2. PROF. ASHRAF HUSAIN

3. Key concept for hypothalamic function is HOMEOSTASIS Its goal is to maintain internal homeostasis There are both neural and hormonal inputs to and outputs from the hypothalamus.

4. Where is the hypothalamus ? Anatomical Location: It consist of group of nuclei present in the floor of third ventricle (which lies between the two thalami) It is a very vascular structure so much so that the nuclei are floating in the blood.

6. Vital anatomical points It is a very small structure and comprises less than 1% of our brain volume Lines third ventricle right above the pituitary Divided into medial and lateral regions by fornix which is a tract of fibres that run from the hippocampus to the mamillary bodies

7. Limited at the anterior by the optic chiasm and anterior commissure Limited at the posterior by the mammillary bodies Hypothalamus is intimately connected to the amygdala which controls emotion

8. HYPOTHALAMIC NUCLEI I. ANTERIOR GROUP: I. ANTERIOR NUCLEUS II. LATERAL HYPOTHALAMIC NUCLEI III. PREOPTIC NUCLEI IV. PARAVENTRICULAR NUCLEI V. SUPRAOPTIC NUCLEUS VI. SUPRACHIASMATIC NUCLEUS

9. HYPOTHALAMIC NUCLEI II. MIDDLE GROUP (INFUNDIBULAR REGION) : I. MEDIAL NUCLEUS I. DORSOMEDIAL NUCLEI II. VENTROMEDIAL NUCLEI II. LATERAL HYPOTHALAMIC NUCLEI III. TUBERAL III. POSTERIOR GROUP : I. MAMMILLARY NUCLEUS II. LATERAL HYPOTHALAMIC NUCLEI III. POSTERIOR NUCLEUS

13. I.AUTONOMIC CONTROL II.TEMPERATURE REGULATION III.HYPOTHALAMIC CONTROL OF PITUTARY SECRETION THROUGH RELEASING OR INHIBITORY HORMONES IV.HYPOTHALAMIC PITUTARY RELATIONSHIP V.CONTROL OF HUNGER, FEEDING AND SATIETY VI.THIRST CONTROL VII.CONTROL OF BODY RHYTHM (CIRCADIAN) VIII.CONTROL OF SLEEP, FEAR AND RAGE IX.SEXUAL BEHAVIOUR HYPOTHALAMIC FUNCTION

16. Hypothalamic control of pituitary secretion

19. FEEDING AND SATIETY Food intake increased by(Lateral feeding centre) Neuropeptide Y Orexin A and B MCH (Melanin conc. Hormone) Ghrelin Food intake decreased by (Medial satiety centre Leptin Bombesin,CCK Somtostatin etc.

20. CONTROL OF FOOD INTAKE Four hypothesis for control of food intake Lipostatic hypothesis: adipose tissues emit humoral signals to the hypothalamus causing reduction in food intake Gut peptide hypothesis: food in GIT causes release of one or more polypeptides these signal the hypothalamus to reduce food intake

21. Glucostatic hypothesis: increased glucose utilization in hypothalamus produces a sensation of satiety Thermostatic hypothesis : reduction in body temperature below a certain level leads to increased appetite and an increased in body temperature above a certain level decreases appetite Leptin (from Adipocytes (fat cells)) this hormone acts on the hypothalamus to decrease food intake & increase energy consumption. It inhibits activity of Neropeptide Y neurons

22. Increase food intake, decreased energy expenditure FAT DEPOTS Increased fat deposition ↓ Increased leptin synthesis Increased plasma leptin concentration HYPOTHALAMUS Increased activation of Leptin receptors Solid arrows indicate stimulation; dashed arrows indicate inhibition

23. Control of hunger, feeding and satiety Hypothalamic regulation of appetite for food depends on the interaction of two areas 1. Feeding center: Site: lateral hypothalamic nucleus. Stimulation: voraciuos eating Lesion: loss of eating (fatal anorexia)

24. 2. Satiety Center: Site: Ventromedial nucleus Stimulation: cessation of eating Lesion: Hyperphagia eg. Hypothalamic obesity. Mechanism of hunger regulation Feeding center is mostly active and is transiently inhibited by activity in the satiety center. SATIETY CENTERFEEDING CENTER INHIBITS

26. SATIETY CENTER (GLUCOSTAT) If glucose utilization increases Feeding center inhibited Loss of appetiteIncrease Food Intake Feeding center unchecked If glucose utilization decreases

27. Thirst control Hypertonicity Osmoreceptors Hypovolumia Baroreceptors Angiotensin II Thirst

28. HYPERTONICITY STIMULATES OSMORECEPTORS SIGNALS HPOTHALAMUS STIMULATES THIRST HYPOVOLEMIA STIMULATES BARORECEPTORS AND ANGIOTENSIN II WHICH IN TURN STIMULATES THE HYPOTHALAMUS TO PRODUCE A THIRST SENSATION

29. Hypothalamic temperature regulating mechanism Thermoregulatory mechanism by the hypothalamus are basically reflex or semi reflex response.

