Internal Environment: Oxygen & Carbon Dioxide (PHYSIOLOGY E2: Part 4)

What are Partial Pressure Gradients?

• Based upon percentages

• P_N2 → 600 mmHg

• P_O2 → 160 mmHg

• P_CO2 → 0.3 mmHg

  • **** DO NOT MEMORIZE THESE VALUES ****

  • NOT IMPORTANT

• Dissolved in blood

  • Dependent upon solubility

  • Establishes partial pressure gradients

What are the Different Partial Pressures of Alveolar Air?

These are values in Alveolar / Arterial blood

• P_H2O → 47 mmHg

• P_N2 → 563 mmHg

• P_O2 → 150 mmHg lowered to 100 mmHg

  • Need to know P_O2 → 100 mmHg

  • Small fluctuations

  • 2,200 mL RV & 350 mL fresh

• P_CO2 → 40 mmHg

  • Also need to know P_CO2 → 40 mmHg

• DO NOT MEMORIZE THESE VALUES!!! (Except 100 & 40 mmHg)

O₂ / CO₂ Net Diffusion Gradients between Lung & Tissues Diagram

• The Only important values you need to know:

  • P_O2 → 100 mmHg

    • P_O2 in arterial blood

  • P_CO2 in alveoli → 40 mmHg

    • P_CO2 in arterial blood (even though its in pulmonary vein)

      • Due to no gas exchange (go thru heart, no gas exchange)

      • When get to aorta & all arterioles, at arterial end of capillary:

        • P_O2 —> 100 mmHg

        • P_CO2 → 40 mmHg

  • When we get to tissues, our tissues are burning Oxygen

    • So P_O2 is less than (<) 40 mmHg

    • Tissues are producing CO₂

      • So P_CO2 → greater than (>) 46 mmHg (but equilibrates to 46)

    • Need to know these numbers for venous blood because thats what goes up for Gas exchange

How is Gas Exchanged?

• Venous P_O2 → 40 mmHg

• Venous P_CO2 → 46 mmHg

• Travels down concentration gradients (partial pressure gradient)

  • If we increase the difference, we increase the rate of exchange

• Increasing difference increases exchange

What influences Gas Exchange?

• Surface Area (SA)

• Membrane thickness

• Solubility

  • CO₂ more soluble than O₂

• Diseases

  • Increase membrane thickness

  • Reduction in surface area (SA)

  • Hoping to Train to See:

    • If Patient has Respiratory Disorder → They probably have acid-base disorder b/c ability to compensate is impaired (for metabolic acidosis or smth like that)

• Fick’s Law of Diffusion

  • Q = ((ΔC x A x β) / (MW (1/2) x ΔX))

How is Oxygen Transported?

• Poorly soluble in plasma (1.5%)

• Attached to hemoglobin (Hb)

  • 98.5%

  • Reduced Hb → not combined with oxygen

  • Oxyhemoglobin → Oxygen combined with the iron (heme) group

• Hemoglobin saturation

What is the Law of Mass Action?

• Reversible Reaction

  • Hb + O₂ ←→ HbO₂

What is the Oxygen-Hemoglobin Saturation Curve

• Utilizes the Law of Mass Action (reversible)

  • We have oxygen + hemoglobin = oxyhemoglobin (can go backwards)

    • If have high Oxygen & high hemoglobin, will form oxyhemoglobin

    • If get to tissues & have low oxygen, & a lot of oxyhemoglobin → will release Oxygen & form hemoglobin independent

• P_O2 and Percentage (%) Hemoglobin (Hb) saturated

  • P_O2 100 mmHg = 97.5% Hb saturated

  • P_O2 60 mmHg = 90% Hb saturated

    • DO NOT MEMORIZE THESE NUMBERS

    • Just know curve & what curve means

      • P_O2 is dissolved

      • % Hb saturated is what’s bound to hemoglobin

        • what’s bound to hemoglobin comes off & replaces what’s dissolved (used by tissue)

  • Steep portion

• As blood P_O2 falls, Hb releases more O₂

  • As P_O2 in tissues gets lower, hemoglobin releases more oxygen (in non-linear way)

• Break in color (Blue to Pink)

  • At 60 P_O2 → at that point, if P_O2 in arterial blood was 60, that would trigger emergency respiration & oxygen need

    • That break in color is when we switch from CO2 driving Respiration to Oxygen Driving Respiration

  • CO2 particularly hydrogen generated by CO2 is what drives normal day-to-day respiration

    • Oxygen doesn’t b/c we don’t get that low

• EX in Class: Euthanasia in Vets (Agonal Breathing)

  • P_O2 has dropped to emergency respiration point

  • brain is already dead but P_O2 has dropped to point that reflexes in carotid body trigger emergency respiration

What are the Influences of Oxygen Affinity?

