The Respiratory System

1
The Respiratory System

• Chapter 16 Part II

2
Lung Volumes and Capacities

• Tidal volume amount of air expired in each
  breath (quiet breathing)
• Vital capacity max amount of air that can be
  forcefully exhaled after a max inhalation, equal
  to the sum of
• inspiratory reserve vol tidal vol expiratory
  reserve vol
• Functional residual capacity sum of the
  residual volume and expiratory reserve volume
• Total min vol Tidal vol at rest X number of
  breaths/min (6L/min)
• During exercise tidal vol and number of
  breaths/min increase to produce a total min
  volume as high as 100 200 L/min
• Anatomical dead space conduction zone (no gas
  exchange occurs)
• Lower O2 and higher CO2 concentrations than the
  external air

3
Restrictive and Obstructive Disorders

• Restrictive Disorders characterized by reduced
  vital capacity but with normal forced vital
  capacity
• e.g. pulmonary fibrosis
• Obstructive disorders vital capacity is normal
  because lung tissue is not damaged
• But expiration is more difficult and takes longer
• Bronchoconstriction increases resistance to air
  flow
• e.g. asthma

4
Obstructive Disorders Asthma

• Normal vital capacity but expiration is retarded
• FEV1 1 sec forced expiratory volume test
  measure rate of expiration

5
Pulmonary Disorders Asthma

• Frequently accompanied by dyspnea (shortness of
  breath)
• Asthma episodes of obstruction of air flow
  through bronchioles
• Caused by inflammation, mucus secretion, and
  bronchoconstriction
• Inflammation contributes to increased airway
  responsiveness to agents that promote bronchial
  constriction
• Provoked by allergic reactions that release IgE,
  by exercise, by breathing cold, dry air, or by
  aspirin

6
Pulmonary Disorders - Emphysema

• Chronic, progressive condition destroys
  alveolar tissue, resulting in fewer and larger
  alveoli
• Reduces surface area for gas exchange and ability
  of bronchioles to remain open during expiration
• Air trapping decrease gas exchange due to
  collapse of bronchiole during expiration
• Commonly occurs in long-term smokers
• Cigarette smoking stimulates release of
  inflammatory cytokines
• Attract macrophages and leukocytes that secrete
  enzymes that destroy tissue

7
Emphysema Destroys Lung Tissue

• Obstruction of lung tissue results in fewer and
  larger alveoli

8
Chronic Obstructive Pulmonary Disease

• COPD involves chronic inflammation accompanied
  by narrowing of airways and destruction of
  alveolar walls
• Most people with COPD are smokers
• Fifth leading cause of death

9
Pulmonary Fibrosis

• Sometimes lung damage leads to pulmonary fibrosis
  instead of emphysema
• Characterized by accumulation of fibrous
  connective tissue
• Occurs from inhalation of particles lt6?m in size,
  such as in black lung disease (anthracosis) from
  coal dust

10
Gas Exchange in the Lungs

• Partial pressure of gases
• Partial pressure pressure that a particular gas
  in a mixture exerts independently
• Daltons Law total pressure of a gas mixture
  (air) is equal to the sum of partial pressures of
  each gas in the mixture
• Atmospheric pressure at sea level is 760 mm Hg
• PATM PN2 PO2 PCO2 PH2O 760 mm Hg
• PO2 (21) PN2 (78) 99 of 760 mm Hg
• Inspired air contains variable amount of moisture
• When reaches respiratory zone saturated 100
  humidity

11
Effect of Altitude on Partial PO2

• With increasing altitude total atm pressure and
  partial pressure of the gases decrease
• Below sea level total pressure increases by 1 atm
  for every 33 feet
• At 33 feet pressure equals 2 X 760

12
Gas Exchange in Lungs Inspired Air - Alveolar
Air

• Driven by differences in partial pressures of
  gases between alveoli and capillaries
• As air enters the alveoli its O2 content
  decreases, CO2 content increases, and air is
  saturated with water vapor

13
Gas Exchange in Lungs

• Facilitated by enormous surface area of alveoli,
  short diffusion distance between alveolar air and
  capillaries, and tremendous density of
  capillaries
• Quickly help to bring O2 and CO2 in the blood and
  air into equilibrium

