Internal Environment- Oxygen & Carbon Dioxide

Chapter 13: 466-486

ICQ #1: Under which of the following conditions would hemoglobin release more O2 to the tissues than normal?

• Metabolic alkalosis

• In the presence of high levels of carbon monoxide → bad news

• Low tissue pCO2 → tissue not active, not going to release oxygen to inactive tissue (high pCO2 will)

• Running a fever (39°C) → have higher metabolic activity when you run a fever, need more oxygen (Hb lets go of more oxygen)

• Under all of these conditions, hemoglobin would release the same amount of oxygen to the tissues

ICQ #1 Explained

• Hb can adjust the amount of tissue it releases

  • can also carry oxygen so tightly under some conditions that it doesn’t release it at all

  • in physiology, important part is releasing it to the tissues

  • conditions same as arterioles (more blood → tissues) for Hb to release more oxygen to the tissues

    • under certain conditions based on tissue need, you’ll get more blood flow to the tissue & Hb will be more generous & release more oxygen to the tissue as a result

      • automatic, happens on its own

• metabolic acidosis: Hb lets go of more oxygen to the tissues

• blood flow & Hb release of oxygen to the tissues are driven by the same forces

ICQ #2: The moment-to-moment control of respiration is:

• O2 sensors in the arterial blood

• O2 sensors in the brain

• CO2 sensors in the arterial blood

• CO2 sensors in the brain

• H+ sensors in the brain

Partial Pressure Gradients (pressure of a single gas in a mixture)

• Based upon percentages

• P_N2 = 600 mm Hg

• P_O2 = 160 mm Hg

• P_CO2 = 0.3 mm Hg

  • all 3 are based on total atmospheric pressure = 760 mm Hg

• Dissolved in blood

  • Dependent upon solubility

  • Established partial pressure gradients

• partial pressure (P_O2 or P_CO2 ) is like a concentration gradient

  • how P_O2 of oxygen is going to determine how much oxygen gets dissolved in the blood

  • P_O2 and P_CO2 determine what is dissolved in plasma

• can put you on pure oxygen, P_O2 of oxygen will go up, but % of Hb saturation will not

  • why doesn’t Hb become more saturated?

    • bc it’s already fully saturated

• when we add more oxygen, we increase the dissolved oxygen in the body

  • it’s the dissolved part that is the usable part that goes into the ETC, picks up H⁺ and becomes water

  • what we use

  • stuff that’s stuck on Hb is a reserve, reservoir for when we use stuff that’s dissolved

• partial pressure determines Hb saturation, not the other way around

Alveolar Air (= arterioles)

• P_H2O = 47 mm Hg

• P_N2 = 565 mm Hg

• P_O2 = 150 mm Hg lowered to 100 mm Hg

  • Small fluctuations

  • 2,200 ml RV & 350 ml fresh

• P_CO2 = 40 mm Hg

Oxygen and CO₂ exchange across pulmonary and systemic capillaries caused by partial pressure gradients

• alveolar PO₂ & arterial PO₂ are the same (in normal conditions)

• if we increase the difference b/w PO₂ in the alveoli & PO₂ in the venous blood, the rate of diffusion of oxygen goes up

  • if we put you on pure oxygen, the rate of diffusion of oxygen into your body would go up

  • if we force you to run around, we would drive PO₂ in muscles down & the rate of diffusion of oxygen into the muscle would go up bc it’s the difference b/w the two, it acts just like a concentration gradient

• CO₂ is an important part of pH

  • if you get rid of too much CO₂ → develop alkalosis

• CO₂ is exactly where it needs to be to maintain your pH

• Normal respiration is driven by CO₂, not oxygen, & it’s driven in response to whatever the pH is in the CNS

• lungs have so much surface area, good at rapid exchange

Gas Exchange

• Venous P_O2 = 40 mm Hg (from 100)

• Venous P_CO2 = 46 mm Hg (from 40)

• Travels down concentration gradients

• Increasing difference increases rate of exchange

Influences on Exchange

• Surface area (A)

