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Critical Analysis On Constantina Case Study

Question

Task: Constantina is a 38yo marathon runner who has presented to her GP clinic after completing a training run. She trains three days per week, and has experienced light-headedness, and significant muscle pain after her last three runs. Whilst talking to the clinic nurse, Constantina admits to feeling lethargic, and like her “heart is racing”. She has also been a little unsteady on her feet and stumbled climbing the stairs in her home the previous evening. She reveals her fluid intake has been lower than usual, and although she is still eating well, her caloric intake has been less than usual. She has lost 2kg in the last month.
Constantina applied Voltaren Emulgel, a topical non-steroidal anti-inflammatory drug (NSAID), to her quadriceps and calves immediately after this morning’s run, hoping to relieve some of her muscle soreness.
A medical history was taken, and urinalysis conducted, identifying the following:
Question 1 (8 marks total)
A. Endometrial tissue contains glandular structures relevant to Constantina’s reproductive function. Note the role of this glandular tissue in reproductive function, including any likely changes from normal in the secretion and resultant effects for Constantina.
B. Considering Constantina and her current circumstances, describe the role of oestrogen and discuss how the levels of this hormone may vary from normal.
Question 2
A. Describe the role of the kidneys in maintaining fluid balance with reference to the role of antidiuretic hormone (ADH). Is Constantina at risk of not maintaining homeostatic fluid mechanisms? Why/why not?
B. What is a urinalysis and what is its significance for this case? With respect to the specific gravity (SG) component of Constantina’s urinalysis result, and using your knowledge of normal kidney function, would you expect this result? Why/why not?
Question 3
A. What is gut motility? Is it likely that Constantina’s gut motility has increased or decreased from normal? Discuss EITHER peristalsis OR segmentation in your response.
B. Why is it important for Constantina to maintain adequate protein intake? Discuss its importance in cellular recovery in your response.
Question 4
A. Constantina has used Voltaren Emugel (containing a NSAID) to ease her aching muscles. Identify the route of administration and discuss how the drug is likely to be absorbed after administration and its likely bioavailability. Justify your answer by discussing whether the drug would be subjected to hepatic first pass.
B. What is the importance of the half-life of a drug? Assuming 100% absorption and the half-life of an NSAID is 8 hours, calculate the % amount of drug that is likely to be present in the blood after 24 hours.
Question 5
A. Consider Constantina’s blood pressure result and discuss whether the mean arterial pressure is likely to be varied from normal. In your answer you must include reference to a possible change in blood viscosity and briefly mention the consequences of any change in BP upon kidney function.
B. Discuss the role of the renin-angiotensin-aldosterone system in the maintenance of blood pressure in Constantina’s circumstance.

Answer

The main aim of the essay is to critically discuss the Constantina case study who has visited GP for experiencing muscle pain, lethargic, high pulse rate and light headedness. She is reported with unsteadiness and complains that she is reluctant towards drinking fluids despite eating well and has also lost 2 kg of weight in last month. The essay will take into account the health data collected from physical examination urinalysis to address the functioning of her body. 

According to the Constantina case study, it is noted that Constantina is a marathon runner and has been experiencing muscle pain. Research on Constantina case study has noted that the major function of the glandular tissue is to secrete glycogen which causes an increase in the flow of blood to the spiral arteries with the response to increasing the progesterone level (Brame, Macedo & Klein, 2017). However, it is also noted from the research of Hackney, Smith-Ryan and Fink (2020) that high-intensity exercise tends to lower the secretion of progesterone that directly affects the menstrual cycle. Relating to the Constantina case study, Constantina gets trained for three days per week has lowered the level of progesterone which in turn causes the low secretion of glycogen from glandular tissue. Thus, it can negatively affect the reproduction of the function of Constantina.

