Chemical Controls of Respiration

A.    Chemoreceptors (CO2, O2, H+)

1.    central chemoreceptors - located in the medulla
2.    peripheral chemoreceptors - large vessels of neck

B.    Carbon Dioxide Effects

1.    a powerful chemical regulator of breathing by increasing H+ (lowering pH)
    
a. hypercapnia            Carbon Dioxide increases -> 
                        Carbonic Acid increases ->
                        pH of CSF decreases (higher H+)- >
                        
DEPTH & RATE increase (hyperventilation)

b. hypocapnia - abnormally low Carbon Dioxide levels which can be produced by excessive hyperventilation; breathing into paper bag increases blood Carbon Dioxide levels

C.     Oxygen Effects

1.    aortic and carotid bodies - oxygen chemoreceptors

2.    slight Ox decrease - modulate Carb Diox receptors
3.    large Ox decrease - stimulate increase ventilation
4.    hypoxic drive - chronic elevation of Carb Diox (due to disease) causes Oxygen levels to have greater effect on regulation of breathing

D.    pH Effects (H+ ion)

1.    acidosis - acid buildup (H+) in blood, leads to increased RATE and DEPTH (lactic acid)

E.    Overview of Chemical Effects

 Chemical                             Breathing Effect

increased Carbon Dioxide (more H+)     increase
decreased Carbon Dioxide (less H+)     decrease

slight decrease in Oxygen             effect CO2 system
large decrease in Oxygen             increase ventilation

decreased pH (more H+)                 increase
increased pH (less H+)                 decrease

Neural Substrates of Breathing

A.    Medulla Respiratory Centers

Inspiratory Center (Dorsal Resp Group - rhythmic breathing) → phrenic nerve→ intercostal nerves→ diaphragm + external intercostals

Expiratory Center (Ventral Resp Group - forced expiration) → phrenic nerve → intercostal nerves → internal intercostals + abdominals (expiration)

1.    eupnea - normal resting breath rate (12/minute)
2.    drug overdose - causes suppression of Inspiratory Center

B.    Pons Respiratory Centers

1.    pneumotaxic center - slightly inhibits medulla, causes shorter, shallower, quicker breaths
2.    apneustic center - stimulates the medulla, causes longer, deeper, slower breaths

C.    Control of Breathing Rate & Depth

1.    breathing rate - stimulation/inhibition of medulla
2.    breathing depth - activation of inspiration muscles
3.    Hering-Breuer Reflex - stretch of visceral pleura that lungs have expanded (vagal nerve)

D.    Hypothalamic Control - emotion + pain to the medulla

E.    Cortex Controls (Voluntary Breathing) - can override medulla as during singing and talking

• Partial Pressures of O₂ and CO₂ in the body (normal, resting conditions):

• Alveoli
  • PO₂ = 100 mm Hg
  • PCO₂ = 40 mm Hg
• Alveolar capillaries
  • Entering the alveolar capillaries
    • PO₂ = 40 mm Hg (relatively low because this blood has just returned from the systemic circulation & has lost much of its oxygen)
    • PCO₂ = 45 mm Hg (relatively high because the blood returning from the systemic circulation has picked up carbon dioxide) 

• While in the alveolar capillaries, the diffusion of gasses occurs: oxygen diffuses from the alveoli into the blood & carbon dioxide from the blood into the alveoli.

• Leaving the alveolar capillaries
  • PO₂ = 100 mm Hg
  • PCO₂ = 40 mm Hg
• Blood leaving the alveolar capillaries returns to the left atrium & is pumped by the left ventricle into the systemic circulation. This blood travels through arteries & arterioles and into the systemic, or body, capillaries. As blood travels through arteries & arterioles, no gas exchange occurs.
• • Entering the systemic capillaries
    • PO₂ = 100 mm Hg
    • PCO₂ = 40 mm Hg
  • Body cells (resting conditions)
    • PO₂ = 40 mm Hg
    • PCO₂ = 45 mm Hg
• Because of the differences in partial pressures of oxygen & carbon dioxide in the systemic capillaries & the body cells, oxygen diffuses from the blood & into the cells, while carbon dioxide diffuses from the cells into the blood.
• • Leaving the systemic capillaries
    • PO₂ = 40 mm Hg
    • PCO₂ = 45 mm Hg
• Blood leaving the systemic capillaries returns to the heart (right atrium) via venules & veins (and no gas exchange occurs while blood is in venules & veins). This blood is then pumped to the lungs (and the alveolar capillaries) by the right ventricle.

