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Lecture

Respiration system.pdf

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Department
Physiology
Course Code
PSL301H1
Professor
Gordon Richardson

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Lecture  1   Respiratory  system:  overview  of  function  and  structure     Case  study   -­‐ John  20  year  old  university  student  has  asthma   -­‐ Condition  usually  controlled  with  medication,  he  occasionally  has  asthma  attacks   -­‐ What  lung  structures  are  affected  during  asthma  attach?   -­‐ If  john  were  to  undergo  lung  function  test  during  asthma  attack,  what  would  you  expect  to   observe?     What  are  the  functions  of  respiratory  system?   -­‐ Exchange  of  gases  between  air  and  blood   -­‐ Regulation  of  body  pH   -­‐ Defense  from  inhaled  pathogens/foreign  particles   -­‐ Vocalization     What  structures  make  up  respiratory  system?   -­‐ Upper  respiratory  tract   o Pharynx   o Vocal  Cords   o Esophagus   o Nasal  Cavity   o Tongue   o Larynx   -­‐ Lower  respiratory  tract   o Right  lung   o Right  bronchus   o Left  lung   o Left  bronchus   o Diaphragm     Respiratory  muscles   -­‐ Muscles  of  inspiration   o Sternocleidomastoids   o Scalenes   o External  intercostal   o Diaphragm   -­‐ Muscles  of  expiration   o Internal  intercostal   o Abdominal  muscle     Pleural  sacs  enclose  lungs     Pleural  activity     Airways   -­‐ Larynx  >  trachea  >  left  primary  bronchus  >  secondary  bronchus  >  bronchiole  >  alveoli   -­‐ Trachea  branches  into  two  primary  bronchi   -­‐ Primary  bronchus  divides  22  more  times  terminating  in  a  cluster  of  alveoli   -­‐ Warm  air  to  37°C   -­‐ Humidify  to  100%   -­‐ Filter  (nose  and  respiratory  cilia)     Filtering  action  of  cilia  that  line  airways   -­‐ Cilia  move  mucus  to  pharynx   -­‐ Dust  particle   -­‐ Mucus  layer  traps  inhaled  particles   -­‐ Watery  saline  layer  allows  cilia  to  push  mucus  toward  pharynx   -­‐ Goblet  cells  secretes  mucus   -­‐ Immune  cells  secrete  antibodies  disable  pathogens     Airways   -­‐ 1  bifurcation  à  R  and  L  main  bronchi  2  –  4  bifurcation  à  lobar  bronchi   o Have  cartilage  to  maintain  their  shape   -­‐ 5  –  11  bifurcation  à  segmental  bronchi  12  –  16  bifurcation  à  terminal  bronchioles   o Stabilized  by  bronchiolar  muscles   -­‐ All  above  =  conducting  airways  (no  gas  exchange)   -­‐ Constitute  an  anatomical  dead  space     Primary  lobule   -­‐ Region  of  gas  exchange   -­‐ Approximately  300  million  alveoli  each  ~  300µm  in  diameter   2 -­‐ Total  xs  area  is  very  large,  ~180cm ,  and  air  velocity  virtually  zero     Alveoli   -­‐ Type  I  alveolar  cell   -­‐ Capillary   -­‐ Type  II  alveolar  cell  (surfactant  cell)   -­‐ Alveolar  macrophage  (engulfs  foreign  particles)   -­‐ Alveolar  gas  exchange  occurs  via  passive  diffusion     How  is  blood  transported  to  and  from  lungs?   -­‐ High  flow  10%  blood  volume   -­‐ Low  pressure  25/8mmHg   -­‐ Heart  (R  ventricle)  à  pulmonary  trunk  à  pulmonary  arteries  à  pulmonary  arterioles  à   capillaries  à  pulmonary  venules  à  pulmonary  veins  à  heart  (atrium)     Pulmonary  vs  systemic  capillaries   -­‐ Pulmonary  capillaries   o Others  cover  for  blocked  capillaries   o A  lot  of  over  lap   o One  emboli  filtered  safely   -­‐ Systemic  capillaries   o Serves  particular  area   o If  blocked,  area  killed     What  defends  respiratory  system  from  pathogens/foreign  particles?   -­‐ Filtering  action  of  nose   -­‐ Mucous  and  action  of  cilia  lining  airways   -­‐ Antibodies  secreted  onto  respiratory  surfaces   -­‐ Macrophages  in  respiratory  tract  including  alveoli     L How  is  lugg  function  measured?   o 0 m a r d V s R p C V i C s 5 V T T . C 0 E V F 1 R 5 C 0 V     Lung  volumes  and  capacities   -­‐VT  =  tidal  volume   -­‐IRV  =  inspiratory  reserve  volume   -­‐RV  =  residual  volume    volume   -­‐VC  =  vital  capacity  =  inspiratory  reserve  volume  +  expiratory  reserve  volume  +  tidal  volume   -­‐IC  =  inspiratory  capacity  =  inspiratory  reserve  volume  +  tidal  volume   -­‐FRC  =  functional  residual  capacity  =  expiratory  reserve  volume  +  residual  volume   -­‐TLC  =  total  lung  capacity  =  inspiratory  reserve  volume  +  expiratory  reserve  volume  +  residual   volume  +  tidal  volume   -­‐Note:  capacities  are  combinations  of  volumes,  volumes  are  unique     Forced  expiratory  volume  and  vital  capacity   6 e 0 x F t r E V s o V V 3 v C L 3 u F 5 e V C . n T = 0 v % l s 0 a c 1 c 5 y 0 -­‐Following  maximal  inhalation:     l o Forced  expiratory  volume  (FEV)  =  volume  of  air  forcefully  exhaled  in  1  second   i t e o c p C h a o  Force  vital  capacity  (FVC)  =  volume  of  air  forcefully  exhaled     g Changes  in  FEV  and  FVC  in  disease   s o n e m F t a V c l a v n e d n V g C s i a n e i     e Lecture  2   p Respiratory  system  –  pulmonary  ventilation   o   c Case  study   e -­‐Shorty  after  birth,  premature  baby  begins  to  breathe  rapidly  (tachypnea)  has  rapid  HR   h (tachycardia)  grunts  when  she  expires  and  has  cyanosis   m -­‐What  is  the  cause  of  these  symptoms?   d -­‐How  would  you  treat  her?   r   _ How  does  air  get  into  lungs?   h -­‐Plung  atm  =  no  breathing   E -­‐Pressure  gradientatm lung  ∴  breath  due  to  Boyle’s  law   c   l Boyle’s  l11: 2 2P V =P V   e -­‐↑  Volume  ↓  Pressure   a -­‐↓  Volume  ↑  Pressure   R   r By  changing  lung  volume  pressure  gradients  develop   V -­‐At  rest,  diaphragm  is  relaxed   n -­‐Diaphragm  contracts,  thoracic  volume  increases   e -­‐Diaphragm  relaxes,  thoracic  volume  decreases   c   R Muscles  of  inspiration   s -­‐Diaphragm   c o Main  muscle  of  breathing   e o Controlled  by  phrenic  nerve  from  spinal  segments  C3-­‐C5   D o Inserted  into  lower  ribs  and  moves  downwards  as  it  contracts  forcing  abdominal  contents   e down  and  forward  thereby  increase  thoracic  volume   H   M External  intercostals,  sternocleidomastoids  and  scalenes  are  inspiratory  muscles   L -­‐Pump  handle  motion  increases  anterior-­‐posterior  dimension  of  rib  cage   -­‐Bucket  handle  motion  increases  lateral  dimension  of  rib  cage     Expiration   -­‐ At  rest,  expiration  is  passive  but  expiratory  muscles  are  used  during  voluntary  expiration  or  when   breathing  frequency  is  high   -­‐ Contract  and  force  rib  cage  inward   -­‐ Decrease  abdominal  volume     Lungs  are  not  fastened  to  thoracic  wall   -­‐ How  does  mvt  of  diaphragm  and  rib  cage  expand  lungs?   -­‐ Recall:  Intrapleural  space   o Filled  with  few  ml  of  fluid  which  lubricates  tissues  as  lungs  expand   o Because  liquid  is  incompressible,  lungs  follow  volume  changes  of  thorax  even  though  lungs   are  not  fastened  to  thoracic  wall   -­‐ Elastic  recoil  of  chest  wall  tries  to  pull  chest  wall  outward   -­‐ Elastic  recoil  of  lung  creates  an  inward  pull     Pneumothorax   -­‐ Apply  wet  dressing  on  wound  to  act  as  one-­‐valve  (out)  and  positive-­‐pressure  at  mouth  to  inflated   lungs     Pressure  change  during  quiet  breathing       Lung  properties  that  influence  breathing   -­‐ Lung  compliance   o Degree  lungs  will  comply  by  changing  their  volume  when  subjected  to  a  change  in   intrapleural  pressure   o Influenced  by   § Elastin  fiber  network   § Surface  tension  in  alveoli   -­‐ Airway  resistance   o Force  that  opposes  mvt  of  air   o Influenced  by   § Type  of  flow   § Airway  diameter     Lung  compliance   C =LV/ΔP   D  the curves for the following clinical conditions: Curves  for  the  following  c1. Emphysemaonditions   1. Emphysema   2. Pulmonary  fibrosis   Pulmonary fibrosis Lung Volume negative Distending pressure positive       Factors  that  affect  compliance:  Elastin  fibers  and  surface  tension   -­‐ Elasticity  of  lungs  decreases  as  we  age   -­‐ Surface  tension  tends  to  shrink  volume  of  alveolus   -­‐ Pressure  inside  alveolus  increases   -­‐ This  pressure  must  overcome  to  inflate  alveolus   -­‐ When  this  effect  for  all  alveoli  are  added  together  the  effect  is  to  make  lung  tissue  behave   elastically     Fig. 17.11     Types  of  flow   -­‐ Laminar   o Resistance  α  Lη/r   4 o L=length  of  tube   o η=Viscosity   o r=radius   -­‐ Turbulent   -­‐ Intermediate     As  pressure  gradient  increases,  flow  becomes  more  turbulent   turbulent Laminar Flow Turbulent Flow - R constant - R varies with flow -silent - noisy -viscosity - density dependent dependent Pressure Gradient Airway Flow     Recall:  Airway   -­‐ 90%  airway  resistance  due  to  trachea  and  bronchi   -­‐ Bronchioles  –  normally  don’t  contribute  to  resistance  because  total  xs  area  is  large  but  diameter   can  change  because  they  are  collapsible  tubes  surrounded  by  smooth  muscle   -­‐ Bronchioconstriction  –  diameter  gets  smaller  (histamine)   -­‐ Bronchiodilation  –  diameter  gets  2arger  (CO ,  epinephri2e  binding  to  β  adrenergic  receptors     At rest, how much air is exchanged per minute? At  rest,  how  much  air  is  exchanged  per  minute?   V T = 500 ml/breath Ventilation = VT X f (breaths/min) V D = 150 ml/breath = 7.5 L/min the dead space volume Alveolar Ventilation = (V T V )Dx f = 5.25 L/min f= 12 - 18 breaths/min FRC = 3000 ml Cardiac output Gas exchange volume = 5 L/min Capillary volume = 70 ml   -­‐ Each  breath  ~500ml  of  fresh  air  enters  lungs  but  first  gas  entering  gas  exchange  is  dead  space  gas   containing  expired  air  from  lungs  so  amount  of  fresh  air  entering  gas  exchange  area  is  only  500-­‐ 150=350ml  each  breath   -­‐ If  normal  