Videos 56-58
What is hemoglobin in vertebrates?
A protein in red blood cells that carries oxygen - Four subunits - each has a heme group (Fe) - Cooperativity - O2 carrying capacity - In RBCs Also binds: CO2, NO, CO, H2S
How do human react to high altitude? (acute, acclimatization, adaptation responses)
Acute responses (initial response) - increased ventilation (brings more O2 in) - erythropoietin production (makes RBCs) - H2S signaling Acclimatization (days) - increased DPG - angiogenesis (makes more capillaries = increased diffusion) - increased hematocrit Adaptation (evolution) - Andes- increased lung volume - Himalayas- increased hyperventilatory response (during exercise, they can increase their rate of breathing more and are able to do more activity at high elevation) - Ethiopian Highlands- increased hemoglobin content
How is the Bohr effect significant in O2 transport?
Allows more O2 to bind at respiratory entrance and more to be delivered! The pH is high in the lungs, thus Hgb has high affinity for O2. - Arterial blood entering tissues has higher PO2, lower PCO2, higher pH than venous blood leaving tissues The pH is low in the tissues, thus Hgb has low affinity for O2 = more delivery - CO2 from metabolism acidifies tissues - Low tissue pH decreases affinity for O2 (increases P50) - CO2 directly increases P50 - More O2 dissociates from hemoglobin and diffuses into tissues If there were no Bohr effect, about 20-25% of oxygen would get delivered to tissues. Instead, about 50% actually gets delivered due to Bohr
What is 2,3-Diphosphoglycerate (2,3-DPG)?
An organic phosphate found in RBCs that has the ability to alter the affinity of Hgb for oxygen - increases P50, decreasing affinity for O2, shift curve to the right
What happens to cooperativity of oxygen binding during exercise?
At rest, most O2 is NOT extracted. When exercising, the O2 is used up more rapidly, and thus more O2 is extracted from hemoglobin - High O2 demand decreases tissue PO2 - O2 delivery enhanced by CO2 and lactic acid (Bohr effect)
What is Pcrit?
Critical PO2 (Pcrit) = Level below which minimal aerobic metabolism can not be supported - below Pcrit is a sign an animal is in hypoxia
What does 2,3-DPG do at high elevation?
less O2 is picked up at lungs and more is delivered - low affinity Hb can improve delivery *image 39
What are book lungs?
organs that have layers of respiratory tissue stacked like the pages of a book - rigid surfaces w/ high SA - rely on diffusion for O2 - common in spiders & scorpions !!
What is the shape of an oxygen binding curve?
sigmoidal
What is cooperative binding?
- Binding one O2 increases affinity to bind 2nd, 3rd, 4th - Loss of 4th increases probability of losing 3rd, 2nd, etc.
What is unique about tracheal system in large insects?
- Dung beetles have sequential opening/closing of different spiracles - there is net unidirectional air flow along length of animal - air is inhaled in abdominal spiracles and exhaled in thoracic spiracles (meaning there must be convection occurring in the system) - Grasshoppers also do this but front spiracles take O2 in and back ones release CO2 *image 12
What are some things that impact hemoglobin affinity?
- H+ - Carbon dioxide Organic phosphates (vertebrates): - Mammals: 2,3-Diphosphoglycerate (2,3-DPG) - Birds: Inositol hexaphosphate (IHP) - Reptiles: Inositol pentaphosphate, ATP - Amphibians: DPG, ATP - Fish: ATP These all decrease affinity for O2 (increase P50), moving the graph to the right (less O2 is picked up but more is delivered to tissue) !!
What are tracheal systems?
- System of air filled tubes that direct transport of O2 to cells and CO2 out of cells - Air enters through branching valved opening called spiracles (open = allows gas exchange, closed = prevents) - Branching continues until we get "tracheoles" right by cells (delivers O2 directly to cell) - This occurs in insects! (ticks, solpugids, pseudoscorpions, millipedes) *image 3 left
How is it possible that antarctic icefish do not have hemoglobin?
- They live in low temperature (-1.9'C) where there is relatively "High" O2 in water (>10 mL/L) - Low activity fish = low metabolic rate - Enlarged heart = allows more blood flow per beat (compensates for low O2) Their bodies require little oxygen and their environment is relatively high in O2 QQ
What are insect air sacs?
- especially found in thorax - structures that provide O2 for flight muscles *image 3 right side
What is hemoglobin in invertebrates?
- relatively large - extracellular - can have many many subunits for O2 binding
What is discontinuous gas exchange?
- tracheal systems take up oxygen & release CO2 in large bursts - this is done to prevent water loss - when spiracles are open = O2 comes in but water is lost - when spiracles are closed = no gas is moved but some water is lost via cuticle (much less); NEGATIVE PRESSURE DEVELOPS - these animals can flash their spiracles open and shut (in a flutter) to get bulk flow of O2 in w/o much water loss - there is a cycle of fluttering (F), then opening spiracles (O), and closing them (C)
What is the root effect?
-when the effect of CO2 or an acid (lower pH) causes a decrease in hemoglobin's affinity and it's carrying capacity for oxygen - this allows fish to fill their sim bladder - lower pH = less binding to O2 = less O2 for swim bladder
What is hemocyanin?
