The respirtory system supplies O2 and removes waste CO2. 

Pulmanary ventilation- the process in which a volume of gas is added to or removed from lungs

Gas exchange- the process in the lung by which blood is re-charged with O2 and dumps the waste CO2

Tranpsort of O2 and CO2 between the tissues and the lungs

Regulaiton of ventilaton= the process by which bodily needs are translated into more rapid or slower ventalation

Gas flows in response to pressure differences.

Qv=P/R

Changes in lung volumes produce pressure differences that drive air movement

PV = nRT

P is pressure in atm, mmHG,

V is volume

R gas constant, T is temp,

R= .082Latm Mol^-1, K^-1

The diaphragm is the major muscle driving normal inspiration.  It sits right under the lungs. It expands when it contracts

This causes inspiration by Increasing the volume of the thoracic cavity.  This decreases the pressure inside the lungs to allow air to flow in when glottis is open.

Resting expiration is passive.  By the lungs and chest wall being expanded it stores mechanical energy in inspiration.  When the inspiratory muslces relax this  creates a recoil effects that makes the lungs contract, there by pushing air out because of the increas in pressure.

external costal- inspiration

Contracton of the internal  intercostal muscles only  help in forceful or stenous expiration. and abdominal muscles ;

Rectus abdominus, transverse abdomius, external obliuqe, internal oblique

The external intercostal muscles expand the thoracic cage by elevating and extending the sternum.  THis helps reduce pressure of the lungs.  Which allows for air to inside lungs. These lie closest to the spinal cord from the thoracic segements

THe internal intercostal muscle does the opposite.  it lowers and compresses the lungs.  This makes the pressure in the Lungs increase.  Which allows air to flow out in experation.  

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Spinal cord    External intercostal,  Internal intercostal

The compliance and recoil tendency of the lung is produced by elastic fibers and by surface tension.

Elasticity is due to elastic fibers in the lung and airways and to the surface tensino.  The elastic fibers include elastin and collagen fibers in the extracellular space surrounding the alveoli, bronchiols and pulmonary capilaries.  This accounts for 1/3 of the recoil tendency.

P = 2y/r , p is pressure, y is surface tension and r is radius of the sphere.

2/3 of recoil tendency is from aggregate surface tension in the millions of alveoli.  The lungs are filed with salin and no air-water interface

Law of Laplace P = 2y/r

y is the surface tension, r is the radius of the sphere, and p is the pressure.

In normal cases if the surface tension on both the smaller and bigger alveoli were the same then are would flow from the smaller one to the bigger one. 

THIS DOES NOT HAPPEN because the surface tension is highly dependent on r,  because the alveoli are not independent- alveoli are connected by alveoli and as one collapses it is supported by its neighbors.

dG = ydA

dG is the increment of surface free energy,  Y is the surface tension and dA is the increment in area.

Pulmonary surfactan lowers the surface tension in the alveoli

The alveolar type 2 cells secret the lipoprotein maerial called sufactant.

It reduces the surface tesnion by interaction of the hydrophilic parts of the surfactant molecules with the water layer next to the alveolar cells and by the interaction of the hydrophobic parts of the surfactant with the air. 

it casues the hysteresi in the lung volume- pressure curve

Stabiliizes alveolar size

Surfacnt reduces the work of breathing

Surfactan keeps alveoli dry.

The lungs and chest wall ussually pull in opposite directions causing a negative intrapleural pressure.

Intrapleural pressure is the pressure within the narrow space between the lung and the chest wall.

Pa- Pb = Plung + Pchest wall = Prs

Pb is the ambient, barometric pressure. 

Pa is the pressure within the alveoli,  

Plung is the pressure due to elastic properties of the lung, 

Pchest wall is the pressure due to the properties of the chestwall.

Prs is the entire respiratory system pressure consting of lung and chest wall.

At extremely low lung volumes, a lage negative pressure must be applied to counteract the expansion recoil tendency of the chest wall. 

Alveolar pressure is markedly less than the outside barometric pressure. 

The pressure on the lung is positive pushing out against the lung to overcome its recoil tendency.  This  This means that the intrapleural press is ALWAYs less than alveolar pressure, or atmospheric pressure.

FRC(Functional Residual Capacity)- this is the volume point of air in lungs after normal expiration.  This is the point where inspiratory and expiratory muscles are relaxed and alvora pressure PA is equal to the ambient barometrix pressure, Pb.  This makes the pressure across the entire respiratory system, Prs = 0.  This occurs when the recoil force of the lungs exactlly balances the expansion force of the chest wall.  At this point the intrapleural pressure is lower than Pa or Pb.  The lung and chset wall are pulling in opposite directions.

