Alterations in Cellular Processes

At its core, pathology is the study of disease. Diseases occur for many reasons. But some, such as cystic fibrosis and Parkinson’s Disease, occur because of alterations that prevent cells from functioning normally.

Understanding of signals and symptoms of alterations in cellular processes is a critical step in diagnosis and treatment of many diseases. For the Advanced Practice Registered Nurse (APRN), this understanding can also help educate patients and guide them through their treatment plans.

For this Discussion, you examine a case study and explain the disease that is suggested. You examine the symptoms reported and explain the cells that are involved and potential alterations and impacts.

resources

Be sure to review the Learning Resources before completing this activity.

Click the weekly resources link to access the resources.

WEEKLY RESOURCES

To prepare:

By Day 1 of this week, you will be assigned to a specific scenario for this Discussion. Please see the “Course Announcements” section of the classroom for your assignment from your Instructor.

by day 3 of Week 1

Post an explanation of the disease highlighted in the scenario you were provided. Include the following in your explanation:

The role genetics plays in the disease.

Why the patient is presenting with the specific symptoms described.

The physiologic response to the stimulus presented in the scenario and why you think this response occurred.

The cells that are involved in this process.

How another characteristic (e.g., gender, genetics) would change your response.

Read
a selection of your colleagues’ responses.

by day 6 of Week 1

Respond
to
at least two
of your colleagues on
2 different days
and respectfully agree or disagree with your colleague’s assessment and explain your reasoning. In your explanation, include why their explanations make physiological sense or why they do not.

Note:
For this Discussion, you are required to complete your initial post before you will be able to view and respond to your peers’ posting. Remember, once you click on Submit, you cannot delete or edit your own posts, and you cannot post anonymously. Please check your post carefully before clicking on Submit!

This topic is closed for comments.

Cheryl Athurine Spence

Nov 30, 2023 10pm

Reply from Cheryl Athurine Spence

Post Discussion 1
st
Response

Hi. Rosy,

I agree with your post. The patient assessment may be a genetic predisposition to the patient’s susceptibility to substance abuse. The scenario presented involves several physiological aspects that can be explained in terms of the patient’s history of substance abuse and the subsequent treatment with naloxone. Genetic factors can indeed play a role in the patient’s susceptibility to substance abuse (Van Den Besselaar et al., 2022). Studies suggest that genetic variations can influence an individual’s predisposition to addiction by affecting neurotransmitter pathways, altering drug metabolism, and controlling the reward and pleasure circuits in the brain. Certain genetic variations can increase the likelihood of developing substance use disorders (SUDs) when exposed to drugs or other addictive substances.

I agree with the explanation that the patient’s symptoms, including burning pain and necrotic tissue, are consistent with rhabdomyolysis. The burning pain over the left hip and forearm and necrotic tissue over the greater trochanter and forearm could indicate a condition known as Rhabdomyolysis (Van Den Besselaar et al., 2022). In cases of substance abuse, especially opioids, prolonged immobility and pressure on specific body parts can lead to reduced blood flow, causing ischemia and subsequent tissue necrosis. Rhabdomyolysis involves breaking skeletal muscle tissue and releasing myoglobin and other intracellular contents into the bloodstream, leading to tissue damage and potentially necrotic areas.

I also agree with the analysis of the physiological response involving hyperkalemia, as indicated by the prolonged PR interval and peaked T waves on the EKG, coupled with the elevated serum potassium level. The EKG changes observed (prolonged PR interval and peaked T waves) and the high serum potassium level (6.9 mEq/L) indicate hyperkalemia. In the context of opioid toxicity and naloxone administration, opioid overdose can lead to the inhibition of the sympathetic nervous system. This inhibition can cause excess acetylcholine release, leading to the shift of potassium out of cells and subsequently elevated serum potassium levels (Van Den Besselaar et al., 2022). Hyperkalemia can result in cardiac conduction abnormalities, such as the EKG changes observed. The physiological response to opioid toxicity, compounded by substance abuse history and subsequent naloxone administration, leads to alterations in sympathetic nervous system activity, which in turn affects potassium homeostasis, resulting in the observed EKG changes and hyperkalemia.

References:

Kruit, N., van den Besselaar, L. R., Kamsteeg, E. J., Verbeeck, W., Snoek, M. M. J., Everaerd, D. S., … & Voermans, N. C. (2021). The etiology of rhabdomyolysis: an interaction between genetic susceptibility and external triggers.
European Journal of Neurology
,
28
(2), 647-659.
https://doi.org/10.1111/ene.14553
Links to an external site.

Van Den Bersselaar, L. R., Hellblom, A., Gashi, M., Kamsteeg, E. J., Voermans, N. C., Jungbluth, H., … & Snoeck, M. M. (2022). Referral indications for malignant hyperthermia susceptibility diagnostics in patients without adverse anesthetic events in the era of next-generation sequencing.
Anesthesiology
,
136
(6), 940-953.
https://doi.org/10.1097/ALN.0000000000004199
Links to an external site.
.

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Patricia Chioma Ayika

Nov 29, 2023 11:52pm
|
Last reply Dec 1, 2023 7:01pm

Reply from Patricia Chioma Ayika

According to this scenario, the patient is probably suffering from rhabdomyolysis, a disorder that causes skeletal muscle tissue to break down and release intracellular components like myoglobin into the bloodstream. Heart problems, renal failure, and electrolyte imbalances are just a few of the consequences that may arise from this.

Genetics’ role

Rhabdomyolysis can be inherited; however, it is most commonly linked to extrinsic factors such trauma, crush injuries, or drug addiction. Certain muscle illnesses might also be predisposed to genetically. Certain individuals may be more prone to muscle breakdown under specific settings due to genetic variables that affect muscle form and function.

.
Symptom Presentation
: • The searing pain over the left forearm and hip is probably caused by muscle tissue necrosis and ischemia in these locations. The patient’s complaints of discomfort after receiving naloxone in the field raise the possibility that they were the victim of an opioid overdose, which can cause respiratory depression and extended immobility. Pressure on the muscles from prolonged immobility might result in ischemia and rhabdomyolysis.

Physiologic Response
: Hyperkalemia is indicated by a prolonged PR interval, peaked T waves on the EKG, and a high serum potassium level (6.9 mEq/L). Large volumes of intracellular potassium are released into the bloodstream during rhabdomyolysis, overriding the body’s natural regulatory systems. Arrhythmias and cardiac arrest are among the cardiac disorders that can result from hyperkalemia.

In conclusion, the patient’s extended immobility after an opiate overdose most certainly resulted in rhabdomyolysis. Contents may be influenced by genetic characteristics, which could result in problems such acute renal damage and hyperkalemia. Further understanding of the appearance and treatment of rhabdomyolysis in individual cases can be gained by taking into account factors such as gender, heredity, and the particular drug implicated.

References

Baltes,A.,Akhtar,W.,&Birstler,.(2020). Predictors of skin and soft tissue infections among sample of rural residents who inject drugs. Harm Reduction Journal 17(96)

https//doi.org10.1186/s12954-020-00447-3

McCaeve, K.L & Huether.S,E,(2019).Pathophysiology: The biologic basic for disease in adults and children (8
th
ed.).St louis.MO:Mosby/Elsevier

Bigham,B.(2017), Are you considering crush injury in overdoses? Emergency and mobile medicine learning network. Retrieve from

https//www.hmoglobaillearningwork,com site/emsworld/article/12317524/are-you/considering-crush-injury-in-narcotic-overdoses

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Ramandeep Kaur

Nov 29, 2023 11:11pm
|
Last reply Dec 3, 2023 1:01am

Reply from Ramandeep Kaur

1. The role genetics plays in the disease.

The usage and addiction to addictive chemicals are influenced by a combination of genetic and environmental factors. Addictions have been found to have a moderate to high heritability. The risk of substance abuse in an individual is related to the extent of genetic connection to a relative with addiction (McCane & Huether, 2019). Addiction vulnerability is a complex interplay of genetic and life experience factors. One extensively studied gene in terms of genetic vulnerability is the D2 subtype. When drugs or alcohol are consumed, the brain is stimulated to release dopamine, a neurotransmitter responsible for pleasure and reward experiences. The presence of the D2 subtype gene affects the response to dopamine. Individuals lacking this gene tend to have a stronger craving for alcohol and consume larger amounts compared to those who possess the gene. This is because individuals without the D2 gene do not experience the benefits of dopamine as strongly as those with the gene, leading them to drink more in order to achieve the same sensation.

Why is the patient presenting with the specific symptoms described?

Due to an opiate overdose, the patient was initially unresponsive. However, after receiving Naloxone in the field, the patient became responsive again. Naloxone, an opioid antagonist, was administered to counteract the effects of the opiate overdose. Opioids can suppress breathing, and an overdose can lead to respiratory depression. The respiratory center is depressed, and the breathing rate falls gradually until respiratory failure occurs (McCane & Huether, 2019). It is probable that the substantial amount of necrotic tissue present over the greater trochanter of the left hip and forearm is a consequence of physical injury sustained during the fall when the patient became unconscious. (Haikin, Herzberger, Aviner, & Cherniavsky, 2012. Necrosis is the term used to describe cellular death caused by inadequate blood and oxygen supply to the tissue. The patient’s condition may indicate the presence of rhabdomyolysis, which is a condition caused by muscle injury resulting from the accident. The EKG results showed an extended PR interval and elevated T waves. Additionally, the serum potassium level was measured at 6.9 mEq/L, indicating high potassium levels that contribute to the longer PR interval and peaked T waves (Weiss, Qu, & Shivkumar, K. 2017). Elevated levels of creatine kinase, myoglobin in the blood and urine, as well as potassium and creatinine in the blood and urine, are indicative of muscle injury. Further investigation is required to identify the specific genes that may be involved in the development of the disease.

The physiologic response to the stimulus presented in the scenario and why you think this response occurred?

Immunosuppression refers to a reduction in the activation or efficiency of the immune system. Certain components of the immune system can suppress other aspects of its functioning, and immunosuppression can occur as an unintended consequence of treating other illnesses. Prolonged drug use and dependency can cause significant damage to various bodily systems, particularly the immune system. Intoxicating substances can directly harm the immune system, or the method of drug administration may increase the likelihood of infections, especially among intravenous drug users.

The cells that are involved in this process.

According to the National Institute on Drug Abuse, opioids work by binding to specific proteins called opioid receptors that are present on nerve cells in various parts of the body, including the brain, spinal cord, and gastrointestinal tract. By attaching to these receptors, opioids alter the brain’s perception of pain and induce a sense of euphoria. Additionally, they can cause a decrease in heart rate and breathing rate.

How another characteristic (e.g., gender, genetics) would change your response.

In general, men have higher rates of illicit drug use compared to women. However, when it comes to opioid use, women tend to be more sensitive to pain and are more likely to experience chronic pain. This higher prevalence of chronic pain among women may contribute to the higher rates of opioid prescriptions among women of reproductive age.

References:

McCance, K. L., & Huether, S. E. (2010).
Pathophysiology: The biologic basis for disease in adults and children
(6th ed.). Mosby Elsevier.

Haikin Herzberger, E., Aviner, S., & Cherniavsky, E. (2012). Posttraumatic fat necrosis presented as cellulitis of the leg.
Case reports in pediatrics
,
2012
.

Weiss, J. N., Qu, Z., & Shivkumar, K. (2017). Electrophysiology of hypokalemia and hyperkalemia.
Circulation: Arrhythmia and Electrophysiology
,
10
(3), e004667.

National Institute on Drug Abuse. (2020, May 28). Sex and Gender Differences in Substance Use. Retrieved November 29,2023, from
https://www.drugabuse.gov/publications/research-reports/substance-use-in-women/sex-gender-differences-in-substance-use
Links to an external site.