  • fixed law of diffusion

  • if the surface area goes up, the rate of diffusion goes up

• Membrane thickness (∆X)

  • if the membrane thickness goes up, rate of diffusion goes down

• Solubility (B)

  • CO₂ more soluble than O₂ (has larger lipid solubility)

  • CO₂ can be moved just fine with a smaller concentration gradient or partial pressure gradient than oxygen

  • O₂ has to have a higher gradient to move across membrane bc it’s just not as soluble

  • all 3 help/impact diffusion

• Diseases

  • Increase membrane thickness

    • inc. thickness oxygen is going to have to travel though in order to get to the vessels running though the lungs

  • Reduction in surface area

  • neg. consequences in ability to exchange gases

• Fick’s Law of Diffusion

  • Q = (∆C * A * B) / (MW1/2 * ∆X)

Gas Transport

• Oxygen

  • Poorly soluble in plasma (1.5%)

    • 1.5% dissolved in plasma

    • what’s keeping us alive

    • non-polar, doesn’t easily dissolve in water/plasma

    • dissolved → drives Hb saturation

  • Attached to hemoglobin (Hb)

    • 98.5%

    • Reduced Hb- not combined with oxygen

      • Hb has low affinity for oxygen

    • Oxyhemoglobin- oxygen combined with the iron (heme) group

    • bound to heme portion

    • when O₂ is bound to Hb, it doesn’t contribute to P_O2 of blood

      • Hb acts as sponge & removes O₂ from the blood so that more can be dissolved

  • Hemoglobin saturation

• P_O2 of dissolved oxygen determines Hb saturation

Oxygen-Hemoglobin Saturation Curve

• Law of Mass Action (reversible reaction)

  • Hb + O₂ ↔ ︎HbO₂ (oxyhemoglobin)

  • at the lungs, you have a lot of oxygen with free Hb, so you drive to oxyHb

  • at the tissues, you have a lot of oxyHb, but not a lot of O₂ so the reaction goes backwards & so the Hb releases the oxygen to the tissues

  • amount of oxygen that Hb releases is not linear, helps us out

• P_O2 & % Hb saturated

  • P_O2 100 mm Hg = 97.5% Hb saturated

  • P_O2 60 mm Hg = 90% Hb saturated

  • Steep portion

    • enables us to have slight changes in our arterial P_O2 to deliver it to the tissues & get it unbound from Hb

• As blood P_O2 falls, Hb releases more O₂

• main job of Hb is going to be delivery of O₂, not just carrying

  • allow tissues to become well-oxygenated

  • Hb is not supposed to hold onto oxygen

Oxygen-hemoglobin (O₂-Hb) dissociation (saturation) curve

Affinity Influences

• ↑ CO₂ causes Hb to release more O₂ - “shifts” the curve to the right

  • ↓ CO₂ causes Hb to release less O₂ (shift left)

  • high CO₂ → high metabolic activity

    • high CO₂ in tissues → arterioles dilate, so now we have more blood flow

  • more blood flow → more Hb → more oxygen release, the tissues are well perfused

  • tissues are more metabolically active, need more oxygen

• ↑ H⁺ concentration (↓ pH) “shifts” the curve to the right

  • ↓ H⁺ causes Hb to release O₂

    • alkalosis, shift left

    • high pH

• 2,3-diphosphoglycate = right shift

  • only has a right shift, doesn’t shift left

  • indication of RBC metabolism, released from RBCs when they are metabolizing

  • bind to Hb, dec. affinity for oxygen

  • enhance O₂ unloading

  • inc. when Hb is chronically undersaturated

• CO = left shift (carboxyhemoglobin)

  • only shifts left

  • less oxygen being delivered to the tissues, don’t have any to give

• ↑ T° = right shift; ↓ T° = left shift

  • exercising/fever, hypothermic

• left shift is not physiologic, only pathologic (if ever given the opportunity, don’t shift left → always bad)

