Respiratory physiology [PDF]

Respiratory System

By Dr. Carmen Rexach Physiology Mt San Antonio College

External vs. internal respiration • External respiration – ventilation – gas exchange

• Internal respiration – cellular respiration

Structure • Conducting zone – Nasal cavity to respiratory bronchioles

• Respiratory zone – Respiratory bronchi – Alveoli

Thoracic cavity • Diaphragm • Pleura • Potential space

Intrapulmonary and intrapleural pressures • Boyle’s law – pressure of a given quantity of gas is inversely proportional to volume • Interpleural space = intrapleural space • Intrapulmonary (intraalveolar) pressure – Pressure in alveoli

• Intrapleural pressure – Pressure in pleural cavity

• Transpulmonary pressure – Intrapleural pressure – intrapulmonary pressure – Keeps lungs inflated

Relationship between intrapulmonary and intrapleural pressure

Pneumothorax • Air in interpleural space is below atm • When wall is breached, air rushes in – GSW, stabbing, trauma

• Result: collapsed lung

Spontaneous pneumothorax • Lung collapses due to air or gas collecting in chest without any sign of traumatic injury • Usually occurs when patient is resting • Symptoms – Sudden chest pain with breathlessness, exaccerbated with deep breathing or coughing

• Risk factors – Male gender (7x’s more likely than in females) • Smoking (22x’s more likely than nonsmokers)

– Smoking females 9x’s more likely than nonsmoking females

Inspiration • Pressure of air exceeds intrapulmonary pressure • Steps: – expansion of thoracic cage – pulls on parietal pleura = increase intrapleural cavity volume – pressure decreased by (subatmospheric) – increased transpulmonary difference – alveoli expand = decreased pressure in alveoli – air moves from high to low pressure = moves in

Expiration • Intrapulmonary pressure greater than atmospheric pressure = air moves out

• Steps: – diaphragm & inspiratory intercostals relax – chest wall recoils – intrapleural pressure approaches preinspirational value – intrapulmonary pressure exceeds atmospheric pressure – air goes out

Physical properties of the lungs • Three properties – Compliance – Elasticity= tendency to recoil – Surface tension

• Two forces resist distension – Surface tension and recoil

• surfactant

Pulmonary ventilation • Normal inspiration = active • Normal expiration = passive • Forced inspiration – Scalenes, pectoralis major, sternocleidomastoid

• Forced expiration – Internal intercostals,abdominals

Pulmonary function tests • Measured by spirometry • Lung volumes and capacities (approximate volume) – Tidal volume = volume of each breath (500ml) – Vital capacity = largest possible tidal volume; amount of

gas that can be forcefully exhaled after maximum inhalation (5000ml)

– Inspiratory reserve volume = volume of gas that can be forcefully inhaled after a normal inhalation (3000ml)

– Expiratory reserve volume = volume of gas that can be forcefully exhaled after an unforced exhalation (1500ml)

– Residual volume = amount of gas remaining in the lungs after a forced expiration (100ml)

– Dead space volume = volume of air in the conduction passageways that is not exchanged (150ml)

Differences by gender

Pulmonary disorders • • • •

Dyspnea Asthma Emphysema COPD =chronic bronchitis + emphysema • Pulmonary fibrosis

bronchi

Normal lung

Chronic bronchitis

asthma

Emphysema

alveoli

Partial pressure of gases • Dalton’s law • PN2 + PO2 + PCO2+ PH2O = PATM = 760mmHg • air = 21% O + 78% N 0.21

760

159mm Hg

0.78

760

593mm Hg

0.0004

760

0.3mm Hg

Other factors influencing pressure • Altitude – Increased = decreased atmospheric pressure – Decreased = increased atmospheric pressure

• 1 atm increase for every 33 feet below sea level

• Temperature – determinant of water vapor composition of air – in body • water vapor = 47mm Hg • effects the partial pressure of O2 = 105 mm Hg in alveoli

Partial pressure of gases in the blood • Gases diffuse quickly due to: – surface area, large capillary bed, short diffusion distance

• Henry’s law = The maximum value of a gas dissolved in a fluid depends on: – the solubility of the gas in fluid – temperature of the fluid – partial pressure of the gases

• Oxygen content of the blood depends on – PO2, # of RBC’s, hemoglobin content – Remember: Oxygen is primarily bound to Hb in RBC’s keeping the amount of O2 in the plasma low

How oxygen is carried in the blood • Normal resting oxygen consumption = 250ml/min • PO2 = 100mm Hg in PV = 20ml O2/100 ml blood – 0.3ml O2 dissolved in plasma – 19.7ml O2 in RBC’s