breathing  rate  (frequency)  is  15  breaths/min  then  ventilation  of  gas  exchange  volume   350*15=5.25L/min   -­‐ So,  actual  ventilation  of  500ml*15=7.5L/min,  2.25L/min  is  wasted  ventilating  dead  space   (150ml*15=2.25L/min)   -­‐ Note:  FRC  acts  as  buffer  against  changes  in  alveolar  gas  composition   -­‐ Alveolar  gas  exchange  volume  is  large  relative  to  tidal  volume  and  capillary  volume  so  fluctuation   in  composition  of  gases  during  breathing  cycles  are  small   -­‐ Imagine  if  FRC=VT  then  during  expiration  lungs  would  empty  completely  and  venous  composition   blood  would  flow  through  unchanged   -­‐ Note:  to  increase  ventilation  of  lungs,  both  tidal  volume  and  breathing  frequency  are  increased     Lecture  3   Respiratory  system  –  gas  exchange  and  gas  transport     How  much  oxygen  and  carbon  dioxide  is  in  air?   Dalton’s  law  of  partial  pressures   -­‐ Total  P atm  =  sum  of  partial  pressures   -­‐ PB=PO  +PCO2  +  PN 2   2 -­‐ PB  is  normally  760mmHg   -­‐ Partial  pressure  =  fractional  concentration  *  total  pressure   -­‐ Note:  fractional  concentration  applies  to  gases  only,  concentration  applies  to  gases  in  liquids  like   blood     Air  is  rapidly  humidified  in  respiratory  tract   -­‐ Water  vapor  pressure  contributes  to  overall  pressure   -­‐ PB=PO  +PCO2  +  PN 2  +PH O 2(47mmHg) 2   -­‐ 760mmHg  –  47mmHg  =  713mmHg   -­‐ Partial  pressure  =  fractional  concentration  *  total  pressure     How  much  oxygen  and  carbon  dioxide  in  alveoli?   -­‐ PO 2=  100mmHg   -­‐ PCO  2  40mmHg     What  determines  how  much  gas  dissolves  in  solution?   -­‐ Partial  pressure  of  gas   -­‐ Solubility  of  gas   -­‐ Temperature  of  solution     How  much  oxygen  and  carbon  dioxide  in  blood?   -­‐ PO 2≤  40mmHg  (Peripheral  tissue)   -­‐ PCO  2  46mmHg  (Peripheral  tissue)     Gas  exchange  occurs  by  passive  diffusion   -­‐ Fick’s  law  of  diffusion   o Gas  transfer  =  constant  *  partial  pressure  gradient  *  area/wall  thickness   -­‐ Note:  constant  includes  solubility  of  gas  in  alveolar  membrane  CO  is  20X  more  soluble 2  than  O   2   Gas  exchange  can  be  affected  in  the  following  conditions   -­‐ Normal  lung   -­‐ Emphysema   -­‐ Fibrotic  lung  disease   -­‐ Pulmonary  edema   -­‐ Asthma     Pulmonary  gas  transfer   Pulmonary Gas Transfer 100 alveolar Pao 2 gas 97 P Ao = 106 80 2 mmHg 2 Po 60 mix pedlmveonnoarysabrloery 40 37 arterial blood arterialized blood inaryry veins 50 pulmonary capillary blood venous admixture in 46 m2Hg alveolar gas Paco 2 Pco PAco = 29 39     How  is  oxygen  transported  in  blood?   -­‐ Dissolved  in  plasma  3ml2  O /L  of  blood   -­‐ Carried  in  RBC  197ml2  O /L  of  blood     Structure  of  hemoglobin   -­‐ 4  proteins   -­‐ 2α  and  2β     Oxygen-­‐hemoglobin  dissociation  curve   -­‐ At  lungs:  98%  of  Hb  saturated 2  with  O   -­‐ At  tissue:  75%  of  Hb  is  saturat2d  with  O   -­‐ Therefore,  98%-­‐73%=25%%  is  release  at  tissue  at  rest   -­‐ Note:  During  exercise, 2PO  at  tissue  is  20mmHg     Several  factors  affect  affinity  of  hemoglobin  for  oxygen   -­‐ Effect  of  pH   -­‐ Effect  of  temperature   -­‐ Effect  of  2CO   -­‐ Decreased  pH,  