• Increased (↑) CO₂ causes Hb to release more O₂

  • Shifts curve to Right

    • More metabolic activity (more CO2), shift to right

  • Decreased (↓) CO₂ causes Hb to release less O₂

    • Shifts to the Left

• Increased (↑) H⁺ concentration (decrease pH)

  • Shifts curve to Right

    • Increased H+ Concentration (decreasing pH) due to more metabolic activity

  • Decreased (↓) H⁺ causes Hb to release less O₂

    • Shift to Left

• 2,3-diphosphoglycerate (2,3-DPG)

  • Shifts Right

• Carbon Monoxide (CO)

  • Shifts Left (Carboxyhemoglobin)

• Increase (↑) in Temperature

  • Shifts Right

• Decrease (↓) in Temperature

  • Shifts Left

• Left Shifts are All Pathologic

• Right Shift can be Pathologic or Physiologic

Partial Pressure of Blood Oxygen (O₂) vs. Percentage (%) Hemoglobin Saturation Graph

• Right Shifted Curve (Factors That Shift Curve to Right)

  • Curve physically shifted to right hand side graph

  • Factors that Shift to Right:

    • P_CO2

    • ACID (H⁺)

    • Increase (↑) Temperature

    • Increase (↑) 2,3-Bisphosphoglycerate

• Under these conditions, hemoglobin releases more oxygen to the tissues

  • Hemoglobin has to transport & release it

  • In Right Shift → causes tissues to have higher Oxygen Availability

    • Tissues are well-oxygenated in conditions of right shift

  • EX: Dozing off in class

    • Shift off to right curve

    • Resp rate drops, CO2 builds up, but tissues very well oxygenated b/c shifted to the right

      • Hemoglobin is releasing more than usual amount oxygen to tissues

• In a Left Shift Curve:

  • In alkalosis, we’re shifting to Left

  • Tissues are hypoxic & have tendency to go into ventricular fibrillation

• Right Shift in Heart:

  • Delivers 80% oxygen to tissue (20% hemoglobin saturation)

• In a HARD RIGHT SHIFT, Hemoglobin doesn’t saturate

  • hemoglobin gets to lungs & hemoglobin can’t carry oxygen from alveoli

  • Begins to carry less oxygen to tissue

  • PATHOLOGIC RIGHT SHIFT

    • EX: Really high fever, severe acidosis

    • Hemoglobin doesn’t pick up O2, doesn’t saturate well

• Fetal Hemoglobin:

  • Left Shifted Curve

  • Need more Oxygen, but doesn’t have big partial pressure differences

  • Hemoglobin has to load much better

• Myoglobin

  • Even further & is LEFT SHIFT

  • Myoglobin in muscle is terminal thing

    • Myoglobin holds Oxygen for the exercising muscle

    • Myoglobin in exercising muscle gets very close to 100% saturated at 10 mmHg

    • Left shift in myoglobin helps maintain oxygen available for exercise

What happens in a Left Shift in Saturation Curve?

• Our tissue is more like 8% oxygenated (8% delivered to tissue)

  • 92% hemoglobin saturated (oxygen still in hemoglobin)

• Tissues are hypoxic

• In the heart Saturation Curve (20 mmHg)

  • Only deliver ~40% of oxygen to tissue

  • Need ~65% oxygen delivery to tissue to function normally

  • Heart tissue will be hypoxic

    • heart will fibrillate

  • For Pts in hypothermia, have high risk of ventricular fibrillation

How is Carbon Dioxide (CO₂) Transported?

• CO₂ + H₂O ←→ H₂CO₃ ←→ H⁺ + HCO₃^-

  • Reaction requires Carbonic Anhydrase

  • 60% CO₂ is transported as HCO₃^- (Bicarbonate)

    • #1 transport of CO2 is bicarb

• 30% CO₂ transported as carbaminohemoglobin

  • #2 transport of CO2 is bound to globin portion of hemoglobin (called carbaminohemoglobin)

• 10% CO₂ dissolved in Plasma

  • #3 Transport is physically dissolved in plasma

What is the Mechanism of Carbon Dioxide Transport?

• All we need to know about Carbon Dioxide Transport

  1. Picking up CO₂ & Dropping off O₂ in tissues

  2. In lungs, we’re Dropping off O₂ to tissues & picking up CO₂ from Tissues

  3. This is saying that oxyhemoglobin will drop off oxygen off, & hemoglobin will bind to CO₂ to make Carbaminohemoglobin

  4. Hemoglobin will bind to Hydrogen to make HbH (Hydrogen Hemoglobin)

  5. Chloride Shift: Bicarbonate-Chloride Exchange

     1. Should shift Bicarbonate out of tissue cell with antiport exchange pump

     2. & shift chloride into cell

What Prevents Hydrogen from Recombining w/ Bicarbonate & going back to Water & Carbon Dioxide?