14
Partial Pressures of Gases in Blood

• When blood and alveolar air are at equilibrium
  the amount of O2 in blood reaches a maximum value
  
• Henrys Law says that this value depends on
  solubility of O2 in blood (a constant),
  temperature of blood (a constant), and partial
  pressure of O2
• So the amount of O2 dissolved in blood depends
  directly on its partial pressure (PO2), which
  varies with altitude

15
Blood PO2 and PCO2 Measurements

• Provide good index of lung function
• At normal arterial blood has about PO2 100mmHg
• PO2 40mmHg in systemic veins
• PCO2 46mmHg in systemic veins

16
Pulmonary Circulation

• Rate of blood flow through pulmonary circuit
  equals flow through systemic circulation
• But is pumped at lower pressure (about 15 mm Hg)
• Pulmonary vascular resistance is low
• Low pressure produces less net filtration than in
  systemic capillaries
• Avoids pulmonary edema
• Pulmonary arterioles constrict where alveolar PO2
  is low and dilate where high
• This matches ventilation to perfusion (blood flow)

17
Lung Ventilation/Perfusion(Blood Flow) Ratios

• Normally, alveoli at apex of lungs are
  underperfused and overventilated
• Alveoli at base are overperfused and
  underventilated

18
Disorders Caused by High Partial Pressures of
Gases

• Total atmospheric pressure increases by an
  atmosphere for every 10m below sea level
• At depth, increased O2 and N2 can be dangerous to
  body
• Breathing 100 O2 at lt 2 atmospheres can be
  tolerated for few hrs
• O2 toxicity can develop rapidly at gt 2
  atmospheres
• Probably because of oxidation damage

19
Disorders Caused by High Partial Pressures of
Gases

• At sea level, nitrogen is physiologically inert
• It dissolves slowly in blood
• Under hyperbaric conditions takes more than hour
  for dangerous amounts to accumulate
• Nitrogen narcosis resembles alcohol intoxication
• Amount of nitrogen dissolved in blood as diver
  ascends decreases due to decrease in PN2
• If ascent is too rapid, decompression sickness
  occurs as bubbles of nitrogen gas form in tissues
  and enter blood, blocking small blood vessels and
  producing bends

20
Regulation of Breathing

• Respiratory muscles controlled by 2 major
  descending pathways
• One controls voluntary breathing
• Another controls involuntary breathing
• Unconscious rhythmic control of breathing
• influenced by sensory feedback from receptors
  sensitive to
• PCO2, pH, and PO2 of arterial blood

21
Brain Stem Respiratory Centers

• Rhythmicity center in medulla oblongata
  generates automatic
• Consists of inspiratory neurons that drive
  inspiration
• and expiratory neurons that inhibit inspiratory
  neurons
• Their activity varies in a reciprocal way and may
  be due to pacemaker neurons

22
Brain Stem Respiratory Centers

• Inspiratory neurons stimulate spinal motor
  neurons that innervate respiratory muscles
• Expiration is passive and occurs when inspiratory
  neurons are inhibited
• Activities of medullary rhythmicity center are
  influenced by centers in pons
• Apneustic center promotes inspiration by
  stimulating inspiratory neurons in medulla
• Pneumotaxic center antagonizes apneustic center,
  inhibiting inspiration

23
Chemoreceptors

• Automatic breathing influenced by activity of
  chemoreceptors
• monitor blood PCO2, PO2, and pH
• Central chemoreceptors are in medulla
• Peripheral chemoreceptors are in large arteries
  near heart (aortic bodies) and in carotids
  (carotid bodies)

24
CNS Controlof Breathing
25
Effects of Blood PCO2 and pH on Ventilation

• Chemoreceptors modify ventilation to maintain
  normal CO2, O2, and pH levels
• PCO2 is most crucial because of its effects on
  blood pH
• H2O CO2 ? H2CO3 ? H HCO3-
• H2O CO2 ? H2CO3
• H2CO3 ? H HCO3-
• Hyperventilation causes low CO2 (hypocapnia)
• Hypoventilation causes high CO2 (hypercapnia)

