The material is prepared for interested students & faculty in the areas of human & veterinary physiology of respiration

1. RESPIRATORY PHYSIOLOGY
Dr. E. Muralinath
Assoc. Professor & Head
Dept. of Veterinary Physiology
College of Veterinary Science, Proddatur, Andhra Pradesh

2. RESPIRATION
 Respiration
 Oxygen taken in & carbon dioxide given out
 Two phases of respiration
 Inspiration: air enters the lungs (active)
 Expiration: air leaves the lungs (passive)
 Two types of respiration
 External respiration: involves exchange of respiratory
gases between lungs and blood
 Internal respiration: involves exchange of gases
between blood and tissues

3. RESPIRATORY SYSTEM PASSAGES
 Nose, pharynx, larynx, trachea, bronchi, lungs

4.  Upper respiratory tract: from nose to vocal cords
 Lower respiratory tract: from trachea to lungs
URT LARYNX LRT
ANATOMY OF RESPIRATORY SYSTEM

5. ANATOMY OF RESPIRATORY SYSTEM
 Pleura: Bilayered serous membrane
 Inner visceral layer attached to lungs
 Outer parietal layer attached to thoracic cavity
 Space in between is called pleural cavity
 Intra-pleural fluid by visceral membrane
 Provides lubrication for lungs
 Creates negative (intrapleural) pressure
 Pleural cavity abnormalities due to accrual of
 Air - Pneumothorax
 Water - Hydrothorax
 Blood - Hemothorax
 Pus - Pyothorax

6.  Trachea splits into
 Primary bronchi (into right & left )
 divides into secondary bronchi
 divides into tertiary bronchi (L10 & R8)
 divides into bronchioles
 Splits into terminal bronchioles
 splits into respiratory bronchioles
 Bronchioles of ≤ 1 mm diameter are called terminal
bronchioles
 Respiratory bronchioles are of ≈ 0.5 mm diameter
ANATOMY OF RESPIRATORY SYSTEM

7. Fröhlich E. Replacement Strategies for Animal Studies in Inhalation Testing. Sci. 2021; 3(4):45.
https://doi.org/10.3390/sci3040045
Trachea to alveolar sacs - 23 divisions
Gas exchange areas are last seven generations
Surface area increases 2.5 cm2 to 11,800 cm2
ANATOMY OF RESPIRATORY SYSTEM

8. VENTILATION
Ventilation is the rate at which air enters & leaves the
lungs
Two types
 Pulmonary ventilation: volume of air moving in and out of
respiratory tract in a given unit of time during quiet
breathing (Minute (respiratory) volume, MV or MRV)
Pulmonary ventilation = Tidal volume x Respiratory rate
= 500 mL × 12/minute
= 6,000 mL/minute
Alveolar ventilation: amount of air utilized for gaseous
exchange every minute
Pulmonary ventilation – Dead space ventilation
Alveolar ventilation = (Tidal volume – Dead space) x RR
= (500 – 150) mL × 12/minute
= 4,200 mL (4.2 L)/minute

9. PULMONARY VENTILATION
 Primarily renew air in
alveoli, alveolar sacs,
alveolar ducts, &
respiratory bronchioles
 Inflow and outflow of air between the atmosphere
and lung alveoli
 Inflation and deflation by downward and upward
movement of the diaphragm to alter the length of
thoracic cavity
 elevation & depression of the ribs to alter the
anteroposterior diameter of thoracic cavity

10. RENEWAL OF ALVEOLAR AIR
With each breath only 1/7th
of the air in alveoli is
replaced
If FRC = 2300 mL, then only
350mL of air is replaced with
each breath
Even after 1 minute, small
quantity of old air will be still
in the alveoli
↑ alveolar ventilation to 2X
can enhance renewal, while
↓ in alveolar ventilation can
slow down renewal

11.  Respiratory muscles
Inspiratory muscles
Diaphragm
 External intercostal
Accessory muscles
scalenus
trapezius
Sternocleidomastoid
Expiratory muscles
 Internal intercostal
Rectus abdominis
Transverses abdominis
PULMONARY VENTILATION

12.  Pressures in Right Ventricle
 Systolic ≈25 mm Hg
 Diastolic ≈ 0 – 1 mm Hg
 Pressures in Pulmonary Artery
 Systolic ≈ 25 mm Hg
 Diastolic ≈ 8 mm Hg
 Mean AP ≈ 15 mm Hg
 Pulmonary Capillary pressure (CP)
 Mean CP ≈ 7 mm Hg
 Left Atrial Pressure
 Mean ≈ 1 - 5 mm Hg (2 mm Hg)
 Blood volume in lungs
 9% of total volume
 450 mL, 70 mL in capillaries
PULMONARY VENTILATION

13.  When oxygen in pulmonary circulation decreases below 70%,
 Vasoconstriction of small arteries & arterioles
 Increase of pulmonary vascular resistance
 Helps deliver more blood to well ventilated alveoli
 Hydrostatic pressure gradient in lungs – Pulmonary blood flow
PULMONARY VENTILATION

14.  Increased Cardiac Output increases mean pulmonary arterial
pressure
 ↑ Blood flow without ↑
pulmonary arterial pressure
during exercise minimizes right
side heart from exertion
 Prevents rise in capillary
pressure
 Prevents development of
pulmonary edema
 ↑ left atrial pressure > 7- 8 mm Hg can ↑ pulmonary arterial &
capillary pressures
 Condition seen with left heart failure
 ↑ load on right heart
 Edema is likely when capillary pressure rises to >30 mm Hg
PULMONARY VENTILATION

15. DEAD SPACE
Dead Space: some portions of the respiratory tract do not
participate in gaseous exchange, although filled with air
Anatomic dead space: areas of the respiratory system (nose,
pharynx, and trachea) that cannot participate in gas exchange
Physiologic dead space: anatomic dead space + areas of
respiratory system that normally are capable of gaseous
exchange, but do not participate in gas exchange due to absent
or poor perfusion
 Bohr equation for measuring physiologic dead space
Vdphys
VT
=
PaCO
2−PĒCO
2
PaCO
2
physiologic dead space (Vdphys), tidal volume (VT), partial
pressure of CO2 in the arterial blood (PaCO
2), and average
partial pressure of CO2 in the entire expired air (PĒCO
2)

16. PHYSIOLOGICAL SHUNT
 Shunted blood: fraction that passes through pulmonary
circulation without being sufficiently oxygenated
 Inadequate ventilation of alveoli provides insufficient
oxygenation of blood in pulmonary capillaries
 A specified fraction of deoxygenated blood passes through the
capillaries without being oxygenated
 Blood flowing through bronchial vessels & not through
pulmonary capillaries (2% of CO)
𝑸𝑷𝑺
𝑸𝑻
=
𝑪𝒊𝑶
𝟐
−𝑪𝒂𝑶𝟐
𝑪𝒊𝑶
𝟐
−𝑪Ṽ𝑶
𝟐
𝑄𝑃𝑆 is the physiologic shunt blood flow/minute, 𝑄𝑇 is cardiac output
per minute, CiO
2 is the concentration of oxygen in the arterial blood
when there is an “ideal” ventilation-perfusion ratio, CaO2 is the
measured concentration of oxygen in the arterial blood, and Cv¯O2 is
the measured concentration of oxygen in the mixed venous blood
 Large value of 𝑄𝑃𝑆 means greater amount of un-oxygenated blood

17. Arterial end of capillary is 30 mm Hg
Venous end of capillary is 10 mm Hg
Mean pulmonary capillary pressure is 7 mm Hg
Mean pulmonary arterial pressure is 15 mm Hg
Mean left atrial pressure is ≈2 mm Hg
Blood takes around 0.8 sec to transit through capillary
When CO increases, blood may take only 0.3 sec to
transit the capillary
PULMONARY CIRCULATION

18.  Alveolar ventilation: amount of air utilized for gaseous
exchange every minute
 Respiratory unit
 structural and functional unit of lung
 site of gaseous exchange
 comprises of
 respiratory bronchioles
 alveolar ducts
 alveolar sacs
 antrum
 Alveoli
 Alveolus has diameter of 0.2 to 0.5 mm
 300 million alveoli with a surface area in contact
with blood capillaries of 70 m2
ALVEOLAR VENTILATION

19.  Respiratory membrane: site of gas exchange
 Consist of
 Alveolar fluid
 Alveolar epithelium epithelial basement
membrane
 Interstitial space between alveolar
epithelium and capillary membrane
 Capillary basement membrane
 Capillary endothelium
 Thickness – 0.6 μm
ALVEOLAR VENTILATION

20. PULMONARY VOLUMES & PRESSURES
 Tidal volume (VT)
 volume change (∆D) with each inspiration/expiration
 Pleural pressure (Ppl)
 pressure between lungs and chest wall pleura
 changes from − 5 to − 7.5 mm of H20
 Alveolar pressure (Palv)
 pressure of air inside alveoli.
 changes (∆Palv) from 0 to −1 cm. of H20
 Trans-pulmonary pressure (Pt)
 differential of Palv & Ppl
 Pt = Palv − Ppl
 measure of recoil pressure

21. PULMONARY VOLUMES
 Tidal volume (VT)
 volume of air inspired or expired with each normal
breath
 Inspiratory reserve volume (IRV)
 maximal extra volume of air inspired over and above
VT
 Expiratory reserve volume
 maximal extra volume of air expired over and above
VT
 Residual volume (RV)
 volume of air left in lungs after a most forceful
expiration

22. PULMONARY CAPACITIES
 Tidal volume (VT): volume of air inspired/expired with each
normal breath
 Inspiratory Capacity (IC): maximal volume of air that can be
inspired after normal expiration
 Vital Capacity (VC): maximal volume of air that be expired
forcefully after a deep inspiration, VC = IRV + TV+ ERV
 Functional Residual Capacity (FRC): Volume of air left in
lungs after normal expiration, FRC = RV + ERV
 Total lung capacity (TLC): amount of air left in lungs after a
deep inspiration, TLC = IRV + EV+ RV + ERV
 Respiratory minute volume (RMV): tidal volume x RR (∼ 6L, 500
mL× 12 breaths/min)
 Maximal voluntary ventilation (MVV): largest volume of gas can be
moved in & out of lungs in 1 min by voluntary effort ∼ 150 L/min

23. RESPIRATION – SPIROMETER
 Apparatus to measure inhaled/ exhaled air volume
 Measure time taken to exhale completely, airway pressures,
flows & volumes
 Volume displacement Collins Spirometer: measure TV,
IRC, ERC, but not RV ( gas dilution, FRC)
Joseph Feher, Quantitative Human Physiology, 2012

24. SPIROGRAM IN DISEASES
 FVC: Forced Vital Capacity (FVC), FEV1: Forced Expiratory
Volume in 1 sec
 Obstructive disorders: ↓ both FEV1 & FEV1/FVC (Asthma)
 Restrictive disorders: ↓ FEV1 but not FEV1/FVC (Fibrosis)

25. PRESSURE VOLUME CURVES IN LUNGS
 Transmural pressure: intrapulmonary pressure − intrapleural
pressure (lungs), intrapleural pressure − outside pressure
(chest wall), intrapulmonary pressure - barometric pressure
(total respiratory system)
 PTR ∞ transmural pressure, lung & chest wall compliance = slope
of the PTR curve (∆V/ ∆P: ∼0.2 L /Cm H2O)
 PW: Pressure in chest
 PL: Pressure in lungs
 PTR : Pressure in total
respiratory system
 PL: 0 mm Hg, Volume = FRC
(RV+ERV), transmural
pressure = 0

26. LUNG COMPLIANCE
 Compliance (C) of Lung + thoracic cavity
 Volume change/unit change in trans-pulmonary
pressure , C α expansibility α
𝟏
𝐬𝐭𝐢𝐟𝐟𝐧𝐞𝐬𝐬
 Measure ‘C’ in relation to Palv or Ppl
 For each unit change in Ppl, compliance of both
lungs within thoracic cavity is 200 mL
 Compliance of lungs alone is twice than above
 Compliance↓: curve shift
right & downwards
(Fibrosis)
 Compliance↑: curve shift
to left & upwards
(Emphysema)

27. LUNG SURFACTANT & COMPLIANCE
 Surfactant: proteins, lipids, Dipolmitylphosphatidylcholine (DPP),
reduces alveolar surface tension (prevents edema)
 Surface tension = 0 (saline filled lungs), P-V curves indicates only
lung tissue elasticity, but not surface tension
 P-V curves from air filled lungs indicates elasticity & surface tension
 Hysteresis: Trans-pulmonary pressure difference between inhalation
& exhalation events