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Ramandeep Kaur

Nov 29, 2023 10:34pm
|
Last reply Dec 2, 2023 9:23pm

Reply from Ramandeep Kaur

1. The role genetics plays in the disease.

Genetics undoubtedly plays a substantial role in the development of heart attacks. Numerous studies have demonstrated that specific genetic variations can heighten the risk of cardiovascular diseases, including heart attacks. For instance, variations in genes responsible for lipid metabolism, blood clotting, and inflammation can contribute to the formation of atherosclerosis, a primary factor underlying heart attacks. Understanding these genetic factors can help identify individuals at higher risk and inform preventative measures and targeted treatments. In a study conducted by McPherson et al. (2016), it was found that genetic factors accounted for approximately 40-50% of the risk of developing coronary artery disease, which often leads to heart attacks. Consequently, individuals who have a family history of heart attacks or cardiovascular diseases may possess a heightened genetic predisposition to developing the condition. Genetics plays a role in all diseases to an extent. Variations and functions in DNA (alone or in combinations) alongside the environment contribute to disease processes. Still, cellular and bodily responses to the environment may differ according to our DNA (Jackson et al., 2018). The immune system has genetic control factors. Still, it is sensitive to environmental drivers, given that these factors serve as a control mechanism for limiting the impact of transmissible pathogens. Susceptibility or resistance to diseases, such as autoimmunity, allergy, and inflammation, can sometimes be linked to genetic compounds (Soderholm et al., 2018), Soo (2018) discussed that secondary immune deficiencies are related to stress and poor nutrition and can be related to hormone imbalances.

Why is the patient presenting with the specific symptoms described?

Based on the patient’s specific symptoms, it is possible that they are experiencing a heart attack. Typical signs of a heart attack include chest pain or discomfort, shortness of breath, lightheadedness, nausea, and pain or discomfort in the arms, neck, jaw, or back. These symptoms occur when there is a reduction or blockage in the blood flow to the heart muscle, resulting in insufficient oxygen supply. The patient’s description of symptoms aligns with the common indicators of a heart attack. It is important for them to seek immediate medical attention. According to the American Heart Association (AHA), chest pain or discomfort is the most common symptom experienced by both men and women during a heart attack.

The physiologic response to the stimulus presented in the scenario and why you think this response occurred
?

The body’s response to the situation described in the scenario, which is a heart attack, occurs when the flow of blood to the heart muscle is interrupted. This interruption can occur when a blood clot forms in one of the coronary arteries, causing a blockage. The blockage then restricts the delivery of oxygen and nutrients to the heart muscle, leading to ischemia. When there is insufficient oxygen, the cells of the heart muscle undergo anaerobic metabolism, resulting in the production of lactic acid. The buildup of lactic acid is responsible for causing the feeling of chest pain or discomfort. Furthermore, the lack of oxygen causes the heart muscle cells to become electrically unstable, which can lead to irregular heart rhythms.

The cells that are involved in this process.

During a heart attack, various cells play a role in the process. The main cells affected are known as cardiomyocytes, which are responsible for the muscle function of the heart. These cells rely on a continuous supply of oxygen and nutrients to carry out their functions effectively. However, when there is a disturbance in the blood flow to the heart muscle, the cardiomyocytes are deprived of oxygen, causing them to malfunction. In more severe cases, this lack of oxygen can result in cell death. In addition to cardiomyocytes, other cells that play a role in a heart attack include endothelial cells, which form the lining of blood vessels, and platelets, which are involved in the formation of blood clots. Inflammatory cells, such as macrophages, also contribute to the progression of atherosclerosis, a condition that can eventually lead to a heart attack.

How another characteristic (e.g., gender, genetics) would change your response?

An individual’s response to a heart attack can be influenced by factors like gender and genetics. Gender differences have been noted in the way heart attacks present and the outcomes that follow. For example, women may experience symptoms that are atypical, such as fatigue, indigestion, or shortness of breath, instead of the typical chest pain commonly associated with heart attacks. The severity and progression of a heart attack can be influenced by genetic factors. Variations in genes related to blood clotting, lipid metabolism, and inflammation can affect an individual’s vulnerability to developing a heart attack. Furthermore, specific genetic variations can impact how an individual responds to medications commonly used in the treatment of heart attacks. Considering gender and genetics can provide valuable information for tailoring personalized treatment and management approaches for heart attacks.

Reference:

Soo, P. (2018, July 28) Pathophysiology CH 10 alterations in immune function [Video file]Retrieved from
https://www.youtube.com/watch?v=Jz0wx1-jTd
Links to an external site.

Soderholm, A. T., Barnett, T. C., Sweet, M. J., & Walker, M. J. (2018). Group A streptococcal pharyngitis: Immune responses involved in bacterial clearance and GAS‐associated immunopathologies.Journal of leukocyte biology,103(2), 193-213

Jackson, M., Marks, L., May, G., & Wilson, J. B. (2018).The genetic basis of disease. Essays in biochemistry,62(5), 643-723.
https://doi.org/10.1042/EBC20170053
Links to an external site.

McPherson, R., Tybjaerg-Hansen, A. (2016). Genetics of Coronary Artery Disease. Circulation Research, 118(4), 564-577. doi: 10.1161/CIRCRESAHA.115.306566

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Cheryl Athurine Spence

Nov 29, 2023 10:14pm
|
Last reply Dec 1, 2023 9:17pm

Reply from Cheryl Athurine Spence

Alterations In Cellular Processes

The paper focuses on a 27-year-old patient who has a substance abuse history and the use of emergency medical services (EMS). The roommate notified the EMS that the patient was lying on the floor unresponsively. During his medical workup by the EMS, the patient was given Naloxone and then regained consciousness. During the assessment, the patient reported burning pain in the forearm and left hip. This paper will, therefore, assess the genetic role, reason the patient presents the specific symptoms, physiological response towards the stimulus, the cell involved, and ways another characteristic would change the response.

The Role of Genetics

The patient presents Rhabdomyolysis, a condition due to prolonged immobility related to prolonged unresponsiveness that delays blood supply to parts of the body that facilitate autolysis and high potassium serum levels. (Kruijt et al. (2020). In such a case, genetics has no role in hyperkalemia, and acute Rhabdomyolysis can result from narcotic drug overdose. However, the primary genetic components that may have had a hand in the condition include lactate dehydrogenase, carnitine, and McCardle’s disease, among other factors.

Reasons for the Presenting Symptoms

The case study evidence points towards different facts concerning the patient’s condition. For instance, once the patient is administered Naloxone, which is an opioid antagonist, he responds, proving that he has opioid drug abuse (Rochester & Graboyes, 2020). The main aim of administering the Naloxone medication, which is an opioid antagonist, is due to its efficacy in knocking opioids and allowing the patient to breathe normally. Therefore, the patient’s discomfort of pain in his forearm and the left hip may have been due to decreased opioid pain-relieving effects. However, there is a high possibility of pain in the forearm and left hip caused by the abrupt fall that the patient experienced.

Physiological Response Towards the Stimulus and the Cell Involved

The physiological response to a stimulus reflects an automatic, unlearned, and instinctive reaction. In the case scenario of the patient, the decrease in adenosine triphosphate (ATP) production may have been due to decreased blood supply to the patient’s forearm and greater trochanter (Kruijt et al., 2020). Such ATP decrease led to increased intracellular calcium, which results in potassium exchange, thus raising serum K+ levels. Consequently, due to Rhabdomyolysis, the calcium and sodium pump becomes dysfunctional, with limited capability to regulate these exchanges. According to Kruijt et al. (2020), the calcium and sodium pump dysfunction causes hypercalcemia and hypokalemia in the extracellular fluids (ECF). Also, the rise of potassium levels depresses the impulse conduction velocity, leading to peaked T-waves and PR interval. When reflecting on the case scenario, patients can elaborate hyperkalemia by recording ECF higher than 5.0mEq/L, while severe hyperkalemia can be illustrated when patients possess serum levels higher or equal to 6.0mEq/L (Kruijt et al., 2020).

Ways Another Characteristic Would Change the Response

When assessing the patient’s case scenario, genetics did not play any role in developing Rhabdomyolysis. The same response would be provided for a female patient. The main reason for such an assumption is the effects of hyperkalemia on the patients, considering that the condition interferes with appropriate electrical signaling to the heart muscle, leading to abnormal ECG results (Kruijt et al., 2020). That is particularly true for individuals with Chronic Obstructive Pulmonary Disease and heart conditions, thus increasing their opioid intake.

Conclusion

The case study reflects a 27-year-old case scenario that has a substance use history. The roommate reports to the EMG that he had been lying down for an unknown period. From evaluation, genetics did not have any role in the patient’s case since Rhabdomyolysis is mainly caused by an interference with appropriate electrical signaling to the heart muscle, leading to abnormal ECG results.

References

Kruijt, N., Bersselaar, L. R., Kamsteeg, E. J., Verbeeck, W., Snoeck, M. M. J., Everaerd, D. S., Abdo, W. F., Jansen, D. R. M., Erasmus, C. E., Jungbluth, H., & Voermans, N. C. (2020). The etiology of rhabdomyolysis: an interaction between genetic susceptibility and external triggers.
European Journal of Neurology
,
28
(2), 647–659. https://doi.org/10.1111/ene.14553

Rochester, E., & Graboyes, M. (2020). Experiences of people who use drugs with naloxone administration: a qualitative study.
Drugs: Education, Prevention and Policy
, 1–8. https://doi.org/10.1080/09687637.2020.1855116

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Courtney Rae Sanders

Nov 29, 2023 10:01pm
|
Last reply Dec 2, 2023 8:55pm

Reply from Courtney Rae Sanders

Week 1 Main Discussion Board Post

Purpose Statement

The purpose of this post is to analyze the pathophysiology seen in a case study of tissue necrosis and hyperkalemia resulting from a substance abuse overdose. Key areas covered will include examining how genetics plays a role in addiction, explaining why pressure ulcers formed over areas of prolonged pressure during unresponsiveness, analyzing the electrolyte imbalance occurring at the cellular level, describing the EKG changes secondary to elevated potassium, and considering how age or genetic predisposition for poor wound healing might alter the degree of tissue damage seen. The aim is to synthesize knowledge from the literature on the multi-systemic response in this emergency and discuss the underlying pathophysiology across the multiple body systems involved all the way to the cellular level.

The Role Genetics Plays in the Disease

An individual’s genetic makeup can influence susceptibility to substance abuse disorders. Variations in genes impacting reward pathways, impulse control, and habit formation may predispose certain patients to addictive behaviors and altered neurocircuitry (Volkow & Koob, 2015). However, environmental factors typically interact with genetics in the development of addiction. Studies of twins have shown alcoholism is approximately 50-60% hereditary, indicating a strong interaction between genetics and environment (Edenberg & Foroud, 2013). Exposure to substances is needed to activate genetic tendencies toward addiction. Childhood trauma, peer influence, and stress also help determine if genetic predispositions manifest clinically (Enoch, 2011). In addition to altering baseline addiction vulnerability, genetic and environmental interactions can also influence treatment outcomes (Ray et al., 2017). For example, variations in dopamine pathway genes seem to affect relapse rates when therapy compliance falters. Overall, the progression from recreational use to compulsive behaviors stems from a combination of genetic tendencies and life experiences.

Why the Patient is Presenting with These Symptoms

The patient is exhibiting necrotic skin and muscle tissue over the left hip and forearm likely due to prolonged pressure on these body areas during a prolonged unresponsive state from overdose. Lying perfectly still for an extended period without positional change or weight-shifting leads to localized external compression and restricted blood flow, culminating in ischemic cellular damage and cell death if prolonged (Black et al., 2010). As pressure duration and intensity increase, perfusion to vulnerable areas like bony prominences decreases, initiating inflammation and lesion development risk (The National Pressure Ulcer Advisory Panel, 2014).

In this patient, altered senses and mental status from the substance abuse prevented adequate movement or rolling to relieve pressure on the affected areas. Psychomotor retardation and decreased pain perception related to heroin and other narcotic use allowed tissue ischemia, hypoxia, free radical injury, and necrosis to advance unchecked for hours without the patient consciously shifting position (Dubick et al. 2018). This unrelieved pressure combined with the patient’s inability to perceive and respond to early warning signs of discomfort and blood flow impairment in the compressed areas contributed to extensive necrosis over the greater trochanter and forearm by the time of ED evaluation.

