AcidBase

1
Acid-Base
pH -log H

• Arterial Blood pH 7.35 7.45
• pHs above 7.8 or below 6.9 not compatible with
  life
• pH 6.9 H 126 nmol/liter
• pH 7.2 H 63 nmol/liter
• pH 7.4 H 40 nmol/liter
• pH 7.8 H 16 nmol/liter
• Greatest source H is metabolism CO2, produced
  by oxidation of glucose or fatty acids, reacts
  with water to form H2CO3

2

• H2CO3 is a volatile acid
• Large amounts removed at the lungs (15,000-25,000
  mmol CO2/day)
• Fixed acids only represent 0.2 of the bodies
  acid production, removal mainly by kidneys, some
  by the GI tract.
• Bicarbonate system able to buffer the fixed acids
  because the CO2 can be removed at the lungs

3
Respiratory Acidosis

• Alteration of alveolar ventilation that results
  in an increase in Pco2 (gt 45 mm Hg in alveoli)
  and hence also arterial Pco2, decreases the
  arterial pH and results in respiratory acidosis.
• Ratio of HCO3-/CO2 is decreased

4
Respiratory Alkalosis

• Excess ventilation, Pco2 in alveoli lt 35 mm Hg
• Get increase in pH
• Ratio of HCO3-/CO2 is increased

5
Regulation of Respiration

• The system works to maintain steady levels of O2
  and CO2 in the arterial blood.
• The respiratory center is located in the pons and
  the medulla oblongata.

Pons
4th Ventricle
Medulla Oblongata
CSF
6
Dorsal respiratory group
Pneumotaxic center
Dorsal respiratory group
Apneustic center
Ventral respiratory group
Phrenic nerve
Vagus Glossopharyngeal

• 3 major collections of neurons located
  bilaterally
• dorsal respiratory group
• ventral respiratory group
• pneumotaxic center

7
Dorsal Respiratory Group

• In the dorsal part of the medulla
• Special neuronal cells discharge spontaneously
  and rhythmically resulting in inspiration. Like
  a pacemaker.
• Impulses travel the phrenic nerve to the
  diaphragm and cause it to contract.
• Located in the nucleus of tractus solitarius,
  this is the end point of the vagus and
  glossopharyngeal nerves.

8
Breathing
Strength Inspiratory Signal
IN
OUT
Time

• Signal begins weakly and increases steadily for
  2 seconds.
• Stops abruptly for 3 seconds. Stops diaphragm
  from contracting and elastic recoil of lung
  causes expiration.
• Results in a steady increase of lung volume

9
Pneumotaxic Center

• Located in the upper pons
• Works in conjunction with the Apneustic Center
  in the lower pons to SWITCH OFF the inspiratory
  signal.
• If signals are strong the inspiratory ramp signal
  will be short. Breathing rate will
• Function is to limit inspiration.

10
Ventral Respiratory Group

• Inactive during normal breathing
• When increased pulmonary ventilation is required,
  signals from the dorsal respiratory group are
  sent to the ventral group.
• Signals are then sent to all the muscles of
  respiration during the cycle of breathing.
• Especially the abdominal muscles for expiration
• Main use Increases inspiration and expiration,
  allowing exchange of large volumes of air.

11
Chemical Control of Ventilation

• AIM To maintain a fairly constant level of O2,
  CO2 and H in the body fluids.
• Direct control, central chemoreceptors CO2 and
  H
• Stimulates inspiration
• Indirect control through peripheral
  chemoreceptors
• Low O2, signal to stimulate respiration
• High CO2 or H stimulates respiration, small
  compared to direct effect

12
Direct Control by CO2 and H at the central
chemoreceptors

• Chemosensitive area of neurons, 0.2mm below
  surface of medulla.
• Very sensitive to changes in H in the CSF and
  interstitial fluid and CO2 in blood.
• CO2 can cross from blood to the CSF. H cannot.
  BUT CO2 reacts and produces H in the CSF.

CSF
Chemo- sensitive area
Dorsal R.G.
H HCO3-
H2CO3
CO2 H2O
13
Central chemoreceptors area

• Chemosensitive area responds to changes in the
  CSF and the interstitial fluid of the medulla
• High PCO2 in blood CO2 diffuses to CSF and
  medulla. H are blocked by blood-brain and
  blood-CSF barrier.
• CO2 reacts with water to form carbonic acid,
  which breaks down to form H and HCO3-
• Not enough protein in CSF to buffer the H
• Chemosensitive area sends signals to DRG,
  respiration increases.

