Update in Anaesthesia Originally published in Update in Anaesthesia, edition 12 (2000) Endocrine Physiology PA Farling*, ME McBrien, D Breslin *Correspondence Email: [email protected] Key to terms used Summary ADH Antidiuretic Hormone T3 Tri-iodothyronine This article will concentrate on basic physiology of the GH Growth Hormone T4 Thyroxine principal endocrine glands, GHRH GH Releasing Hormone GHRIH GH Release Inhibiting Hormone the pituitary, thyroid, and adrenal glands. Other LH Luteinising Hormone FSH Follicular Stimulating Hormone endocrine glands which TSH Thyroid Stimulating Hormone DDAVP Desmopressin will not be discussed here include the pancreas, the ACTH Adrenocorticotropic Hormone CRH Corticotrophin Releasing Hormone hypothalamus, parathyroids and gonads. In addition, the liver, kidney, lungs, INTRODUCTION parts which partly surround the posterior lobe and the gastrointestinal tract, pineal The endocrine system acts through chemical infundibulum (Figure 1). The distal part forms most gland and thymus produce messengers, hormones, to coordinate many bodily of the anterior lobe. The intermediate part, a thin many other hormone-like substances. functions. It maintains the internal environment sheet of non-functional glandular tissue and a narrow (homeostasis), controls the storage and utilisation of cleft separates the anterior lobe from the posterior energy substrates, regulates growth and reproduction lobe. The infundibular part of the anterior lobe is a and, perhaps of greatest importance to anaesthetists, narrow upward projection which partially encircles controls the body’s responses to external stimuli, the infundibulum. particularly stress. The blood supply to the pituitary gland is by branches THE PITUITARY GLAND of the internal carotid and anterior cerebral arteries. Anatomy The anterior lobe also receives venous blood from PA Farling the hypothalamus via the hypothalamo-hypophyseal The pituitary gland lies within a dural covering in a Consultant portal system of veins (Figure 2), which transmits depression of the skull base (sella turcica). On each Department of releasing factors to the pituitary from the lower tip side lie the cavernous sinus containing the carotid Anaesthetics of the hypothalamus. The veins of the pituitary drain arteries and the III, IV and VI cranial nerves. The Royal Victoria Hospital into the cavernous sinuses. pituitary gland is attached to the hypothalmus in Belfast BT12 6BA the floor of the third ventricle by the pituitary stalk UK (infundibulum), which passes though an aperture in the fold of dura mater forming the roof of the sella ME McBrien turcica (diaphragma sellae). Consultant Department of Hypothalamus Pituitary stalk The pituitary gland is made up of two parts: Anaesthetics The posterior lobe (neurohypohysis) is the expanded Royal Victoria Hospital inferior end of the infundibulum, and is developed Belfast BT12 6BA embryologically from the brain. The infundibulum UK contains axons of neurones from the supraoptic and paraventricular nuclei of the hypothalamus which Pars anterior D Breslin terminate on the surface of capillaries in the posterior Pars posterior Research Fellow lobe onto which they secrete the two posterior Department of pituitary hormones, antidiuretic hormone (ADH) Anaesthetics Pars intermedia and oxytocin. The Queen’s University The anterior lobe (adenohypophysis) is much larger Belfast BT9 7BL than the posterior lobe, and itself consists of three Figure 1. The pituitary gland UK Update in Anaesthesia | www.worldanaesthesia.org page 52 Hypothalamus (detector) Releasing hormones Anterior lobe of pituitary gland (control centre) Inhibition Trophic hormones to target Stimulation (endocrine) glands Target gland (effector) Figure 2. The hypothalamo-hypophyseal portal system Raised blood levels of target gland hormone Human anterior pituitary cells have traditionally been classified according to their staining characteristics into chromophobes, Utilisation of hormones acidophils or basophils. With more modern techniques of immunochemistry and electron microscopy, it is now possible Lowered blood levels of target to distinguish five cell types: 1. somatotropes, which secrete gland hormones growth hormone (GH); 2. lactotropes, which secrete prolactin; 3. thyrotropes, which secrete thyroid stimulating hormone (TSH); 4. Figure 4. Negative feedback regulation of secretion of hormones by the gonadotropes, which secrete luteinising hormone (LH) and follicle- anterior lobe of the pituitary gland stimulating hormone (FSH); and 5. corticotropes, which secrete adrenocorticotropic hormone (ACTH). They control a wide range Secretion from the posterior pituitary is controlled by nerve fibres of functions (Figure 3). There are also functionally inert cells