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Respiratory System.Pdf

Respiratory System.Pdf

Respiratory System - Overview:

Assists in the detection Protects system of odorants Respiratory (debris / pathogens / dessication)

System 5 3

4 Produces sound (vocalization) Provides surface area for (between air / )

1

2 For the body to survive, there must be a constant supply of Moves air to / from gas O2 and a constant exchange surface disposal of CO 2 Marieb & Hoehn (Human Anatomy and , 8th ed.) – Table 19.1

Respiratory System Respiratory System

Functional Anatomy: Functional Anatomy:

Trachea Epiglottis Naming of pathways: • > 1 mm diameter = bronchus

Upper Respiratory • Conduction of air • < 1 mm diameter = bronchiole System • Gas exchange Primary • < 0.5 mm diameter = terminal bronchiole Bronchus • Filters / warms / humidifies Lower Respiratory Bronchi System incoming air bifurcation (23 orders) 1) External nares 5) Larynx 2) Nasal cavity • Provide open airway Green = Conducting zone • chamber • channel air / food Purple = Respiratory zone 3) Uvula • voice production (link) 4) Pharynx 6) Trachea 7) Bronchial tree • Nasopharynx Bronchiole 8) Alveoli • Oropharynx Terminal Bronchiole Respiratory Bronchiole • Laryngopharynx Alveolus

Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.1 Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9

Respiratory System Respiratory System

Functional Anatomy: Functional Anatomy: Respiratory Mucosa / Submucosa: How are inhaled debris / pathogens cleared from ? Near Near trachea alveoli Nasal Cavity: Epithelium: Particles > 10 µm Pseudostratified Simple columnar cuboidal Conducting Zone: Particles 5 – 10 µm Cilia No cilia Respiratory Zone: Escalator Particles 1 – 5 µm Mucosa: Lamina Propria (areolar tissue layer): Mucous membrane (epithelium / areolar tissue)  smooth  smooth muscle muscle

Mucous No glands mucous glands Cartilage:

Rings Plates / none Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9 Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.2

1 Respiratory System Respiratory System

Functional Anatomy: Pseudostratified ciliated Functional Anatomy: columnar epithelium

Trachea Right primary bronchus wider, shorter & steeper Goblet cells: ( blockage hazard) Unicellular mucous secreting glands

Bronchus (> 1 mm diameter) • 1º = Extrapulmonary bronchi • 2º  = Intrapulmonary bronchi

Esophagus : Inflammation of airways Pseudostratified ciliated columnar epithelium Tough, flexible tube Smooth muscle 15 – 20 tracheal (~ 1” diameter) cartilages (C-shaped) • Protect airway Cartilage plate • Allow for food passage

Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9 Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9

Respiratory System Respiratory System

Functional Anatomy: Mucous glands rare – Why? Functional Anatomy: Pseudostratified Surrounded by fine ciliated columnar elastic fibers epithelium Respiratory bronchiole Cartilage plates? Terminal Alveolar bronchiole sac

Thick smooth muscle Type I Pneumocytes: • Simple squamous; forms wall of alveoli Allergic attack =  = Total surface area: • Alveolar pores (1 – 6 / alveoli) 75 - 90 m2 (~1/2 tennis court) Type II Pneumocytes: Sympathetic stimulation (NE; 2 receptors) • Leads to bronchodilation 200 m • Cuboidal / round; secrete surfactant • Reduces surface tension (stops alveoli collapse)

Synthetic drugs (e.g., albuterol) E (medulla) triggers Alveolar macrophages: Bronchiole trigger response response (< 1 mm diameter) • Clear debris on alveolar surface Parasympathetic stimulation (ACh; muscarinic receptors) • Leads to bronchoconstriction Alveoli Alveolar (300 million / ) pores Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.9 Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.8

Respiratory System Respiratory System Pneumonia: Functional Anatomy: Thickening of respiratory membrane Respiratory Physiology:

Gas exchange occurs readily in the alveoli of the lung via simple diffusion across the respiratory membrane

0.1 – 0.5 m thick includes: 1 1) Pulmonary ventilation (pumping air in / out of )

2) External respiration (gas exchange @ blood-gas barrier) 2 3) Transport of respiratory gases (blood)

4) Internal respiration (gas exchange @ tissues)