PA= PB ,  Prs=0

[image]

Spirometers measure lung volumes and allow identificatino of several lung volumes and lung capacites.

[image]

Tidal volume(TV)- the amount of air breathed in and out during normal, restful breathing.  Usually around .5 L.

Inspiratory volume(IRV) the additional volume of air that can be inspired at the end of normal or tidal inspire3d.  Typicall for young adults it's about 3L.

Expiratory reserve volume,(ERV)- the additional volume of air that can be expired after a normal or tidal expiration. Typical value is about 1.1L

Residual Volume,(RV)- this is the volume remaining in the lung after a maximum expiration.  Even max effor cannot void the lungs of all air.  THis can only be measured by gas dilution and body plethysmography.  This is usually about 1.2L

To calc Functional Residual Capcity(FRC) - the volume of aire remaing in the lungs after normal or tidal expiration. 

FRC= RV(residual volume) + ERV(Expitory Residual Volume)

Inspiratory capcity (IC)- volume that can be inspired after a normal or tidal experation.

IC= IRV(Inspiratory reserve volume) + TV(tidal volume)

Vital Capcity(VC): this is the sum of all voumes above the residual volume, expiratory reserve volume, tidal volume and inspiratory reserve volume.

VC = ERV + TV + IRV 

Total Lung capacity(TLC) - the maximum volume of air that the respiratory systems an hold.

TLC = VC + RV

Pulmonary Ventilation- this is the rate at which air moves out of the lungs.

QV = TV x RR(respirtory rate)

Resting pulmonary ventilation is the respiratory minute volume.

Forced vital Capacity- this is a clinically useful measure of the ability to move air quickly.

A person is connected to a spirometer,

They breathe in as deeply as possible and then expire as completely and rapidly as possible.  The volume of air expired this way is the FVC.

FEV1, FEV2, and FEV3.  Refer to the seconds at which volume was expired.

Maximal mid-expiratory flow rate- the averaged forced expiratory flow rate from 25% to 75% of FVC.

[image]

a spirometer could calc airway resitance by Calculating th flow of air.  As well as the Change in pressure in the lungs.   It would then divide the pressure by flow.

R = P/Qv

Laminar flow- This flow has a resitance that's independent of flow. This is a linear relationship

Turbulent flow-  This is a non-linear relation between flow and pressure difference. 

deltaP = K₂ x Qv²

K2 is a coefecient.

turbulent Re greater than 2000

laminar flow.  R = delta P/Qv = K1

Turbulent flow

R=DeltaP/ Qv = K2 x Qv

R total= K1 +K2Qv

Delta P = K1Qv + K2Qv²

Contraction of the muscles give bronchoconstricion, Parasympathetic stimulation constricts 

Relaxation of the muscles give bronchodilation. Sympathetic stimulation dilates.

Respiratory quotient is quoteint of  CO2 produced diveded by the O2 consumed.This usually depends on the type of material being used for energy.  Fats ussually give off a R of .7

RQ = QCO²/QO² 

Respiratory exchange ratio is the ration of CO2 to O2 exchange with the body and the atmosphere.At steady state it's the same as Respiratory qooteint.  But as metabolic rate changes so does the exchange ratio.

Oxygen is driven into the blood by diffiusion.

Respiratory system exchanges blood gasses w/ atm gasses, gases dissolve in water, gases diffuse across alveolar membrane passively

PV = nRT

P is the pressure, V is the volume, 

n is the number of gas moles, 

R is the gas constant .082L/atm mol K, 8.312 joules/mol k

T is the temp

Partial pressure is the amount of pressure each gas contributes.

P = (nA/V)*RT + (nC/V)*RT

Vapor pressure is the partial pressure of water in the gas phase this is at equilibrium with liquid water. At this point rate of evaporation is equal to rate of condensation.

Gas phase at equilibrium will be saturated with water vapor.

The vapor pressure at body temperature is 47mmhg. This is at 37degrees C or.  310K.

P_A= f_A(P_B-P_H2O)

PB is the barometric pressure. And Fa is the mole fraction of dry air.

PA is the waterd saturated air.

XA= βA*PA

XA is the mole fraction of Gas A in the aqueos phase.

Ba is the solubility

PA is the partial pressure of the gas in the gaseous phase at equilibrium with the  atmosphere.

