First Year BVMS

Veterinary Physiology

Endocrinology Notes
I.A.Jeffcoate. April 2010

CONTENTS Introduction (hormone definition & properties) The Hypothalamo-Hypophyseal system Anterior Pituitary Hormones The Posterior Pituitary gland Calcium and Phosphate regulation Growth Hormone The Adrenal gland The Adrenal medulla The Adrenal cortex The Thyroid gland The Pancreas Additional reading list C Cunningham; SHS - Sjaastad, Hove & Sand.

Page 1 3 4 5 6 9 9 10 10 12 13 14

Recommended references in the text: B&L - Berne & Levy, Third Edition;

Introduction
(endocrines,hormones, definition & properties) Endocrinology is the physiology of the hormone secreting (ie. Endocrine) glands and the study of endocrine (or humoral from Latin body fluids) control systems (B&L Chapter 44; C. Chapter 32, pp369-378). Compare exocrine secretions, often via ducts, onto surfaces such as skin and mucosal epithelium. By definition, a hormone is any substance secreted crine into endo the bloodstream and carried to distant parts, where it changes the function of specific (target) tissues". Hormones may exert local paracrine effects after diffusing from the site of secretion to adjacent tissue. If endocrine target tissues are deprived of hormonal support, they atrophy (ie shrink and become non-functional). The classic example of this is loss of colour and size of a cockerels comb and wattle after castration which can be restored by testosterone therapy. Both hormones and the autonomic nervous system (ANS) serve as efferent pathways for

distribution of signals to control body systems. While the latter tends to be responsible for fast changes in body function like heart rate, the hormones tend to control more sustained processes like growth and reproduction. However, the ANS and endocrine systems are not separate self-contained systems as a great deal of integration of neural and humoral signalling is required to maintain the steady state ie homeostasis. This integration occurs in the hypothalamus (more later and see 1st yr Prof NE ANS notes. The following notes will detail the endocrine efferent arms in these signalling processes.) Some general points about hormones (1) (2) Hormones vary in size and composition tremendously eg peptides, proteins, Hormones are secreted into the blood and can reach almost any organ so they glycoproteins, steroids. have the potential for very diffuse effects. Most, however, have very specific effects (SH&S Table 5.1), ensured by the fact that target organs or tissues have specific hormone receptors. (3) Most hormones have a relatively short half-life (disappearance rate) in the blood. Elimination occurs in faeces and urine, often after degradation in the liver, kidney, lungs and blood. Elimination is important and allows for a fine tuning between secretion and plasma concentration and prevents hormones accumulating in the blood (SH&S p207). Release and excretion of hormones usually occurs roughly in parallel and urinary or faecal hormone (metabolite) concentration is increasingly seen as a useful clinical indicator of secretion rate. (4) Endocrine abnormalities can occur due to many faults. Commonly, disorders in either hormone secretion or its plasma elimination affect plasma concentration, while receptor malfunction will prevent hormone action. (5) Most hormones are present in only small concentrations in blood plasma (free hormone) because they are rapidly bound (and rendered inactive) to plasma components. Binding protein + Free hormone Bound hormone Only free hormone can diffuse out of blood into the ECF and bind to its target cells. Control of hormone secretion, negative feedback Secretion must be coupled to body requirements to maintain a steady state (ie Homeostasis). In its simplest form hormone secretion is controlled by plasma concentration of a hormonally controlled variable, thus plasma glucose concentration controls insulin secretion. Raised plasma glucose stimulates insulin secretion which is then reduced when plasma glucose returns to its ideal setting. More complicated feedback loops, such as those of the hypothalamus/anterior pituitary/adrenal gland (SHS Table 5.8) involve one or more

intermediate hormones (long-loop systems). Feedback loops usually have a negative effect on hormone secretion. In a very few systems, feedback may operate positively to enhance hormone secretion, such as when oestrogen stimulates LH release and ovulation. Peripheral nerve innervation In certain instances the endocrine gland is neural (e.g. adrenal medulla, posterior pituitary) and neural innervation is required to stimulate hormone release. In addition, the autonomic nervous system may play a role in modulating hormone secretion rather more indirectly, e.g. control of adrenal aldosterone synthesis via renin/angiotensin. Genetics affect endocrinology Considerable variation exists between individuals in their ability to elaborate and secrete hormones or in various aspects of target tissue function and hormone inactivation/elimination. Such differences may account for the variations in body weight, reproductive activity etc between animals.

