This patient has a history of substance abuse which could be a concluding factor to the sudden loss of consciousness and other symptoms exhibited by him. Considering the fact that the patient received naloxone in the field and became responsive proves that he has been consuming opioids, either injectable or oral, in large quantities. Compliant of burning pain over his hip and forearm shows that he is suffering from rhabdomyolysis, a complex condition caused by injured or damaged skeletal muscles. This condition can result from a traumatic or non-traumatic causes which in this case, drug abuse is one of the non-traumatic contributing factor to the development of rhabdomyolysis in this patient. Due to the disruption in the integrity of skeletal muscles, rhabdomyolysis leads to the release of intracellular muscle proteins including myoglobin, creatine kinase and electrolytes into the blood stream which could be a life threatening condition. (Torres et al, 2015). The role of genetics in the development of rhabdomyolysis could be an inherited neuromuscular disorder. The genetic predisposition of rhabdomyolysis include muscular dystrophies, metabolic muscle disorder, mitochondrial disorder, and intramuscular calcium release and excitation-contraction coupling. (Scalco et al, 2015).
The symptom of burning pain over his left hip and forearm experienced by the patient is as a result of the muscle injury incurred while taking opioids in large quantities leading to necrosis and tissue damage. Cell injury and death result when the body has been exposed to “toxic chemicals, infections, physical trauma, and hypoxia”. (McCance & Huether 2019). The abnormal EKG reading and elevated serum potassium levels are due to the release of calcium and potassium from damaged muscles into the blood stream which could not be cleared by the kidney. (Torres et al, 2015). Additionally, the symptom of unresponsiveness was caused by opioid overdose.
The physiological response to the stimulus in this scenario is the quick return of responsiveness after the patient received naloxone which is a reversal agent for opioid overdose. Naloxone, an opioid antagonist, attaches to opioid receptors, reverses and block the effect of other opioids. Also, it restore normal breathing to persons whose respiration has been slowed or stopped due to opioid overdose. (NIDA 2022, January 11). The cells to which naloxone binds in this process is called the mu-opioid receptors. As a mu-receptor antagonist, naloxone works within two minutes when administered intravenously and last between 60 to 90 minutes. (Edinoff et al, 2021).
Genetics and the environment are another characteristics that will change the response as it is a contributing factor to why most individuals who abuse drugs are opioid dependent while others are not. The risk for someone becoming a drug addict can be dependent on their genes and the environment. Their are individuals with the single polymorphism gene that protect them from becoming dependent on opioid. The environment and lifestyle affects an individual’s vulnerability to drug use and addiction. (Wang et al, 2019).
First, it should be mentioned that we do not know how long the patient was unconscious and what this patient overdosed on. Naloxone (Narcan) was used as treatment of choice, which caused patient to regain consciousness. Narcan can quickly reverse an opioid overdose. It is an opioid antagonist. As a result, it binds to opioid receptors, blocking and reversing the effects of other opioids (Naloxone Drug Facts, 2022). However, it is important to note that single Narcan application may not be enough as we are not aware of substance and amount taken.
Second, patient presents with necrotic tissue over left great trochanter as well as the forearm. Necrotic tissue is cause by decries oxygenated blood to body parts. It may be caused by many things including injury, cold, or chemicals. Pt could have potentially fallen as a result of overdose, which could have caused rhabdomyolysis. Rhabdomyolysis is the breakdown of damaged muscle that leads to the leaking of the contents of muscle cells into the blood, which may harm organs. Potassium plays a major role in regulating the skeletal muscle blood flow (Buttner, & Buns, 2022). In the information provided patient presents with increased K+ level at 6.9 mEq/L, which is a contributing factor of rhabdomyolysis. Rhabdomyolysis is usually associated with hyperkalemia due to renal failure. Aside from that muscle breakdown could be indicated by muscle protein creatine kinase (CK) levels in blood, which we were not provided with (Rhabdomyolysis, 2023).
Third, patient presents with abnormal EKG results involving prolonged PR interval and peaked T waves. Elevated serum K+ can cause EKG abnormalities. An elevated serum potassium level (> 5.2 mmol/L) is referred to as hyperkaliemia. EKG alterations typically do not appear until hyperkalemia has reached a significant level (6.0 mmol/L). An increase in T wave amplitude is the first sign of hyperkalemia (Buttner, & Buns, 2022).
In case of genetics, information was never provided if this patient belongs to a certain race. It is known that this patient is a potential 27 year old male. Genetically speaking, it can be assumed that heredity plays a part in one’s future. For example, it may be possible to predict whether a person would develop an addiction to substances by counting the amount of a certain type of dopamine receptor known as D2. It responds to the presence of dopamine. If one is lacking this gene the compulsion to consume will be increased (Price, 2018).
In terms of gender the difference comes with age and weight. This will determine dosage and potential amount of treatment required. Older people tend to respond slower compared to younger people. In terms of wight dosage might be adjusted to prevent Narcan rebound effect. The body only retains the effects of Narcan for 30 to 90 minutes. If a powerful opioid is present in the body, it is possible for a person to continue to feel the effects of an overdose even after naloxone wears off or to require additional doses (Naloxone Drug Facts, 2022). Environment plays a big role in addiction treatment as well.
Necrosis is the typical type of cell death with severe cell swelling and breakdown of organelles. (Jog & Caricchio, 2014). The patient had gangrenous necrosis based on the patient history of substance abuse and symptoms. Since the patient’s history of substance abuse contributed to hypoxia, a lack of oxygen supply, ATP production was decreased. This type of tissue necrosis results from a severe hypoxic injury due to blockage or arteriosclerosis.
Genetics is the study of genes and heredity traits. Genes influence all aspects of the body’s structure and function, so any error in one of the genes can lead to a recognizable genetic disease (McCance & Huether, 2019). Genetics plays a role in the disease to determine if the patient carries specific disease-causing mutations (McCance & Huether, 2019). In the case of the patient in the scenario, the necrotic tissue could result from genetic mutation or the use of substance abuse by the patient. The DNA must replicate itself accurately during cell division to preserve genetic code for subsequent generations.
The patient presents with the symptoms because of the release of bradykinins, obstruction, and pressure. Dead cell causes a burning sensation and pain. Also, the fluid shift has changed due to cell necrosis. Potassium is the primary intracellular electrolyte and is highly regulated due to its role in neuromuscular function (McCance & Huether, 2019). The cell hypoxia leads to hyperkalemia by diminishing the efficiency of cell membrane active transport causing a change in cell membrane permeability, leading to the escape of potassium to ECF (McCance & Huether, 2019). The EKG reading of prolonged PR interval and peaked T wave occurs due to hyperkalemia.
Cells involved are the endoplasmic reticulum and mitochondria, the plasma membrane rupture, and the cell lysis. The physiological response to the stimulus in the scenario is EKG result and burning pain. One problem that causes necrosis is the use of chemical agents, such as substance abuse (Khalid, n.d.). The patient had burning pain due to the necrotic tissue, and research shows that lack of oxygen causes necrosis (Khalid, n.d.). When tissue has a problem, it affects the transport of electrolytes across the cell, resulting in electrolyte imbalance. The Prolong PR and peaked T were caused due to hyperkaliemia. In the scenario provided, whether the patient is male or female was not cleared. However, based on research evidence, males are more likely to develop necrosis than females (Ortona et al., 2014).
Normal serum potassium level ranges from 3.5 mEq/L to 5.5 mEq/L. There is no difference in potassium level between females and males. Serum potassium level more than 5.5 mEq/L is considered more than normal and it is referred as hyperkalemia (Jain, Ong & Warnock, 2013). There is always need to rapidly treat such a condition given that a potassium level more than 6.5mEq/L result in high mortality rate and morbidity, which means it should be treated as an emergency (Jain, Ong & Warnock, 2013). The patient may be suffering from hyperkalemic period paralysis which is amplified by taking of drugs. Drugs such as opioids can increase chances of hyperkalemic episodes. Hyperkalemic periodic paralysis is associated with changes in SCN4A gene. This is an inherited condition which results in increase in serum potassium levels.
