flux is positive/negative

Flux (J) = blood pressure - osmotic pressure

J = (Pgc - Pbs) - 1(pi gc - pi bs)

GC = glomerular capillary

BS = bowman space

why pi bowman space = 0? because proteins are not filtered into the tubule so omsotic pressure is always 0

flux is + ? favor filtration

flux - ? not favor filtration

resistance of afferent and efferent arterioles

influence __?

RAA and REA

resistance of afferent and efferent arterioles **influence filtration rate**

increasing diameter of afferent art. increases globular pressure

AA: blood coming to center = glomerulus + bowman space

EA: blood going away from center

resistance AA increase? less blood to glomerulus = decreased filtration

resistance AA decrease? filtration increases

REA increase? filtration increases, vasoconstriction, because less blood is leaving capillary = more blood staying in glomerulus = filtration high

glomerulus filtration rate

def

how to measure it

high GFR = ?

input, output

how much blood is filtered in a given time

also establishes rates of other processes like secretion and reabsorption

GFR high = kidney function is high

measure GFR:

* measure clearance of molecule that is filtered but NOT reabsorbed or secreted (inulin)
* renal clearance: volume of plasma from which a substance is completely removed per time
* blood = input, urine = output
* inulin polysacc from plants cannot use it so only filtered out
* Liters per hour

clearance of inulin - idk this

inulin clearance = U\[inulin\] x Vu / P\[inulin\] = GFR

inulin clearance = urine inulin concentration x urine volume / plasma inulin concentration

if clearance of substance < GFR, substance is REABSORBED

if clearance of substance > GFR, substance is SECRETED

filtered load, % reabsorbed, % water reabsorbed

other things to calculate if Vu and plasma and urine concentrations known

filtered load of a compound: Pion x GFR (amount filtered from plasma in mg or moles per hour)

% ion reabsorbed = filtered load - excreted load / filtered load

% water reabsorbed = GFR - Vu / GFR

* majority of water will be reabsorbed, 180L water filtered through but average 1L urine / day

urinary excretion rate = Uion x Vu

clearance of creatinine v inulin

lnulin must be injected to determine GFR

clinically easier to use creatine to estimate GFR

creatinine is filtered + small amount secreted

over or underestimation of GFR with small secretion of creatinine? overestimation because GFR and urine vole. should be the same but secretion adds creatine into urine os its an overestimation

tubular reabsorption

proximal tubule: major reabsorption site, very isosmotic, selective reabsorption, equal osmolarity to blood, most H2O, NaCl and glucose are reabsorbed immediately here, energy required

distal tubule: active NaCl reabsorption in thick limb

loop of Henle: passive H2O and NaCl reabsorption in thin limb, max osmolarity 1200, because of reabsorption filtrate reaching Loop of Henle contains little glucose or amino acids,

nephron structural unit of kidney

proximal tube is 300 osmolarity which is equal to the blood

urine can be diluted 10x than normal (300 → 30)

urine can be concentrated 4x than normal (300 → 1200)

40x range in concentration/dilution of urine

wide range of urine concentration

what is reabsorption driven by

active transport of Na

reabsorption and active Na transport

Na,K,Cl,glucose,water

1. water: passive, follows Na, Cl, glucose
2. glucose transferred by cotransporters with Na into the epithelium, secondary active transporter
3. K goes into epithelial cell, concentration is high, K leaves to blood where \[K\] is low
4. Cl maintains electroneutrality and leaves tubular fluid to blood
5. NaK pump: uses ATP, active, tubular fluid to blood = reabsorption, \[Na\] inside epithelium is low, Na cotransported with HCO3

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density of cotransporters on lumenal side can limit reabsorption - the more transporters = more reabsorption

reabsorption limited by transport maximum for each substance - glucose

normally: glucose filtered, 100% reabsorbed

Pglucose: 1 mg/ml

Tm glucose: 320 mg/min

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Diabetic:

Pglucose > 2mg/ml, 200mg/ 100ml

> Tm, glucose excreted

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glucose in urine = bad = diabetic

tubular secretion

2 major reasons why

gets rid of excess K

* why high K bad? muscles are contracting too much and cause problems = overexcitation
* K in interstitial fluid must be removed

H HCO3 NH3 for acid base balance

toxins:drugs, conjugated to organic acids, enter tubule via transporters, can’t diffuse back into blood due to high polarity

occurs mostly in distal tubules (except for H secretion) most other ions decrease steadily as they are reabsorbed

K in filtrate rises in distal and collecting ducts

K is example of compound that is filtered, reabsorbed AND secreted

too high plasma K can cause muscle convulsions

proximal tubule: K absorbed via passive cotransporters driven by basolateral Na/K ATPase that drives glu, Na and H2O absorption, tubular fluid → blood

distal tubule: excess K secreted by reverse process, blood → tubular fluid

renal blood flow

glomerulus flow rate

renal blood flow

glomerulus flow rate

how is urine concentrated?

what limbs do

what vasa recta do

Loop of Henle

function asymmetry ascending and descending limbs

selective permeability in different parts of the tubule

standing osmotic gradient in renal medulla

corticomedullary osmotic gradient

maintained by

where is highest salt content, highest osmolarity

gradient maintained by absorption of NaCl from loop of Henle urea from collecting duct

cortical nephron

medulla area has high salt content, high osmolarity

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Loop of Henle establishes NaCl gradient in medullary interstitum

2 functions of Loop of Henle

asymmetry of H2O and NaCl permeability in Loop allows it to work as a countercurrent multiplier

2 functions: 1) establish standing osmotic gradient 2) maintain standing osmotic gradient

how is the standing osmotic gradient established? by countercurrent multiplier function

how is a countercurrent multiplier working

pumping → equilibriate → fluid advanced → repeat

Active reabsorption of NaCl

Juxtamedullary nephron

Water leaves descending passively following the ions that leave the ascending

Ascending limb and interstitial fluid wants to maintain a 200mOms difference

Descending limb wants to be equal the osmolarity as interstitial fluid Increasing osmolarity as loop of henle the deeper into the medulla

Counter current multiplication: enables the effects of the gradient to increase (started with 300 and goes up to 700, but actually gets to 1200.. How? Urea on slide 6?)

single effect

The difference produced by use of metabolic energy between adjacent parts of the two oppositely flowing fluid streams in a countercurrent multiplier system



Stannding osmotic gradient is established and maintained, once gradient is established you don’t need to establish again because it should be maintained as you live

collecting duct

Lower portion of collecting duct also permeable to urea

high concentrations in filtrate cause urea to diffuse out into inner medulla interstitium near base of collecting duct

responsible for additional 500-600mOsm in the standing gradient

final step in urine concentration

As filtrate flows down collecting duct, water diffuses into interstitium, depending on duct permeability

If H2O conservation is needed, ADH (antidiuretic hormone) opens water channels, H2O is absorbed, concentrated urine is produced

if H2O conservation not needed, duct (CD) remains impermeable water = dilute urine

top to bottom concentration gradient

side to side gradient is equivalent