The Hypothalamo-Hypophyseal System (SH&S p208)

This term describes the functional link between the hypothalamus and the pituitary gland.

The pituitary gland lies beneath the hypothalamus and comprises a posterior lobe(neurohypophysis), neural tissue derived from the hypothalamus and an anterior lobe(adenohypophysis), glandular tissue embryologically derived from the roof of the mouth (B&L, Chapter 48; C, Fig 32-10). The two lobes, though attached (forming the hypophysis), are not functionally linked. Removal of the hypophysis (hypophysectomy) can be achieved by approaching through the mouth and has dramatic effects such as arrested growth (young animal); infertility and atrophy of gonads and reproductive activity; suppression of lactation and involution of mammary glands; atrophy of thyroid gland and adrenal cortex (and disruption of growth and metabolism). The functions of the pituitary gland were originally illustrated in the hypophysectomised animal by administering pituitary gland extracts (replacement therapy) and noting the recovery of various body functions. So it was determined that the anterior pituitary (adenohypophysis) produces several trophic hormones (-trophins) each of which supports other endocrine activities, some being generalised (eg metabolism) some being very specific (eg gonadal germ cell stimulation). (For further details read C, Table 32-1).

Anterior Pituitary Trophic Hormones Name Growth hormone Luteinizing hormone Follicle stimulating hormone Prolactin Thyroid stimulating hormone Adrenocorticotrophic hormone Abbreviation GH LH* FSH* Prl* TSH ACTH Role/class somatotrophin gonadotrophin gonadotrophin gonado/lactotrophin thyrotrophin corticotrophin Summary of effects Stimulate growth and metabolism Stimulate gonads & gametes Mainly milk secretion Stimulate thyroid activity Stimulate adrenal cortical activity

Table 1. Summary of adenohypophyseal hormones * Gonadotrophins support reproduction in both sexes and will be considered in more detail in reproduction, Term 5. The Hypothalamus regulates the release and synthesis of each adenohypophyseal hormone by means of specific releasing hormones each of which is synthesised in a cluster (nucleus) of hypothalamic neurones and released from nerve endings directly into specialised portal blood vessels (hypothalamo-hypophyseal portal blood vessels), which flow from a 10 capillary plexus around nerve endings in the basal hypothalamus to a 20 plexus amongst pituitary cells. Table 2 lists the major hypothalamic releasing hormones alongside the pituitary hormone each controls (+ = stimulate, - = inhibit).

Name Growth hormone releasing hormone Growth hormone inhibiting hormone (somatostatin) Gonadotrophin releasing hormone Prolactin inhibitory factor Thyrotrophin releasing hormone Corticotrophin releasing hormone

Structure peptide dopamine peptide

Abbreviation GHRH GHIH GnRH PIF TRH CRH

Action
+ GH - GH

+ LH , + FSH - PRL + TSH (plus prolactin) + ACTH

Table 2. Summary of hypothalamic releasing hormones By integrating afferent and efferent neural and endocrine signals the hypothalamus is the major player in achieving homeostasis. Its position in the brain also

allows environmental stimuli, which are best detected by the nervous system, to trigger endocrine changes. eg. Fright raises sympathetic tone and adrenaline release, and stimulates CRH / ACTH release to trigger cortisol secretion. Annual daylength changes alter GnRH secretion to regulate seasonality of reproduction.