The symptoms of hyperkalemic periodic paralysis can begin from childhood and may continue to adulthood. The condition is associated with muscle weakness during the episode of high potassium levels in the blood. As a result of the muscle weakness, the patient would be lying on one side of the body for a long time. This caused the ED to show large amount of necrotic tissue. Large amount of necrotic tissues involves cutting off of blood supply to a certain area of the body, resulting in death of the tissues. Similarly, an increase of serum potassium above 6.5 mEq/L leads to prolonged PR interval (Parham et al., 2006). This is given that it leads to a longer action potential.
Naloxone is used for treatment of opioid overdose (NIDA, 2022). The different opioids include fentanyl, heroin, morphine, and oxycodone. Individuals who have signs of opioid overdoes are given naloxone. In case the patient was suspected of an opioid overdose, naloxone reverses and blocks the effect that opioids have on the body.
Cells involved in naloxone action include µ-opioid receptor. These receptors control a variety of physiological functions. Such functions include mood, memory, motivation, temperature and respiration. Opioids such as fentanyl and morphine are used to treat severe pain due to the fact that these drugs target these receptors.
Other causes of hyperkalemia would be kidney diseases which impacts the function of the kidney. Kidneys are involved in balancing serum potassium levels. The kidney usually works to filter potassium and ensure it is balanced in the body (Hollander-Rodriguez & Calvert, 2006). If the functioning of kidney is not good, it will not be able to remove excess potassium in the body. People with kidney diseases and who take diets with high potassium will likely suffer hyperkalemia
The main root of diagnosis for this patient is substance abuse. There are many factors both genetic and environmental that put someone at risk for developing substance use abuse. According to the NIHs, National Institute on Drug Abuse, NIDA, half of a persons risk of being an alcohol, nicotine or tobacco user depends on his or her genetic makeup. Besides for genetic factors, environmental factors such as social circles, financial bracket and emotional trauma can put someone at greater risk for developing substance abuse (NIDA, 2019).
The selected patient scenario seems to be describing an individual who has experienced an opioid overdose. As a result of the overdose the patient was found by EMS in an unresponsive state. Naloxone, a reversal agent for opioids was administered, causing the patient to gain consciousness (CDC, 2023). Upon becoming responsive, it seems the patient was experiencing tremendous pain radiating over his left hip and forearm. Based on the given information, it seems that the patient was experiencing this pain before and perhaps as a result took pain medications. Deeming the patients history of abusive patterns, I would deduce that the patient was overmedicating on some opioids to reduce his pre existing pain.
Often times as a result of substance abuse, a condition called rhabdomyolysis can occur ( F, Fernandez, et al. 2019). Rhabdomyolysis, along with necrosis is what I would attribute to the intense pain felt over his left hip and forearm. Rhabdomyolysis, is a life threatening condition that is caused by injury to the skeletal muscles, in this case the injury being the substance abuse (CDC,2023).The abuse substance impairs the skeletal muscles ability to produce or use ATP or it causes an increase in the ATP demand that exceeds the bodies ATP production ability. As a result the muscle tissue breaks down rapidly releasing intracellular muscle components into the bloodstream. This can lead to electrolyte imbalances, kidney disorders and other dysregulations in the body. In this situation, as a result of the muscle breakdown, there is a shift in the K+ and Na+ gradients. The increase in intracellular Ca+ due to the muscle breakdown causes an electrolyte shift in the membrane, often causing increased potassium in the blood, also known as hyperkalemia. The increased potassium level of 6.9 this patient is experiencing has caused the peaked T waves due to the gradient shift. The increased potassium causes increased excitability in the electrical conduction of the heart, causing the peaked T waves as well as the prolonged PR interval seen on the EKG reading (Mckance & Heuther, 2019).
Being that the patient was found unconscious and had a period of time with potential hypoxia to all extremities and a potential infection prior to the overdose, the necrosis, and essentially tissue death found over the greater trochanter and forearm is not surprising. Oftentimes following an episode of opioid overdose, a person is driven into respiratory depression, which causes a decrease in oxygenation leading to hypoxia which can in turn cause necrosis to parts of the body (Alyssa, 2022).
Had the patient been of older age, with multiple comorbidities I am certain my assessment and interpretation of this case would be different. The older the person is , the more sensitive their body becomes to drug metabolization. As a result an older patient may have worse adverse effects from an overdose than a 27 year old individual and they may be affected from a lower “overdose” than someone who is of younger age. Additionally, having comorbidities can cause the overdose symptoms to be exacerbated or may lead to additional complications (Public citizen, 2019).
In regards to this post about the 27-year-old patient, I believe that he is suffering from rhabdomyolysis. The description of this patient having substance abuse and then being found on the floor after many many hours fits with this diagnosis . His elevated potassium level is also a sign of rhabdomyolysis. When reading an article on the National Kidney Foundation website, I have found that patients can go into acute kidney failure with rhabdomyolysis. If they are severly dehydrated after being found on the floor after hours or days, the kidneys will be affected. When the kidneys are affected this can cause a patient to become hyperkalemic. (National Kidney Foundation Staff, 2023). Also his irregular cardiac rhythms on his EKG for this as well. When doing research on this topic, I came upon an article on WebMD. In summary, Rhabdomyolysis can be caused by many factors. Factors could be traumatic or non. They could be the result of a car crash for example or a fall placing a patient on their back or side for long periods of time. Burns or snake bites can also be culprits. Finally, muscles strained at an extreme level when working out, use of alcohol or drugs, seizures or high body temperature can weight in. (Stuart, Annie. 2021).
I feel that substance abuse has a genetic factor. From research I have done over time, and observations at the hospital, I have learned that those with mental health disorders such as depression, personality disorders and schizophrenia are more at risk to develop addictive habits. Also, reoccuring rhabdomyolysis can also have a genetic factor. My thoughts after reading a genetics website, is that reocurring rhabdomyolysis can include genetic factors such as metabolic myopathy, disorders of intramuscular calcium release, mitochondrial disorders and muscular dystrophies. (Blueprint Genetics Staff, 2022).
The cells involved in Rhabdomyolysis include skeletal muscle cell damage. After reading more on the unmc website, I have learned that the cellular membrane is affected. This can lead to the release of toxic intracellular constituents. These could be released into the blood stream. (Giannoglou, Chatzizisis and Misirli, 2006.)
If only one factor was changed in this scenario, age, my response would be different. While in this scenario, a twenty-seven year old is involved and the prognosis to make it through is very high. If this was an elderly patient, their change of complete recovery is low. This may lead to many dialysis sessions for them. This also may lead to limited mobility for them. They may find themselves needing placement in a nursing home when they were once independent.
- The role genetics plays in the disease.
A multitude of environmental and genetic factors may play a role in an individual’s risk of becoming dependent on substances. Family studies have shown that up to 50% of a person’s risk of becoming addicted to substances relies on their genetic makeup (NIDA, 2019).
- Why the patient is presenting with the specific symptoms described.
He likely presents with the burning and necrotic tissue over left hip and forearm due to loss of circulation to these areas. He had an unknown down time prior to being found, and if he was laying on these areas for an extended period of time, there’s a risk of loss of circulation and perfusion to the affected areas. The elevated potassium will cause changes in EKGs including peaked T waves.
- The physiologic response to the stimulus presented in the scenario and why you think this response occurred.
The stimulus in this scenario was the Narcan. Narcan is an opioid antagonist, it blocks the receptors that opioids bind to, creating a reversal effect (Narcan: How It’s Given, How It Works, Uses, and More, 2021). The Narcan effectively reversed the effects of the opioid medication taken by the patient, causing him to regain consciousness.
- The cells that are involved in this process.
Neurons are involved in this process. Neural cells have receptors that bind to various hormones and chemicals, either produced by the body or introduced via medications.
