IMAGE: a good image, but a caption/side box explaining it in more depth/including names and functions of molecules not described in the text would further assist comprehension

IMAGE: the below image does not seem to add much to the section, especially since the information it highlights is in a side box and potentially less vital to begin with

• may be more useful to replace with an image diagraming some of the discussed mechanisms of action such as those involving renin or ACE (the image would then need to be moved to its appropriate area)

IMAGE: this is an image displaying concurrent vs counter current flow; it is helpful but to make understanding easier exact % values should be added along the entire length of the tubes (not just "near 0" at the ends of the tubes)

IMAGE: would be much more helpful if the important structures highlighted in this section were pointed out with the addition of arrows or replacement of a similar but more detailed image

IMAGE: this image is very helpful and should be included in the chapter, however would be much more helpful/understandable if included later on in the in-depth mid-term responses section

BOX: blood doping section (even the whole paragraph) could be made into a side box; while I think the flow is fine, this doesn't feel as necessary to know and instead more like interesting additional knowledge

• could even include examples of this (Lance Armstrong)

REMOVE: these first few sentences are repeated from a few paragraphs above; while some of this info may provide helpful context for the upcoming section, try to remove unnecessary repetition ex: "As previously mentioned, hemoglobin can bind four oxygen or four carbon dioxide molecules at a time. Heme groups bind oxygen in an unusual way due to protein cooperativity."

ADDITION: this section is very dense and hard to follow overall, may be useful to somewhere include a brief summary of the key takeaways

• HIF activates EPO transcription
• HIF degraded under normal levels of O2 (no EPO)

ADDITION: while it may seem wasteful/inefficient to constantly produce HIF-2 when it is going to be degraded immediately in the presence of oxygen, it is incredibly important to always have this transcription factor present so that low oxygen levels can be responded to as quickly as possible (low oxygen is a huge issue for the body)

BOX: I was unable to put both of these terms in the same box for some reason (this is the section I edited), but that format may be more aesthetically pleasing if possible

ADDITION: indicate how places where O2 is picked up are the places where CO2 will be dropped off "...will release carbon dioxide in areas of low carbon dioxide concentration, although these respective areas are opposite those of oxygen binding and release."

edit: this is discussed to some extent in the final sentence of the paragraph, but it may still be helpful to explicitly state that these locations are the reverse for oxygen

CLARIFICATION: as mentioned above, the body does not have O2 sensors; this should be altered to keep wording consistent with this fact ex: "..release oxygen exactly where it is being used, indicated by the the lower pH caused by carbonic acid, which communicates a lower oxygen concentration without requiring oxygen sensors."

DEFINITION: hemoglobin A1c

CLARIFICATION: distinguish posterior pituitary vs. hypothalamus/what is meant by including both (see similar tag above)

CLARIFICATION: reword ex: "...the term "antidiuretic hormone" is regularly used rather than "vasopressin" due to..."

BOX: interesting side note: all mitochondrial DNA is inherited from the mother

BOX: I am curious about the mechanisms/desired impacts of this involved in reproductive medications

ADD: expand a little further to make this even more interesting!

• cholera causes diarrhea which leads to severe dehydration that can result in death only hours after the onset of symptoms if left untreated (this highlights how strong of a mechanism this is)

IMAGE: consider including one of the images displaying hyperpolarization/depolarization (membrane potentials and/or the movement of ions) for one of the situations described in this section to help reader's visualize these processes

MOVE: the two sections of this sentence seem contradictory (K+ is more important vs. there is a balance b/w Na+ and K+)

• include the 2nd half of the sentence earlier or later in the section so it does not disrupt the flow of talking about K+'s role
• suggestion: "... low sodium is less of a stimulus than high potassium. High potassium levels are a stronger indication of physiological vulnerability, as it usually antagonizes the effects of sodium. This makes their relative concentrations very important. With that said, high potassium levels do have similar effects to low sodium levels, and a balance in their respective concentrations must be maintained for normal functioning."

BOX? this section as well as additional info that should be added (see annotation for "death is inevitable" might be better in a side box (may disrupt the flow once explanation is added)

ADDITION/CLARIFICATION: expand on why this is the case

• aldosterone is needed for proper electrolyte balance (sodium, potassium, etc)
• this balance (having enough salt) is necessary for many processes, including maintaining homeostatic blood pressure

ADD: continue this sentence to clarify the negative feedback (ex: "...inhibits the production of renin, therefore inhibiting the production of both angiotensin I and II")

CLARIFICATION: released from the posterior pituitary but produced in the hypothalamus (the current wording makes it sound like the posterior pituitary and the hypothalamus are the same thing)

ADD: if not included in previous sections of the text, it may be helpful to explain the meaning behind this name in a side box

• "-ase" signifies that it is an enzyme
• what comes before the "-ase" typically describes what the enzyme does (telling you it does something to angiotensinogen)

ADD: a potential idea for an interesting side box is that fish also use countercurrent flow in both their gills (to maximize O2 capture), as well as in their swim bladder (for adding and removing O2 in order to achieve the desired buoyancy at different depths)

CLARIFICATION/ADD: I feel like this is essentially one of the main/most important points for understanding countercurrent flow (what it is and why it is necessary). Because of this it should probably be emphasized more (maybe mentioned earlier in the section or reworded to highlight the statement more).

• in addition, I think understanding countercurrent flow can be made easier when comparing it to concurrent flow

CLARIFICATION: why highlight this? if it is considered an important fact that these molecules are moved using active transport, explain why (is this somehow different than expected, different than what is seen in other cells, etc)

REMOVE (repetitive)

(capitalize)

CLARIFICATION: confused by what this sentence is meant to say

• should this say "shorter-term"?
• OR reword to make more clear: "When short-term responses are insufficient in accommodating changing blood pressure.."

REMOVE: this is both fairly repetitive, as well as unnecessary in this section discussing short-term responses

REMOVE/CLARIFICATION: may want to substitute "normal" for a different word/phrase, this can often sound offensive/hurtful to those who do not belong to a certain group

CLARIFICATION: this sentence is incredibly long and confusing to follow, try to reformat or break into smaller segments to make it more readable

possible rewrite idea: "...circulate blood. Blood moves through the pulmonary system (where oxygen and carbon dioxide are exchanged..), through the hepatic and renal systems (where blood...), and finally into all other cells..."

ADDITION: include an introductory sentence discussing what this section will be about (jumping right into hemoglobin without mentioning how it relates to pH makes this confusing/hard to follow)

I get it!

glossary?

glossary

core

I get it!

needs context (would be interesting to explain this role in more depth, even in a side box if it feels too disconnected/disrupts the section's flow)

repeated (multiple sentences in this section, although likely intentional/helpful)