week 6 discussion answers

CF is a fatal, inherited condition that causes the pancreas, the lungs, and other organs to accumulate with creamy, thick mucus. The cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation is the cause of it (Meoli et al., 2021). This gene regulates the flow of water and salt into and out of cells. People with cystic fibrosis have a mutation in the CFTR gene, which affects how well salt and water enter and exit cells. It causes the mucus in the digestive tract and lungs to thicken and become sticky. By blocking the airways and trapping bacteria, the mucus causes infection and inflammation. Additionally, it prevents the pancreas from producing the necessary digestive enzymes, which results in improper digestion (Meoli et al., 2021). Cystic fibrosis is a progressive disease, meaning it typically worsens over time. In the early stages of CF, patients may have no symptoms or mild respiratory problems. However, as the disease progresses, they may experience chronic coughing and wheezing, shortness of breath, and extreme fatigue. Common symptoms include salty-tasting skin, persistent hunger, weight loss, and infertility. Mucus in the lungs suffocates the airways and traps bacteria, which causes infections, significant lung damage, and, ultimately, respiratory failure. The mucus in the pancreas prevents the body from releasing the digestive enzymes required to break down food and assimilate essential nutrients. The evaluation of someone with CF will usually involve several tests to assess the disease's severity and monitor for any complications. These tests may include lung function tests, X-rays, CT scans, and sweat tests. A physical examination may reveal evidence of malabsorption, such as poor growth or weight loss (Meoli et al., 2021). The doctor also looks for signs of respiratory problems, such as wheezing or coughing (Meoli et al., 2021). A family history of CF is often the first clue that a person may have the condition. The most accurate technique for diagnosing CF is a sweat test to gauge the amount of salt. People with CF have abnormally heightened salt levels in their sweat (Meoli et al., 2021). Genetic testing can validate a CF prognosis. This test looks for changes (mutations) in the CFTR gene. There is no cure for CF, but treatments can help manage the symptoms and improve quality of life. Pulmonary (lung) treatments for CF include chest physical therapy (CPT) and postural drainage (McCance & Huether, 2018). CPT is a technique that uses clapping and percussion to help loosen and remove mucus from the lungs. Postural drainage is a position-based drainage technique that uses gravity to help clear mucus from the lungs. Bronchodilators drugs can open up the airways in the lungs, and steroids help to reduce swelling in the airways (McCance & Huether, 2018). In some cases, oxygen therapy can treat low blood oxygen levels. A lung transplant is an option for people with end-stage CF who are not responding to other treatments. Since there is currently no treatment for CF, which has no known cure, efforts are being made to control its symptoms. Gene therapy, however, shows promise as a possible CF treatment. It entails using a virus altered to carry the healthy gene to deliver a copy of the CFTR gene to lung cells (McCance & Huether, 2018). Once the virus enters the cells, the healthy gene is inserted into the cells' DNA. The hope is that this will enable the cells to produce a functional CFTR protein, improving the symptoms of CF. The ethical dimensions of gene therapy must be considered when treating a life-limiting disease like CF (McCance & Huether, 2018). One moral concern is gene therapy's potential to be used to "fix" people considered to be genetically imperfect (McCance & Huether, 2018). Another concern is the cost of gene therapy, which could exclude many people from accessing this potentially life-saving treatment.

Reference:

McCance, K. L., & Huether, S. E. (2018). Pathophysiology-E-book: the biologic basis for disease in adults and children. Elsevier Health Sciences.

Meoli, A., Fainardi, V., Deolmi, M., Chiopris, G., Marinelli, F., Caminiti, C., ... & Pisi, G. (2021). State of the Art on Approved Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators and Triple-Combination Therapy. Pharmaceuticals, 14(9), 928. https://doi.org/10.3390/ph14090928

Acute Kidney Injury (AKI)

RIFLE Criteria

          Lopes and Jorge (2013) describe the RIFLE criteria for acute renal dysfunction and failure: risk, injury, failure, loss of kidney function, and end-stage kidney disease. To be classified as “risk,” the serum creatine (SCR) is high x 1.5 or low glomerular filtration rate (GFR) greater than 25%, and the urine output (UO) is < 0.5 mL/kg/h x 6 h. In “injury,” the SCR is high x 2 or low GFR > 50 %, and the UO is < 0.5 mL/kg/h x 12 h. In “failure,” the SCR is high x 3 or low GFR > 75 % or if it is baseline SCR >353.6 μmol/L higher than SCR > 44.2 μmol/L, and the UO is < 0.3 mL/kg/h x 24 h or anuria for 12 h. In “loss of kidney function,” there is a complete loss of the function of the kidneys for more than four weeks. In “end-stage kidney disease,” there is a complete loss of the function of the kidneys for more than three months (Lopes & Jorge, 2013).

