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Functional AnatomyFunctional Anatomy

The main function of respiratory system is to take The main function of respiratory system is to take in Oin O22 & give out CO & give out CO22. It also regulates acid-base . It also regulates acid-base

balance & heat & participates in phonation & balance & heat & participates in phonation & vocalization. Respiratory system is divided into vocalization. Respiratory system is divided into extrathoracic & intrathoracic partsextrathoracic & intrathoracic parts::

Extrathoracic partExtrathoracic part: Nose, nasopharynx (& mouth : Nose, nasopharynx (& mouth & oropharynx), larynx and upper part of trachea& oropharynx), larynx and upper part of trachea

Intrathoracic partIntrathoracic part involves lower part of trachea, involves lower part of trachea, carina, two main bronchi (primary bronchi), other carina, two main bronchi (primary bronchi), other bronchial tree (about 34 generations): Lobar bronchial tree (about 34 generations): Lobar bronchi (secondary bronchi), lobular or segmental bronchi (secondary bronchi), lobular or segmental bronchi (tertiary bronchi), terminal bronchioles, bronchi (tertiary bronchi), terminal bronchioles, respiratory bronchioles, alveolar ducts, atria, respiratory bronchioles, alveolar ducts, atria, alveolar sacs and alveolialveolar sacs and alveoli..

Functionally, the respiratory system is divided into Functionally, the respiratory system is divided into two main zones: two main zones: Conductive zone:Conductive zone: no gas exchange, no gas exchange, transmits air to next zone, anatomical dead space, transmits air to next zone, anatomical dead space, from nose to terminal bronchioles & from nose to terminal bronchioles & respiratory respiratory zone:zone: gas exchange, involves transitional zone, gas exchange, involves transitional zone, from respiratory bronchioles to alveolifrom respiratory bronchioles to alveoli..

The alveolar epithelial wall is composed of three The alveolar epithelial wall is composed of three types of cellstypes of cells : :

Type I pneumocytes: Squamous epithelial cells Type I pneumocytes: Squamous epithelial cells Type II pneumocytes: Secrete surfactantType II pneumocytes: Secrete surfactantThird type: Alveolar macrophagesThird type: Alveolar macrophages

Respiratory membrane: 6 µ in diameter, surface Respiratory membrane: 6 µ in diameter, surface area 140 marea 140 m2 2 , six layers, six layers : :

11 . .Alveolar fluid lining alveoli (with surfactant)Alveolar fluid lining alveoli (with surfactant)22 . .Single layer of squamous alveolar epitheliumSingle layer of squamous alveolar epithelium

33 . .Basement membrane of alveolar epitheliumBasement membrane of alveolar epithelium44 . .Narrow interstitial spaceNarrow interstitial space

55 . .Basement membrane of capillary endotheliumBasement membrane of capillary endothelium66 . .Single layer of squamous capillary endotheliumSingle layer of squamous capillary endothelium

Functions of upper respiratory systemFunctions of upper respiratory system

Warming upWarming up of air (within body temperature) of air (within body temperature)HumidificationHumidification of air (about fully saturated with of air (about fully saturated with

water vapor, otherwise, lung crusting & infection)water vapor, otherwise, lung crusting & infection) . . FiltrationFiltration of large foreign particles: Nostrils' hair of large foreign particles: Nostrils' hair

Turbulent precipitationTurbulent precipitation: Particles larger than 6μ in : Particles larger than 6μ in diameter on mucous coat of nose & nasopharynxdiameter on mucous coat of nose & nasopharynx..

Gravitational precipitation Gravitational precipitation : Smaller than 6μ dia. : Smaller than 6μ dia. particles within bronchioles, taken up by alveolar particles within bronchioles, taken up by alveolar

macrophages or exhaled outmacrophages or exhaled out . .Mucous coat & cilia, move to cough or swallowMucous coat & cilia, move to cough or swallow

Muscles of respirationMuscles of respiration

Normal quiet breathing: Contraction & relaxation Normal quiet breathing: Contraction & relaxation of diaphragm, changes vertical dimension of chest. of diaphragm, changes vertical dimension of chest. Inspiration (inhalation): Active, negative pressure, Inspiration (inhalation): Active, negative pressure,

syringe-like mannersyringe-like manner . .Expiration (exhalation): Passive, relaxation of dia-Expiration (exhalation): Passive, relaxation of dia-phragm & elastic recoil of lung, thoracic & abdom-phragm & elastic recoil of lung, thoracic & abdom-

inal tissues, raises pressureinal tissues, raises pressure

Heavy inspiration: Increases anteropost. + vertical Heavy inspiration: Increases anteropost. + vertical dimensions, (exteral intercostal muscles+ diaph.), + dimensions, (exteral intercostal muscles+ diaph.), + elevation of thoracic cage: sternomastoids, elevation of thoracic cage: sternomastoids, scalenes, serratus ant. & pectoralis minorscalenes, serratus ant. & pectoralis minor..Heavy expiration: Internal intercostal & abd. mHeavy expiration: Internal intercostal & abd. m..