28. VENTILATION-PERFUSION RATIO
 Alveolar ventilation: Amount of air utilized each minute
for gaseous exchange (VA)
 Perfusion: Pulmonary capillary blood flow (Q.)
 Ventilation-perfusion ratio (VA/Q.):
(VA/Q.) =
𝐀𝐥𝐯𝐞𝐨𝐥𝐚𝐫 𝐯𝐞𝐧𝐭𝐢𝐥𝐚𝐭𝐢𝐨𝐧 (𝐕𝐀)
𝐀𝐦𝐨𝐮𝐧𝐭 𝐨𝐟 𝐛𝐥𝐨𝐨𝐝 𝐩𝐞𝐫𝐟𝐮𝐬𝐢𝐧𝐠 𝐚𝐥𝐯𝐞𝐨𝐥𝐢 𝐞𝐚𝐜𝐡 𝐦𝐢𝐧𝐮𝐭𝐞 (𝐐.)
VA = (500 – 150) mL × 12/minute = 4,200 mL/minute
Q. = 5,000 mL/minute
VA/Q. = 4,200/5000 = 0.84
 Range of VA/Q. = 0 to ∝ (infinity)

29. VENTILATION & PERFUSION
Anatomical factors affecting V/P ratio
Physiological dead space, reflecting wasted air
Physiological shunt, reflecting wasted blood
Physiological factors affecting V/P ratio
Ratio ↑, if ventilation increases without change in
blood flow
Ratio ↓, if blood flow increases without change in
ventilation
Ratio varies by alveolar position in relation to lung
height (zones of lung)
Pathological factors
 Chronic Obstructive Pulmonary Diseases (COPD)
Alveolar damage
V/P ratio ↓

30. LUNG PERFUSION ZONES
Zero blood flow
Intermediate blood flow
Continuous blood flow
 All areas of lung are not equally perfused
 Depends on relative location within the lungs
 Broadly three zones

31.  Ventilation-perfusion ratio signifies gaseous exchange
 Affected by both alveolar ventilation and blood flow
 Ventilation without perfusion = dead space
 Perfusion without ventilation = shunt
VENTILATION-PERFUSION RATIO

32. PULMONARY CIRCULATION
 Pulmonary blood vessels
 Pulmonary artery (right & left branch) that carries
deoxygenated blood from right ventricle to lung alveoli
 Pulmonary veins carry oxygenated blood to the left atrium
 Pulmonary ccapillaries innervate respiratory units
 Bronchial artery
 Bronchial artery pumps oxygenated blood to all structures
of lungs
 Innervates connective tissue, septa, large & small bronchi
 Lymphatics
 Lymph vessels are located in connective tissue spaces
circumscribing terminal bronchioles that lead into right
thoracic lymph duct

33. DIFFERENT FRACTIONS OF AIR
Inspired air that is inhaled during inspiration
Alveolar air that is present in alveoli of lungs
Expired air that is exhaled during expiration
Difference between Inspired & Alveolar air
Atmospheric air only partially replaces alveolar air with
each breath (70% only)
Oxygen in alveolar air diffuses into pulmonary capillaries
constantly
Carbon dioxide in pulmonary blood diffuses into alveolar
air constantly
Respiratory passage humidifies dry atmospheric air
before reaching alveoli
Alveolar air

34.  Air entering the respiratory passages is rapidly humidified
by the water in mucus linings of the membranes
 Partial pressure that the water molecules constantly exert
on the surface to escape through the surface is called
water vapor pressure (PH2O)
 Water vapor pressure in air inside respiratory cavities at
room temperature is 47 mm Hg (PH2O)
 Water vapor pressure depends on temperature, more the
temperature more the vapor pressure for a given volume
of water
 Water vapor pressure at 0°C = 5 mm Hg
at 100°C = 760 mm Hg
VAPOR PRESSURE

35. Gases dissolved in water or in body tissues also exert pressure
Partial pressure of gas: Rate of diffusion of each gas in an
admixture of gases is directly proportional to pressure caused by
that gas alone
Partial pressure of a gas in a solution is determined by its
concentration & solubility coefficient of the gas
Solubility of CO2 is more in water than O2
Henry’s law: Partial pressure of a gas is ∞ dissolved gas
concentration & 1/ solubility coefficient
Partial pressure of gas =
𝑪𝒐𝒏𝒄𝒆𝒏𝒕𝒓𝒂𝒕𝒊𝒐𝒏 𝒐𝒇 𝑫𝒊𝒔𝒔𝒐𝒍𝒗𝒆𝒅 𝒈𝒂𝒔
𝑺𝒐𝒍𝒖𝒃𝒊𝒍𝒊𝒕𝒚 𝑪𝒐𝒆𝒇𝒇𝒊𝒄𝒊𝒆𝒏𝒕
 In atmospheric air, 79 % N2 & 21 % O2 (760 mm Hg)
 Then, 79 % of 760 mm Hg is N2 ( 0.79 X 76 0 = 600.40 mm Hg,
21 % of 760 mm Hg is O2 = 0.21 X 760 = 159.60 mm Hg)
PARTIAL PRESSURE OF GASES
Solubility
coefficients of
different gases

36.  Diffusing Capacity: volume of gas diffusing through the
respiratory membrane each minute for a unit pressure gradient
 Oxygen - 21 mL/minute/1 mm Hg (1X)
 Carbondioxide - 400 mL/minute/1 mm Hg (20X > Oxygen)
Diffusing Capacity is directly proportional to pressure gradient
(∆𝐏), solubility of gas in fluid medium (S) & surface area of RM (A)
Diffusing Capacity is indirectly proportional to molecular weight of
the gas (MW) & thickness of respiratory membrane (D)
DC =
∆𝐏 𝐱 𝐒 𝐱 𝐀
√𝐌𝐖 𝐱 𝐃
 Fick’s law of diffusion: amount of a substance (J) crossing a given
area is directly proportional to area of diffusion (A), concentration
gradient (dc/dx) and diffusion coefficient (D), J = −𝐃 𝐱 𝐀 𝐱
𝐝𝒄
𝐝𝒙
GASEOUS DIFFUSION
Relative diffusion
coefficients of
different gases

37. PHYSICAL LAWS OF GASES
Define relationships among pressure, temperature, volume &
the amount of gas
Boyle’s law: at constant temperature, Pressure α
1
𝑉𝑜𝑙𝑢𝑚𝑒
;
P1V1 =P2V2 , explains altitudes’ effect on gases in body cavities
Charles law: for a fixed mass of gas, at constant pressure,
volume α Temperature; or
𝑽𝟏
𝑻𝟐
=
𝑽𝟐
𝑻𝟐
, explains effects of temp. on
gas volume, explains gas thermometer working
Gay Lussac’s law: at constant volume, Pressure α
Temperature;
𝑷𝟏
𝑻𝟏
=
𝑷𝟐
𝑻𝟐
, explains working of pressure relief
valves in gas containers
Avogadro’s law: Equal volumes of gases at same pressure &
temperature have same number of molecules (6.023x1023 ,
Avogadro’s number)

38. DIFFUSION OF O2 (FROM ALVEOLUS TO
PULMONARY BLOOD)
Alveoli
Venous end (VE)
PO2 = 104 mm Hg
O2 content = ~19.8 mL%
Arterial end (AE)
PO2 = 40 mm Hg
O2 content = ~14 mL%
pO2 =104 mm Hg
PO2 in atmosphere= 159; alveoli = 104, (∆P) = 55 mm Hg
RBC exposed to O2 in pulmonary capillary for only 0.75 S (rest) &
0.25 S (severe exercise)
PO2 in pulmonary capillary (AE)= 40 mm Hg, alveoli = 104 mm Hg
Pressure gradient (∆P) = (104 – 40) = 64 mm Hg
Arterial blood has ≈ 19.8 mL of O2 /dL: 0.29 mL in plasma & 19.5 mL
bound to hemoglobin
Capillary

39. Oxygen (O2) is transported from alveoli to tissues by pulmonary
blood in two major forms
Simple Physical solution
O2 dissolves in plasma, 0.3 mL/100 mL (3%)
 Combination with Hemoglobin (Hb)
O2 combines with Hb (oxygenation, not oxidation),
reversibly, PO2 gradient bound
Hemoglobin molecules contains 2α & 2β chains
1 hemoglobin molecule has 4 iron atoms (Fe+2)
1 iron atom combine with 1 O2 molecule
97% O2 is transported in blood as oxyhemoglobin
Oxygen Carrying Capacity of Hemoglobin: amount of oxygen
transported by 1 gram of hemoglobin is 1.34 mL
TRANSPORT OF OXYGEN IN BLOOD

40.  Oxygen carrying capacity of blood: the amount of oxygen
transported by blood
 Normal hemoglobin levels in blood is 15 gram % (15g/dL)
 O2 carrying capacity of hemoglobin is 1.34 mL/g
 15 g % of hemoglobin carries (15 x 1.34) 20.1 mL/dL of
oxygen
 Hemoglobin is 95% O2 saturated, 19 mL/dL of oxygen
 O2 Saturation of Hemoglobin: condition when hemoglobin is
unable to hold/carry any additional amount of O2
 depends upon partial pressure of O2
 defined by oxygen- hemoglobin dissociation curve
 O2 - Hemoglobin dissociation curve: Progressive ↑ in %
hemoglobin bound to oxygen as blood PO2↑, termed %
saturation of hemoglobin
TRANSPORT OF OXYGEN IN BLOOD

41.  ‘S’ shaped curve
 Upper part indicates oxygen uptake by hemoglobin in lungs
 Lower part indicates oxygen dissociation from hemoglobin
O2 – HB DISSOCIATION CURVE
Arterial
blood
Venous
blood
Exercise
(VO
2
)

42.  In normal conditions
 5 mL of O2 transported from lungs to tissues in each 100
mL blood
 During heavy exercise
 Muscle interstitial fluid PO2 may fall from 40 mm Hg
(normal) to very low value (15 mm Hg)
 Oxygen left bound to Hemoglobin was only 4.4 mL/100 mL
of blood
 Nearly, 15 millilitres of oxygen should be delivered to
tissues by each 100 mL of blood
 It is 3X more than normal amount delivered
 Cardiac output (CO) may rise to 7X normal, a total 21X
fold increase in O2 delivered in heavily exercising athletes
 Hemoglobin dissociation curve is highly dynamic &
depends on various factors

43.  Several factors regulate hemoglobin (Hb) affinity to O2
at different sites
 Partial pressure of O2: ↑O2 in alveoli enhances O2 loading
of blood, useful mode in obstructive diseases
 Partial pressure of CO2: ↑CO2 can ↑O2 loading in lungs &
↑O2 release at tissues, and vice versa
 H+ ion conc.: A lower pH or a higher H+ conc. can ↑O2
loading in lungs & ↑O2 release at tissues, and vice versa
 Body temperature: Higher body temperature (e.g., during
exercise 2-3°C, can ↑O2 delivery in muscle
 2,3 Bisphospho-glycerate (2,3 − BPG): 2,3 − BPG in RBCs ↑ O2
loading in lungs & ↑O2 release at tissues (E.g., Hypoxia, higher
BPG levels ↑ O2 release at tissue)
HbO2 + 2,3-BPG ↔Hb − 2,3-BPG + O2
FACTORS AFFECTING O2 – HB
DISSOCIATION CURVE

44. Shift of O2– Hb dissociation curve significantly to right
Exercising muscles release excess CO2, which displace more O2
from hemoglobin
Muscles release several acids that increase H+ concentration in
muscle capillary blood
Muscle temperature rises 2°to 3° Celsius that ↑ oxygen
delivery to muscle fibers
All these factors cause right shift of curve releasing more O2
even at PO2 low range of 15 - 40 mm Hg
In lungs, shift occurs in the opposite direction, hence blood
can pickup of extra amounts of O2 from alveoli
EXERCISE

45. O2-HB DISSOCIATION CURVE SHIFT
 Oxygen-hemoglobin dissociation curve Right
shift:
 Decrease of PO2
 Increase in PCO2 (Bohr effect)
 Increase in H+ ions concentration
 Elevated body temperature
 Excess of 2,3-diphosphoglycerate (DPG) in RBC
 Oxygen-hemoglobin dissociation curve Left
shift:
 Type of hemoglobin (Fetal vs. adult), fetal Hb. has
more affinity for O2
 Decrease in H+ ion conc. & increase in pH
(alkalinity)