• This is because Bicarbonate is pumped out of cell & no longer available

• Chloride is in

• Hydrogen dissociated from Hemoglobin & not allowed to interact with Bicarbonate & pumped out of cell

Differences between Bohr Effect vs. Haldane Effect?

• Deals with Reduced Hemoglobin (which isn’t common)

  • Deals with more pathological conditions

What influences the Rhythmic Breathing Patterns?

• Medullary Respiratory Center

  • Rostral Ventromedial Medulla (Pre-Botzinger Complex)

    • Pacemaker

    • Rely in Pre-Botzinger to breathe quietly

    • Feeds into Dorsal Respiratory Group (DRG)

    • Fires about every 5-6 sec & tells DRG to fire for 2 seconds & stop firing

  • Dorsal Respiratory Group (DRG)

    • Stimulation = Inspiration

      • DRG causes diaphragm to contract & cause (some) external intercostals to contract

      • In order to inhale (over 2 secs & stops)

      • Everything relaxes (to passively exhale)

    • Lack of stimulation = expiration

  • Ventral Respiratory Group (VRG)

    • Inspiratory & Expiratory Neurons

    • Active Inspiration & Expiration

    • VRG is triggered when you think about breathing (conscious thought)

  • Normal moment-by-moment quiet breathing is handled by medulla of brain

    • Fracture of C1 is often fatal (b/c takes out Pre-Botzinger or DRG)

      • Sometimes can take out either Pre-Botzinger or DRG

        • Patient has to continually think about breathing

• Pontine Respiratory Centers

  • Pneumotaxic Center

    • Limits duration of Inhalation by the DRG

    • Tells DRG to stop inhaling

  • Apneustic Center

    • Prevents inhibition of the DRG

    • Tells DRG to keep inhaling

      • Both centers balance each other out

  • Pons augments & makes breathing look smooth

    • Damage to Pontine Centers (E.G. central pontine myelinolysis) causes ragged breathing

• Phrenic Nerve

What is enough to handle quiet Breathing?

• Pre-Botzinger Complex

• Dorsal Respiratory Group (DRG)

  • Anytime we need modification to breathing, we pull in Ventral Respiratory Group (VRG)

  • Sympathetic NS changes bronchial diameter (dilate bronchioles) but doesn’t effect rate

    • Rate effected through high brain coming down & tying to Ventral Respiratory Group (VRG)

What are the Influences of Chemical Factors on Respiration?

• Decrease in P_O2 in Arterial Blood

  • Low Oxygen in Arterial Blood is only important when getting below (<) 60 mmHg (emergency mechanism)

    • EX: Agonal gasp/breathing at this area

  • Oxygen only has depressive effect on Central Nervous System (< 60 mmHg)

    • stop respiration (Respiration stops when O2 levels below 60)

      • happens at death

• Increase in P_CO2 in Arterial Blood (Increase in H+ in brain ECF)

  • CO₂ itself in arterial blood only has weak stimulation

  • CO₂ in Arterial blood converts to Hydrogen (H⁺) in brain

    • Hydrogen in brain dominate control of ventilation

      • When hyperventilating

  • Respiration stops b/c CO2 in brain is above 70-80 mmHg

    • happens during death

• Increase [H+] in Arterial Blood

  • Important in Acid-Base Balance

• ** In most cases, they’re influencing the Pre-Botzinger (Pacemaker) **

• Have Peripheral Receptors & Central Receptors

  • Peripheral → aortic arch & carotid body receptors (same ones as blood pressure)

  • Central → Associated w/ Pre-Botzinger Complex

• EX: What’s Danger of Sleep Apnea?

  • Hypertensive Crisis while Sleep

  • Wake up w/ possible scleral haemorrhage, or possible aneurysm

  • Due to Blood Pressure & Respiratory Centers (Peripheral) tied together

• Normal Walk-around drive for respiration:

  • Hydrogen concentration in brain from CO2

Heart to Medullary Control Center Connection

How does the Medullary Respiratory Center regulate Arterial CO₂ Partial Pressure (P_CO2)?

