$4-D-1-05 PATHOPHYSIOLOGY OF HYPONATREMIC ENCEPHALOPATHY A. Arieff 1 1.) Veterans Affairs Medical Center and University of California, San Francisco Hyponatremia is the most common metabolic abnormality seen in a general hospital population, affecting about 1% of all postoperative patients, of whom about 10% develop metabolic encephalopathy and about 2% suffer permanent brain damage. Recent studies of patients with hyponatremic encephalopathy have demonstrated that age and gender are the among the most important factors in predicting the development of permanent brain damage. In adults, the gender distribution among patients with either hyponatremia or hyponatremic encephalopathy is similar. However, the relative risk of permanent brain damage is more than 25 times higher for menstruant women than for either men or postmenopausal women. Neurological manifestations of hyponatremia may be observed when plasma sodium is less than the normal value. Symptoms most commonly include nausea, emesis, weakness and headache but can include muscular twitching, grand mal seizures, coma and respiratory insufficiency. Hyponatremic encephalopathy and resultant brain damage occurs as a consequence of a specific sequence of disturbances in fluid -electrolyte homeostasis: a) Initially, hyponatremia leads to a movement of water into brain cells which is facilitated by vasopressin (AVP); c) As cytotoxic brain edema progresses, the brain begins to compensate by extrusion of osmotically active cation (Na + and K+), attempting to lower the osmolality without substantial gain of water, a process which is accelerated by certain hormones and impaired by others; e) AVP and/or estrogen have direct effects on cerebral blood vessels to decrease both cerebral perfusion and decrease ATP synthesis, impairing outward transport of Na + and K +, leading to increasing edema, f) if serum sodium is not corrected, there will be eventual brain herniation and secondary occlusion of cerebral vessels, which can lead to respiratory arrest and hypoxic brain damage. Virtually all hyponatremic patients have increased blood levels of AVP. Estrogens stimulate AVP release, while androgens appear to suppress it. In addition, estrogens may antagonize brain adaptation via the Na+-K + ATPase system while androgens may enhance such adaptation. Systemic hypoxemia and hyponatremia are far more deleterious than either factor alone because hypoxia impairs the ability of the brain to adapt to hyponatremia. More than 50 patients with symptomatic hyponatremia who had an arterial pO2 below 50 mm Hg when the hyponatremia was diagnosed have now been reported. The radiologic findings in patients with hyponatremic encephalopathy are usually diffuse cerebral demyelinative lesions, similar to those found with hypoxic encephalopathy. Conventional wisdom in the past has been that the time required for the serum sodium to fall, as well as the magnitude of the decline in serum sodium, were major determinants of brain damage, but recent data suggests that neither of these factors are important in the genesis of hyponatremic brain damage.
$4-C2-1:01 THERMOSENSITIVITY OF MORMOEAL ~NFLUENCES
P. H i n c k e l
and G. K u h n e n
der U n i v e r s i t ~ t ,
The thermosensitivity of t h e brainstem, especially o f the h y p o t h a l a m u s , has been demonstrated by experiments with thermal stimulation In the last decades. The present experiments In g o a t s compare the t h e r m o s e n s l t i v i z y of the h y p o t h a l a m u s with the t h e r m o s e n s l t l v l t y of the whole brain. R e s p i r a t o r y e v a p o r a t i v e heat loss (REHL) and s e l e c t i v e brain c o o l i n g (3BC} were ~est~d. Thermal 5 t i m u l a t i o n of the h y p o t h a l a m u s at c o n s t a n t e x t r a h y p o t h e l a m l c brain t e m p e r a t u r e resulted In 80 % of the r e s p o n s e of the whole b r a i n for both, R E M L and SBC. REHL Is a m e c h a n i s m w h i c h is d r l v e n by thermal ~l~n~18 of brain and trunk, w h e r e a s SBC £s driven by b r a i n t e m p e r a t u r e only. H e a t i n g of one h e m i s p h e r e of the b r a i n r e s u l t e d In SEC of the I p s i l a t e r a l h e m i s p h e r e but not of the c o n t r = I n t e r a l one. In a d d i t i o n v a s o d i l a t a tlon of the nasal m u c o s a w a s s e e n i p s l l a t e r a l l y and t h a t of the ears bilaterally. The b a s i s for the a b o v e d e s c r i b e d t h e r u o s e n s l t l v l t y of the b r a i n s t e m are neuronal thermosensltive structures which are predominantly located within h y p o t h a l a u l c areas. In the rat and in the guinea pig a d d i t i o n a l b r a l n s t e m regions such as the s u b c o e r u l e u s a r e a and d i f f e r e n t raphe n u c l e i have b e e n s h o w n to be i n v o l v e d in the control of thermal adaptive changes. On the one hand s u b c o e r u l e u s and raphe neurons changed their spike rate characteristics after cold a c c l i m a t i z a t i o n and on the o t h e r hand heat p r o d u c t i o n t h r e s h o l d d l s p l a c e m e n t s w e r e o b s e r v e d a f t e r l e s i o n s in both regions. T h e s e t h r e s h o l d d i s p l a c e m e n t s could be c o n c e i v e d as s i m u l a t l o n s of natural adaptive a l t e r a t i o n s . Moreover, thermoreactlve neurons in the raphe s y s t e m were Influenced by systemic applications of estra4[Iol and p r o g e s t e r o n e . The glme c o u T s e of t1~se n e u r o n a l c h a D g e s was in g o o d a c c o r d a n c e with the p h a r m a c o k i n e t l e s of the t w o s t e r o i d s and seems to be r e s p o n s i b l e for the t h e r m o r e g u l a t o r y changes in the female proestrus. ( S u p p o r t e d by the DFG Ku 8 0 7 / I - 1 , 2 and by the Land H e s s e n M I - A T G 9 9 / 1 5 3 0 )