Scenario 1: Syndrome of Antidiuretic Hormone (SIADH) A 77-year-old female was brought to the clinic by her daughter who stated that her mother had become slightly confused over the past several days. She had been stumbling at home and had fallen twice but was able to walk with some difficulty. She had no other obvious problems and had been eating and drinking. The daughter became concerned when she forgot her daughter’s name, so she thought she better bring her to the clinic. Struggling to meet your deadline ? Get assistance on NURS 6501 Knowledge Check: Endocrine Disorders done on time by medical experts. Don’t wait – ORDER NOW! Meet My Deadline HPI: Type II diabetes mellitus (DM) with peripheral neuropathy x 30 years. Emphysema. Situational depression after death of spouse 6-months ago SHFH: – non contributary except for 40 pack/year history tobacco use. Meds: Metformin 1000 mg po BID, ASA 81 mg po qam, escitalopram (Lexapro) 5 mg po q am started 2 months ago Labs-CBC WNL; Chem 7- Glucose-102 mg/dl, BUN 16 mg/dl, Creatinine 1.1 mg/dl, Na+116 mmol/L, K+4.2 mmol/L, CO237 m mol/L, Cl–97 mmol/L. The APRN refers the patient to the ED and called endocrinology for a consult for diagnosis and management of syndrome of inappropriate antidiuretic hormone (SIADH). Question: 1.     Define SIADH and identify any patient characteristics that may have contributed to the development of SIADH

Selected Answer: SIADH happens when increased ADH is produced in the body, causing water retention and electrolyte imbalance. Hypothalamus produces ADH, and the posterior pituitary secretes and stores ADH. ADH regulates water in the body through water retention, and it constricts blood vessels. It accomplishes this with kidneys. ADH causes renal tubules to retain water. An increased level of ADH causes extra water retention in the body, resulting in hyponatremia with hypo-osmolality and high urine osmolality. Causes of SIADH can be damage to the hypothalamus or posterior pituitary gland or ADH being produced somewhere else. The symptoms continue to become more severe if the SIADH goes untreated, including confusion, hallucinations, seizures, and even coma. Based on the patient history, this patient has emphysema and currently smokes 40 packs of tobacco a year. The current lab work shows that patient’s carbon dioxide level is elevated at 37. The normal range for serum carbon dioxide is 23-29. Also, their sodium level is abnormal at 116. The normal range of serum sodium ranges between 135-and 145. When the serum sodium level is too low, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) diagnosis is possible Correct Answer: SIADH is a group of symptoms that occurs when antidiuretic hormone (ADH, arginine vasopressin) is secreted in the absence of osmotic or physiologic stimuli. These stimuli include: Increased serum osmolality, decreased plasma volume, and hypotension. A decrease in plasma osmolality normally inhibits ADH production and secretion. SIADH is characterized by fluid retention, dilutional hyponatremia, hypochloremia, concentrated urine, and lack of intravascular volume depletion. SIADH is characterized by normal to increased blood volume in normoproteinemia, nonedematous, and hyponatremic patients with normal renal and endocrine function. Response Feedback: [None Given]

In this exercise, you will complete a 10- to 20-essay type question Knowledge Check to gauge your understanding of this module’s content.

Also Check Out:

Possible topics covered in this Knowledge Check include:

• Diabetes
• Hyper- and hypothyroidism
• Adrenal disorders
• Parathyroidism (hyper and hypo)

• Checks & balances / negative feedback

• Syndrome of Inappropriate Antidiuretic Hormone
• Pheochromocytosis
• Diabetes insipidus
• Diabetic ketoacidosis

The role genetics plays in the disease

Cystic Fibrosis is a multiorgan disease that affects the airways, digestive tract, and reproductive organs. The Cystic Fibrosis Transmembrane Conductance (CFTCR) Gene mutation is called F508delCFTR. The CFTCR protein is an activated Chloride channel on the surface of many types of epithelial cells, including those lining airways, bile ducts, the Pancreas, sweat ducts, paranasal sinuses, and the Vas Deferens (McCance & Huether, 2019). The most important effects are on the Lungs, and respiratory failure is almost always the cause of death. The typical features of CF lung disease are mucus plugging, chronic inflammation, and chronic infection of the small airways. The mucus plugging results from increased production of mucus. An increased number and size of Goblet Cells change the mucus’s physicochemical properties and impair mucociliary clearance (McCance & Huether, 2019).

