Internal Respiration & Pleural Effusions (LEC#8)

• Lecture 8 covers internal respiration and control of ventilation.

Pleural Effusions

• Characterized by fluid accumulation in the pleural space.
• Classified as either transudate or exudate.
• Fluid accumulates within the pleural space.
• Transudates result from increased pulmonary capillary hydrostatic pressure (Pcap), which is the blood pressure in the pulmonary capillaries serving the alveoli.
  • Transudates are watery with less protein/fewer cells, moving easily across the capillary membrane.
• Occurs due to an increase in pulmonary capillary hydrostatic pressure.
• Decreased capillary oncotic pressure, a pressure from plasma proteins, can also cause transudate fluid accumulation – a pressure created by albumins and other plasma proteins in the capillary
• Exudates are fluids accumulated because of inflammation (ex. pneumonia, cancer, pulmonary embolism) or when the pleural blood vessels have increased permeability
  • Exudates are protein and cell rich, exuding from capillaries and collecting in the pleural cavity.
• Patients may experience dyspnea, pleuritic chest pain, and cough.
• Auscultation may reveal reduced respiratory sounds, rales, or dull breathing sounds.

Lung Volumes and Capacities

• Tidal Volume: 500 mL
• Inspiratory Reserve Volume: 3100 mL (1900 mL)
• Expiratory Reserve Volume: 1200 mL (700 mL)
• Residual Volume: 1200 mL (1100 mL)
• Inspiratory Capacity: 3600 mL (2400 mL)
• Vital Capacity: 4800 mL (3100 mL)
• Total Lung Capacity: 6000 mL (4200 mL)
• Functional Residual Capacity: 2400 mL (1800 mL)
• Inspiratory capacity represents the maximum volume of air that can be inspired after a normal expiration.

Pulmonary Ventilation Factors

• Two main physical factors affecting pulmonary ventilation are airway resistance and alveolar surface tension.
• Airway resistance is greatest in mid-sized bronchi.
• Alveolar surface tension is a factor of lung compliance or distensibility/stretch of lung tissue.
• Surfactant helps reduce alveolar surface tension.
• Compliance can be attenuated by factors.
• Surfactant is produced by the body.
• The relationship between reduced alveolar surface tension and the pulmonary capillaries should be taken into account.
• Secretion of surfactant by type II alveolar cells causes a decrease in lung surface tension, thus decreasing the work required to breathe.

Lung Structures

• Alveolar sacs are found in the respiratory zone of the airways.
• Intrapleural pressure is always negative with ventilation.
• Abdominal and internal intercostal muscles are contracted to forcefully blow out the candles on a birthday cake.

Elastic Recoil

• Elasticity is the tendency of an object to return to its original shape after being deformed.
• Elasticity generates a recoil force.
• Healthy lungs recoil inward, pulling away from the chest wall or thorax.
• The thorax tends to recoil outward, pulling away from the lung, creating two opposite recoil forces.
• Two opposite recoil forces move in opposing directions, generating a suction-like effect. It is measured as a negative atmospheric pressure in the space between the lung and chest wall.
• Properties of elasticity include contributions from elastic and collagen fibers in lung parenchyma, and forces generated by surface tension of the liquid film around the alveoli.

Lung Compliance and Elasticity

• Compliance represents the change in volume of a structure in relation to the change in pressure across the structure, expressed as Compliance = ΔV/ΔP.
• Pulmonary pathologies can change compliance and elasticity
• COPD (emphysema) involves damage to the alveolar walls and respiratory membranes.
  • Breakdown of elastic tissues results in loss of elastin.
• Interstitial lung diseases causing inflammation and scarring lead to pulmonary fibrosis. Compliance
• Compliance is how much effort is required to stretch the lungs and chest wall.
  • High compliance means lungs and chest wall easily expand.
  • Low compliance means the lungs and chest wall resist expansion.
• Pulmonary compliance is related to elasticity and surface tension.
• Surface tension modulates the compliance and elasticity of the lungs.
• The lungs are very compliant, but have the right amount of elasticity to recoil back.
• The compliance triangle involves the three factors that affect compliance which are surface tension, elasticity of the chest wall, and elasticity of the lungs.
• A patient with pulmonary edema, a condition causing lung tissue to fill with fluid, must generate a bigger pressure gradient between the atmosphere and the alveoli to fill the same volume of lung, decreasing lung compliance.

Pulmonary Ventilation and Gas Laws

• Boyle's law describes the relationship between pressure and volume of a gas.
• Gases always fill the container they are in.
  • Pressure varies inversely with volume if amount of gas is the same and container size is reduced.
• Mathematically: P1V1 = P2V2

Dalton's Law

• States that the total pressure exerted by a mixture of gases is equal to the sum of the pressures exerted independently by each gas.
• Partial pressure is the pressure exerted by each gas in a mixture, directly proportional to its percentage in the mixture.