26
Effects of Blood PCO2 and pH on Ventilation
27
Effects of Blood PCO2 and pH on Ventilation

• Brain chemoreceptors are responsible for greatest
  effects on ventilation
• H can't cross BBB but CO2 can, which is why it
  is monitored and has greatest effects
• Rate and depth of ventilation adjusted to
  maintain arterial PCO2 of 40 mm Hg
• Peripheral chemoreceptors do not respond to PCO2,
  only to H levels

28
Effects of Blood PCO2 and pH on Ventilation

• Rise in blood CO2 increases H
• lowers pH of CSF
• thereby stimulates chemoreceptor neurons in the
  medulla oblongata

.
29
Effects of Blood PO2 on Ventilation

• Hypoxemia low blood PO2 () has little effect on
  ventilation
• Does influence chemoreceptor sensitivity to PCO2
• PO2 has to fall to about half normal before
  ventilation is significantly affected
• Emphysema blunts chemoreceptor response to PCO2
• Oftentimes ventilation is stimulated by hypoxic
  drive rather than PCO2

30
Comparison of PCO2 and PO2 Effects on Ventilation
31
Effects of Pulmonary Receptors on Ventilation

• Lungs have receptors that influence brain
  respiratory control centers via sensory fibers in
  vagus
• Unmyelinated C fibers are stimulated by noxious
  substances such as capsaicin
• Causes apnea followed by rapid, shallow breathing
• Irritant receptors are rapidly adapting respond
  to smoke, smog, and particulates, causes cough
• Hering-Breuer reflex mediated by stretch
  receptors activated during inspiration
• Inhibits respiratory centers to prevent
  overinflation of lungs

32
The Loading and Unloading Reactions

• Loading reaction deoxyhemoglobin (reduced
  hemoglobin) and oxygen combine to form
  oxyhemoglobin
• Occurs in the lungs
• Unloading reaction oxyhemoglobin dissociates to
  yield deoxyhemoglobin and free oxygen molecules
• Occurs in the systemic capillaries

33
Hemoglobin (Hb) and O2 Transport

• Hb has 4 globin polypeptide chains
• 4 heme groups that bind O2
• Each heme has a ferrous ion that can bind one
  molecule of oxygen
• each Hb can carry 4 O2
• 280 million hemoglobin molecules per RBC
• Each can carry over a billion oxygen molecules

34
Hemoglobin (Hb) and O2 Transport

• Normal heme contains Fe2 - can share electrons
  and bond with oxygen (oxyhemoglobin)
• loads with O2 to form oxyhemoglobin in pulmonary
  capillaries
• Deoxyhemoglobin (reduced hemoglobin)
  oxyhemoglobin dissociates to release oxygen
• Unloading in tissues
• Affinity of Hb for O2 changes with a number of
  physiological variables

35
Hemoglobin (Hb) and O2 Transport

• Most O2 in blood is bound to Hb inside RBCs as
  oxyhemoglobin
• Each RBC has about 280 million molecules of Hb
• Hb greatly increases O2 carrying capacity of blood

36
Hemoglobin (Hb) and O2 Transport

• Methemoglobin contains oxidized ferric iron
  (Fe3)
• Lacks electron to bind with O2
• Blood normally contains a small amount
• Carboxyhemoglobin heme combined with carbon
  monoxide
• Carbon monoxide (CO) bond 210 times stronger than
  oxygen bond
• CO poisoning heme cannot bind O2

37
Hemoglobin (Hb) and O2 Transport

• O2-carrying capacity of blood depends on its Hb
  levels
• Anemia, Hb levels are below normal
• Polycythemia, Hb levels are above normal
• Hb production controlled by erythropoietin (EPO)
• Production stimulated by low PO2 in kidneys
• Hb levels in men are higher because androgens
  promote RBC production

38
Hemoglobin (Hb) and O2 Transport

• High PO2 of lungs favors loading
• Low PO2 in tissues favors unloading
• Ideally, Hb-O2 affinity should allow maximum
  loading in lungs and unloading in tissues

39
Oxyhemoglobin Dissociation Curve

• Gives of Hb sites that have bound O2 at
  different PO2
• Reflects loading and unloading of O2
• Differences in saturation in lungs and tissues
• Steep part of curve, small changes in PO2 cause
  big changes in saturation