The Physiologic Response and Why It Occurred

The EKG findings of a prolonged PR interval and peaked T waves indicate hyperkalemia. The patient’s elevated serum potassium stems directly from extensive muscle death in the necrotic tissue. Potassium leaks out of dying muscle cells in the necrotic skin and tissue areas during cellular breakdown (Thompson Bastin & Cook, 2014). The measured serum potassium of 6.9 mEq/L reflects a significant spike from the normal range of 3.5-5.0 mEq/L. This degree of hyperkalemia impacts cardiac cellular depolarization and repolarization by reducing cardiac cell excitability and disrupts coordinated electrical activity causing the EKG changes (Kardalas et al., 2018).

The Cells Involved in This Process

The dying cells in the pressure ulcers include skin cells like keratinocytes and fibroblasts as well as fat cells and vascular cells from the blood vessels. Underlying muscle cells both skeletal and smooth muscle fibers also die as the wounds extend deeper. As all these cells swell and burst, their contents spill out. One vital intracellular component lost is potassium. There are very high levels of potassium inside healthy cells. But once cell membranes rupture, this potassium floods out into the extracellular space and into the bloodstream.

Too much potassium outside cells causes problems. Cardiac muscle cells rely on special pumps in their membranes to carefully control potassium movement in and out. Excess potassium outside heart cells impedes these pumps (Kay & Hoekstra, 2021). This prevents heart cells from passing electrical signals smoothly to contract in sync. Clinically, extra fluid potassium slows electrical conduction through the heart tissue. On EKGs, widened intervals and tall, peaked T waves reflect the underlying cellular issues. If severe and unchecked, deadly heart rhythm issues can occur. So, the dying skin and muscle cells releasing potassium explains the patient’s high blood potassium and corresponding EKG changes.

How Other Characteristics Would Change the Response

The patient’s gender would likely not impact the response and presentation in this scenario. However, if the patient had certain genetic variations associated with an increased risk of pressure ulcers or poor wound healing, the tissue damage may manifest more quickly or severely (Lootens et al., 2009). Additionally, older age leading to decreased skin integrity could have exacerbated the pressure ulcer development.

References

Black, J.M., Edsberg, L.E., Baharestani, M.M., Langemo, D., Goldberg, M., McNichol, L., Cuddigan, J. (2011). Pressure ulcers: avoidable or unavoidable? Results of the National Pressure Ulcer Advisory Panel Consensus Conference. Ostomy Wound Management. 57(2):24-37.

Dubick, M.A., Holcomb, J.B., and McManus, J.G. (2018). Unusual Pressure Ulcer Presentations in Military Casualties from Iraq and Afghanistan Wars. Military Medicine, 39(11/12): 683–686.

Edenberg, H. J & Foroud T. (2013). Genetics and alcoholism. Nature Reviews Gastroenterology & Hepatology 10, 487–494. https://doi.org/10.1038/nrgastro.2013.86

Enoch M. A. (2011). The role of early life stress as a predictor for alcohol and drug dependence. Psychopharmacology, 214(1), 17–31. https://doi.org/10.1007/s00213-010-1916-6

Kardalas, E., Paschou, S. A., Anagnostis, P., Muscogiuri, G., Siasos, G., & Vryonidou, A. (2018). Hypokalemia: a clinical update. Endocrine connections, 7(4), R135–R146. https://doi.org/10.1530/EC-18-0109

Kay, J., & Hoekstra, T. (2021). Hyperkalemia. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK554500/

Lootens, L., Brassine, L., Geys, H., Pottel, H., Peeraer, L., & Devuyst, O. (2009). Genetic predisposition to pressure ulcers: A case-control study. Journal of Investigative Dermatology, 129(8), 1946-1952. https://doi.org/10.1038/jid.2009.37

Ray, L. A., Bujarski, S., & Roche, D. J. O. (2017). How age of onset influences the risk and recovery for alcohol dependence. Addiction, 112(12), 2118–2130. https://doi.org/10.1111/add.13925

The National Pressure Ulcer Advisory Council (2014). Pressure ulcer stages revised by NPUAP. Washington, D.C.: National Pressure Ulcer Advisory Council.

Thompson Bastin, M. L., & Cook, A. M. (2014). Electrolyte and acid-base disorders in the emergency department. Emergency Medicine Clinics of North America, 32(3), 437–448. https://doi.org/10.1016/j.emc.2014.06.003

Volkow, N. D., & Koob, G. F. (2015). Brain disease model of addiction: Why is it so controversial? The Lancet. Psychiatry, 2(8), 677–679. https://doi.org/10.1016/S2215-0366(15)00236-9

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Gilliatt Gilliatt

Nov 29, 2023 9:40pm
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Last reply Nov 30, 2023 2:28am

Reply from Gilliatt Gilliatt

Alterations in Cellular Processes

Understanding and identifying alterations in cellular processes is critical for diagnosing and treating diseases. As an advanced practice nurse, this knowledge is essential for developing targeted interventions and educating and guiding our patients on restoring normal cellular functions and mitigating the impact of these alterations on their overall health as part of the treatment plan.

The Role of Genetics in the Disease

In the case study scenario of a 27-year-old male patient with a history of substance abuse, based on him being found unresponsive until Naloxone was administered by EMS (Emergency Medical Services), responders in the field suggest a likely Opioid overdose. Naloxone is a drug that classifies as an Opioid antagonist. Naloxone binds to Opioid receptors, particularly the mu-opioid receptors that drugs like Heroin or Morphine target in the central nervous system. When Naloxone binds to the Opiate receptors, it blocks the Opioids, preventing them from causing respiratory depression, sedation, hypotension, and analgesia (
Naloxone Hydrochloride- Naloxone Hydrochloride Injection, Solution
, 2019).

Substance abuse disorder is complex because it is not caused by one factor; genetics, environment, and the person’s behavior could all be contributory. In a GWAS (Genome-Wide Association) study in Peking, they found that genes encoding Opioid receptors such as OPRMI (mu opioid receptor) are involved in a person’s response to Opioid drugs. Genetic variations in these receptors can influence an individual’s response to substances (Chang et al., 2022). The young man in this scenario could have the genetic factors plus other environmental influences such as stress, trauma, or social factors that added to his risk of substance abuse disorder.

Patient’s symptoms, physiologic responses, and the cells involved in the process:

The unresponsive 27-year-old male was found lying on the floor for unknown amounts of time and has a history of substance abuse, indicating a possible Opioid drug overdose that was immediately reversed with the administration of Naloxone, a potent Opioid antagonist. Opioids interact with specific Opioid receptors: Mu, Delta, and Kappa opioid receptors that are found in the brain and spinal cord to affect pain (Dezfulian et al., 2021), mood (Banks, 2020), and addiction (Quirion et al., 2020). When these receptors are activated, they promote pain relief and euphoria, making Opioid use highly susceptible to abuse. Opioids also inhibit GABA-mediated ( Gamma-Aminobutyric Acid) neurotransmitters, leading to sedation and decreased alertness (Otsu & Aubrey, 2022), which is evident in this scenario as the patient was found to be unresponsive.

The patient suffered Hypoxia (lack of sufficient oxygen) before resuscitation with Naloxone. Cellular injury due to lack of oxygen affects the Mitochondria’s ability to produce ATP (Adenosine Triphosphate), the primary energy currency of the cell. Eventually, the cells try to adapt by creating ATP through anaerobic means, using up glycogen in place of oxygen (McCance & Huether, 2019a). Still, over time, this decreased ATP causes cell damage and lactic acid production, further disturbing the sodium-potassium pump mechanism. The cells start retaining the sodium inside, not allowing potassium inside, leaving it circulating intracellularly, thus causing the elevated serum K+ level of 6.9 mEq/L. A potassium concentration of 5.0 mEq/L in the blood is Hyperkalemia. Elevated potassium levels affect the electrical conduction of the heart; the tall T waves and prolonged PR interval in the EKG readings are signs of serious disturbance in cardiac depolarization and repolarization that ultimately progresses to ventricular fibrillation or cardiac arrest (McCance & Huether, 2019b).

The burning pain over the left hip where the greater trochanter bone is and his forearm, which upon examination at the ED showed tissue necrosis on those pressure point sites, was now felt because Naloxone has reversed Opioid effects of pain perception inhibition. Pressure injuries that the patient sustained were caused by the compression of the soft tissues between the bony prominences of his hip and forearm against the ground, which is an external hard surface. The pressure injuries, over time, progressed to tissue death or necrosis. The external injury from immobility causes damage to the Mitochondria, resulting in impaired ATP production, eventually causing less and less regeneration of new cells, leading to cell death or necrosis (McCance & Huether, 2019a).

How another characteristic would change your response?

If the age of the patient were changed from 27 to 80 years old, the outcome of the scenario would have resulted in death. With everything that this 27-year-old patient went through: history of substance abuse, receiving Naloxone for reversal, elevated potassium level, abnormal EKG, necrosis of the hip and arm tissues, the likelihood of an 80-year-old man waking up and recovering with a favorable overall prognosis is slim.

As the human body ages, it undergoes a decline in the cellular and molecular processes compared to a young adult. Some of those changes are Telomere shortening, which contributes to cellular aging, less efficiency in DNA repair, leading to genomic instability, and increased levels of Cytokines that cause chronic inflammation that affects the heart and brain. Increased Cytokines are associated with triggering the onset of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis (McCance & Huether, 2019a). While aging is a natural and unavoidable part of life, the severity of multiple organ damage and skin necrosis from the above scenario changes the trajectory of treatment, including discussion of advanced directive planning as an appropriate part of the treatment goal.

References

Banks, M. L. (2020). The rise and fall of kappa-opioid receptors in drug abuse research. In
Substance use disorders
(pp. 147–165). Springer International Publishing.
https://doi.org/10.1007/164_2019_268
Links to an external site.

Chang, X., Sun, Y., Muhai, J., Li, Y., Chen, Y., Lu, L., Chang, S., & Shi, J. (2022). Common and distinguishing genetic factors for substance use behavior and disorder: An integrated analysis of genomic and transcriptomic studies from both human and animal studies.
Addiction
,
117
(9), 2515–2529.
https://doi.org/10.1111/add.15908
Links to an external site.

Dezfulian, C., Orkin, A. M., Maron, B. A., Elmer, J., Girotra, S., Gladwin, M. T., Merchant, R. M., Panchal, A. R., Perman, S. M., Starks, M., van Diepen, S., & Lavonas, E. J. (2021). Opioid-associated out-of-hospital cardiac arrest: Distinctive clinical features and implications for health care and public responses: A scientific statement from the american heart association.
Circulation
,
143
(16).
https://doi.org/10.1161/cir.0000000000000958
Links to an external site.

McCance, K. L., & Huether, S. E. (2019a). Altered cellular and tissue biology: Environmental agents. In
Pathophysiology: The biologic basis for disease in adults and children
(8th ed., pp. 50–52, 88-94). Elsevier.

McCance, K. L., & Huether, S. E. (2019b). The cellular environment: Fluids and electrolytes, acids and bases. In
Pathophysiology: The biologic basis for disease in adults and children
(8th ed., pp. 117–118). Elsevier.

Naloxone Hydrochloride- naloxone hydrochloride injection, solution. (2019, September). Hospira Inc..
https://labeling.pfizer.com/ShowLabeling.aspx?id=4541
Links to an external site.

Otsu, Y., & Aubrey, K. R. (2022). Kappa opioids inhibit the gaba/glycine terminals of rostral ventromedial medulla projections in the superficial dorsal horn of the spinal cord.
The Journal of Physiology
,
600
(18), 4187–4205.
https://doi.org/10.1113/jp283021
Links to an external site.

Quirion, B., Bergeron, F., Blais, V., & Gendron, L. (2020). The delta-opioid receptor; a target for the treatment of pain.
Frontiers in Molecular Neuroscience
,
13
.
https://doi.org/10.3389/fnmol.2020.00052
Links to an external site.

Expand discussion thread from Gilliatt Gilliatt

1 Reply

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Noel Floribert

Nov 29, 2023 8:52pm

Reply from Noel Floribert

The scenario depicts a patient who has a history of substance abuse and was found unconscious. The patient was treated with naloxone, which suggests an opioid overdose. The necrotic tissue in areas of prolonged pressure, such as the hip and forearm, indicates that the patient was immobile for an extended period, resulting in pressure ulcers.

The EKG findings reveal a prolonged PR interval, peaked T waves, and a serum potassium level of 6.9 mEq/L, indicating hyperkalemia. Hyperkalemia is a condition where the potassium level in the blood is higher than average and can be life-threatening. It affects the cardiac function and can lead to arrhythmias.