3 Respiratory Membrane: 1) Type I pneumocytes 2) Endothelial cells of 4 3) Fused basement membranes

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.9 Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.19

2 Respiratory System Respiratory System

Pulmonary Ventilation: Pulmonary Ventilation:

Simplified Model: = ~ 760 mm Hg

(Consider Patmospheric = 0 mm Hg) Trachea Trachea Visceral pleura Lung Pressure relationships in the thoracic cavity:

Parietal Pleural 1) Intrapulmonary Pressure (w/in the alveoli): pleura cavity • Static conditions = 0 mm Hg Thoracic wall • (inspiration) = Ppul slightly negative

Intrapulmonary • (expiration) = Ppul slightly positive Lung pressure (Ppul = 0 mm Hg) 2) (w/in ): • Always relatively negative (~ - 4 mm Hg) • Prevents lungs from collapsing

Pleural cavity Diaphragm Intrapleural pressure Diaphragm Thoracic Diaphragm (Pip = - 4 mm Hg) wall

atmospheric pressure = Patm = 0 mm Hg

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.12

Respiratory System Respiratory System

Pulmonary Ventilation: Pulmonary Ventilation:

Why is the intrapleural pressure negative? Pulmonary ventilation is a mechanical process that depends on thoracic cavity volume changes Answer: Interaction of opposing forces

Forces equilibrate at Pip = - 4 mm Hg Boyle’s Law: Forces acting to collapse lung: P1V1 = P2V2 1) Elasticity of lungs Surface tension of 2) Alveolar surface tension serous fluids keep lungs “stuck” to P = pressure of gas (mm Hg) Force resisting lung collapse: chest wall V = volume of gas (mm3)

1) Elasticity of chest wall P1 = initial pressure; V1 = initial volume

P2 = resulting pressure; V2 = resulting volume

Pneumothorax: 3 3 Example: 4 mm Hg (2 mm ) = P2 (4 mm ) P2 = 2 mm Hg (“sucking chest wound”) Puncture of chest wall; results in inability to CHANGING THE VOLUME RESULTS IN INVERSE generate negative pressure CHANGE OF PRESSURE and expand the lungs Costanzo (Physiology, 4th ed.) – Figure 5.9 Martini et. al. (Fundamentals of Anatomy and Physiology, 7th ed.) – Figure 23.13

Respiratory System Respiratory System

Pulmonary Ventilation: Pulmonary Ventilation:

Pulmonary ventilation is a mechanical process that depends on Pulmonary ventilation is a mechanical process that depends on thoracic cavity volume changes thoracic cavity volume changes

0 mm Hg 0 mm Hg Inspiration: Inspiration: Muscular expansion of thoracic cavity - 4 mm Hg Muscular expansion of thoracic cavity - 6 mm Hg A) Contraction of diaphragm A) Contraction of diaphragm • Lengthens thorax (pushes down) • Lengthens thorax (pushes liver down) B) Contraction of external intercostal muscles B) Contraction of external intercostal muscles • Widens thorax • Widens thorax 0 mm Hg - 1 mm Hg Results in:

• Reduced intrapleural pressure (Pip)

• Reduced intrapulmonary pressure (Ppul)

Results in decreased pressure in thoracic Diaphragm cavity and air enters Diaphragm

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.13

3 Respiratory System Respiratory System Internal pressure Pulmonary Ventilation: can reach +100 mm Hg Pulmonary Ventilation: (e.g., why you should exhale when lifting weights)

Pulmonary ventilation is a mechanical process that depends on thoracic cavity volume changes

Results in increased pressure 0 mm Hg Expiration: in thoracic cavity; air exits Retraction of thoracic cavity - 4 mm Hg A) Passive Expiration • Diaphragm / external intercostals relax • Elastic rebound (lungs rebound)

B) Active (“Forced”) Expiration +10 mm Hg • Abdominal muscles contract • Internal intercostals contract

Eupnea: Hyperpnea: Quiet Forced breathing Diaphragm (active inspiration; (active inspiration; (passive expiration) (active expiration)

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.13 Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.14

Respiratory System Respiratory System

Respiratory Distress Syndrome Pulmonary Ventilation: Pulmonary Ventilation: (e.g., pre-mature babies)

Several physical factors exist influence pulmonary ventilation Several physical factors exist influence pulmonary ventilation