• Reason why hydrogen has to be tied to CO2 is because:

  • Hydrogen itself doesn’t cross blood-brain barrier b/c it’s ionized (charged)

  • CO₂ is lipid-soluble so crosses blood-brain barrier to convert to Hydrogen in brain

Acid-Base Disorders Presentation (By: Dr. Wolfshohl)

• Won’t ask any Specific questions on the exam regarding his slides

  • He doesn’t write questions for exam

  • However, understanding his material WILL HELP

  • EX: Won’t ask for U in MUDPILES when he brings it up in class

    • Understanding Anion gap, & things that influence it is important (b/c we also cover it!) however

1. Which is true?

• 1. A Left ventricle became

• 2.

• 3. Cardiac output same on left than right side

• 4. Caridac outpu

• 5.

2. 50 y/o man w/ CO 6 L/min.

6L = 6000mL/min
6000mL/75 = 80mL/beat

preload = 120mL
80/120 = 66%
6000

3. Hypothetial arteriole

1. Constricting vessel at point A (increase pressure) would increase flow

   1. Will increase pressure gradient to increase flow rate

2. Velocity has to do with surface area (point C to D is will slow

   1. Has surface area increases, velocity will go down (TRUE)

3. Nitric Oxide (NO) release from endothelial

4. False b/c A1 stimulation would decrease flow b/c of vasoconstriction

5. Pressure is lowest at D (TRUE)

   1. due to pressure gradient

4. What would decrease venous return?

A. Venous valves collapsing
B. Decreased sympathetic activity

C. Vein Capacitance

• How much blood the vein will actually hold

• If the vein holds onto more blood, it is actually not returning to the heart (which is venous return)

D. A & B, not C

E. A, B, & C

5. An increase in which would increase Glomerular Filtration rate (GFR)?

A. Local nitric oxide release in the afferent arterioles of the kidneys

B. Total body dilation of arterioles

• If dilating everything, then whole blood pressure drops

• Not enough blood flowing through afferent arteriole (not as much dilation of afferent arterioles in kidney)

C. An increase in Plasma proteins

D. A & B

E. All of the above

6. Billy (195.8 lb) injects himself w/ 11 g heavy water

• Find volume of heavy water

  • 19.3 mg / dL = (11,000 mg) / (x dL)

  • Find Volume & convert to percentage

8. Hyperventilation can result in muscle spasms. which is true?

A. plasma proteins have higher affinity for Ca2+ than H+, making more Ca2+ bioavailable

• If plasma have high affinity → it would make it not bioavilable

• A is incorrect

B. an increase in pH makes less CA2+ bioavailable

C. A decrease in H+ ECF concentration causes threshold to drop & cell becomes hyperexcitable

• alkalosis = less free H = proteins in the blood that want to bind to something (they can either bind H or Ca) = so if theres less H they will pick Ca = if they bind Ca less is freely floating in  the ECF so essentially you lower ECF [ca] so threshold lowers = easier to cause excitability and you get muscle spasms

• basically the proteins have to grab either H or Ca and if H were green marbles and Ca were blue marbles in a bag, they just reach in and grab one. If you cnage the amount of marbles in the bag, i.e. hyperventilate, you get rid of green marbles and youre more likely to take the blue ones out of the bag if you reach your hand in. that's what albumin is doing

D. B & C are correct (TRUE)

Hyperventilation → Alkalotic

• hyperventilate = less co2

  less co2= less acid

  less acid = alkalosis

  alkalosis = low H

  low H = high affinity for Ca

  less free Ca in blood lowers threshold so we spasm

• Less hydrogen, more calcium would be bound so less calcium would be bioavailable

9. Given following labs

• Since pH is low, we know it’s acidosis

• Since P_CO2 is low,

• Bicarbonate levels are also low

What does vomiting cause?

• Vomiting causes alkalosis (metabolic alkalosis)

  • Vomiting is always metabolic

• Body compensates w/ respiratory acidosis

• vomit = lose acid = so body is basic
  need to compensate with some kind of acid so you compensate with respiratory acidosis

• Question 10!

• Question’s won’t be as hard on exam

11. Billy lost complete function of Dorsal REspiratory Group (DRG), which may occur?

• He can still breathe, he just has to THINK ABOUT IT

12. Why does billy go to Denver to train?

• if we’re higher in altitude is there less or more oxygen available in the air

  and do our tissues still need the same amount of oxygen

  A. Immediate left shift of oxyhemoglobin curve stimulates 2,3-DPG compensatory mechanism

  B. After acclimation, an overall right shift in the oxyhemoglobin curve increases overall oxygen capacity

• High Altitude would cause immediate left shift

  • since theres less o2 we're gonna shift left so that our body releases more oxygen to the tissues

• cool so since theres less o2 we're gonna shift left so that our body Carries more oxygen to the tissues
  
  then when we're back to normal levels the curve will shift right to compensate and more O2 gets released
  
  athletic advantage, more capacity etc