The most critical condition highlighted in the scenario is hyperkalemia. It is an abnormally high level of potassium in the blood. Potassium is an essential electrolyte required for various bodily functions, particularly in regulating nerve and muscle cell function, including that of the heart. Normal potassium levels range from about 3.5 to 5.0 millimoles per liter (mmol/L), and levels above 5.0 mmol/L are generally hyperkalemic. Furthermore, the patient is experiencing pain, indicating that the patient experienced rhabdomyolysis (Weir & Rolfe, 2010).

What is hyperkalemia?

Hyperkalemia is a medical condition with too much potassium in the blood. Several factors can contribute to the development of hyperkalemia.

Kidney Dysfunction: The kidneys are critical in filtering and excreting potassium. Any kidney function impairment can lead to potassium accumulation in the blood.

Medications: Certain drugs, such as ACE inhibitors, potassium-sparing diuretics, and NSAIDs, can increase potassium levels.

Cellular Destruction: Severe burns, trauma, or rhabdomyolysis can release large amounts of potassium from inside cells into the bloodstream. Metabolic factors of acidosis may cause potassium to shift from cells into the blood.

Excessive Potassium Intake: This is less common but can occur with overuse of potassium supplements or in patients with renal impairment. According to Cabral et al. (2020), the diagnosis is confirmed when the serum creatine kinase (CK) level is > 1000 U/L or at least 5x the upper limit of normal. Other essential tests to request include serum myoglobin, urinalysis to check for myoglobinuria, and a complete metabolic panel, including serum creatinine and electrolytes (Cabral et al., 2020).

Symptoms of Hyperkalemia

The symptoms of hyperkalemia can be nonspecific and vary depending on the level of potassium elevation. Some symptoms of hyperkalemia may include muscle weakness or paralysis, nausea, irregular heartbeats (arrhythmias), and slow, weak, or absent pulse.

Diagnosis and Treatment

Hyperkalemia, characterized by high potassium levels in the blood, is usually diagnosed through blood tests and electrocardiograms (ECGs). The treatment of hyperkalemia depends on the severity of the condition and the underlying cause. Medications such as diuretics, potassium binders, or insulin can be prescribed to treat the condition. In severe cases where the kidney function is impaired, dialysis is recommended.

The patient suffering from hyperkalemia must follow dietary restrictions and avoid consuming potassium-rich foods. If the condition is severe, it can lead to life-threatening heart rhythm problems and requires prompt treatment. Since the patient has abnormal EKG findings and a history of substance abuse, continuous cardiac monitoring is essential. Treatment options include administering calcium gluconate to stabilize the heart’s electrical activity, insulin with glucose to drive potassium back into cells, and potassium-binding agents or diuretics to remove excess potassium from the body.

The necrotic tissue on the hip and forearm requires the attention of a wound care specialist or surgeon. Treatment might include debridement, antibiotics for infection, and appropriate wound care. The patient needs to be evaluated for rhabdomyolysis, which is a condition that occurs when muscle tissue breakdown releases harmful substances into the blood. This can be done through blood tests and urine analysis.

The underlying substance abuse problem needs to be addressed, and the patient must be referred to addiction services, counseling, and support groups. It is crucial to continuously evaluate the patient’s cardiac, renal, and overall health status, as complications can arise from hyperkalemia, substance abuse, and pressure ulcers. Educating the patient about the dangers of substance abuse, the importance of pressure ulcer prevention, and the need for regular medical follow-ups is also vital. A multidisciplinary team, including emergency physicians, cardiologists, surgeons, psychiatrists, and social workers, must address all aspects of the patient’s condition.

Role of Genetics in Hyperkalemia

While hyperkalemia can be linked to genetics, it is usually associated with genetic disorders that affect kidney function or potassium regulation. For example, certain genetic conditions like familial hyperkalemic hypertension or inherited forms of renal tubular acidosis can make individuals more susceptible to hyperkalemia. However, in the given scenario, there is no direct indication that genetics play a role. In this case, hyperkalemia is more likely to be related to the patient’s medical condition and history of substance abuse (NIDA, 2019).

Specific Symptoms Presentation.

The EKG results of the patient indicate that they have hyperkalemia. This condition is caused by an elevated potassium level in the serum, which in this case is 6.9 mEq/L. Hyperkalemia can affect the heart’s conduction system, leading to changes in the EKG. The prolonged PR interval in the EKG shows that the atrial-ventricular conduction is delayed, while the peaked T waves indicate that the potassium directly affects the cardiac myocytes.

Physiologic Response to the Stimulus

Hyperkalemia can cause several physiological responses in the body. These include cardiac effects and impacts on muscle and nerve cells. High potassium levels can directly affect the heart’s electrical activity, resulting in observed EKG changes. Excessive potassium can also disrupt the normal gradient across cell membranes, essential for nerve and muscle function, including cardiac muscle.

The hyperkalemic state in this patient could have been caused by various factors, including kidney dysfunction, tissue breakdown due to prolonged immobility or pressure, leading to the release of intracellular potassium, and metabolic disturbances due to substance abuse.

Three types of cells play a significant role in hyperkalemia: cardiac myocytes, muscle cells, and kidney cells. High potassium levels can negatively affect the cardiac myocytes, leading to EKG changes. In cases of rhabdomyolysis, damaged muscle cells can release potassium into the bloodstream, worsening hyperkalemia. Kidney cells regulate potassium levels, and any dysfunction in this process can lead to hyperkalemia (Weir & Rolfe, 2010).

Impact of Other Characteristics such as Gender and Genetics

Hyperkalemia can affect the electrical activity of the heart and muscles throughout the body. Although gender does not significantly impact the physiological response to hyperkalemia, the underlying causes and risk factors may vary between males and females.

If there is a genetic predisposition to electrolyte imbalances or kidney disorders, it is essential to thoroughly investigate familial diseases and adopt a different approach to long-term management.

In summary, the management and investigation of hyperkalemia may vary based on individual patient characteristics, such as underlying genetic conditions or other health issues.

Reference

Cabral, B. M. I., Edding, S. N., Portocarrero, J. P., & Lerma, E. V. (2020). Rhabdomyolysis.
Disease-a-month : DM
,
66
(8), 101015. Retrieved from
https://doi.org/10.1016/j.disamonth.2020.101015
Links to an external site.

NIDA. (2019, August 5). Genetics and Epigenetics of Addiction Drug Facts. Retrieved from https://nida.nih.gov/publications/drugfacts/genetics-epigenetics-addiction on 2023, November 29

Weir, M. R., & Rolfe, M. (2010). Potassium homeostasis and renin-angiotensin-aldosterone system inhibitors.
Clinical Journal of the American Society of Nephrology: CJASN
,
5
(3), 531–548. https://doi.org/10.2215/CJN.07821109

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Brittney Muhammad

Nov 29, 2023 8:47pm

Reply from Brittney Muhammad

Week 1 Discussion:

A 27yo patient with a history of substance abuse is found unresponsive by EMS after being called by the patient’s roommate. The roommate states that he does not know how long the patient had been lying there. The patient received naloxone
in the field and has become responsive. He complains of burning pain over his left hip and forearm. Evaluation in the ED revealed a large amount of necrotic tissue over the greater trochanter as well as the forearm. EKG demonstrated prolonged PR interval and peaked T waves. Serum potassium level is 6.9
mEq
/L.

The role genetics plays in
the disease
:

Genetics play a major role in any disease process.
The purpose of understanding how genetics play a role in disease processes helps to understand why certain individuals are more susceptible to certain diseases versus others.
However, s
tudies
conducted involving families found that at least half of a person’s risk of becoming addicted to any substance depends on his or her genetic makeup (NIDA, 2019). According to the Oxford English Dictionary (2008), genetics is defined as the scientific study of inherited variations in living organisms, and of the cellular and molecular processes responsible for this.
Genes are units of DNA that make up the human genome.
People’s
individual
genes
can either
increase their risk for or protect them from certain diseases.

Why is the patient presenting with the specific symptoms described?

The patient presented
as unresponsive, with necrotic tissue on his left hip and forearm, hyperkalemic, and abnormal EKG. The necrosis on his left hip and forearm could possibly be injection sites for the substance the patient is using. Necrotic tissue can cause hyperkalemia, which presents as peaked T waves and prolonged PR interval on an EKG.

The physiological response to the stimulus presented in the scenario and why you think this response occurred.

According to Cleveland Clinic (2022) necrosis is the death of cells in your body tissues. Necrotic skin tissue occurs when blood flow to your body tissue is blocked secondary to injury, infection, or disease. In the case of this patient, his necrotic skin tissue caused intracellular potassium shifts. Cellular
injury causes a release of large quantities of intracellular potassium to shift into the extracellular space that presents as hyperkalemia
(Simon, et al, 2023)
.

The cells that are involved in this process.

The cells used in the process of necrotic tissue
are oncotic cells. Oncotic cells turn necrotic through lysis and spillage of cellular contents before cells can be recognized by phagocytes
(Fink, et al, 2005)
. Necrotic cells release molecules that act as signals to promote inflammation.

How
would gender change my response?

Gender does play a role in severity of
necrotic tissue damage. Necrosis in cells from males
are
PARP-1
(recognizes DNA damage and facilitates DNA repair)
dependent
(Wang, et al, 2019)
, while
cells from female’s are PARP-1 independent. Estrogen
also
has a survival component in female cells. Estrogen and PARP-1 are determinants in
gender bias
to cell death.

References:

Wang, Y., Luo, W., & Wang, Y. (2019). PARP-1 and its associated nucleases in DNA damage response.

DNA repair
,

81
, 102651.
https://doi.org/10.1016/j.dnarep.2019.102651
Links to an external site.

Fink, S. L., & Cookson, B. T. (2005). Apoptosis,
pyroptosis
, and necrosis: mechanistic description of dead and dying eukaryotic cells.

Infection and immunity
,

73
(4), 1907–1916.
https://doi.org/10.1128/IAI.73.4.1907-1916.2005
Links to an external site.

Simon, L., Hashmi, M., & Farrell, M. (2023, September 4).

Hyperkalemia
. NIH. Retrieved November 29, 2023, from

https://www.ncbi.nlm.nih.gov/books/NBK470284/

Necrosis
. (2022, August 9). Cleveland Clinic.

https://my.clevelandclinic.org/health/diseases/23959-necrosis
Links to an external site.

Genetics
. (2008). Oxford English Dictionary.

https://www.oed.com/dictionary/genetics_n?tl=true
Links to an external site.

NIDA. 2019, August 5. Genetics and Epigenetics of Addiction
DrugFacts
. Retrieved from https://nida.nih.gov/publications/drugfacts/genetics-epigenetics-addiction on 2023, November 29

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Tricia Loper

Nov 29, 2023 7:43pm

Reply from Tricia Loper

NURS-6501N-41 Week 1 Discussion Initial Post

The Role Genetics Plays in The Disease

Genetics can increase the risk of drug addiction. Studies show that about 50% of opioid addiction is genetically related (Deak & Johnson, 2021). The use of opioids can change the chemical makeup of the brain by flooding the brain with dopamine over prolonged period. Another factor that plays a role in the disease is environmental factors such as age of exposure, financial stress, and lifestyle (NIH, June 2018).

Why The Patient Is Presenting with The Specific Symptoms Described

The patient was found unresponsive and due to her history, she was suspected of having had an opioid overdose. Opioid toxicity can severely depress the respiratory system and heart rate which can cause loss of consciousness of reduce response to stimuli. Opioid agonist binds to G-protein receptors which then interferes with the production of the enzyme adenylyl cyclase due to reduction in adrenaline production. This leads to a decrease in intracellular cyclic adenosine monophosphate (cAMP) levels due to reduces ATP production (Pathan & Williams, 2012).

The necrosis noted to her greater trochanter and forearm are caused by injury over a prolonged period due to immobility. The continued pressure to those areas with the reduced oxygenation and nutrition to those cells caused cell death by necrosis. Toxin and ischemic injury cause the rupture of the skin cell’s sarcolemma which causes and increase in cytoplasmic calcium that leads to increased mitochondrial calcium that leads to apoptosis and mitochondrial dysfunction reducing ATP and causing rhabdomyolysis (Giannoglou, Chatzizisis, & Misirli, 2007).

