Hypothalamus and Its Connections PDF

THE NEUROENDOCRINE SYSTEM MELDI A. ANUTA, M.D., FPNA, FPCP Davao Medical School Foundation  CHAPTER OBJECTIVES To learn the location and boundaries of the hypothalamus & the various nuclei that make up this important area To review the main connections of the nuclei,...

THE NEUROENDOCRINE SYSTEM MELDI A. ANUTA, M.D., FPNA, FPCP Davao Medical School Foundation  CHAPTER OBJECTIVES To learn the location and boundaries of the hypothalamus & the various nuclei that make up this important area To review the main connections of the nuclei, especially the connections between the hypothalamus & the pituitary gland To review some of the common clinical problems involving the hypothalamus  INTRODUCTION THE HYPOTHALAMUS PLAYS A KEY ROLE IN THE NEUROENDOCRINE SYSTEM BY VIRTUE OF ITS CONNECTION TO THE PITUITARY GLAND. THE PITUITARY HORMONES ARE INFLUENCED BY RELEASING HORMONES PRODUCED BY THE HYPOTHALAMUS.  ADDENDUM The case that follows is one of the cases that involve the Neuroendocrine system. There are other cases - e.g. Diabetes insipidus; uncontrolled milk production etc.  CASE A 16-year-old girl Rapidly weight loss (1 year) Very choosy eater (claims she was getting fat & must diet) Personality change Fear of strangers Impatience & irritability Cessation of menstruation for 3 months  CASE Calorie counting (forcibly forced self to vomit) Obvious signs of weight loss with hollow facial features, prominent bones, and wasted buttocks Cold extremities & low blood pressure of 85/60 mm Hg No further abnormalities discovered  CASE DIAGNOSIS : Anorexia nervosa MANAGEMENT : Admitted Psychologic treatment Primary treatment is to restore the patient's weight by persuading the individual to eat adequate amounts of food.  THE HYPOTHALAMUS 0.3% of the total brain Controls the ANS & the endocrine system and thus indirectly controls body homeostasis Lies in the center of the limbic system  ADDENDUM IMAGINE THE HYPOTHALAMUS AS A MINUSCULE STRUCTURE AT THE CENTER OF THE BRAIN. SMALL AS IT IS, IT PLAYS A VITAL ROLE BECAUSE IT CONTROLS AND INFLUENCES THE MASTER GLAND.  HYPOTHALAMUS ONE OF THE MOST IMPORTANT OUTPUT CONTROL PATHWAYS OF THE LIMBIC SYSTEM CONTROLS MOST OF THE VEGETATIVE AND ENDOCRINE FUNCTIONS OF THE BODY AS WELL AS MANY ASPECTS OF EMOTIONAL BEHAVIOR Adams & Victor’s Principles of Neurology 12th edition  LOCATION & RELATED STRUCTURES part of the diencephalon that extends from the region of the optic chiasma to the caudal border of the mammillary bodies Below the thalamus & forms the floor & the inferior part of the lateral walls of the third ventricle Caudally, merges into the tegmentum of the midbrain Lateral boundary - Internal capsule  PREOPTIC AREA an area anterior to the hypothalamus that, for functional reasons, is often included in the hypothalamus extends forward from the optic chiasma to the lamina terminalis & the anterior commissure  RELATED STRUCTURES (ANTERIOR TO POSTERIOR) OPTIC CHIASM TUBER CINEREUM & INFUNDI- BULUM MAMMILLARY BODIES  THE HYPOTHALAMIC NUCLEI Small nerve cells that are arranged in groups or nuclei For functional reasons, includes the preoptic area Divided into medial and lateral zones (markers : columns of the fornix & the mammillothalamic tract) Coronal section of the cerebral hemispheres showing the position of the hypothalamic nuclei  paraventricular periventricular dorsomedial fornix Lateral hypothalamic ventromedial Optic tract supraoptic arcuate Sagittal section of the brain showing the hypothalamic nuclei. A: Medial zone nuclei lying medial to the plane of the fornix and the mammillothalamic tract. B: Lateral zone nuclei lying lateral to the plane of the fornix and the mammillothalamic tract.  MEDIAL ZONE – ANTERIOR TO POSTERIOR 1) part of the preoptic nucleus 2) the anterior nucleus, which merges with the preoptic nucleus 3) part of the suprachiasmatic nucleus 4) the paraventricular nucleus 5) the dorsomedial nucleus 6) the ventromedial nucleus 7) the infundibular (arcuate) nucleus 8) the posterior nucleus LATERAL ZONE – ANTERIOR TO POSTERIOR 1) part of the preoptic nucleus 2) part of the suprachiasmatic nucleus 3) the supraoptic nucleus 4) the lateral nucleus 5) the tuberomammillary nucleus 6) the lateral tuberal nuclei Some of the nuclei overlap both zones.  