Why is the patient presenting with the specific symptoms described

Salt and fluid absorption and secretion are two processes that are fundamental to epithelial function and whole-body fluid homeostasis and, as such, are tightly regulated in epithelial tissues. The loss of this homeostasis is the reason the baby taste salty. The CFTR anion channel plays a significant role in regulating secretion and absorption in a diverse range of epithelial tissues, including the airways, the GI and reproductive tracts, sweat, and salivary glands. It is not surprising then that defects in CFTR function are linked to disease. Including life-threatening secretory diarrheas, such as cholera, and the inherited disease, cystic fibrosis (CF), one of the most common life-limiting genetic diseases in Caucasian populations (Saint-Criq & Gray, 2017).

For this reason, if the mother has even more children, then there is a high probability that her other children will have Cystic Fibrosis. More recently, CFTR dysfunction has been implicated in the pathogenesis of acute pancreatitis, chronic obstructive pulmonary disease (COPD), and hyper-responsiveness in asthma, underscoring its fundamental role in whole-body health and disease (Saint-Criq & Gray, 2017). These dysfunctions cause her baby to have stomach swelling, poor digestion with a good appetite, and the reason her other child has respiratory infections like Pneumonia.

CFTR regulates many mechanisms in epithelial physiology, such as maintaining epithelial surface hydration and regulating luminal PH. Recent studies have identified luminal pH as an essential arbiter of epithelial barrier function and innate defense, particularly in the airways and GI tract. The different operational roles of CFTR in epithelial function describe its characteristics in three different tissues: the airways, the Pancreas, and the sweat gland (Saint-Criq & Gray, 2017).

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

           Cystic fibrosis (CF) is a common, life-threatening, multisystemic, autosomal recessive disorder which is another reason why if the mother had even more children, they could have Cystic Fibrosis. In the last few years, giant steps have been made regarding understanding CF pathophysiology, allowing the scientific community to propose mechanisms that cause various CF clinical manifestations. Following the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989, along with the structure and function of the CFTR protein. Since then, more than 2,000 variants of the CFTR gene and their impact on the amount and function of the CFTR protein (Bergeron & Cantin, 2019).

The role of the CFTR protein as an ion channel transporting chloride and bicarbonate and its repercussions on different epithelial cell-lined organs and mucus are now better understood, which also describes why the baby taste salty. The susceptibility to infection in CF includes abnormalities in the airway surface liquid’s composition, volume, and acidity. Changes in the submucosal gland’s anatomy and function and deficiencies in the mucociliary clearance system. These CF complications are why her children have respiratory congestion and Pneumonia. Numerous hypotheses explain the excessive inflammatory response in CF. These complications involve impaired mucociliary clearance, persistent hypoxia, lipid abnormalities: protease, antiprotease disproportion, and oxidant and antioxidant imbalance (Bergeron & Cantin, 2019).

The cells that are involved in this process

Cystic fibrosis (CF) is a hereditary disease mostly related to ΔF508 CFTR mutation, causing a proteinopathy characterized by multiple organ dysfunction, primarily lung chronic inflammation and infection (Signorelli et al., 2021). This information informs us that if the mother had even more children, they would likely have Cystic Fibrosis. Defective autophagy and accumulation of the inflammatory lipid ceramide have therapeutic targets. Increased lipids and cholesterol were reported in the airways of CF patients, along with altered triglycerides and cholesterol levels in plasma, thus suggesting disease-related dyslipidemia (Signorelli et al., 2021). Myriocin, an inhibitor of sphingolipids synthesis, significantly reduces inflammation and activates TFEB-induced response to stress, enhancing fatty acid oxidation and promoting autophagy. Myriocin ameliorates the response against microbial infection in CF models and patients’ monocytes. Here we show that CF broncho-epithelial cells exhibit an altered distribution of intracellular lipids (Signorelli et al., 2021). Lipid accumulation by enhanced synthesis of fatty acids-containing molecules and Myriocin can reduce such accumulation. These events cause the thick mucus and mucus to plug into the lungs. Myriocin modulated the transcriptional profile of CF cells to restore autophagy, activate an anti-oxidative response, stimulate lipid metabolism, and reduce lipid peroxidation (Signorelli et al., 2021).

Moreover, lipid storage may be altered in CF cells since we observed a reduced expression of lipid droplets in related proteins (Signorelli et al., 2021). To note, Myriocin up-regulates the expression of genes involved in lipid droplet biosynthesis and maturation. We suggest that targeting sphingolipids de novo synthesis may counteract lipids accumulation by modulating CF altered transcriptional profile, thus restoring autophagy and lipid metabolism homeostasis (Signorelli et al., 2021).