30. BODY TEMPERATURE 1. INVERTEBRATES CANNOT ADJUST BODY TEMPERATURE AND IT DEPENDS ON ENVIRONMENT 2. VERTEBRATES BODY TEMPERATURE FLUCTUATES OVER A CONSIDERABLE RANGE DUE TO RUDIMENTARY BODY TEMPERATURE REGULATING MECHANISM POIKILOTHERMIC COLD BLOODED 3. MAN IS HOMEOTHERMIC AND MAINTAINS HIS BODY TEMPERATURE CONSTANT INSPITE OF WIDE VARIATIONS IN ENVIRONMENTAL TEMPERATURE WARM BLOODED

31. NORMAL BODY TEMPERATURE ORAL TEMPERATURE 37 DEGREES CENTIGRADE (98.6 DEGREES FAHRENHEIT) CORE TEMPERATURE(RECTAL TEMPERATURE) 0.5 DEGREES CENTIGRADE ABOVE ORAL TEMPERATURE SKIN TEMPERATURE LOWER THAN ORAL TEMPERATURE SCROTAL TEMPERATURE REGULATED AT 32 DEGREES CENTIGRADE

32. THE EXTREMITIES ARE COOLER THAN THE REST OF THE BODY FEET IS COOLER THAN HAND CORE TEMPERATURE VARIES LEAST WITH CHANGES IN ENVIRONMENTAL TEMPERATURE HYPERPYREXIA IS HIGH TEMPERATURE OVER 41DEGREES CENTIGRADE (106 DEGREES FAHRENHEIT) HYPOTHERMIA LOW BODY TEMPERATURE 3 DEGREES OR LESS

33. FACTORS NORMALLY AFFECTING TEMPERATURE 1. DIURNAL VARIATION 0.5 TO 0.7° C MOSTLY 2. LOWEST AT ABOUT 6 AM AND DURING SLEEP 3. AGE INFANT IRREGULAR AGED SUBNORMAL 1. RISE IN BASAL TEMPERATURE AT TIME OF OVULATION IN FEMALES 2. EXERCISE AS HIGH AS 40 ° C HAS BEEN RECORDED AFTER EXERCISE 3. EMOTION TEMPERATURE RISES DUE TO UNCONCIOUS TENSING OF THE MUSCLES

34. HYPERTHYROIDISM BMR INCREASES AND BODY TEMPERATURE INCREASES HYPOTHYROIDISM BMR DECREASES AND BODY TEMPERATURE DECREASES

35. MECHANISMS OF HEAT LOSS (% OF HEAT LOSS AT 21 DEGREE C) RADIATION AND CONDUCTION 70% VAPORIZATION OF SWEAT = 27% RESPIRATION = 2% URINATION AND DEFECATION =1% MECHANISMS OF HEAT GAIN BASIC METABOLIC PROCESSES FOOD INTAKE(SDA) MUSCULAR ACTIVITY

36. DURING A HOT HUMID DAY SWEAT SPREADS OVER THE SKIN THERE IS REDUCED EVAPORATION OF SWEAT PERSON FEELS HOT

37. AFFERENTS FOR TEMPERATURE CONTROL SENSORY COLD RECEPTORS: 1. SKIN 2. DEEP TISSUES 3. SPINAL CORD 4. EXTRAHYPOTHALAMIC PARTS OF BRAIN 5. HYPOTHALAMUS

38. THRESHOLD CORE TEMPERATURE FOR TEMPERATURE REGULATION RESPONSE THRESHOLDS (WHEN THRESHOLD IS REACHED RESPONSE BEGINS) - 35.5 DEGREES CENTIGRADE FOR SHIVERING - 36 DEGREES CENTIGRADE FOR NON SHIVERING THERMOGENESIS -36.8 DEGREES CENTIGRADE FOR VASOCONSTRICTION - 37 DEGREES CENTIGRADE FOR SWEATING & VASODILATATION

39. HEAT GAIN 1. METABOLISM 2. FOOD(SDA) 3. MUSCULAR ACTIVITY HEAT LOSS 1. CONDUCTION 2. CONVECTION 3. RADIATION 4. EVAPORATION SKIN,LUNGS 5. URINATION DEFECATION

40. BASAL METABOLISM 30 TO 40 KCAL PER SQ METER PER HOUR 1700 KCAL PER DAY MALE 1500 KCAL PER DAY FEMALE MODERATE ACTIVITY 2500 TO 3000 KCAL PER DAY HEAVY WORK 6000 KCAL PER DAY SHORT BURSTS OF SEVERE EXERCISE 10-16 TIMES BASAL LEVEL

41. SPECIFIC HEAT OF WATER ONE CALORIE RAISES THE TEMPERATURRE OF 1 GM WATER BY 1 DEGREE CENTIGRADE HENCE IF NO HEAT IS LOST OUR BODY TEMPERATURE WOULD RISE BY 1 DEGREE CENTIGRADE PER HOUR