A) B) Surface tension in alveoli

Q = Airflow (L / min) Surface tension generated as neighboring liquid on the surface P = Pressure gradient (mm Hg) of alveoli are drawn together by attractive forces Q = P / R Pressure required to R = Airway resistance (mm Hg / L / sec) keep alveolus open

P = Collapsing pressure on alveolus (dynes / cm2) Airflow is directly proportional to pressure difference between outside air 2T T = Surface tension (dynes / cm) and alveoli and inversely proportional to resistance of the airway Law of Laplace: P = r r = Radius of alveolus (cm) Resistance determined by Why don’t the smallest airways provide the highest resistance? Poiseuille’s Law: Medium-sized Surfactant bronchi 8Lη Reminder: R = Parasympathetic system produces 4 r bronchial constriction Problem? Terminal ( diameter =  resistance) R = Resistance

η = Viscosity of inspired air Resistance Sympathetic system produces Dipalmitoyl L = Length of airway bronchial dilation phosphatidylchorine (DPPC) r = Radius of airway ( diameter =  resistance) Bifurcation stage Costanzo (Physiology, 4th ed.) – Figure 5.12

Respiratory System Respiratory System : Pulmonary Ventilation: Pulmonary Ventilation: Amount of air moved into / out of lung during single respiratory cycle

Several physical factors exist influence pulmonary ventilation Respiratory Volumes / Capacities:

C) (spirometric reading)

Measure of change in lung volume that occurs with a given Increases with: transpulmonary pressure • Body size Inspiratory reserve • Gender Volume (IRV) Inspiratory • Conditioning capacity C = Lung compliance (cm3 / mm Hg) (~ 3100 ml) V L (~ 3600 ml) L 3 VL = Lung volume (cm ) CL = (~ 4800 ml)  (P – P ) Ppul = Intrapulmonary pressure (mm Hg) pul ip Ppi = Intrapleural pressure (mm Hg) Decreases with: Resting Tidal Volume (~ 500 ml) (Transmural pressure) • Age Expiratory reserve Barrel Chest volume The higher the lung compliance, the easier Emphysema: (~ 1200 ml) Functional it is to expand the lungs at a given pressure Increased lung compliance due residual to loss of elastic fibers capacity Total lung Determined by: Residual volume (~ 1200 ml) (~ 2400 ml) capacity 1) Elasticity of lung (~ 6000 ml) Fibrosis: 2) Surface tension Decreased lung compliance due (Male) to scar tissue build-up (Female ~ 4200 ml) Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.16

4 Cardiovascular System – Vessels Respiratory System Physiologic : Anatomic dead space plus any Pathophysiology: Pulmonary Ventilation: ventilated alveoli that might not participate in gas exchange Forced vital capacity (FVC) is the total volume of Not all inhaled air participates in gas exchange; this air that can be forcibly expired after maximal inspiration; volume is referred to as dead space this is a useful measure of lung disease

Anatomic Dead Space: Rule of Thumb: Volume of air found in the Anatomical dead space in a healthy young adult is equal to 1 ml / pound conducting airways, including of ideal body weight FEV = Forcefully expired volume the nose  bronchioles

FEV1

FVC < 0.8 > 0.8 • Both FEV and FVC low but • Both FEV and FVC low but 0.8 1 1 FEV1 decreased more than FVC decreased more than FVC FEV1

Costanzo (Physiology, 4th ed.) – Figure 5.6 Costanzo (Physiology, 4th ed.) – Figure 5.3

Respiratory System Respiratory System

Pulmonary Ventilation: Respiratory Physiology:

Ventilation rate is the volume of air moved into an out of the lungs per unit time

Minute Volume: Respiration includes: 1 VM = f (breaths / minute) x VT (tidal volume) 1) Pulmonary ventilation (pumping air in / out of lungs) = 12 breaths / minute x 500 mL 2) External respiration (gas exchange @ blood-gas barrier) = 6000 mL / minute 2 3) Transport of respiratory gases (blood) = 6.0 liters / minute 4) Internal respiration (gas exchange @ tissues) Alveolar Ventilation: (or physiologic dead space)

VA = f (breaths / minute) x (VT (tidal volume) - VD (anatomic dead space)) 3 = 12 breaths / minute x (500 mL - 150 mL)

4 = 4200 mL / minute Available for gas transfer… = 4.2 liters / minute Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.19