- How another characteristic (e.g., gender, genetics) would change your response.
Gender would be a topic to explore more fully in its effect on substance use disorder. According to The National Institute on Drug Abuse (NIDA) (2022), men are more likely than women to use illicit drugs. However, women are just as likely as men to develop substance abuse disorder (NIDA, 2022). I don’t think that this consideration would change my overall view and diagnosis of the patient, but it is an important factor to consider. There are also other factors to consider, such as other mental health diagnoses, socioeconomic status, and other diagnoses affecting overall health.
There are scientifically proven factors that can influence the development of substance abuse, genetic factors being one. Genetic factors and variations play a significant role in establishing individual differences in addiction risk. Genetic studies have shown an overlap in genetic variants that influence risk towards different classes of drugs. The most extensive study to date on 1.2 million individuals that assessed common genes in alcohol and nicotine use has identified genes involved with dopaminergic and glutamatergic neurotransmission, genes involved with transcription and translation, and brain development (Volkow et al., 2019). Genetic studies have also revealed an important genetic contributor that influences a vulnerability for disorders characterized by pathological tendencies to violate social norms or engage in oppositional behaviors, which substance abuse is characterized.
In this case study, the patient presented with loss of consciousness (LOC) but became responsive after receiving naloxone. He complains of a burning sensation over his left hip and forearm, and an Emergency Department (ED) exam revealed a significant amount of necrotic tissue over those areas. An EKG of the patient showed prolonged PR intervals and peaked T waves, and a lab result revealed a potassium level of 6.9 mEq/L. The patient likely has a decreased LOC due to injection or ingestion of an opioid substance. These substances decrease the central nervous system and autonomic functions necessary for living, such as blood pressure, respiration, heart rate, and body temperature (Somerville et al., 2017). This occurred due to the injection or ingestion of more substances than the body could handle, causing depression in body functions. The necrotic tissue over his left hip and forearm could be from infections at substance injection sites or from the injected substances blocking blood flow to those areas. The necrotic tissue could also result from hypoxia due to the decompensation of his central nervous system and autonomic functions when unconscious. Necrotic tissue is painful and caused by cell death. Alcohol and social drugs, especially opioids, can significantly alter cellular function and injure cellular structures resulting in cell death (McCance & Huether, 2019, p. 61). The EKG results show hyperkalemia by the peaked T waves and prolonged PR intervals. It was confirmed with the lab work that showed elevated serum potassium. A typical range for serum potassium is 3.5 – 5.0 mEq/L, so it’s clear that his levels are elevated. This could be an acute episode of hyperkalemia commonly triggered by the introduction of medications or substances affecting potassium homeostasis, and illness or dehydration also can be triggers (Hollander-Rodriguez & Calvert, 2006). The presence of typical electrocardiographic changes or a rapid rise in serum potassium indicates that this hyperkalemia is potentially life-threatening.
Due to the potential of this patient to have sustained a hypoxic injury, along with the other external stimuli such as substance use and loss of consciousness, cellular death took place. McCance & Huether (2019) state that with necrosis, there is a rapid loss of the plasma membrane structure, organelle swelling, and mitochondrial dysfunction (p. 87). Necrosis is common with ischemic and hypoxic injuries along with infections and trauma, which the patient could have sustained all three. Also, with ischemic and hypoxic injury comes a shift in extracellular potassium. This can cause the patient’s hyperkalemia. McCance & Huether (2019) also mention that as cells die, the plasma membrane’s sodium-potassium (Na+-K=) pump and sodium-calcium exchange start to fail, which increases the intracellular accumulation and sodium and calcium, leading to the cells swelling and diffusing potassium out of the cell into the extracellular space. These cellular processes are involved in the physiological response of the patient.
After reviewing the body and cellular processes involved in this case study, I don’t believe variables in characteristics of the patient would change my responses. Given the circumstances these physiological responses could have happened regardless of sex, race, or family history.
The disease for the case scenario described is a combination of disease processes, caused initially by a suspected drug overdose. The disease processes are respiratory depression secondary to drug overdose and acute kidney failure secondary to rhabdomyolysis and first-degree heart block. Opioid overdose causes respiratory depression, which decreases the amount of oxygen getting to the cells in the body and cause organs to shut down and cells to become damaged or die. The patient has a history of drug abuse and arouses after administration of Narcan, which suggests that this was the culprit. Because we do not know how long the patient was down, we only have symptoms to assume he was down for an extended period of time. The necrotic tissue over his greater trochanter and forearm, along with burning pain, indicate pressure injuries from being down for a long time. The pressure to the tissue deprives the cell of oxygen and nutrients resulting in cell tissue death of the epithelium. His elevated serum potassium levels indicate an acute kidney injury that may be due to the process of muscle cell breakdown releasing myoglobin, potassium, creatine kinase, phosphate and urate into the bloodstream, which damaged kidney cells, increasing potassium levels, which result in a peaked T wave (Cleveland Clinic, n.d.). Prolonged PR interval may be due to the excess of drug use damaging cardiac cells (McCance & Huether, 2019).
Genetics play a large part in the disease of addiction and drug abuse. It has been shown that addiction is genetic. Addiction may be worsened by environmental factors such as poverty, poor home life and environment. Another characteristic that would change my response is if the patient did not have a known history of drug abuse and did have a history of chronic kidney failure. If he did not have a history of drug addiction than I would think that this was not a genetic trait. If he had a history of chronic kidney failure, I would lean more towards the initial issue being acute kidney failure and possibly not metabolizing his medication appropriately, causing him to become unresponsive (McCance & Huether, 2019).
The role genetics plays in the disease.
This patient presents with Rhabdomyolysis from decreased blood supply to the area, causing autolysis. Torr & Mortimore (2022) explain that the characteristic of Rhabdomyolysis is the rapid dissolution of damaged or injured skeletal muscle that can result from many mechanisms. The authors further explain that Rhabdomyolysis causes muscular cellular breakdown, which can cause fatal electrolyte imbalances. From the explanation, one will conclude that in this case, genetics play a less important role as Rhabdomyolysis developed due to compression of muscle compartments because of prolonged immobility and substance abuse but not due to genetics.
Why is the patient presenting with the specific symptoms described?
The patient presents with specific symptoms because, according to (Torr & Mortimore, 2022). damage to muscles (muscle necrosis) due to Rhabdomyolysis in the hip explains the burning pain over the hip. Also, elevated potassium level is due to leakage of intracellular potassium into circulation resulting in Hyperkalemia, and ECG findings are consistent with this Hyperkalemia. McCance et al. (2019) defined Hyperkalemia as ECF greater than 5.0mEq/L and severe Hyperkalemia as serum levels greater than or equal to 6.0mEq/L.
Explain the physiologic response to the stimulus presented in the scenario and why you think this response occurred.
Zimmerman (2022). emphasizes that most drugs can directly affect the skeletal muscles, resulting in Rhabdomyolysis. The writer explains further that researchers found that individuals addicted to cocaine had a reduced gray matter volume compared with individuals who did not have a cocaine dependency. Qeadan, & Madden. (2022) state that naloxone is an opioid antagonist that temporarily reverses respiratory depression and sedation and dramatically reduces opioid overdose fatalities.
Prolonged lying down, as evident from the incident, the patient was lying down from an unknown time which could have raised the compartment pressure in vulnerable muscle compartments like the leg, hip, volar aspect of the hand, and gluteal regions (Zimmerman, 2022). McCance et al. (2019) explain that decreased blood supply to the greater trochanter and forearm caused a decrease in ATP production. The decreased ATP caused an increase in intracellular calcium. As calcium increases, there will be an exchange of potassium, and serum K+ levels will rise.
The cells that are involved in this process.
