Hypothalamus Roy Bachar, class of 2006

Transcription

1 Hypothalamus Roy Bachar, class of 2006

2 Learning Objectives 1. Describe the parts of the pituitary gland and how it communicates with the hypothalamus. 2. Describe the functions of the hypothalamus and effects of lesions: control of ADH, oxytocin, vasopressin control of circadian rhythms control of body temperature control of appetite

3 Overview 1. The hypothalamus controls homeostatic functions such as body temp, water intake, feeding, circadian rhythms. 2. The hypothalamus controls these functions by connections with: the pituitary gland autonomic centers in the brainstem and spinal cord. Chris Cohan, Ph.D. Dept. of Pathology/Anat Sci Jacobs School of Medicine

4 Hypothalamus Functions Monitors body conditions Hormone levels Light (time of day) Thirst (blood osmolality) Body temperature Appetite Adjusts body conditions

5 Hypothalamus Functions Monitors body conditions Hormone levels Light (time of day) Thirst (blood osmolality) Body temperature Appetite Adjusts body conditions hormone secetion metabolism, sleep water retention cool or heat eat or not

6 Hypothalamus Functions Cortex Awareness of needs Emotional status thirsty, hungry, cold, hot Monitored conditions Hypothalamus ANS Symp Parasymp adjust visceral organs BP, heart rate, sweating Endocrine hormone release via pituitary metabolism, water retention

7 Hypothalamus Violates BBB! Monitor components in blood and secrete hormones areas must lack BBB some hypothalamic nuclei chemosensory median eminence of hypothalamus posterior pituitary pineal gland neurosecretory

8 Function Nuclei Deficit Endocrine supraoptic paraventricular arcuate periventricular preoptic Metabolic, growth, response to stress, gonad function Water intake Circadian Rhythm Memory Supraoptic paraventricular Diabetes insipidus hyper/hypo Na + /K + suprachiasmatic Lose daily rhythm of metabolism, hormones, behavior mammillary bodies Memory consolidation Body Temp Appetite anterior posterior ventromedial lateral, arcuate body temp ß body temp overeating/obesity ß starvation/anorexia

9 Hypothalamus Location At the base of the hemisphere w borders: midbrain, thalamus, 3rd ventricle, optic chiasm It has connections with cortex - emotional/visceral pituitary - endocrine control brainstem spinal cord Parasympathetic NS Sympathetic NS

10 Hypothalamic Symptoms Symptoms: autonomic (body temp), feeding (obesity/starvation), sleep, endocrine (thirst, menstrual), emotional (aggressiveness, sexual), memory 20 year-old bookkeeper with bifrontal headaches, polydipsia, polyuria, no menses for 10 months. Later: unprovoked laughter, crying, rage, insatiable appetite, variable temp year-old woman unconscious after falling down stairs and hitting head. On day 4: blood osmolality declined and sodium levels became unstable. 52 year-old man developed chills on 85 summer day. Admission: 103 shivering not sweating, bitemporal hemianopia.

11 Control of Endocrine Function Hypothalamus communicates with the pituitary gland in the release of hormones via neurosecretory cells. Hypothalamus pituitary hormone release

12 Pituitary and Hypothalamus chiasm Pituitary has a anterior and posterior lobe Highly vascularized - Superior and Inferior Hypophyseal arteries form several capillary beds. No BBB Proximity to optic chiasm bitemporal hemianopia!

13 Pituitary Development Forms from 2 parts: Brain + Pharynx 1. extension of diencephalon (hypothalamus) 2. outgrowth of pharynx (Rathke s Pouch) Anterior pituitary Adenohypophysis Gland Posterior pituitary Neurohypophysis CNS

14 1A. Endocrine Functions Anterior Pituitary Monitor hormone levels in blood Axons from arcuate, periventricular nuclei release hypophysiotropic hormones into capillary bed in proximal part of infundibular stalk and median eminence. Hormones travel down hypophyseal portal vessels to second capillary bed in anterior pituitary where they promote or inhibit the release of other hormones from anterior lobe pituitary cells.

15 Hypophysiotropic Hormones GHRH Somatostatin (-) CRH TRH Somatostatin (-) GnRH GnRH TRH, VIP Dopamine (-) Ant Pituitary Hormones Growth Hormone (GH) Adrenocorticotropic Hormone (ACTH) Thyroid Stimulating Hormone (TSH) Follicle Stimulating Hormone (FSH) Luteinizing Hormone (LH) All cells Target Adrenal cortex Thyroid Gonads Gonads Some Actions Stim growth, protein synthesis Cortisol secretion Iodine, hormonogenesis, T3, T4 Ovulation, spermatogenesis Ovary/sperm maturation Prolactin (PRL) Mammary Glands Milk production Dopamine acts as a hormone on anterior pituitary to inhibit prolactin secretion. Antipsychotic meds - D2 receptor blockers!