Respiratory System Respiratory System

Pulmonary Ventilation: Gas Exchange:

Gas exchange in the respiratory system refers to diffusion of Gas exchange in the respiratory system refers to diffusion of

O2 and CO2 in the lung and in the peripheral tissues O2 and CO2 in the lung and in the peripheral tissues

Basic Properties of Gases: Basic Properties of Gases:

A) ’s Law of Partial Pressures: A) Dalton’s Law of Partial Pressures:

The total pressure of a gas is equal to the sum of the pressure of its constituents The total pressure of a gas is equal to the sum of the pressure of its constituents

Patmosphere: For dry gases: Patmosphere: For humidified gases: 21% 760 mm Hg 21% 760 mm Hg P = P x F P = (P – P ) x F O2 X B O2 X B H2O

PX = of gas (mm Hg) PX = Partial pressure of gas (mm Hg)

PB = Barometric pressure (mm Hg) PB = Barometric pressure (mm Hg) F = Fractional of gas P = Water vapor pressure at 37C (47 mm Hg) H2O 79% 79% F = Fractional concentration of gas N N 2 PO = 760 x 0.21 2 P = (760 – 47) x 0.21 2 O2 P = 160 mm Hg O2 PO = 150 mm Hg % Composition of Atmospheric Air % Composition of Atmospheric Air 2

5 Respiratory System Note: Respiratory System At equilibrium, the partial pressure Gas Exchange: of a gas in the liquid phase equals Gas Exchange: the partial pressure in the gas phase

Gas exchange in the respiratory system refers to diffusion of Gas exchange in the respiratory system refers to diffusion of (the “bends”) O and CO in the lung and in the peripheral tissues O and CO in the lung and in the peripheral tissues Respiratory 2 2 2 2 membrane

Basic Properties of Gases: CO2 >> O2 >> N2 Basic Properties of Gases: Solubility: How much of a gas will dissolve in a B) Henry’s Law: liquid at a given partial pressure C) Fick’s Law: Gases in a mixture dissolve in a liquid in proportion to their partial pressures The transfer of a gas across a membrane depends on the driving force, gas solubility, and the surface area available for transport

CX = PX x Solubility DAP directly proportional C = Concentration of dissolved gas (mL X / 100 mL blood) VX = The driving force for diffusion of a gas is the X inversely proportional partial pressure difference of the gas, P = Partial pressure of gas (mm Hg) x X not the concentration difference Solubility = Solubility of gas in blood (mL X / 100 mL / mm Hg)

VX = Volume of gas transferred per unit time 60 [O2] = PO x Solubility D = Diffusion coefficient of the gas (includes solubility) P P 2 O2 O2 A = Surface area in lung 100 40 in blood [O2] = 150 x 0.003 P = Partial pressure difference of the gas X = Thickness of the membrane [O2] = 0.45 mL / 100 mL blood

Respiratory System Respiratory System In solution, only dissolved gases Gas Exchange: contribute to partial pressures Gas Exchange:

Unlike alveolar air, where there is only one form of gas, Gas transport in the lungs: blood is able to carry gases in addition forms

PX

Bound gas Dissolved gas Chemically modified gas Gases bind directly The higher the solubility to plasma or of a gas, the higher the Gases react with blood to concentration of the gas components to form in solution new products

Total gas concentration = Dissolved gas + Bound gas + Chemically modified gas

Costanzo (Physiology, 4th ed.) – Figure 5.16

Costanzo (Physiology, 4th ed.) – Figure 5.17 Costanzo (Physiology, 4th ed.) – Figure 5.18 Respiratory System Respiratory System