within arising in the hypothalamus which pass along nerve axons and the gland known as null cells. terminate on blood vessels in that part of the gland. Secretion from the anterior pituitary is controlled by hormones called Anterior pituitary hypothalamic releasing and hypothalamic inhibitory hormones (or Growth FSH LH TSH Prolactin ACTH factors) carried from the hypothalamus to that part of the gland hormone by the hypothalamo-hypophyseal portal system. These hormones act on the glandular cells of the anterior pituitary to regulate their secretion. Gonads Many organs Thyroid Breasts Adrenal HORMONES OF THE ANTERIOR PITUITARY GLAND and tissues Secretes Breast cortex Protein thyroxine development Secretes synthesis triopthyronine and milk cortisol Growth hormone carbohydrate production and lipid Effects metabolism • Promotes the growth of bone, cartilage and soft tissue via the effects of insulin-like growth factor, IGF-1 (formerly known as Figure 3. The widespread effects of the pituitary gland somatomedin C), whose production is increased in the liver, kidney and other tissues in response to GH. If excess GH levels are Control of pituitary secretion by the hypothalamus present before fusion of the epiphyses occurs, gigantism occurs. Almost all hormone secretion by the pituitary is controlled by After the epiphyses are closed, linear bone growth is no longer either hormonal or nervous signals from the hypothalamus. The possible and excess GH leads to acromegaly, which can cause a hypothalamus receives signals from almost all possible sources in number of clinical problems relevant to anaesthesia (Table 1). the nervous system, and is itself under negative feedback control • Increases the rate of protein synthesis in all cells of the body. (Figure 4) from the hormones regulated by the pituitary gland. This means that when there is a low level of hormone in the blood • Fat mobilisation by release of fatty acids from adipose tissue. supplying the hypothalamus, it produces the appropriate releasing • Decreases the rate of glucose utilisation throughout the body due hormone or factor which stimulates the release of the hormone by to diminished uptake of glucose by cells (i.e. it is counter the pituitary and this in turn stimulates the target gland to produce regulatory to insulin). and release its hormone. As a result, the blood level of that hormone • Increases hepatic glucose output. rises and inhibits the secretion of releasing hormone or factor by the hypothalamus. • Stimulates erythropoiesis. page 53 Update in Anaesthesia | www.anaesthesiologists.org • Na+ and K+ excretion are reduced, while Ca2+ absorption from triiodothyronine (T3) by the thyroid gland. Persistently elevated the intestine is increased. levels of TSH lead to hypertrophy of the thyroid, with increased vascularity. Regulation GH release from the anterior pituitary is under the control of the Regulation hypothalamus which secretes both a releasing hormone (growth TSH is produced and released from the anterior pituitary in response hormone releasing hormone - GHRH) and an inhibitory hormone to thyrotropin releasing hormone released from the hypothalamus (growth hormone release-inhibiting hormone - GHRIH, or and carried to the pituitary via the hypothalamohypophyseal portal somatostatin) into the hypothalamo-hypophyseal portal system. GH system. The hypothalamus can also inhibit TSH secretion via the and IGF-1 produce negative feedback effects on the hypothalamus effects of released somatostatin, in the same way that GH inhibition and pituitary. occurs. Free T3 and free T4 in the plasma exert a negative feedback The stimuli that increase GH secretion fall into three general effect on the hypothalamus and the pituitary to regulate the categories: circulating levels of these hormones. • Hypoglycaemia and fasting. Follicle stimulating hormone and luteinizing hormone • Increased amounts of certain amino acids in the plasma. • Stressful stimuli. Effects Secretion of GH is reduced in response to increased concentrations of In men, FSH stimulates spermatogenesis by the Sertoli cells in the glucose, free fatty acids or cortisol in the plasma, and is also reduced testis. In females, FSH causes early maturation of ovarian follicles. during rapid eye movement sleep. In men, LH causes testosterone secretion by the Leydig cells in the testis. In females, LH is responsible for the final maturation of Prolactin ovarian follicles and oestrogen secretion from them. Effects Regulation Prolactin stimulates secretion of milk and has a direct effect on the In males and females, LH and FSH production by the anterior breast immediately after parturition. Together with oestrogen and pituitary is regulated by release of gonadotropin releasing hormone progesterone, prolactin