16 1B. Control of Water Intake Posterior Pituitary Supraoptic and paraventricular nuclei monitor blood osmolality send axons to posterior lobe where they release antidiuretic hormone (ADH) and oxytocin near capillaries. Hormones enter the systemic circulation. These neuropeptides are synthesized in the cell body and transported to terminals where they are stored. Action potentials control their release based on Ca influx in terminals. ADH - increases reabsorption of water by the kidney; also a vasoconstrictor Oxytocin - contraction of uterine smooth muscle during childbirth and contraction of mammary smooth muscle for milk ejection

17 1B. Control of Water Intake Posterior Pituitary SIADH syndrome of inappropriate ADH secretion caused by some tumors, drug side effects (carbamazepine) excess water retention leads to hyponatremia Diabetes Insipidis - Bilateral lesions cause inability to reabsorb water by kidney (excessive water excretion).

18 2. Sleep and Other Acivities are Controlled by a Brain CLOCK Suprachiasmatic Nuc- brain s circadian clock physiologic and metabolic activities rise and fall daily: body temp, blood flow, hormone levels, metabolic rate, alertness. Axons from the retina synapse in SCN where electrical activity oscillates spontaneously with 24 hr periodicity. Activity of single neurons from SCN Light entrains activity

19 2. Brain CLOCK SCN Hypothalamic nuc Sympathetic NS pineal Pituitary Pineal hormone secretion Melatonin secretion (Promotes sleep Affects brainstem Antigonadotropic)

20 3. Memory Function Mammillary Body - involved in memory by connections with the hippocampus Bilateral lesions affect memory consolidation Wernicke s Encephalopathy - thiamine deficiency

21 4. CVS - BP, contractility Stress, anxiety, anger, fear, joy can alter cardiovascular function by connections between cortex and hypothalamus, which controls CV centers in medulla. Hypothalamus influences autonomic centers - + from Dr. Hogan

22 5. Response to Hypoglycemia Hypothalamus monitors serum glucose level. Low glucose hypothalamus Pituitary ACTH cortisol growth hormone ANS Adrenal Epi release

23 Functions controlled by pairs of nuclei with opposing effects Body Temperature Appetite

24 6. Control of Body Temp ANS: vasoconstrict Endo: thyroid Behavioral Defended Variable room temperature Effector(s) furnace posterior nuc air conditioner anterior nuc Sensor thermometer monitors blood temp from Dr. Hogan thermostat Controller Set point 98.6

25 6. Control of Body Temp Anterior Nuc - body temp (A/C) Posterior Nuc - body temp Temperature-sensitive neurons monitor blood temp. Activate Anterior Nuc or Posterior Nuc. Ant Nuc Post Nuc Hormonal metabolism metabolism Visceral vasodilate vasoconstrict, erector pilli Somatic sweat shiver Bilateral lesions of Anterior Nuc - overheating, shivering Bilateral lesions of Posterior Nuc - lower body temp, sweating Immature at birth - need to keep infants warm/dry!

26 7. Control of Appetite Brain regulates food intake through integrated input/output control: 1. Integrated afferent information Endocrine signals from adipose tissue and gut hypothalamus Autonomic signals from gut vagus medulla Behavioral psychosocial factors (cortical) 2. Integrated efferent response Hormonal changes in metabolism distension I like to eat when ghrelin Autonomic sympathetic/parasympathetic activity to gut (secretion, motility) Somatic motivational changes for eating Disorders in control lead to obesity, anorexia, and associated complications.

27 7. Control of Appetite Cortex Am I hungry or full? Caudal Brainstem Solitary Tract Nucleus Hypothalamus (melanocortin system) Arcuate Nuc ventromedial nuc BBB lateral nuc others Taste CN VII, IX, X GI Signals - CN X distension, CCK Cranial Nerves (autonomic) Adipose Tissue Leptin Gut Hormones insulin, ghrelin etc Hormonal (endocrine)

28 7. Control of Appetite Cortical Hormonal Brainstem SIGNALS Arcuate Nucleus Ventromedial Nuc Lateral Nuc Controlled by balanced activity of 2 nuclei. Ventromedial Nuc - Lateral Nuc - appetite (satiety center) appetite (hunger center) Bilateral lesions of Ventromedial Nuc - overeating/obesity Bilateral lesions of Lateral Nuc - anorexia/starvation

29 7. Eating Disorders 1) Recent experiments in mice have identified an area that controls binge eating behavior. (Science 356:853) 2) Prader-Willi and Angelman Syndromes are 2 closely related genetic disorders: Result from loss of function mutation on chromosome 15 Both involve similar regions on chromosome 15 PWS is due to a LOF on the paternal chromosome AS is due to a LOF on the maternal chromosome Although similar regions/genes are involved, different clinical deficits result.

30 7. Prader-Willi Syndrome One of the top 10 genetic defects (1:14,000) Involves obesity (loss of appetite control), stunted growth, delayed sexual development, psychiatric problems (OCD), hypotonia Continuous urge to eat/insatiable appetite inevitably leads to obesity, diabetes Genetic defect probably involves VM dysfunction