46. DIFFUSION OF O2 (PERIPHERAL
CAPILLARY BLOOD TO TISSUE CELLS)
PO2, arterial blood = 95, interstitium = 40, venous blood = 40 mm Hg
O2 readily reaches to cells from blood
Pressure gradient (∆P) = (95 – 40) = 55 mm Hg
5 mL of O2 for each 100 mL blood, diffuses away into cells
Cells: PO2 = 23 mm Hg
Venous end
PO2 = 40 mm Hg.
O2 content = ~14 mL%
Arterial end
PO2 = 95 mm Hg
O2 content = ~19 mL%
IS: PO2 = 40 mm Hg

47. Bohr Effect
Presence of CO2 ↓ affinity of hemoglobin for O2
 Postulated by Christian Bohr in 1904
Deoxygenated blood binds H+ more actively than does
Oxygenated hemoglobin
Continuous metabolic activity in the tissues, reduces PO2 and
increases PCO2
Higher CO2 moves readily into blood
O2 is quickly displaced from blood & enters the tissues
Presence of CO2 decreases affinity of hemoglobin for O2
This enhances additional release of O2 to tissues and oxygen
dissociation curve shifts to right
Higher level of PCO2 , PO2 H+ , BPG all contribute significantly to
Bohr effect
BOHR EFFECT

48.  Utilization coefficient (UC):
 Amount of blood that gives up it’s O2 to tissues
 Normal value is 25%, ↑ 70-80% during heavy exercise
 UC can be 100% at higher metabolism/poor blood
supply
 At basal level:
 Tissues need ≈ 5 mL O2 for each 100 mL of blood, and
PO2 must fall under 40 mm Hg for normal PO2 delivery
to tissue
 During Heavy exercise:
 Normal tissue require ~ 20% more O2,
 Achieved by steep slope of dissociation curve
 Increase in tissue blood flow due to low PO2
 Delivery occurs even when ∆P = 15 – 40 mm Hg

49. HEMOGLOBIN vs. MYOGLOBIN
 Iron-containing pigment found in skeletal muscle
 No Cooperative binding is seen
 Binds only 1 mole of O2 per mole of protein when
compared to Hgb. that binds 4 moles of O2 per mole of
protein
 Has higher affinity for O2 than Hgb, and hence offers a
positive affinity gradient required for a favourable transfer
of O2 from Hgb in the blood to myoglobin in cells
 The steep slope of the curve shows that O2 is released at
very low PO2 that usually occurs during exercise
 Higher levels of myoglobin are seen in muscles that have
sustained contractions
 In case of hypoxia or other similar conditions, myoglobin
may serve as an oxygen supplier to the cells
(O2 − Hb Vs. O2 − Myob) Dissociation Curve

50. PCO2 in cells = 46, interstitium = 45, arterial blood = 40 mm Hg
CO2readily reaches blood from cells
Pressure gradient (∆P) = (46 – 40) = 6 mm Hg
4 mL CO2 /100 mL blood carried away to lungs (48 % vs. 52 %)
Cells: pCO2 = 46 mm Hg
DIFFUSION OF CO2 (TISSUE TO PERIPEHRAL
CAPILLARIES)
Venous end
PCO2 = 45 mm Hg.
CO2 content = ~52 mL%
Arterial end
PCO2 = 40 mm Hg
CO2 content = ~48 mL%
IS: pCO2 = 45 mm Hg

52. CO2 DISSOCIATION CURVE
 Reflects the dependence
of total blood CO2 on
PCO2
 Normal blood PCO2 ranges
between 45 & 40 mm Hg
 Blood CO2 content is ≈ 52
V% in tissues, & 4 V% is
exchanged in lungs,
dropping to 48 V% in
lungs
 CO2 content can reach 70
V% if PCO2 rises to 100
mm Hg

53. CO2 DISSOCIATION CURVE
 CO2 content in oxygenated blood is 48 V% at a PCO2 of 40 mm
Hg & 52 V% when PCO2 is 46 mm Hg
 Haldane effect: O2 combining with hemoglobin tends to displace
CO2 from blood (shift curve to right), resulting in increased
transport of CO2. This is due to combination of O2 with
hemoglobin in lungs that makes hemoglobin a stronger acid.
First described by John Scott Haldane in 1860. Displaces CO2
from blood into alveoli in 2 ways
 Highly acidic hemoglobin has less tendency to combine
with CO2 (removes most CO2 in carbamino form )
 Highly acidic CO2 releases excess H+ ions that bind with
HCO3
- to form Carbonic Acid (CA). CA then dissociates
into H2O & CO2 , and CO2 leaves blood into the alveoli
and, finally, into air

54. Carbon dioxide transported in blood from tissue to alveoli in
four different forms
 Dissolved form (7% of CO2)
 CO2 dissolves in blood plasma fluid
 0.3 mL CO2 transported in each 100 mL of plasma
 CO2 in plasma at 45 mm Hg = 2.7 mL/dL (2.7 V %) & at 40 mm
Hg = 2.4 mL/dL (2.4 V %), ∆ = 0.3 V %
 Bicarbonate form (63% of CO2)
 CO2 in RBCs combines with H2O → Carbonic acid (CA)
 Carbonic anhydrase enhances CA formation 5000X (RBCs)
 CA (99.9%) in RBCs dissociates into HCO3
- & H+ ions
 H+ ions combine with Hgb. – buffers any change in pH
 HCO3
- ions diffuse into plasma
 If Carbonic anhydrase is blocked, PCO2 can rise to 80 mm Hg
TRANSPORT OF CARBON DIOXIDE

55. TRANSPORT OF CARBON DIOXIDE
Chloride Shift or Hamburger Phenomenon
 discovered by Hartog Jakob Hamburger in 1892
 Exchange of a Cl- for a HCO3
- across RBCs membrane
 NaCl in plasma dissociates into Na+ & Cl-
 Exchange of HCO3
- for Cl- maintains electrolyte
balance
 Anion exchanger 1 acts as an anti-porter in RBCs
membrane and helps exchange these two ions
 Na+ combines with HCO3
- in plasma & forms sodium
bicarbonate & transported in blood to lungs
 H+ ions dissociated from CA are buffered by
hemoglobin

56.  Reverse Chloride Shift in Lungs:
 Cl- ions are moved back into plasma from RBC
 HCO3
- is converted back into H2O & CO2
 When blood reaches alveoli, sodium bicarbonate
in plasma dissociates into Na+ & HCO3
- ions
 HCO3
- ions moves into RBCs & chloride ion moves
out of RBCs into plasma
 Na+ & Cl- combine to form NaCl
 HCO3
- ion inside RBCs combines with H+ ion to form
carbonic acid (CA)
 CA dissociates into H2O & CO2, expelled out
TRANSPORT OF CARBON DIOXIDE

57.  Carbamino compounds form
 30% of CO2 is transported as Carbamino compounds
 CO2 transported in combination (reversibly) with hemoglobin
and plasma proteins
 CO2 + hemoglobin → carbamino hemoglobin or
carbhemoglobin
 CO2 + plasma proteins → Carbamino protein
 Carbamino hemoglobin & Carbamino proteins are together
called carbamino compounds
 Carbamino hemoglobin > Carbamino proteins, because
plasma proteins are only half of the quantity of hemoglobin
 Carbonic Acid form
 CO2 combines with water of plasma to form carbonic acid
 Transport of CO2 in this form is negligible
TRANSPORT OF CARBON DIOXIDE

58. TRANSPORT OF CARBON DIOXIDE

59. DIFFUSION OF CO2 (PULMONARY
BLOOD TO ALVEOLI)
Alveoli
Venous end
PCO2 = 40 mm Hg
O2 content = ~48 mL%
Arterial end
PCO2 = 45 mm Hg
CO2 content = ~52 mL%
PCO2 = 40 mm Hg
Capillary
PCO2 in atmospheric air = 0.3 mm Hg, in alveoli = 40 mm Hg
CO2readily reaches from atmosphere to alveoli
PCO2 in alveoli = 40 mm Hg, in blood = 45 mm Hg
Pressure gradient (∆P) = (46 – 5) = 5 mm Hg

60. BLOOD GAS CONTENT

61. PO2 & PCO2 OF BLOOD

62. DIFFUSION OF CO2 (ALVEOLI TO
ATMOSPHERIC AIR)
PCO2 in alveoli = 40 mm Hg, atmospheric air = 0.3 mm Hg
CO2 readily diffuses under large ∆P ≈ 40 mm Hg
Respiratory exchange ratio (R):
=
net CO2 output
net O2 uptake
, value depends on metabolic source
 Carbohydrates = 1, Proteins = 0.803, Fats = 0.7, balanced
ration, R = 0.825
 Respiratory Quotient (RQ): Molar ratio of CO2 production to
O2 consumption
 RQ = R, when balanced ration is fed, 0.825 (value increases
with exercise)

63.  Respiration is an involuntary process
 Process is variable even under some physiological
conditions that change one or both, force & rate of
respiration
E.g., Exercise, emotional states
 Respiratory changes normalizes rather quickly with the
help of regulatory mechanisms
 Regular breathing patterns are under control of two
regulatory mechanisms:
 Neural mechanism
 Chemical mechanism
REGULATION OF RESPIRATION

64. NEURAL REGULATION
Neural regulatory mechanism includes three components
Respiratory centers
Afferent nerves
Efferent nerves
 Respiratory centers are group of neurons that control rate,
rhythm & force of respiration
 Bilaterally located in the reticular formation of brainstem
(Pons & Medulla Oblongata)
 Location wise, respiratory centers are classified into two
groups, Pontine & Medullary Centers
 Efferent & Afferent nerves participate in communication of
sensory & motor components of signal transmission

65. Nervous system exerts a precise control over alveolar
ventilation rate
PO2 & PCO2 are maintained
Respiratory Centers
Dorsal respiratory group
Expiratory center
Ventral respiratory group
Inspiratory center
Pontine Centers
Apneustic center
↑depth of Respiration
Pneumotaxic center
Switch between inspiration & expiration
NEURAL REGULATION
Pontine
Medullary

66.  Dorsal Respiratory Group (DRG) is also termed ‘Inspiratory
center’
 Location
 Extends along length of medulla
 NTS & surrounding reticular formation
 Sensory input via. vagal & glossopharyngeal nerves
 Peripheral Chemoreceptors
 Baroreceptors
 Lung receptors
 Functions
 Generate inspiratory ramp & respiratory rhythm
 Cyclic bursts of inspiratory action potentials
 Inspiratory signal ↑ steadily in a ramp fashion for about 2
s. & then stops for 3 s, followed by next respiratory cycle
DORSAL RESPIRATORY GROUP

67. VENTRAL RESPIRATORY GROUP
 Ventral Respiratory Group (VRG) is also termed
‘Expiratory Center’
 Location
 Anterior & lateral to dorsal group of neurons
 Concentrated in Nucleus Ambigus & Nucleus Retroambigus
 Both inspiratory & expiratory neurons are present
 Function
 Inactive during quiet respiration
 Active during forced breathing
 Supports extra respiratory drive
 Provides strong expiratory signals to abdominal muscles
during heavy exercise

68.  Pneumotaxic center
 Location
In the nucleus parabrachialis of upper pons
 Function
 Inputs inspiratory area & controls “switch-off” ramp point
 Limits filling phase (inspiration) of the respiratory cycle
Strong signal decreases filling & vice versa
Causes secondary increase in breathing rate (10X)
Apneustic Center
Location
Reticular formation of lower pons
Function
Stimulates DRG & ↑depth of inspiration
Stimulation leads to Apneusis (prolonged inspiration
followed by inefficient expiration)
PNEUMOTAXIC CENTER

69.  Efferent Pathway
 Nerve fibers from respiratory centers reaches anterior-lateral
columns of SC & terminates on motor neurons in anterior horn
cells of cervical & thoracic spinal cord segments
 These continue as
 Phrenic nerve fibers (C3 - C5), diaphragm
 Intercostal nerve fibers (T1 - T11), ext. intercostal muscles
 Efferent nerves from respiratory centers via. Vagus nerve
NEURAL CONNECTIONS OF
RESPIRATORY CENTERS
 Afferent Pathway
 Sensory inputs from Peripheral chemoreceptors & baroreceptors
enters respiratory centers via glossopharyngeal & vagus nerve
 Sensory inputs from stretch receptors of lungs via. vagus nerve
 Afferent pathway impulses ends by controlling thoracic cage &
lungs via. efferent nerve fibers

70. RHYTHMICITY OF INSPIRATORY
IMPULSES (Medullary centers)
During Inspiration: DRG inspiratory neurons inhibit VRG neurons
During Expiration: VRG expiratory neurons inhibit DRG neurons
Apneustic center Pneumotaxic center
(limits inspiration duration)
Prolonged inspiration
Normal respiration & rhythmic impulses
Dorsal Respiratory Group (DRG)
Respiratory muscles
Phrenic & Intercostal nerves
Inspiratory ramp
signal: initially AP
amplitude is small and
increases steadily
Action potential
amplitude
increases steadily
Ramp signals not
continuous: 2s
(inspiration), 3s stop
(Expiration)
Slow and steady inspiration
Lungs fill air steadily

