Respiratory System

1
Respiratory System

• Lecture 2
• Gas Exchange Regulation

2
Gas Exchange

• occurs between blood alveolar air
• across respiratory membrane
• by diffusion due to concentration gradient
• differences between O2 CO2 concentrations
• measured by partial pressures
• greater difference in partial pressures?greater
  rate of diffusion
• need to understand partial pressures diffusion
  of gases into out of liquids to understand gas
  exchange

3
Daltons Law of Partial Pressure

• air-mixture of gases water vapor
• consists of N2-78-most abundant, O2-20.9water,
  CO2, Argon
• atmospheric pressure is result of collision of
  all gas molecules
• at any time 78.6 of collisions involve N2
  20.9 involve O2
• each gas contributes to total pressure in
  proportion to its relative abundance-Daltons Law
• PressureTotal Pressure1 Pressure2 ...
  Pressuren
• pressure contributed by one gas is partial
  pressure
• directly proportional to of gas in mixture
• all partial pressures added total pressure
  exerted by gas mixture 760mm Hg
• PN2-parital pressure nitrogen 78.6 X 760 mm
  Hg-597 mm Hg
• PO2 20.9 X 760 159 mm Hg

4
Henrys Law

• at a given temperature, amount of gas in solution
  is directly proportional to partial pressure (pp)
  of gas
• when gas mixture is in contact with liquid, each
  gas dissolves in proportion to its partial
  pressure
• actual amount in solution at given pp depends on
  solubility of that gas in that liquid

5
Partial Pressures in Alveoli Alveolar
Capillaries

• oxygen diffuses from alveolar air (PP is 105mm
  Hg) into blood in pulmonary capillaries where PO2
  is 40 mm Hg
• when O2 is diffusing from alveolar air into
  deoxygenated blood CO2 is diffusing in opposite
  direction
• PCO2 of deoxygenated blood is 45 mm Hg
• PCO2 of alveolar air-40 mm Hg
• CO2 diffuses from deoxygenated blood into alveoli
• left ventricle pumps oxygenated blood into aorta
  through systemic arteries to systemic
  capillaries
• exchange of O2 CO2 between systemic
• capillaries tissues cells
• PO2 of blood in systemic capillaries is 100 mmHg
  
• in tissue cells it is 40mm Hg
• as oxygen diffuses out of capillaries into
  tissues carbon dioxide diffuses in opposite
  direction
• PCO2 of cells is 45 mm Hg
• it is 40mm Hg systemic capillary blood

6
Diffusion at Respiratory Membrane

• efficient
• large PP differences across membrane
• larger PP?faster diffusion
• capillary alveolar membranes are fused?
  distances for diffusion-small
• gases are soluble in lipid- pass through
  surfactant layer easily
• surface area is huge

7
Gas Transport

• Major function of blood
• O2
• Co2

8
Oxygen Transport

• dissolved in plasma
• normal PO2 of alveoli, 100ml of blood contains
  0.3ml of O2
• carried in RBC bound to hemoglobin

9
Hemoglobin

• 4 subunits
• 2? 2ß globular protein chains
• each has one heme group
• each heme has one iron
• each Fe can bind one O2
• every Hb can carry 4 O2s
• there are 280 X 106 Hb molecules/RBC
• each RBC could carry billion O2 molecules

10
Oxyhemoglobin

• Hb O2? HbO2-
• oxyhemoglobin
• reversible
• Fe-O2 bond-weak
• easily broken without altering either Hb or O2
• HbO2? O2 Hb
• deoxyhemoglobin

11
Amount of Oxygen Bound to HB

• PO2 of plasma
• most important factor determining how much O2
  binds to Hb
• actual amount bound/maximum that could bind
  saturation
• all binding sites occupied-100 saturation

12
Oxyhemoglobin Dissociation Curve

• plots saturation Hb (number of O2 bound)
  against PO2
• relates saturation of Hb to PP of O2

13
HbO2 Dissociation Curve

• not linear-S-shaped
• steep slope-flattens or plateaus
• shape due to subunits of Hb
• each time Hb binds one O2? shape changes
  slightly? increases ability of Hb to bind another
  O2
• when PO2 is between 60 -100mmHG, Hb is 90 or
  more saturated with oxygen
• blood picks up nearly full load of O2 from lungs
  even when PO2 alveolar air is as low as 60mmg
  Hg
• increasing PO2 above 80mm Hg adds little to O2
  content of blood
• PO2 lt 50 mm, small drops in PO2 cause large
  release of O2

14
Importance of Oxyhemoglobin Dissociation Curve

• shape of Hb saturation curve extremely important
• over steep initial slope?very small decreases in
  PO2? results in very large changes in amount of
  O2 bound or released from Hb
• ensures near normal O2 transport even when O2
  content of alveolar air decreases (important at
  high altitudes)
• slope of curve allows blood to have high O2
  content at fairly low PO2s
• PO2 can fall considerably-without greatly
  reducing oxygen supply

15
Factors Affecting Affinity of O2 Hb

• various factors increase or decrease affinity
  (tightness of bond) of Hb to O2
• factors will shift curve to left (higher
  affinity) or to right (lower affinity)
• left-more O2 is bound than released
• right-more O2 is released than bound
• pH
• pCO2
• temperature
• BPG

16
Hb pH

• as pH decreases ?shape of Hb changes?releases O2
  more readily?slope of curve changes? saturation
  decreases
• more O2 released
• curve shifts to right
• effect of pH on Hb saturation is Bohr Effect