Pathophysiology

          McCance and Huether (2014) state that AKI results from insufficient kidney volume, low blood flow, or injury from something toxic that results in changes in renal function. A slight renal function change may be related to significant morbidity and mortality. There are three categories of kidney injury; they are prerenal, intrarenal, and postrenal. If treated early, most AKI is reversible. The most common AKI is prerenal acute kidney injury. When the arterial blood volume goes down, it results in renal hypoperfusion; this results in an elevation of BUN and plasma creatinine levels. In the early stages of hypoperfusion, a protective autoregulatory mechanism and tubuloglomerular feedback mechanisms maintain GFR at a stable level through afferent arteriolar dilation and efferent arteriolar vasoconstriction. The decrease in filtration pressure is related to the decline of GFR. Low fluid volumes lead to poor perfusion from dehydration, diarrhea, fluid shifts, blood loss, renal vasoconstriction, and alterations in renal regional blood flow, microthrombi, or kidney edema that restricts arterial blood flow. AKI may occur during chronic kidney failure if sudden stress is imposed on already slow-working kidneys, quickly leading to end-stage kidney disease. If blood volume is not restored, blood pressure and oxygen delivery can cause cell injury and acute tubular necrosis and apoptosis or acute interstitial necrosis, a more severe form of AKI (McCance & Huether, 2014).

          Intrarenal acute kidney injury (AKI) can be from ischemic acute tubular necrosis (ATN), nephrotoxic ATN, acute glomerulonephritis, vascular disease, allograft rejection, or interstitial disease. The most common cause of intrarenal AKI is related to ATN from ischemia; most cases are seen after surgery but are associated with severe sepsis. The terms acute tubular necrosis and acute kidney injury are sometimes used interchangeably, but the conditions differ because acute kidney injury can occur without ATN. ATN is generally described as postischemic or nephrotoxic, or it can be a combination of both. Postischemic ATN occurs because of hypotension, hypoperfusion, and hypoxemia, producing ischemia and reduced levels of ATP, creating toxic oxygen-free radicals that lead to cell swelling, injury, and necrosis. Then, the inflammatory cells activate and complement, and the release of inflammatory cytokines contributes to tubular injury. Damage is most severe in the outer medulla, with scattered necrosis in the cortex and loss of cells along the tubular epithelium. The glomeruli become severely diseased, or renal microvascular disorders can cause intrinsic kidney injury. Oliguria is commonly seen with intrarenal AKI (McCance & Huether, 2014).

          The rarest AKI is postrenal acute kidney injury; it is seen in urinary tract obstruction affecting the kidneys bilaterally. The block causes an increase in intraluminal pressure upstream from the site of obstruction with a gradual decrease in GFR. There are several hours of anuria with flank pain followed by polyuria is a characteristic finding. This type of AKI can occur after diagnostic catheterization of the ureters, a procedure that may cause edema with obstruction of the tubular lumen. Oliguria is defined as less than 400 ml of urine output per day. Three explanations contributing to oliguria are renal blood flow alterations, tubular obstruction, and back leaks (McCance & Huether, 2014).

Clinical Manifestations

          AKI clinically progresses in three phases: initiation phase, maintenance phase, and recovery phase. In the initiation phase, reduced perfusion lasts 24 to 36 hours. Prevention of injury is possible during this phase. In the maintenance or oliguric phase, there is established renal injury and dysfunction after the initiating event has been resolved and may last from weeks to months. Urine output is low, serum creatinine is high, blood urea nitrogen is high, and serum potassium levels increase; metabolic acidosis develops, and there is salt and water overload. The recovery phase is the time injury can repair to normal renal function. GFR returns to normal, but the regenerating tubules cannot concentrate the filtrate. Diuresis is expected during this phase, with decreased serum creatinine and urea levels and increased creatinine clearance (McCance & Huether, 2014).