40
Oxyhemoglobin Dissociation Curve

• Affected by changes in Hb-O2 affinity due to pH
  and temperature
• Affinity decreases when pH decreases (Bohr
  Effect) or temp increases
• Occurs in tissues where temp, CO2 and acidity are
  high
• Causes Hb-O2 curve to shift right and more
  unloading of O2

41
(No Transcript)
42
Effect of 2,3 DPG on O2 Transport

• RBCs have no mitochondria so no aerobic
  respiration
• 2,3-DPG a byproduct of glycolysis in RBCs
• Production is increased by low O2 levels
• Causes Hb to have lower O2 affinity, shifting
  curve to right

43
Effect of 2,3 DPG on O2 Transport

• Anemia total blood Hb levels fall, causing each
  RBC to produce more DPG
• Fetal hemoglobin (HbF) has 2 gamma-chains in
  place of beta-chains of HbA
• HbF cant bind DPG, causing it to have higher O2
  affinity
• Facilitates O2 transfer from mom to baby

44
Anemia

• Production of 2,3-DPG inhibited by oxyhemoglobin
  so a reduction in RBC content of oxyhemoglobin
  increases DPG production
• Lowers affinity of Hb for O2 higher proportion
  converted to deoxyhemoglobin by unloading of its
  O2

45
Sickle-cell Anemia

• Affects 8-11 of African Americans
• HbS has valine substituted for glutamic acid at 1
  site on b chains
• At low PO2, HbS crosslinks to form a
  paracrystalline gel inside RBCs
• Makes RBCs less flexible and more fragile

46
Thalassemia

• Affects primarily people of Mediterranean descent
• Has decreased synthesis of alpha or beta chains
• Increased synthesis of gamma chains

47
Muscle Myoglobin

• Red pigment found exclusively in striated muscle
• Slow-twitch skeletal and cardiac muscle fibers
  are rich in myoglobin
• Has only one globin binds only one O2
• Has higher affinity for O2 than Hb is shifted to
  extreme left
• Releases O2 only at low PO2
• Serves in O2 storage, particularly in heart
  during systole

48
CO2 Transport

• CO2 transported in blood in three forms
• as dissolved CO2 (10) in the plasma (CO2 21
  times more soluble than O2 in water)
• as carbaminohemoglobin (20) attached to an amino
  acid in hemoglobin
• as bicarbonate ion, HCO3-(70) that accounts for
  most of the CO2 carried by blood
• In RBCs carbonic anhydrase catalyzes formation of
  H2CO3 from CO2 H2O
• Favored by the high PCO2 found in capillaries of
  systemic circulation

49
Chloride Shift

• High CO2 levels in tissues causes the reaction
  CO2 H2O ? H2CO3 ?
  H HCO3- to shift right in RBCs
• Results in high H and HCO3- levels in RBCs
• H is buffered by proteins
• HCO3- diffuses down concentration and charge
  gradient into blood causing RBC to become more
  positive
• So Cl- moves into RBC (chloride shift)

50
Carbon Dioxide Transport and the Chloride Shift

• CO2 transported as
• Dissolved CO2 gas
• Carbaminohemoglobin
• H2CO3 and HCO3-
• When bicarbonate diffuses out of the RBCs
• Cl- diffuses in to retain electrical neutrality
• This exchange is the chloride shift

51
Reverse Chloride Shift

• Blood reaches pulmonary capillaries
  deoxyhemoglobin converted to oxyhemoglobin
• Oxyhemoglobin has weaker affinity for H than
  deoxyhemoglobin so H released within RBCs
• Attracts bicarbonate (HCO3-) from plasma combines
  with H to form carbonic acid (H2CO3)
• H HCO3- ? H2CO3
• Lower PCO2 as in pulmonary capillaries carbonic
  anhydrase catalyzes conversion of H2CO3 to CO2
  H2O

52
Reverse Chloride Shift

• In lungs
• CO2 H2O ? H2CO3 ? H HCO3-, moves to left as
  CO2 is breathed out
• Binding of O2 to Hb decreases its affinity for H
• H combines with HCO3- and more CO2 is formed
• Cl- diffuses down concentration and charge
  gradient out of RBC (reverse chloride shift)

53
Acid-Base Balance of the Blood

• Blood pH is maintained within narrow pH range by
  lungs and kidneys (normal 7.4)
• Bicarbonate most important buffer in blood
• H2O CO2 ? H2CO3 ? H HCO3-
• Excess H is buffered by HCO3-
• Kidney role to excrete H into urine

