Clase 42 Fisiología Respiratoria - Regulación de la Respiración (IG:@doctor.paiva)

Regulation of Respiration

Overview of Respiratory Regulation

• The class focuses on the regulation of respiration, including generalities, respiratory centers, and chemical control mechanisms.

• Respiration is a mixed process (voluntary and involuntary) aimed at maintaining optimal levels of oxygen, carbon dioxide, and hydrogen in tissues.

Nervous System Control

• The nervous system regulates respiration through the cerebral cortex (voluntary control) and the brainstem (involuntary control). The brainstem includes the pons and medulla oblongata.

• Central chemoreceptors in the medulla respond to changes in carbon dioxide pressure and hydrogen ion concentration; peripheral chemoreceptors are located in carotid bodies and aortic bodies.

Functionality of Chemoreceptors

• Peripheral chemoreceptors primarily detect decreases in oxygen levels but also respond to increases in carbon dioxide and hydrogen ions.

• The respiratory center integrates signals from various body parts including the heart, lungs, afferent nerves, cerebellum, and brainstem for effective breathing regulation.

Structure of Respiratory Centers

• The respiratory center consists of neuronal groups located bilaterally in both the pons and medulla oblongata. This includes pneumotaxic centers that regulate breathing patterns.

• Dorsal group neurons activate inspiration by controlling respiratory rhythm; they receive sensory information from cranial nerves IX (glossopharyngeal) and X (vagus).

Mechanism of Inspiration

• Dorsal group neurons send signals to diaphragm muscles via phrenic nerve to initiate contraction for inhalation; this occurs through progressive ramp-like discharges lasting about two seconds.

• Interruption of these signals leads to passive expiration due to elastic recoil from lungs and abdominal viscera compressing thoracic cavity.

Role of Pre-Bötzinger Complex

• A complex known as pre-Bötzinger functions as a pacemaker for rhythmic breathing throughout life; it sends continuous action potentials regardless of other brain activity interruptions.

Inhibitory Signals from Pneumotaxic Center

Respiratory Control Mechanisms

Intense Respiratory Signals

• The intense signal from the toxic center leads to premature disconnection of the inspiratory ramp, reducing normal inspiration duration from two seconds to half a second.

• This results in shorter inspiration and expiration times, increasing respiratory frequency to 30-40 breaths per minute.

• Conversely, weak signals delay disconnection after five seconds, leading to longer inspiration and decreased respiratory frequency.

Central and Ventral Groups

• The central group located in the medulla oblongata contributes additional respiratory impulses but remains inactive during normal breathing.

• It activates only under overstimulation, such as during intense exercise, sending signals to enhance inspiration.

• The ventral group also boosts inspiration by directly stimulating abdominal and intercostal muscles when high ventilation is required.

Reflexes in Breathing Regulation

• Stretch receptors in bronchi activate when lung volume exceeds 1500 ml, sending inhibitory signals via the vagus nerve to prevent excessive inflation.

• This reflex acts as a protective mechanism against over-inflation of the lungs by interrupting inspiratory signals.

Chemical Control of Respiration

• The primary goal of respiration is maintaining adequate levels of oxygen, carbon dioxide, and hydrogen ions in tissues; chemoreceptors detect changes in these substances.

• Central chemoreceptors are sensitive to hydrogen ion concentration changes within the medulla oblongata's chemosensitive zone.

Role of Carbon Dioxide

• Hydrogen ions stimulate this area directly; however, they struggle to cross the blood-brain barrier compared to carbon dioxide.

• Carbon dioxide easily crosses this barrier due to its lipophilicity and indirectly increases hydrogen ion concentration through reactions with water forming carbonic acid.

Changes in Carbon Dioxide Partial Pressure and Respiratory Regulation

Role of Carbon Dioxide in Respiratory Control

• Changes in the partial pressure of carbon dioxide significantly increase ventilation, while changes in blood pH have a much lesser effect.

• The respiratory center's response to elevated carbon dioxide is strong initially but diminishes over 1 to 2 days, reducing its excitatory capacity by up to five times.

• Chronic increases in carbon dioxide lead to a weaker stimulation of the respiratory center over time.

Mechanisms of Adaptation

• Adaptation occurs through two main mechanisms: bicarbonate diffusion across the blood-brain barrier and renal reabsorption of bicarbonate.

• Bicarbonate from the blood diffuses into the cerebrospinal fluid, decreasing hydrogen ion concentration and normalizing pH levels.

• Renal reabsorption of bicarbonate raises blood bicarbonate levels, further stabilizing pH despite increased carbon dioxide.

Implications for Chronic Respiratory Acidosis

• In chronic respiratory acidosis (e.g., COPD), patients exhibit elevated carbon dioxide levels with normal pH due to increased bicarbonate concentrations.

Peripheral Chemoreceptors and Their Function

Sensitivity to Oxygen Levels

• Peripheral chemoreceptors primarily respond to oxygen changes, with secondary sensitivity to carbon dioxide and hydrogen ions; they are located mainly in carotid bodies and aortic bodies.

• Signals from carotid bodies reach the respiratory center via the glossopharyngeal nerve, while signals from aortic bodies travel through the vagus nerve.

Activation Threshold

• Peripheral receptors detect arterial oxygen decreases; they activate significantly when oxygen drops below 70 mmHg but become highly sensitive below 60 mmHg.

Physiological Mechanism Behind Chemoreceptor Activation

Cellular Response Mechanisms

• Activation involves inhibition of potassium channels in glomus cells within carotid bodies; three theories explain this process:

• Theory One: Decreased oxygen leads to increased cyclic AMP that inhibits potassium channels.

• Theory Two: A unique transmembrane protein containing iron captures oxygen; low oxygen levels deactivate potassium channels indirectly.

• Theory Three: Reduced oxygen inhibits mitochondrial oxidase activity affecting potassium channel function.

Importance of Potassium Channel Inhibition

Effect of Hypoxia on Ventilation

Mechanism of Action in Response to Potassium Concentrations

• An increase in potassium concentrations leads to depolarization, resulting in an action potential that opens voltage-dependent calcium channels.

• The influx of calcium triggers the release of neurotransmitters, notably acetylcholine and dopamine, with ATP recently identified as a key excitatory neurotransmitter.

Neurotransmitter Interaction and Respiratory Stimulation

• Released neurotransmitters activate receptors that open sodium channels, causing depolarization and sending stimuli to the dorsal respiratory center.

• In hypoxic conditions where oxygen partial pressure exceeds 60 mmHg, carbon dioxide and hydrogen ion concentrations primarily regulate ventilation in healthy individuals.

Factors Influencing Respiratory Control

• Voluntary control from the cortex allows for conscious inspiration and expiration; airway irritation can trigger reflex actions like sneezing or coughing.

• Pulmonary stretch receptors are activated when pulmonary capillaries distend, stimulating the respiratory center during conditions such as pulmonary edema or congestive heart failure.

Impact of Edema on Respiratory Function

• Cerebral edema can depress the respiratory center following traumatic brain injury due to swelling affecting cerebral arteries and blood flow.

• Anesthetics can also depress the respiratory center; overdoses of anesthetics or narcotics are common causes of respiratory depression and arrest.

Overview of Respiratory Centers' Functions

• The dorsal group receives information from chemoreceptors and stretch receptors, regulating rhythm and inspiration by signaling diaphragm and external intercostal muscles.

• Overstimulation during exercise activates central groups enhancing inspiration while also signaling accessory muscles for increased effort.

Regulation by Pneumotaxic Center