Physiologic Response to Stimulus and Why It Occurred

Naloxone is an opioid antagonist and when used it broke the opioid bond with the G-protein receptor reversing the effects of the opioid drug allowing for the patient to become responsive. Once responsive the patient was able to feel pain from her injuries due to the pain receptors being blocked by the opioid antagonist. The pain experienced is likely related to the breakdown of the muscular tissue cells. The elevated potassium level could likely relate to the kidney injury from the rhabdomyolysis and opioid toxicity which increased potassium conduction.

How Another Characteristic (e.g., gender, genetics) Would Change Response

I do not believe that gender or genetics being different would change the outcome of the disease process. I do think that had the patient been older than there would be the potential that the effects of the disease and resulting outcomes would likely have been exacerbated.

References

Deak, J. D., & Johnson, E. C. (2021). Genetics of substance use disorders: a review.
Psychological medicine
,
51
(13), 2189–2200. Retrieved on November 29, 2023, from
https://doi.org/10.1017/S0033291721000969
Links to an external site.

Giannoglou, G. D., Chatzizisis, Y. S., & Misirli, G. (2007). The syndrome of rhabdomyolysis: Pathophysiology and diagnosis. European Journal of Internal Medicine, 18(2), 90–100. Retrieved on November 29, 2023, from
https://doi.org/10.1016/j.ejim.2006.09.020
Links to an external site.

NIDA. 2018, June 6. Understanding Drug Use and Addiction DrugFacts. Retrieved on November 29, 2023, from
https://nida.nih.gov/publications/drugfacts/understanding-drug-use-addiction
Links to an external site.
.

Pathan, H., & Williams, J. (2012). Basic opioid pharmacology: an update.
British Journal of Pain
,
6
(1), 11–16. Retrieved on November 29, 2023, from
https://doi.org/10.1177/2049463712438493
Links to an external site.

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Nchetaka Okeke

Nov 29, 2023 6:28pm

Reply from Nchetaka Okeke

The role genetics plays in the disease.

The patient in this scenario has a history of drug abuse. Substance use disorders (SUDs) are heritable psychiatric disorders that are influenced by both environmental and genetic factors (Deak & Johnson, 2021). According to Deak and Johnson (2021), studies conducted on twins and families have revealed that approximately 50% of the risk for opioid dependence can be attributed to genetic factors that accumulate over time. Based on the presenting symptoms, it is likely the patient is experiencing rhabdomyolysis, which is a medical condition characterized by the rapid breakdown of skeletal muscle tissue, that a combination of environmental factors such as strenuous exercise and febrile infection and a predisposing genetic makeup can cause. Therefore, an individual may need a combination of external triggers and genetic predisposition to exceed the threshold for developing rhabdomyolysis (Kruijt et al., 2021). In addition, genetic diseases, including disorders of glycolysis or glycogenolysis, lipid metabolism defects, or mitochondrial disorders, can cause rhabdomyolysis (Kodadek et al., 2022).

Why the patient is presenting with the specific symptoms described.

Substance abuse or substance addiction, as described in the scenario provided, can be related to opioid use. This assumption is based on the fact that the patient responded positively to naloxone, a commonly used opioid reversal agent, as he became responsive when it was administered. Necrosis in the greater trochanter and the forearm occurs due to skeletal muscle injury from a possible fall or immobilization with pressure to the tissue for an unknown period, as the roommate did not know how long he had been lying there. Rhabdomyolysis is a medical condition in which the skeletal muscle is destroyed, causing the release of intracellular contents such as electrolytes, enzymes, and myoglobin into the bloodstream. This leads to systemic complications. Muscle necrosis is the common cause of both traumatic and non-traumatic cases of rhabdomyolysis (Kodadek et al., 2022, Lugo-Fagundo et al., 2022). Additionally, decreased blood supply in the tissue and decreased ATP production can cause tissue necrosis (Kodadek et al., 2022). This muscle breakdown can disrupt the body’s electrolytes, like potassium. Increased amounts of serum potassium can cause EKG changes and arrhythmias. This explains the prolonged PR interval and peak T waves on the EKG.

The physiological response to the presented stimulus and its cause.

Physiologically, with rhabdomyolysis, the plasma membrane of the muscle cell, called the sarcolemma, breaks down, leading to a shift in the sodium-potassium gradients. As a result, excess potassium enters the bloodstream, leading to hyperkalemia. Hyperkalemia causes EKG changes in the heart muscle, which becomes hyperexcitable. The persistent depolarization inactivates sodium channels, which creates a prolonged PR interval. Peaked T waves are also a result of hyperkalemia due to the increase in action potential and decreased repolarization, which occurs because the ventricles become sensitive to potassium (McCance & Huether, 2019). The patient also sustained necrosis. Necrosis is the death of cells that occurs after cell injury becomes irreversible. In the case of gangrenous necrosis, severe hypoxic injury is the cause, commonly from a blockage in blood flow, such as the patient’s weight compressing onto his hip and forearm. Coagulative necrosis is also part of this condition, where protein denaturation leads to albumin in soft tissues changing from a transparent, gelatinous state to firm and opaque. This causes areas of necrosis to appear tight, shiny, and dark. (McCance & Huether, 2019).

The cells that are involved in this process

The cells are myofibers and myoglobin made from protein and can be found in the endoplasmic reticulum (ER) and ribosome, which are the cells’ protein factories (McCance & Huether, 2019).

How another characteristic (e.g., gender, genetics) would change my response
.

If this situation involved a female or an individual with no known medical history, I would still consider the possibility of rhabdomyolysis. Although rhabdomyolysis is more common in males, gender does not impact how pathophysiology changes occur at a cellular level (Cabral et al., 2020).

References

Cabral, B. M. I., Edding, S. N., Portocarrero, J. P., & Lerma, E. V. (2020). Rhabdomyolysis.
Disease-a-Month
,
66
(8), 101015. https://doi.org/10.1016/j.disamonth.2020.101015

Deak, J. D., & Johnson, E. C. (2021). Genetics of substance use disorders: A review.
Psychological Medicine
,
51
(13), 2189–2200.
https://doi.org/10.1017/S0033291721000969
Links to an external site.

Kodadek, L., Carmichael Ii, S. P., Seshadri, A., Pathak, A., Hoth, J., Appelbaum, R., Michetti, C. P., & Gonzalez, R. P. (2022). Rhabdomyolysis: An American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document.
Trauma surgery & acute care open
,
7
(1), e000836. https://doi.org/10.1136/tsaco-2021-000836

Kruijt, N., van den Bersselaar, L. R., Kamsteeg, E. J., Verbeeck, W., Snoeck, M. M. J., Everaerd, D. S., Abdo, W. F., Jansen, D. R. M., Erasmus, C. E., Jungbluth, H., & Voermans, N. C. (2021). The etiology of rhabdomyolysis: an interaction between genetic susceptibility and external triggers.
European journal of neurology
,
28
(2), 647–659.
https://doi.org/10.1111/ene.14553
Links to an external site.

Lugo-Fagundo, E., Lugo-Fagundo, C., Weisberg, E. M., & Fishman, E. K. (2022). CT of rhabdomyolysis as a sequela of drug abuse.
Radiology Case Reports
,
17
(12), 4727–4729.
https://doi.org/10.1016/j.radcr.2022.09.035
Links to an external site.

McCance, K. L. & Huether, S. E. (2019).
Pathophysiology: The biologic basis for disease in adults and children
(8th ed.). St. Louis, MO: Mosby/Elsevier.

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Sheila Sargent

Nov 29, 2023 5:26pm
|
Last reply Dec 1, 2023 5:56pm

Reply from Sheila Sargent

The patient is presenting with symptoms of possible rhabdomyolysis. Due to the unknown length of time he was unconscious and lying in the same position, he may have compartment syndrome. The edema with rhabdomyolysis can cause fascial compartment pressure, which will cause necrotic tissue. There can be a breakdown of the sarcolemma membrane around the fiber of the skeletal muscle cells, releasing the intracellular content into the bloodstream (Lugo-Fagundo et al., 2022). This can include potassium, creatine kinase, phosphate, urate, and myoglobin. The kidneys are responsible for ridding the body of this waste. If the amounts are more than the kidneys can handle, the kidneys can be damaged, which may lead to kidney failure. High serum levels of creatine kinase and potassium can cause damage to the heart and irregular heart rhythm (Clevland Clinic, 2023).

The Role of Genetics

There is evidence to show that some genetic disorders may predispose someone to rhabdomyolysis. These can include some types of muscular dystrophies, fatty acid metabolism disorders, glycogen metabolism disorders, and metabolic and mitochondrial disorders (Kruijt et al., 2020).

People with disorders that cause muscle contraction or increased serum creatine kinase levels have a higher risk of rhabdomyolysis (Carneiro et al., 2021). Damage to the skeletal muscles with severe muscle contraction or prolonged immobility can increase the risk of intracellular content being released into the bloodstream (Paternostro et al., 2021).

With this patient, there is not adequate genetic history information given to know if there could be a genetic component along with the drug use and prolonged immobilization.

Why the Patient is Presenting with the Specific Symptoms and the Physiologic Response

The patient has been lying for an undetermined amount of time. He is found to have necrotic tissue on his left trochanter and forearm, where he has complained of pain. From potentially extended immobility, he may have compartment syndrome with edema causing fascial compartment pressure, which caused the necrotic tissue. The breakdown of the sarcolemma membrane around the fiber of the skeletal muscle releases intracellular content into the bloodstream (Lugo-Fagundo et al., 2022). This caused elevated potassium and possible creatine kinase, which could be affecting his heart rhythm.

Cells Involved

There is damage to the membrane of the skeletal muscle cells, which allows the release of intracellular content into the blood (Lugo-Fagundo et al., 2022). Cardiomyocytes may be damaged from the intracellular content that has been released.

How Another Characteristic Would Change Your Response

There is a higher rate of males that get rhabdomyolysis, possibly due to a higher muscle mass, but females are still affected (Carneiro et al., 2021). Because this is possibly drug-induced, it is unknown if there could be a predisposition.

Sheila Sargent

References

Carneiro, A., Viana-Gomes, D., Macedo-da-Silva, J., Lima, G. H. O., Mitri, S., Alves, S. R., Kolliari-Turner, A., Zanoteli, E., Neto, F. R. de A., Palmisano, G., Pesquero, J. B., Moreira, J. C., & Pereira, M. D. (2021). Risk factors and future directions for preventing and diagnosing exertional rhabdomyolysis.
Neuromuscular Disorders
,
31
(7), 583–595. https://doi.org/10.1016/j.nmd.2021.04.007

Cleveland Clinic. (2023, February24).
Rhabdomyolysis: Symptoms, Treatments
. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/21184-rhabdomyolysis

Paternostro, C., Gopp, L., Matthias Tomschik, Krenn, M., Weng, R., Bointner, K., Jäger, F., Zulehner, G., Rath, J., Berger, T. M., Zimprich, F., & Hakan Çetin. (2021). Incidence and clinical spectrum of rhabdomyolysis in general neurology: a retrospective cohort study.
Neuromuscular Disorders
,
31
(12), 1227–1234. https://doi.org/10.1016/j.nmd.2021.09.012

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Pamela Lee Salisbury Smith

Nov 29, 2023 4:58pm

Reply from Pamela Lee Salisbury Smith

Main Question

Discussion: Week I, Case Study

A 27-year-old patient with a history of substance abuse is found unresponsive by emergency medical services (EMS), after being called by the patient’s roommate. The roommate states that he does not know how long the patient had been lying there. The patient received naloxone in the field and has become responsive. He complains of burning pain over his left hip and forearm. Evaluation in the ED revealed a large amount of necrotic tissue over the greater trochanter, as well as the forearm. EKG demonstrated prolonged PR interval and peaked T waves. Serum potassium level 6.9 mEq/L.

Questions

The role genetics play in the disease.

Opioid addiction is a disease that has a genetic component, and according to Wang, Chen, Lee, and Cheng (2019), there is a relationship between genetic markers and phenotypes. Sperm and egg cells have genetic variation, with varying sequences of DNA among individuals in a population. It is noted by Wang et al. (2019) that the genetic variance of heroin is the greatest at 0.54. There is a linkage of chromosomes 2, 17, and an area located within chromosome 14q to opioid addition (Wang et al., 2019).

