Blair Evan T, Clemmer John S, Harkey H Louis, Hester Robert L, Pruett W Andrew
University of Mississippi Medical Center, School of Medicine, Jackson, Mississippi, USA.
University of Mississippi Medical Center, Department of Physiology and Biophysics, Center for Computational Medicine, Jackson, Mississippi, USA.
World Neurosurg. 2017 Nov;107:429-436. doi: 10.1016/j.wneu.2017.07.175. Epub 2017 Aug 7.
Disturbances in water and electrolyte homeostasis are common after transsphenoidal surgery. These disorders are variable and unpredictable, increasing patient risk and complicating postsurgical treatment. Clinically, it is generally accepted that damage to the pituitary is the cause, but the mechanisms behind the response variability and underlying pathophysiology remain unknown.
To test the hypothesis that changing the degree of damage to the pituitary stalk produces a spectrum of water and electrolyte disturbance along which all presentations of postsurgical water and electrolyte disturbances can be identified.
We used HumMod, a large mathematical model of physiology, to simulate pituitary stalk damage at differing fractions: 20%, 40%, 60%, and 80%. The damaged neurons were modeled to undergo a 5-day countdown to degeneration and release stored antidiuretic hormone as they die, as is proposed to occur.
Lower pituitary damage (20%) resulted in transient polyuria and intermediate damage (40%) was associated with delayed polyuria and diabetes insipidus. Higher levels of damage (60% and 80%) showed a triphasic pattern of diabetes insipidus.
We postulate that our model provides a plausible mechanistic explanation for some varieties of postsurgical water and electrolyte disturbances, in which increasing damage to the pituitary potentiates the likelihood of a full triphasic response. However, our simulation shows that merely modifying the level of damage does not produce every presentation of water and electrolyte imbalance. This theory suggests that other mechanisms, which are still unclear and not a part of this model, may be responsible for postoperative hyponatremia and require further investigation.
经蝶窦手术后水和电解质稳态紊乱很常见。这些紊乱情况多变且不可预测，增加了患者风险并使术后治疗复杂化。临床上，一般认为垂体损伤是病因，但反应变异性背后的机制及潜在病理生理学仍不清楚。
检验垂体柄损伤程度改变会产生一系列水和电解质紊乱这一假设，据此可识别术后所有水和电解质紊乱表现。
我们使用大型生理数学模型HumMod模拟不同损伤比例（20%、40%、60%和80%）的垂体柄损伤。按照所提出的情况，对受损神经元建模，使其经历5天的退化倒计时，并在死亡时释放储存的抗利尿激素。
较低程度的垂体损伤（20%）导致短暂性多尿，中度损伤（40%）与延迟性多尿和尿崩症相关。较高程度的损伤（60%和80%）呈现尿崩症的三相模式。
我们推测，我们的模型为某些术后水和电解质紊乱类型提供了合理的机制解释，其中垂体损伤增加会增强完全三相反应的可能性。然而，我们的模拟表明，仅仅改变损伤程度并不会产生所有水和电解质失衡表现。该理论表明，其他尚不清楚且不属于此模型一部分的机制可能导致术后低钠血症，需要进一步研究。