71. Pre-bötzinger complex
Additional respiratory center found in animals
Location
Group of neurons (pacemaker) placed in the Ventro-
lateral part of medulla
Functions
Generate rhythmic respiratory impulses
Fibers from Medullary centers innervate this group
Respiratory Centers' Regulation
Higher brain regions
Sends inhibitory impulses directly to DRG neurons
Olfactory tubercle, Anterior cingulate gyrus, posterior orbital
gyrus of cerebral cortex genu of corpus callosum all inhibit
respiration
 Impulses from motor area & Sylvian area of cerebral cortex
cause forced breathing
NEURAL CONNECTIONS

72.  Reflex due to stimulation of stretch receptors of lungs is termed
‘Hering-Breuer Reflex’
 Hering-Breuer inflation reflex
 Stimulation of stretch receptors on bronchi & bronchial
valves reach DRG neurons via. vagal afferent fibers &
inhibit inspiration
 Protective reflex limiting inspiration & overstretching of
lungs
 operates only at high tidal volume of 1,000 mL or more
 Hering-Breuer deflation reflex
 It occurs during expiration
 As lungs stop stretching during expiration, lungs deflate
STRETCH RECEPTORS OF LUNGS

73.  Impulses from J Receptors of Lungs
 Juxtacapillary receptors on respiratory membrane
 These are sensory nerve endings of vagus nerve
 Pathological stimulus for J Receptors
 Pulmonary congestion, Pulmonary edema
 Pneumonia, Over inflation of lungs
 Microembolism in pulmonary capillaries
 Chemical Stimulation of J Receptors
 Histamine, Halothane, Bradykinin Serotonin &
Phenyldiguanide
 Effects of J Receptors Stimulation
 Causes apnea, hyperventilation, bradycardia, hypotension
 J receptor activation may result in hyperventilation in patients
affected with pulmonary congestion & left heart failure
J RECEPTORS OF LUNGS

74.  Impulses from Irritant Receptors of Lungs
 Irritant receptors are located on bronchi & bronchiolar
walls
 Stimulated by chemicals; like Ammonia & Sulfur dioxide
 Deliver afferent impulses to respiratory centers via vagus
 Stimulation produces a protective reflex characterized by
hyperventilation & bronchospasm
 Impulses from Baroreceptors
 Physiologically not an important mechanism
 Respond to blood pressure changes
 Located in carotid sinus & aortic arch
 Increased BP activates Baroreceptors that send inhibitory
impulses to vasomotor center, causing reflex decreases in
BP & respiration

75.  Impulses from Proprioceptors
 Proprioceptors respond to body position changes
 Located in joints, tendons & muscles
 Proprioceptors are stimulated during muscular exercise
 Send impulses to cerebral cortex via. somatic afferent
nerves
 Results in hyperventilation (send impulses to medullary
centers)
 Impulses from Thermoreceptors
 Cutaneous receptors responding to environmental
temperature changes
 Two types for receptors for cold & warmth
 Send impulses to cerebral cortex via. somatic afferent nerves
 Cerebral cortex stimulates respiratory centers & causes
hyperventilation

76.  Impulses from Pain Receptors
 Respond to pain stimulus
 Impulses are then sent to cerebral cortex via somatic
afferent nerves
 Cerebral cortex stimulates respiratory center & causes
hyperventilation
 Impulses from chemoreceptors
 Respond to chemicals in blood
 Hypoxia (decreased PO2), Hypercapnea (increased
PCO2), and pH (Increased H+)
 Two types
 Central chemoreceptors
 Peripheral chemoreceptors

77. NEURAL REGULATION BY VARIOUS RECEPTORS

78. Central Chemoreceptors
Located in brain, deeply & in proximity DRG neurons
These are neurons of chemosensitive area
In close contact with blood & cerebrospinal fluid
Responsible for 70 - 80% of augmentation of ventilation when
Hypercapnea sets in
 Increased H+ is the major stimulus, although H+ cannot cross
blood brain barrier, but CO2 can cross BBB
Excess levels of CO2 is washed away & respiration is brought to
normalcy
Chemoreceptors DRG neurons ↑Ventilation
Central Chemoreceptors
Located in brain, deeply & in proximity DRG neurons
These are neurons of chemosensitive area
In close contact with blood & cerebrospinal fluid
Responsible for 70 - 80% of augmentation of ventilation when
Hypercapnea sets in
 Increased H+ is the major stimulus, although H+ cannot cross
blood brain barrier, but CO2 can cross BBB
Excess levels of CO2 is washed away & respiration is brought to
normalcy
Chemoreceptors DRG neurons ↑Ventilation

79. Peripheral chemoreceptors
Present in Carotid & Aortic region
Most potent of stimuli is Hypoxia, due to potassium
channels in glomus cells of peripheral chemoreceptors
Hypoxia closes oxygen sensitive K+ channels, causes
depolarization & action potential generation
Impulses via. the Hering & Aortic nerves, excites DRG
neurons
Excitatory impulses reaches respiratory muscles &
↑ventilation
Hypercapnea (increased PCO2), and decreased pH
(Increased H+) are not a significant stimulus for these
receptors

80. NEURAL REGULATION BY CHEMORECEPTORS

81. Cellular metabolism is the major source of acids in blood
Changes in H+ concentration in body is buffered by
Blood buffers
Chemical acid-base buffer systems
Cannot eliminate or add H+ from or to body but keeps
H+ levels pegged (uncompensated) until kidneys/lungs
can restore the balance (compensated)
Respiratory centers via. Lungs regulate CO2 (H2CO3)
Kidneys can excrete either excess acid/alkali in urine
CO2 generated by cellular metabolism is converted to H2CO3
 H2CO3 is ionized releasing high levels of H+ (> 12,500 mEq/d)
Most CO2 is eliminated by lungs & small quantities of H+ are
excreted by kidneys
REGULATION OF PH

82. Acid base balance in blood is controlled by Blood buffers: Act
very fast, within seconds
 Plasma Proteins
 Effective buffer as both free carboxyl & amino groups
dissociate
 E.x., RCOOH ↔ RCOO− + H+˙
 Hemoglobin
 Dissociation of imidazole groups present on histidine
residues in hemoglobin
 Hemoglobin has 6X more buffering capacity than plasma
proteins because of the presence of large quantities of
hemoglobin in blood & each hemoglobin molecule has 38
histidine residues
 Deoxyhemoglobin (Hb) is a weaker acid than
oxyhemoglobin (HbO2), and therefore a better buffer,
because the imidazole group of Hgb. dissociate less than
those of HbO2

83.  Carbonic acid–bicarbonate system (CA − H2CO3)
 Dissolved CO2 content is respiration controlled (Open system)
 Kidney’s exercise additional control on HCO3
−plasma levels
H2CO3 ↔ H+ + HCO3
−
Handerson Hassalbach equation for this system is
pH = pK + log
[HCO3
−]
[H2CO3]
, pKa is low (= 3) &
measuring H2CO3 is hard. H2CO3 is in equilibrium with CO2
H2CO3 ↔ CO2 + H2O
pH = pKˊ+ log
[HCO3
−]
[CO2]
= 6.1+ log
[HCO3
−]
[CO2]
pH = 6.10 + log
[HCO3
−]
0.0310 X PCO2
(dissolved CO2 quantity
is ∞ PCO2 & sol. coefficient of CO2 is 0.0301 mol /L /mm Hg)
 HCO3
− is hard to measure in blood, but PCO2 & H+ can be measured
& estimate HCO3
−

84.  If H+ is added to blood → ↑ in H2CO3 & ↓ in HCO3 – levels
 Excess H2CO3 is dehydrated & CO2 excreted in lungs
 If CO2 removal is mismatched to H2CO3 formation, additional H+
retention is needed for, ↓ plasma HCO3– to half, ↑pH from 7.4 to
6.0 (undesirable)
 Excess ↑ in H+ concentration is avoided due to
 Excess H2CO3 is removed by eliminating CO2 in lings
 ↑ H+ causes an additional stimulation of respiration
 Additional ↓in PCO2 & ↑ H2CO3 removed
 A net ↑H+ concentration ↓ pH to only 7.2 or 7.3, instead of rising
all the way to 6.0
 The reaction of CO2 + H2O ↔ H2CO3 is very slow in either direction,
in absence of Carbonic Anhydrase enzyme
 Hemoglobin ↑ buffering capacity of blood by binding free H+
produced by reducing H2CO3, movement of HCO3
–into plasma

85. ACIDOSIS & ALKALOSIS
 pH of arterial plasma is ≈7.40 and slightly > venous
plasma
 ↓ in pH below 7. 4 (acidosis) & ↑ in pH above 7.4
(alkalosis)
 Variations of up to 0.05 pH units do not usually produce
any detrimental effects on acid-base homeostasis
 Acid-Base disorders are categorized into
 Respiratory acidosis
 Respiratory alkalosis
 Metabolic acidosis
 Metabolic alkalosis
 In reality, combinations of these disorders can manifest
clinically

86. ACIDOSIS & ALKALOSIS
 Respiratory Acidosis: A short-term ↑ in arterial PCO2 above
that required (> 40 mm Hg, hypoventilation)
 Respiratory Alkalosis: A short term ↓ in PCO2 below that
required (< 35 mm Hg, hyperventilation). The ↓CO2 shifts the
equilibrium of CA–HCO3- system to a lower [H+] & higher pH
 Metabolic Acidosis: Addition of strong acids to blood
increases [H+] & ↓pH (E.x., Aspirin overdose). However, this
does not include a change in PCO2)
 Metabolic Alkalosis: Results due to fall in free [H+] due to
addition of alkali, or removal of large amounts of stomach
acids (vomiting)

87. COMPENSATED VS. UNCOMPENSATED
METABOLIC ACIDOSIS & ALKALOSIS
 Shift in pH during metabolic acidosis or alkalosis appears
along an isobar line  PCO2 doesn’t change in
uncompensated metabolic
acidosis/alkalosis (40 mm Hg)
 HCO3- concentration ↓ (14 meq/L)
& ↑ (30 meq/L) with acidosis &
alkalosis, respectively
 Most common types are
compensated (rarely uncompensated)
acidosis & alkalosis
 Two major compensatory systems
 Respiratory compensation
 Renal compensation

88. Mixed Apnea
It is a combination of central & obstructive apnea
 Commonly seen in premature or full-term babies
Due to underdeveloped brain/respiratory system
Hyperventilation
Forced breathing, where both respiratory rate & force ↑ moving
large volume of air, in & out of lungs
May cause dizziness, discomfort & chest pain
Conditions causing hyperventilation
Exercise elevates PCO2 (hypercapnea) → stimulation of
respiratory centers → hyperventilation → CO2 wash out
Can be produced voluntarily (voluntary hyperventilation)
Effects of hyperventilation
 Excess CO2 is eliminated, ↓PCO2, inhibits respiratory
centers causing apnea
Apnea → short period of Cheyne-Stokes breathing →
normal breathing

89.  Hypoventilation: ↓ Pulmonary ventilation caused by
↓in rate/force of breathing
 Conditions causing hypoventilation
 Suppression of respiratory centers or drugs or partial
paralysis of respiratory muscles
 Effects of Hypoventilation
 Results in development of hypoxia & hypercapnea → ↑
both rate & force of respiration → dyspnea → lethargy,
coma & death
 Hypoxia: Required quantity of oxygen cannot enter the
lungs & ↓ availability of oxygen to tissues
 Causes of hypoxia: Four important factors
 Oxygen tension in arterial blood
 Oxygen carrying capacity of blood
 Velocity of blood flow
 Utilization of oxygen by the cells

90.  Classification of Hypoxia: There are four types
 Hypoxic hypoxia: ↓oxygen in blood (arterial hypoxia)
 Causes:
 Low oxygen tension in inspired air
 High altitude
 Breathing air in closed space
 Breathing gas mixture containing low PO2
 Decreased pulmonary ventilation due to
respiratory disorders
 Obstruction of respiratory passage (asthma)
 Hindrance to respiration (Poliomyelitis)
 Respiratory center depression (tumors)
 Pneumothorax
 Respiratory disorders causing inadequate
lung oxygenation & gaseous exchange
 Impaired alveolar diffusion (emphysema)