The Posterior Pituitary Gland

Also known as the neurohypophysis, the posterior lobe of the pituitary secretes two hormones oxytocin (OT) and vasopressin (co-named anti-diuretic hormone, ADH). Both are synthesised in the hypothalamus and pass down nerve axons (the hypothalamo-neurohypophyseal tract) into the neurohypophysis, where they are stored. OT or ADH secretion requires appropriate stimulation of the nerve cell bodies in the hypothalamus, ie by neurohumoral reflex (C, pages 379-382). Actions ADH acts upon the collecting ducts of the renal tubules increasing permeability to water and thus causing increased water uptake and concentration of the urine (hence its name antidiuretic hormone). It also has vasopressor actions (hence its name vasopressin) on peripheral arterioles to help sustain blood pressure, important after haemorrhage and in circulatory adjustments eg after standing. ADH also stimulates thirst. Oxytocin stimulates contraction of reproductive tract smooth muscle eg during parturition and also stimulates contraction of myoepithelial cells in the mammary gland to cause let-down of pre-formed milk. ADH - Stimulation and Control (SHS Fig 5.6) 1) Hypothalamic Osmoreceptor cells must lose water and shrink if extracellular fluid osmolarity increases, such as after loss of water by dehydration or diarrhoea. Osmoreceptors in turn initiate release of ADH which ensures renal water conservation and triggers thirst. Negative feedback occurs when restored ECF osmolarity inhibits osmoreceptor action. ADH secretion is strongly inhibited by alcohol, less strongly by cortisol and thyroxine. 2) If blood pressure falls, afferent impulses from stretch receptors in the right atrium signal vasopressin to be secreted. Vasopressin secretion is inhibited when normal blood pressure is regained. Emotional and surgical stress stimulate vasopressin and, consequently, these are factors which may cause hypertension.

OT Stimulation and control . 1) OT stimulates uterine smooth muscle contraction mainly during parturition. Its receptors are induced by hormone changes in late pregnancy. OT release is triggered after the initiation of parturition when the fetus is moving down towards the cervix. OT role is to reinforce myometrial contraction and herald the final phase of parturition, expulsion of the fetus from the birth canal. OT probably has analogous effects on sperm transport in the male tract during ejaculation and also in the female tract during copulation, as plasma concentrations are high under these circumstances. 2) OT release during milk let-down and parturition are true neuroendocrine reflexes, OT being the humoral efferent arm of the reflex, while suckling provides the neural afferent arm. OT stimulates expulsion of formed milk from storage in mammary alveoli and ducts. It acts on myoepithelial cells which surround both the alveoli and small ducts. OT release may also be conditioned by other stimuli such as the sight or smell or crying of the young. OT release or its effectiveness can be over-ridden by concurrent stress, which may raise adrenaline and cortisol levels. This explains the inhibition of milk let-down in stressed animals. Disorders of Posterior Pituitary Function Deficiency of ADH (caused by disease damage of the posterior pituitary or by head injury), results in excessive water loss through increased urine flow (polyuria, PU). The urine in this case has low specific gravity. This condition is known as diabetes insipidus (DI) from diabetes (excess urine) insipidus (weak and watery) and is characterised by a raging thirst (polydipsiaPD) and continued urine formation even during dehydration. Treatment of this form of PD/PU necessitates life-long replacement with synthetic ADH. (See C, Clinical correlations, pp519-521).

Calcium & Phosphate Regulation

The calcium ion plays an central role in many processes, eg: muscle contraction, blood coagulation, enzyme activity, neural excitability, hormone release, membrane permeability, structure (skeleton). Calcium ion homeostasis involves maintenance of stable plasma calcium ion concentration (Ca++) and is largely achieved by three hormones, which have a net effect on (Ca++) as follows:
*0 *1 *2

parathyroid hormone, PTH (Ca++) calcitonin, CT (Ca++) vitamin D (Ca++)