14
Effect of Blood CO2 on basal respiration

• PCO2 has a greater effect on respiration
• Normal blood PCO2 range is 35-60 mmHg. This is
  the range at which ventilation rate is most
  sensitive to change.

15
Adaptation of central chemoreceptors

• CSF pH 7.32
• Not as much buffering as blood so can have rapid
  change of pH.
• If pH is low for a long period of time, HCO3- is
  transported across the blood-brain barrier. This
  will then prevent high stimulation of the
  respiration system over a long period of time.
• HCO3- is renal compensation, more effective in
  the CSF than in the blood, as CSF buffering
  lower.

16
Reflex mechanisms of respiratory control

• Pulmonary stretch receptors
• Receptors in the airways and lung
• Pulmonary vascular receptors (J receptors)
• The cardiovascular system (peripheral
  chemoreceptors)
• Muscles and tendons

17
Pulmonary stretch receptors

• Hering-Breuer inflation reflex
• Stretch receptors situated in the smooth muscle
  of the large and small airways
• Called slow adapting pulmonary stretch receptors
  as activity maintained with sustained stretch
• Discharge when lung is distended, travels via the
  vagus nerve
• Slows respiratory frequency by increasing the
  time of expiration
• Not initiate until 800-1000ml tidal volume
• Abrupt deflation, leads to an increase in
  respiration frequency, maybe stretch receptors as
  well as irritant and J receptors.

18
Receptors in the airways and lungs

• Irritant receptors
• Mechanical or chemical irritation of the airways
  results in a reflex cough or sneeze,
  bronchoconstriction.
• Located in the nasal mucosa, upper airways,
  tracheobronchial tree and possibly the alveoli.
• Those in larger airways respond to stretch also,
  but rapidly adapt and activity decreases rapidly
  during a sustained stimulus
• Except for those in the nasal mucosa, signals
  sent via the vagus
• Maybe involved in bronchoconstriction in asthma
• Immersion of face in water, results in apnea,
  bronchoconstriction, laryngeal constriction,
  response of receptors in the nose to water.

19
Reflexes from Pulmonary vascular receptors

• J receptors
• are believed to be in the walls close to the
  capillaries (juxta-capillary)
• Respond quickly to chemicals in the pulmonary
  circulation
• Impulses pass up the vagus in slowly conducting
  nonmyelinated fibers
• Result in rapid, shallow breathing
• Intense stimulation causes apnea
• Increased stimulation caused by pulmonary
  vascular congestion (rapid breathing)
• Decreased stimulation by decreased flow through
  capillaries (decreased ventilation)

20

• Bronchial C-fibers
• Respond quickly to chemicals in the bronchial
  circulation
• Response to stimulation includes rapid shallow
  breathing, bronchoconstriction and mucous
  secretion

21
Reflexes from the Cardiovascular system

• Arterial Chemoreceptors
• Largest number are in the carotid bodies
• Also in aortic bodies.
• Special blood supply feeds the bodies. Very high
  blood flow through the bodies results in little
  alteration of PO2 compared to the artery.

(Hering)
22
Carotid body nerve impulses / second
Arterial PO2 (mm Hg)

• Arterial PO2 low, chemoreceptors send signals to
  dorsal respiratory group.
• Aortic bodies via the vagus nerve
• Carotid bodies via the glossopharyngeal nerve
• Impulse rate sensitive at PO2 60-30 mm Hg which
  is where O2-Hemoglobin dissociates most rapidly.

23

• High CO2 and H also stimulates the
  chemoreceptors (7 x less effective than by
  direct effect on central chemosensitive area).
  Receptors in the carotid respond to pH in humans.
• If air has low O2, blood PO2 is low,
  chemoreceptors fire to respiration. But
  respiration blows off CO2 so blood PCO2 and
  H. The respiration rate does not increase
  greatly.
• Effect of low PO2 can be great if CO2 and H is
  not decreased by respiration or breathing low
  O2 for days allows time for adaptation.
• Responsible for increased ventilation in response
  to arterial hypoxemia
• Rapid response

24
High CO2 and Low O2

• Combined effects is greater than just adding the
  response of low O2 and high CO2.