Pulmonary volumes and capacitiesPulmonary volumes and capacities

Pulmonary volumes are:Pulmonary volumes are:1-Tidal volume (VT): Volume inspired & expired 1-Tidal volume (VT): Volume inspired & expired each quiet breath. It is about 500 ml.each quiet breath. It is about 500 ml.2-Inspiratory reserve volume (IRV): Maximum 2-Inspiratory reserve volume (IRV): Maximum volume can be inspired above VT. About 3000 ml.volume can be inspired above VT. About 3000 ml.3-Expiratory reserve volume (ERV): Maximum 3-Expiratory reserve volume (ERV): Maximum amount expired after VT. About 1100 ml.amount expired after VT. About 1100 ml.4-Residual volume (RV): Volume remaining after 4-Residual volume (RV): Volume remaining after the most forceful expiration. About 1200 ml.the most forceful expiration. About 1200 ml.

Pulmonary capacities are:Pulmonary capacities are:1-Inspiratory capacity (IC)= VT + IRV ≈ 3500 ml.1-Inspiratory capacity (IC)= VT + IRV ≈ 3500 ml.2-Functional residual capacity (FRC)2-Functional residual capacity (FRC) FRC = ERV + RV ≈ 2300 ml.FRC = ERV + RV ≈ 2300 ml.3-Vital capacity (VC) = VT+ IRV+ERV ≈ 4600 ml.3-Vital capacity (VC) = VT+ IRV+ERV ≈ 4600 ml.4-Total lung capacity (TLC) = VC + RV ≈ 5800ml.4-Total lung capacity (TLC) = VC + RV ≈ 5800ml.

All these volumes & capacities are in average sized All these volumes & capacities are in average sized healthy young males but, they are about 20%-25% healthy young males but, they are about 20%-25% less in females. They are also lower in older, less in females. They are also lower in older, shorter, asthenic, black complexion, lowlander and shorter, asthenic, black complexion, lowlander and smoker subjects than in younger, taller, athletic, smoker subjects than in younger, taller, athletic, white complexion, highlander and non-smoker white complexion, highlander and non-smoker subjects respectivelysubjects respectively

Pulmonary and alveolar ventilationPulmonary and alveolar ventilation

Normal respiratory rate (or respiratory frequency Normal respiratory rate (or respiratory frequency “RF”) is 12-15 BPM. “RF”) is 12-15 BPM. Pulmonary ventilation (or Pulmonary ventilation (or minute respiratory vol.)minute respiratory vol.) ==VTx RF which is amount VTx RF which is amount of air moved into respiratory passages each min. of air moved into respiratory passages each min. 500 ml x 12 to 15 BPM = 6000 to 7500 ml\ min500 ml x 12 to 15 BPM = 6000 to 7500 ml\ min. . About 150 ml is wasted inside dead space (VD).About 150 ml is wasted inside dead space (VD).Alveolar ventilation (VA) is total amount reaches Alveolar ventilation (VA) is total amount reaches respiratory zone each minute: VA=RF x (VT-VD)respiratory zone each minute: VA=RF x (VT-VD)VA=(12 to 15)x( 500 - 150 )= 4200 to 5250 ml\minVA=(12 to 15)x( 500 - 150 )= 4200 to 5250 ml\min

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Anatomical and physiological dead spaceAnatomical and physiological dead space

Conductive zone is anatomical DS: There is pulm. Conductive zone is anatomical DS: There is pulm. ventilation but no pulm. Perfusion. When there is ventilation but no pulm. Perfusion. When there is alv. ventilation but perfusion temporarily blocked; alv. ventilation but perfusion temporarily blocked; this is called physiological DS (e.g. at apex of lung this is called physiological DS (e.g. at apex of lung during upright position: blood pools into base). during upright position: blood pools into base). When block is permanent, it is pathological DS. When block is permanent, it is pathological DS.

When there is perfusion, but no ventilation, oxyg-When there is perfusion, but no ventilation, oxyg-enated Bd will be mixed with deoxygenated Bd & enated Bd will be mixed with deoxygenated Bd & condition is called shunt. e.g. of anatomical shunt is condition is called shunt. e.g. of anatomical shunt is oxygenated Bd returned to left atrium via pulm. vv oxygenated Bd returned to left atrium via pulm. vv which is mixed with deoxygenated Bd from lung which is mixed with deoxygenated Bd from lung tissues. e.g. of physiological shunt is at base of lung tissues. e.g. of physiological shunt is at base of lung during upright position. during upright position.

e.g.s of pathological shunt are congenital anomalies e.g.s of pathological shunt are congenital anomalies like patent ductus arteriosus (PDA) & patent like patent ductus arteriosus (PDA) & patent foramen ovale (PFO). Patent=open. foramen ovale (PFO). Patent=open. Ductus arteriosus (a bv that allows Bd to bypass Ductus arteriosus (a bv that allows Bd to bypass baby's lungs before birth) fails to close after birth. baby's lungs before birth) fails to close after birth. Foramen ovale (a normal opening between left & Foramen ovale (a normal opening between left & right atria of fetal heart) fails to close after birthright atria of fetal heart) fails to close after birth

Forces controlling lung volumesForces controlling lung volumes

Pleural pressure (intrapleural pressure) Pleural pressure (intrapleural pressure)

Space between visceral & parietal pleurae is filled Space between visceral & parietal pleurae is filled with pleural fluid: lubrication, sliding & prevents with pleural fluid: lubrication, sliding & prevents separation. The pressure inside the pleural space is separation. The pressure inside the pleural space is pleural or intrapleural pressure: always negative pleural or intrapleural pressure: always negative

about -5 to -7.5 cmH2O (1cmH2O = 0.75 mmHg)about -5 to -7.5 cmH2O (1cmH2O = 0.75 mmHg) . .The pressure inside alveoli is alveolar pressure = The pressure inside alveoli is alveolar pressure = about -1 to +1 cmHabout -1 to +1 cmH22O. Difference between pleural O. Difference between pleural

and alveolar pressures is transpulmonary pressureand alveolar pressures is transpulmonary pressure..

