Physiology #18: Resp physiology 4

• CO2 is produced during cell metabolism
• CO2 diffuses 20x more easily than O2- so readily crosses cell membranes and physical barriers

• #1 bicarbonate ions in the plasma
• #2 bound to Hb
• #3 dissolved in Plasma

• dissolved in plasma: amount of CO2 dissolved in plasma is proportional to PaCO2 and its solubility coefficient. CO2 is 22x more soluble than O2
• combined with plasma proteins: ie with albumin or glycoproteins
•    -combine to form "carbamino compounds"
•    -are relatively small number of aa groups on proteins that are able to do this
•    -accounts for small fraction of transport
•    -combined with water in plasma to form H2CO3 (carbonic acid)

• Overall these 3 mechanisms (dissolved in plasma, combined with plasma proteins, combined with water in plasma to make carbonic acid) only account for ~10% of total CO2 transport in the body
• this is not adequate for transporting the huge quantity that is produced from metabolism, so other mechanisms are required

Reactions in RBCs are the most important for CO2 transport

• CO2 readily diffuses from plasma onto RBC's
• RBC's have many more terminal protein groups that can react with CO2 to form carbamino compounds: has more buffering capacity
• inside RBC's the hydration reaction with water is enhanced by carbonic anhydrase enzyme - once formed H2CO3 quickly dissociates into H+ and HCO3- ions inside the RBC
• CO₂ + H₂O <->H₂CO₃ <-> HCO₃^- + H₊
• There is a high [enzyme] in RBC's so they can convert 90% of CO2 which keeps PCO2 low so CO2 can always diffuse into RBC

• As more and more HCO3- is formed from the hydration of CO2, it diffuses out of the RBC's along its diffusion gradient into the plasma
• "chloride shift" --> Cl- diffuses into the RBC's to maintain electrical neutrality (Cl- draws water into cell)
• water also diffuses into cells so RBC's in venous blood are slightly larger than those found in arterial blood
• MOST CO2 THAT IS PRODUCED IS TRANSPORTED AS HCO3-

• when venous blood reaches the capillaries in the lungs, CO2 that was dissolved in solution (plasma) diffuses out of the blood along its gradient into the alveoli
• ventilation of alveoli keeps CO2 levels low, maintaining the gradient for diffusion of CO2

• Loss of CO2 in the plasma pulls CO2 out of the RBC
• reactions in RBC now reverse: CO2 comes off proteins, dehydration of H2CO3 forms CO2 and water
• Oxygenation (increase O2) of Hb helps reverse these reactions and enhances the release of CO2 into the alveoli for elimination form the body through ventilation

system is designed to maintain arterial CO2 levels around 40mmHg (35-45mmHg)

• If CO2 is increased it becomes a stressor on the body (stimulates a sympathetic response that increases heart rate, blood pressure, ventilation)
• -"fight or flight" reflex to deliver more blood (and therefore more CO2) to the lungs

increase BP, increase blood flow and cardiac output, want blood to get to lungs to get rid of CO2

• 1. CO2 in the blood (artery, vein) with blood gas analyzer  (aspire blood sample and put in gas analyzer)
• 2. expired air (end-tidal) with a capnograph (measure on intubated animal)

• 1. Sensors (peripheral and central) that gather info about CO2, O2, and pH, movement etc...
• 2. central controller in the brain to coordinate info and determine what actions to take
• 3. effectors (muscles) to induce a response and to ventilate the animal

to maintain normal levels of O2 (100mmHg) and CO2 (40mmHg) in arterial blood

• peripheral chemo R's
• central chemo R's
• lung stretch R's
• muscle and joint R's

all feed into DRG inspiratory center

• peripheral chemo R's are sensitive to CO2, O2 and H+
• while central chemo R's are sensitive to H+ only

• located near ventral surface of medulla
• sensitive to changes in H+ levels in the interstitial fluid of the brain (but the BBB is not permeable to H+ ions)
• CO2 is freely diffusible and indirectly exerts a stimulating effect on respiration altering H+ levels in the brain

• ventilation (increased tidal V and respiratory rate) is stimulated by increases in PaCO2-
• CO2 combines with water in the brain and there is an increase in H+ so central chemoR's detect this
• central chemo R's are excitatory to the inspiratory center (DRG) and cause increases in tidal V and resp rate

• located in areas that are highly diffuse with arterial (oxygenated) blood: aortic bodies (sensors) along arch of the aorta, carotid bodies at bifurcation of carotid arteries
• respond to changes in H+, PaCO2, and PaO2 - responsive to partial pressures of O2 and CO2, not the amount/content (ie active at high altitude but not if patient is anemic)

• low O2 or High CO2
• * O2 and CO2 are not dependant of content they are dependant of partial pressure

• increase PaCO2 (central chemo R's)
• low O2 or high CO2 (peripheral chemo R's)

• stimulate ventilation through:
• vagus nerve (aortic bodies)
• glossopharyngeal nerve (carotid bodies)

• Peripheral chemo R's ~30% in response to changes in CO2
• Central chemo R's ~70%

• respond to changes in arterial CO2 levels
• when arterial O2 levels decrease these R's become very active and stimulate ventilation as a last ditch attempt to bring O2 into the body
• happens when PO2 is less than 50mmHg

• Dorsal Respiratory Group (DRG) in the medulla
• ventral respiratory group (VRG) in the medulla
• Pneumotaxic center in the rostral pons
• Apneustic center in caudal pons

• collections of neurons that are located in the brainstem - medulla and pons
• generates the rhythmic, periodic pattern of regular breathing
• allows for unconscious adjustments to breathing pattern with exercise, disease, and swallowing etc...
• cortex also plays a role (ie conscious changes)

• Generates the basic rhythm of breathing
• receives input from the glossopharyngeal and vagal nerves
•    -mechanoR's in pleura (respond to stretch)
•    -peripheral chemo R's (respons to O2, CO2 levels)
• output is relayed via the phrenic nerve to the diaphragm  -stimulates contraction to initiate inspiration
• generates tidal ie normal breathing

• (not active in most cases, only when need active component)
• expiration is normally a process due to elastic recoil of the lungs and chest wall
• VRG is not usually active with normal respiration
• primarily responsible for expiration when there needs to be an active component (ie exercise)

• inhibits inspiration by regulating inspiratory rate and V
• involved in "fine tuning" of respiratory rhythm since normal rhythm can still exist in absence of this center

• least understood of the four areas, no consensus as to its role in respiration
• believed to be involved in deep breathing (apneustic breathing ie hold breath for a while then take exaggerated breath)
• can be seen in certain situations: ketamine based anesthesia, brain injury or tumors (high ICP)

pale pink, have O2 but no RBC

• O2
• perfusion
• RBC's

• diaphragm
• intercostal muscles
• abdominal muscles
• accessory muscles

central controller ensures that they all function in a coordinated manner