42. HEAT LOSS BY EVAPORATION OF WATER THROUGH LUNGS AND SKIN INSENSIBLE PERSPIRATION PASSAGE OF WATER BY DIFFUSION THROUGH SKIN INSENSIBLE BECAUSE IT CANNOT BE SEEN OR FELT LUNGS ON AVERAGE WATER IS LOST FROM THE LUNGS IS ABOUT 300 ML/DAY AND EQUIVALENT HEAT IS NEARLY 200 KCAL

43. HEAT LOSS CONDUCTION HEAT LOSS BY DIRECT CONTACT CONVECTION THE AIR IN IMMEDIATE CONTACT WITH SKIN IS WARMED THE HEATED MOLECULES MOVE AWAY AND COOLER ONES COME IN TO TAKE THEIR PLACE AND SO ON RADIATION HOT OBJECTS EMIT INFRARED HEAT RAYS,IT DEPENDS ON SURFACE AREA DIFFERENCE OF TEMPERATURE BETWEEN THE SKIN AND THE SURROUNDING OBJECTS

44. SKIN LOSS INSENSIBLE PERSPIRATION IT IS ABOUT 600 TO 800 ML PER DAY EQUIVALENT TO HEAT LOSS OF 400 KCAL SWEATING : RISE OF TEMPERATURE CAUSES SWEATING SWEATING MAY BE UPTO 1.7 LITRES PER DAY. IT MAY BE THERMAL,EMOTIONAL EXERCISE, SYMPATHETIC OVERACTIVITY, GUSTATORY SWEATING

45. Skin (cold receptors) Increase Heat Production Shivering Hunger Increase Voluntary activity Increase secretion of Adrenalin, noradrenalin, TSH Cutaneous Vascular Counter current exchange. Posterior Hypothalamus Decrease Heat loss Cutaneous Vasoconstriction Curling up – decrease body surface area Above mechanisms results in raising the body temprature

46. Skin (Heat receptors) Increase Heat Loss Cutaneous vasodilatation Sweating Increase perspiration Anterior Hypothalamus Decrease Heat production Anorexia Apathy Inertia Above mechanisms results in decrease in the body temperature

47. FEVER THERMOSTAT HAS BEEN RESET TO NEW POINT ABOVE 37 DEGREES CENTIGRADE ACTUAL BODY TEMPERATURE IS BELOW NEW SET POINT LEADS TO INCREASED TEMPERATURE RAISING MECHANISM CHILLY SENSATION DUE TO CUTANEOUS VASOCONSTRICTION AND SHIVERING

48. PATHOGENESIS OF FEVER ENDOTOXINS CYTOKINES PRODUCTION (PGE2) LOCAL RELEASE OF PROSTAGLANDIN IN HYPOTHALAMUS ASPIRIN REDUCES PG SYNTHESIS

49. PATHOGENESIS OF FEVER

50. BENEFITS OF FEVER BENEFICIAL RESPONSE TO INFECTION AND OTHER DISEASES eg.(ANTHRAX,PNEUMONIA) INCREASE IN TEMPERATURE REDUCES BACTERIAL GROWTH INCREASE IN TEMPERATURE INCREASES ANTIBODY PRODUCTION SLOWS THE GROWTH OF SOME TUMORS) VERY HIGH TEMPERATURE ARE HARMFUL

51. HYPERTHERMIA TEMPERATURE > 41 DEGREES CENTIGRADE (106 ° F) FOR PROLONGED PERIODS RESULTS IN PERMANENT BRAIN DAMAGE OVER 43 DEGREES CENTIGRADE eg. HEAT STROKE DEVELOPS & CAUSES DEATH

52. MALIGNANT HYPERTHERMIA GENE MUTATION CAUSING INCREASED CALCIUM RELEASE DURING MUSCULAR CONTRACTION DUE TO STRESS MUSCLE METABOLISM IS INCREASED IN THIS CONTRACTED STATE THIS CAUSES AN INCREASE IN HEAT PRODUCTION IN MUSCLE AND MARKED RISE IN BODY TEMPERATURE AND MAY BE FATAL IF NOT TREATED

53. OTHER IMPORTANT DISORDERS OF TEMPERATURE HEAT STROKE HEAT EXHAUSTION (CIRCULATORY DEFICIENCY WITH DEHYDRATION AND SALT DEFICIENCY HYPOTHERMIA

54. SKIN OR BLOOD IS COOLED LEADING TO REDUCED METABOLIC RATE AND PHYSIOLOGICAL PROCESS HEART RATE BP AND RESPIRATORY RATE REDUCES AS RECTAL TEMPERATURE REACHES 28 DEGREES CENTIGRADE THE ABILITY TO SPONTANEOUSLY RETURN TO NORMAL TEMP IS LOST IF PERSON SURVIVES THEN REWARMING RETURNS TO NORMAL STATE

55. HUMANS TOLERATE BODY TEMPERATURE LOWS OF 21 TO 24 DEGREES CENTIGRADE CERTAIN SURGERIES ARE DONE UNDER INDUCED HYPOTHERMIAS