HYPOTHALAMIC LINES OF COMMUNICATION (1) nervous connections (2) the bloodstream (3) cerebrospinal fluid  AFFERENT NERVOUS CONNECTIONS PATHWAY ORIGIN DESTINATION Medial and spinal lemnisci, tractus Viscera and somatic Hypothalamic nuclei solitarius, reticular formation structures Visual fibers Retina Suprachiasmatic nucleus Medial forebrain bundle Olfactory mucous Hypothalamic nuclei membrane Auditory fibers Inner ear Hypothalamic nuclei Corticohypothalamic fibers Frontal lobe of cerebral Hypothalamic nuclei cortex Hippocampohypothalamic fibers; Hippocampus Nuclei of mammillary possibly main output pathway of body limbic system Amygdalohypothalamic fibers Amygdaloid complex Hypothalamic nuclei Thalamohypothalamic fibers Dorsomedial and Hypothalamic nuclei midline nuclei of thalamus Tegmental fibers Tegmentum of midbrain Hypothalamic nuclei Sagittal section of the brain showing the main afferent pathways entering the hypothalamus EFFERENT NERVOUS CONNECTIONS It contains two main efferent fiber systems—the mammillotegmental tract and the mammillothalamic tract of Vicq d’Azyr (named for the physician to Louis XV and XVI, a paramour of Marie Antoinette), which connects the mammillary nuclei with the anterior thalamic nucleus. Adams & Victor’s Principles of Neurology 12th edition  EFFERENT NERVOUS CONNECTIONS PATHWAY ORIGIN DESTINATION Descending fibers in reticular Preoptic, anterior, posterior, Craniosacral formation to brainstem and and lateral nuclei of parasympathetic and spinal cord hypothalamus thoracolumbar sympathetic outflows Mammillothalamic tract Nuclei of mammillary body Anterior nucleus of thalamus; relayed to cingulate gyrus Mammillotegmental tract Nuclei of mammillary body Reticular formation in tegmentum of midbrain Multiple pathways Hypothalamic nuclei Limbic system Sagittal section of the brain showing the main efferent pathways leaving the hypothalamus  Connections of the Hypothalamus With the Hypophysis Cerebri 1) nerve fibers that travel from the supraoptic & paraventricular nuclei to the posterior lobe of the hypophysis 2) long & short portal blood vessels that connect sinusoids in the median eminence & infundibulum with capillary plexuses in the anterior lobe of the hypophysis Hypothalamohypophyseal Tract The hormones VASOPRESSIN and OXYTOCIN are synthesized in the nerve cells of the supraoptic and paraventricular nuclei. The hormones are passed along the axons together with carrier proteins called NEUROPHYSINS and are released at the axon terminals. Here, the hormones are absorbed into the bloodstream in fenestrated capillaries of the posterior lobe of the hypophysis.  VASOPRESSIN Antidiuretic hormone Produced in the supraoptic nucleus Function – vasoconstriction Antidiuretic function - increased absorption of water in the distal convoluted tubules & collecting tubules of the kidney  ADDENDUM A RELATIVELY COMMON CLINICAL SCENARIO INVOLVING ADH IS THE DEVELOPMENT OF DIABETES INSIPIDUS IN PATIENTS WHO HAVE UNDERGONE PITUITARY SURGERY. WITH LOSS OF POSTERIOR PITUITARY CONNECTION, THERE IS UNCONTROLLED DIURESIS OF DILUTE URINE DUE TO FAILURE OF CONTROLLING FLUID AND ELECTROLYTE REABSORPTION IN THE RENAL TUBULES.  OXYTOCIN Produced mainly in the paraventricular nucleus Stimulates the contraction of the smooth muscle of the uterus Causes contraction of the myoepithelial cells that surround the alveoli & ducts of the breast  The supraoptic nucleus, which produces vasopressin, acts as an OSMORECEPTOR. Should the osmotic pressure of the blood circulating through the nucleus be too high, the nerve cells increase their production of vasopressin, and the antidiuretic effect of this hormone will increase the reabsorption of water from the kidney. By this means, the osmotic pressure of the blood will return to normal limits.  