increased  temperature,  increased  PCO2    decrease  affinity  of  H2  for  O   -­‐ Effect  of  CO  on  Hb  binding  to  O  called  Bohr  effect   2 2   Physiological  significance  –  effect  of  pH   -­‐ pH  =  726  O  saturated  =  83%   -­‐ pH  =  7.4  O  saturated  =  75%   2 -­‐ pH  =  722  O  saturated  =  63%   -­‐ Therefore,  at  tissues  more  oxygen  is  released  when  pH  is  low   -­‐ Note:  there  is  less  effect  2t  high  PO  in  alveoli     Different  forms  of  Hb  made  during  development   -­‐ Fetal  Hb  has  greater  affinity2  for  O  than  maternal  Hb     How  is  carbon  dioxide  transported  in  blood?   1. Carbamino  CO  at 2PO  (v2nous  blood)  at  PO  1002  (arterial  blood)   2. CO  2s  bicarbonate   3. Dissolved  CO   2 -­‐ At  lungs  PCO 2  drops  from  46mmHg  to  40mmHg   -­‐ Dissolved  change  0.6ml/100ml  -­‐  10%   -­‐ Carbamino  change  1.8ml/100ml  -­‐  30%   -­‐ Bicarbonate  change  3.6ml/100ml  -­‐  60%   -­‐ Total  change  6ml  CO /102ml  100%   -­‐ Note:  at  any  given  PCO 2  blood  carries  less  carbon  dioxide  greater  PO   2   o This  effect  called  Haldane  effect     Most  CO 2 transported  as  bicarbonate   At  tissue   -­‐ Carbonic  anhydrase  enzyme  catalyzes  reaction   -­‐ Hemoglobin  buffers  hydrogen  ions  (in  RBC)   -­‐ Bicarbonate  leaves  RBC  and  chloride  enters  in  exchange  “chloride  shift”   At  lungs   -­‐ Carbonic  anhydrase  enzyme  catalyzes  reaction     -­‐ H  dissoCO transport: At tissuesobin   -­‐ Bicarbonate  enters  RBC  and  chloride  leaves  in  exchange  “chloride  shift”     CO 2  transport:  at  tissues   CO transport: At lungs 2     CO 2  transport:  at  lungs   Figure 18.11     Figure 18.11 Summary   Lecture  4  –  Chemical  regulation  of  breathing   Pulmonary ventilation matches O uptake/consumption 2 Pulmonary  ventilatio2  matches  O2  uptake/consumption  and  Feedback Regulation of Breathing  Pulmonary Feedback  regulation  of  breathing   Ventilation Metabolic Carbon Dioxide Production Gas Exchange Pco Carbon 2 Dioxide stores Pco Po Oxygen Po 2 Ventilation 2 2 stores Metabolic As ventilation increases, arterial PCO drops2 Pulmonary Ventilation Chemoreflexes The Metabolic Hyperbola Oxygen Consumption 30   As breathing is   increased, more 25 Alveolar PCO 2 CO P2oduction CO is “blown off” As  ventilation  increases,  arteriCO2  drops:  the  metabolic  hyperbola   Alveolar Ventilation 2 -­‐ As  breathing  is  increased,  mor2  CO  is  “blown CO2  falls.  If   and PCO 2alls. 20 If breathing is breathing  is  reduced, CO2  rises   reduced, PCO 2ises. -­‐ Shape  and  position  of  metabolic  hyperbola  is  determined  by  rate  of   The shape and production  of  2O  by  metabolism   10 position of the   Ve5tilation L/min metabolic hyperbola is determined by the 0 rate of production of CO by metabolism. 0 10 20 30 40 50 60 70 2 Arterial Pco mmHg How  CO  and  O  monitored   2 2 -­‐ Central  chemoreceptors:   o Located  in  medulla  oblongata  and  scattered  in  other  brain  tissue   o Detect  [H ]  in  CSF   -­‐ Peripheral  chemoreceptors   o  Located  in  carotid  (mainly)  and  aortic  bodies   o Detect  [H ]  in  blood  –  sensitivity  increased  when  P  falls   O2   Central and Peripheral medulla oblongata How do chemoreceptors
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