Respiratory Physiology Part Two

1
Respiratory Physiology Part Two

• Acid-Base Balance
• Gas Transfer in Air
• Lung Ventilation
• Pulmonary Circulation
• Heat Water Loss

2
Regulation of Body pH

• Body pH in animals is normally slightly alkaline
  i.e. fewer H than OH- ions in body e.g. human
  blood plasma at 370C pH 7.4
• Changes in cellular pH arise as a result of
  cellular functions as a means of regulatory
  control e.g. stimulation of glycolysis in frog
  muscle by insulin
• Cells also undergo changes in pH as a result of
  external influences e.g. cells become acidotic
  during hypoxia because of an imbalance between
  proton production resulting form hydrolysis of
  ATP to ADP proton consumption by NAD in those
  tissues subjected to anaerobic metabolism

3
Regulation of Body pH

• 1. H Production Excretion H Distribution
• H produced through metabolism of ingested foods
  excreted on continuous basis - the largest pool
  of H greatest flux in H traffic is associated
  with metabolic production of CO2 (which at the pH
  of the body reacts with H2O to form H HCO3-)
  fig 13-10a - at respiratory surface, HCO3- is
  converted to CO2 which is then excreted fig
  13-10b
• If CO2 production excretion are balanced, the
  overall effect of CO2 flux on body pH will be zero

4
Regulation of Body pH

• 1. H Production Excretion H Distribution
  cont
• if CO2 excretion lt production CO2 accumulates
  body will be acidified if the reverse, body pH
  will rise terrestrial vertebrates can vary the
  rate of CO2 excretion to maintain body pH
•  ingestion of meat usually results in net intake
  of acid, whereas ingestion of plant food often
  results in net intake of base overall effect of
  food ingestion metabolism is a small continual
  production of acid body pH is maintained by
  excreting this acid via the kidney in terrestrial
  vertebrates or across regions of body surface
  such as gills of fishes or skin of frogs

5
Regulation of Body pH cont

• 1. H Production Excretion H Distribution
  cont
• if lung ventilation is reduced so CO2 excretion
  drops below CO2 production, body CO2 levels rise
  and pH will fall decrease in body pH
  respiratory acidosis reverse effect rise in pH
  due to increased lung ventilation respiratory
  alkalosis (using respiratory to differentiate
  changes otherwise related to metabolism of kidney
  function e.g. anaerobic metabolism results in
  net acid production which reduces body pH these
  changes metabolic acidosis vs. vomiting
  chloride loss bicarbonate increase with
  increase in pH metabolic alkalosis)

6
Regulation of Body pH cont

• 1. H Production Excretion H Distribution
  cont
• body fluids are electroneutral I.e. sum of anions
  sum of cations normal electrolyte status of
  human plasma is depicted in fig. 13-15 p. 541
  (sum of bicarbarbonate, phosphates protein
  anions buffer base
• most cell membranes are much more permeable to
  CO2 than H or bicarbonate cell membrane
  permeability to H (while usually low) often is gt
  permeable to K, Cl- HCO3- (notable exception
  is RBC membrane which is very permeable to HCO3-
  and Cl- but not very perm to H)

7
Regulation of Body pH cont

• An increase in extracellular PCO2 causes an
  increase in both bicarbonate H concentration
  thus creating gradients for CO2, HCO3- H
  across the cell membrane
• In cells that are very permeable to CO2 but not
  very permeable to H or bicarbonate, such a
  situation leads to rapid movement of CO2 into the
  cell as CO2 is converted to HCO3-, the
  intracellular pH falls sharply
• Acidification associated with increased PCO2
  often occurs much more rapidly in intracelluar
  compartment than in the extracelluar compartment
  because carbonic anhydrase (which catalyzes the
  conversion of CO2 to HCO3-,) is present inside
  cells but not always in extracellular fluid

8
Regulation of Body pH cont

• proton-exchange anion exchange mechanisms in
  plasma membrane play NB role in adjusting
  intracellular pH
• An acid load in the cell is accompanied by H
  efflux coupled to Na influx by HCO3- influx
  coupled to Cl- efflux the movement of HCO3-
  into the cell is equivalent to movement of H out
  of the cell because HCO3- ions that enter the
  cell are converted to CO2, releasing OH- ions
  increasing pH the CO2 so formed leaves the cell
  is converted to HCO3-, releasing protons
• This cycling of CO2 HCO3- (Jacobs-Stewart
  Cycle) functions to remove H ions form cell
  interior in the face of an intracellular acid
  load such as that generated by anaerobic
  metabolism