(See B & L Chap 47, C, pp 416-423, Dukes, pp 777-780, McDonald, Chap 4, SHS p245) Many other hormones play an indirect role in Ca++ homeostasis. The phosphate ion (PO4- -) is regulated by the same hormones. It is vital to cell energetics (eg cATP) and is an important buffer in the body and in urine (more detail in Acid-Base, Term 5). It is also a major component of bone where Ca++ and PO4- - are laid down together. There is a limited solubility of CaPO4 in body fluids and since PO4- - uptake from the gut cannot be regulated some PO4- - must be continually excreted, a process stimulated by both PTH and CT in the kidney. This is also required to buffer fixed acid excreted in urine. The amount of fixed acid is high in carnivores due to dietary amino acid metabolism. Ca++ and PO4- - turnover with ECF and tissue pools are shown in B&L, Figs 47-1/2. NOTE: The magnesium ion (Mg++) is also required by several body and cell systems and is regulated in a similar manner to Calcium. Parathyroid hormone PTH is synthesised and stored in secretory granules within "chief" cells of the parathyroid glands, which lie within or close to the thyroid gland but which are embryologically distinct. Chief cells are stimulated to secrete PTH by lowered (Ca++) or increased PO4- -. Actions of PTH: Initially (acutely) it increases the activity of osteocytes (deep bone cells) and osteoblasts (which line capillaries) - the so-called osteocyte-osteoblast pump. (B&L Fig 47-4, SHS Fig 6.7). Slower (chronic) effects of PTH include stimulation of osteoclast activity which causes bone resorption and overall bone remodelling. Hydroxyproline is a product of bone collagen dissolution and may be used as a clinical indicator of osteoporosis (Figs. 4.18 & 4.20 McDonald). PTH acts on the proximal convoluted tubule to decrease reabsorption of PO4- - and acts on the distal convoluted tubule to enhance Ca++ reabsorption.

PTH increases activation of Vit D, thereby promoting increased absorption of dietary Ca++. Calcitonin (Thyrocalcitonin, CT) is secreted by C-cells found among thyroid follicular cells. Raised plasma (Ca++) is the main physiologic stimulus for its release. Actions of CT: Antagonises PTH effects on reabsorption of calcium from bone. Blocks Ca++ reabsorption by renal distal tubule epithelial cells and also promotes renal PO4- - wastage and inhibits gut Ca++ absorption via reduced Vit D activation. Physiological significance of CT: Participation with PTH to provide a dual negative feedback control of plasma (Ca++). CT helps to cope with hypercalcaemia after feeding, protects against excessive Ca++ loss during pregnancy, plays a dual role with PTH in cyclic resorption of Ca++ during hibernation and deposition during arousal (McDonald, Fig 4.34). Cholecalciferol (Vitamin D3) Formed in skin by ultraviolet (sunlight) irradiation of ergosterol (D2) to form cholecalciferol (D3). This is converted in liver to 25-hydroxy cholecalciferol (25-OH-CC) which is then converted to the active form 1,25-dihydroxy cholecalciferol (1,25-DiOH-CC) in the kidney. 1,25-DiOH-CC promotes intestinal Ca++ absorption and its deposition in bone. Various factors modulate the crucial rate limiting step in formation of 1,25-OH-CC in the kidney:Stimulatory Low dietary Ca++ Vit. D deficiency PTH Low serum (Ca++) Low serum (P04- -)* GH, PL, PRL, E2** * Helps ensure resorption from bone to replace plasma PO4- -. ** Growth hormone, placental lactogen, oestradiol and prolactin become important in upregulating Ca homeostasis during pregnancy, lactation and growth (to meet fetal/neonatal requirements), by increasing 1,25-DiOH-CC formation, thus promoting intestinal Ca++ absorption. Inhibitory High serum (Ca++) High serum (P04- -) CT

