D115 Task 1 Advanced Pathophysiology Analysis Example

Pathophysiology of Acute Decompensated Heart Failure with Reduced Ejection Fraction in a 64-Year-Old Adult After Fourteen Days of Over-the-Counter Naproxen

[Author Name]

Leavitt School of Health, Western Governors University

D115 Advanced Pathophysiology for the Advanced Practice Nurse

Task 1

[Course Instructor]

August 11, 2026

Composite case written as a model document. No real patient, clinician or employer is described.

Case Presentation and the Mechanistic Question

The patient is a composite 64-year-old man with ischemic cardiomyopathy who reaches the emergency department after six days of worsening breathlessness. His left ventricular ejection fraction was measured at 30 percent eight months earlier, one month after an anterior ST elevation myocardial infarction treated with a drug eluting stent to the left anterior descending artery. He now sleeps on three pillows, wakes twice a night short of breath, and cannot carry groceries up one flight of stairs without stopping to rest. His home regimen is lisinopril 20 mg daily, carvedilol 12.5 mg twice daily, furosemide 40 mg daily, and atorvastatin 40 mg nightly, and he reports taking all four without missed doses.

Two exposures precede the decompensation. For the last fourteen days he has taken naproxen 500 mg twice daily, bought without a prescription for a painful shoulder, and for nine of those days he ate restaurant meals while family visited. He weighs 92.4 kg against a documented dry weight of 87.9 kg, a gain of 4.5 kg in nine days. Vital signs are blood pressure 148/92 mm Hg, heart rate 104 beats per minute in sinus rhythm, respiratory rate 24 breaths per minute, and oxygen saturation 91 percent on room air. Jugular venous pressure is 12 cm of water at 45 degrees, an S3 gallop is present, crackles reach the mid lung fields bilaterally, and pitting edema is 2+ to mid shin.

Laboratory and imaging data complete the picture. N-terminal pro B-type natriuretic peptide is 4,820 pg/mL against a stable outpatient value of 910 pg/mL nine months ago. Serum creatinine is 1.7 mg/dL, risen from 1.1 mg/dL at the same visit, for an estimated glomerular filtration rate of 41 mL/min/1.73 m2, and serum sodium is 132 mEq/L with potassium 4.6 mEq/L. The chest radiograph shows upper lobe vascular redistribution and small bilateral pleural effusions. The question this paper answers is narrow and mechanistic: why did a chamber that had been compensated for eight months lose that compensation in nine days, and which mechanism accounts for each finding above?

Normal Control and Where This Patient Departed From It

Cardiac output is the product of heart rate and stroke volume, and stroke volume is set by preload, afterload and contractility. Preload acts through the Frank-Starling relationship, in which greater end diastolic sarcomere length raises the calcium sensitivity of troponin C and the number of actin-myosin cross bridges formed per beat. Afterload is wall stress, which by the Laplace relationship rises with chamber radius and falls with wall thickness. Contractility depends on calcium handling: influx through L-type channels, calcium induced calcium release through the ryanodine receptor, and reuptake by SERCA2a under the control of phospholamban. A healthy ventricle holds reserve in all three variables and can recruit it on demand.

Circulating volume is governed by two opposing arms. Reduced renal perfusion and reduced distal sodium delivery trigger renin release, and the resulting angiotensin II constricts the efferent arteriole, drives proximal sodium reabsorption, and stimulates adrenal aldosterone secretion, which opens epithelial sodium channels in the collecting duct. Against that, atrial and ventricular stretch releases natriuretic peptides that act through particulate guanylyl cyclase receptors and cyclic GMP to produce natriuresis, vasodilation, and suppression of both renin and aldosterone. Renal prostaglandins E2 and I2 sit between the two arms, holding the afferent arteriole open so that glomerular filtration survives while angiotensin II constricts the efferent side.

This patient left that balance eight months ago. Infarction removed roughly a quarter of the left ventricular mass, and the surviving myocytes responded with eccentric hypertrophy: sarcomeres added in series, the cavity dilated, and the chamber grew more spherical, which stretched the mitral annulus and produced functional regurgitation. Fetal gene reprogramming shifted myosin heavy chain expression and lowered SERCA2a density, so calcium reuptake slowed and diastolic relaxation stiffened. Ejection fraction settled at 30 percent, and resting output was preserved only because heart rate, circulating volume and neurohormonal tone were all held above their normal set values. By the time he was stable at home, his compensations were already running near their ceiling.

Mechanism of the Decompensation

Naproxen removed the prostaglandin arm. Nonselective cyclooxygenase inhibition strips renal PGE2 and PGI2 synthesis, so the afferent arteriole loses its vasodilator brake at the exact moment angiotensin II is constricting the efferent arteriole; filtration pressure falls and creatinine rises from 1.1 to 1.7 mg/dL. The same inhibition blunts furosemide, which reaches its site of action only by active secretion into the proximal tubular lumen and depends in part on prostaglandin mediated renal blood flow for delivery. A 40 mg oral dose that had been adequate now fails to clear a threshold it used to clear easily, and sodium excretion falls below sodium intake.