9
Regulation of Body pH

• Factors influencing intracellular pH cont -
  Intracellular pH remains stable if rate of acid
  loading (from metabolism or from influx into the
  cell) is equal to rate of acid removal any
  sudden increase in cell acidity will be countered
  by factors influencing intracellular pH
• a. buffering by physical buffers (e.g proteins
  phosphates) located within the cell
• b. reaction of HCO3 with H ions, forming CO2,
  which then diffuses out of cell
• c. passive diffusion or active transport of H
  ions from the cell
• d. cation-exchange mechanisms (Na/H
  Na/NH4), anion-exchange mechanisms (HCO3-/Cl-)
  or both in plasma membrane

10
Regulation of Body pH cont

•  2. Factors influencing intracellular pH cont
• pH influences many cellular activities some
  positively, some negatively e.g. many enzymes are
  inhibited by low pH such as those involved with
  glycolysis
• 3. Factors influencing body pH stable body pH
  requires that acid production be matched to acid
  excretion in mammals, this is achieved b
  adjusting the excretion of CO2 via the lungs
  excretion of acid or bicarbonate via the kidneys
  (remember the A-type acid-excreting B-type
  cells base-excreting in aquatic animals,
  external body surfaces have the capacity to
  extrude acid in ways similar to that of
  collecting duct of mammalian kidney (e.g. skin of
  frogs gills of freshwater fishes have an ATPase
  on apical surface of epithelium that excretes
  protons fish gills also have apical HCO3-/Cl-
  exchanger)

11
Regulation of Body pH cont

• Factors influencing body pH cont - Temperature
  can have a marked effect on body pH because the
  dissociation of water varies with temperature
  the pH of neutrality is 7.00 only at 250C
• ability of body to redistribute acid between body
  compartments has functional significance because
  some tissues are more adversely affected by
  changes in pH than others e.g. brain is
  particularly sensitive whereas muscles tolerate
  much larger oscillations in pH

12
Gas Transfer in Air Lungs

• Remember lungs gills are quite different are
  ventilated indifferent ways (the dissimilarities
  exist because the density viscosity of H2O are
  both approximately 1000 times greater than those
  of air and water contains only 1/30 as much
  molecular O2 PLUS gas molecules diffuse 10,000
  times more rapidly in air than in H2O PLUS air
  breathing consists of the reciprocal movement of
  air into out of lungs whereas water breathing
  consists of a unidirectional flow of H20 over
  gills

13
Functional Anatomy of the Lung

• complex network of tubes sacs with the actual
  structure varying among species fig. 13-21 p. 546
• sizes of terminal air spaces in lungs becomes
  progressively smaller from amphibians to reptiles
  to mammals while total number of air spaces per
  unit volume become greater
• focus on mammalian lung consists of millions of
  blind-ended interconnected spaces (alveoli)
  main airway (trachea) subdivides to form bronchi
  bronchioles which branch repeatedly leading to
  terminal bronchioles respiratory bronchioles
  each of which is connected to terminal alveolar
  ducts alveoli
• Total cross-sectional area of airway increases
  rapidly as a result of extensive branching
  (although the diameter of individual air ducts
  decreases from trachea to terminal bronchioles)

14
Gas Transfer in Air Lungs cont

• gases are transferred across thin-walled alveoli
  airways leading to terminal bronchioles
  constitute nonrespiratory portion (i.e. no gas
  transfer) of lung alveoli are interconnected by
  series of holes (pores of Kohn) which allow
  collateral movement of air significant factor
  in gas distribution during lung ventilation
• air ducts leading to respiratory portion of lung
  contain cartilage a little smooth muscle
  lined with cilia epithelium of ducts secretes
  mucus, which is moved toward the mouth by cilia
  (mucus escalator) keeps lungs clean in
  respiratory portions of lung, smooth muscle
  replaces cartilage contraction of this smooth
  muscle can have a marked effect on the dimensions
  of the airways in the lungs

15
Gas Transfer in Air Lungs cont

• Diffusion Barrier crossed by O2 moving from air
  to blood is made up of
• 1. an aqueous surface film
• 2. epithelial cells of alveolus
• 3. interstitial layer
• 4. endothelial cells of capillaries
• 5. blood plasma
• 6. membrane of RBCs Fig. 13-22b p. 547

16
Gas Transfer in Air Lungs cont

• 3 types of lung epithelial cells
• 1. Type I (most abundant) squamous cells with
  thin plate-like structure extends between 2
  adjacent alveoli
• 2. Type II laminated body within cells with
  surface villi they produce surfactant (more
  later)
• 3. Type III rich in mitochondria numerous
  microvilli (NaCl uptake from lung fluid?)
  number of alveolar macrophages wander over
  surface of respiratory epithelium

