1. Human Physiology Respiratory Requlation
by Talib F. Abbas

2. Regulation of Respiration
Spontaneous respiration is produced by rhythmic discharge of motor neurons that innervate the respiratory muscles. This discharge is totally dependent on nerve impulses from the brain; breathing stops if the spinal cord is transected above the origin of the phrenic nerves. The rhythmic discharges from the brain that produce spontaneous respiration are regulated by alterations in arterial PO2, PCO2, and H+ concentration, and this chemical control of breathing is supplemented by a number of non-chemical influences.

3. NEURAL CONTROL OF BREATHING
Two separate neural mechanisms regulate respiration
The voluntary system is located in the cerebral cortex and sends impulses to the respiratory motor neurons via the corticospinal tracts.
The automatic system is driven by a group of pacemaker cells in the medulla.
Impulses from these cells activate motor neurons in the cervical cord activate the diaphragm via the phrenic nerves, and those in the thoracic spinal cord activate the external intercostal muscles.

5. MEDULLARY SYSTEMS respiratory control pattern generator
pre-Bِtzinger complex (pre-BOTC) on either side of the medulla between the nucleus ambiguus and the lateral reticular nucleus.
Neurons in the pre-Botzinger complex discharge rhythmically in brain slice preparations in vitro, and if the slices become hypoxic, discharge changes to one associated with gasping. Addition of cadmium to the slices causes occasional sigh-like discharge patterns. There are NK1 receptors andμ-opioid receptors on these neurons, and, in vivo, substance P stimulates and opioids inhibit respiration.

6. MEDULLARY SYSTEMS
. However, it is now known that 5HT4 receptors are present in the pre-Botzinger complex and treatment with 5HT4 agonists blocks the inhibitory effect of opiates on respiration in experimental animals, without inhibiting their analgesic effect. In addition, dorsal and ventral groups of respiratory neurons are present in the medulla. However, lesions of these neurons do not abolish respiratory activity, and they apparently project to the pre-Botzinger pacemaker neurons.

7. Medullary involuntary control of Respiration
DRG, dorsal group of respiratory neurons; VRG, ventral group of respiratory neurons; NPBL, nucleus parabrachialis (pneumotaxic center); 4th vent, fourth ventricle;IC, inferior colliculus; CP, middle cerebellar peduncle. The roman numerals identify cranial nerves. IO, inferior olive;
LRN, lateral reticular nucleus; NA, nucleus ambiguus; XII, nucleus of
12th cranial nerve; 5SP, spinal nucleus of trigeminal nerve.

8. PONTINE & VAGAL INFLUENCES
pneumotaxic center
Kolliker–Fuse nuclei of the dorsolateral pons.
The normal function of the pneumotaxic center is unknown, but it may play a role in switching between inspiration and expiration. Stretching of the lungs during inspiration initiates impulses in afferent pulmonary vagal fibers. These impulses inhibit inspiratory discharge. This is why the depth of inspiration is increased after vagotomy and apneusis develops if the vagi are cut after damage to the pneumotaxic center.

9. Chemical Requlation of Respiration
A rise in the PCO2 or H+concentration of arterial blood or a drop in its PO2 increases the level of respiratory neuron activity in the medulla, and changes in the opposite direction have a slight inhibitory effect.
Chemoreceptors -> chemical control of respiration.
The chemical regulatory mechanisms adjust ventilation in such a way that the alveolar PCO2 is normally held constant.
, the effects of excess H+ in the blood are combated.
link between metabolism and ventilation is CO2, not O2.

10. Respiratory Control

11. CAROTID & AORTIC BODIES
There is a carotid body near the carotid bifurcation on each side, and there are usually two or more aortic bodies near the arch of the aorta. Each carotid and aortic body (glomus) contains islands of two types of cells, type I and type II cells, surrounded by fenestrated sinusoidal capillaries. The type I or glomus cells are closely associated with cuplike endings of the afferent nerves. The glomus cells resemble adrenal chromaffin cells and have dense-core granules containing catecholamines that are released upon exposure to hypoxia and cyanide. The cells are excited by hypoxia, and the principal transmitter appears to be dopamine, which excites the nerve endings by way of D2 receptors. The type II cells are glia-like, and each surrounds four to six type I cells.

13. CHEMORECEPTORS IN THE BRAIN STEM
medullary chemoreceptors.
They are separate from the dorsal and ventral respiratory neurons and are located on the ventral surface of the medulla.
Recent evidence indicates that additional chemoreceptors are located in the vicinity of the solitary tract nuclei, the locus ceruleus, and the hypothalamus.
The chemoreceptors monitor the H+concentration of cerebrospinal fluid (CSF), including the brain interstitial fluid. CO2 readily penetrates membranes, including the blood– brain barrier, whereas H+and HCO3–penetrate slowly. The CO2 that enters the brain and CSF is promptly hydrated. The H2CO3 dissociates, so that the local H+concentration rises.The H+concentration in brain interstitial fluid parallels the arterial PCO2.

14. EFFECTS OF EXERCISE
Of course, many cardiovascular and respiratory mechanisms must operate in an integrated fashion if the O2 needs of the active tissue are to be met and the extra CO2 and heat removed from the body during exercise. Circulatory changes increase muscle blood flow while maintaining adequate circulation in the rest of the body.
What causes intense ventilation during exercise?
The brain, on transmitting motor impulses to the exercising muscles, is believed to transmit at the same time collateral impulses into the brain stem to excite the respiratory center.

15. Interrelation Between Chemical Factors and Nervous
Interrelation Between Chemical Factors and Nervous: Factors in the Control of Respiration During Exercise
chemical factors play a significant role in bringing about the final adjustment of respiration required to keep the oxygen, carbon dioxide, and hydrogen ion concentrations of the body fluids as nearly normal as possible.
Possibility That the Neurogenic Factor for Control of Ventilation During Exercise Is a Learned Response

17. Thank you