**3. Etiology of POCD**

4 Recent Advances in Arthroplasty

Surgery induced stress response leads to [1] the activation of the sympathetic nervous system, [2] increased secretion of pituitary hormones, and [3] immunological as well as

Activation of the sympathetic nervous system leads to an increased secretion of catecholamines from the adrenal medulla and of norepinephrine from presynaptic nerve terminals. It results in such cardiovascular effects as tachycardia and hypertension

The secretion of adrenocorticothropic hormone (corticotrophin, ACTH), growth hormone (GH) and arginine vasopressin (AVP) increases; the secretion of thyroid-stimulating hormone (TSH) as well as of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) may increase or decrease. As a result, the secretion of cortisol and aldosterone increases; that of insulin often decreases, while that of glucagone usually decreses; and, finally, decreases, and the secretion of thyroxine and tri-iodothyronine decreases. All those changes influence the metabolism of carbohydrates, proteins and fat as well as that of salt

Immunological and hematological changes include cytokine production, acute phase reaction, neutrophil leucocytosis and lymphocyte proliferation (Desborough, 2000). Cytokines - mainly interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α) and IL-6, released from activated leukocytes, fibroblasts and endothelial cells - play an important role in the systemic inflammatory reaction (Desborough, 2000). Some authors (Blaise, et al., 2007; Singh & Antognini, 2010; Van Munster et al., 2009) suggest that inflammation plays a substantial role in the pathogenesis of POCD. Their claim was supported by the observation that cyclooxygenase-2 (COX-2) inhibitors protect the amyloid β-induced memory disturbances in mice (Blaise, et al., 2007). The animal studies also showed that the development of POCD in rats was associated with glial activation and the expression of proinflammatory cytokines within the hippocampal region (Blaise, et al., 2007). Some studies revealed the role of interleukin-18 (IL-18) in the neuroinflammation and neurodegeneration of the central nervous system. Patients with a defect in the IL-18 cytokine promoter gene had a higher concentration of serum amyloid peptides (Fodale, et al., 2010). The amyloid β peptide concentration was related to learning and memory deficiences as well as to neurodegeneration. Continuous infusion of amyloid β peptide in rats resulted in learning and memory impairments. Higher levels of amyloid β peptide in the hippocampus were observed in older rats when compared to those in younger ones (Fodale, et al., 2010). Some anesthetic agents can influence the amyloid β production. Isoflurane increases the amyloid β production through an alteration in the processing of amyloid precursor protein; desflurane also causes an increase, but only in the presence of hypoxia. Propofol and thiopental do not

**2. Surgery induced stress response and risk factors of POCD** 

significantly change the amyloid precursor protein (Fodale, et al., 2010).

The following were counted as risk factors of POCD in an early postoperative period: advanced age, a general anesthesia rather than a regional one, an increasing duration of anesthesia, poor education, re-operation, postoperative infections, postoperative respiratory complications, lower preoperative level of consciousness, and treatment with cholinergic drugs and benzodiazepines, but also sleep deprivation, isolation, noise, bright light and such physiologic disturbances as hyponatremia or hypoalbuminemia as well as male sex, depression or reduced activity in daily life (Blaise, et al., 2007; Canet et al., 2003; Fines & Severn, 2006; Kyziridis, 2006; Singh & Antognini, 2010; Veering, 1999). Oddly enough, there

hematological changes (Desborough, 2000).

(Desborough, 2000).

and water (Desborough, 2000).

The high incidence of cognitive dysfunction in orthopedic patients can result (apart from the above mentioned risk factors) from long bone fractures, prolonged immobilization, and partially from perioperative stress (Wu, et al., 2004) or a surgery technique. Colonna et al. concluded that the incidence of cerebral embolization after lower extremities arthroplasties was up to 40 – 60% (Colonna et al., 2002). Thromboembolic events played an important etiological role. There were described fatal cerebral embolizations that constituted complications accompanying long bones fractures (Riding et al., 2004), total knee replacements (Jenkins, Chung, Wennberg, Etchells, & Davey), hip arthroplasties (Fallon, Fuller, & Morley-Forster, 2001), and vertebroplasties (Scroop, Eskridge, & Britz, 2002) in which the embolic material passed into the brain through an open foramen ovale (Sukernik, Mets, & Bennett-Guerrero, 2001), although postmortem examinations did not reveal it (Colonna, et al., 2002).