Gas Exchange: Systemic tissues undergo Gas Exchange: reversal of pattern observed at lung Patmosphere: 760 mm Hg DAP Gas transport in the lungs: Gas exchange across the alveolar / pulmonary barrier is described as either diffusion-limited or -limited VX = x O2 = 21% PX = PB x F CO2 = 0% Diffusional coefficient 20x greater Diffusion-limited: Perfusion-limited: for CO2 than for O2 The total amount of gas transported The total amount of gas transported O2 = 21% across the alveolar / capillary barrier is across the alveolar / capillary barrier is CO2 = 0% Lung air modified by gas exchange: limited by the diffusional process limited by blood flow P = (P – P ) x F X B H2O 1) O2 into blood; CO2 out of blood 2) Mixture of fresh and residual air O2 = 14% CO2 = 6% P = 60 O2 P = (P – P ) x F X B H2O Partial pressure PCO = 6 2 gradient maintained across entire length of capillary Example: Example: Carbon Nitrous (gas does not equilibrate) Partial pressure monoxide oxide gradient not maintained The amount of O2 / CO2 across length of capillary transferred corresponds to the (gas equilibrates) needs of the body Composition reflects 1:1 exchange rate Due to rapid diffusion metabolic activity of body of gases, equilibrium reached ?  gas transport =  diffusion rate  gas transport =  blood flow

6 Respiratory System Respiratory System

Gas Exchange: Pathophysiology:

Under normal conditions, O2 transport into pulmonary capillaries In certain pathologic conditions, O2 transport is a perfusion-limited process becomes diffusion limited Lung fibrosis

PO equilibrium never Exercise Rest 2

“wiggle room” reached

PO does not equilibrate until

(mm (mm Hg) 2

2 hemoglobin saturated

O Outcome: P Remember: Decreased PO2 in systemic P only measures free O2 Alveolar wall thickens; slows , especially O concentration 2 down diffusion rate during physical activity

Time in pulmonary capillary (s) DAP Start of End of VX = capillary capillary x

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.18 Costanzo (Physiology, 4th ed.) – Figure 5.19

Respiratory System Respiratory System

Respiratory Physiology:

A man climbs to the top of a tall mountain where the barometric pressure is measured at 50 mm Hg.

What are the implications to transport Respiration includes: into pulmonary capillaries for A) Pa , 1 O2 B) rate, and C) exercise 1) Pulmonary ventilation (pumping air in / out of lungs)

2) External respiration (gas exchange @ blood-gas barrier) 2 3) Transport of respiratory gases (blood) Exercise Rest Driving force: 50 – 25 = 25 mm Hg 4) Internal respiration (gas exchange @ tissues)

DAP 3 “shortness VX = of breath” x

4

Costanzo (Physiology, 4th ed.) – Figure 5.19 Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.19

Respiratory System Respiratory System

Oxygen Transport in Blood: Oxygen Transport in Blood:

O2 is carried in two forms in blood: dissolved and bound to hemoglobin O2 is carried in two forms in blood: dissolved and bound to hemoglobin

A) Dissolved O2: B) O2 bound to hemoglobin:

Accounts for 2% of total O2 content of blood Accounts for remaining 98% of total O2 content of blood

Henry’s Law: Recall: CX = PX x Solubility The concentration of dissolved Globular : O is proportional to the partial CX = Concentration of dissolved gas (mL X / 100 mL blood) 2 2  & 2  subunits each containing a moiety PX = Partial pressure of gas (mm Hg) pressure of O2 Solubility = Solubility of gas in blood (mL X / 100 mL / mm Hg) • 4 O2 / hemoglobin (ferrous state – Fe2+) Grossly insufficient to meet the bound to [O ] = P x Solubility demands of the tissues 2 O2 3+ Oxyhemoglobin = O2 bound to hemoglobin Shouldn’t O2 oxidize iron (ferric state – Fe )? [O2] = 100 x 0.003 At rest, tissues require 250 mL O2 / min Deoxyhemoglobin = No O2 present [O ] = 0.30 mL / 100 mL blood No – bonds prevent this… 2 O2 delivery = CO x [dissolved O2] = Iron in ferric (Fe3+) state BUT – if it does happen: O2 delivery = 5.0 L / min x 0.3 mL O2 / 100 mL • Does not bind O2 3+ 2+ O2 delivery = 15 mL O2 / min Methemoglobin reductase – reduces Fe to Fe

7 Respiratory System Respiratory System

Oxygen Transport in Blood: Oxygen Transport in Blood:

O2 is carried in two forms in blood: dissolved and bound to hemoglobin O2 is carried in two forms in blood: dissolved and bound to hemoglobin

B) O2 bound to hemoglobin: B) O2 bound to hemoglobin:

Hemoglobin structure demonstrates a developmental shift Amount of O2 bound to hemoglobin determined by the hemoglobin concentration and by the O2-binding capacity of that hemoglobin

O2-binding Capacity: PUTTING IT ALL TOGETHER:

The maximum amount of O2 that can be bound to hemoglobin per volume of blood O2 Content:

(Assumes hemoglobin 100% saturated) The actual amount of O2 per unit Adult hemoglobin volume of blood (hemoglobin F - HbF) ( - HbA) Under normal conditions: O2 = (O2-binding capacity x % saturation) + 22 22 • 1.0 g of hemoglobin can bind 1.34 mL 02 content dissolved O2 • [hemoglobin A] = 15 g / 100 mL

THUS O2 Delivery to tissues:

The actual amount of O2 delivered Hemoglobin F has a higher O2-binding = 15 g / 100 mL x 1.34 mL O2 / g HbA to the tissues affinity for O2 than hemoglobin A, capacity facilitating O transfer across 2 O -binding O2 the 2 = x O2 content of blood capacity = 20.1 mL O2 / 100 mL blood delivery

Respiratory System Respiratory System Reminder: Oxygen Transport in Blood: Each hemoglobin as the capacity to Oxygen Transport in Blood: bind 4 O2 molecules

O2 is carried in two forms in blood: dissolved and bound to hemoglobin O2 is carried in two forms in blood: dissolved and bound to hemoglobin

B) O2 bound to hemoglobin: B) O2 bound to hemoglobin:

The % saturation of hemoglobin is a function of the P of blood Under normal, resting conditions, arterial blood hemoglobin is 98% saturated O2 and only ~ 25% of O2 is unloaded at tissues Small drop in P O2 “wiggle room” equates to large increase in O 2 O unloaded to Points to Ponder: Sigmoid curve O2-hemoglobin Dissociation Curve: unloading 2 resting tissues Describe relationship between percent saturation 1) Hemoglobin is almost completely saturated of Hb and partial pressure of oxygen at a PO of 70 mm Hg P50 2 Point at which 50% Additional O2 ~ complete of Hb saturated THE PERCENT SATURATION OF unloaded to ADAPTIVE SIGNIFICANCE? HEME SITES DOES NOT INCREASE saturation exercising Change in value is LINEARLY AS PO INCREASES tissues an indicator for a 2 2) The unloading of O2 occurs on the steep change in affinity portion of the dissociation curve of Hb for O 2 Sub-unit : ( P50 =  affinity) Oxygenation of first heme group facilitates ADAPTIVE SIGNIFICANCE? oxygenation of other heme groups

Tissues Tissues Lungs (exercising) (at rest) Costanzo (Physiology, 4th ed.) – Figure 5.20 Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.20

Respiratory System 2,3-DPG = 2,3-diphosphoglycerate Respiratory System 2,3-DPG = 2,3-diphosphoglycerate Oxygen Transport in Blood: • Byproduct of RBC glycolysis Oxygen Transport in Blood: • Byproduct of RBC glycolysis • Binds to  chains of hemoglobin • Binds to  chains of hemoglobin

O2 is carried in two forms in blood: dissolved and bound to hemoglobin O2 is carried in two forms in blood: dissolved and bound to hemoglobin

B) O2 bound to hemoglobin: B) O2 bound to hemoglobin:

The O2-hemoglobin dissociation curve can shift to the right or the left The O2-hemoglobin dissociation curve can shift to the right or the left depending on local conditions in the blood depending on local conditions in the blood

Right shift = Decreased Hb affinity for O2 Left shift = Increased Hb affinity for O2

• Facilitates unloading of O2 • Hinders unloading of O2

A)  P A)  P CO2 Bohr CO2 B)  pH effect B)  pH ‘Adaptive Complex’ C)  temperature C)  temperature Increased P50 D)  2,3-DPG Decreased P50 D)  2,3-DPG

Influence Hb saturation by modifying Increased affinity of hemoglobin F () hemoglobin’s three-dimensional structure ? due to  2,3-DPG binding ?