Hypophyseal Portal System Neurosecretory cells situated mainly in the medial zone of the hypothalamus are responsible for the production of the releasing hormones & release-inhibitory hormones. The hormones are packaged into granules & are transported along the axons of these cells into the median eminence & infundibulum. Here, the granules are released by exocytosis onto fenestrated capillaries at the upper end of the hypophyseal portal system.  The Hypothalamic Releasing & Inhibitory Hormones Hypothalamic Regulatory Anterior Pituitary Hormone Hormone Functional Result Growth hormone–releasing Growth hormone (GH) Stimulates linear growth hormone (GHRH) in epiphyseal cartilages Growth hormone–inhibiting Growth hormone (reduced Reduces linear growth in hormone (GHIH) or production) epiphyseal cartilages somatostatin Prolactin-releasing hormone Prolactin (luteotropic Stimulates lactogenesis (PRH) hormone, LTH) Prolactin-inhibiting hormone Prolactin (luteotropic Reduces lactogenesis (PIH), dopamine hormone, LTH) (reduced production) Corticotropin-releasing hormone Adrenocorticotropic hormone Stimulates adrenal gland (CRH) (ACTH) to produce corticosteroids and sex hormones Thyrotropin-releasing hormone Thyroid-stimulating hormone Stimulates thyroid gland (TRH) (TSH) to produce thyroxine Luteinizing hormone–releasing Luteinizing hormone (LH) Stimulates ovarian follicles hormone (LHRH), ? follicle- and follicle-stimulating and production of stimulating releasing hormone hormone (FSH) estrogen and (FRH) progesterone  HYPOTHALAMIC FUNCTIONS AUTONOMIC CONTROL ENDOCRINE CONTROL NEUROSECRETION TEMPERATURE REGULATION REGULATION OF WATER & FOOD INTAKE EMOTION & BEHAVIOR CONTROL OF CIRCADIAN RHYTHMS VEGETATIVE FUNCTIONS OF THE HYPOTHALAMUS CARDIOVASCULAR BODY TEMPERATURE BODY WATER UTERINE CONTRACTION AND MILK EJECTION GASTROINTESTINAL FUNCTIONS AND FEEDING  The hypothalamus has a controlling influence on the autonomic nervous system & appears to integrate the autonomic & neuroendocrine systems, thus preserving body homeostasis. Essentially, the hypothalamus should be regarded as a higher nervous center for the control of lower autonomic centers in the brainstem & spinal cord.  Electrical stimulation of the hypothalamus shows that the anterior hypothalamic area & the preoptic area influence parasympathetic responses; these include lowering of the blood pressure, slowing of the heart rate, contraction of the bladder, increased motility of the gastrointestinal tract, increased acidity of the gastric juice, salivation, and pupillary constriction.  Stimulation of the posterior & lateral nuclei causes sympathetic responses which include elevation of blood pressure, acceleration of the heart rate, cessation of peristalsis in the gastrointestinal tract, pupillary dilation, & hyperglycemia. ??? Parasympathetic & sympathetic centers  ENDOCRINE CONTROL The nerve cells of the hypothalamic nuclei control the hormone production of the anterior lobe of the hypophysis (pituitary gland). Growth hormone Prolactin (luteotropic hormone) Adrenocorticotropic hormone Thyroid-stimulating hormone Luteinizing hormone Follicle-stimulating hormone  Some of these hormones act directly on body tissues. Others act through an endocrine organ, which produces additional hormones that influence the activities of tissues. Negative & positive feedback mechanisms  Functions of the Main Hypothalamic Nuclei Supraoptic nucleus Synthesizes vasopressin (antidiuretic hormone) Paraventricular nucleus Synthesizes oxytocin Preoptic and anterior nuclei Control parasympathetic system Posterior and lateral nuclei Control sympathetic system Anterior hypothalamic nuclei Regulate temperature (response to heat) Posterior hypothalamic nuclei Regulate temperature (response to cold) Lateral hypothalamic nuclei Initiate eating and increase food intake (hunger center) Medial hypothalamic nuclei Inhibit eating and reduce food intake (satiety center) Lateral hypothalamic nuclei Increase