17
Lung Ventilation - Terminology

• 1. Eupnea normal, quite breathing at rest
• 2. Hyperventilation/Hypoventilation increase
  (or decrease) in amount of air moved into or out
  of lungs by changes in rate/depth of breathing
  such that ventilation no longer matches CO2
  production blood CO2 levels changes
• 3. Hyperpnea increase lung ventilation due to
  increased breathing in response to elevated CO2
  production (e.g. during exercise)
• 4. Apnea absence of breathing
• 5. Dyspnea laboured breathing
• 6. Polypnea increased in breathing rate
  without increase in depth of breathing

18
Lung Ventilation cont

• amount of air moved into or out of lungs with
  each breath tidal volume
• air exchanged between alveoli environment
  passes through nonrespiratory sections i.e. at
  end of exhalation (expiration) air in
  nonrespriatory sections is high in CO2/low in O2
  is first to be inhaled with next breath at
  end of inhalation (inspiration) air in
  nonrespiratory sections is high in O2 low in
  CO2 is first exhaled volume of air not
  involved in gas transfer anatomic dead-space
  volume (some air may be supplied to nonfunctional
  alveoli or some alveoli may be ventilated at too
  high a rate, increasing volume of air not
  direclty involved in gas exchange physiological
  dead-space volume which includes the anatomic
  dead-space)

19
Lung Ventilation cont

• amount of fresh air moving into/out of alveolar
  air sacs TV minus anatomic dead-space volume
  referred to as alveolar ventilation volume only
  this air is involved in gas exchange
• maximum amount of air moved into or out of lungs
  vital capacity of lungs
• O2 content is lower CO2 content is higher in
  alveolar gas than in ambient air because only a
  portion of the lungs gas volume is changed with
  each breath
• O2 CO2 levels in alveolar gas are determined by
  both rate of gas transfer across respiratory
  epithelium rate of alveolar ventilation
  (alveolar ventilation depends on breathing rate,
  tidal volume anatomic dead-space volume)

20
Lung Ventilation cont

• Artificial increases in anatomic dead space (such
  as those produced in humans breathing through a
  length of hose) result in a rise in CO2 a fall
  in O2 in the lungs these activates
  chemoreceptors, leading to an increase in TV
• Animals with long necks (giraffe trumpeter
  swan) tracheal length therefore anatomic
  dead-space volume, is greater than those with
  short necks in order to maintain adequate gas
  partial pressures in lungs, long-necked animals
  have high tidal volumes
• RR TV vary considerably among animals e.g.
  humans 12/min TV at rest 10 of total lung
  volume

21
Lung Ventilation cont

• In summary, O2 CO2 levels in alveolar gas are
  determined by ventilation rate of gas transfer
• Ventilation of respiratory epithelium is
  determined by RR, TV anatomic dead-space volume

22
Pulmonary Circulation

• 1. pulmonary circulation deoxygenated blood
  from pulmonary artery from heart (taking up O2
  giving up CO2)
• 2. bronchial circulation smaller supply
  comes from systemic (body) circulation supplies
  lung tissues themselves with O2 other
  substrates fro growth maintenance

23
Pulmonary Circulation cont

• birds mammals BPs in pulmonary circulation lt
  those in systemic circulation this lower BP
  reduces filtration of fluid into lung extensive
  lymph drainage of lung tissues also helps ensure
  that no fluid collects in lung NB features
  because any fluid collecting in lung increases
  diffusion distance between blood air reduces
  gas transfer
• Pulmonary vessels are very distensible subject
  to distortion by breathing movements
• Arterial BP (also therefore blood flow) increases
  with distance form the apex of the lung in
  bottom half of vertical lung, where venous
  pressure exceeds alveolar pressure, blood flow is
  determined by the difference between arterial
  venous BPs

24
Pulmonary Circulation cont

• mammalian pulmonary circulation lacks
  well-defined arterioles, both sympathetic
  adrenergic parasympathetic cholinergic fibers
  innervate smooth muscle around pulmonary blood
  vessels bronchioles
• reduction in either O2 levels or pH cause local
  vasoconstriction of pulmonary blood vessels
• CO in pulmonary circuit is equal to CO to
  systemic circuit in mammals birds (vs.
  amphibians reptiles which have a single or
  partially divided ventricle that ejects blood
  into both the pulmonary systemic circulation,
  the ratio of pulmonary to systemic blood flow can
  be altered

