icepik

A 40 yr old fit female, with no previous history of acute pathological conditions endured a penetrating wound resulting in total obliteration of right dorsal horn of spinal cord segment at T6 vertebrae and total obliteration of the left ventral horn, spinal cord segment level T6 vertebrae. 4 days was given to her for the spinal cord edema to subside, and an examination was taken. What neurological clinical manifestations do you think one would find? My answer: Left side would lose sensation at and below the level of T6 (ventral horn = sensory protopathic?) right side would have flaccid paralysis at T6 level, and spastic paralysis below T6 I know my answer is VERY basic. help is muchhhhhh appreciated!! -Much Love

I did some more digging. You are right, that it's actually ACTH effect on Cortisol. I decided to post what I wrote up, in case anyone wants to take a look. ACTH levels increase rapidly for the first couple months. No cortisol is being produced up until about the 5th month. During this period, barely any cortisol is being produced, despite rising levels of ACTH. The adrenocortical is basically absolutely “insensitive” to ACTH. Massive negative feedback from the exogenous hormones has probably down-regulated the number of ACTH receptors. Thus, the levels of ACTH were not enough to stimulate production of cortisol (high threshold). Therefore its sensitivity to ACTH is very, very low, post-steroidal therapy. As the adrenocortical begins to recover from the massive negative feedback effect, and as ACTH production ramps up and beyond “normal” levels, the adrenocortical begins to produce cortisol. Sensitivity is still very low, but the seesaw effect between low sensitivity and high stimulus (levels of ACTH), is able to produce some cortisol. Therefore, we can say, the adrenocortical is still very low, but attainable. The high levels of ACTH, combined with the low levels of cortisol produced suggest the responsiveness of the adrenocortical is also very low. As the amount of ACTH increases, and as the adrenocortical further recovers, both the sensitivity and responsiveness increases. The rising slope of the cortisol line gives a primitive interpretation /indication of the rising responsiveness. At the end of the 10th month, ACTH production begins to decrease, but cortisol levels stay the same. We can assume that the adrenocortical has fully recovered from negative feedback, and has reached its “normal” state. The subsequent plateau of the cortisol line suggests that the “normal” responsiveness of the adrenocortical has been achieved. The responsiveness of the adrenocortical to ACTH after month 10 has not changed and thus this measurement can be considered its maximal responsiveness. The decrease in ACTH at the end is very important. It shows us that the sensitivity of cortisol has drastically changed. The same level of ACTH that produced a very,very low amount of of cortisol (shown at month 5), now produces a “normal” amount of cortisol shown at month 12, suggesting sensitivity has increased. Less ACTH is required to produce a response. In summary, as the cortisol levels begin to increase, the sensitivity of the adrenocortical begins to increase. This is the minimum amount of ACTH to cause the adrenocortical to produce cortisol. Since the adrenocortical is recovering from negative feedback, its states are changing, and sensitivity is also changing/increasing. Responsiveness is best shown when the cortisol level plateaus. Despite rising ACTH levels, the cortisol is “capped” and this is the maximal responsiveness of the adrenocortical.

The graph represents the plasma level of ACTH and Cortisol, over a 12-month duration, post-corticotropin therapy. What do you think the graph tells us us about the adrenocortical sensitivity and responsiveness to corticotropin. I came across this question, and I was unsure about the context of "responsiveness" and "sensitivity" as it relates to hormones and physiology in general. I'm hoping someone out there has experience with using these two terms, in regards to this scenario. This question is not about the mechanisms of negative feedback. It is solely to explain the difference between response and sensitivity using the graph. What does this graph tell you about the responsiveness and sensitivity of the adrenocortical? My explanation: Maximal responsiveness - maximal effect of a hormone on target cells. Sensitivity - concentration of hormone at which half maximal response is seen. "Response" in this example can be defined as : the TIME taken for the both glands to return to producing normal levels of hormones, after 1. Adrenocortical Sensitivity: Adrenocotical takes 12 months to produce a normal amount of cortisol. ACTH takes about 3 months to produce a normal amount of cortisol. However, it increases above and beyond that amount, and takes 12 months to return to normal producing capabilities. Therefore both of them takes the equal amount of time to reach normal levels, and both of them can be considered to have the same sensitivity to corticotropin. 2. Adrencortical responsiveness: Relatively small responsiveness to corticotropin compared to pituitary. The plasma concentration of cortisol, i.e. the response of the adrenocortical (to chronic absence of corticotropin) is much smaller than the ACTH concentration (the response of the pituitary). Furthermore, ACTH concentration increases over the normal plasma concentration suggesting a much higher responsiveness by the pituitary. Note: my definition for "response" changes when I described adrenocortical responsiveness. I have no clue how to apply these simple principles, and I hope someone can enlighten me. Thanks, IP!

WOW, thanks for that detailed response! You definitely clarified the question for me. I like how you added the equations along with the actual mechanistic explanation. I'm at med school, and the professor phrases our questions really bad. I knew that the membrane potential would (obviously) never exceed Ena. As voltage increased, the potassium gates would further limit it's Em from reaching Ena. Thanks again!

The reason I asked this question is because I got it wrong on my exam. But, the answer choices were poorly given. The question states that a person takes a drug that doesn't close the voltage sodium gates in neurons. The only two possible choices were that 1. The action potential fires normally, but with an increasing action potential or the 2. magnitude of the membrane potential would stay between Ek and ENa. The amplitude of the action potential would increase because sodium will flow in much faster than the na/k pump can pump out, and although as voltage increases, the efflux of potassium due to the increased permeability ( voltage gated potassium would stay open as sodium is constantly depolarizing). I believe both answers are correct. The action potential magnitude would reach close to the Ena value since sodium is rushing in much faster, and the slow closing potassium gates willl not influence this. Used my iphone to type this. Sorry for errors.

What scenarios are possible, if one consumes a drug that blocks the closing of the voltage-gated Sodium gates? a) Would the action potential fire as usual, but the amplitude of the action potential be higher? b) Would the action potential be between the value of Ek and Ena? Also, if the voltage gates are never closed, there will be no depolarization phase right? Would that still count as an action potential if the membrane never repolarize? -OR- Would the increase in membrane potential, keep activating more and more potassium channels as well, and keep the value between Ek and Ena?