91.  ↑ number of non-functioning alveoli (fibrosis)
 ↑ number of fluid filled alveoli (Pneumonia)
 Lung collapse (bronchiolar obstruction)
 Surfactant deficiency
 Abnormal pleural cavity (pneumothorax)
 Increased venous admixture (bronchiectasis)
 Cardiac disorders causing low blood flow &
decreasing oxygen transport
 O2 availability & diffusion are both normaI, but
inadequate pumping of blood from heart
(congestive heart failure)
 Anemic hypoxia: inability of blood to carry sufficient O2
due to decreased oxygen carrying
capacity of blood
 Causes
 Decreased RBCs number: RBCs number decrease
(Hemorrhage, Bone marrow disorders)

92.  Decreased blood hemoglobin content: ↓count or
altered size, structure, shape of RBCs (mirocytes,
spherocytes, sickle cells, poikilocytes etc.)
 Formation of altered hemoglobin: Quantity of Hgb.
available O2 transport decreases (Poisoning with
chlorates, nitrates, ferri-cyanides causes oxidation of
iron into ferric form (methemoglobin)
 Combination of Hgb. with other gases: Hemoglobin
combines with CO2, H2 S or nitrous oxide & becomes
unavailable for O2 transport
 Stagnant/Hypokinetic Hypoxia: ↓ blood flow velocity
 Causes
 Congestive cardiac failure
 Hemorrhage
 Surgical shock
 Vasospasm
 Thromboembolisms

93.  Histotoxic hypoxia: Inability of tissues to utilize oxygen
 Causes: Cyanide or Sulfide poisoning
 Effects
 Damage cellular oxidative enzymes & paralyse
cytochrome oxidase system
 Characteristically, inability of cells to use O2 even if
delivered to site of oxidation
 Effects of hypoxia (Immediate vs. Delayed Effects)
 Immediate Effects
 Blood
 ↑ erythropoietin production from kidney → ↑RBCs
count
 ↑ oxygen carrying capacity of blood
 Cardiovascular system
 Stimulation of cardiac & vasomotor centers
 Initial↑ in Rate & force of cardiac contraction, ↑ BP &
↑ CO, but all decreases later

94.  Respiratory system
 Chemoreceptor stimulation ↑ respiratory rate
 Excess CO2 removed causing alkalemia
 Respiration becomes shallow & periodic
 ↓Rate, ↓force of breathing & respiratory centers’ failure
 Digestive system
 Loss of appetite, nausea & vomiting
 Mouth dryness & ↑ thirst
 Renal system
 ↑ erythropoietin production from JG apparatus in kidney
 Urine turns alkaline
 Central nervous system
 depressed, apathetic & loss of self control
 uncontrolled emotional expressions (ill tempered,
rudeness)
 Loss of memory, weakness, fatigue
 If left untreated, loss of consciousness, coma & death

95.  Hypoxia: Delayed Effects
 Subject becomes highly irritable
 Show signs of mountain sickness viz. nausea, vomiting,
depression, weakness & fatigue
 Hypoxia treatment
 O2 therapy is considered most helpful
 Administered 100% O2 /combination with another gas
 Treatment performed in two ways
 Subjects head is put in a ‘tent’ containing O2
 Subject made to breathe O2 with mask/nose tube
 O2 administered at normobaric/hyperbaric pressures
 Normobaric O2 therapy
 O2 supplied at normal 1 ATA (760 mm Hg)
 Well tolerated, however longer duration of O2
therapy ( > 8 hr) may cause pulmonary edema &
heart failure

96.  Hyperbaric O2 therapy
 O2 supplied at 2 to 3 ATA
 Well tolerated for 5 hr
 ↑ in fraction of dissolved O2 in arterial blood
 ↑ in tissue PO2 (>200 mm Hg)
 O2 toxicity may develop (longer durations)
 Efficacy of O2 Therapy
 Although best option, efficacy depends on hypoxia type
 100 % − Hypoxic hypoxia
 ≈ 70% − Anemic hypoxia
 < 50% − Stagnant hypoxia
 ≈ 0% − Histotoxic hypoxia
 Oxygen toxicity
 ↑ O2 content in tissues beyond a critical level
 Pure O2 breathing at 2 − 3 ATA (hyperbaric oxygen)
 Excess O2 is predominantly transported, dissolved in plasma

97.  Effects of oxygen toxicity
 Tracheobronchial irritation & pulmonary edema
 ↑ Metabolic rate & ↑ heat generation by tissues
 Tissues appear burnt , damage of cytochrome system & tissue
 Neural disorders such as hyperirritability, ↑muscular twitching,
ringing in ears & dizziness
 Hypercapnea
 ↑ CO2 content in blood
 Causes
 Blockage of respiratory pathways (asphyxia)
 ↑CO2 content in inspired air
Effects
Respiration
Respiratory centers are stimulated leading to dyspnea
Blood
Blood pH↓ & turns acidic

98.  Cardiovascular System
 Tachycardia, increased BP & skin flushing due to
peripheral vasodilatation
 Central nervous system
 Headache, depression and laziness, muscular rigidity, fine
tremors, convulsions, giddiness & loss of consciousness
 Hypocapnea
 ↓ CO2 content in blood
 Causes
 Hypoventilation
 Prolonged hyperventilation removing excess CO2
 Respiration
 Respiratory centers depressed
 ↓rate, ↓force of respiration

99.  Blood
 ↑ Blood pH resulting in respiratory alkalosis
 ↓ Ca2+ concentration causing tetany with
neuromuscular hyperexcitability & carpopedal
spasm
 Central Nervous System
 Mental confusion, dizziness, muscular twitching &
loss of consciousness
 Asphyxia
 Simultaneous Hypoxia & hypercapnea, due to airway
obstruction
 Causes
 Conditions causing acute obstruction of air passages
 Strangulation
 Hanging
 Drowning

100.  Effects of Asphyxia
 Condition develops in 3 stages
 Stage of Hyperpnea
 1st stage, lasts for a minute
 Deep & rapid breathing
 Stimulation of respiratory centers by excess CO2
 Dyspnea & cyanosis follows
 Stage of Convulsions
 2nd stage, lasts for less than a minute
 Hypercapnea leads to convulsions violent expiratory
efforts, ↑ heart rate, ↑BP & loss of consciousness
 Stage of Collapse
 3rd stage lasts for 3 minutes
 Severe hypoxia leads to CNS depression, convulsions,
respiratory gasping, dilatation of pupils, ↓heart rate,
loss of reflexes & death
 Duration is only 5 minutes, prompt treatment will be life saving

101.  Dyspnea
 Difficulty in breathing or ‘air hunger’
 Conscious breathing leading to discomfort, dyspnea
 Dyspnea point: Increased ventilation (5X), severe breathing
discomfort
 Causes
 Physiological dyspnea: Severe muscular exercise
 Pathological dyspnea
 Respiratory disorders
 Mechanical or nervous hindrance in airways, as
seen in Pneumonia, Pulmonary edema, Pleural
effusion, poliomyelitis, pneumothorax & Asthma
 Cardiac Disorders
 Left ventricular failure, Decompensated mitral
stenosis
 Metabolic Disorders
 Diabetic acidosis, uremia & ↑ H+ concentration

102.  Dyspneic index
 Index between breathing reserve & maximum breathing
capacity (MBC)
 Breathing reserve = MBC – RMV (respiratory minute volume)
 Normal value is 95%, dyspnea occurs, when index is < 60%
Periodic breathing
Abnormal or uneven respiratory rhythm
Two types
Cheyne-Stokes breathing
Biot breathing
Cheyne-Stokes breathing
Periodic breathing characterized by rhythmic
hyperpnea and apnea
Two alternate patterns of breathing is observed
Hyperpneic period
Apneic period

103. Hyperpneic period
Initially, shallow breathing, then respiratory force
↑ gradually & reaches maximum (hyperpnea)
↓ incrementally & reaches minimum (apnea)
incremental ↑ followed by incremental ↓ in force of respiration
is called ‘waxing & waning of breathing’
Apneic period
Respiratory force ↓ to minimum, breathing ceases momentarily
 This is followed by hyperpneic period & the cycle is repeated
 Duration of each cycle is ≈ 1 minute
Occasionally, waxing & waning occurs despite no apnea
Cause of waxing & waning
Forced breathing eliminates excess CO2 from blood
Respiratory centers become inactive ↓PCO2 , causing apnea
With apnea, CO2 ↑ (hypercapnea) & PO2 ↓(hypoxia), respiratory
centers activated, respiratory force ↑ to maximum, cycle repeats

104. Conditions causing Cheyne-Stokes Breathing
Occurs in both physiological & pathological conditions
Physiological conditions: During deep sleep, in high
altitude, prolonged voluntary hyperventilation, during
hibernation in animals, new born babies, after severe
muscular exercise.
Pathological conditions: During increased intracranial
pressure, advanced cardiac diseases leading to cardiac
failure, advanced renal diseases, leading to uremia,
premature infants & narcotics poisoning
 Biot breathing
 Features
 A form of periodic breathing characterized by period of
apnea & hyperpnea, but no waxing & waning
 After apnoeic period, hyperpnea occurs abruptly

105.  Causes of Abrupt Apnea & Hyperpnea
 Apnea causes CO2 accumulation, stimulates respiratory
centers, leading to hyperventilation
 Hyperventilation removes excess CO2, respiratory centers are
inert causing apnea
Causes
Not noticed in physiological conditions
Pathological nervous disorders having lesions or brain injuries

106.  Cyanosis
 diffused bluish coloration of skin & mucus membrane
(lips, cheeks, ear lobes, nose, fingertips) due to
presence of reduced hemoglobin (5 -7 g/dL ) in blood
 Causes
 Disorders causing arterial or stagnant hypoxia (not
in anemic or histotoxic hypoxia)
 Disorders causing alterations in hemoglobin, like
formation of methemoglobin or sulfhemoglobin
 Disorders of blood causing polycythemia
 Carbon monoxide poisoning
 Exposure to Carbon monoxide can lead to death
 Carbon monoxide causes more deaths than other gases
 Sources of gas
 gasoline engine exhausts, coal mines, gases from
guns, deep wells & drainage system

107.  Carbon monoxide (CO) toxicity
 Displaces O2 from hemoglobin, & affects O2 carrying capacity
 Hemoglobin has 200 X more affinity to CO vs. O2
 PCO of 0.4 mm Hg in alveoli is adequate to cause 50%
hemoglobin saturation with CO
 A PCO of 0.6 mm Hg is lethal
 Formation of carboxyhemoglobin left shift of oxygen-
hemoglobin dissociation curve & ↓ O2 unloading
 CO affects Cytochrome oxidase system in cells
 Despite hypoxia, feedback mechanisms fail to alert respiratory
centers (as PO2 do not change)
 Symptoms
 Breathing air with
 1% CO causes headache & nausea (15-20% Hb sat.)
 > 1% CO leads to convulsions, cardiorespiratory arrest,
loss of consciousness & coma (30-40% Hb sat.)
 When Hb sat. becomes > 50%, CO causes death

108.  Treatment for CO toxicity
 Immediate termination of CO exposure
 Provide assisted ventilation/artificial respiration
 Administer 100% O2 to replace CO in blood
 Provide breathing air mixed with few % CO to stimulate
respiratory centers
 Atelectasis
 Partial or total lung collapse
 ↓ PO2 in blood leading to respiratory disturbances
 Causes
 Increased surface tension inside lungs due to deficient
inactivation of surfactant
 Bronchiolar obstruction & collapse of attached alveoli
 Accumulation of air, fluid, blood or pus in pleural spaces
 Effects
 ↓ PO2 leads to Dyspnea

109.  Pneumothorax
 Accumulation of air in pleural space
 ↑Intrapleural pressure (+ ve) & lung collapse
 Causes
 Damage of lungs, chest wall, piercing wounds etc.
 Types
 Open pneumothorax
 Pleural cavity opens to exterior, air moves in & out
through opening during respiration
 Injured lungs may collapse, cause hypoxia, hypercapnea,
dyspnea, cyanosis, asphyxia
 Closed pneumothorax
 A temporary opening lets air into pleural cavity
 After would seals, air in the cavity is reabsorbed
 Tension pneumothorax
 Wounds on chest or lungs may act as a fluttering valve
 Traps air inside the cavity, ↑ Intrapleural pressure (>1
ATA), collapse of lungs, death

110.  Pneumonia
Lung inflammation, accumulation of blood cells, formation of
fibrin & exudates in alveoli
Affected area becomes consolidated
Causes
Bacterial infection
Viral infection
Exposure to noxious chemicals
Types
Lobar pneumonia
Lobular pneumonia
Bronchopneumonia (lobular with bronchial inflammation)
Effects
Fever, chest pain, shallow breathing, cyanosis, insomnia &
delirium (caused by cerebral hypoxia: ex, mental state of
confusion, illusion, hallucination, disorientation, hyper-
excitability and memory loss)