Airways resistanceAirways resistance

Greatest resistance to air flow is in larger bronchi Greatest resistance to air flow is in larger bronchi near trachea (not in smaller airways due to large near trachea (not in smaller airways due to large number of these airways “about 65000 parallel number of these airways “about 65000 parallel terminal bronchioles” & very small amount of air terminal bronchioles” & very small amount of air passing through each. But under certain disease passing through each. But under certain disease conditions, greatest resistance occurs in smaller conditions, greatest resistance occurs in smaller airways because they’re occluded by secretory airways because they’re occluded by secretory products & greater % of sm. muscles in their wallsproducts & greater % of sm. muscles in their walls

Direct sympathetic control of bronchiolar smooth Direct sympathetic control of bronchiolar smooth muscles is weak but, circulating EPI (& to a lesser muscles is weak but, circulating EPI (& to a lesser extent NE) hormones cause bronchodilatation. extent NE) hormones cause bronchodilatation. Vagal (parasym.) stimulation results in secretion of Vagal (parasym.) stimulation results in secretion of Ach: causes bronchoconstriction (BC). Atropine Ach: causes bronchoconstriction (BC). Atropine (anticholinergic) blocks action of Ach, relieves BC. (anticholinergic) blocks action of Ach, relieves BC. Irritation of resp. epith. with noxious gases (as SOIrritation of resp. epith. with noxious gases (as SO22) )

cigarette smoke, fumes, dusts, infection …. results cigarette smoke, fumes, dusts, infection …. results in reflex nervous & local (non nervous) BCin reflex nervous & local (non nervous) BC

BC is due to allergic reaction (between antibody BC is due to allergic reaction (between antibody & antigen) e.g., when histamine, slow reactive & antigen) e.g., when histamine, slow reactive substance of anaphylaxis or other substances are substance of anaphylaxis or other substances are released from mast cells in response to exposure to released from mast cells in response to exposure to allergens like pollen in air, or other sensitizing allergens like pollen in air, or other sensitizing

agents. This is a type of immune reactionagents. This is a type of immune reaction..

Surface tension and surfactantSurface tension and surfactant

Surface tension is the ability of fluid molecules on Surface tension is the ability of fluid molecules on surface with air for extra strong attraction surface with air for extra strong attraction resulting in tendency of surface to contract. resulting in tendency of surface to contract. Surface tension of alv. fluid results in alv. collapse Surface tension of alv. fluid results in alv. collapse (atelectasis) but this is prevented by presence of a (atelectasis) but this is prevented by presence of a surface active agent secreted by type II alveolar surface active agent secreted by type II alveolar epithelium which is called surfactant. It reduces epithelium which is called surfactant. It reduces

surface tension from 50 dyne\cm to 5-30 dyne\cmsurface tension from 50 dyne\cm to 5-30 dyne\cm..

Surfactant is complex mixture of phospholipids, Surfactant is complex mixture of phospholipids, other lipids, proteins, CHO, Caother lipids, proteins, CHO, Ca++++ & some ions & some ions..

Activity of surfactant depends on conc. & orient-Activity of surfactant depends on conc. & orient-ation of phospholipids molecules on surface, while ation of phospholipids molecules on surface, while importance of glycoprotein & Caimportance of glycoprotein & Ca++++ is to enhance is to enhance spread of phospholipids over surface. Thyroid & spread of phospholipids over surface. Thyroid & glucocorticoids accelerate maturation of glucocorticoids accelerate maturation of surfactant, cigarette smoking reduces its surfactant, cigarette smoking reduces its productionproduction..

Pressure that causes alv. collapse is alv. collapse pr. Pressure that causes alv. collapse is alv. collapse pr. : about 4 cmH2O in presence of surfactant. : about 4 cmH2O in presence of surfactant. Alveolar collapse pressure = 2T \ rAlveolar collapse pressure = 2T \ r , where T is , where T is

surface tension, r is radius of alvsurface tension, r is radius of alv . . In many premature babies radius of alv. is about In many premature babies radius of alv. is about 1\4th normal with no secretion of surfactant which 1\4th normal with no secretion of surfactant which increase alv. collapse pr. to 40 cmH2O or more & increase alv. collapse pr. to 40 cmH2O or more & baby dies from alv. collapse (RDS or hyaline baby dies from alv. collapse (RDS or hyaline

membrane disease)membrane disease) . .

Lung complianceLung compliance

It is the extent to which lung volume expands for It is the extent to which lung volume expands for each unit increase in transpulmonary pressure.each unit increase in transpulmonary pressure.Lung compliance=ΔV\ ΔPLung compliance=ΔV\ ΔP where ΔV is change in where ΔV is change in lung vol. & ΔP is change in transpulmonary pr.lung vol. & ΔP is change in transpulmonary pr.Total compliance is about 200 ml\cmH2O, while Total compliance is about 200 ml\cmH2O, while compliance of lungs & thorax is 110 ml\cmH2O.compliance of lungs & thorax is 110 ml\cmH2O.Compliance is decreased in restrictive pulmonary Compliance is decreased in restrictive pulmonary diseases (pulmonary fibrosis, pleurisy, pleural diseases (pulmonary fibrosis, pleurisy, pleural effusion….) while it is increased in emphysemaeffusion….) while it is increased in emphysema