Costanzo (Physiology, 4th ed.) – Figure 5.22 Costanzo (Physiology, 4th ed.) – Figure 5.22

8 Respiratory System Respiratory System

Pathophysiology: Transport in Blood:

Carbon monoxide poisoning is catastrophic CO2 is carried in three forms in blood: dissolved, bound to - for O2 delivery to tissues hemoglobin, and as (HCO3 )

A) Dissolved CO2:

1) CO decreases O2 bound to Hb Accounts for 5% of total CO2 content of blood Example: • CO binds to Hb with an affinity that is 250x greater than that of O 2 Henry’s Law: (forms )

CX = PX x Solubility

CX = Concentration of dissolved gas (mL X / 100 mL blood)

PX = Partial pressure of gas (mm Hg) Solubility = Solubility of gas in blood (mL X / 100 mL / mm Hg) Left shift “cherry ” [CO ] = P x Solubility 2 CO2 2) CO causes left shift of dissociation curve [CO2] = 40 x 0.07 (Arterial blood) • Heme groups not bound to CO have [CO ] = 2.80 mL / 100 mL blood an increased affinity for O2 2

Costanzo (Physiology, 4th ed.) – Figure 5.22

Respiratory System Respiratory System

Carbon Dioxide Transport in Blood: Carbon Dioxide Transport in Blood:

CO2 is carried in three forms in blood: dissolved, bound to CO2 is carried in three forms in blood: dissolved, bound to - - hemoglobin, and as bicarbonate (HCO3 ) hemoglobin, and as bicarbonate (HCO3 )

- B) CO2 bound to hemoglobin: C) CO2 converted to HCO3 : Plasma Accounts for 3% of total CO2 content of blood Accounts for remaining 92% of total CO2 content of blood

Diffuses into (contributes to Reminder: REVERSABLE RBCs CA the ) The binding of CO to hemoglobin 2 + - causes a conformational change CO2 + H20 H2CO3 H + HCO3 • CO2 binds to the terminal reducing the affinity of Hb amino groups on for O2 (right shift) 1) Carbon dioxide (CO ) combines with water (H O) to form carbonic (H CO ) IN TURN 2 2 2 3 • Reaction catalyzed by (CA) When less O2 is bound to Hb, + - 2) H2CO3 dissociates into hydrogen (H ) and bicarbonate ion (HCO3 ) = CO2 bound to hemoglobin the affinity of Hb for CO2 increases - (the ) • HCO3 released into plasma • H+ buffered in RBC by deoxyhemaglobin

Respiratory System Respiratory System

Carbon Dioxide Transport in Blood: Gas Transport - Review:

Tissue – Blood Interface: CO2 is carried in three forms in blood: dissolved, bound to - hemoglobin, and as bicarbonate (HCO3 )

- C) CO2 converted to HCO3 :

Accounts for remaining 92% of total CO2 content of blood

Chloride shift: To maintain charge balance in RBCs, - - a Cl is exchanged with a HCO3 as - the HCO3 leaves the cell • Band three protein functions as passive transporter

Costanzo (Physiology, 4th ed.) – Figure 5.24 Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.10

9 Respiratory System Respiratory System Note: Recall: The carries blood from Carbonic anhydrase also embedded Gas Transport: Ventilation / Perfusion Relationships: the right ventricle and returns blood in respiratory membrane to the left atrium Lung – Blood Interface: Pulmonary blood flow is regulated primarily by altering the resistance of the arterioles

Mechanisms of Regulation:

A) Partial pressure of alveolar O2 B) Vasoactive Chemicals

Reduces pulmonary Hypoxic  PA flow to poorly O2 vasoconstriction ventilated alveoli Vasoconstrict vessel

Thromboxane A2 Mechanism of Action: Source: Endothelium Action: Vasoconstriction • If PA falls below 70 mm Hg, voltage-gated O2 Prostacyclin 2+ Ca gates open in vascular smooth muscle, leading to contraction Source: Endothelium Action: Vasodilator

Can act locally (blocked alveolus) or globally (high altitude)

Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.10

Respiratory System Respiratory System

Ventilation / Perfusion Relationships: Control of Breathing:

The distribution of pulmonary blood flow with the lung is uneven Breathing is regulated so the lungs can maintain the due to the effects of gravity Pa and Pa within a normal range O2 CO2

Zone 1: Apex of lung Low blood Amphetamines / Caffeine: Gravitational Medullary Respiratory Centers: flow  activity Effect P > P > P alveoli arterial vein 1) Ventral Respiratory Group PRCs • Pulmonary capillaries compressed Lower vessel • Inspiratory center Oscillating rhythm of neuronal pressures by surrounding alveoli firing / quiescence • ‘Pacesetter’ (12 – 15 breaths / min) VRG