Henry's Law

• Describes gas mixtures in contact with liquids.
• Each gas dissolves in the liquid in proportion to its partial pressure
• At equilibrium, partial pressures in the two phases will be equal
• Amount of each gas that will dissolve depends on partial pressure in contact with liquid, solubility, and temperature.
• Partial pressure of the gas in contact with the liquid.
• Solubility: CO₂ is 20× more soluble in water than O2, and little N2 will dissolve.
• Temperature: solubility decreases as liquid temperature rises.
• Atmosphere mainly consists of nitrogen and oxygen.
• Alveoli contain more carbon dioxide.

External and Internal Respiration

• External respiration involves pulmonary gas exchange between alveoli and pulmonary capillaries.
• Internal respiration involves capillary gas exchange between blood capillaries and body tissues.
• External respiration (pulmonary gas exchange) involves the exchange of O2 and CO2 across respiratory membranes.
• Influenced by partial pressure gradients and gas solubilities, thickness and surface area of respiratory membrane, and ventilation-perfusion coupling (matching of alveolar ventilation with pulmonary blood perfusion)
• Oxygen saturation is important in V/Q coupling.
• Oxygen binds to hemoglobin in a dependent manner, and a variety of factors can influence O2-Hb binding.

Factors Influencing O2-Hb Association

• PO2, temperature, blood pH, PCO2, and concentration of BPG
• An increase in hydrogen ions, CO2, temperature and BPG will shift the oxygen hemoglobin saturation curve to the right
• Po₂ heavily influences binding and release of O2 with hemoglobin
  • The amount of O2 in the blood is critical to influence hemoglobin saturation.
• Temperature influences oxygen transport such that oxygen occupies less hemoglobin at higher temperatures, and oxygen unloading is enhanced at higher temperature.
• Increased CO2 pressure enhances oxygen unloading
• Increased hydrogen ion concentration (pH) enhances oxygen unloading
• As cells metabolize glucose, they use O2 causing increases in PCO2 and H+ in capillary blood
• Elevated PCO2 and pH occurs mostly in capillaries of the systemic circuit.
• Cells in systemic circuit metabolize glucose, use O2, and release CO2.
• Resulting in increased carbon dioxide pressure and increased hydrogen ion concentration that weakens the Hb-O2 bond.
• 2,3-bisphosphoglycerate (diphosphoglycerate) is produced by RBCs during glycolysis. BPG levels rise when O2 levels are low.
• Bohr effect is when declining blood pH (acidosis) and increasing Pco₂ causes Hb-O2 bond to weaken.
• O2 unloading occurs where needed most.
• Heat production in active tissue directly/indirectly decreases Hb affinity for O2, allowing increased O2 unloading to active tissues.

Carbon Dioxide Transport

• Carbon dioxide is transported in the blood in three forms:
  • Dissolved in plasma (7-10%)
  • Chemically bound to Hb (approx. 20%), with CO2 bound to the globin part of hemoglobin forming carbaminohemoglobin (CO2 + Hb ↔ HbCO2)
  • As bicarbonate ions in plasma (70%)
• At the lungs, CO2 transport is reversed in pulmonary capillaries
  • HCO3 moves into RBCs, while Cl¯ moves out of RBCs back into plasma.
  • HCO3 and H+ forms to H2CO3, H2CO3 splits by carbonic anhydrase into CO2 and water, and finally CO2 diffuses into alveoli.
• The greatest percentage of CO2 is transported in the blood as bicarbonate ions.
• Increased H+ concentration would make the oxygen-hemoglobin dissociation curve shift right.

Control of Ventilation

• Respiratory rhythms- regulated by higher brain centers (medulla oblongata and pons)
• Chemoreceptors
• Other reflexes
• Pons: Interacts with the medullary respiratory centers to smooth the respiratory pattern.
• Medulla has 2 areas for center clusters which include Ventral respiratory group (VRG) which contains rhythm generators whose output drives respiration and Dorsal respiratory group (DRG) which integrates peripheral sensory input and modifies the rhythms generated by the VRG.

Neural Controls

• Neural controls involve neurons in the reticular formation of the medulla and pons.
• Medullary respiratory centers include clustered neurons in two areas of the medulla:
  • Ventral Respiratory Group (VRG)
  • Dorsal Respiratory Group (DRG)
• Pontine respiratory centers interact with the medullary respiratory centers to smooth the respiratory pattern.
• The Dorsal Respiratory Group (DRG) integrates peripheral sensory input and modifies the rhythms generated by the VRG.