Why the patient is presenting with the specific symptoms as described.

The patient has hyperkalemia, as indicated by a 6.9 serum potassium level. This is most likely due to the sustained injury of the patient being unresponsive and lying on one side for an extended amount of time. Cell hypoxia resulted, and intracellular fluid moved into the extracellular fluid space, resulting in decreased absorbency of the cell membrane (McCance & Huether, 2019). The resulting ischemia was induced by decreased oxygen, nutrients, and adenosine triphosphate (ATP) (McCance & Huether, 2019).

The Electrocardiogram (EKG) results revealed a prolonged PR interval and peaked T waves, which are related to increased potassium levels (McCance & Huether, 2019). According to McCance and Huether (2019, EKG dysrhythmia is evident in hyperkalemia, resulting in bradycardic arrythmias and conduction delay.

The patient has a large amount of necrotic tissue over the greater trochanter and foreare and is complaining of burning pain in these areas. Necrosis arises from cell death and autolysis, that results in cell homicide to the tissues, and the plasma membrane surrounding the cell is not able to perform optimally and wastes are not being expelled from the tissues (McCance & Huether, 2019). Multiple events occurred from this injury, including ATP reduction, sodium and potassium pump failure, cellular edema, ribosome detachment, and mitochondrial edema (McCance & Huether, 2019). The patient’s complaints of burning pain is a result of having continued pressure on his leg obstructing the blood flow and bradykinins release. Bradykinins, as noted by McCance and Huether (2019), are responsible for the dilation of blood vessels, and are aided by prostaglandins that excite the nerve ending that cause pain.

The physiologic response to the stimulus presented in the scenario, and why you think this response occurred.

The physiologic response to the stimulus presented in the scenario is disuse atrophy, due to the patient’s prolonged disuse of the muscle. This resulted from decreased endoplasmic reticulum and myofilaments of the atrophied muscle, due a reduction in oxygen, nerve loss, and amino acid uptake (McCance & Huether, 2019).

The cells that are involved in this process.

The eukaryotic cells, which are located within the cytosol and are responsible for the cytoskeleton, are involved in this process.

How another characteristic (e.g., gender, genetics) would change your response.

Genetics play an important part in wound stages and healing. Men usually have more muscle mass than women. An older male or female may have presented with more involved symptoms due to skin integrity, decreased nutritional values, and decreased muscle tone.

References

McCance, K. L., & Huether, S. E. (2019
). Pathophysiology; The biologic basis for disease in adults and

Children
(8
th
ed.). Elsevier.

Wang, S. C., Chen, Y. C., Lee, C. H., & Cheng, C. M. (2019). Opioid addiction, genetic susceptibility, and

medical treatments: A Review.
International Journal of Molecular Science,
20(17).

https://doi.org/10.3390/ijms20174294
Links to an external site.

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Willie Schley

Nov 29, 2023 3:17pm
|
Last reply Dec 3, 2023 12:57am

Reply from Willie Schley

Week 1: Discussion

The case study presents a 27-year-old male with a history of substance abuse found unconscious for an unknown amount of time. After the use of naloxone, the patient awakens in severe pain at the possible site of impact from a fall that presents with necrosis. The patient also presents with prolonged PR intervals and peaked T waves. The purpose of this discussion is to focus on the predisposition this patient may have had to his substance abuse illness and the possible progression of his symptoms post-overdose.

The role genetics plays in this disease.

Substance abuse or substance use disorder has been extensively studied to determine underlying factors that predispose patients to this disease. According to an NIH (2023) study, there are genetic markers that indicate potential substance use disorders. This does not mean that having these markers automatically means a person will develop substance use disorders. But it does mean that they are predisposed and the knowledge of that may allow them to make decisions in life to help prevent that unfortunate disease from taking over their lives. The data for this was collected from a study involving over 1 million people, with the discovery of multiple molecular patterns that show an underlying addiction risk (NIH, 2023).

Why the patient is presenting with the specific symptoms described?

The reason the patient reacted the way he did in the scenario is that naloxone is an opioid antagonist that binds to opioid receptors, negates, and reverses the effects opioids have on the CNS, allowing for an increase in neural excitability (NIH, 2022). Therefore, the decreased pain effects the patient felt from the opioids wore off and he was able to feel pain from the necrotic tissue.

The physiologic response to the stimulus presented in the scenario and why you think this response occurred. The cells that are involved in this process.

The response to the stimulus could be due to rhabdomyolysis. With the knowledge that the patient was found unconscious on the floor for an unknown amount of time, and the necrosis was found on his left side, it is reasonable to assume that the patient suffered a muscle injury to both of those sites when falling to his left side. Due to the overdose, the patient may have suffered from hypoxemia which may have increased the speed of muscle death because no oxygenated blood cells were getting to the injured muscle tissue. Furthermore, hypoxia can also cause insufficient ATP production and sarcolemma dysfunction (Qiao, Cheng, Liu, & Yin, 2016). These conditions lead to failed cellular homeostasis, ionic imbalances, and cell death (Galber, Carissimi, Baracca, & Giorgio, 2021). Wrapping this all together, there is hypoxia resulting in impaired gas exchange, increasing CO2, muscle death, decreased ATP resulting in ionic imbalances and cell death, and sarcolemma dysfunction resulting in increased calcium and potassium in the bloodstream. This is the perfect environment for rhabdomyolysis.

The finding for the patient also resulted in prolonged PR interval and peaked T waves due to hyperkalemia. With an increase in potassium, the resting potential of the heart is altered, and the cell membranes become depolarized due to the imbalance between sodium and potassium, increasing myocardial excitability (Hunter & Bailey, 2019). The greater the levels of K+, the greater this effect becomes. A higher level of K+ will eventually create PR intervals so long that they may and action potential decreases significantly resulting in peaked T waves (Hunter & Bailey, 2019).

How another characteristic (e.g., gender, genetics) would change your response?

According to studies, men are more likely to develop rhabdomyolysis than women. This is because men seem to be more prone to exertional rhabdomyolysis than women due to a high increase in creatine kinase after exertion (Clarkson, Rawson, & Tarnopolsky, 2017).

Another factor that could play a role in the response the patient had is genetics. As previously discussed, some patients are predisposed to addictive behavior. If this patient was one of those patients, then that could’ve been the cause leading to the overdose. If the patient did not have those genetics, he may not have been in the situation to have the response in the first place. Or the patient may have had a metabolic myopathy that pushed him into muscle death even faster and increased the rate of cellular death and necrosis (Blueprint Genetics, 2023).

References

Blueprint Genetics. (2023). Metabolic Myopathy and Rhabdomyolysis Panel. Retrieved from https://blueprintgenetics.com/tests/panels/neurology/metabolic-myopathy-and-rhabdomyolysis-panel/#:~:text=However%2C%20recurrent%20rhabdomyolysis%20is%20often,mitochondrial%20disorders%20and%20muscular%20dystrophies.

Clarkson, P. M., Rawson, E. S., & Tarnopolsky, M. A. (2017). Perspectives on Exertional Rhabdomyolysis. Sports Med, 47(1), S33-S49. doi:10.1007/s40279-017-0689-z

Galber, C., Carissimi, S., Baracca, A., & Giorgio, V. (2021). The ATP Synthase Deficiency in Human Diseases. Life (Basel), 8(11), 325. doi:10.3390/life11040325

Hunter, R. W., & Bailey, M. A. (2019). Hyperkalemia: pathophysiology, risk factors and consequences. Nephrology Dialysis Transplantation, 34(3), iii2–iii11. doi:10.1093/ndt/gfz206

NIH. (2022). Naloxone DrugFacts. Retrieved from https://nida.nih.gov/publications/drugfacts/naloxone

NIH. (2023). New NIH study reveals shared genetic markers underlying substance use disorders. Retrieved from https://nida.nih.gov/news-events/news-releases/2023/03/new-nih-study-reveals-shared-genetic-markers-underlying-substance-use-disorders

Qiao, H., Cheng, H., Liu, L., & Yin, J. (2016). Potential factors involved in the causation of rhabdomyolysis following status asthmaticus. Allergy, Asthma & Clinical Immunology, 12(43), 2. doi:https://doi.org/10.1186/s13223-016-0149-6

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Yasmine Hewitt

Nov 29, 2023 2:45pm
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Last reply Dec 3, 2023 12:56am

Reply from Yasmine Hewitt

Based on the patients’ complaints, elevated serum potassium level, and EKG results, the disease highlighted in the scenario suggests Rhabdomyolysis. Rhabdomyolysis is the rapid breakdown of muscle that causes the release of intracellular contents, including protein pigment myoglobin, into the extracellular space and bloodstream( McCance et.al,2019)Ingestion of the illicit drugs as suspected can cause rhabdomyolysis. Rhabdomyolysis can be caused by acquired predispositions such as; sepsis, drugs/toxins, crush injuries. In additions, the disease can be by genetic defects such as; metabolic muscle disorders, mitochondrial disorders, muscular dystrophies, and disorders of intramuscular calcium release. Genetic disorders of fatty acid metabolism plays a role “defects in the beta-fatty acid oxidation pathway lead to disorders of fatty acid metabolism, frequently characterized by exercise intolerance, muscle pain and episodes of rhabdomyolysis related to prolonged aerobic exercise and other triggers such as fever, fasting, stress, and drugs (Scalco et. al, 2015).

Muscle injury and necrosis caused by rhabdomyolysis is direct myocyte injury which disrupts the ATP, Ion channels, and plasma membrane resulting in loss of intracellular electrolyte equilibrium. The muscle injury (trauma, exercise, thermal dependent syndromes) or lack of ATP (Medicines, electrolyte, hereditary and metabolic disorders, intense exercise, ischemia) in a muscle cell results in intracellular sodium and calcium influx(Scalco et. al, 2015). Due to the injury water is drawn into the cell with sodium leading to swelling and disruption of intracellular and membranous structures.The presence of excessive intracellular calcium leads to activation of actin-myosin cross-linkage, myofibrillar contraction, and depletion of ATP. (Scalco et. al, 2015). Excessive calcium in the cell promotes cell membrane dissolution and disruption of ion channels. With reperfusion, leukocytes migrate into the damaged muscle and cause an increased number of cytokines, prostaglandins, and free radicals, causing further myolysis, necrosis of muscle fibers, and release muscle breakdown products like potassium and myoglobin, creatine kinase, phosphate, uric acid, and various organic acids into the bloodstream. (Stanley et. al,2023) This in turn leads to the complications of hyperkalemia and hyperphosphatemia.

The stimulus in this scenario was caused by opioid overdose. The patient was found unresponsive then became responsive due to naloxone, an opioid antagonist, which suggest the patient overdosed on an opioid, and is very likely due to medical history of substance abuse. Due to the patients last known well time and uncertainty of how, and if the patient fell would suggest that the necrosis is due to the impaired perfusion caused by rhabdomyolysis. The patient could have been lying there for a long period of time before he was noticed which would cause the severe necrosis to the forearm and greater trochanter found in the ED. The serum potassium level of 6.9 would constitute hyperkalemia. Hyperkalemia found in the patient blood work is caused by the release of potassium and phosphorus from the damaged cell, leading to the increase in potassium in the blood level. Progressive hyperkalemia may result in ECG changes, including peaked T wave, flattened P wave, prolonged PR interval, ST depression, and prolonged QRS duration. Besides, hypokalemia may associate with a peaked P wave, prolonged PR interval, prominent U wave, shallow T wave, and ST depression (Teymouri et. al,2022).

Reference :

McCance, K. L., Huether, S. E., Brashers, V. L., & Rote, N. S. (2019). Chapter 45. In
Pathophysiology: The biologic basis for disease in adults and children
. essay, Elsevier.

Scalco, R. S., Gardiner, A. R., Pitceathly, R. D., Zanoteli, E., Becker, J., Holton, J. L., Houlden, H., Jungbluth, H., & Quinlivan, R. (2015). Rhabdomyolysis: a genetic perspective.
Orphanet journal of rare diseases
,
10
, 51.
https://doi.org/10.1186/s13023-015-0264-3
Links to an external site.