water intake (thirst center) Suprachiasmatic nucleus Controls circadian rhythms  TEMPERATURE REGULATION Anterior portion - mechanisms that dissipate heat loss (dilatation of skin blood vessels & sweating, which lower the body temperature). Posterior portion - vasoconstriction of the skin blood vessels & inhibition of sweating; there also may be shivering, in which the skeletal muscles produce heat Body temperature at 98.0°F to 98.6°F when measured orally and 1° higher rectally REGULATION OF FOOD & WATER INTAKE Stimulation of the lateral region -hunger / increase in food intake (hunger center) - Bilateral destruction results in anorexia Stimulation of the medial region - inhibits eating & reduces food intake (satiety center) - Bilateral destruction results in uncontrolled voracious appetite Stimulation of other areas in the lateral region of the hypothalamus - immediate increase in the desire to drink water (thirst center)  prefrontal cortex EMOTION & BEHAVIOR hypothalamus limbic system  The hypothalamus is believed to be the integrator of afferent information received from other areas of the nervous system & brings about the physical expression of emotion. Increase the heart rate Elevate the blood pressure Cause dryness of the mouth, flushing or pallor of the skin, & sweating Can produce a massive peristaltic activity  Stimulation of the lateral hypothalamic nuclei may cause the symptoms and signs of rage, whereas lesions of these areas may lead to passivity. Stimulation of the ventromedial nucleus may cause passivity, whereas lesions of this nucleus may lead to rage.  Lesions of the anterior part of the hypothalamus seriously interfere with the rhythm of sleeping and waking. The suprachiasmatic nucleus, which receives afferent fibers from the retina, appears to play an important role in controlling the biologic rhythms. Nerve impulses generated in response to variations in the intensity of light are transmitted via this nucleus to influence the activities of many of the hypothalamic nuclei. CONTROL OF CIRCADIAN RHYTHMS body temperature adrenocortical activity eosinophil count renal secretion Sleeping and wakefulness, although dependent on the activities of the thalamus, the limbic system, & the RAS, are also controlled by the hypothalamus. HYPOTHALAMIC SYNDROMES Global hypothalamic syndrome Sarcoidosis Histiocytosis X (Letterer-Siwe disease, HandSchüller-Christian disease, & eosinophilic granuloma Erdheim-Chester disease Idiopathic lymphocytic hypophysitis Tumors (metastatic carcinoma, lymphoma, craniopharyngioma, & a variety of germ-cell tumors, including germinomas, teratomas, embryonal carcinoma, & choriocarcinoma) Irradiation Adams & Victor’s Principles of Neurology 12th edition HYPOTHALAMIC SYNDROMES Disorders of sodium & fluid homeostasis DI SIADH Cerebral salt wasting (Nelson syndrome) Disorders of puberty Precocious puberty Failure of puberty Adiposogenital Dystrophy (Froehlich Syndrome) Adams & Victor’s Principles of Neurology 12th edition HYPOTHALAMIC SYNDROMES Disorders of weight Prader-Willi syndrome (obesity, hypogonadism, hypotonia, mental retardation, & short stature) Septooptic dysplasia (de Morsier syndrome) (optic atrophy , absence of the septum pellucidum, hypothalamic dysfunction, heterotopias) Idiopathic hypopituitarism Dwarfism Acromegaly Gigantism Anorexia nervosa & Bulimia Diencephalic syndrome of Russel Adams & Victor’s Principles of Neurology 12th edition HYPOTHALAMIC SYNDROMES Systemic effects Disturbances of temperature regulation Malignant hyperthermia Neuroleptic malignant syndrome Cardiovascular disorders Gastric complications Neurogenic pulmonary edema Disorders of consciousness & personality Periodic Somnolence & Bulimia (Kleine- Levin Syndrome) Adams & Victor’s Principles of Neurology 12th edition HYPOTHALAMIC SYNDROMES Neuroendocrine Syndromes Related to the Adrenal Glands Cushing Disease & Cushing Syndrome Adrenocortical insufficiency (Addison’s disease) Adams & Victor’s Principles of Neurology 12th edition THANK YOU