In reproductive function, the role of oestrogen is to maintain the bone strength, increase cholesterol level and sexual characteristic. The research by Schmitz et al. (2015) found that women engaged in more than 100 min of exercise per week, the level of oestrogen vary from normal and causes its low secretion. Constantina being engaged in strenuous exercise impact the low level of oestrogen thus leading to menstrual imbalance. Oestrogen also functions to increase blood pressure as it causes the formation of superoxide in the brain (Schmitz et al., 2015). It is also noted that the blood pressure of Constantina is lower thus it can be said that due to a low level of oestrogen, the prevalence of hypotension has occurred or negatively impacted the physiological function.

Concentrating on Constantina case study it is noted that due to excess exercise, the prevalence of lethargy, unsteadiness and lower in fluid intake has occurred. Research has noted the role of the kidney in maintaining the fluid volume in the body (haemostasis) that reabsorb the water and excrete in the form of urine through the influence of antidiuretic hormone (Wiig, Luft & Titze, 2018). ADH acts on the late distal tubules and collecting duct leading to phosphorylation of aquaporin-2 that increases the movement of water due to osmotic gradient and thus reabsorption of water by kidney takes place and haemostasis is maintained (Masuda et al., 2020). Constantina is at risk of homeostatic fluid imbalance which is attributed to the fact of high specific gravity (1.035), dryness of lips, poor skin turgor, and dark circles under eyes. Research by Rosinger (2015) indicated that high specific gravity of urine shows extreme dehydration (>1.030) and as Constantina has reported less intake of fluid, thus loss of body fluid has not been replenished and causes the risk of not maintaining homeostatic fluid mechanisms.

Urinalysis is a urine test that is done to detect the function of the kidney (Musa, 2015). In the present Constantina case study, it is conducted to find the rationale for a poor health issue of Constantina. The specific gravity of urine noted in the report is high where research suggests that it reflects the dysfunction in renal tubules in responding to ADH hormone (Rosinger, 2015). Similarly, kidney functions to regulate the water absorption, but due to renal dysfunction, the reabsorption of water is prevented and increases the excretion of urine due to the reverse osmotic gradient that leads to an upsurge in the concentration of solute in urine (Masuda et al., 2015. Thus, water loss from the body leads to dehydration and the high specific gravity of urine which is expected in the Constantina case study as she is at risk of homeostatic fluid imbalance.

It is noted in the Constantina case study that she has lost 2 kg of weight despite eating well which is associated with low body volume and dehydration. Gut motility is the movement of food from the mouth to the large intestine which takes place due to synchronized contraction and stretching of muscles known as peristalsis. The research by Cremer et al. (2016) noted that water is the medium through which the food moves down through the intestine by increasing peristalsis movement. In the situation of dehydration large intestine absorbs water present in food and making its passage difficult. Thus, from the evidence, it can be said that the peristalsis movement of Constantina is likely to decrease.

The research by Weber, Davies & Grune (2015) considered in the context of Constantina case study noted that protein is included in the diet to repair cells, tissue, promote growth and take in metabolic activities after each training session. Constantina being a marathon runner and undergo strenuous exercise, which has resulted in muscle pain thus indicates damage to muscle tissue. Recent evidence has shown that ingestion of protein during or following the exercise is crucial to maintain the integrity of the cell and accelerates repair of the damaged cell by breaking down of protein into amino acid (Stokes et al., 2018). Thus, it is significant for Constantina to maintain adequate diet and intake of protein because protein cannot be stored in the body and it is central in providing the skeleton muscle with components that are required to optimise recovery. 

As discussed in the Constantina case study, in order to get relief from muscle pain, Constantina has used Voltaren Emugel which contains NSAID. It is administered topically over the affected are area. The main component of the Voltaren Emugel is Diclofenac sodium which is absorbed from the GI tract. Research by Mahdi et al. (2016) noted that Diclofenac is a carboxylic acid constituent that is known to get completely absorbed when administered topically and it differs from other NSAIDs due to the fact that it undergoes first-pass effect. In support of that, Zhang et al. (2016) noted that only 60% of the drug reaches the systematic circulation suggesting its low bioavailability. 