Calcium homeostasis in the laying hen Eggshell principally consists of calcium carbonate laid down on an organic matrix. Formation of each eggshell may require about 1/10 of stored body Ca++. A wild bird laying a small clutch can manage with stores and from dietary sources it can obtain. The demand for calcium in an actively laying commercial bird, producing perhaps 280 eggs/year, is considerable and extra Ca++ must be provided. Before commencement of lay, the hormones oestradiol and testosterone, which are synthesised and secreted from immature ovarian follicles, stimulate Ca++ deposition in medullary bone. Elevated plasma PTH concentrations during the laying period promote reabsorption of Ca++ from bone stores. In addition, oestradiol promotes activation of vitamin D3 and efficient absorption of dietary Ca++. Plasma CT concentrations are low during the laying period. Calcium homeostasis during hibernation (Ca++) must be maintained during hibernation despite low metabolic activity. This is achieved by altering the ratio of PTH and CT. During hibernation, low CT and raised PTH ensures that Ca++ can be gradually reabsorbed into the bloodstream from bone stores (i.e. progressive osteoporosis). After arousal, the balance shifts in favour of CT to allow bone Ca++ reserves to be restored. Disorders of (Ca++) regulation Hyperparathyroidism results in high (Ca++) due to excessive PTH levels. Osteomalacia including excessive bone resorption, bone softness or fractures etc may occur. There are several causes: 1 Hyperparathyroidism is caused by a parathyroid adenoma secreting excess PTH. 2 Hyperparathyroidism can be due to one of two important causes:1) Renal: caused by disease or incompetence of the kidney tubule (as in chronic renal failure) results in hyperphosphataemia and failure to reabsorb filtered Ca++. This causes a reduction in (Ca++), therefore triggering increased PTH secretion, which causes progressive osteoporosis. 2) Dietary: Diets with (i) low Ca++, (ii) excess PO4- - with low to normal Ca++, or (iii) inadequate amounts of Vit D3 cause hypertrophy of the parathyroid gland and excess PTH secretion leading to severe skeletal problems. This may occur in puppies and kittens fed heart or liver or a predominantly meat diet with imbalanced Ca++ to PO4- - ratio. Hypocalcaemia causes paresis (cow) or tetany (bitch): Usually seen around parturition and initiation of lactation, e.g. parturient paresis in high-producing dairy cows (see C, p422, Clinical example SHS p249)

Growth Hormone (GH, Somatotrophin, *BST)

Small protein hormone (MW 27,000) B&L pp 914-920, SHS p213. Secretion: From the adenohypophysis under influence of hypothalamic releasing hormones (Table 2). Stimulated by low blood glucose, exercise, progesterone (pregnancy). Actions of GH: Induces growth in soft tissues, cartilage and bone. It enhances amino acid transport into cells and protein synthesis. It also antagonises insulin and causes lipolysis and glycogenolysis, thereby enhancing substrate availability. GH is essential for lactation in cattle (*bovine somatotrophin, BST can be used to extend lactation and increase yield). GH antagonises insulin and tends to hyperglycaemia. GH has important (indirect via somatomedins) effects on bone growth, stimulating replication of cartilage in the epiphyseal growth plates (B&L Fig 48-21) which then ossify under influence of GH and other growth factors. Thyroxine, Insulin and Cortisol may be permissive in this process. Gonadal steroids are stimulatory at low dose but the high levels at puberty cause ossification of the growth plate stopping long bone growth. GH is also involved with insulin in stimulating growth of skeletal muscle. T4 and cortisol are inhibitory. Gonadal steroids (and hence also anabolics) also play a role by increasing muscle sensitivity to GH, though sex differences exist. Control of GH: Pituitary GH release and synthesis is under the control of hypothalamic somatostatin and GH-releasing factor (see Table 2) and (B&L Fig 48-20). GH modulated by exercise and energy substrate levels in the blood (particularly glucose and arginine). Ghrelin, only recently characterised, is a neuropeptide transmitter/hormone which also causes GH release. It is released from the gastric mucosa between meals and has a role in appetite and maintaining blood glucose between meals. Lee HM, Wang G, Englander EW et al. Ghrelin, a new
gastrointestinal endocrine peptide: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology. 2002;143(1):185-90.

Disorders of GH secretion Excess GH secretion causes giantism in young animals (ie growth before normal closure of long bones). Excess GH after puberty will cause continued cartilage growth, jaw growth and coarsened features, hyperglycaemia and diabetes mellitus, a disease called acromegaly. Deficiency of GH secretion is usually manifested only in immature animals (or childhood) when pituitary (as opposed to thyroidal) dwarfism will result due to failure of long-bone growth.