Elastic and non-elastic workElastic and non-elastic work

Work of breathing is elastic & non-elastic workWork of breathing is elastic & non-elastic workElastic (compliance) workElastic (compliance) work: Is work required to : Is work required to overcome elastic forces of lungs & chest (65% of overcome elastic forces of lungs & chest (65% of total work). total work). Two thirds of lung elastic forces are due to surface Two thirds of lung elastic forces are due to surface tension & one third is due to elasticity of lung tension & one third is due to elasticity of lung tissues themselves. tissues themselves. Compliance work = ΔV . ΔP \ 2Compliance work = ΔV . ΔP \ 2

Non-elastic workNon-elastic work: which is subdivided into:: which is subdivided into:••Airways resistance workAirways resistance work: Required to overcome : Required to overcome resistance to air movement through respiratory resistance to air movement through respiratory passages which is about 28% of total work passages which is about 28% of total work ••Tissue resistance workTissue resistance work: Required to overcome : Required to overcome viscosity of lung & chest tissues which is about 7% viscosity of lung & chest tissues which is about 7% of total workof total work

In restrictive pulmonary diseases (pulmonary In restrictive pulmonary diseases (pulmonary fibrosis, pleurisy, pleural effusion….) compliance fibrosis, pleurisy, pleural effusion….) compliance & tissue resistance work are especially increased & tissue resistance work are especially increased while in obstructive airway diseases (emphysema, while in obstructive airway diseases (emphysema, chronic bronchitis, chronic bronchial asthma….), chronic bronchitis, chronic bronchial asthma….), airways resistance work is especially increased & airways resistance work is especially increased & work of expiration becomes even more than work work of expiration becomes even more than work of inspiration. At rest, only 3-5% of body energy of inspiration. At rest, only 3-5% of body energy for ventilatory process, rising 50 folds in exercise for ventilatory process, rising 50 folds in exercise especially in respiratory diseased subjects. especially in respiratory diseased subjects.

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Diffusion of gasesDiffusion of gases

A mixture of gases inside a container exerts a total A mixture of gases inside a container exerts a total pr. against its walls which equals the sum of partial pr. against its walls which equals the sum of partial pr.s of its component gases. Partial pr. of each gas pr.s of its component gases. Partial pr. of each gas is proportional to its conc. within mixture. Partial is proportional to its conc. within mixture. Partial pr. of oxygen is Ppr. of oxygen is PO2O2, of carbon dioxide is P, of carbon dioxide is PCO2CO2 & of & of

water vapor is Pwater vapor is PH2OH2O. Alv. P. Alv. PO2 O2 is Pis PAAO2O2, while arterial , while arterial

PPO2O2 is P is PaaO2O2 & same thing for CO & same thing for CO22. .

Henry's law states that partial pr. of dissolved gas Henry's law states that partial pr. of dissolved gas is directly proportional to conc. of its molecules & is directly proportional to conc. of its molecules & inversely proportional to its solubility coefficient in inversely proportional to its solubility coefficient in solvent. Solubility coefficient of COsolvent. Solubility coefficient of CO22 in water is 20 in water is 20

times more than Otimes more than O22 so as diffusion of CO so as diffusion of CO22 across across

respiratory membrane. Diffusion of gases is along respiratory membrane. Diffusion of gases is along partial pr. gradient (from higher to lower)partial pr. gradient (from higher to lower)

Partial pr.s of alv. gases are different from inspired Partial pr.s of alv. gases are different from inspired gases due to humidification, Ogases due to humidification, O22 is continuously up is continuously up

taken to & COtaken to & CO22 is continuously added from pulm. is continuously added from pulm.

capillary. POcapillary. PO22 of pulmonary vein (95 mmHg) is of pulmonary vein (95 mmHg) is

different from that of pulmonary capillary (104 different from that of pulmonary capillary (104 mmHg) due to anatomic shuntmmHg) due to anatomic shunt

Factors affecting diffusion rate Factors affecting diffusion rate The diffusion rate of OThe diffusion rate of O22 is about 230ml\min & is about 230ml\min &

4600 ml\min during exercise. Diffusion rate of gas 4600 ml\min during exercise. Diffusion rate of gas molecules across biological membranes is affected molecules across biological membranes is affected by several factors summarized in equationby several factors summarized in equation::

Another factor, temperature which is directly pro-Another factor, temperature which is directly pro-portional to D but it is constant in healthy humanportional to D but it is constant in healthy human

Diffusion rate is greatly reduced inDiffusion rate is greatly reduced in::Pulmonary fibrosis: Increased thickness of RMPulmonary fibrosis: Increased thickness of RMEmphysema: Decreased surface area of RMEmphysema: Decreased surface area of RMHigh altitude: Reduced pr. gradient of OHigh altitude: Reduced pr. gradient of O22

(hypoxia)(hypoxia)

Diffusing capacityDiffusing capacity

Diffusing capacity (DL) is vol. of gas diffuses across Diffusing capacity (DL) is vol. of gas diffuses across RM each min. for RM each min. for ΔΔP = P = 1 mmHg1 mmHg . .

At rest, DAt rest, DLO2LO2 =21 ml\min. mmHg & during exercise =21 ml\min. mmHg & during exercise

about 65 ml\min. mmHg (increased Bd flow, ideal about 65 ml\min. mmHg (increased Bd flow, ideal distribution & increased surface area of RM due to distribution & increased surface area of RM due to

capillary distension). Dcapillary distension). DLCO2LCO2 = 20 times D = 20 times DLO2LO2..