STPD - Standard Temperature Pressure Dry

0C= 273.6K

1atm = 760mmhg

0 water vapor.

Lung volume rates, and movements of volume in the lung is measured in BTPS, or Body Temperature and Pressure, Saturated.

VBTPS = .2104VSTPD

BTPS- Has the temp of 310.16K.

PH2O - is 47mmhg

PV=nRT

STPD PV1 = nRT1

BTPS PV2 = nRT2

if n is constant

V2 = (T2/T1)(P1/P2)(V1)

this solves for V2 which is V of BTPS

A. Outer most layer Alveolar Lining, Alvolar Cell

B.Interstitial Fluid

C. Endothelial Cell

D. Red Blodd cells.

Each layer has a permability p = K_sD_s/σ 

[image]Ks is the partion coeficent,

Ds- the diffusion coefficent 

o- is the thickness of the membrane barrier. 

High soulibilty and high concentrations, High Ks alow for gasses to move more rapidly

Large diffusion coefficents(Ds). Help gass move more rapidly.  These are products of the gases itself, not the system. 

And short or small thickness(O).  the alveoli membrane is about .5microns thick.

The pressure gradient drives flow.

Qs= (AksαDs/o)*ΔP

Qs = DL* ΔP

DL is the Diffusion capacity.

DL= Qs/ΔP

units are ml per min per, pressure.

 this is the flow per unit of partial pressure.

Alvolar Ventilation-  QA = VR(TV-VD)

VR is the resperation rate

TV is the tidal Volume

VD is the Anatomic Dead Space. 

Pulmonary ventalition- this is the rate at which air is entering or leaving the lungs.

QP= VR*TV

VR-respitory rate TV-averge tidal volume.

QA = (Qco2/PAco2)*(PB-47)

QA is the alveolar ventallation,

QCo2 is  the Production of CO2

PACO2 - the partial pressure of CO2 in alveolar air.

PB is the barometric pressure.

P_AO² = f_iO²(PB-47) - (1/R)*P_CO²

PB is the barametric pressure 

fiO2 - is the mole fraction of inspired O2

Pco2 is the partial fracton of co2

R is the respitory quotient

[image]

A. Blood remains in the capilaries for about .75secs.

B. PVO2 is about 40 mmhg, PVCo2 is about 46mmhg

C.Blood is equilibrated between the plasma and capilaries in .25secs.

D.During exercise Cardiac Output is increased.

figure 6.4.2

HbO₂ = ([O₂]^h / (K + [O₂]^h)) X HbO₂max

this is a measure of the cooperativity of binding. 

HbO2 - the concentration of O2 bound to hemoglobin.

h is the Hill coefficent.

If O2 increases the affinity for the next binding site. its Positively cooperative.  h > 1.0

Q_a([O₂]_a-[O₂]_v) = Q_O2

Q_{a -}the cardiac out put.

QO2- the total oxygen consumption in units of ml O2 at STPD min^-1

[O₂]_a -the arterial blood total concentration of O2.

[O₂]_v- this is the venous blood total of O2

All terms must be expressed in STPD.

The alveolar capillaries have a large surface area and small diffusion distances, so the blood in the alveolar capillaries equilibrates with alveolar air.  Some blood that perfuses poorly ventilated regions of the lungs or from anatomic shunts contributes volume but less O2 to the arterial blood.  ThIs is a venous admixture that reduces the Partial pressure of O2 from 102mmhg to 95mmhg.  The gradients for O2 diffusion from alveolar air to blood and from blood to tissue are much greater than the gradients for CO2 diffusion because the higher solubility of CO2 enables a faster diffusion

Oxygen travels to the interstitial fluid.  From here the blood diffuses futher through the cytosol.  From the cytosol oxygen flows to the lowest Partial O2 pressure at the Mitochondria. Fig. 6.4.3

Arteriolar blood PO2 - 95mmhg

PIsfO2 - 40mmhg

PcyO2- less than 40mmhg

PmitO2- Less than Pcytosol

Myoglobin sotres O2 in oxidative muscle and may enhaance diffusion.

It stores the oxygen for use  during heavy exercise.  It also enhances diffusion throught he cytosol by carrying the oxygen.  By binding O2, myoglobin(Mb) provides a second diffusive pathway for O2 through the cell cytosol.

H+ increase also shuts the curve down and to the right. 

Increased in PCO2 also shifts the curve down and to the right.

An increase in temperature shifts the curve down and to the right.