Considering the fact of low bioavailability of Voltaren Emugel, half of life is considered as the crucial pharmacokinetic factor because it tends to estimate the duration of time the medicine will persist or show its action or remove from the body. Assuming 100% absorption of the NASID drugs, its half-life is 8 hours. After the next 8 hours, 50% of the drug will remain in the blood. In the next 8 hours, at 16hrs, 25% of the drug will remain in the blood. After the next 8 hours at 24 hours, only 12.5% of the drug will remain in the blood. 

The report of Hawryluk et al. (2015) considered in this Constantina case study analysis shows that mean arterial pressure in humans is considered to be 70mm Hg or above up to 100 mmHg and may lead to tissue perfusion and oxygen delivery. The relation of blood viscosity and blood pressure shows the change in the mean arterial pressure. Research by Zimmerman et al. (2017) has noted that when there are increases in blood viscosity, the total peripheral resistance (TPR) tends to augment its level and cause a decrease in the flow of blood. As the arterial blood pressure is dependent on the cardiac output and total peripheral resistance, there must be an upsurge in the systolic blood pressure and hence blood pressure must be high to maintain the circulation of blood volume. The blood pressure noted in the physical examination of Constantina is 87/58 mm Hg which is lower as the normal range is 120/90 mm Hg. It suggests that low blood pressure causes less blood viscosity with the response to low total peripheral resistance. Therefore, the flow of blood is increased and causes a decrease in mean arterial pressure. Research has also shown that a decrease in blood pressure leads to low blood volume and its inadequate flow in the glomerulus (Wagener & Bakker, 2015).

Blood pressure is also regulated renin-angiotensin-aldosterone system where the release of renin by the kidney is stimulated in response to low blood pressure as noted in the Constantina case study. It causes the stimulation of angiotensinogen to form angiotensin I which in turn causes the production of angiotensin II that is considered as the main effector of RAAS (Muñoz-Durango et al., 2016). It further causes the release of aldosterone hormones that act on the kidney and cause absorption of sodium from the epithelium and transfer it to the circulation of blood. Thus, increase the blood sodium level and blood volume which causes an upsurge in the blood pressure. 

Lastly from the above discussion on Constantina case study, it can be concluded that she has been encountring an issue of dehydration and hypotension lined with the high specific gravity of urine and low blood pressure. Considering the Constantina case study, it is also clear that it is important to administer fluid to replenish the loss of water and guide her to maintain good health.

Reference
Bramer, S. A., Macedo, A., & Klein, C. (2017). Hexokinase 2 drives glycogen accumulation in equine endometrium at day 12 of diestrus and pregnancy. Reproductive Biology and Endocrinology, 15(1), 4. Constantina case study Retrieved from https://doi.org/10.1186/s12958-016-0223-4

Cremer, J., Segota, I., Yang, C. Y., Arnoldini, M., Sauls, J. T., Zhang, Z., ... & Hwa, T. (2016). Effect of flow and peristaltic mixing on bacterial growth in a gut-like channel. Proceedings of the National Academy of Sciences, 113(41), 11414-11419. Retrieved from https://doi.org/10.1073/pnas.1601306113

Hackney, A. C., Smith-Ryan, A. E., & Fink, J. E. (2020). Methodological considerations in exercise endocrinology. In Endocrinology of Physical Activity and Sport (pp. 1-17). Humana, Cham. Retrieved from https://doi.org/10.1007/978-3-030-33376-8_1

Hawryluk, G., Whetstone, W., Saigal, R., Ferguson, A., Talbott, J., Bresnahan, J., ... & Manley, G. (2015). Mean arterial blood pressure correlates with neurological recovery after human spinal cord injury: analysis of high frequency physiologic data. Journal of neurotrauma, 32(24), 1958-1967. Retrieved from https://doi.org/10.1089/neu.2014.3778

Mahdi, M. H., Conway, B. R., Mills, T., & Smith, A. M. (2016). Gellan gum fluid gels for topical administration of diclofenac. International journal of pharmaceutics, 515(1-2), 535-542. Retrieved from https://doi.org/10.1016/j.ijpharm.2016.10.048

