An 18-year-old male with a history of headaches presents to the emergency department with complaints of severe headache. His vitals are:
CT scan of the brain showed diffuse cerebral edema but no acute intracranial bleed. ECG demonstrates sinus tachycardia but is otherwise normal. Despite multiple administrations of antihypertensives, his blood pressure is still 194/110, and he is admitted for hypertensive crisis. Workup demonstrates mild hypokalemia. Hormonal studies were significant for elevated plasma renin and aldosterone levels, but normal renin/aldosterone ratio. Plasma metanephrines, thyroid-stimulating hormone, T3, T4, and free T4 are normal. Imaging shows a juxtaglomerular mass on the right kidney and no evidence of renal artery stenosis.
Which of the following regarding his diagnosis is correct?
Correct Answer: D
The patient presents with hypertensive crisis, hypokalemia, high plasma aldosterone, and high plasma renin, but normal renin/aldosterone ratio which suggests secondary hyperaldosteronism from excess renin. Normal plasma metanephrines rules out pheochromocytoma or paraganglioma. The presence of a juxtaglomerular mass further suggests that this patient’s symptoms are likely due to a juxtaglomerular cell tumor secreting renin, or reninoma.
Renin is normally secreted from the juxtaglomerular kidney cells in response to: (1) a decrease in renal perfusion pressure detected via stretch receptors in the vascular walls of the juxtaglomerular cells and (2) signaling from the macula densa when sodium delivery to the distal tubule decreases. It hydrolyzes angiotensinogen into angiotensin I, which is further cleaved in the lungs by endothelial-bound angiotensin-converting enzyme (ACE) into angiotensin II, a potent vasoconstrictor peptide. Angiotensin II also acts on the adrenal glands to release aldosterone, which stimulates the epithelial cells in the distal tubule and collecting ducts of the kidney to increase reabsorption of sodium and water and excretion of potassium and hydrogen ions. This results in an increase in intravascular volume, hypertension, hypokalemia, and metabolic alkalosis.
While abdominal ultrasonography is noninvasive and easily performed, it may miss small lesions. Contrast-enhanced computed tomography or magnetic resonance imaging is recommended as the diagnostic modality of choice. Medical management consists of antihypertensives, particularly ACE inhibitors, angiotensin receptor blockers (ARBs), and aldosterone antagonists. Definitive treatment is by surgical resection with most patients becoming and remaining normotensive.
A 68-year-old male with a history of coronary artery disease/myocardial infarction treated with a drug-eluting stent and controlled hypertension develops microscopic hematuria and is scheduled for cystoscopy. His medication list includes metoprolol XL 100 mg daily, losartan 50 mg daily, atorvastatin 80 mg daily, and aspirin 81 mg. His preoperative examination is unremarkable, and patient reports exercise capacity >4 METs. Per his instructions from his surgeon, he has continued taking all his medications except for holding his lisinopril and metformin the night before. After an uneventful induction and intubation, the patient’s blood pressure drops from 132/68 to 70/42 mm Hg, with pulse continuing at 66 beats/min. The patient’s five-lead electrocardiogram demonstrates sinus rhythm but with new 1 mm ST depressions in his precordial leads. End-tidal CO2 and pulse oximetry are unchanged. The blood pressure does not improve with repeated boluses of phenylephrine and ephedrine, or with a fluid bolus of 500 mL, necessitating vasopressin and epinephrine boluses. Bedside transthoracic echocardiogram demonstrates a hyperdynamic and collapsed LV, no wall motion abnormalities, no valvular lesions, and no pericardial effusion. Decision is made to postpone the patient’s elective surgery and awaken him. Upon emergence, the patient’s blood pressure recovers to 124/62 mm Hg and pulse 60 beats/min. The patient is extubated successfully with no neurological sequelae.
Which of the following is the most likely etiology of the patient’s hypotension?