Increase 2,3DPG also shifts the curve downa and to the right.

These all give reduced affinity for O2.  This helps dissociate O2 from Hb.This results in more O2 being delivered. At constant PO2.

A decrease in H+,2,3DPG, temperature. will give an increase in affinity.

dissolved as CO2 - 10% of total transport,

as

HCO3-: 85% 

 hemoglobin as carbaminohemoglobin.- 5%

Trasnport of the CO2  partially involves cholride shift. 

1. after co2 is dissolved acrross the tissue cell.It is hydralzed by carbonic anhydrase to form the acid H2CO3

2. this then disssasociates rapidly rapidly.  to form H2CO3.  The HCO3 exchanges for CL- across the red blood cell membrane.(CHLORIDE SHIFT)

3.  THis makes CO2 combine with NH2 groups on the hemoglobin forming carbaminohembglobin.

Less 6.9 causes coma

Greater Than 7.8 death with tetany and convulsions

Normal range is 7.35 and 7.44

Acidemia, Acidosis is having a [H+]  below 7.35

Alkolosis ph greater than 7.44 

High sensitivety is due to to the binding (absorption, association) or unbinding (desorption, dissociation) of H to or from ionizable groups on amino acids that make up proteins.  Ph also greatly effects enzymes.

Alkalosis- a ph higher than 7.44

Acidosis- blood has a ph lower than 7.35

Chemical Buffer- respond rapidly and are the first line of defense in acid-base imbalances.  Resists changes but can not fully restore

Respiratory system- works by adjusting plasma PCO2, increasing PCO2 lowers pH lv, Decreasing  PCO2 raises pH lv.

The renal system- this works by adjusting [HCO3-] , increase ins HCO3 raises ph.  Decrease in HCO3 decrease ph. this is complete change.

Jf = Kf[HA] 

Jr= Kr[H][A-]

when Jf= Jr= KD, dissociation constant. Strong acid = large KD

kD= [A-][H]/[HA]  , units are M 

Association constant Ka is the inverse of KD. Strong Ka = Strong Base.

units M to -1

Plasma buffers:

Protein Buffers

Bicarbonate buffer system 

Phosphate buffers

This states that all buffers in a solution are simultaneously in equilibrium with one [H+].

This also means that  adjustments of a single buffer system will adjust them all through changes in [H+].  This makes the bicarbonate very important because its physiologicaly  adjusted.

Hypoventilation causes respiratory acidosis(a decreased pH) 

Hyperventilation causes respiratory alkalosis(a increase in pH)

the Respiratory system responds to Alkalosis by hypoventilating.  This raises the plasma PCO2 and adjusts plasma pH back towards normal.  This only works partially, kidneys are needed to adjust [HCO3-].   

*factors that cause Alkalosis,  A loss in [H+],  vomiting, alkali treatment for peptic ulcers.

The body responds to Acidosis by with hyperventilation. Hyper ventalation lowers plasma PCO2 and adjusts plasma pH back to normal.  The increased ventilatory drive results from stimulation of chemosensors for ph that hyelp control ventilatory drive.  Again Kidneys are needed for full recovery.

*Factors that induce Acidosis(increased or non-secretion of [H+]. diarrhea, in which buffer HCO3- is lost, diabetes melitus in which metabolic acid production is increased, and Renal Tubular acidosis- where kidneys fail to excrete compensated by

external intercostal muscle

intercostal muscle

abdominal muslces

Voluntary control arises from the cerebral cortex

Involuntary control arises from centers in the medulla and pons

Both area project to the spinal motor neuros that control respiratory muscles, but via different pathways. Cutting through the brainstem above the pons removes all voluntary control and only automatic mechanisms in the brainstem drive ventilation.

Cell bodies of motor neurons that activate the diaphragm are located in C3-C5.

These axons collect in phernic nerve. 

Cellbodies of intercostal muscles are located in the thoracic spinal cord. 

Abodominal muscles are controlled by thoracic and lumbar neurons

DRG(Dorsal Respiratory group)- the source of normal respiratory rhyth. location Medulla

Respiratory Group; receives a variety of inputs (afferent signals over the glossopharyngeal & vagus nerves), excites inspiratory motorneurons; located in the dorsal medial medula; projects to PRG & VRG, indicating the time of inspiration the same time it begins

VRG(Ventral Respiratory group) - Located in the ventral region of the Medula

has inspiratory/I neurons that fire AP's during inspiration and E neurons (expiratory) that fire AP's during the expiratory phase.
*If cut off, no respiration at all.
**2 theories of respiratory pattern origin:

(1) cellular pacemakers – neurons w/ voltage and time-dependent channels that produce rhythmic behavior at the cellular level – some neurons identified in the pre-Botzinger compled in rostral VRG;

(2) rhythm generation is a system property that arises from interactions between neurons due to patterns of inhibition and excitation along w/ appropriate sensory input – in the mature animal, experiments suggest the respiratory rhythm is a network property requiring interaction among neurons.