• right shift is a physiologic shift that occurs during exercise

  • not all good, can be bad

• right shift: Hb releasing more oxygen to the tissues than normal

• left shift: Hb gets to the tissues w/ oxygen & doesn’t let it go

  • tissues in left shift are deprived of oxygen

Fig. 13-26, p. 488

Carbon Dioxide

• CO₂ + H₂O ↔︎ H₂CO₃ ↔︎ H⁺ + HCO₃^-

  • Reaction requires carbonic anhydrase (at 1st arrow)

  • 60% of CO₂ is transported as HCO₃^-

    • majority

    • Hb is so large that it can transport O₂ & CO₂ simultaneously

    • throw same CO₂ on it, ability to carry O₂ drops, right shift

  • carbonic buffer system

    • as CO₂ goes up, it will combine w/ H₂O, & bc of carbonic anhydrase (CA), we end up w/ an inc. in acid & bicarb

      • what happens in tissues

    • in lungs, dec. CO₂, rxn will go ← so we can expire CO₂

• 30% transported as carbaminohemoglobin

• 10% dissolved in plasma

  • when we exhale CO₂, we get rid of the dissolved portion & then the other portions replace what was exhaled

Tissue Cells, Alveoli

Rhythmic Breathing Patterns

• Medullary Respiratory Center

  • Rostral Ventromedial Medulla Pre-Botzinger Complex

    • Pacemaker

      • tied to skeletal muscle, motor neurons

      • has the ability to respond to pH, pH sensitive

      • fires every 3-5 seconds

  • Dorsal Respiratory Group (DRG)

    • Stimulation = inspiration

    • Lack of stimulation = expiration

    • DRG will keep us alive, but not very active

    • diaphragm & inspiratory muscles to allow for tidal volume

    • DRG has no inherent pacing activity

      • as long as you’ve got your pacers, DRG is minimum you need to stay alive

      • responsible for quiet breathing in

      • not responsible for active exhalation

      • contracts the muscles of inspiration for abt. 2 seconds, move in abt. half a liter of air (all inhalation requires muscle contraction

      • pacer stops firing & DRG stops firing & so muscles passively relax

        • all of quiet exhalation is passive

  • Ventral Respiratory Group (VRG)

    • Inspiratory and expiratory neurons

      • abdominal muscles help you forced inhale

      • abdominal muscles, internal intercostals → expiratory neurons

    • Active inspiration and expiration

    • VRG is tied to dorsal group

    • conscious input has to go through the ventral group

• if we want to add any active, take a deep breath & hold it, inc. respiration w/ exercise, we have to add the ventral group

• get punched in stomach → knock breath out

  • can breathe, quiet system is trying to fight abdominal muscles (cramp)

  • inspiratory muscles are very wimpy, can’t breathe against it

• have other muscles of inspiration that elevate our ribcage, sternum… can use those but have to think abt. it

• have to get yourself calmed down enough to take a deep breath in

Fig. 13-29, p. 494

Rhythmic Breathing Patterns 2

• Pontine Respiratory Centers (fine-tuning)

  • Pneumotaxic center

    • Limits duration of inhalation by the DRG (DRG stops inhaling)

      • inhibitory to DRG, protective over over-inhaling of lungs

  • Apneustic center

    • Prevents inhibition of the DRG

      • inhibitory to pneumotaxic center

    • both centers end up w/ a nice, smooth breathing pattern

  • Phrenic nerve

    • everything runs through this nerve

Influence of Chemical Factors on Respiration

Location of Peripheral Chemoreceptors

Effect of increased arterial P_CO2 on ventilation

Alveolar and arterial partial pressure (P_O2 or P_CO2) (mm Hg)

Regulation

• Arterial P_O2

  • not a very sensitive driver of respiration, have to get it below 60 mmHg before it’s going to drive respiratory response

• Arterial P_CO2

  • primary regulator of respiration

  • bicarb. system (CO₂ + H₂O ↔︎ H₂CO₃ ↔︎ H⁺ + HCO₃^-)

    • really needs to be converted into H⁺ before it starts driving respiration

• Indirect increases in ventilation

• Modification

  • Involuntary

  • Voluntary

• Problems

Table 13-9 Oxygen- and Carbon Dioxide-Related Variables During Exercise