Diffusion of ODiffusion of O22 & CO & CO22 across RM takes 0.3 s, across RM takes 0.3 s,

while Bd traverses pulm. capillary within 0.75s. at while Bd traverses pulm. capillary within 0.75s. at rest. This is called rest. This is called safety factorsafety factor for exercise when for exercise when Bd velocity in pulm. capillary becomes 0.3sBd velocity in pulm. capillary becomes 0.3s

When Bd is saturated with OWhen Bd is saturated with O22 & CO & CO22 , it must be , it must be

replaced by perfusion so; uptake of Oreplaced by perfusion so; uptake of O22 & output of & output of

COCO22 is is perfusion limitedperfusion limited. Another toxic gas (CO) . Another toxic gas (CO)

has no Bd saturation limits & it is has no Bd saturation limits & it is diffusion limiteddiffusion limited

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Ventilation/perfusion ratioVentilation/perfusion ratio

Normal alveolar ventilation/perfusion ratio (VA/Q) Normal alveolar ventilation/perfusion ratio (VA/Q) is about 0.85 (5100 ml/min/6000 ml\min = 0.85).is about 0.85 (5100 ml/min/6000 ml\min = 0.85).In blocked ventilation; VA= zero, VA/Q= zero & in In blocked ventilation; VA= zero, VA/Q= zero & in blocked perfusion; Q = zero, VA/Q = ∞blocked perfusion; Q = zero, VA/Q = ∞In either case there is no gas exchange.In either case there is no gas exchange.In upright position, Bd shifts from top to bottom of In upright position, Bd shifts from top to bottom of lung, so, at top;VA/Q=2.2 & at bottom, VA/Q=0.5 lung, so, at top;VA/Q=2.2 & at bottom, VA/Q=0.5

Normal Obstructed ventilation Obstructed perfusion

VA\Q = 0.85

PO2=104 PCO2=40

PO2=104 PCO2=40 PO2=149 PCO2=0.3 PO2=104 PCO2=40

PO2=40 PCO2=45 PO2=104 PCO2=40

VA\Q = zero

VA\Q = ∞ PO2=40

PCO2=45 PO2=149 PCO2=0.3

Transport of gases to the tissuesTransport of gases to the tissues

Gas exchange in pul. capillaries: external respira-Gas exchange in pul. capillaries: external respira-tion while in tissue capillaries: internal respiration. tion while in tissue capillaries: internal respiration. About 97% of OAbout 97% of O22 is transported in combination is transported in combination

with hemoglobin (Hb) in RBC & only 3% in with hemoglobin (Hb) in RBC & only 3% in dissolved state in water of plasma & cells while dissolved state in water of plasma & cells while COCO22 is transported in three forms: is transported in three forms:

- In the form of bicarbonate (HCO- In the form of bicarbonate (HCO33) …. 70% ) …. 70%

- With Hb & other plasma proteins….... 23%- With Hb & other plasma proteins….... 23%- In dissolved state………………..……... 7%- In dissolved state………………..……... 7%

COCO22 is diffused from tissue cells to interstitial space is diffused from tissue cells to interstitial space

& then through capillary membrane to be & then through capillary membrane to be dissolved in plasma, but major amount diffuses dissolved in plasma, but major amount diffuses into RBC to combine with water or Hb to form into RBC to combine with water or Hb to form carbonic acid or carbaminohemoglobin carbonic acid or carbaminohemoglobin respectively.respectively.COCO22 + Hb = CO + Hb = CO22HbHb

Carbonic anhydrase (CA) enzymeCarbonic anhydrase (CA) enzyme

COCO22 + H + H22O ===================== HO ===================== H22COCO33

Carbonic acid is dissociated into bicarbonate & HCarbonic acid is dissociated into bicarbonate & H++

HH22COCO33 ↔ HCO ↔ HCO33-- + H + H++

HH++ will be buffered with Hb (which is strong acid- will be buffered with Hb (which is strong acid-base buffer), while HCObase buffer), while HCO33

-- is antiported with Cl is antiported with Cl--

(chloride shift). This is why venous RBC has Cl- (chloride shift). This is why venous RBC has Cl- odour & its plasma is alkaline. In pulm. capillary, odour & its plasma is alkaline. In pulm. capillary, the events are reversed.the events are reversed.

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Oxygen-hemoglobin dissociation curveOxygen-hemoglobin dissociation curveO

2-H

b S

atu

rati

on

Partial Pressure of Oxygen (mmHg)

100 %

50 %

0 %40 1008060200

100 %

50 %

0 %

100 %

50 %

0 %40 1008060200 40 1008060200 40 1008060200

p50 = partial pressure of O2

at which 50% of Hb is boundwith O2

• If p50 ↓, O2-Hb affinity increases

• If p50 ↑, O2-Hb affinity decreases

When POWhen PO22 is high: favours loading of Hb with O is high: favours loading of Hb with O22

(increased % of saturation of Hb with O(increased % of saturation of Hb with O22) & when ) & when

POPO22 is low: favours unloading of O is low: favours unloading of O22 from Hb. The from Hb. The

relation between POrelation between PO22 & % of saturation of Hb with & % of saturation of Hb with

OO22 is drawn as O is drawn as O22-hemoglobin dissociation curve:-hemoglobin dissociation curve:

POPO22 = 95 mmHg→ 97% saturation = 95 mmHg→ 97% saturation

POPO22 = 40 mmHg→ 75% saturation = 40 mmHg→ 75% saturation

POPO22 = 28 mmHg→ 50% saturation (p50) = 28 mmHg→ 50% saturation (p50)

Decreased p50: shift to left and upward Decreased p50: shift to left and upward Increased p50: shift to right and downwardIncreased p50: shift to right and downward

Factors cause right shift (increased p50) are:Factors cause right shift (increased p50) are:1. Decreased pH1. Decreased pH2. Increased CO2. Increased CO22

3. Increased temperature3. Increased temperature4.Increased DPG (Diphosphoglycerate) 4.Increased DPG (Diphosphoglycerate) This right shifting in tissue capillaries favours This right shifting in tissue capillaries favours unloading of Ounloading of O22 to the tissues to the tissues

The opposite factors occur in pulmonary capillaries The opposite factors occur in pulmonary capillaries & cause right shift (decreased p50) which favours & cause right shift (decreased p50) which favours loading of Oloading of O22 to Hb. Presence of large amounts of to Hb. Presence of large amounts of

Hbf (fetal Hb) in Bd is another factor that causes Hbf (fetal Hb) in Bd is another factor that causes left shift & favours loading of Oleft shift & favours loading of O22 from the maternal from the maternal

circulation to fetal circulation. Fetal Hb has more circulation to fetal circulation. Fetal Hb has more affinity to combine Oaffinity to combine O22 than adult Hb than adult Hb

Bohr's effectBohr's effect states that reduced CO states that reduced CO22 & H & H++ conc. conc.

increase Oincrease O22 binding with Hb in pulm. capillaries & binding with Hb in pulm. capillaries &

that increased COthat increased CO22 & H & H++ conc. increase O conc. increase O22 release release

from Hb in tissue capillaries. from Hb in tissue capillaries. Haldane's effectHaldane's effect states that increased binding of O states that increased binding of O22

with Hb displaces COwith Hb displaces CO22 from Bd in pulm. capillaries from Bd in pulm. capillaries

to alveoli & that increase release of Oto alveoli & that increase release of O22 from Hb from Hb

will increase COwill increase CO22 uptake from cells by Bd in tissue uptake from cells by Bd in tissue

capillaries.capillaries.

The volume of OThe volume of O22 carried by each 100ml of Bd is carried by each 100ml of Bd is

called vol% which also increases with POcalled vol% which also increases with PO2.2.

In normal subjects, each 100ml of Bd contains 15 g In normal subjects, each 100ml of Bd contains 15 g of Hb, & each gram of Hb can bind 1.34 ml of Oof Hb, & each gram of Hb can bind 1.34 ml of O22

1.34 x 15 = 20 vol% (100% saturation=20vol%) 1.34 x 15 = 20 vol% (100% saturation=20vol%) which means when Hb is 100% saturated; 20ml of which means when Hb is 100% saturated; 20ml of OO22 can be carried by each 100ml of Bd. can be carried by each 100ml of Bd.

In anemic (or polycythemic) patients; Bd contains In anemic (or polycythemic) patients; Bd contains less (or more) grams of Hb so; vol% is lower (or less (or more) grams of Hb so; vol% is lower (or higher) than 20% at same 100% saturation of Hb.higher) than 20% at same 100% saturation of Hb.

Partial pressure of oxygen (mmHg)

Percent of saturation of H

bw

ith O2

Vo l

u me

P erc

ent

Polycythemia

Normal

Anemia

In all 3 conditions the O2-haemoglobin saturation is 100% but the total O2 content differs

At POAt PO22= 95 mmHg (arterial)→ 19.4 vol% = 95 mmHg (arterial)→ 19.4 vol%

At POAt PO22= 40 mmHg (venous)→ 14.4 vol%= 40 mmHg (venous)→ 14.4 vol%

19.4 – 14.4 = 5 vol%: (5 ml O19.4 – 14.4 = 5 vol%: (5 ml O22 consumed by tissue consumed by tissue

with each 100 ml of Bd at rest), but during exercise, with each 100 ml of Bd at rest), but during exercise, venous POvenous PO22 falls to 15 mmHg at which vol% is 4.4 falls to 15 mmHg at which vol% is 4.4

19.4 – 4.4 = 15 vol%:(15 ml O19.4 – 4.4 = 15 vol%:(15 ml O22 consumed by tissue consumed by tissue

during exercise)during exercise)

Carbon dioxide volume percent curveCarbon dioxide volume percent curve

PCO2 (mmHg)

CO

2 vo

l%

Venous

Arterial

464045

50

55

When PCOWhen PCO22 increases, vol% of CO increases, vol% of CO22 increases. increases.