Muscle cells are mainly involved in this process. Due to damage to the muscle cells, the
myoglobin in the muscle cells leaks into the blood and causes renal toxicity (nephrons are next
involved in pathology) and metabolic acidosis. Muscle ischemia can further cause nerve damage (nerve cells). Extracellular fluid shift resulting in shock due to hypovolemia Hyperkalemia due to leaked intracellular potassium ions, which can induce dysrhythmias (myocardial cells) (McCance et al., 2019)
How would another characteristic (e.g., gender, genetics) change your response?
Gender: Rhabdomyolysis occurs less in females than males. Burning pain in females could be more attributed to local tamponade due to immobility. It does not mean that females do not have the disease. On the other hand, this case presentation of Rhabdomyolysis lacks a genetic component because the illness occurred due to prolonged immobility and substance abuse.
Without more information or medical history of the patient, the underlying disease is substance use disorder. More specially, in this case, opioid use disorder. This is evidenced by the background history given by the patient’s roommate and the fact the naloxone made the patient responsive. There have been several research studies conducted on opioid addiction and genetics. In a review of opioid addiction and genetics Crist, Reiner, and Berrettini (2019) conclude that the risk for opioid abuse is increased significantly by genetics. Twin and family studies have estimated the heritability to be 23-54%. Several genes have been studied and identified as risk factors for opioid use disorder. A few of those genes include Mu-opioid Receptor, Delta-Opioid Receptor, Dopamine Receptor D2, and Brain-derived Neurotrophic Factor.
The patient presented as unresponsive, which is a side effect of opioid overdose. Opioid overdoses cause respiratory and central nervous system depression which can lead to hypoxic brain injury or death (Chimber & Moleta, 2018). The drug naloxone was given by emergency medical services (EMS), which caused them to become responsive. Naloxone is an opioid antagonist drug that reverses the effects of opioids. Upon reversal of the opioids in the patient’s system, the patient regained normal respiratory status and regained consciousness. The patient complained of pain in his left hip and forearm. Upon evaluation in the emergency department (ED), necrotic tissue was found on his forearm and greater trochanter. The pain was caused by these deep tissue injuries from both ischemic and hypoxic injuries, lack of oxygen to the body from the overdose, and decreased blood flow from laying for an unknown period. This creates local cell death and then autolysis, leading to necrosis. The changes in the EKG are a direct result of the patient’s increased potassium levels (hyperkalemia). According to Najjar (2022), “peaked T waves, usually seen when K levels are between 5.5-6.5mmol/15) Shortened QT and ST-segment elevation may follow. As K rises to 7-8mmol/L or above, the disappearance of P waves and QRS complex widening may develop”. The unknown downtime could contribute to rhabdomyolysis, which is a kidney function impairment and tissue breakdown. As a result, the patient is at high risk for tissue necrosis and an increase in potassium.
A complete medical history may change my response to this scenario. The increased potassium levels could be in part due to underlying kidney disease. The necrotic tissue could be related to IV drug use or other unknown variables. The exact drugs on board and events leading to the event could shed light on the current presentation. More testing such as a CPK level, WBC, and CT to reveal is there is gas in the wound, if an infection is present, or if in fact, the patient is in rhabdomyolysis. Additionally, race, gender, and family history would be helpful for determining genetic predispositions.
Influence of Genetics in Necrotizing Soft Tissue Infection
Genetics is important in determining the susceptibility and severity of NSTIs. Genetic variations in the genes linked with the innate immune system can influence the risk of developing NSTI. In particular, the Toll-like receptor pathways, responsible for recognizing invading pathogens by the immune system, are associated with NSTI risk (Hua et al., 2018). In addition, polymorphisms in genes involved in the inflammatory response may also increase the susceptibility to NSTI and the severity of the infection. A study by Fernando et al. (2019) also identified genetic variations in the genes involved in coagulation and fibrinolysis that can increase the risk of developing NSTI and affect the outcome of the infection. Furthermore, other genetic factors, such as gender, age, and race, may also influence the risk and severity of NSTI and the response to treatment (Stevens et al., 2021). As such, it is crucial to consider the genetic factors when assessing the risk of NSTI in patients and tailor the treatment according to the individual’s genetic profile.
Analysis of Patient’s Symptoms
The patient is experiencing acute discomfort over their left hip and forearm, protracted PR interval, and serum potassium level of 6.9 mEq/L because of the necrotizing soft tissue infection. NSTI is a critical infection that results in tissue necrosis, or death of cells and tissues, due to bacterial toxins and enzymes (Shumba et al., 2019). These toxins and enzymes cause inflammation and tissue damage, resulting in the burning pain the patient is experiencing in the limbs. The EKG changes, such as the prolonged PR interval and peaked T waves, can be attributed to the high serum potassium level, often seen in cases of NSTI due to the systemic release of potassium from the damaged tissue (Thänert et al., 2019). The prolonged PR interval could also be attributed to the inflammation of the myocardium, which is often seen in cases of NSTI. These symptoms indicate necrotizing soft tissue infection and require prompt treatment to prevent further tissue damage.
The Physiologic Response to Necrotizing Soft Tissue Infection
The physiologic response to the NSTI in the scenario is likely an immune response. When the body is exposed to a pathogen, the innate immune system responds by producing inflammatory cytokines, such as interleukin-1, as well as chemokines, such as CXCL8, to recruit inflammatory cells to the site of infection (Hua et al., 2018). This process activates the pro-inflammatory pathways, releasing inflammatory mediators such as histamine, prostaglandins, and leukotrienes, which cause the burning pain the patient is experiencing in the limbs (Fernando et al., 2019). In addition, releasing these inflammatory mediators also activates the coagulation pathways, which can lead to prolonged PR interval and peaked T waves seen on the EKG (Thänert et al., 2019). The elevated serum potassium level is likely due to the systemic release of potassium from the damaged tissue (Thänert et al., 2019). In this light, inferring that the patient’s body is responding to the necrotizing soft tissue infection with an immune response to eliminate the pathogen and restore tissue homeostasis would be valid.
The Cells Involved
In the scenario, the cells involved in the immune response to the necrotizing soft tissue infection are neutrophils, macrophages, and lymphocytes. Neutrophils are the primary cells involved in the innate immune response to infection. They are responsible for the production of inflammatory cytokines and chemokines and for the phagocytosis of bacteria (Hua et al., 2018). Macrophages are also involved in the innate immune response. They are responsible for the production of inflammatory mediators, such as histamine, prostaglandins, and leukotrienes, which cause the burning pain the patient is experiencing in the limbs (Fernando et al., 2019). In addition, macrophages play an essential role in the clearance of dead and damaged tissue. On the other hand, lymphocytes are involved in the adaptive immune response and are responsible for producing antibodies, which help neutralize bacterial toxins and enzymes (Shumba et al., 2019). Therefore, the definite functionality of each type of cell is essential in mounting an effective immune response to the necrotizing soft tissue infection.
Impact of Patient Characteristics on Clinical Response
Characteristics such as gender and genetics can both affect the response to the NSTI in the scenario. Studies have shown that women are more likely to develop NSTI than men due to differences in the immune response and skin thickness (Hua et al., 2018). In addition, genetic variations in the genes associated with the innate immune system can influence the risk of developing NSTI and the severity of the infection (Hua et al., 2018). For example, polymorphisms in the genes associated with the Toll-like receptor pathways can increase the risk of developing NSTI and affect the outcome of the infection (Fernando et al., 2019). Furthermore, genetic variations in genes involved in the inflammatory response, coagulation, and fibrinolysis can also increase the risk of developing NSTI and the severity of the infection (Fernando et al., 2019). As such, it is important to consider the gender and genetic factors when assessing the risk of NSTI in patients and to tailor the treatment according to the individual’s gender and genetic profile.
Conclusion
Necrotizing soft tissue infection is a severe infection that can lead to tissue necrosis and death of cells and tissues due to bacterial toxins and enzymes. The patient in the scenario likely presents with specific symptoms due to the infection. The toxins and enzymes cause inflammation and tissue damage, resulting in a burning pain in the limbs and changes in the EKG. The cells involved in the immune response to the infection are neutrophils, macrophages, and lymphocytes, responsible for producing inflammatory cytokines, chemokines, inflammatory mediators, and antibodies. Gender and genetics can both affect the response to the infection. It is important to consider these factors when assessing the risk of NSTI in patients and tailor the treatment according to the individual’s gender and genetic profile.