Partial pressure of CO2 and O2 in circulation

Vascular resistance in lungs • Vascular resistance – fetal = collapsed lungs, resistance is high – birth = drops • subatmospheric intrapulmonary pressure opens blood vessels • stretching of lungs at inspiration • dilation of pulmonary arterioles due to increased alveolar PO2 • foramen ovale and ductus arteriosus close

– adult = low pressure/low resistance • blood flows to lungs and to systemic circulation at same rate • pulmonary 1/10th of systemic vascular resistance

Ventilation/perfusion ratios (V/P) – Ventilation = respiration rate x tidal volume – Perfusion = pulmonary blood flow = heart

rate x right ventricular SV – Nearly matched under normal conditions • apex of lung – overventilated & underperfused – apex =3.4:1 – larger alveoli

• base of lung – underventilated & overperfused – base = 0.6:1

Disorders caused by high partial pressures of gases • Oxygen toxicity – PO2 > 2.5 atm – oxidation of enzymes, nervous system damage, coma, death

• Nitrogen narcosis – > one hour down – rapture of the deep, drowsiness, “intoxication”

• Decompression sickness – formation of N2 bubbles in blood – channels blocked, joint & muscle pain = the bends

Hyperbaric oxygen therapy • 100% oxygen at >1atm (US = 2.0-2.4 atm abs) • Duration:60-90 min. • Result: Arterial PO2 = 1200mmHg • Benefits: – Enhanced fibroblast replication – Activation of osteoclasts – Stimulation of capillary growth – Upregulation vascular endothelial growth factor – Upregulation of platelet derived growth factor

CID: 2006 (43):188-192

Hyperbaric treatment for diabetic foot ulcers

40 days after hyperbaric treatment & skin graft Before hyperbaric treatment

Brain stem respiratory centers • Medulla oblongata – rythmicity center • dorsal group (phrenic nerve) & ventral group (intercostals) • I neurons = inspiration = spinal motor neurons innervate respiratory muscle • E neurons = fire during expiration and inhibit I neurons

• Pons – apneustic center -- constant I neuron stimulation – pneumotaxic center -- inhibitory = cyclic inhibition

• Chemoreceptors -- respond to changes in PCO2, pH, PO2 – central – peripheral = aortic and carotid bodies

Irritant and Inflation Reflex • Pulmonary irritant reflexes

– Reflex constriction to prevent particulates from entering lungs – Stimulate cough in trachea & bronchi, sneeze in nasal cavity

• Inflation reflex

– Stretch receptors respond to lung inflation – Inhibitory signals sent to allow expiration to occur – Hering-Breuer Reflex

Control of ventilation: blood CO2 • Chemoreceptors control rate & depth of breathing by measuring PCO2, PO2, pH – Hypoventilation = hypercapnia – Hyperventilation = hypocapnia

• reflex control of ventilation – goal: to maintain relatively constant PCO2 = 40 mm Hg

• chemoreceptors in ventral medulla – – – – –

increased arterial PCO2 = inc [H+] blood CSF = CO2 crosses blood blain barrier to stimulate receptors Periphery = rise in [H+] decreases blood pH = stimulus In the brain, CO2 levels directly stimulate receptors in the periphery, H+ levels provide the stimulus

Peripheral chemoreceptors

Effects of blood PO2 on ventilation • Indirect influence by changing chemoreceptor sensitivity to CO2 – low PO2 = increased sensitivity – high PO2 = decreased sensitivity

• effect of breathing pure oxygen – dilutes effect of CO2

• Chronic CO2 exposure

– diminished response (emphysema)

Hemoglobin

Hemoglobin • 2 α & 2 β chains = quaternary structure • 4 hemes = each heme has one Fe and will bind with one oxygen molecule • 280 million Hb per RBC x 4 = >1 billion molecules of oxygen per RBC • Hb + O2 = oxyhemoglobin • Hb - O2 = deoxyhemoglobin • oxygen saturation = statistical average of all oxygen bound relative to total amount that can be bound

What binds to hemoglobin? • • • • •

oxyhemoglobin = Hb + O2 deoxyhemoglobin = Hb - O2 carbaminohemoglobin = Hb + CO2 carboxyhemoglobin = Hb + CO methemoglobin = Fe3+ instead of Fe2+ – cannot bind oxygen – normally represents 1-2% of Hb

• Sulfhemoglobin = Hb + Sulfur

Unusual conditions

• Sulfhemoglobinemia

– Increased amounts of sulfur, usually drug induced – Blood is green due to binding of sulfur to Hb

• Methemoglobinemia – – – –

Increased amount of Fe3+ on Hb Blood appears chocolate brown in color Patients look “blue” NOTE: Venous blood is not blue in normal people!! It just looks blue through skin because veins run deeper than arteries

Hemoglobin concentration • oxygen carrying capacity of the blood = maximum amount that can be bound by Hb