Stanley M, Chippa V, Aeddula NR, et al. Rhabdomyolysis. [Updated 2023 Apr 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK448168/
Links to an external site.

Teymouri, N., Mesbah, S., Navabian, S. M. H., Shekouh, D., Najafabadi, M. M., Norouzkhani, N., Poudineh, M., Qadirifard, M. S., Mehrtabar, S., & Deravi, N. (2022). ECG frequency changes in potassium disorders: a narrative review.
American journal of cardiovascular disease
,
12
(3), 112–124.

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Rippanjot Kaur

Nov 29, 2023 2:27pm
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Last reply Dec 1, 2023 10:24pm

Reply from Rippanjot Kaur

Discussion

Genetics can influence the patient’s presentation, especially if the patient’s genetics are exposed to substance abuse. Some people may develop genetic susceptibility as a result of substance use disorders and may experience variations in genes due to drug metabolism (Sanchez-Roige et al., 2022). Also, genetic factors can affect the individual’s response to specific substances and the complications these substances may cause. Understanding the genetic component can help develop effective measures and treatment plans, considering the patient’s unique genetic elements and potential complications.

The specific symptoms demonstrated by the patient show potential cases of rhabdomyolysis. The use of naloxone indicates the presence of excessive opioid use, which can cause mobility problems, muscle compression, and increased risk of rhabdomyolysis (Jordan & Morrisonponce, 2023). The release of myoglobin may cause symptoms of burning pain. Myoglobin is described as the breakdown of muscle tissue into the bloodstream. The EKG findings are signs of hyperkalemia, a complication caused by rhabdomyolysis. The increased level of serum also shows an increased risk of rhabdomyolysis. The patient’s potassium is 6.9 mEq/L, and the normal range in healthy individuals is 3.5-5.0 mEq/L. With an increase in extracellular potassium, the cell is more irritable due to faster repolarization, and this irritability is exhibited by the peaked T waves and prolonged PR interval (McCannce & Huether, 2019).

Naloxone acts as a reverse mechanism of the opioid-induced drug, which results in the patient becoming responsive (Jordan & Morrisonponce, 2023). However, the patient is likely to experience prolonged symptoms of immobility and muscle tissue breakdown, which can cause rhabdomyolysis. In addition, the continuous release of myoglobin in damaged muscle tissue can result in acute kidney problems. The EKG changes and peaked T waves demonstrate the risk of hyperkalemia, which is highly attributed to arrhythmias. The burning pain may be caused by the effects of myoglobin, which can affect various body organs and tissues.

Rhabdomyolysis is a severe medical issue when damaged muscle tissues produce protein and electrolytes in the blood. In extreme cases, rhabdomyolysis can cause permanent disability (CDC, 2023). Evidence of extensive necrotic tissue on the greater trochanter and forearm indicates the possibility of extensive muscle damage. Damaged muscles produce myoglobin, which can cause renal tubular injury, increasing the risk of acute kidney problems.

Another characteristic that would have influenced my response is the presence of genetic predisposition of a specific opioid receptor. This characteristic can affect the severity of opioid toxicity and complications. Besides, factors such as gender can also play a crucial role in determining the primary diagnoses, as the distribution and elimination of drugs from the body might vary depending on the body’s metabolism and composition.

References

(2023, February 9).
Rhabdomyolysis
. Centers for Disease Control and Prevention.
https://www.cdc.gov/niosh/topics/rhabdo/default.html#:~:text=Rhabdomyolysis%20(often%20called%20rhabdo)%20is,permanent%20disability%20or%20even%20death
Links to an external site.

Jordan, M. R., & Morrisonponce, D. (2023).
Naloxone
. StatPearls Publishing LLC.
https://www.ncbi.nlm.nih.gov/books/NBK441910/
Links to an external site.

McCance,K.L.& Huether,S.E(2019). Pathophysiology: The biologic basis for disease in adults and children(8
th
ed.).St Louis,MO:Mosby/Elsevier.

Sanchez-Roige, S., Kember, R. L., & Agrawal, A. (2022). Substance use and common contributors to morbidity: A genetics perspective.
eBioMedicine
,
83
, 104212.
https://doi.org/10.1016/j.ebiom.2022.104212
Links to an external site.

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Paige Devecka

Nov 29, 2023 2:12pm
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Last reply Dec 3, 2023 12:53am

Reply from Paige Devecka

Initial Discussion Post

After evaluation of the patient and the clinical manifestations provided, I determined the patient is in Rhabdomyolysis from injuries sustained from the fall and the prolonged time he was in the same position while unconscious before his roommate found him. One of the main causes of Rhabdomyolysis is “long-lasting muscle compression such as that caused by prolonged immobilization after a fall or lying unconscious on a hard surface during illness or while under the influence of alcohol or medication” (Stuart, 2023). This current circumstance resulted in the necrosis and breakdown of muscle on this patient’s grater trochanter and forearm on the side he was laying on. This muscle breakdown is causing the pain that the patient is reporting on admission. This muscular deterioration resulted in red and white skeletal muscle cell breakdown and subsequent death, shown by the necrotic tissue. “Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle constituents into the circulation” (Bhai & Dimachkie, 2023). As the cells become necrotic, the intracellular potassium leaks outside of the cell which is evident by the raised serum potassium level.

Rhabdomyolysis is a serious syndrome due to a direct or indirect muscle injury. It results from the death of muscle fibers and cells and release of their contents into the bloodstream. “Common complications of rhabdomyolysis include very high levels of potassium in the blood, which can lead to an irregular heartbeat or cardiac arrest and kidney damage”. (Stuart, 2023). The clinical manifestation of raised serum potassium is directly resulting the cardiac function of this patient, with the EKG showing prolonged PR interval with peaked T waves as a result of the increased potassium within the blood due to the breakdown of skeletal muscle cells. Evidenced based practice articles, “showed peaked T wave, as well as expanded QRS complex and low P amplitude, are important changes that can guide us to immediate diagnosis” (Teymouri et al., 2022). These clinical manifestations within this 27-year old patient are evidence that he is suffering from complications of Rhabdomyolysis after being incapacitated in the same position for a unknown amount of time resulting in this muscle breakdown from the trauma his muscle cells sustained.

Genetic factors can be referenced for both the patient’s history of substance abuse and susceptibility to Rhabdomyolysis. According to “recent genetic and neuroscience research implicating
GABRA2
and the 2 subunit in substance use. The present findings corroborate the current literature that suggests
GABRA2
variation may exert effects on illicit drug-seeking behavior, perhaps through substance-related reward pathways” (Mallard et al., 2018). This gene can be a contributing factor to the patient’s history of substance abuse and incapacitation resulting from the use. “a number of Mendelian genetic defects have been identified to increase rhabdomyolysis susceptibility, including a number of genes implicated in muscle metabolism and mitochondrial function (e.g.,
ACADVL
,
CPT2
,
PYGM or LPIN1)”
(Kruijt et al.
,
2020). Although these specific genes would not result in the Rhabdomyolysis, they can be attributed to the increased susceptibility to the disorder after the event trigger.

After a diagnosis occurs, providers are able to begin treatment for this condition such as using IV fluids to dilute the intracellular fluid in the blood stream while continuing to monitor cardiac function and assess for other potential complications such as seizures.

References:

Bhai, & Dimachkie. (2023). Rhabdomyolysis: Clinical manifestations and diagnosis. UpToDate. https://www.uptodate.com/contents/rhabdomyolysis-clinical-manifestations-and-diagnosis#:~:text=CLINICAL%20MANIFESTATIONS%20—%20Rhabdomyolysis%20is%20a,and%20myoglobinuria%20may%20be%20present.

Kruijt, N., van den Bersselaar, L. R., Kamsteeg, E. J., Verbeeck, W., Snoeck, M. M. J., Everaerd, D. S., Abdo, W. F., Jansen, D. R. M., Erasmus, C. E., Jungbluth, H., & Voermans, N. C. (2021). The etiology of rhabdomyolysis: an interaction between genetic susceptibility and external triggers. European journal of neurology, 28(2), 647–659. https://doi.org/10.1111/ene.14553

Mallard, T. T., Ashenhurst, J. R., Harden, K. P., & Fromme, K. (2018). Gabra2, alcohol, and illicit drug use: An event-level model of genetic risk for polysubstance use.
Journal of Abnormal Psychology
,
127
(2), 190–201. https://doi.org/10.1037/abn0000333

Stuart. (2023). Rhabdomyolysis: Symptoms, causes, and treatments. WebMD. https://www.webmd.com/a-to-z-guides/rhabdomyolysis-symptoms-causes-treatments#:~:text=Rhabdomyolysis%20Causes,-There%20are%20many&text=A%20crush%20injury%20such%20as,influence%20of%20alcohol%20or%20medication

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Nisha Krishnan Rayan
(She/Her)

Nov 29, 2023 12:52pm
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Last reply Dec 3, 2023 12:52am

Reply from Nisha Krishnan Rayan

Substance use disorder (SUD) is strongly influenced by both environmental and hereditary risk factors. Previous molecular genetic studies, such as the genome-wide association study (GWAS), have shown that opioid addiction is not only environmental but also heritable (Wang, S., et al., 2019). Both classical genetic research and molecular genetic research support this. GWAS supports the idea that some genes related to opioid receptors, the dopaminergic system, and the serotonergic system are linked to opioid addiction. As was already noted, the opioid receptor system in the brain is linked to reward circuits in the brain, and opioid addiction is linked to behavioral patterns like tolerance, cravings, and withdrawal symptoms (Wang, S., et al., 2019). The above findings suggest that opioid addiction is a complex disease.

The patient’s roommate discovered him unconscious after an unknown period. He had overdosed on opiates and was treated with naloxone. The opioid antagonist naloxone reversed the depressive effects of opiate overdose on the central nervous system and respiratory system. The patient suddenly complains of severe pain in his left hip and forearm, which he may not have been experiencing previously due to the opiates’ effects. Opiates’ pain-relieving properties are also lost when they are reversed (Vallerand & Sanoski, 2020).

Due to the respiratory-depressive effects of opiate overdose, the patient was most likely in a state of respiratory acidosis resulting from the ineffective gas exchange and retention of CO2. Respiratory acidosis can be subcategorized as acute, chronic, or acute and chronic. In acute respiratory acidosis, there is a sudden elevation of PCO2 because of a failure of ventilation. This could be due to CVA, the use of CNS depressants such as opioids, or the inability to use respiratory muscles due to disorders such as myasthenia gravis, muscular dystrophy, or Guillain-Barre syndrome (Patel & Sharma, 2023).

We must consider the possibility that the patient is suffering from rhabdomyolysis because of the potential hypoxia from respiratory failure while he was unconscious and muscle injuries on the arm and hip. Muscle cell necrosis can result from prolonged periods of oxygen deprivation to muscles, ultimately precipitating rhabdomyolysis. Potential complications of rhabdomyolysis include hyperkalemia, compartment syndrome, and acute kidney injury (Toress, P. et al., 2015).

Rhabdomyolysis is a complex medical condition involving the rapid dissolution of damaged or injured skeletal muscle. When skeletal muscle integrity is compromised, intracellular muscle components such as myoglobin, creatine kinase (CK), aldolase, and lactate dehydrogenase, as well as electrolytes, are released directly into the bloodstream and extracellular space. Rhabdomyolysis can present as an asymptomatic illness with elevated CK levels or as a fatal condition with severe electrolyte imbalances (hyperkalemia), acute renal failure (ARF), and disseminated intravascular coagulation. While direct traumatic injury is the most common cause of rhabdomyolysis, other potential causes include drugs, toxins, infections, muscle ischemia, metabolic and electrolyte abnormalities, genetic disorders, prolonged bed rest or exertion, and temperature-induced conditions like neuroleptic malignant syndrome (NMS) and malignant hyperthermia (MH). (Toress et al., 2015).

The tall T wave in the EKG shown was due to the hyperkalemia reported. The T wave on an electrocardiogram (EKG) typically represents ventricular repolarization. Ventricular repolarization is the process by which the ventricular myocytes return to their negative resting potential so they can depolarize again (Levis, J.T. 2013). T-wave changes are secondary to electrolyte abnormalities in the myocardium since the EKG is representative of the electricity of the heart. The outflow of potassium from the myocyte during repolarization is necessary to restore resting membrane potential. When there is hyperkalemia, the electrochemical gradient for potassium to flow out of the cell is skewed, altering the repolarization phase. These changes in the action potential are reflected by abnormalities in the T wave on an EKG.