54
Effect of Bicarbonate on Blood pH

• HCO3- released into plasma from RBCs buffers H
  produced by ionization of metabolic acids (lactic
  acid, fatty acids, ketone bodies)
• Binding of H to hemoglobin also promotes
  unloading of O2

55
Acid-Base Balance of the Blood

• CO2 produced by tissue cells through aerobic cell
  respiration
• Transported by blood to the lungs where it can be
  exhaled
• 2 major classes of acids in the body
• Volatile acid carbonic acid can be converted to
  a gas
• e.g. CO2 in bicarbonate buffer system can be
  breathed out
• H2O CO2 ? H2CO3 ? H HCO3-
• All other acids are nonvolatile and cannot leave
  the blood
• e.g. lactic acid, fatty acids, ketone bodies

56
Acid-Base Balance of the Blood

• Acidosis when pH lt 7.35 and Alkalosis when pH
  gt 7.45
• Respiratory acidosis caused by hypoventilation
• Causes rise in blood CO2 and thus carbonic acid
• Respiratory alkalosis caused by
  hyperventilation
• Results in too little CO2
• Metabolic acidosis results from excess of
  nonvolatile acids
• e.g. excess ketone bodies in diabetes or loss of
  HCO3- (for buffering) in diarrhea
• Metabolic alkalosis caused by too much HCO3- or
  too little nonvolatile acids
• e.g. from vomiting out stomach acid

57
Acid-Base Balance of the Blood

• Normal pH is obtained when ratio of HCO3- to CO2
  is 20 1
• Henderson-Hasselbalch equation uses CO2 and HCO3-
  levels to calculate pH
• pH 6.1 log HCO3-
  0.03PCO2

58
Ventilation and Acid-Base Balance

• Ventilation usually adjusted to metabolic rate to
  maintain normal CO2 levels
• With hypoventilation not enough CO2 is breathed
  out in lungs
• Acidity builds, causing respiratory acidosis
• With hyperventilation too much CO2 is breathed
  out in lungs
• Acidity drops, causing respiratory alkalosis

59
Effect of Exercise and High Altitude on
Respiratory Function

• Changes in ventilation and oxygen delivery occur
  during exercise and acclimatization to a high
  altitude
• These changes help compensate for
• The increased metabolic rate during exercise
• The decreased arterial PO2 at high altitudes

60
Ventilation During Exercise

• Arterial blood gases and pH do not significantly
  change during moderate exercise
• Because ventilation increases to keep pace with
  increased metabolism
• arterial PO2, PCO2, and pH remain fairly constant
  

61
Ventilation During Exercise

• During exercise, breathing becomes deeper and
  more rapid
• delivering much more air to lungs (hyperpnea)
• 2 mechanisms have been proposed to underlie this
  increase
• With neurogenic mechanism, sensory activity from
  exercising muscles stimulates ventilation and/or
  motor activity from cerebral cortex stimulates
  CNS respiratory centers
• With humoral mechanism, either PCO2 and pH may be
  different at chemoreceptors than in arteries
• Or there may be cyclic variations in their values
  that cannot be detected by blood samples

62
Lactate Threshold and Endurance Training

• The maximum rate of oxygen consumption before
  blood lactic acid levels rise as a result of
  anaerobic respiration
• Occurs when 50-70 maximum O2 uptake has been
  reached
• Endurance-trained athletes have higher lactate
  threshold, because of higher cardiac output
• Have higher rate of oxygen delivery to muscles
  and greater numbers of mitochondria and aerobic
  enzymes

63
Acclimatization to High Altitude

• Involves increased ventilation, increased DPG,
  and increased Hb levels
• Hypoxic ventilatory response initiates
  hyperventilation which decreases PCO2 which slows
  ventilation
• Chronic hypoxia increases NO production in lungs
  which dilates capillaries there
• NO binds to Hb and is unloaded in tissues where
  may also increase dilation and blood flow
• NO may also stimulate CNS respiratory centers
• Altitude increases DPG, causing Hb-O2 curve to
  shift to right
• Hypoxia causes kidneys to secrete EPO which
  increases RBCs

64
Acclimatization to High Altitude