111.  Bronchial asthma
 Labored breathing with wheezing
 A paroxysmal disorder as attack starts & stops abruptly
 Bronchiolar constriction due to spastic contraction of
bronchiolar smooth muscles causing airway obstruction
 Mucus membrane edema & mucus accumulation in lumen
can exacerbate the condition
 Greater difficulty is experienced during expiration than
Causes
 Inflammation of air passage due to leukotrienes from
eosinophils & mast cells → bronchiospasm
 Hypersensitivity of afferent (glossopharyngeal vagal)
ending in larynx & afferent (trigeminal) endings in nose
 Pulmonary edema & lung congestion due to left
ventricular failure (Cardiac asthma)

112.  Effects of Asthma
Incomplete deflation of lungs rises
Residual volume
Functional Residual Capacity
Parameters that decrease in asthma includes
Tidal volume
Vital capacity
Forced expiratory volume in 1 second (FEV1)
Alveolar ventilation
Partial pressure of oxygen in blood
Respiratory acidosis
dyspnea and cyanosis

113.  Pulmonary edema
 Serous fluid accumulation in alveoli & interstitial spaces of lungs
 Transudation causes atelectasis & dyspnea
 Causes
 ↑Pulmonary capillary pressure due to LV /mitral valve failure
 Pneumonia
 Breathing harmful chemicals like chlorine or sulfur-dioxide
 Effects
 Severe respiratory distress, cough with bloody expectoration,
cyanosis & cold extremities
 Pleural effusion
 Presence of large quantity of fluid in pleural cavity
 Causes
 Lymphatics blockage
 Transudation into interstitial spaces due to LV failure
 Pleuritis leaking capillary endothelium & fluid accumulating
in pleural cavity

114.  Pulmonary tuberculosis
 Pathological disease commonly affecting lungs
 Macrophages invade infected tissue & causes fibrous
 Affected tissue is called tubercle
 Cause
 Infection by tubercle bacilli
 Effects
 Affected alveoli non-functional due to respiratory
membrane thickening
 Diffusing capacity of respiratory membrane ↓
 Lung tissue damage followed by formation of large
abscess cavities
 Emphysema
 An airways obstructive diseases causing extensive lung
damage
 Reduced surface area of alveolar walls

115.  Causes of Emphysema
 Cigarette smoking, exposure to oxidant gases & untreated
bronchitis
 Pathogenesis of Emphysema
 Smoke/gases irritate bronchi and bronchioles, leading to
chronic inflammation & damage to alveolar mucus membrane
 ↑ Mucus secretion & ↓ movements of epithelial cells cilia,
both of which obstruct air ways
 Damage to lung elastic tissue (release of proteases & elastase
infiltrating leucocytes in damaged tissue)
 Effects of Emphysema
 Airway resistance increases, especially during expiration
 Lungs become floppy & loose due to alveolar damage
 ↓Pulmonary capillary number, ↑pulmonary vascular
 resistance causing pulmonary hypertension
 Ventilation-perfusion ratio ↓ affecting blood aeration
 Chronic emphysema leads to hypoxia & hypercapnea
 Causes prolonged, severe air hunger (dyspnea) & death

116. EXERCISE EFFECTS ON IMPORTANT
PHYSIOLOGICAL PROCESS
 Exercise
A specific type of physical activity that is planned, structured
and repeatedly done to improve or maintain physical fitness
Physiological modifications in body during exercise aimed at
Ensuring uninterrupted supply of nutrients & O2 to muscles
& other involved tissues
Prevent excessive rise in body temperature
Classification of exercise is based on type of muscle
contractions
Dynamic exercise
Isotonic muscular contractions & joint movements
Shortening of muscle fibers against a load
E.g., swimming, bicycling, walking
Södergren et, al. BMC Public Health 8, 352 (2008)

117. ↑Heart rate, ↑contractile force, ↑ CO & ↑ systolic BP
No change in diastolic BP, PR doesn’t change
Static exercise
Isometric muscular contraction, no joint movements
E.g., Pushing heavy objects
↑Heart rate, ↑contractile force, ↑ CO & ↑ systolic BP
& ↑ diastolic BP, ↑ PR
Classification based on type of metabolism
Aerobic exercise
Requires large amounts of O2
 Activities are of lesser intensity, but lasts for a longer
duration
Fats are utilized in O2 presence for energy production
E.g., Jogging, Swimming, Cycling, Hockey, Tennis
Anaerobic exercise
Exertion (short period) followed by rest

118.  Glycogen is burned in the absence of O2 for energy
 Lactic acid is produced that causes fatigue
 E.g., Push-ups, Weightlifting, sprinting
Classification based on severity of exercise
Mild exercise
Simple exercise such as slow walking
No significant change in cardiovascular function
E.g., Slow walking
Moderate exercise
No strenuous muscular activity, but lasts longer
E.g., Fast walking, slow running
Severe exercise
Strenuous muscular activity for shorter duration
E.g., Fast running (400-500 meters)

119.  Effects of exercise
 Blood
 Causes mild hypoxia
 Stimulates JG apparatus that secretes erythropoietin
 Activates bone marrow releasing more red blood cells
 ↑PCO2 & ↓blood pH
 Excessive sweating occurs to relieve body of excess heat
generated during exercise, this leads to
 Fluid loss
 Reduced blood volume
 Hemoconcentration
 Dehydration in extreme cases
 Heart
 ↑ Heart rate
 Normal restring rate, 72-80 beats/minute
 Moderate exercise, ↑180 beats/minute
 Severe exercise, ↑ 240 - 260 beats/minute

120. ↑ Heart rate due to
↓ Vagal tone
Proprioceptors’ stimulation
↑ PCO2
↑ body temperature stimulating SA node
↑ Catecholamines in circulation
Cardiac output
Normal resting value, 5L/minute
Moderate exercise, 20L/minute
Severe exercise, 35 L/minute
↑ CO due to ↑Heart rate & ↑ Stroke volume
↑Heart rate due to ↓ Vagal tone
↑ Stroke volume due to ↑ contractility
↑sympathetic nervous activity ↑both heart rate &
contractile force
Venous return
↑ VR due to ↑ muscle pump activity, respiratory pump activity,
splanchnic vasoconstriction, ↑mean systemic filling pressure
Resting
Moderate exercise

121.  Skeletal muscle blood flow
 Resting condition, 3 − 4 mL/100 g muscle/minute
 Moderate exercise, 60 − 80 mL/100g muscle/minute
 Severe exercise, 90 − 120 mL/100g muscle/minute
 ↑ Blood flow due to vasodilation
 ↑ Increased sympathetic cholinergic activity
 ↑ PCO2 (Hypercapnea)
 ↓ PO2 (Hypoxia)
 ↑ K+ (Hyperkalemia)
 ↑ Lactic acid
 ↑ Temperature
 ↑ Adrenaline (Adrenal medulla)
 Blood pressure
 Moderate exercise (isotonic muscle contraction)
 ↑ Systolic blood pressure due to ↑ heart rate & stroke
volume
 No change in diastolic pressure as peripheral resistance is
not affected

122.  Severe exercise (isotonic muscle contraction, length changes)
 Large ↑ in systolic pressure due to ↑ heart rate & stroke
volume
 ↓ Diastolic pressure due to vasodilatation & ↓ Peripheral
resistance
 Severe exercise (isometric muscle contraction, no change in
length)
 ↑ Systolic pressure due to ↑ heart rate & ↑ stroke volume
 ↑ diastolic pressure due to vasoconstriction & ↑ peripheral
resistance
 Post exercise period
 ↑ Accumulation of metabolic end products viz. Lactic acid,
Adenosine, Bradykinin etc. causes Vasodilation
 BP↓ slightly, but recovers to normal resting value once
metabolites are washed away from blood

123.  Metabolism in Aerobic & Anaerobic exercise
 Initially, first 3-5 minutes
 Muscles use in situ stored glycogen for energy
 No oxygen/fats utilized, ‘anaerobic metabolism’
 Lactic acid produced, causes muscle soreness
 Next 15-20 minutes
 Liver glycogen goes to muscles, initiates aerobic metabolism
No lactic acid produced, muscle soreness decreases
 Finally,
 Fats mobilized for energy, some converted to glucose
 Three major effects of exercise on circulation
 Sympathetic activation ↑ heart rate, contractility, release
of heart from parasympathetic inhibition
 Vasoconstriction in major tissues, vasodilation in active
muscles, ↑total PR & ↑Blood pressure
 ↑ Mean systemic filling pressure, ↑VR & ↑CO

124.  Pulmonary ventilation
 Amount of air that enters & leaves lungs each minute
= Tidal volume x Respiratory rate
= 500 mL x 12 = 6 L/minute
 Hyperventilation
 ↑ force & rate of respiration
 Moderate exercise
 RR = 30/minute; Tidal volume = 2,000 mL
 Pulmonary ventilation = 30 X 2000 = 60 L/min
 Severe exercise
 Pulmonary ventilation > 100 L/minute
 Factors ↑ pulmonary ventilation in exercise
 Higher brain centers
 Central & Peripheral Chemoreceptors
 Proprioceptors
 Body temperature
 Acidosis

125.  Higher brain centers
 ↑ rate & depth respiration, even in anticipation of exercise
 Psychic phenomenon due to activation of Sylvian & motor cortex
 Augments respiration by stimulating respiratory centers
 Chemoreceptors
 Hypoxia & Hypercapnea stimulates respiratory centers
 ↑ both rate & force of respiration
 Proprioceptors
 Stimulate cerebral cortex through somatic afferent nerves
 Cerebral cortex stimulates respiratory centers & causes
hyperventilation
 Body temperature
 ↑ Muscular activity, ↑ventilation by stimulating respiratory
centers
 Acidosis
 ↓ pH in blood stimulates respiratory centers & causes
hyperventilation

126.  Diffusing capacity for oxygen
 ↑ in blood flow in pulmonary capillaries
 ↑in diffusing capacity of O2 across respiratory membrane
 Resting condition = 21 mL/minute
 Moderate exercise = 45 to 50 mL/minute
 Oxygen Consumption
 ↑ in O2 consumption by active skeletal muscles
 ↑ vasodilatation ↑ blood flow & ↑ O2 diffused into muscle
 O2 utilized by muscles ∞ to available O2 , linear relation
 Oxygen debt
 Excess amounts of O2 is required by muscles during recovery
from exercise to reverse some metabolic processes
 Synthesis of glucose from accumulated lactic acid
 ATP & creatine phosphate resynthesis
 Restoration of O2 separated from Hemoglobin & Myoglobin
 O2 required is 6 X resting state requirement

127.  VO2 max
 Amount of oxygen consumed under maximal aerobic
metabolism
 Maximal CO X Maximal O2 consumed by muscle
 Males, VO2 max = 35 to 40 mL/kg. bd. Wt. /minute
 Females, VO2 max = 30 to 35 mL/kg bd. Wt. /minute
 During exercise, VO2 max ↑ 50%
 Respiratory Quotient
 Molar ratio of CO2 production to O2 consumption
 In resting condition = 1.0
 During exercise = 1.5 to 2.0
 At the end of exercise, respiratory quotient = 0.5

128. PHYSIOLOGICAL RESPONSES TO
EXCERCISE
Increased Work Rate
No change in mean
arterial PCO2 (PACO2)
with ↑ work rate
VE ↑ with ↑ work rate
Vco2 ↑ with ↑ work
rate
VO2↑ with ↑ work rate
pH ↓ with ↑ work rate
HCO3
- ↓ with ↑ work
rate

129. Altitude
Region of earth located above sea level
Significance of altitude
Altitude↑, Barometric pressure ↓
Altitude↑, VO2 is constant, but PO2↓
Adverse effect: Tissue hypoxia
Factors affecting Physiology at high altitudes
Hypoxia
Expansion of gases
Fall in atmospheric temperature
Light rays
HIGH ALTITUDE PHYSIOLOGY

130. PARTIAL PRESSURES & ALTITUDE

131.  Expansion of gases on the body
 Gas volume ↑ with ↓ Barometric pressure
 High altitude↑ volume of all gases in atmosphere
Gases in GIT & Alveoli expand
causing discomfort, pain & even
rupture of alveoli
Decompression sickness: Rapid
ascent to ≥ 30,000 feet altitude
make blood gases evolve as bubbles
 ↓ Atmospheric temperature
 At 10,000 ft height, temperature
drops to 0°C
 Temperature ↓ with↑ in
altitude
 Frostbite occurs if body is not
covered by warm clothing