The Adrenal Gland

Comprises two anatomically and functionally distinct endocrine glands (SHS p221, B&L Fig
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50-1): (1) The Adrenal Medulla (of neural crest origin, secretes catecholamines - adrenaline) (2) The Adrenal Cortex (of mesodermal origin, 3 zones, secretes corticosteroids)

1) The adrenal medulla

This is a sympathetic nervous system ganglion which secretes adrenaline and some noradrenaline directly into the bloodstream rather than innervating post-ganglionic fibres. (B&L, pp971-977; C, pp411-416) Actions of adrenal catecholamines: Not essential to life but serve as a useful extension of the sympathetic nervous system, secreting adrenaline in times of 'fight or flight.' Effects of adrenaline include: increased heart rate and force of contraction; vasoconstriction of blood vessels in skin and splanchnic bed and vasodilation of blood vessels to skeletal muscle; dilation of lung airways; relaxation of gut smooth muscle; arousal of CNS (e.g. anxiety, breathing stimulation); increased availability of glucose and promoted catabolism of fats; dilation of the pupils. On a day to day level catecholamines importantly stimulate K+ uptake by cells which is important for maintaining ECF Na+ : K+

2) The adrenal cortex

The cortical hormones are all steroids (corticosteroids). Three classes of hormone are secreted from the adrenal cortex: Mineralocorticoids (e.g. aldosterone; B&L Fig 50-7) Glucocorticoids (e.g. cortisol; B&L Fig 50-3) Sex steroids (e.g. androgens; B&L Fig 50-6) Actions of corticosteroids: Mineralocorticoids: Aldosterone action leads to conservation of ECF sodium and lowers potassium thereby controlling the composition and volume of body fluid. Quantitatively speaking, Na:K is chiefly adjusted by aldosterone sensitive cells in the distal renal tubule but epithelia in the sweat glands, salivary glands and gastrointestinal tract are also similarly stimulated by aldosterone to conserve Na. Glucocorticoids: Cortisol is not essential but has a very important role in a very diverse range of metabolic processes and helps the body cope with stress. In general, glucocorticoids are involved in fat mobilisation; they promote the conversion of protein to carbohydrate and the conversion of the carbohydrate to glycogen for storage. Synthesis of corticosteroids: (SHS Fig 5.18) Zoning of adrenal corticosteroid synthesis is achieved by virtue of the location of certain key enzymes within the cortex (B&L, Figs 50-3/4/6). Thus:
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essential to life important but not essential unimportant

Zona glomerulosa contains 18-hydroxysteroid dehydrogenase for aldosterone production. Zonae fascicularis and reticularis contain 17x-hydroxylase for cortisol synthesis. The corticosteroids are synthesised from cholesterol (see B&L Fig 50-3) which may be taken up from the circulation (stimulated by ACTH) or synthesised within the gland. About 2 - 10% of cortisol is found free in plasma, the bulk being tightly (but reversibly) bound to a specific carrier protein, transcortin or corticosteroid-binding globulin (CBG). Aldosterone is secreted in much smaller quantities than the glucocorticoids and has a low affinity for CBG but it is weakly bound to other plasma proteins. Actions of adrenal corticosteroids: Glucocorticoids (eg cortisol, corticosterone). (C, pp399-400; B&L, pp958-966; C, table 33-3). Fetal production triggers parturition and organ maturation (especially lung alveoli). In adults, Glucocorticoids mobilise amino acids from skeletal muscle (see Cushings), stimulate amino acid uptake by the liver and induction of hepatic enzymes for gluconeogenesis. Cortisol is required for normal hepatic glucose formation. Glucocorticoids tend to increase carbohydrate synthesis and storage but decrease its utilisation, hence causing a trend to hyperglycaemia (see Cushings). Cortisol plays a permissive role on the actions of thyroxine and catecholamines (adrenaline) with regard to their lipolytic actions. Cortisol inhibits the normal inflammatory process and reduces the immune response (see Cushings) hence corticosteroid therapy is very common in medicine (see C, p401). Mineralocorticoids (aldosterone, B&L, 968-971). Principal role is to maintain high Na+: K+ in the plasma by promoting Na reabsorption and K secretion by the distal tubule of the nephron. This is based on exchanging intra-tubular Na+ with extracellular K+ (or H+).