Zone 2: Middle of lung 2) Dorsal Respiratory Group Barbiturates / Opiates / : Medium blood • Expiratory center  respiratory center activity P > P > P flow arterial alveoli vein • Active during forced exhalation • Minimal compression; blood flow driven DRG by Partial vs. Palveoli difference Pontine Respiratory Centers: 1) Apneustic Center Intercostal Zone 3: Base of lung nerves High blood • Triggers prolonged inspiratory gasps flow Phrenic nerve Parterial > Pvein > Palveoli 2) Pneumotaxic Center • The greatest number of capillaries open; • Turns off inspiration Higher vessel high arterial and venous pressures pressures • Limits size of tidal volume

Randall et al. (Eckert Animal Physiology, 5th ed.) – Figure 13.26 Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.23

Respiratory System Respiratory System

Control of Breathing: Control of Breathing:

Hypercapnia: Increased PCO2 in arterial blood Chemical Factors: Depth and rate of breathing can be modified in response : Decreased PCO2 in arterial blood A) P to changing demands on the body CO2 • Most potent respiratory stimulant (maintained @  3 mm Hg)

Most important factors regulating • Mediated via central / peripheral ventilation are chemical Can cross blood-brain barrier

Can not cross blood-brain barrier

Peripheral  CO2 =  ventilation chemoreceptors (+)  CO2 =  ventilation • Carotid body (IX) • Aortic arch (X) (+) (CSF)

Ultimately leads to change in pH of cerebral spinal fluid

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24 Costanzo (Physiology, 4th ed.) – Figure 5.32

10 Respiratory System Respiratory System

Control of Breathing: Control of Breathing: Chemical Factors: Depth and rate of breathing can be modified in response A) P CO2 to changing demands on the body • Most potent respiratory stimulant (maintained @  3 mm Hg) Addition factors contribute to • Mediated via central / peripheral chemoreceptors ventilation regulation B) P Issue for individuals O2 with COPD: • Minor respiratory stimulant ( O2 =  ) Continual high levels of Hering-Breuer Reflex: • Mediated via peripheral chemoreceptors P in system results in CO2 • Stimulated by P < 60 mm Hg in arterial blood P taking over regulation When lung / airways stretched, O2 O2 inspiratory center inhibited IF RESPIRATORY DISTRESS Lung C) Arterial pH stretch OCCURS Peripheral receptors • Independent of changes in arterial PCO chemoreceptors 2 (+) • Compensatory mechanism for metabolic acidosis • Carotid body (IX) • Aortic arch (X) (+) Vagus (X) • Mediated by peripheral chemoreceptors (carotid body only) (CSF) (-) nerve Central chemoreceptors (+)

Function in anticipatory Joint / muscle response to exercise stretch receptors

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24

Respiratory System Respiratory System Laryngeal spasm Control of Breathing: (e.g., sarin gas) Control of Breathing:

Depth and rate of breathing can be modified in response Depth and rate of breathing can be modified in response to changing demands on the body to changing demands on the body Higher control centers; Addition factors contribute to Voluntary control over breathing Addition factors contribute to ventilation regulation ventilation regulation

Hypoventilation: Decrease breathing rate / depth Pain / emotional stimuli (+ / -) acting through hypothalamus Hyperventilation:

(+ / -) Increase breathing rate / depth

Lung Nasal cavity = Sneeze Lung Rate / depth of respiration stretch stretch exceeds demands for Lower conduction system = receptors receptors O2 delivery / CO2 removal (+) (+) (cessation of breathing) (+) Vagus (X) (+) Vagus (X) (CSF) (-) (CSF) (-) nerve nerve Central (-) Central (-) chemoreceptors chemoreceptors (+) Epiglottis closes; (+) Irritant thoracic cavity shrinks Irritant receptors receptors Joint / muscle Joint / muscle stretch stretch receptors Epiglottis opens; receptors air forcefully released (~ 100 mph) Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24 Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figure 22.24

Respiratory System

formaldehyde benzene vinyl chloride arsenic ammonia hydrogen

~ 3,400 deaths / year contributed to second- hand smoke…

Increase in lung cancer 1900 = Rare… rates correlated with rise 1956 = 29,000 deaths in smoking among adult 1978 = 105,000 deaths men and women 2004 = 160,440 deaths

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