17
Bohr Effect

• Hb acts as buffer for H
• when H bind to amino acids in Hb
• they alter its structure slightly decreasing its
  oxygen carrying capacity
• increased H ion concentration causes O2 to
  unload from Hb
• binding of O2 to Hb causes unloading of H from
  Hb
• elevated pH (lowered H) increases affinity of
  Hb for O2
• shifts O2-Hb dissociation curve to left

18
Hb Temperature

• higher temperature
• curve shifts to right
• unloading of O2 from Hb is increased
• lower temperatures
• curve shifts to left
• O2 binds more to Hb

19
Hb Carbon Dioxide

• increase in CO2
• shifts curve to right
• more O2 released
• decrease in CO2
• shifts curve to left
• more O2 bound

20
Hb BPG

• BPG-2,3 biphosphoglycerate
• produced by RBC during glycolysis
• higher levels
• unloading of oxygen increased
• shifts to right
• BPG decreases
• curve shifts to left
• more oxygen is bound
• amount of BPG generated drops as RBCs age
• BPG drops too low?O2 irreversibly bound to Hb

21
CO2 Transport

• dissolved in plasma
• 7
• transported as HCO3 (bicarbonate ion)
• 70
• bound to HB
• 23
• attaches to NH2 groups (amino) of histidine
• Carbaminohemoglobin HB-CO2

22
Transport as HCO3

• converted to carbonic acid
• unstable
• dissociates to hydrogen bicarbonate ions
• HCO3- diffuses from RBCs into plasma
• exchanges one HCO3- for one Cl-
• chloride shift
• maintains electrical neutrality

23
AT LUNG
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AT TISSUES
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Control of Respiration

• normally cellular rates of absorption
  generation of gases are matched by capillary
  rates of delivery removal
• rates are identical to rates of O2 absorption
  CO2 excretion at lungs
• if absorption excretion become unbalanced
• homeostatic mechanisms restore equilibrium
• changing blood flow O2 delivery
• locally regulated
• changing depth rate of respiration
• respiratory centers in brain

26
Respiratory Centers in Brain

• usually breath without conscious
  thought-involuntary
• depends on repetitive stimuli from brain
• automatic, unconscious cycle of breathing
  controlled by respiratory centers in medulla
  pons
• medullary rhymicity area
• pneumotaxic center
• apneustic center

27
Medullary Rhymicity Center

• controls basic rhythm of respiration
• has an inspiratory expiratory area
• nerves project to diaphragm by phrenic nerve to
  intercostals by intercostal nerves
• quiet breathing
• neuron activity increases for 2 sec. ?stimulates
  inspiratory muscles
• rib cage expands as diaphragm contracts
• inhalation occurs
• output ceases abruptly? muscles relax?elastic
  parts recoil? exhalation (lasts 3 seconds)
• neurons begins to fire again
• cycle repeats

28
Pneumotaxic Apneustic Centers

• located in pons
• regulates shift from inspiration to expiration
• regulate respiratory rate depth of respiration
  in response to sensory stimuli or input from
  other brain centers
• pneumotaxic center-upper pons
• transmits inhibitory impulses to inspiratory
  area
• helps turn off inspiratory area before lungs
  become too full of air
• increased pneumotaxic output? quickens
  respiration by shortening duration of each
  inhalation?breathing rate increases
• decreased output?slows respiratory pace
• depth of respiration increases
• apneustic center sends stimulating impulses to
  inspiratory area
• activates it producing prolonged inhalation.
• result is long, deep inhalations

29
Regulation of Respiratory Centers

• conscious or voluntary control
• inhale or exhale at will
• input form cerebral motor cortex stimulates motor
  neurons to stimulate respiratory muscles
  bypassing medulla centers
• limited-impossible to override chemoreceptor
  reflexes
• nerve impulses from hypothalamus limbic system
  also stimulate respiratory center
• allows emotional stimuli to alter respiration

30
Respiratory Reflexes

• brain centers regulate respiratory rate depth
  of respiration
• in response to sensory stimuli or input from
  other brain centers
• sensory information comes from
• central chemoreceptors
• peripheral chemoreceptors
• proprioceptors
• stretch receptors
• information from these alters patterns of
  respiration
• changes are respiratory reflexes

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Chemoreceptors

• central chemoreceptors
• neurons in brainstem that respond to changes in
  pH of cerebrospinal fluid
• stimulation increases depth rate of respiration
• peripheral chemoreceptors
• carotid aortic bodies of large arteries
• respond to PCO2, pH PO2 of blood

33
Respiratory Reflex-CO2

• Hypercapnia
• increase in PCO2
• CO2 crosses blood brain barrier rapidly
• rise in arterial PCO2 almost immediately
  elevates CO2 levels in CSF?pH decreases? excites
  central chemoreceptors? stimulates respiratory
  centers ?increases depth rate of breathing
• rapid breathing moves more air in out of
  lungs?alveolar CO2 decreases? accelerates
  diffusion of CO2 out of alveolar capillaries?
  homeostasis restored
• results in hyperventilation

34
Chemoreceptor Reflexes-CO2

• hyperventilation? hypocapnia
• low PCO2
• central peripheral chemoreceptors are not
  stimulated
• Inspiratory center sets its own pace
• CO2 accumulates
• homeostasis restored

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Stretch Receptors

• found in smooth muscles of bronchi bronchioles
  in visceral pleura
• lung inflation
• signal inspiratory apneustic areas via vagus
  nerve
• Inhibits both
• Hering-Breuer Reflex

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