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Regulation of corticosteroid secretion Glucocorticoids: Cortisol secretion requires (ACTH, see Tables 1&2) (B&L, pp956-958). ACTH secretion is regulated by cortisol negative feedback blocking CRH action or secretion. Cortisol is released in a circadian pattern (high early am). Acute stress (eg animal capture, handling or pain) raises plasma cortisol concentrations. Chronic stress (eg disease or environmental) causes increased activity of entire hypo-pit-adrenal axis and may lead to gland enlargement and raised cortisol. Mineralocorticoids: Minor involvement of ACTH. Aldosterone secretion mainly controlled by the renin-angiotensin system and the juxta-glomerula apparatus (JGA) in the kidney nephron. There are 3 major stimuli to JGA for release of the enzyme renin: 1) renal perfusion, i.e. a fall in blood pressure in the afferent arteriole indicative of a drop in central blood pressure (the JGA functions as a baroreceptor) 2) sodium ion concentration in the distal tubule detected by the macula densa cells of the JGA 3) sympathetic nervous tone to the JGA (often after decreased systemic blood pressure). Renin causes formation of angiotensin I in the circulation. Angiotensin I is converted to angiotensin II in the lungs. Angiotensin II is biologically active and has the following major effects: (1) Vasoconstriction of peripheral arterioles to raise systemic blood pressure (2) (3) Stimulation of aldosterone raising renal Na and thereby water reabsorption. Stimulation of thirst

Disorders of adrenocortical function (SHS p225) Adrenocortical insufficiency (Addison's disease, see B & L p970). Deficiency of aldosterone secretion, often complicated by the loss of cortisol secretion, causes Na+ wastage/ K+ retention and dehydration while cortisol deficiency causes weakness, fatiguability and possibly hypoglycaemia. The patient requires life-long mineralocorticoid and glucocorticoid replacement therapy.

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Adrenocortical hyperfunction (Cushings syndrome). Appears in 3 forms:- (B&T 7-64/65): (1) adrenal tumours secrete cortisol independently of ACTH (2) non-pituitary ACTH- or CRH-secreting tumours (3) excess pituitary production of ACTH (Cushing's disease). Relatively common in older dogs, Cushing's (hypercortisolism) causes signs which can be predicted from the normal actions of cortisol (see above eg muscle wasting, fat redistribution, immunosuppression).

Thyroid gland (SHS p216)

The thyroid gland accumulates inorganic iodide for synthesis of the hormones thyroxine (T4) and tri-iodothyronine (T3). T4:T3 varies with species. Thyroid hormones are essential for growth and control metabolic rate. Thyroid hormone actions: On mitochondria, to increase metabolic rate and O2 consumption. Thyroxine causes increased protein catabolism (i.e. increased N2 excretion and loss of muscle mass) and increased fat oxidation (weight loss). Normal bone growth and CNS function are dependent upon normal thyroid function (hence dwarfism and cretinism if deficient). Thyroxine plays a permissive role in GH action and it also plays very important roles in hibernation (reduced T4 ), thermogenesis (increased T4 in response to cold stress), lactation (one of a complex of hormones required for milk production) and reproduction. Regulation of thyroxine: The basic thyroid unit (B&L, Fig 49-1) is the thyroid follicle comprising a single layer of epithelial cells surrounding a fluid-filled (colloid) cavity(C, pp389-396; B&L, Chapter 49). Thyroid gland function is regulated by TSH and plasma TSH levels are controlled by the negative feedback influence of T4/T3. Inorganic iodide is removed from the plasma (B&L, pp937-938), under the control of TSH, for T4 and T3 synthesis within the thyroid follicular cell. T4 secretion from stores in colloid is stimulated by TSH. T4 and T3 are quickly bound (and inactivated) in the blood to serum proteins (particularly thyroxin binding globulin, TBG). Only a small fraction of T4 is unbound or free in the blood. As with all hormones, only free hormone is active. Disorders of thyroid function (SHS p217) Hypothyroidism: Autoimmune deterioration of thyroid function (10 hypo-), Decreased TSH secretion (20 hypo-), Rarely, Iodine deficiency may lead to thyroid gland enlargement known as goitre (for better iodine trapping, see McDonald Figs 3.4 & 3.5), when increased TSH secretion (less negative feedback from T4 or T3) increases thyroid gland cell number. In young, hypothyroidism reduces myelination of nerve fibre tracts and vascularisation of the

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CNS leading to impaired neural development (cretinism). Linear growth is also retarded leading to thyroid dwarfism cf pituitary (GH) dwarfism. In adults, lethargy and obesity, cold intolerance occurs. Treatment by hormone replacement. Hyperthyroidism stimulates CNS activity and metabolic rate and is characterised by nervous, jumpy, 'hyper behaviour, ravenous eating but weight loss. Treatment by surgical or radiological (I131) gland ablation.