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

The Objective is to describe, at a gastrointestinal level, the general, nutritional, and genetic characteristics and the evolution of CF carriers with/ without neonatal screening. The patients and method are a Retrospective study carried out in 4 public referral hospitals in the Metropolitan Region. The diagnosis of CF confirmed with two positive sweat tests (Gibson and Cooke method) was considered an inclusion criterion. Those patients with unconfirmed neonatal screening tests through Immunoreactive Trypsinogen (IRT) or with only one positive sweat test were excluded. Sex, age, nutritional status, date of diagnosis, clinical presentation at the onset, evolution, and therapies received were recorded as clinical variables, and as laboratory ones, genetic study utilizing a diagnostic panel with 36 mutations (Zuloaga et al., 2021).

The results showed that 127 patients were included. Respiratory manifestations (recurrent obstructive bronchial syndrome and Pneumonia) were present in >60% and gastrointestinal ones (mainly malabsorption and malnutrition syndrome) in >80% of patients. On average, diagnostic confirmation took four months. The diagnosis guided by IRT was associated with better nutritional outcomes in the evolution of the patient. In 81.1% of the patients, a genetic study was performed. The most frequent mutations were those associated with DF508 (deletion of phenylalanine 508). 5.8% of the patients presented mutations not included in the gene panel used (Zuloaga et al., 2021). This study shows that both the baby and her child would fit into these characteristics, and it is known that the baby is positive for Cystic Fibrosis

 In conclusion, Gastrointestinal CF appears with pancreatic, intestinal, and hepatic pathology throughout life. Malnutrition is a frequently present factor that worsens the prognosis. Managing gastrointestinal manifestations and malnutrition is relevant to improving CF patients’ morbidity and mortality (Zuloaga et al., 2021). The availability of the human genome sequence and tools for interrogating individual genomes provide an unprecedented opportunity to apply genetics to medicine. Mendelian conditions, caused by dysfunction of a single gene, offer powerful examples illustrating how genetics can provide insights into disease (Cutting, 2015). Cystic fibrosis is a more common lethal autosomal recessive Mendelian disorder (Cutting, 2015). Recent progress in elucidating disease mechanisms and causes of phenotypic variation, as well as in the development of treatments, demonstrates that genetics plays an essential part in cystic fibrosis research 25 years after discovering the disease-causing gene (Cutting, 2015).

References

Bergeron, C., & Cantin, A. M. (2019). Cystic Fibrosis: Pathophysiology of Lung Disease. Seminars in respiratory and critical care medicine, 40(6), 715–726. 

Cutting G. R. (2015). Cystic fibrosis genetics: from molecular understanding to clinical application. Nature reviews. Genetics, 16(1), 45–56. https://doi.org/10.1038/nrg3849

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

Ratchford, T. L., Teckman, J. H., & Patel, D. R. (2018). Gastrointestinal pathophysiology and nutrition in cystic fibrosis. Expert review of gastroenterology & hepatology, 12(9), 853–862. https://doi.org/10.1080/17474124.2018.1502663

Saint-Criq, V., & Gray, M. A. (2017). Role of CFTR in epithelial physiology. Cellular and molecular life sciences: CMLS, 74(1), 93–115. 

Signorelli, P., Pivari, F., Barcella, M., Merelli, I., Zulueta, A., Dei Cas, M., Rosso, L., Ghidoni, R., Caretti, A., Paroni, R., & Mingione, A. (2021). Myriocin modulates the altered lipid metabolism and storage in cystic fibrosis. Cellular signalling, 81, 109928. 

Zuloaga, N., Vivallos, N., Faúndez, R., González, M., Navarro, E., Chávez, E., & Araya, M. (2021). Manifestaciones gastrointestinales en fibrosis quística en una población pediátrica [Gastrointestinal manifestations of cystic fibrosis in children]. Andes pediatrica:revista Chilena de pediatria, 92(4), 526–533. https://doi.org/10.32641/andespediatr.v92i4.2693

This 101-question exam is a test of your knowledge in preparation for your certification exam. No outside resources, including books, notes, websites, or any other type of resource, are to be used to complete this exam. You are expected to comply with Walden University’s Code of Conduct.

This exam will be on topics covered in Weeks 1, 2, 3, 4, 5, and 6. Prior to starting the exam, you should review all of your materials. This exam is timed with a limit of 2 hours for completion. When time is up, your exam will automatically submit.

(Note: It is strongly recommended that you take the Knowledge Check at least 48 hours before taking the Midterm exam.)

In Module 5, you will analyze processes related to neurological and musculoskeletal disorders through case study analysis. To do this, you will analyze alterations in the relevant systems and the resultant disease processes. You will also consider patient characteristics, including racial and ethnic variables, which may impact physiological functioning and altered physiology.

In the Week 7 Knowledge Check, you will demonstrate your understanding of the topics covered during Module 5. This Knowledge Check will be composed of a series of questions related to specific scenarios provided. It is highly recommended that you review the Learning Resources in their entirety prior to taking the Knowledge Check, since the resources cover the topics addressed. Plan your time accordingly.