At PCOAt PCO22 = 40 mmHg (arterial); vol% = 48 = 40 mmHg (arterial); vol% = 48

At PCOAt PCO22 = 45 mmHg (venous); vol% = 52 = 45 mmHg (venous); vol% = 52

52% - 48% = 4% (4 ml of CO52% - 48% = 4% (4 ml of CO22 is cleared away is cleared away

from tissue with each 100 ml of blood perfusing from tissue with each 100 ml of blood perfusing that tissue at rest) that tissue at rest)

Respiratory quotientRespiratory quotient

Person with pulmonary ventilation of 7.5 L/min Person with pulmonary ventilation of 7.5 L/min breathes 10,800 L of gas each day. From this gas, breathes 10,800 L of gas each day. From this gas, he takes in 420 L of Ohe takes in 420 L of O22 (19 moles/day)& gives out (19 moles/day)& gives out

340 L of CO340 L of CO22 (15 moles/day). The ratio of CO (15 moles/day). The ratio of CO22

expired/Oexpired/O22 inspired is respiratory quotient (RQ) inspired is respiratory quotient (RQ)

RQ = CORQ = CO22 out/O out/O22 in = 340/420 = 0.81 in = 340/420 = 0.81

In cellular resp. of glucose, COIn cellular resp. of glucose, CO22 out=O out=O22 in; RQ = 1 in; RQ = 1

RQ for metabolizing fat is only 0.7, the overall RQ RQ for metabolizing fat is only 0.7, the overall RQ < 1 because diet is mixture of carbohydrates & fat< 1 because diet is mixture of carbohydrates & fat

Control of breathing (regulation of respiration)Control of breathing (regulation of respiration)

*Voluntary neural control*Voluntary neural control: directly from cerebral : directly from cerebral cortex via corticospinal tracts to spinal neurons of cortex via corticospinal tracts to spinal neurons of resp. muscles. It regulates certain activities like resp. muscles. It regulates certain activities like breath holding, hyper-, hypo-ventilation & forceful breath holding, hyper-, hypo-ventilation & forceful respiratory maneuversrespiratory maneuvers*Involuntary neural control*Involuntary neural control: : Respiratory centerRespiratory center (responsible for autonomic resp.) & (responsible for autonomic resp.) & Pulmonary Pulmonary receptorsreceptors (responsible for pulmonary reflexes) (responsible for pulmonary reflexes)*Central & peripheral chemical control*Central & peripheral chemical control

Respiratory center in the brain stemRespiratory center in the brain stemRespiratory neurons either type I (inspiration) or Respiratory neurons either type I (inspiration) or type E (expiration). Resp. center is composed of type E (expiration). Resp. center is composed of several groups of these neurons:several groups of these neurons:1.Dorsal respiratory group (DRG)1.Dorsal respiratory group (DRG)2.Ventral respiratory group (VRG)2.Ventral respiratory group (VRG)3.Pneumotaxic center3.Pneumotaxic center4.Apneustic center 4.Apneustic center

DRGDRG located in nucleus of tractus solitarius & reti- located in nucleus of tractus solitarius & reti-cular substance of medulla, participates in basic cular substance of medulla, participates in basic resp. rhythm (quiet insp.), only type I neuronsresp. rhythm (quiet insp.), only type I neuronsVRGVRG located ant. & lateral to DRG in nucleus am- located ant. & lateral to DRG in nucleus am-biguous rostrally& nucleus retroambiguus caudally biguous rostrally& nucleus retroambiguus caudally It is inactive during quiet breathing, contributes to It is inactive during quiet breathing, contributes to resp. control of heavy breathing, receives signals resp. control of heavy breathing, receives signals from DRG, contains both types I and E neurons.from DRG, contains both types I and E neurons.

Pneumotaxic centerPneumotaxic center located dorsally in nucleus located dorsally in nucleus parabrachialis of pons (Kölliker-Fuse nucleus) & parabrachialis of pons (Kölliker-Fuse nucleus) & operates in association with operates in association with apneustic centerapneustic center in in lower pons to control depth of insp. They switch off lower pons to control depth of insp. They switch off ramp signal of DRG to block over inhalation.ramp signal of DRG to block over inhalation.

Pulmonary receptorsPulmonary receptors1.Stretch receptors1.Stretch receptors: in bronchial & bronchiolar sm, : in bronchial & bronchiolar sm, when lungs overinflate; they overstretch& transmit when lungs overinflate; they overstretch& transmit signals via vagus to DRG, to switch off insp. This is signals via vagus to DRG, to switch off insp. This is called Hering-Breuer reflexcalled Hering-Breuer reflex2.Irritant receptors2.Irritant receptors: cough, sneeze & bronchocons-: cough, sneeze & bronchocons-triction reflexes. Receptors for cough found along triction reflexes. Receptors for cough found along bronchial tree (larynx & carina), send impulses via bronchial tree (larynx & carina), send impulses via vagus nerve to medulla & sneeze receptors found in vagus nerve to medulla & sneeze receptors found in nasal airways, impulses via trigeminal to medullanasal airways, impulses via trigeminal to medulla

3.J-receptors3.J-receptors: sensory nerve endings in alv. wall in : sensory nerve endings in alv. wall in juxtaposition to pulm. capillaries give the person a juxtaposition to pulm. capillaries give the person a feeling of dyspnea during engorgement of pulm. feeling of dyspnea during engorgement of pulm. capillaries or edema like in congestive heart failure.capillaries or edema like in congestive heart failure.