A protein containing copper that binds to oxygen in arthropods and molluscs - still has cooperative binding and bohr effect like hemoglobin - blood is green due to the copper
What animal can live at the highest elevation in North america? How does it do this?
Deer mouse (Peromyscus maniculatus) - Have low P50 Hb (high affinity for O2) in high-elevation populations -> associated with higher survival rate at high elevations - Their Lower critical temperature = 24-27'C and they spend their entire life at about 10'C!! They must always have a MR just to stay warm. - They have higher lung diffusion capacity (can pick up more O2 from air and get it to alveoli better), high density of capillaries (allows more O2 transport to cells), high cardiac output (stroke volume, heart rate which delivers more blood to tissues), high-affinity Hb (can increase O2 carried in blood stream), and so on!
How can we calculate the amount of O2 delivered to tissues?
Difference between arterial and venous blood = O2 delivered to tissues
How is MR impacted by tracheal systems?
Higher metabolism => greater O2 consumption => lower PO2 in inner tracheae => larger PO2 gradient => faster diffusion Overall: Higher MR = greater oxygen gradient = larger partial pressure gradient in the system *image 4
During hypoxia, what do we see happening to hemoglobin?
Improved ability of hemoglobin to pick up O2 and maintain hemolymph O2 content - in daphnia, there is increased hemoglobin levels (a lot of a new hgb is synthesized) - this new hgb has decreased P50 = allowing it to pick up O2 even when it is low in env't *image 28
How is mammal and reptile ventilation different from large insects?
Mammal, amphibian, & reptile lungs use tidal ventilation - bi-directional air flow Insect tracheae compresses and expands to pump air thru the system and to tissues in a coordinated pattern - net unidirectional
How do aquatic insects breathe?
Many have structures, called plastrons, on their cuticles that allow aerial respiration - These are hydrophobic structures that repel water - Surface tension prevents fluid from entering air space - A permanent (constant volume) air space is created for O2 diffusion - Often referred to as a "physical gill" since it functions similarly and can allow the insect to live under water indefinitely *image 31
What are some ways that animals can respond to hypoxia?
Move to new microhabitat - e.g. air-breathing fishes Increase O2 uptake - high affinity hemoglobin - lower organic phosphates - more hemoglobin - hyperventilation Increase O2 delivery - more capillaries - higher organic phosphates Decrease O2 demand - lower metabolic rate Anaerobic metabolism - end products
Does Blood/Hemolymph obey Henry's Law?
NO - hemoglobin binding is nonlinear since it uses cooperativity *image 13
Do all animals have a venous reserve?
NO ex: octopus -> Nearly all O2 delivered to tissues even while inactive - thus they cannot do much aerobic swimming and tend to swim in bursts (Note: Octopi have hemocyanin)
Do all sizes of animals have hemoglobins and hemocyanin?
NOPE - smaller animals do not necessarily need these and thus do not have them ex: hagfish only have myoglobin (no hemoglobin or cooperative binding)
Do all species in a particular population do discontinuous gas exchange?
Nope, some individuals may follow it, others may not!
What is P50?
PaO2 value at which hemoglobin is 50% saturated, normally 26.6 torr - P50 = PO2 when half hemes are bound to O2 - High affinity = low P50 = curve towards left - Always some dissolved O2 still present = important for delivery of O2 to tissues
Bohr effect vs Root effect
Root effect is distinguished from the Bohr effect - Bohr is where the curve is shifted to the right due to lower affinity, whereas the root effect causes the curve to be shifted downward as there is a reduction of O2 bound to hemoglobin even at saturation
What is the name for the O2 that is not taken up by tissues (but can be if needed)?
Venous reserve - about 25% of O2 makes it to the tissues regularly, the other 75% is reserved for strenuous exercise
What can be seen in an x-ray image of a tracheal system?
Ventilation !! - compression and expansion of tracheae was seen - we previously though it was only diffusion working in this system, but it is clear convection is playing some type of role too
What are some possible reasons why an animal would use discontinuous gas exchange?
Water conservation (most likely reason) pH/CO2 regulation Reduce oxidative stress (ex: ROS) Prevent infection & parasite infestation No adaptive reason Respiratory neurobiology
How does Pcrit change in aquatic organisms in low vs high O2?
Well oxygenated stream = high Pcrit Poor oxygenated stream = low Pcrit (animal can withstand more variation in O2 levels) These characteristics are likely due to hemoglobin -> poorly oxygenated env't is more likely to have high affinity, low P50 hemoglobin *image 29, 30
Max O2 capacity depends on...
amount of O2 binding proteins - ex: seals have a lot of hematocrit, allowing long dives w/o breathing
What is the Bohr effect?
the regulation of hemoglobin binding by hydrogen ions and carbon dioxide - if we increase partial pressure of CO2 or the conc of H+ ions, it lowers the pH and decreases hemoglobin affinity for O2 (graph shifts right) - decreases P50 and the amount of O2 bound THIS ALLOWS INCREASED OXYGEN DELIVERY TO THE LUNGS
Where is gas exchange in tracheal systems?
tracheoles - similar to small trachea - close to all cells in the body
Shape of O2 binding curve depends on...
type of O2 binding proteins and modulators