Masuda, T., Muto, S., Fukuda, K., Watanabe, M., Ohara, K., Koepsell, H., ... & Nagata, D. (2020). Osmotic diuresis by SGLT2 inhibition stimulates vasopressin?induced water reabsorption to maintain body fluid volume. Physiological Reports, 8(2), e14360. Retrieved from https://doi.org/10.14814/phy2.14360

Muñoz-Durango, N., Fuentes, C. A., Castillo, A. E., González-Gómez, L. M., Vecchiola, A., Fardella, C. E., & Kalergis, A. M. (2016). Role of the renin-angiotensin-aldosterone system beyond blood pressure regulation: molecular and cellular mechanisms involved in end-organ damage during arterial hypertension. International journal of molecular sciences, 17(7), 797. Retrieved from https://doi.org/10.3390/ijms17070797

Musa, M. U. (2015). The role of urine investigations in urology practice. Open Journal of Orthopedics, 5(04), 90. Retrieved from https://www.scirp.org/html/4-2010264_55622.htm

Rosinger, A. (2015). Heat and hydration status: Predictors of repeated measures of urine specific gravity among Tsimane’adults in the Bolivian Amazon. American journal of physical anthropology, 158(4), 696-707. Retrieved from https://doi.org/10.1002/ajpa.22813

Schmitz, K. H., Williams, N. I., Kontos, D., Domchek, S., Morales, K. H., Hwang, W. T., ... & Galantino, M. L. (2015). Dose–response effects of aerobic exercise on estrogen among women at high risk for breast cancer: a randomized controlled trial. Constantina case study Breast cancer research and treatment, 154(2), 309-318. Retrieved from https://doi.org/10.1007/s10549-015-3604-z

Stokes, T., Hector, A. J., Morton, R. W., McGlory, C., & Phillips, S. M. (2018). Recent perspectives regarding the role of dietary protein for the promotion of muscle hypertrophy with resistance exercise training. Nutrients, 10(2), 180. Retrieved from https://doi.org/10.3390/nu10020180

Wagener, G., & Bakker, J. (2015). Vasopressin in cirrhosis and sepsis: physiology and clinical implications. Minerva anestesiologica, 81(12), 1377-1383. Retrieved from https://www.researchgate.net/profile/Jan_Bakker/publication/268228215_Vasopressin_in_cirrhosis_and_sepsis_Physiology_and_clinical_implications/links/569d7f2108ae16fdf07999ec/Vasopressin-in-cirrhosis-and-sepsis-Physiology-and-clinical-implications.pdf

Weber, D., Davies, M. J., & Grune, T. (2015). Determination of protein carbonyls in plasma, cell extracts, tissue homogenates, isolated proteins: focus on sample preparation and derivatization conditions. Redox biology, 5, 367-380 Retrieved from. https://doi.org/10.1016/j.redox.2015.06.005

Wiig, H., Luft, F. C., & Titze, J. M. (2018). The interstitium conducts extrarenal storage of sodium and represents a third compartment essential for extracellular volume and blood pressure homeostasis. Acta physiologica, 222(3), e13006. Retrieved from https://doi.org/10.1111/apha.13006

Zhang, Y., Han, Y. H., Putluru, S. P., Matta, M. K., Kole, P., Mandlekar, S., ... & Yang, Z. (2016). Diclofenac and its acyl glucuronide: determination of in vivo exposure in human subjects and characterization as human drug transporter substrates in vitro. Drug Metabolism and Disposition, 44(3), 320-328. Retrieved from https://doi.org/10.1124/dmd.115.066944

Zimmerman, R., Tsai, A. G., Vázquez, B. Y. S., Cabrales, P., Hofmann, A., Meier, J., ... & Intaglietta, M. (2017). Post-transfusion increase of hematocrit per se does not improve circulatory oxygen delivery due to increased blood viscosity. Constantina case study Anesthesia and analgesia, 124(5), 1547. Retrieved from https://dx.doi.org/10.1213%2FANE.0000000000002008

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