132. PHYSIOLOGICAL CHANGES AT
HIGH ALTITUDE
 Hypoxia
 Reduced availability of oxygen to tissues due to changes in
 Oxygen tension in arterial blood
 Oxygen carrying capacity of blood
 Velocity of blood flow
 Utilization of oxygen by cells
 Hypoxia is of several types
1) Hypoxic hypoxia 2) Anemic hypoxia
3) Stagnant hypoxia 4) Histotoxic hypoxia
 Acute effects on several organs including, blood, CVS,
respiration, digestive system, kidneys & CNS
 Delayed effects depends on degree of hypoxic exposure, &
manifest as mountain sickness, nausea, vomiting, depression,
weakness & fatigue

133.  Light Rays
Ultraviolet rays of sunlight injure skin tissue
Sunrays reflected by snow may injure eye retina
Severity depends on steepness of ascension to high altitude
E.g., Milder in slow ascent vs. severe in rapid ascent
 Mountain sickness
 Disorder of adverse effects due to hypoxia at high altitude
 Common in first time climbers
 Rapid onset (< a day), before acclimatization starts
 Symptoms
 Digestive System
 Loss of appetite, nausea, vomition due to expansion of
gases in GI tract
 Cardiovascular System
 ↑ Heart rate, ↑ contraction force

134.  Respiratory System
 ↑ Pulmonary BP due to ↑ blood flow & ↑ vasodilatation
 Leads to pulmonary edema & breathlessness
 Nervous System
 Acute exposure to hypoxia at elevated places results in
vasodilatation in brain
 Auto control blood flow mechanism of brain fails to
compensate for hypoxia
 Cerebral edema as both capillary Pressure & leakage ↑
 Headache, depression, disorientation, irritability, lack of
sleep, weakness & fatigue
 Treatment
 Mountain sickness symptoms subside by breathing of O2

135. Acclimatization
Adjustments that a body makes in high altitudes
 Slow process, takes several days to weeks to acclimatize to low
PO2 to minimize hypoxia effects
Acclimatization enables further ascension
Changes during Acclimatization
Blood
↑erythropoietin secretion from JG apparatus of kidney
↑ RBC, ↑ PCV (45 - 59%), ↑Hemoglobin (15 g% to 20 g%)
↑ O2 carrying capacity of blood, to compensate for hypoxia
Cardiovascular System
↑ Heart rate, ↑contractility & CO in response to hypoxia
Vasodilatation in brain, heart & muscles leading to↑ tissue
blood flow
ACCLIMATIZATION

136.  Respiratory System
Hypoxia stimulates chemoreceptors causing a 65% ↑ in
pulmonary ventilation
↑ blood flow to heart ↑ CO causing Pulmonary hypertension
Seldom right ventricular hypertrophy also develops
↑ Diffusing capacity of gases enables more diffusion of O2
Other tissues
Residents who are acclimatized for high altitude dwelling have
more Cellular oxidative enzymes in their cells, that enhance
oxidative metabolism vs. cells of sea level dwellers
Mitochondrial content of the cells is high in fully acclimatized
persons

137. SUMMARY

138. AVIATION PHYSIOLOGY
Study of physiological responses of the body in Aviation
Environment (AE)
Two types of forces play on the body in AE
Accelerative forces
Centrifugal forces
Accelerative forces
Acceleration is rate of change of velocity
Accelerative forces develop in flight during linear, radial/
centripetal & angular acceleration
Accelerative forces cause severe physiological changes
Gravitational forces
A major accelerative force
Directionality of G force is key to physiological effects
Force/gravity pull upon the body is expressed in G unit
Weight (W)/F = Mass x Gravity = 1 G

139. G is same for stationary object in all directions on earth surface
E.g., An animal weight is same regardless of the body posture
If G ↑ to 5 G during acceleration, momentary force of gravity on
body = 5 X body weight
In a moving object
 A sudden change in acceleration/direction can centrifuge a
person in opposite direction
G Positive − acceleration
G Negative − deceleration
During flight, +ve G & −ve may occur altering physiology
Effects of gravitational forces on the body
Positive G
Primarily affects blood circulation
Acceleration at 4 to 5G causes blood pooling in lower parts
(limbs, abdomen etc.) of the body
Blood flow↓, CO↓ affecting circulation to head & eyes
Results in hypoxic damage to these organs

140.  Grayout
 Graying of vision due to hypoxic effects on retina
 No vision impairment
 Grayout is a loud call out for ↓ blood flow to head
 Blackout
 Total vision loss due to hypoxic effects on retina
 Although consciousness & muscular activities are intact, risk of
loosing consciousness increases
 Loss of consciousness
 At > 5G, hypoxia effects peak leading to loss of consciousness
 Unconsciousness may be occur, but brief, ≈ 15 seconds
 However, reorientation may take more than 10 -15 minutes
 If subject is a lone pilot, he risks loosing control over his wheel
 Bone fractures
 Around forces of 20 G, bones (e.g., spine) become susceptible
to fractures even while sitting

141.  Effects of negative G
 Negative G encountered while flying/accelerating downwards
 Hyperemia
 Occurs at – 4 to – 6 G
 Blood is pushed upwards of the body
 Blood flow to head ↑ abnormally
 Brain edema
 Congestion
 Flushing of face
 Mild headache
 G forces at this level are almost compatible with
normal flight operations
 Redout
 Occurs upon exposure to –15 G to –20 G forces
 Vision gets blurred & visual field suddenly turns red
 Caused by engorged blood vessels in head due to
dilatation & congestion of blood vessels in head & eyes

142.  Brain tissue spared due to CSF accumulation in cranium
 High pressure exerted by CSF acts as a cushion
 Loss of Consciousness
 High negative G ↑ pressure in chest & neck blood
vessels
 Bradycardia & arrhythmia may occur
 Blood pooling in head resulting in unconsciousness
 Prevention G force effects on the body
 Abdominal Belts
 Prevents blood pooling in abdominal blood vessels &
helps to postpone Grayout or blackout
 Anti-G Suit
 Apply positive pressure on lower body parts
 Prevents blood pooling in lower body parts
 Postpone Grayout or blackout

143. SPACE PHYSIOLOGY
Space Physiology: Study of physiological body responses in
space & spacecrafts
Factors that challenge survival of life in space
Atmosphere
Spacecraft/spacelab maintains terrestrial coordinates
of temperature, humidity & gas composition
Radiation
Astronauts wear pressurized launch & entry suits (LES)
Gravity
Affects body weight in space
Astronauts experience weightlessness in space due to
microgravity

144.  Effects of travel by spacecraft
 Space travellers experience intense symptoms during lift off &
re-entry phases
 Accelerative forces are least experienced in spacecrafts vs.
aircraft, as speed /direction changes are minimal in spacecrafts
 Most adaptive physiological changes in space travel happen
due to weightlessness
 Cardiovascular & renal systems
 Fluid shifts from lower parts to upper body parts
 Enlargement of heart to handle ↑ blood flow
 Fluid accumulation in upper body, eyes & head
 Renal compensation
 Kidneys excrete large quantities of fluid & ↓blood
volume
 Heart size
 Decreases as heart now pumps only this reduced
amount of blood, against a zero gravity

145.  Astronauts experience dizziness in space due to
diminished blood flow to head
 Astronauts do not feel thirsty during space travel
 Kidneys excrete electrolytes with water, so
osmolality does not change
 Thirst centers remain inactive
 Blood
 ↑ Fluid excretion by kidney
 ↓ Plasma volume
 ↓ RBC count, space anemia
 Musculoskeletal System
 Muscles need not support the body against
gravity
 Astronauts float in space due to microgravity
 ↓Muscle mass, ↓ strength, ↓ endurance
 ↑Activity of Osteoclasts in bones & excess Ca2+ is
removed through urine

146. Immune System
Space travel supresses immune system in the body
Space Motion Sickness
Due to microgravity
Short period (2-3 days) of Nausea, vomiting, Headache,
malaise
Motion sickness caused
 Abnormal stimulation of vestibular apparatus
 Fluid shift

147. DEEP SEA PHYSIOLOGY
Expedition into deep seas is fraught with dangers of high
barometric pressures of depth on human/animal body
Pressure increases by 1 atmosphere (atm) for every 10 m/33 ft.
descent below sea level
Two major problems
↑ Compression of body & internal organs
↓ Gas volumes
 Nitrogen narcosis
 Unconsciousness or stupor
produced by nitrogen (N2)
 An altered mental state alike
alcohol like intoxication
 Not seen at sea level, but common in divers breathing
compressed air under high pressure
 Compressed air breathing levels out the surrounding high
pressure acting on abdomen & chest

148. Mechanism of N2 narcosis
Nitrogen is a fat soluble gas
Under high pressure, N2 escapes vasculature & dissolve in body
fat depots including neuronal membranes
Dissolved N2 acts as an anaesthetic & inhibits neuronal
membrane excitability & causes narcosis
N2 remains dissolved in fat till the person remains in deep sea
Symptoms of N2 narcosis
At 120 feet depth
Symptom begin to manifest
At 150 to 200 feet depth
Person becomes euphoric & looses the sense of
seriousness, & feels drowsy
At 200 to 250 feet depth
 The diver becomes extremely fatigue, weak, looses focus &
judgment, diminished ability to perform skilled work
At depths > 250 feet
 The diver becomes unconscious

149. Prevention
Substituting helium for N2 with O2, so helps dilute O2
Limiting the depth of dives
Following safe diving procedures & proper upkeep of
equipment, & minimizing work effort during diving
Abstaining from alcohol consumption, at least during 24 h.
period, prior to diving
Treatment
Symptoms disappear as soon as the diver returns to 60 feet
depth
Unlike alcohol consumption, N2 narcosis does not have any
hangover effect
 If diver looses consciousness, the physician should be
immediately consulted

150.  Decompression Sickness
 Condition seen in divers upon rapid ascent to the sea level from
an area of high atmospheric pressure like deep sea
 Synonymously referred to as; dysbarism, compressed air
sickness, caisson disease, bends or diver’s palsy
 Causes
 High barometric pressure causes compression of gases & ↓
volume of gases in the body
 N2 (80%), compression under high pressure, causes N2 to escape
from vasculature & dissolve in fat tissues
 On a rapid ascension, the dissolved gases decompress & N2
escape organs very rapidly & forms bubbles
 Bubbles lodge in blood vessels & may cause air embolism
 Tunnel workers using caissons (pressurized chambers) also
develop decompression (caisson disease) sickness
 Can occur even in those who ascends rapidly in an aircraft
without taking adequate precaution

151.  Symptoms
Primarily due to N2 bubbling out from tissues
Severe joint pain due to N2 in myelin sheath of sensory
nerve fibers
Numbness, pricking (paraesthesia) & itching
Transient paralysis due to N2 bubbles in myelin sheath
of motor nerve fibers
Muscular cramps & myopathy
Coronary arterial blocks due to lodging of N2 bubbles
followed by ischemia
Blood vessel occlusion in brain & spinal cord
Dizziness, shortness of breath & choking
Finally, fatigue, unconsciousness & death
Prevention
When returning to sea level, slow ascension is warranted
Regular periods of short stay at different depths
This allows N2 to go into blood, without forming bubbles

152. Treatment
First, recompression should be performed by holding the diver
in a recompression chamber
 Diver is then brought back to atmospheric pressure by
gradually reducing the pressure
Hyperbaric oxygen therapy can also be helpful
 Scuba diving
 SCUBA (Self Contained Underwater Breathing Apparatus)
 Divers & underwater tunnel workers use SCUBA to mitigate ill
effects of increased barometric pressure on body
 Easy to carry & contains air cylinders, valve system & mask
 Facilitate breathing gas mixture without high pressure
 Valve systems allow only optimal amount of air entering &
leaving the masks
 Limitation
 Only supports for a shorter stay underwater
 Beyond depths > 150 feet, diver can only stay for few minutes

153. HOT & COLD EXPOSURE
 Exposure to cold
 Cold exposure tends to ↓ body temperature
 Body maintains near constant core temperature in two ways
 Heat production
1. Enhancing metabolism 2. Shivering
Heat gain center
Cold
Sympathetic centers
Adrenal Medulla
↑ Catecholamines
↑ Cell metabolism
Heat gain center
Cold, < 25°C
Posterior hypothalamus
Primary motor center
↑ Shivering
Heat production

154.  Severe Cold exposure
 Exposure to severe cold leads
to death
 Survival time is temperature
dependent
 Exposure to 0°C for 20 -
30 minutes, body
temperature ↓ to < 25°C
Heat gain center
Cold
Sympathetic centers
Cutaneous vasoconstriction
↓ Blood flow
↓ Sweat secretion
↓ Heat loss
 Body maintains near constant
core temperature by
 Prevention of heat loss
 Survives if put in hot water tub (43°C)
 Survival time
 at 9°C is ~1 hour
 at 15.5°C is ~ 5 hours