Cells, cytoplasm, and organelles:

• Cytoplasm consists of a gelatinous solution and contains microtubules (which serve as a cell's cytoskeleton) and organelles

• Cells also contain a nucleus within which is found DNA (deoxyribonucleic acid) in the form of chromosomes plus nucleoli (within which ribosomes are formed)

• Organelles include:

1. Endoplasmic reticulum : 2 forms: smooth and rough; the surface of rough ER is coated with ribosomes; the surface of smooth ER is not , Functions include: mechanical support, synthesis (especially proteins by rough ER), and transport
2. Golgi complex consists of a series of flattened sacs (or cisternae) functions include: synthesis (of substances likes phospholipids), packaging of materials for transport (in vesicles), and production of lysosomes
3. Lysosome : membrane-enclosed spheres that contain powerful digestive enzymes , functions include destruction of damaged cells & digestion of phagocytosed materials
4.  Mitochondria : have double-membrane: outer membrane & highly convoluted inner membrane
   1. inner membrane has folds or shelf-like structures called cristae that contain elementary particles; these particles contain enzymes important in ATP production
   2. primary function is production of adenosine triphosphate (ATP)
5. Ribosome-:composed of rRNA (ribosomal RNA) & protein , primary function is to produce proteins
6. Centrioles :paired cylindrical structures located near the nucleas , play an important role in cell division
7. Flagella & cilia - hair-like projections from some human cells
   1. cilia are relatively short & numerous (e.g., those lining trachea)
   2. a flagellum is relatively long and there's typically just one (e.g., sperm)

• • Villi  Projections of cell membrane that serve to increase surface area of a cell (which is important, for example, for cells that line the intestine)

1.Rhythmicity ( Chronotropism ) :  means the ability of heart to beat regularly ( due to repetitive and stable depolarization and repolarization )  . Rhythmicity of heart is a myogenic in origin , because cardiac muscles are automatically excited muscles and does not depend on the nervous stimulus to initiate excitation and then contraction . The role of nerves is limited to the regulation of the heart rate and not to initiate the beat.

There are many evidences that approve the myogenic and not neurogenic origin of the rhythmicity of cardiac muscle . For example :
-  transplanted heart continues to beat regularly without any nerve supply.
-  Embryologically the heart starts to beat before reaching any nerves to them.
-  Some drugs that paralyze the nerves ( such as cocaine ) do not stop the heart in given doses.

Spontaneous rhythmicity of the cardiac muscle due to the existence of excitatory - conductive system , which is composed of self- exciting non-contractile cardiac muscle cells . The SA node of the mentioned system excites in a rate , that is the most rapid among the other components of the system ( 110 beats /minute ) , which makes it the controller or ( the pacemaker ) of the cardiac rhythm of the entire heart.

Mechanism , responsible for self- excitation in the SA node and the excitatory conductive system  is due to the following properties of the cell membrane of theses cells :
1- Non-gated sodium channels
2- Decreased permeability to potassium
3- existence of slow and fast calcium channels.

These properties enable the cations ( sodium through the none-gated sodium voltage channels , calcium through calcium slow channels) to enter the cell and depolarize the cell membrane without need for external stimulus.

The resting membrane potential of non-contractile cardiac cell is -55 - -60 millivolts ( less than that of excitable nerve cells (-70) ) . 

The threshold is also less negative than that of nerve cells ( -40 millivolts ).

The decreased permeability to potassium from its side decrease the eflux  of potassium during the repolarization phase of the pacemaker potential . All of these factors give the pacemaker potential its characteristic shape

Repeating of the pacemaker potential between the action potentials of contractile muscle cells is the cause of spontaneous rhythmicity of cardiac muscle cells.

Factors , affecting the rhythmicity of the cardiac muscle :

I. Factors that increase the rate ( positive chronotropic factors) :
1. sympathetic stimulation : as its neurotransmitter norepinephrine increases the membrane permeability to sodium and calcium.
2. moderate warming : moderate warming increases temperature by 10 beats for each 1 Fahrenheit degree increase in body temperature, this due to decrease in permeability to potassium ions in pacemaker membrane by moderate increase in temperature.
3. Catecholaminic drugs have positive chronotropic effect.
4. Thyroid hormones : have positive chronotropic effect , due to the fact that these drugs increase the sensitivity of adrenergic receptors to adrenaline and noreadrenaline .
5. mild hypoxia.
6. mild alkalemia : mild alkalemia decreases the negativity of the resting potential.
7. hypocalcemia.
8. mild hypokalemia

II. Factors that decrease rhythmicity ( negative chronotropic):

1.Vagal stimulation : the basal level of vagal stimulation inhibits the sinus rhythm and decrease it from 110-75 beats/ minute. This effect due to increasing the permeability of the cardiac muscle cell to potassium , which causes rapid potassium eflux , which increases the negativity inside the cardiac cells (hyperpolarization ).
2. moderate cooling
3. severe warming : due to cardiac damage , as a result of intercellular protein denaturation. Excessive cooling on the other hand decrease metabolism and stops rhythmicity.
4. Cholenergic drugs ( such as methacholine , pilocarpine..etc) have negative chronotropic effect.
5. Digitalis : these drugs causes hyperpolarization . This effect is similar to that of vagal stimulation.
6. Hypercapnia ( excessive CO2 production )
7. Acidemia.
8. hyper- and hyponatremia .
9. hyperkalemia
10. hypercalcemia
11. Typhoid or diphteria toxins.

 Acute Obstructive Disorders
 1.    Heimlich maneuver
 2.    Bypass, tracheostomy w/catheter to suck up secretion