Substance use disorders (SUD) affect men and women differently. Although men have a higher prevalence, women with addictive disorders have a more vulnerable profile and are less likely to enter treatment than men (Fonseca, F., et al., 2021). The most relevant data show that female substance use is increasing, and the gender gap may be closing. Men and women use drugs for different reasons. Women progress rapidly from drug use to addiction. Females face severe consequences as a result of drug use, including pregnancy complications and more serious medical issues (Fonseca, F., et al., 2021).

References

Fonseca, F., Robles-Martínez, M., Tirado-Muñoz, J.
et al.
A Gender Perspective on Addictive Disorders
Curr Addict Rep

8
, 89–99 (2021). https://doi.org/10.1007/s40429-021-00357-9

Levis, J. T. (2013). ECG diagnosis: hyperkalemia.
The Permanente journal
,
17
(1), 69
https://doi.org/10.7812/TPP/12-088
Links to an external site.

Patel S., Sharma S. Respiratory Acidosis [Updated June 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Retrieved from:
https://www.ncbi.nlm.nih.gov/books/NBK482430/
Links to an external site.

Torres, P. A., Helmstetter, J. A., Kaye, A. M., & Kaye, A. D. (2015). Rhabdomyolysis pathogenesis, diagnosis, and treatment
Ochsner journal
,
15
(1), 58–69.

Vallerand, A. H., Sanoski, C. A., & Deglin, J. H. (2020). Naloxone. In Davis’s drug guide for nurses (17th ed.), In Nursing Central for Apple iOS (Version 1.44) [Mobile application software] Retrieved from
https://nursing.unboundmedicine.com/nursingcentral
Links to an external site.

Wang, S. C., Chen, Y. C., Lee, C. H., & Cheng, C. M. (2019). Opioid Addiction, Genetic Susceptibility, and Medical Treatments: A Review,
International journal of molecular sciences
,
20
(17), 4294 https://doi.org/10.3390/ijms20174294

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Mofo Ngoupaye
(He/Him)

Nov 29, 2023 6:28am
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Last reply Dec 3, 2023 12:51am

Reply from Mofo Ngoupaye

Main post

Substance use disorder is a curable mental illness that alters a person’s brain and behavior, causing them to be unable to manage their consumption of substances such as legal or illicit drugs, alcohol, or prescriptions. (National Institute of Mental Health, n.d.). It is a major health issue that greatly contribute to morbidity and death rate all over the world. Scientists uncovered genes that are typically inherited throughout addiction problems, independent of the drug consumed, by going through genetic data from over 1 million people. (NIDA, 2023). This research proves that genetics plays a significant role in the occurrence of substance abuse in people who suffer from substance abuse disorders. According to the symptoms described in the scenario, the patient must have swallowed a large amount of heroin, opioids or fentanyl since he became responsive after receiving Naloxone which is an antidote to opioid and other substance such as Fentanyl and heroin overdose. According to CDC (2023), when administered in time, naloxone is a life-saving medicine that may reverse an overdose from opioids such as heroin, fentanyl, and prescription opioid. (Para.1). Naloxone is used to treat opioid toxicity, especially to reverse respiratory depression caused by opioid usage. It can help with accidental or purposeful overdoses, as well as acute or chronic toxicity. “Opioid receptors are abundant in the respiratory center in the cerebral cortex, thalamus, peripheral chemo and baroreceptors in the carotid bodies and vagi, and mechanoreceptors of the airways and lungs. Stimulation of these receptors leads to irregular and slow breathing, eventually developing hypercapnia and hypoxia.” (Dhaliwal and Gupta, 2023, Para. 18). Thanks to extensive research and evidence-based practices, scientists were able to create Naloxone which is a drug that helps to quickly reverse the horrible effect of substance overdose. According to Jordan and Morrisonponce (2023) Naloxone is a pure, competitive opioid antagonist with a high affinity for the mu-opioid receptor, allowing opioid actions to be reversed. The beginning of effect varies depending on the method of administration; however, it can be as quick as one minute when administered intravenously or intraosseously.

The pain to left hip, forearm, and necrotic tissue found in patient in left greater trochanter and forearm is one evidence that patient was using needles to inject himself with illicit substances. By injecting himself with illicit substances, and without proper aseptic techniques, this patient caused his skin to be infected causing the burning pain he is experiencing. People who inject illicit substances usually use the same syringe many times and inject themselves without using alcohol swab to disinfect their skin which make them more at risk to develop soft tissue and skin infection. The entry of pathogens into the skin causes the development of localized skin and soft tissue infection in people who inject drugs. Bacteria can enter the body through the skin, tainted medicines, or injection equipment such as syringes and associated accessories. Foreign materials and substances in the skin and surrounding tissue might hinder blood and lymphatic outflow, further predisposing to localized infections near the injection site. (Saldana et al, 2020). The patient has an abnormal EKG with prolonged PR interval and peaked T waves with an elevated potassium level of 6.9 mEq/L. These abnormalities are evidence that patient must have a bad kidney function or the drugs he used must have caused a metabolic reaction that cause his potassium level to rise. Rhabdomyolysis is a syndrome that can be caused using some prescription medicines as well as in addition to alcohol, heroin, cocaine, amphetamine, methadone, tramadol, and LSD. This syndrome is characterized by muscle cell degeneration and the spread of muscle cellular components throughout the circulation. This condition can cause the discharge of muscle cell chemicals such as potassium, lactate dehydrogenase, uric acid, and myoglobin into extracellular and circulatory fluid. (Bakak, et al. 2017). Since it is unclear how long this patient has been on the floor unconscious, one can assume that his metabolism might have cause a shock. The shock he experienced might have caused rhabdomyolysis and hyperkalemia.

Gender and genetics will not have changed my response; however, age would have changed my response. This case study is about a 27-year-old male; however, if the patient was elderly with many other comorbidities, the prognostic for him to be alive by the time the emergency medical service arrive will have been poor.

References

Babak, K., Mohammad, A., Mazaher, G., Samaneh, A., & Fatemeh, T. (2017). Clinical and laboratory findings of rhabdomyolysis in opioid overdose patients in the intensive care unit of a poisoning center in 2014 in Iran.
Epidemiology and health
,
39
, e2017050.
https://doi.org/10.4178/epih.e2017050
Links to an external site.

Center of Disease Control and Prevention. (2023).
Lifesaving Naloxone.
https://www.cdc.gov/stopoverdose/naloxone/index.html
Links to an external site.

Dhaliwal, A., Gupta, M. (2023).
Physiology, Opioid Receptor.
National Library of Medicine.
https://www.ncbi.nlm.nih.gov/books/NBK546642/
Links to an external site.

Jordan, M. R., Morrisonponce, D. (2023).
Naloxone
. National Library of Medicine.
https://www.ncbi.nlm.nih.gov/books/NBK441910/
Links to an external site.

National Institute on Drug Abuse. (2023, March 22).
New NIH study reveals shared genetic markers underlying substance use disorders.
Retrieved from
https://nida.nih.gov/news-events/news-releases/2023/03/new-nih-study-reveals-shared-genetic-markers-underlying-substance-use-disorders
Links to an external site.
on 2023, November 28

National Institute of Mental Health. (n.d.).
Substance Use and Co-Occurring Mental Disorders.
https://www.nimh.nih.gov/health/topics/substance-use-and-mental-health
Links to an external site.

Saldana, C. S., Vyas, D. A., & Wurcel, A. G. (2020). Soft Tissue, Bone, and Joint Infections in People Who Inject Drugs.
Infectious disease clinics of North America
,
34
(3), 495–509.
https://doi.org/10.1016/j.idc.2020.06.007
Links to an external site.

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Bernadette Flores

Nov 28, 2023 11:51pm
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Last reply Dec 2, 2023 4:33pm

Reply from Bernadette Flores

Main Discussion Post

After reading this case study, I will explain three possible diseases that occurred to this patient. Since the patient was found unresponsive due to the use of substance abuse, the patient may have a significant history of drug use. Due to the pain and necrotic tissue, rhabdomyolysis could have occurred and caused these injuries. The abnormal EKG and elevated potassium levels could also indicate rhabdomyolysis and hyperkalemia. In the patient-provided case study scenario, I will explain these diseases in detail and how they all cause rhabdomyolysis.

The Role Ge
netics Plays in the Disease

Rhabdomyolysis is considered acute and often severe skeletal muscle damage resulting in the release of intracellular muscle components into the bloodstream, which can cause cell and tissue death (Scalco, et al, 2015). There are both genetic and acquired causes of rhabdomyolysis in patients, depending on their family history and drug use. Metabolic muscle disorders and muscular dystrophies can cause patients to develop this disease along with alcohol and drug use.

Why the Patient is Presenting with the Specific Symptoms Described,
The Physiologic Response to the Stimulus Presented in the Scenario and Why You Think This Response Occurred

Due to the breakdown in skeletal muscle fibers that then leak into the bloodstream, high levels of potassium in the blood can disrupt the heart’s normal rhythm, causing the patient to have a prolonged PR interval and peaked t waves in his EKG (Miller, 2022). This explains why the patient’s potassium was 6.9 mEq/L and shows why he had an abnormal EKG initial reading. A complication known as compartment syndrome can also occur from prolonged immobility. The sustained muscle compression and increased pressure from lying on a hard surface for too long can cause necrotic tissue (Miller, 2022). As the patient in this case study was found to be unconscious for an unknown amount of time, the patient could have developed the complication of compartment syndrome in his left hip and forearm from lying on his left side for an extended period of time. Given the patient’s substance abuse history, Narcan was used to help reverse the effects of the drug used and allowed the patient to become responsive. Naloxone aka Narcan, is a pure opioid antagonist that completely displaces narcotics from the opioid receptor sites in the brain’s central nervous system (Gibson, 2022). As this medication replaces the receptor sites, it allows the patient to regain consciousness and become responsive by eliminating the narcotic.

The Cells That Are Involved in This Process

Different cellular levels are involved in the process of rhabdomyolysis. The skeletal muscle cell is damaged, leading to the release of toxic intracellular material into the blood circulation (Giannoglou, et al, 2007). Rhabdomyolysis causes an increase in intracellular free-ionized calcium due to cellular energy depletion or direct plasma membrane rupture (Giannoglou, et al, 2007). The increased intracellular calcium activates several proteases, intensifies skeletal muscle cell contractility, induces mitochondrial dysfunction, and increases the production of reactive oxygen species, ultimately resulting in skeletal muscle cell death (Giannoglou, et al, 2007). This disease mainly affects muscle cells which can then cause the symptoms provided in this scenario such as hyperkalemia, necrotic tissue, and increased muscle pain.

How Another Characteristic Would Change Your Response

Genetics would change my response in this scenario. In the case study provided, the patient seemed to self-inflict the symptoms of rhabdomyolysis by ingesting an unknown number of narcotics, which is considered an acquired complication. If the patient had specific genetic issues such as inherited metabolic disorders of skeletal muscle, abnormal glycogen storage affecting muscle, and disorders of fatty acid oxidation (Scalco, et al, 2015), the responses and explanations would differ from the current case study being presented.

References

Giannoglou, G. D., Chatzizisis, Y. S., & Misirli, G. (2007). The syndrome of rhabdomyolysis: Pathophysiology and diagnosis.
European Journal of Internal Medicine
,
18
(2), 90–100. https://doi.org/10.1016/j.ejim.2006.09.020

Gibson, J. L. . P. (2022). Naloxone.
Salem Press Encyclopedia of Health
.

Miller, S. P. (2022). Rhabdomyolysis.
Salem Press Encyclopedia
.

Scalco, R. S., Gardiner, A. R., Pitceathly, R. D. S., Zanoteli, E., Becker, J., Holton, J. L., Houlden, H., Jungbluth, H., & Quinlivan, R. (2015). Rhabdomyolysis: a genetic perspective.
Orphanet Journal of Rare Diseases
,
10
(1), 1–15. https://doi.org/10.1186/s13023-015-0264-3

Alterations in Cellular Processes

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