In understanding the nature of opioid overdose, we must explore how opioid work in the human body. Opioids are a general class of plant-based alkaloids and synthetic drugs that, when ingested, smoked, or given IM or IV, attach to the four available opioid receptors. Most opioid drugs bind to G-protein-coupled receptors, including μ, δ, and κ opioid receptors (Volpe et al., 2011). When opioids attach to these receptor sites, this act by i) closing voltage-sensitive calcium channels (VSCCs), (ii) stimulating potassium efflux leading to hyperpolarization, and (iii) reducing cyclic adenosine monophosphate (cAMP) production via inhibition of adenylyl cyclase. Overall, this results in reduced neuronal cell excitability, leading to reduced transmission of nerve impulses and inhibition of neurotransmitter release. This reduction in nerve impulses relaxes an individual and causes respiratory depression, for an individual to lose consciousness (Montandon, G. (2022). Naloxone is an antidote and replaces the opioids at the receptor site, thus restoring neural excitability to normal levels and restoring normal respiration and mental state.
When individuals are allowed to stay in one position, it causes pressure, especially on bony promises or any other place, by restricting blood supply to the tissue. This restriction of blood supply cuts the oxygen supply to the tissue, thus disrupting the Na/K channel that operates with ATP that requires oxygen supply. The cascade of chemical changes impairs the cell wall integrity and allows the potassium to move out to ECF (Extracellular fluid) from ICF (intracellular fluids). This movement of K (Potassium) into ECF causes hyperkalemia and hyperexcitability of nerves and thus causes cardiac tissue to cause prolonged PR interval and peaked T wave. Now we shall restore the K to a normal range of 3.5 – 5.5 mEq/L and see of there is enough pain control if the individual was using it for pain.
Explanation of Disease
Based on the patient’s history of drug use, reaction to Narcan, and necrotic tissue, it appears that the patient could have overdosed with a drug that could be laced with a substance known as “Rizzy” powder or a synthetic opioid, desomorphine also known “the flesh-eating zombie drug” (Houck & Ganti, 2019). It is also possible that the necrotic tissue is non-related however, due to the location of necrotic tissue and drug history this could be considered. The differential diagnosis of skin manifestations in IV drug users should include both infection and the direct caustic effects of agents. According to McCance, K. L. & Huether, S. E. (2019), it was estimated that 2.1 million people in the US suffer from substance use disorders related to prescription opioid pain relievers, and an estimated 467,000 people were addicted to heroin. Often these laced substances causing necrosis are in opioids and heroin.
The Role Genetics Plays in Disease and Other Characteristics Effect on Response.
An individual’s genotype is the person’s genetic makeup, and the phenotype reflects the interaction of the genotype and environment (McCance & Huether, 2019). Together, these characteristics create epigenetic marks that can affect the health and expression of the traits of that person passed to a child. If a person uses a drug such as cocaine, the DNA can be marked by increasing proteins common in addiction (NIDA, 2019). Therefore, a person’s genetics can increase their risk of addiction and drug-seeking behavior.
Multifactorial diseases in adults include coronary heart disease, hypertension, breast cancer, colon cancer, diabetes mellitus, obesity, AD, alcoholism, schizophrenia, and bipolar affective disorder (McCance & Huether, 2019). An example according to NIDA (2019), is a community that provides healthy after-school activities has been shown to reduce vulnerability to drug addiction, and data show that access to exercise can discourage drug-seeking behavior. This effect is more pronounced in males than in females. The environment’s effect on the phenotype in that community can then take what could have been a mild genetic trait and multiply the risk for addictive behavior.
Why the patient is presenting with the specific symptoms described
According to McCance & Huether, (2019) Hyperkalemia (potassium levels >5.0 mEq/L) may be caused by increased potassium intake, a shift from ICF to ECF potassium, or decreased renal excretion. At the cellular level, the potassium shifts from the intracellular fluid to the extracellular fluid related to decreased renal function. This also can present as a prolonged PR interval and tall, peaked T wave on an electrocardiogram. In this case, due to the likelihood of respiratory depression, hypoxia could have led to hyperkalemia by diminishing the ability to transport through the cell membrane and causing the escape of potassium to the extracellular fluid (McCance & Huether, 2019). The patient’s responsiveness was likely due to an opioid or heroin overdose laced with some substance, causing the necrotic tissue as discussed in the first paragraph under the explanation of the disease.
The physiologic Response to the Stimulus
Naloxone is an opioid antagonist that blocks opioid receptors from being activated. When administered in the body it travels to receptors and can even move the opioid off the receptor sites. Removing the opioid from the cell all around the body and brainstem can restore multiple organ functions including the drive to breathe (NIDA, 2022). This likely occurred in the patient scenario when the medication was administered, and he regained consciousness.
The Cells that are Involved in this Process.
At a cellular level, opioid receptors are found on nerve cells around the body. They carry out regulatory effects by inhibiting neuronal activity. Opioids block voltage-dependent calcium channels, activate potassium channels, and inhibit ATP, reducing neurotransmitter release. This occurs along the brainstem and throughout the body affecting all major systems (Reeves et al., 2022). When opioids are introduced into the body, the brain produces a relaxed feeling also relaxing the brainstem and therefore breathing. The spinal cord and other peripheral nerves also slow down pain signals. When someone has opioid dependence, they must increase their doses to continue to get the desired feeling. Such high doses can then create an overdose that magnifies all the actions to the point where the patient then becomes unresponsive and often stops breathing. Over time, frequent opioid use makes the body dependent on drugs. When the opioids are taken away, the body reacts with withdrawal symptoms such as headache, racing heart, sweats, vomiting, diarrhea, and tremors (Cleveland Clinic, 2022).
In the highlighted scenario, the patient presents with an acute opioid overdose. This is highlighted by his history of substance abuse, his unresponsiveness upon his initial presentation, and his response to the naloxone. The response from the patient to the stimuli is a result of the opioid receptor antagonist, naloxone, binding to the opioid receptors and reversing or blocking the effects of the opioids (NIDA, 2017).
The patient is also presenting with hyperkalemia and a prolonged PT interval. This is because the patient’s level is greater than 6, which indicated severe hyperkalemia. With severe hyperkalemia; the ST segment becomes depressed, which leads to prolonged PT intervals. The burning and pain the patient is feeling are most likely due to necrotic tissue over the greater trochanter and forearm (McCAnce et al., 2019).
As far as genetics are concerned, there have been studies done that have reported that there are genetic factors that contribute to addictive behaviors, as well as relapse. This study also stated that there is a 31% genetic effect on drug abuse (Mistry et al., 2014). Also, men are at greater risk of overdose verses women (NIDA, 2022). therefore my response would change if the gender was different.
Upon looking at this case study, the first thing that comes to mind regarding this situation is hypoxic injury due to a lack of oxygen circulating in the bloodstream because of an overdose and respiratory depression. Hypoxia is one of the most common causes of cellular injury. A hypoxic state will result in a decrease in adenosine triphosphate (ATP) production (McCance, et. al., 2019). From here, anaerobic metabolism will attempt to maintain ATP levels to avoid cellular injury and death.