155. Extreme cold exposure effects
Loss of thermoregulation
If body temperature
↓ to ≈ 34.4°C, hypothalamic thermoregulation is
inhibited
↓ to < 25°C, hypothalamus thermoregulation is
completely lost, & shivering does not occur
Additionally, low temperature inhibit metabolic heat
production
Person develops sleep or coma due to CNS depression
Frostbite
Freezing of body surfaces upon cold exposure
Sluggishness of blood flow is the prime culprit
 Common to exposed extremities, ear lobes, digits
Mostly seen in mountaineers, skiers etc.
May lead to permanent damage of cells followed by thawing
and gangrene formation

156.  Heat exposure: Heat exposure causes
Heat exhaustion
Occurs due to excessive water & salt loss, in sweat
A warning bell for body getting too hot with symptoms
Increased heart rate
Increased cardiac output
Cutaneous vasculature dilatation
Increased moisture of the body
Blood pressure drop
Muscle weakness & uneasiness
Mild dyspnea
Dehydration exhaustion
Heat exposure results in dehydration Due to excessive
sweating
↓ Cardiac output , ↓ Blood pressure
 Person may collapse if treatment is not initiated
immediately

157. Heat cramps
Continuous & copious sweating due to heat exposure
Reduced salt & water levels in body cause painful cramps
Heat stroke
Serious hyperthermia due to exposure to extreme heat
 ↑ in body temperature above 41°C
 Severe Physical & neurological discomfort
Severe form of heat injury, often fatal if immediate
treatment is not initiated
Hypothalamus loses the power of regulating body
temperature
 Sunstroke is a form of heat stroke caused due to exposure to
summer weather in deserts & tropics
 Susceptibility to Heatstroke/Sunstroke is high in
 Infants, old people with renal/cardio-pulmonary disorders
 People doing physical labour under sun
 Sportsmen doing continuous sports activities

158. Common symptoms of Heatstroke are
Nausea & vomiting, dizziness & headache
Abdominal pain, breathing Difficulties
Vertigo, confusion, muscle cramps, Convulsions
Paralysis, unconsciousness
Brain damage & coma, if not treated immediately
Heat Stroke & Humidity
Heatstroke incidence may depend on humidity
 If air is dry
Body may tolerate exposure to 54.4°C for several hours
If air is 100% humid
 Body exposure to 41°C also causes heatstroke
 Prevention
 Heatstroke or sunstroke can be avoided by the following
measures
 Avoid dehydration
 Take frequent breaks from work (under sun)
 Wear light clothes

159.  Treatment
 Initiate treatment before organ damage starts
 Move the subject away from hot environment & send to
medical center for treatment
 Cooling body, immediately is the usual treatment
 Subject must be immersed in cold water
 Subject may be sprayed cold water on skin
 Cooling head & neck should be done first
 Rub ice cubes on head & neck or place ice packs under
armpits & groins
 Body cooling efforts shall continue until body
temperature falls to ≈ 35°C

160. Artificial Respiration (AR) /Assisted Ventilation (AV)
Lack of O2 supply to brain, even for < 5 min, may cause
ischemia & irreversible damage
AR is a procedure applied to patients when their breathing
ceases without cardiac arrest
Indications for AR
To ventilate alveoli & stimulate respiratory centers
To revive O2 supply quickly, before heart fails
Conditions where breathing ceases
Gas poisoning
Accidents
Electrocution
Anesthesia
Drowning
ARTIFICIAL RESPIRATION

161.  Methods of Artificial Respiration
 There are of two types
 Manual methods
 Mechanical methods
 Manual methods
 Applied swiftly without any mechanical assistance
 Loosen clothes & any jewellery around persons neck &
chest regions
 Clear of mucus, saliva & any foreign particles from the
persons mouth & throat
 Manoeuvre the tongue so that it is out of the way of
airways
Manual methods are mainly four types
Mouth-to-mouth method
Holger Nielsen method
Mouth to mask method

162. Mouth-to-mouth method
Subject is laid in the supine position & resuscitator
should kneel at the subjects’ side
 Resuscitator then keep his thumb on subject’s mouth, &
pull the lower jaw downwards
Subjects’ nostrils should be closed with thumb & index
finger of the other hand
 Resuscitator should take a deep breath & forcefully
exhale air into the subjects’ mouth
 Volume of exhaled air must be 2 X tidal volume, to
optimally expand lungs
 The resuscitator then remove his mouth from that of
the subject
 Now, a passive expiration occurs in the subject due to
elastic recoil of the lungs
 This procedure is repeated at 12 − 14 times a minute, till
normal respiration is restored

163.  Advantage
 Most effective method as CO2 in resustators’ expired air
can directly stimulate subjects’ respiratory centers &
augment respiration
 Disadvantage
 Close contact between the mouths of resuscitator &
subject might not be acceptable for various reasons
 Holger Nielsen Method/Back Pressure Arm Lift Method
 Place Subject in a prone position & turn head to one side
 Subjects’ hands are placed under the cheeks by flexing at
the elbows & abduction at the shoulders
 Resuscitator then kneel beside the head of the subject
 Resuscitator has to place his palms over subjects’ back &
bends forward with flexion at elbow & apply pressure on
the subjects’ back
 Resuscitators’ weight plus pressure applied on subjects’
back compresses subjects’ chest & expels air

164. Now, resuscitator should lean back & simultaneously draw subject’s
arm forward by holding it just above elbow, so that thoracic cage
expands & air flows into lungs
The procedure is repeated 12 times per minute, until normal
respiration is restored
 Mouth to mask method
Subject is laid in the supine position & resuscitator
should kneel/stand at the subjects’ side
 A mask is fixed on to patients airways & air is blown into
subjects nostril through the mask
 Hygienic & effective, capable of delivering up to 3 L of VT
 Bag-Valve-Mask method
 A self-inflating air bag connected to an inspiratory &
expiratory valves will be attached to the subjects mask
 A specific amount of air can be pumped into subjects
airways by squeezing the air bags
 This method may lead to hyperventilation, higher pressure
development in airways & cause gastric insufflation

165. Mechanical ventilation methods are of two types
 Drinker method
 Ventilation method
 Drinker Method
 Iron lung chamber or tank respirator equipment is used
 Tank respirator has an airtight iron chamber
 Subjects’ torso is placed inside this chamber while the head
stay outside the chamber
 Repeated cycles of negative & positive pressures are
maintained inside the chamber
 During each cycle when pressure turns,
 Negative, inspiration occurs
 Positive, expiration occurs
 Patient resustated using this method can survive for
 a longer time (around 1 year) until restoration of natural
respiratory function
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166. Ventilation Method (Mechanical Ventilation)
 Required when subject needs artificial respiration for longer
duration
 Mode of breath delivery
 Assisted mode: inspiratory effort is triggered by patient &
ventilator delivers breath
 Mandatory mode: Ventilator delivers a set of breaths at a
set tidal volume/inspiratory pressure
MV is of two types
Invasive mechanical ventilation
Noninvasive mechanical ventilation
 Indications for MV
Air way disease of compromise (PaO2 < 60 mm Hg)
Subject is obtunded or has dynamic airways (trauma
oropharyngeal infection)
Airway obstruction (Angioedema, bronchospasm, COPD)

167. Hypoventilation resulting in hypercapnic (PCO2 > 52 mm
Hg) respiratory failure
Impaired central respiratory drive (drug overdose)
Respiratory muscle weakness (myositis)
Peripheral nervous system defects (myasthenia gravis,
Guillain-Barre syndrome)
Restrictive ventilator disorders (Pneumothorax,
pleural effusion)
Hypoxemic respiratory failure due to poor exchange of
O2, Hypocapnea (PCO2 < 35 mm Hg), ↑ breathing work,
orthopnea with eyes closed during breathing
Alveolar filling defects ( Pneumonia, ARDS)
Pulmonary vascular defects causing ventilation
perfusion mismatches (Embolism in lungs vasculature)
Diffusion defects (extreme lung fibrosis)
Increased ventilator demand (severe circulatory failure)
During sepsis, shock & acidosis

168. Apparatus used to assist respiration in subjects with respiratory
difficulties is termed, ‘Ventilator’
Breaths are delivered via. a rubber tube inserted into subjects
trachea (Endotracheal intubation)
An external pump then drives air/oxygen into subjects lungs,
intermittently, under positive pressure
Air moves in (inspiration) & out (expiration), each cycle
Cycles of inspiration & expiration occur at a pre-set rate
Phases of Invasive Mechanical Ventilation
Trigger phase: Initiation of inspiration (by patient effort or
by ventilator)
Inspiratory phase: Inhalation of air into patient
Cycling phase: A brief momentary pause between the end
of inspiration & start of expiration
Expiratory phase: A period of passive expiration of air
INVASIVE MECHANICAL VENTILATION

169. Mechanical Ventilation utility depends on compliance, elastance &
resistance in the air ways of the patient
Pressure, volume & flow requirements during each respiratory
cycle are described as
Paw= P0 + (R x flow) + (Vt x ERS)
Paw = Airway pressure
P0 = Alveolar pressure at onset of inspiration
R = Resistance to flow, Vt = Tidal volume
ERS = Elastance of respiratory system (= 1/compliance)
 Pplat = Plateau pressure, airway pressure measured by an end
inspiratory occlusion
Compliance, CRS =
Vt
(Pplat− P0)
Resistance, R =
(𝑷𝒆𝒂𝒌 𝒑𝒓𝒆𝒔𝒔𝒖𝒓𝒆 − Pplat)
𝒇𝒍𝒐𝒘
 Compliance: Volume change with a unit pressure change (dV/dP)
 PEEP = Positive End Expiratory Pressure: Pressure measured by
an end expiratory occlusion

170. Common modes of invasive MV
Volume-limited Assist Control ventilation (VAC)
Pressure-limited Assist Control ventilation (PAC)
Synchronized Intermittent Mandatory Ventilation
with Pressure Support Ventilation (SIMV-PSV)
Controlled Mechanical Ventilation (CMV) (volume
or pressure, limited)
Intermittent Mandatory Ventilation (IMV)
Airway Pressure Release Ventilation (APRV)

171. Volume-limited Assist Control ventilation (VAC)
Tidal volume (VT): Set at a fixed volume based on the subjects’
ideal body weight or predicted body weight (PBW), not actual
body weight (normal range is 8 −10 mL/kg. PBW, or raised even
up to 15mL/Kg. PBW). In protective lung strategies (ARDS), VT
kept low, 4 − 8 mL/kg. PBW
Respiratory rate: Set at 12 − 16 breaths per minute. To avoid
severe hypercapnea/acidosis, RR can be ↑ to ≈ 35 BPM
Inspiratory flow rate: Usually maintained at 40 − 60 L/min, to
maintain an inspiratory & expiratory duration ratio of 1:2 or 1:3.
In cases of COPD, flow can be raised up to 90 L/min
Fraction of Inspired O2: FIO2 set at minimal levels (usually ≈
40 %) to achieve pulse oximetry readings of 90 − 96 %, Initially
use 100 %, later ↓ to 40 − 60% depending on patient’s need)
Positive End Expiratory pressure: PEEP is set to ↑ FRC &
Stent open alveoli. Usually set at 0−4 cm H20 (normal lung) or
4−8 cm H20 in diseased lungs, depends on oxygenation needs
 Gas flow pattern is set
 Ventilator regulated

172. Trigger sensitivity: Flow trigger vs. pressure trigger. Pressure
trigger set at −1 to −2 cm H2O. In auto-PEEP, flow trigger (0.5 −
2L/min) preferred
 Pressure-limited Assist Control ventilation (PAC)
 Inspiratory pressure (Pi): Usually set at 8 −12 cm H2O above
PPEP (normal lung), 10 − 20 cm H2O above PEEP (diseased
lungs). mainly dependent on VT & RMV requirements
 Inspiratory time (Ti): Usually set for 1 second, to achieve I:E
ratio of 1:2 or 1:3
 PEEP & FIO2 : Set as in VAC
 SIMV-PSV mode:
 Pressure support: start with 5 − 10 cm H2O when patient is
taking spontaneous breaths (Respiratory Minute ventilation
can be targeted)
 Tidal volume: Set similar to VAC, minute ventilation goals can
be targeted
 Airway Pressure Release Ventilation mode
 Set 4 variables: P - high, P - low, T- high, T- low
 Preset pressure is applied
 Controlled by ventilator + R & E