25

• Arterial Baroreceptors
• Stretch receptors that are responsive to changes
  in pressure
• Situated in carotid sinuses and aortic arch
• Effects of stimulation by elevated blood pressure
  are apnea and bronchodilation.

26
Receptors in muscles and tendons
Total ventilation (L/min)
Heavy
Moderate
O2 consumption (L/min)

• Increased metabolism, increased alveolar
  ventilation.
• But there is negligible change in arterial PO2,
  PCO2 and pH
• Proprioceptors at the joints of the limbs are
  excited during movement and ? pulmonary
  ventilation.
• Higher centers in the brain that transmit
  impulses to contracting muscles are believed to
  also transmit signals to the respiratory center

27
Arterial PCO2
Diffusion into CSF and medulla interstitial
Arterial PO2
Arterial pH
pH
Stimulation of chemosensitive area
Firing Carotid Aortic bodies
Stimulation DRG
Stimulation VRG
Higher centers of brain during exercise
Respiration
Proprioceptors during movement
28
Other Factors Affecting Respiration

• Overdose of anesthetics or narcotics
• Certain anesthetics not used now due to
  depression of respiratory center
• Periodic breathing - short and deep breath, then
  not breathe for an interval of time
• e.g. Cheyne-Stokes breathing

29
Pulmonary Abnormalities

• Pulmonary emphysema
• Pneumonia
• Atelectasis
• Asthma
• Tuberculosis
• Dyspnea

30
Pulmonary Emphysema

• Excess air in lungs. Usually means obstructive
  and destructive process
• Disease Chronic infection, excess mucus and
  inflammatory edema chronic obstruction of
  smaller airways difficult to expire
  entraps air in airways overstretching
  destruction
• Physiological effects
• airway resistance and diffusing capacity
• Lack of capillaries, vascular resistance,
  pressure, results in right heart failure.
• Death due to hypoxia and high blood CO2.

31
Pneumonia
Emphysema
Normal
Pneumonia

• Inflammatory condition of lung, usually
  infection.
• Infection in alveoli pulmonary membrane
  inflamed and porous cells and fluid move
  into alveoli spread of infection

32
Pulmonary artery 60 sat.
Right vein 60 sat.
Left vein 97 sat.
Aorta 1/2 97 1/2 60 Mean 78

• Two major pulmonary abnormalities
• decreased surface area of respiratory membrane.
• No air flow through infected lung.
• Result
• diffusing capacity low PO2 and high PCO2

33
Atelectasis

• Means collapse of alveoli. Occurs by
• Airway obstruction - air entrapped passed
  blockage is absorbed by blood and collapses the
  alveoli. If lung not pliable then negative
  pressure builds in alveoli and sucks fluid in
  from the interstitial. Results in edema and
  massive collapse.
• Lack of surfactant - respiratory distress
  syndrome in premature babies. in surfactant
  secreted in alveoli, surface tension too high to
  be counteracted by the negative pressure of
  pleural cavity. Alveoli collapse.

34
Asthma

• Spastic contraction of smooth muscles in the
  bronchioles causes diameter of airways.
• Mast cells lie in lung interstitium. IgE
  antibodies are bound to these cells. Pollen
  (antigen for IgE) is breathed in and binds to IgE
  antibodies. Results in mast cells degranulating
  or bursting.

35

• Histamine and leukotrienes released
  Contraction of smooth muscle thick mucus in
  bronchiolar lumen edema in walls of small
  bronchiolar.
• intrapulmonary pressure compresses outside of
  bronchioles during expiratory effort.
• Result can inspire but hard to expire

36
Tuberculosius

• Tubercle bacilli cause invasion of macrophages
  and walling-off lesion by fibrous tissue to form
  tubercle.
• Walling-off helps prevent spread of infection.
• 3 untreated patients walling-off fails and
  destruction of lung and abscess cavities form.
• Results in reduced vital capacity, reduced
  surface area of respiratory membrane, increased
  thickness of respiratory membrane.

37
Dyspnea

• Means mental anguish associated with inability to
  ventilate - air hunger
• Factors involved
• abnormality of respiratory gases, especially
  excess CO2
• amount of work involved to respire
• state of mind
• Emotional dyspnea - respiratory functions normal
  but unable to ventilate properly, e.g. fear of
  crowds or small spaces.