ATP is generated from glycogen in the event that there is not sufficient oxygen to produce ATP. However, after glycogen stores deplete, anaerobic metabolism stops, thus decreasing ATP again. A lack of oxygen plays a big part in the progression of cell injury in reduced blood supply to tissues/cells. Activated oxygen species cause the destruction of cellular membranes as well as their structure. The reduction in ATP levels causes the sodium-potassium pump in the plasma membrane and the sodium-calcium exchange to fail. This will result in the swelling of cells as well as the diffusion of potassium out of the cell into the extracellular fluid (ECF). Cell membrane damage will allow a large amount of calcium to rapidly enter the cell resulting in swelling. As a result of this swelling and damage to organelles, necrosis occurs, a common type of cell death (McCance, et. al., 2019). This is the cellular process that appears to have happened over the patient’s greater trochanter and forearm. Interestingly, avascular necrosis is most common around the hip joint. As far as the patient’s forearm is concerned, if it was soft tissue, one could argue that he was experiencing skin necrosis which results in a lack of blood flow to body tissues. Both are commonly found in substance abuse (Cleveland Clinic, n.d.).
Hyperkalemia, or a high serum potassium level, is defined as greater than 5.0mEq/L. In this case study, the patient has a high potassium level of 6.9mEq/L. In this case, the excess potassium could be linked to the potassium shift from the intracellular fluid (ICF) to the ECF due to decreased ATP. The extra potassium will be excreted as long as renal function remains intact. The prolonged PR interval found on EKG is due to cellular membranes being hypopolorized as the resting membrane potential becomes more positive. This means that the cell is more irritable due to the cell rapidly repolarizing, and action potentials are initiated more quickly. This is due to the resting membrane potential and the threshold potential being shortened. If left hyperkalemia is left untreated, it can lead to arrhythmias (Viera, 2015). To aid in helping decrease ECF potassium, calcium gluconate can be used or a calcium binder. Another option would be a cation exchange resin such as Kayexalate (Pitt, et. al., 2015).
In my opinion, neither genetics nor gender played a role in the development of tissue necrosis or the EKG changes that were present from hyperkalemia. The cellular response, to my understanding, would remain the same if the patient was female or of any race.
Genetics plays a role, to a greater or lesser extent, in all diseases. Variations in our DNA and differences in how that DNA functions (alone or in combinations), alongside the environment (which encompasses lifestyle), contribute to disease processes. (Jackson, Marks, May, & Wilson, 2018). When reviewing genetics, all DNA holds the instruction guide for building a human. While DNA is considered, mutations may occur that alter the genetic material or disease processes potentially alter the cell’s ability to build, heal or otherwise reproduce. Genetic testing and therapy as well as medical treatment can alter gene structuring, but humans have the ultimate responsibility to care for positive therapeutic results by being an advocate for a return to health and wellness.
This patient described presented with a potential opioid overdose. Naloxone is a medicine that rapidly reverses an opioid overdose. It is an opioid antagonist. This means that it attaches to opioid receptors and reverses and blocks the effects of other opioids. Naloxone can quickly restore normal breathing to a person if their breathing has slowed or stopped because of an opioid overdose. But naloxone has no effect on someone who does not have opioids in their system, and it is not a treatment for opioid use disorder. (NIDA, 2022)
Upon regaining consciousness, the patient reported a burning sensation over the left hip and forearm. A burning sensation is due to cellular damage at the site of injury and the nerve endings responding to painful stimuli. Upon arrival to the emergency department, it was further noted necrotic tissue over the greater trochanter and forearm. Cellular death leads to cellular dissolution, or necrosis (McCance and Huether, 2019). External cellular injury that causes necrosis involves damage to mitochondria with the formation of mitochondrial permeability (pg 88).
The physiologic response is gangrenous necrosis; which is not a distinctive type of cell death but refers to larger areas of tissue death. This type of tissue death results from severe hypoxic injury, commonly occurring due to arteriosclerosis or blockage of major arteries, especially in the lower extremities (pg. 88, McCance & Huether). The outer area of the necrotic tissue should be reddened and inflamed. Inflammation does not indicate infection, but that the tissue is damaged and the inflammation is a systemic response to limit the extent of damage.
Hypoxia results from reduced amounts of oxygen. This occurs due to lack of air, loss of hemoglobin or hemoglobin function, (such as blood loss) or consequences of respiratory or cardiovascular disease. Hypoxia has the potential to induce inflammation.
Ischemia is often caused by a blockage or narrowing of arteries. If the ischemic tissue is not reperfused or opened, tissue death occurs.
The patient is hyperkalemic with a potassium of 6.9mEq/L. This can be fatal if not reversed. The patient is already symptomatic, presenting with a prolonged PR interval and peaked T waves. The potassium is maintained in the intracellular fluid (ICF). When the potassium is allowed to shift to the extracellular fluid and rises greater than 5.0 mEq/L, this can cause muscle weakness, dysrhythmias and present with changes in electrocardiograms. In situations of hypoxia, this may lead to hyperkalemia by diminishing the efficiency of the cell membrane, resulting in the potassium escaping out to the ECF. Burns may cause cell trauma and loss of ICF potassium to the ECF (pg 117, McCance & Huether, 2019).
Some characteristic of genetics is the patient is showing an opioid addiction. If a genetic study were to be completed, this patient may have a genetic link toward dependency of one type or another. Another genetic process is the patient’s age. This person is young, so hopefully will respond positively to treatment modalities and heal well with cellular mitosis and repair occurring at the site of inflammation and tissue destruction. If the patient has a history of arteriosclerosis in the lower extremities, the patient will be predisposed to cellular destruction due to chronic hypoxia over time. Another characteristic chronic disease process would prolong or prevent possible cellular repair. Diabetes Mellitus would be a chronic disease example. Diabetes would prolong the healing process as well as destroy cellular growth.
The diagnosis for this patient is Rhabdomyolysis (Myoglobinuria) it has been reported in individuals found unresponsive and immobile for long periods, such as drug overdoses. Rhabdomyolysis is the rapid breakdown of muscle and can cause hyperkalemia (because of the release of intracellular potassium into the circulation. McCance & Huether, Pg. (1430).
The role genetics plays in the disease.
Genetics did not play a role in the patient developing rhabdomyolysis. It was from the patient’s substance abuse and the unknown downtime causing muscle damage.
Why is the patient presenting with the specific symptoms described?
The patient is experiencing burning pain in the left hip and forearm due to the obstruction of blood flow to those areas that have been compressed causing ischemia and necrosis. Rhabdomyolysis is characterized by the presence of muscle pain. Because of the release of intracellular potassium into the circulation, EKG showed prolonged PR intervals and peaked T waves usually associated with Hyperkalemia.
The physiologic response to the stimulus presented in the scenario and why you think this response occurred.
The physiologic response was the patient became responsive because Naloxone is an opioid antagonist that binds to opioid receptors and can reverse and block the effects of the drug that was taken. SAMHSA.gov, (Jan 25, 2023).
The cells that are involved in this process.
Muscle cell Rhabdomyolysis is a condition characterized by time, leading to muscle hypoxia. Conditions leading to skeletal muscle ischemia. Kodadek L, et al (2022).
How another characteristic (e.g., gender, genetics) would change your response.
Genetics: People with McArdle disease (GSDV) Muscular dystrophies and Metabolic myopathies are associated with exercise intolerance and exertional rhabdomyolysis.
Gender: Woman have lower incidence of developing rhabdomyolysis
Introduction
Substance abuse history and response to naloxone are the two crucial issues in the case study that is being presented. Following the administration of naloxone, it was determined that the left hip and forearm injuries were due to an opioid overdose. Respiratory depression, which results in acidemia and an electrolyte imbalance, is another side effect of opioid usage (World Health Organization, 2021). The reported EKG abnormalities are brought on by hyperkalemia. The patient experiences damage to the left hip and forearm, where necrotic tissue forms, and all of the symptoms combined lead to the diagnosis of rhabdomyolysis. Rhabdomyolysis is the rapid breakdown of muscle that causes delta lesions to force the release of intracellular chemicals into the bloodstream (McCance & Huether, 2019). Hyperkalemia can also happen when there has been significant muscle injury. Another risk factor for rhabdomyolysis is substance usage. The greater trochanter’s necrotic tissue is most likely related to heroin injection. The discussion aims to explore rhabdomyolysis, the role genetics play, why the patient is displaying the particular symptoms, the physiologic response to the stimulus, how the cells are involved in the process, and how different traits would vary my reaction.