Ventral Respiratory Group (VRG)

• Rhythm-generating and integrative center
• Consists of network of neurons in brain stem that extends from spinal cord to pons-medulla junction
• Sets eupnea, which is normal respiratory rate and rhythm (12-15 breaths/minute)
• VRGs inspiratory neurons excite inspiratory muscles via phrenic (diaphragm) and intercostal nerves (external intercostals).
• Expiratory neurons inhibit inspiratory neurons.

Dorsal Respiratory Group (DRG)

• Network or neurons (pre-Botzinger complex) located near root of cranial nerve IX (9th cranial nerve is glossopharyngeal nerve)
• Group integrates input from peripheral stretch, chemoreceptors and chemo receptors, then sends info to VRG neurons
• Important for generating breathing rhythm

Forceful Respiration

• During forceful inspiration, DRG expiratory neurons signal to intercostals, diaphragm, and VRG.
• Also during forceful inspiration, VRG expiratory neurons via DRG signal accessory muscles of inspiration.
• During forceful expiration, DRG inspiratory neurons and VRG inspiratory neurons become inactive.
• Furthermore, VRG expiratory neurons signal to accessory muscles of expiration.

Pontine Respiratory Centers

• Neurons in this center influence and modify activity of VRG.
• Act to smooth out transition between inspiration and expiration and vice versa.
• Transmit impulses to VRG that modify and fine-tune breathing rhythms during vocalization, sleep, and exercise. Lesions in this area of the brain lead to apneustic breathing

Respiratory Rhythm

• The basic respiratory rhythm is generated in the pre-Bötzinger complex in the ventral respiratory group (VRG).
• Depth: The rate will be determined by the firing rate of the respiratory center in stimulating the respiratory muscles.
  • The greater the stimulation, the greater the number of motor units excited, increasing depth of inspiration (I.e., motor unit recruitment)
• Rate: Is determined by how long the center is active
• Rate and Depth Both are modified by changing body demands

Factors Affecting Depth and Rate

Respiratory centers are affected by:

• Chemical factors
• Influence of higher brain centers
• Pulmonary irritant reflexes
• Inflation reflex
• Chemical factors are the most important factor for depth and rate of inspiration.
• Changing levels of PC02, P02, and pH are the most important chemicals.
  • Levels of these chemicals are sensed by the central chemoreceptors (located throughout, found in aortic arch and carotid arteries and by the peripheral the chemoreceptors (located throughout brain stem)

Role of Carbon Dioxide

• Most potent and most closely controlled variable.
• The influence of PC02, Is the most potent and most closely controlled variable
• If blood PC02 levels rise (hypercapnia), CO2 accumulates in brain and joins with water to become carbonic acid
• Increased H+ stimulates central chemoreceptors of brain stem, which synapse with respiratory regulatory centers
• Respiratory centers increase depth and rate of breathing, which act to lower blood PC02, and pH rises to normal levels
• Peripheral chemoreceptors in aortic and carotid bodies sense arterial O2 levels.
• Declining Po₂ normally has only slight effect on ventilation because of huge O₂ reservoir bound to Hb.
• Requires substantial drop in arterial Po₂(below 60 mm Hg) to stimulate increased ventilation.
• When excited, chemoreceptors cause respiratory centers to increase ventilation.
• Arterial pH can also modify respiratory rate and rhythm even if CO2 and O2 levels are normal, this is mediated by peripheral chemoreceptors
• Decreased pH may reflect CO2 retention, accumulation of lactic acid, or excess ketone bodies - The respiratory system controls attempt to raise pH by increasing respiratory rate and depth
• Summary of chemical factors:
  • Rising CO2 levels are the most powerful respiratory stimulant, normally, blood P02 affects breathing only indirectly by influencing peripheral chemoreceptor sensitivity to changes in PC02, When arterial P02 falls below 60 mm Hg, it becomes major stimulus for respiration - (via peripheral chemoreceptors), and changes in arterial pH resulting from CO2 retention or metabolic factors act indirectly through peripheral chemoreceptors.
• Influence of higher brain centers which include Hypothalamic controls and cortical controls.
• Hypothalamic controls are through limbic system, it has modify rate and depth of respiration; e.g., breath holding that occurs in anger or gasping with pain Change in body temperature changes rate
• Cortical controls. direct signals from cerebral motor cortex that bypass medullary controls voluntary breath holding at least until brain stem reinstates breathing when blood CO2 and H⁺ becomes critical Receptors in bronchioles respond to irritants such as dust, accumulated mucus, or noxious fumes Receptors communicate with respiratory centers via vagal nerve afferents Promote reflexive constriction of air passages

Inflation Reflex

• Hering-Breuer Reflex (inflation reflex)
• Stretch receptors in pleurae and airways are stimulated by lung inflation
  • Send inhibitory signals to medullary respiratory centers to end inhalation and allow expiration

  • May act as protective response more than as a normal regulatory mechanism