• normal = polycythemia (common at high altitudes)

• RBC/Hb production – erythropoietin – androgens

Properties of Hb:O2 binding • Hb binds reversibly with O2 • Molecular oxygen associates and dissociates from Hb very rapidly – Blood is in the exchange capillaries less than one second

• The sigmoid shape of the oxyhemoglobin dissociation curve is caused by molecular interactions of the four heme groups

Loading and unloading reactions • Loading reaction • Unloading reaction • Determined by: – PO2 of the environment – Affinity of Hb for oxygen

Oxyhemoglobin dissociation curve • Relationship between PO2 and oxygen saturation of Hb • Oxygen reserve – 80% saturation even at PO2 of 40 mm Hg • Effects of high PO2 • Can be modified by physiological and pathological factors – pH – temperature – 2,3-DPG

Oxyhemoglobin dissociation curve

Effect of pH, temperature, &2,3 DPG on Oxygen transport • incr [H+], PCO2, 2,3-DPG, temperature = decr affinity of Hb for oxygen = incr unloading – entire curve shifts to the right of the standard curve

• decr [H+], PCO2, 2,3-DPG, temperature = incr affinity of Hb for oxygen = incr loading – entire curve shifts to the left of the standard curve

2,3-DPG (diphosphoglyceric acid) • Product of anaerobic respiration in RBC’s • increases with decrease in oxyhemoglobin • result: increased unloading of oxygen at tissues • conditions – anemia – high altitudes – transfer maternal to fetal circulation (Hbf)

Shifts in oxyhemoglobin dissociation curve

Inherited defects in hemoglobin structure/function • Sickle cell anemia (HbS) – valine replaces glutamic acid on β chain

• thalassemia – Mediterranean ancestry – 2 forms; α & β thalassemia – increased γ chain production, decreased oxygen unloading

Muscle myoglobin • Special functions – middleman – oxygen storage function

• Slow twitch fibers & cardiac muscle cells • rhabdomyolysis

How is CO2 carried in blood?

• 1/10 = dissolved • 1/5 = carbaminohemoglobin • 7/10 = bicarbonate – CO2 + H20

H2CO3

• Carbonic anhydrase – in RBC’s

H+ + HCO3-

Chloride shift: tissue level • Equation shifts to the right – H2O + CO2

• Steps:

H2CO3

H+ + HCO3-

– CO2 diffuses out of the tissue cells into the blood – CO2 moved into the red blood cells – Combines with H2O in the presence of carbonic anhydrase to produce carbonic acid – Carbonic acid dissociates producing H+ + HCO3– H+ buffered by hemoglobin, facilitating the offloading of O2 – net positive charge in RBC results in chloride shift – Chloride moves into the RBC in exchange for HCO3– Bohr effect • increased oxygen unloading • continued H2CO3 production • enhanced transport of CO2

Chloride Shift: Tissue Level

Chloride shift: Pulmonary capillaries • Hb oxygenated • decrease in affinity for H+ • Reverse chloride shift as Cl- moves out and HCO3- moves in • HCO3- + H+ H2CO3 • Carbonic acid dissociates to CO2 & H2O • CO2 expired out • Remember: – H+ is buffered by Hb in RBC – HCO3- goes into the plasma and buffers incoming H+

Reverse Chloride Shift

Ventilation and acid-base balance • Acidosis and alkalosis • Regulated by respiratory system – Respiratory acidosis – Respiratory alkalosis

• Regulated by the kidneys – Metabolic acidosis – Metabolic alkalosis

Ventilation during exercise • Neurogenic – sensory nerve activity = stimulates respiratory muscles – cerebral cortex = brain stem alteration of ventilation

• humoral – cyclic variations in values of PCO2 & pH stimulates chemoreceptors (small amounts)

• anaerobic threshold and endurance training – anaerobic threshold = maximum rate of oxygen consumption attained before blood lactic acid levels rise due to anaerobic respiration

– adaptations in athletes =incr mitochondria, aerobic enzymes; incr oxygen utilization by muscles, lower % oxyhemoglobin in venous blood

Higher altitudes

• Conditions differ

– rapid fatigue: decreased PO2, oxygen content of blood

decreased (PO2 =69-74mmHg, oxyhemoglobin saturation = 9293%)

• Changes in ventilation – hypoxic ventilatory response: decr arterial PO2 =

hyperventilation = respiratory alkalosis • mediated by incr in pH, stabilizes after a few days

– cannot increase PO2 greater than inspired air

• Hemoglobin affinity for oxygen decreased – greater unloading due to 2,3-DPG

• Hemoglobin and RBC production – tissue hypoxia stimulates increased erythropoietin – increased viscosity due to increase in RBC’s