The role genetics plays in the disease
A combination of hereditary and nongenetic variables typically influences the chance of having a common disease. In some circumstances, a genetic predisposition may work with an environmental condition to significantly raise the chance of developing a disease over time compared to either component acting alone (McCance & Huether, 2019). There may be a hereditary component to rhabdomyolysis, although typically, that is only seen in those with malignant hyperthermia, metabolic muscle abnormalities, or mitochondrial disorders (Scalco et al., 2015). I do not know enough about the circumstances of this case for me to tell if the man has these conditions. As far as I am aware, the patient has a long history of substance misuse, which is most likely what caused their rhabdomyolysis. Given that genetics affects substance abuse disorders, the two have a genetic connection. Evidence shows that genes related to the dopamine and gamma-aminobutyric acid (GABA) systems play a role (Prom-Wormley et al., 2017). Mesolimbic dopamine neurons are the critical component of the opioid function mechanism, and direct stimulation of -opioid receptors on GABA receptors lowers GABA release and causes dysregulation of these cells (Prom-Wormley et al., 2017). As a result, opioids increase dopamine levels in the brain’s frontal cortex (Prom-Wormley et al., 2017). The exact variant encoding the opioid receptors (OPRM1, rs1799971, A118G) has frequently been associated with opioid use in addition to previously characterized genes essential to dopaminergic signaling (e.g., ANKK1/DDRD2, DRD1, and DBH) (Prom-Wormley et al., 2017).
Why the patient is presenting with the specific symptoms described
Because of the naloxone delivery, the patient is awake and speaking when arriving at the emergency room. Naloxone prevents the effects of opioid medicines, including analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia, and physical dependency, by attaching to the μ-opioid receptors in the central nervous system (CNS) (National Center for Biotechnology Information, 2023). The patient is now conscious but complains of burning on the left hip and forearm, which are covered in necrotic tissue because the muscle has broken down due to intracellular contents leaking through the sarcolemma membrane (McCance & Huether, 2019).
The physiologic response to the stimulus presented in the scenario and why you think this response occurred, and The cells that are involved in this process
The ECG data show that hyperkalemia, a longer PR interval, and peaked T waves are the physiological responses to the pain or injury to the left hip and forearm following the injection of naloxone. The sodium-potassium pump maintains low levels of potassium cells in the resting muscle, notably in the heart, for this condition, which results in this type of reaction characteristic of rhabdomyolysis (Stanley et al., 2022). When leukocytes enter a damaged muscle, they release more cytokines, prostaglandins, and free radicals that cause myolysis and necrosis of the muscle fibers as well as the release of potassium into the bloodstream, a byproduct of muscle breakdown (Stanley et al., 2022). A junctional rhythm followed by a ventricular dysrhythmia or asystole can result from a prolonged PR that hyperkalemia-related excess potassium generates (Mugmon, 2011).
How another characteristic (e.g., genetics, gender) would change your response
Let’s say you take away the history of drug abuse and the naloxone delivery, which puts a person at risk of overdosing. The same symptoms could indicate acute or chronic kidney disease in an elderly adult, possibly linked to polypharmacy. However, I do not know the patient’s gender or genetic history in this particular instance.
Genetics plays a crucial role in identifying people susceptible to opioid addictions. The reason I believe this is possible is that from my experience working at a psych hospital, many of the patients coming in for detox and opioid use disorder have either or both parents who have a history of opioid use or substance use disorder. Research has shown that the A118G variant of the opioid receptor (MOR) gene, OPRMI, has been robustly shown to have a significant association with opioid addiction (Reed & Kreek, n.d).
In the case study, the patient was unresponsive due to opioid overdose which was evident by his response to naloxone which is an opioid receptor antagonist. Administration of this medication caused a physiologic response by binding to the opioid receptors and reversing the effects of opioids the patient had taken by restoring normal respiration (National Institute on Drug Abuse, n.d). The patient also complained of a lot of burning pain in his hip and forearm which I believe is due to the necrotic tissue on those sites. The possibility of this patient getting these symptoms can be compared to symptoms of rhabdomyolysis which can be triggered by opioid overdose. One of the categories of causes of rhabdomyolysis is non-exertional or non-traumatic causes like drugs or toxins, infection, or electrolyte disorders (Babak et al. 2017). This is the reason the patient also presented with hyperkalemia which is one of the complications of rhabdomyolysis. Hyperkalemia is responsible for the EKG demonstrating a prolonged PR interval and peaked T waves.
The cells involved in the process of this scenario are in specific tissues or brain areas. As for the possibility of other characteristics changing the response to this scenario, a person who is not susceptible through genes may have limited stimuli when taking opioid substances. The individual genetic variability in conjunction with chronic pain, both affecting stress and reward systems lead to differential responses to opioids and may determine the transition risk from therapeutic use to opioid addiction (Gerra et al. 2021).
Explanation of the disease highlighted in the scenario
The breakdown and necrosis of muscle tissue and the release of intracellular content into the bloodstream cause rhabdomyolysis. The term rhabdomyolysis refers to the disintegration of striated muscle, which releases muscular cell constituents into the extracellular fluid and circulation
(Cabral et al.,2020). Regular and illegal drugs cause rhabdomyolysis together. In this scenario, patient has a history of substance abuse. Rhabdomyolysis is a potentially lethal clinical syndrome that results from the necrosis of muscle fibers, with the passage of its components into the circulation.
The role genetics plays in the disease.
Rhabdomyolysis is the acute breakdown of myofibres resulting in systemic changes that can be life-threatening. Environmental triggers, including trauma, exercise, toxins, infections, and gene defects, can precipitate rhabdomyolysis. Defects in muscular dystrophy and myopathy genes can trigger rhabdomyolysis (Cabrera et al.,2022).
Why the patient is presenting with the specific symptoms described.
In this scenario, the roommate mentioned he didn’t know how long the patient was on the floor. The patient has a large amount of necrotic tissue over the greater trochanter as well as the forearm. Patients who remain on the floor for a long time are at risk of developing rhabdomyolysis. If a person cannot move or get off the floor, tissue necrosis can occur at the point of contact, and skeletal muscle is destroyed, releasing its contents into the bloodstream. This can eventually lead to crushing syndrome, which includes rhabdomyolysis, hyperkalemia, dysrhythmias, and acute kidney injury, and can be fatal. EKG manifestation of hyperkalemia is peaked T-waves that signal myocardial hyperexcitability(Zeng &Tomlinson,2021). Then myocardial conduction disorders appear (i.e., prolonged PR, QRS widening, loss of P-waves, and bradycardia). Substance abuse, mainly Cocaine abuse, also causes systemic adverse effects like stroke, myocardial infarction, arterial dissection, vascular thrombosis, and rhabdomyolysis.
The physiologic response to the stimulus presented in the scenario and the reason for the response occurred.
Patients who remain on the floor for a long time are at risk of developing rhabdomyolysis. Many factors can cause rhabdomyolysis. Muscle cells contain a significant amount of potassium, and when disruption of the cell’s membrane occurs, its escape into circulation results in hyperkalemia. Also, substance abuse can result in kidney damage and also can cause the potassium level to be elevated.
The cells that are involved in this process and another characteristic( e.g., gender,genetics)would change the response
The cells that are involved in this process are muscles. Rhabdomyolysis can occur in all age groups and both sexes. The disease appears more frequent among males, African-Americans, those aged <10 and >60 years old, and in persons with a body mass index >40 kg/m2 [4]. The etiology of rhabdomyolysis may also vary depending on the age. Among adults, the most cited causes are trauma and drugs.