Central chemical controlCentral chemical control: chemosensitive areas of : chemosensitive areas of respiratory center, bilateral aggregation of neurons respiratory center, bilateral aggregation of neurons beneath ventral surface of medulla, sensitive to beneath ventral surface of medulla, sensitive to changes in Hchanges in H++ & PCO & PCO22, direct stimulus for these , direct stimulus for these

neurons is Hneurons is H++, when increased in Bd;the area signal , when increased in Bd;the area signal resp. center to increase activity (hyperventilation) resp. center to increase activity (hyperventilation)

Peripheral chemical controlPeripheral chemical control: pp chemoreceptors, : pp chemoreceptors, sensitive to changes in POsensitive to changes in PO22, PCO, PCO22 and H and H++. They . They

are: are: Carotid bodies, aortic bodiesCarotid bodies, aortic bodies & & othersothers. . Carotid bodiesCarotid bodies, largest in number, located at bifur-, largest in number, located at bifur-cations of common carotid arteries, afferent signals cations of common carotid arteries, afferent signals pass via Hering nerves to IXth cranial nn & then to pass via Hering nerves to IXth cranial nn & then to DRG. DRG. Aortic bodiesAortic bodies located along arch of aorta & located along arch of aorta & afferent signals pass via Xth cranial nn to DRG. afferent signals pass via Xth cranial nn to DRG. OthersOthers are few in number, along large arteries. are few in number, along large arteries.

Control of breathing during exerciseControl of breathing during exerciseWhen motor cerebral cortex orders muscles to When motor cerebral cortex orders muscles to contract; it sends collaterals to respiratory center contract; it sends collaterals to respiratory center to increase activity. This may be more or less than to increase activity. This may be more or less than actual need. Proprioceptive endings in muscles & actual need. Proprioceptive endings in muscles & joints send impulses to adjust activity but final joints send impulses to adjust activity but final precise adjustments are by chemical control aided precise adjustments are by chemical control aided by changes in POby changes in PO22, PCO, PCO22 and H and H++..

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RespirationRespiration

HypoxiaHypoxiaLow level of POLow level of PO22 is hypoxia. In blood it is called is hypoxia. In blood it is called

hypoxemia. Four types of hypoxia:hypoxemia. Four types of hypoxia:1.Hypoxic hypoxia: most common, decline in PaO1.Hypoxic hypoxia: most common, decline in PaO22..

2.Anemic hypoxia: HbO2.Anemic hypoxia: HbO22 is declined due to anemia is declined due to anemia

or CO poisoning.or CO poisoning.3.Stagnant hypoxia: blood flow is reduced.3.Stagnant hypoxia: blood flow is reduced.4.Histotoxic hypoxia: tissue can not utilize O4.Histotoxic hypoxia: tissue can not utilize O22 due due

to enzymatic inhibition caused by poisons or drugs to enzymatic inhibition caused by poisons or drugs e.g. cyanide poisoning.e.g. cyanide poisoning.

Hypoxic hypoxia caused by congenital CV disease Hypoxic hypoxia caused by congenital CV disease (PDA, PFO…), lung failure, pulm. fibrosis, pulm. (PDA, PFO…), lung failure, pulm. fibrosis, pulm. emphysema, Vemphysema, VAA/Q imbalance, pump failure (fatigue /Q imbalance, pump failure (fatigue

of resp. muscles, pneumothorax or bronchial obstr-of resp. muscles, pneumothorax or bronchial obstr-uction) & depression of resp. center (drugs like uction) & depression of resp. center (drugs like heroine, morphine, pithidine) …heroine, morphine, pithidine) …

Patterns of breathingPatterns of breathing

EupneaEupnea: normal rhythmic breathing (12-15 BPM) : normal rhythmic breathing (12-15 BPM) ApneaApnea: no breathing, : no breathing, dyspneadyspnea: conscious shortness : conscious shortness of breathing (as in asthma). of breathing (as in asthma). HypopneaHypopnea: decrease : decrease (& (& hyperpneahyperpnea increase) in rate or depth of increase) in rate or depth of breathing regardless of consciousness. If hypo- & breathing regardless of consciousness. If hypo- & hyper-pnea are not with metabolic requirements; hyper-pnea are not with metabolic requirements; they they hypohypo- & - & hyperhyper--ventilationventilation & lastly & lastly tachypneatachypnea: : rapid shallow breathing. rapid shallow breathing.

2 sec. 3 sec. 2 sec. 3 sec. 2 sec. 3 sec. 2 sec.

Abnormal patterns of breathing are:Abnormal patterns of breathing are:1. 1. Chyne-Stoke breathingChyne-Stoke breathing: usually seen in patients : usually seen in patients with brain damage or chronic illness and also in with brain damage or chronic illness and also in some infants & in healthy persons during sleep some infants & in healthy persons during sleep especially high altitudes.Characterized by repeated especially high altitudes.Characterized by repeated cycles of gradually increasing & decreasing tidal cycles of gradually increasing & decreasing tidal volume & respiratory frequency.volume & respiratory frequency.

2. 2. Coupled or grouped breathingCoupled or grouped breathing: in new comers to : in new comers to high altitudes where PCOhigh altitudes where PCO22 is high & characterized is high & characterized

by double, triple or more breaths followed by by double, triple or more breaths followed by apnea for several seconds relieved by deep breath. apnea for several seconds relieved by deep breath. 3. 3. Periodic breathingPeriodic breathing: in patients with increased : in patients with increased intracranial pr. or mid brain lesions & characteri-intracranial pr. or mid brain lesions & characteri-zed by irregular periods of apnea alternated with zed by irregular periods of apnea alternated with periods of normal breathing.periods of normal breathing.

4. 4. Apneustic breathingApneustic breathing: in patients with pontine : in patients with pontine lesions due to loss of pneumotaxic and\or apneustic lesions due to loss of pneumotaxic and\or apneustic centers characterized by sustained cramp like insp. centers characterized by sustained cramp like insp. efforts relieved irregularly by sudden gasp of deep efforts relieved irregularly by sudden gasp of deep expiration. expiration.