The neurohormonal arms then escalate without opposition. Falling effective arterial volume raises renin, angiotensin II and aldosterone, and distal sodium reabsorption climbs through the epithelial sodium channel, so the restaurant sodium load of those same nine days is retained rather than excreted, and each retained 140 mEq of sodium obligates roughly a liter of water. Non-osmotic vasopressin release adds free water in excess of sodium, which is why the serum sodium reads 132 mEq/L; dilutional hyponatremia in this setting is a severity marker rather than a salt deficit. Sympathetic outflow drives the heart rate to 104, shortening diastole, cutting coronary perfusion time, and raising oxygen demand in a ventricle that is already supply limited.

The counter-regulatory arm is present but ineffective. Wall stretch has raised N-terminal pro B-type natriuretic peptide more than fivefold, yet natriuresis does not follow, because receptor density falls, neprilysin degrades the active peptide, and the congested kidney answers weakly. Congestion itself now becomes the renal insult: a jugular venous pressure of 12 cm of water is transmitted backward to the renal veins, raises renal interstitial and intratubular pressure, and lowers the net transglomerular gradient. The rising creatinine here is a congestion problem before it is a perfusion problem. Intestinal wall edema then reduces absorption of the oral diuretic, and the loop closes on itself.

From Mechanism to Manifestation and Therapeutic Target

Each finding traces to one of those steps. Orthopnea appears because recumbency returns splanchnic and lower limb volume to a chamber that cannot accept it, raising pulmonary capillary pressure within minutes. Crackles and pleural effusions appear once that pressure exceeds roughly 18 to 20 mm Hg and pulmonary lymphatic clearance is overwhelmed, so Starling forces at the alveolar capillary barrier move fluid into the interstitium and then into the alveolus. The S3 is the sound of rapid early filling stopping abruptly in a dilated, stiff chamber. An oxygen saturation of 91 percent reflects ventilation-perfusion mismatch across flooded lung rather than a diffusion barrier.

Mapping the mechanism onto therapeutic targets is where advanced practice reasoning shows. Loop diuretics behave as threshold agents, so the answer to a blunted response is a dose large enough to exceed the natriuretic threshold, given intravenously while gut edema persists, rather than the same small dose more often, and adding a thiazide type agent addresses the distal tubular hypertrophy that follows chronic loop exposure. An angiotensin receptor neprilysin inhibitor acts directly on the peptide resistance node this case exposes, blocking degradation of natriuretic peptides while blocking the AT1 receptor, and it calls for a 36 hour interval after an angiotensin converting enzyme inhibitor because overlapping bradykinin accumulation carries angioedema risk.

Aldosterone escape and myocardial fibrosis argue for mineralocorticoid receptor antagonism, while sodium glucose cotransporter 2 inhibition adds osmotic diuresis and a modest natriuretic effect that does not depend on the presence of diabetes; beta blockade is held at its current dose through congestion rather than started or increased. The single reversible node in this case, though, is the one the patient controlled: the naproxen. Heart failure affects roughly 6.7 million adults in the United States, and close to one in five hospital stays for it is followed by another within 30 days, so removing an avoidable trigger carries weight equal to any dose change argued above.

References

Agency for Healthcare Research and Quality. (2023). Healthcare Cost and Utilization Project statistical briefs. U.S. Department of Health and Human Services. https://www.hcup-us.ahrq.gov/reports/statbriefs/

Centers for Disease Control and Prevention. (2024). About heart failure. U.S. Department of Health and Human Services. https://www.cdc.gov/heart-disease/

Hall, J. E., & Hall, M. E. (2021). Guyton and Hall textbook of medical physiology (14th ed.). Elsevier.

Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin, M. M., Deswal, A., Drazner, M. H., Dunlay, S. M., Evers, L. R., Fang, J. C., Fedson, S. E., Fonarow, G. C., Hayek, S. S., Hernandez, A. F., Khazanie, P., Kittleson, M. M., Lee, C. S., Link, M. S., ... Yancy, C. W. (2022). 2022 AHA/ACC/HFSA guideline for the management of heart failure: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation, 145(18), e895-e1032. https://doi.org/10.1161/CIR.0000000000001063

National Heart, Lung, and Blood Institute. (2022). Heart failure. U.S. Department of Health and Human Services, National Institutes of Health. https://www.nhlbi.nih.gov/health/heart-failure

Rogers, J. L. (Ed.). (2023). McCance & Huether's pathophysiology: The biologic basis for disease in adults and children (9th ed.). Elsevier.