Question 1: The role genetics plays in the disease
Answer: Not sure what role genetic with EKG with prolong PR interval and peaked T waves
Question 2: Why the patient is presenting with:
1) burning pain over his left hip and
2) prolonged PR interval and peaked T waves,
3) elevated potassium level 6.9mEq/L
Answer: The patient is presenting with the above symptoms due to the tissue damage that allowed the escape of potassium from the ICF into the ECF. This created abnormal high level of potassium level that caused irritation to the neuromuscular system. The imbalance of the ICF and ECF potassium create hypo polarization that led to the excited or irritable contraction of the heart muscle. “Symptoms of hyperkalemia vary, but common characteristics are muscle weakness or paralysis and dysrhythmias with changes in the electrocardiogram”, Brashers & Rote (2019).
Question 3: Why do you think the physiologic response to the stimuli response occurred?
Answer: I think the physiologic response to the stimuli presented occurred because the tissue damage caused imbalance of ICF and ECF electrolytes imbalance which caused the increase of fluid and protein to the site of damage. The damage site was blocked from oxygen, nutrient, and movement of debris. This blockage damages the tissue over the greater trochanter and necrotic.
Question 4: What are the cells that are involved in this process?
Answer: The Na+-K+ ATPase pump, liver and muscle cells, kidney cells
Question 5: How another characteristic, such as gender or genetics would change your response?
Answer: A person pre-genetic to cardiac, diabetic, or missing kidney problems may prove fatal or suffer more bodily damage.
This patient is suffering from Necrosis of tissue in the greater trochanter and forearm. Necrosis is irreversible injury to cells that can eventually lead to cell death (Khalid & Azimpouran, 2022). The cause of this disease could be from chronic IV drug use. The patient is presenting with these systems because death or injury of cell or tissue causes an inflammatory reaction which results in pain. The patient was unresponsive on arrival due to drug overdose, this is apparent because naloxone was effective at reversing the unresponsiveness. Researchers used to believe that necrosis was an uncontrolled process, but recent studies show that necrosis can be controlled under genetic and chemical manipulations (McCall, 2010). Although, other genetic diseases like diabetes can put an individual at greater risk for necrosis. The form of necrosis that patient in this case study has is most likely due to infection from chronic IV drug use. The Necrotic tissue was caused by infection by a species of Clostridium which is an anaerobic bacteria (McCance & Huether, 2019). This bacterium produces enzymes and toxins that can destroy connective tissue, and death can occur from shock (McCance & Huether, 2019). Cell injury usually starts occurring before any signs or symptoms occur. This patient has an elevated potassium level of 6.9 which is likely due to necrotic tissue, when a cell is damaged, it causes the release of intracellular potassium into the blood, increasing the blood potassium levels (Simon et al., 2022). The prolonged PR interval and peaked T waves seen on the patients EKG is due to the patient hyperkalemia, as potassium is one of the essential electrolytes in cardia cells (Teymouri et al., 2022). IV drug users are at greater risks for bacteria infections that can affect that blood vessels and body tissues (Rose et al., 2022). Other characteristics that would change my response are age, medical history, and medication use.
Genetics plays a crucial role in disease processes with varying environmental factors. Our genes are distinct from who we are, which are passed on from one generation to the other. Genetics and different environmental factors decide how individuals are affected by addictions. According to (Demery-Poulos & Chambers, 2021), as illustrated by the dual use of naltrexone, alcohol- and opioid-induced rewards stem from the same neurological pathway. Accordingly, there are genes implicated in both addictions, such as the dopamine receptor D2 (DRD2) and OPRM1. A frequently studied polymorphism of DRD2 is the TaqIA SNP (rs1800497, G > A) in the ankyrin repeat and kinase domain containing one gene (ANKK1), located 10 kb downstream of DRD2. This SNP results in the loss of an N-glycosylation site that is necessary for proper membrane presentation. Carriers of TaqIA (A1+) have a 30% decreased DRD2 density in the striatum, reducing basal reward sensation This can lead to drug-seeking behavior to achieve increased stimulation; in support of the Reward Deficiency Syndrome, the A1 allele has been associated with higher heroin consumption. In a 2019 study by Li et al., heroin-addicted carriers of the A1 allele showed increased brain reactivity to heroin-related cues in the prefrontal, mesolimbic, and visuospatial attention regions. This may indicate that heroin has a greater influence on the executive function and reward system of A1 carriers. Genes are driving factors which explains why some individuals can easily get addicted to drugs. Genes determine the ability of individuals to have drug and alcohol-seeking behavior that leads to addiction.
This patient was found unresponsive by emergency medical services; the patient was unresponsive to the use of opioids; the patient was administered naloxone. According to (Yackuboskey, Deborah 2016), deaths related to opioid overdose may be prevented if the person receives early intervention via 911 notification, basic life support, and timely administration of an opioid antagonist, such as naloxone. This medication blocks or reverses the effects of the opioid substance; it has proven effective in reversing the effects of an opioid overdose and decreasing the number of deaths attributed to it. Naloxone may be administered via intravenous, intramuscular, subcutaneous, and intranasal routes. Intranasal naloxone is the preferred route due to ease and speed of delivery, gentler awakening, safety, and cost-effectiveness. Emergency medical care is still necessary, even after the administration of naloxone.
The patient also presented with complaints 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. Patient presentation is the sign of rhabdomyolysis, rhabdomyolysis is the rapid breakdown of muscle that changes the release of intracellular contents, including protein pigment myoglobin, into the extracellular space and bloodstream. Myoglobinuria has been reported in individuals found unresponsive and immobile for a prolonged period after drug and alcohol overdoses (McCance & Huether, 2019). Also, according to (Cabral, et., al 2020) Medications and recreational drugs are important causes of rhabdomyolysis. Drug-induced rhabdomyolysis encompasses a large group of substances that can affect muscles either by interfering with ATP production or by increasing the permeability of the sarcolemma permitting leakage of intracellular contents.
Furthermore, according to (Cabral, et., al 2020) under physiologic conditions, the sarcolemma membrane is lined with different pumps, channels, and exchangers. The most important of which is the Na-K-ATP-ase pump, which actively transports 3 sodium (Na+) out of the cell in exchange for every 2 potassium (K+) transported intracellularly to support a negative membrane potential. This negative potential draws Na+ inside, in exchange for calcium (Ca2+) via the Na+/Ca2+ exchanger, thus supporting low intracellular Ca2+ concentration. Tightly regulated calcium homeostasis. is essential for proper cell function – to maintain levels of calcium when the muscle is at rest and to allow the increase that is necessary for actin–myosin binding and muscle contraction
The cells involved are intracellular fluid and extracellular fluid, according to (McCane & Huether, 2019) potassium shifts from the intracellular fluid to the extracellular fluid occur with a change in cell membrane permeability (e.g., from cell hypoxia, acidosis, or insulin deficiency). Hypoxia can lead to hyperkalemia by diminishing the efficiency of cell membrane active transport, resulting in the escape of potassium to the extracellular fluid
Another characteristic will change my response, a different individual who lacks the D2 receptor will be less likely to be susceptible to drug addiction which can lead to a drug overdose. Genes determine our physiological characteristics, and they can influence the development and function of the brain.
The presented 27-year-old patient appears to be in opioid overdose as evidenced by the fact that she responded to Naloxone. Genetics plays a role in how fast individuals metabolize a drug (CYP2D6 and P450 enzymes). Some genes are associated with an increased likelihood of developing opioid dependency (OPRM1 gene). Knowing how genetic variations play a role in opioid metabolism, helps with identifying risk groups and with modification of prescription medications (“Update on the pharmacogenomics of pain management,” n.d.).
The physiologic response to Naloxone occurs as a result of Naloxone’s ability to block opioid receptor cells in the brain. Naloxone is also associated with the stimulation of endorphins releasing cells in the brain (“Update on the pharmacogenomics of pain management,” n.d.).
The patient is also appearing to have cardiac arrhythmia as evidenced by high T waves and increased PR intervals. If left untreated, changes in the EKG resulting from a high potassium level can cause a life-threatening V-tach and cardiac arrest. The patient also suffers from a bacterial infection as evidenced by necrotizing tissue over the forearm.