          After one day of a hypotensive event, oliguria can be seen and lasts 1 to 3 weeks. The duration depends on the time frame of ischemia and the initiation of treatment. Anuria is uncommon and suggests bilateral renal artery occlusion, obstructive uropathy, or acute cortical necrosis. If non oliguric renal failure is seen, it means less severe injury and is associated with toxin exposure. The renal tubules have impaired reabsorption, concentration, and dilution abilities. Urine output of greater than 2 L per day may be evident, but the BUN and plasma creatinine concentrations increase (McCance & Huether, 2014).

          Early signs depend on the origin of renal failure. In a trauma, surgery, or people in a catabolic state may have more rapid elevations in BUN level. Those mentioned are more likely to get hyperkalemia and metabolic acidosis related to decreased potassium levels and hydrogen excretion. Hyperphosphatemia is seen as related to decreased renal phosphate excretion. Fluid retention may cause edema. A patient with cardiac issues might display symptoms of congestive heart failure. Nausea, vomiting, and fatigue accompany uremia and electrolyte imbalances. Wound healing is delayed, and the risk of infection is more significant. Nonoliguric renal failure generally has a better prognosis because of fewer complications and regeneration of the tubular epithelium. Patients with oliguria may require dialysis to lessen symptoms of renal failure (McCance & Huether, 2014).

          Diuresis is seen as renal function improves during the recovery phase. During the early diuretic phase, the tubules still recover secretory and reabsorptive function. Sodium and potassium are lost in the urine, and the risk for hypokalemia is greater. Volume depletion may ensue, with fluid losses of 3 to 4 L/day. Fluid and electrolyte balance must be carefully monitored, and excessive urinary losses must be replaced. Return to normal status may take 3 to 12 months. Approximately 30% of individuals do not fully recover a normal GFR or tubular function and progress to end-stage kidney disease (McCance & Huether, 2014).

Evaluation

          The diagnosis of AKI is related to the cause of the disease. A good H&P can help differentiate the reason for AKI. A prerenal cause would be associated with a history of blood volume loss or poor kidney perfusion. Intrinsic causes would be related to exposure to nephrotoxins and infection. Postrenal causes are associated with obstructive uropathies or blockage. A simple UA  may provide helpful diagnostic clues to changes in tubular function (McCance & Huether, 2014).

          A helpful diagnostic tool is to assess the ratios of the BUN to plasma creatinine concentration and fractional excretion of sodium. These tests reflect the ability of renal tubule reabsorption. When AKI is prerenal, the salt, water, and urea are reabsorbed. In the recovery phase, plasma creatinine concentration provides an index of renal function. Serum creatinine levels change if glomerular filtration is lost. Diagnosis delays contribute to disease progression and mortality. Advances are being made in using biomarkers to assess kidney injury before the elevation of serum creatinine level (McCance & Huether, 2014).

Treatment

          Prevention of AKI and hydration are key for AKI, as there is no specific treatment for acute renal failure. The primary goal is to maintain the individual’s life until renal function recovers. Management of AKI is replacing fluids and correcting electrolyte imbalances, managing blood pressure, preventing and treating infections, maintaining nutrition, and keeping the patient from certain drugs or metabolites that are not excreted and can be toxic. Carefully calculate fluid and electrolyte replacement, urine loss, and insensible losses (McCance & Huether, 2014).

          Dialysis can be initiated if the potassium level is too high and cannot be managed with dietary changes. Careful monitoring of the electrocardiogram for peaking T waves is essential for individuals with hyperkalemia. Continuous renal replacement therapy is done for patients with intractable hyperkalemia, acidosis, or severe fluid overload. It is mainly used in critically ill people with multiple organ dysfunction or sepsis (McCance & Huether, 2014).

References

Lopes, J. A., & Jorge, S. (2013). The RIFLE and AKIN classifications for acute kidney injury: a critical and comprehensive review. Clinical kidney journal, 6(1), 8–14. https://doi.org/10.1093/ckj/sfs160

McCance, K.L. & Huether, S.E. (Eds.). (2014). Pathophysiology: The biologic basis for disease in adults and children. (7th. ed.). Elsevier Mosby. https://online.vitalsource.com/books/9780323088541