Located in Carotid bodies and Aortic bodies(ontop of the aortic arch). 

They detect changes in arterial PO2, PCO2, and pH. 

Carotid are primary,  Aortic bodies are Secondary. 

The ventilatory response to lowering PaO2 is almost exclusively determined by the carotid bodies.  The only sensory for oxygen comes from carotid bodies.

Chemosenosrs firing rate increase with PaCO2, with decreased pH and decreased PaO2.

PaO2 is more important than PaCO2

The carotid body is innervated by the carotid sinus nerve, and sensory info travels to the brainstem through the glossopharyngeal nerve, cranial nerve IX.

The aortic bodies are innervated by the vagus nerve, cranial nerve X.

Chemosenosrs firing rate increase with increased PaCO2, with decreased pH and decreased PaO2.

PaO2 is more important than PaCO2

Their located in 3 zones that reside in the ventral medulla.  Theres

Rostrally area,  Top area, right below pons

Intermediate area, right next to Glosspohayngeal, vagus and spinal accesary.  The middle

Caudal cchemosensitive area.  Bottom of medulla.  Right about hypoglossal nerve.

The hyperventilatory response (measured by integrated response of the phrenic nerve) occurs when the pH is unchanged but ↑PCO2 or when PCO2 is unchanged and ↓pH. So, central chemoreceptors respond to either PCO2 or the pH as independent stimuli.
They are also functionally & structurally separated from blood by the blood-brain barrier. ↑ blood PaCO2 → increased CSF PCO2 → increase CSF [H+] → decreases pH, which chemoreceptors sense (and in response, increase firing rate) → increased respiration.

The central chemoreceptors respond with a hyperbventilatory response of the phrenic nerve.  This occurs when there are changes in PCO2 despite there being no changes in O2  This also occurs when pH is change while PCO2 is stable.  This means that central chemorecpors respond to  ph or PCO2 independtly.

They respond to a decrease in pH in the CSF is an increased firing rate.  This inturn increases respiration.

Increased respiration during exercise may be neural and may involve learning.
With heavy exercise, ↑ O2 consumption, CO2 production, H+ generation from metabolic acids, which ↓ PaO2, ↑PaCO2, leading to increased ventilatory drive.
BUT, moderate exercise: PAO2, PaCO2, & blood pH stay moderately the same. “wtf?”

1. passive     movement of limbs ↑ ventilation, direct nervous stimulation of     limbs ↑ ventilation... These suggest that muscles and joints     notify the respiratory centers about their activity through sensory     afferents, stimulating ventilation. (Muscle mechanoreceptors &     nociceptors make largest contribution to hyperpnea of exercise)     Motors systems may drive muscles that send collaterals to the     respiratory system to simultaneously drive ventilation – a     feedforward mechanism in which the motor system anticipates the     respiratory demands of its commands & adjusts ventilation in     advance.   
2. Altered     sensitivity of the central controllers to input from the peripheral     & central chemoreceptors. Feedforward input from motor systems     or muscle afferences could alter the response of the brainstem     respiratory neurons so the same input from chemoreceptors produces a     larger ventilatory drive.

** also, it may involve learning. More practice, i.e., more exercise, “teaches” the nervous system how much ventilation is necessary to prevent disorders of blood gases or pH with different exercise intensities.

During excersie the body moderates concentration levels close enough so that PaO2 and PaCO2 and blood pH are normal.  At higher rates HCO3 might fall. 

Test in animals show that movement of limbs and joints stimulate ventilation. The muscle system and respiratory system have a feedfoward michanism in which the motor system anticipates the respiratory demands of its commands, and adjusts ventilation in advance of those demands rather than waiting for discrepanices of respiratory gases or ph to stimulate ventilation . 

Combining the input of the feedfoward mechanism with chemoresports could produce a larger ventilatory drive.

Respiratory response is also has conditioning contributed to the amount of ventilation.  Each exercise teasches the nervous system how much ventilation is necessary to prevent disorders of the blood gases or pH with each intensity of exercise.