The Pancreas (SHS p228)

The pancreas has both endocrine and exocrine functions. Endocrine is restricted to the Islets of Langerhans which comprise only about 2% of the pancreas (C, pp404-411; B&L, Chap 46). The two pancreatic hormones of major importance are insulin and glucagon. Actions: Insulin and glucagon actions are mutually antagonistic. Insulin promotes carbohydrate (particularly glucose), amino acid and fatty acid entry into cells (removal from the circulation after a meal, also most importantly cell K+ and Mg++ uptake). Glucagon stimulates catabolic processes resulting in glucose liberation into the bloodstream, particularly hepatic glycogenolysis (B&L, pp859-867; C, table 33-5). Insulin stimulates anabolic reactions such as:- liver glycogenesis; liver and skeletal muscle amino acid uptake and protein synthesis; adipose tissue fat synthesis and storage. Brain and CNS cells have no insulin receptors and must rely solely on simple diffusion of glucose so the correct blood glucose level is obviously vital. Regulation of insulin secretion This is a complex interaction of many different factors (B&L, pp856-859). There is a continuous basal insulin secretion from -cells modulated by the autonomic nervous system. The sympathetic branch decreases while the parasympathetic branch increases insulin secretion. Raised plasma insulin is a characteristic feature of the post-prandial state. Increased blood glucose (hyperglycaemia) is the most important stimulus for insulin release, the cells being sensitive to blood glucose concentration. Glucose is the most important substrate which will cause insulin secretion. Others are amino acids (especially arginine) and fatty acids. Glucagon and certain gastrointestinal hormones such as gastrin, secretin and pancreozymin also directly stimulate insulin release.

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Disorders of insulin homeostasis Diabetes mellitus (uncontrolled flow of sweet urine) is the relative or total absence of insulin and is fatal if untreated (see B & L, p872-874;Vander, Fig. 15-10 for progression of diabetes). Hypoglycaemia resulting from excessive production of insulin may also occur. Control and actions of Glucagon Secreted by the -cells of the pancreatic islets. Hyperglycaemia inhibits and hypoglycaemia stimulates its release (B&L, pp868-871). Raised plasma glucagon is characteristic of the fasting state. Sympathetic nervous stimulation also increases glucagon secretion (Note: while generally decreasing insulin). Amino acids, especially arginine, apparently stimulate both insulin (for amino acid uptake and protein synthesis) and glucagon (for glucose maintenance) release eg after feeding in carnivores. Energy mobilisation/storage( B&L, p871). Additional Reading list All medical physiology texts have an Endocrinology section which will be useful but the cases may appear irrelevant. The following veterinary texts are good:Vander = Vander et al, Human Physiology Third edition. Very good for description of concepts and integration of systems but less good for details. McDonald = LE McDonald, Veterinary endocrinology and reproduction Third edition. Very good for details of veterinary significance, text maybe over-detailed and hard to follow. Best & Taylor = Physiological basis of medical practice Ninth edition Chapter 7. Very good for Integration of growth and metabolism & pathophysiology of adrenals and thyroid. Dukes = Dukes, Physiology of domestic animals.12th Edition. The latest edition is up to date. Contains useful revision and self-evaluation material all is relevant to course. Sjaastad,Hove,Sand (Scand. Vet Press) Physiology of Domestic Animals. Chapter 5. Clear text and simple diagrams make this worth looking at. BSAVA Manual of Canine and Feline Endocrinology. Very clear concise text with clinical emphasis. 3rd edition available from 2005.

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