Correct Answer: B
Losartan is a highly selective angiotensin (AT1) receptor blocker (ARB), and like other ARBs and ACE inhibitors, is used for treatment of hypertension, heart failure, and prevention of cardiac remodeling after myocardial infarction. By displacing angiotensin II from the AT1 receptor, ARBs antagonize AT1-receptor–induced vasoconstriction, aldosterone, catecholamine and arginine-vasopressin release, water intake, and hypertrophic responses. During general anesthesia, maintenance of blood pressure is dependent on the RAAS and AT1 activation. By blocking AT1, losartan may precipitate severe hypotension under general anesthesia. Chronic AT1-blockade can also reduce the vasoconstrictor response to alpha1 receptors activated by norepinephrine, causing resistance to direct and indirect pharmacologic intervention, as seen in this patient. Clinical studies have shown that vasopressin can restore the sympathetic response and is useful in cases of refractory hypotension in patients with chronic RAAS inhibition undergoing general anesthesia. Norepinephrine, with much more potent alpha1 activation than phenylephrine, is also recommended as it may have a more favorable effect on splanchnic perfusion and oxygen.
While the patient’s NPO status may result in hypovolemia, the lack of response to a fluid bolus makes hypovolemia alone a less likely cause of this patient’s hypotension during general anesthesia. The patient reported great exercise capacity, no symptoms of heart failure, no signs of acute infarction on ECG, and return to normal blood pressure after discontinuation of general anesthesia, making an acute myocardial infarction or pulmonary embolism unlikely.
An 18-year-old male with multiple stab wounds to his abdomen is brought by ambulance to the trauma bay. He is bleeding profusely, with HR 128 beats/min, BP 72/41 mm Hg, SpO2 92% on 15 L oxygen via nonrebreathing face mask. Of the following statements regarding this patient’s renin-angiotensin-aldosterone system (RAAS), which is FALSE?
Correct Answer: A
There are many compensatory biological and neuroendocrine mechanisms in response to acute hypovolemic shock. In the juxtaglomerular apparatus, renin is released in response to three stimuli:
Renin hydrolyzes angiotensinogen into angiotensin I, which is further cleaved in the lungs by endothelial-bound ACE into angiotensin II, a potent vasoconstrictor which acts directly on the AT1-receptor on arteriolar smooth muscles to maintain systemic perfusion. Angiotensin II also acts on glomerular arterioles, with greater vasoconstrictive effect on efferent arterioles than afferent. This preserves glomerular pressure and the glomerular filtration rate in shock states.
Angiotensin II also stimulates the adrenal glands to release aldosterone, which triggers the epithelial cells in the distal tubule and collecting ducts of the kidney to increase reabsorption of sodium and water and excretion of potassium and hydrogen ions.
Which of the following lab results is most consistent with isolated hypoaldosteronism?
Correct Answer: C
Aldosterone is the main mineralcorticoid hormone produced by the zona glomerulosa of the adrenal cortex. It promotes sodium retention and potassium excretion by:
Hypoaldosteronism presents with hyperkalemia and an associated mild (normal anion gap) metabolic acidosis. Although aldosterone plays a key role in sodium homeostasis, isolated hypoaldosteronism is not typically associated with sodium wasting as the kidney compensates via angiotensin II. Hyponatremia is also uncommon, as ADH is not released in a patient who is otherwise euvolemic. The presence of hyponatremia should warrant workup for primary adrenal insufficiency and other causes. Option C demonstrates eunatremia, mild non-gap metabolic acidosis and hyperkalemia, making it the right answer.
The potassium imbalance in hypoaldosteronism can also impair urinary excretion of ammonium, a condition called type 4 renal tubular acidosis. The most common causes of acquired hypoaldosteronism are hyporeninemic hypoaldosteronism, pharmacologic inhibition of angiotensin II or aldosterone, heparin therapy, and critical illness. Hyporeninemic hypoaldosteronism is common in patients with mild to moderate renal insufficiency due to diabetic nephropathy or chronic interstitial nephritis but can also occur in acute glomerulonephritis and in patients taking nonsteroidal anti-inflammatory drugs or calcineurin inhibitors. Pharmacologic inhibition of angiotensin II with medications such as ACE inhibitors, angiotensin II receptor blocks, and aldosterone receptor blockers are often initiated to improve survival in patients with heart failure and to prevent cardiac remodeling. Heparin has a direct toxic effect on the production of aldosterone in the adrenal cortex. Decreased adrenal production can occur in severely ill patient, whereas stress-induced production of cortisol may divert substrates away from aldosterone production.
Treatment is with replacement therapy with mineralocorticoid effect, such as fludrocortisone.
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