25
Mechanisms for Ventilation of Lung

• these vary by species reflecting functional
  anatomy of lungs associated structures
  primarily consider mammals
• lungs elastic, multi-chambered bags suspected
  within the pleural cavity (aka thoracic cavity)
  open to exterior via single tube (trachea) fig.
  13-28 p. 552 walls formed by ribs diaphragm
  lungs fill most of thoracic cage, leaving a
  low-volume pleural space between lungs thoracic
  wall this space is sealed filled with fluid
  fig 13-28 p. 552

26
Mechanisms for Ventilation of Lung cont

• lungs elasticity creates pressure below
  atmospheric pressure in fluid-filled pleural
  space (fluid provides flexible, lubricated
  connection between outer lung surface thoracic
  wall (thus, when thoracic cavity changes volume,
  gas-filled lungs do too)
• pneumothorax when thoracic cage is punctured
  air is drawn into pleural cavity lungs collapse
  
• during normal breathing thoracic cage is
  expanded contracted by series of skeletal
  muscles, diaphragm external internal
  intercostals muscles these muscle contractions
  are determined by activity of motor neurons
  controlled by the respiratory center within the
  medulla oblongata

27
Mechanisms for Ventilation of Lung cont

• volume of thorax increases as ribs are raised
  moved outward by contraction of external
  intercostals by contraction (lowering) of
  diaphragm fig. 13-30 p. 552 (contraction of
  diaphragm accounts for 2/3 of increase in
  pulmonary volume increase in thoracic volume
  reduces alveolar pressure air is drawn into
  lungs relaxation of diaphragm external
  intercostals muscles reduces thoracic volume
  raises alveolar pressure forcing air out of
  lungs (generally, inhalation is controlled and
  exhalation is passive)

28
Pulmonary surfactants

• Lung wall tension depends on properties of wall
  surface tension at the liquid-air interface
  surface tension is a force that tends to minimize
  the area of a liquid surface causing liquid
  droplets to form a sphere (makes surface film
  resistant to stretch)
• Fluid lining is not simply water but surfactant
  lipoprotein complexes that bestow very low
  surface tension on liquid-air interface

29
Roles of Surfactants

• 1. low surface tension of fluid lining alveoli
  allows alveoli to expand easily during breathing
  reduces effort of inflating lung (as noted
  above)
• 2. alveoli fold as their volume decreases
  would stick/become glued together by surface
  tension if not for surfactant (reducing surface
  tension to allow easy inflation of collapsed
  alveoli) when lung volume is reduced extremely,
  the lung will collapse atelectasis however, due
  to presence of surfactant, even a collapsed lung
  can be re-inflated easily

30
Roles of Surfactants cont

• 3. allow newborn babies to inflate their lungs
  (in mammals, surfactant appears in fetal lung
  prior to birth without surfactant babies
  cannot inflate lungs called neonatal
  respiratory distress syndrome)
• 4.  reduce resistance to blood flow by increasing
  compliance of capillary-alveolar sheet
• 5. increase osmotic pressure of lung fluid
  reducing water flux across lung epithelium

31
Heat Water Loss

• increases in lung ventilation not only increase
  gas transfer but also result increased losses of
  heat water
• cool, dry air entering lungs of mammals is
  humidified (by H2O evaporation from surface of
  respiratory epithelium) heated as air in
  contact with respiratory surface becomes
  saturated with H2O vapor comes into thermal
  equilibrium with blood exhalation of this hot,
  humid air results in considerable loss of heat
  H2O because evaporation of H2O cools nasal
  mucosa, temperature gradient exists along nasal
  passages (cool at tip of nose, warm towards
  glottis) (cooling of exhalant air in nasal
  passages results in conservation of both heat
  water) structural variety in nasal passages
  among vertebrates

32
Regulation of Gas Transfer

• energy is expended in ventilating respiratory
  surface with air(or water) in perfusing
  respiratory epithelium with blood significant
  selective pressure in favour of evolution of
  mechanisms for close regulation of ventilation
  perfusion in order to conserve energy

33
Neuronal Regulation of Breathing

• Medullary respiratory center respiratory
  muscles activated by spinal motor neurons which
  receive inputs from neurons that constitute
  medullary respiratory center (such control can be
  very precise allowing extremely fine control of
  air flow e.g. whistling, singing, talking)

34
Neuronal Regulation of Breathing cont

• Inhalation of lungs stimulates pulmonary stretch
  receptors in bronchi bronchioles which have a
  reflex inhibitory effect via vagus nerve on
  medullary inspiratory center thus on
  inspiration medulla contains a central rhythm
  generator that drives pattern generator within
  medullary respiratory center to cause breathing
  movements (remember mechanorecptors
  chemoreceptors provide info to medullary
  respiratory center too fig. 13-46 p. 566)