Endocrine System PDF

Endocrine System It contains glands with no ducts, but their hormones are carried directly to the blood by blood sinusoids or fenestrated blood capillaries. It includes: 1-Glands: e.g: pituitary, supra renal, thyroid,parathyroid &pineal body. 2-Masses of cells: e.g:ovary,testis,thymus,…. 3-Scattered...

Endocrine System It contains glands with no ducts, but their hormones are carried directly to the blood by blood sinusoids or fenestrated blood capillaries. It includes: 1-Glands: e.g: pituitary, supra renal, thyroid,parathyroid &pineal body. 2-Masses of cells: e.g:ovary,testis,thymus,…. 3-Scattered cells: all over the body:e.g.:APUD. - Hormones are: Chemical substances Secreted by special cells Affect distant organs They regulate the biochemical reactions in the body They regulate the processes of the body as the growth, maturation , regeneration & reproduction Chemical structure of hormones: Protein (polypeptide) hormones Steroid hormones Amino acid hormones 1- Hormones secreted by anterior pituitary 1- Adrenal cortex hormones - Thyroxine - FSH (follcle stimulating hormone) - Cortisol - Adrenaline - TSH (thyroid stimulating hormone) - Aldosterone - Noradrenaline - ACTH (adrinocorticotrophic hormone) 2- Gonadal hormones - LH (leutinizing hormone) - Ovary: - PRL (prolactin) - Estrogen - GH (growth hormone) - Progesterone 2- Hormone secreted by posterior pituitary - Testes : - ADH Testosterone - OXYTOCIN 3- Insulin & glucagon (pancreas) 4- Parathyroid hormone 5- Hypothalamic hormones 6- Calcitonin hormone Interrelation between the endocrine system & the Nervous system Hypothalamo - Hypophyseal portal circulation Hypothalamo – Hypophyseal tract - Blood system (vascular connection ) - Nervous connection - Connect between hypothalamus and anterior - Connect between hypothalamus and posterior pituitary pituitary - Carry Releasing & Inhibiting hormones - Carry the 2 hormones formed in the secreted from the hypothalamus to affect anterior hypothalamus pituitary ADH----in Supraoptic nucleus - ex TSH ---thyroid stimulating hormone Oxytocin—in paraventricular nucleus in FSH ---follicle stimulating hormone hypothalamus ACTH ---adrinocorticotrophic hormone to Posterior pituitary to be stored then released - Mechanism of action of hormones: - The hormone to exert its action should BIND to RECEPTOR - The receptors of hormones are: 1- Large proteins 2- Specific receptor for single hormone (key and lock) 1  3- Located either on: - Surface of cell -----for protein hormones - Cytoplasm----------for steroid hormones - Nucleus-------------for thyroid hormones 4- They are dynamic - May increase --- up regulation --- decrease hormone level - May decrease --- down regulation --- increase hormone level. - Mechanism of action of hormones: According to chemical nature of hormone: 1- Protein hormones & polypeptides, glycoprotein hormones (NON GENOMIC action): - The hormone is named (1st messenger) - Hormone combine with receptor on cell membrane (protein can not cross cell membrane) form hormone receptor complex the hormone receptor complex act through 2nd messenger formed which may be: Adenyl cyclase -- c-AMP Inositol- diacyl glycerol 2nd messenger c-GMP 2nd 2nd messenger system system messenger Hormone + receptor Hormone + receptor ↓ Receptor bind to G protein Activates enzyme PHOSPHOLIPASE – C ↓ G protein activates ADENYL CYCLASE enzyme This enzyme increase break down of ↓ phospholipid in the cell membrane into two ++++ transformation of ATP to 2nd messengers c-AMP IP3 , & DAG (2nd messenger) (cause the effect) ↓ 1- Inositol tri phosphate (IP3) c-AMP activates PROTEIN KINASE Increase mobilization of Ca++ from ↓ mitochondria & endoplasmic reticulum Phosphorylates proteins in cell (it perform the effect) (add phosphate group to it) Change chemical reactions 2- Di acyl glycerol (DAG) Cause the effect Activate protein kinase C ↓ Phosphodiestrase break Protein kinase C phosphorylates proteins c-AMP to AMP 2-Steroid hormones - (GENOMIC action ---- activate the GENES to inrease protein formation ----form action of hormone). - Steroid hormone pass cell membrane bind to receptor in the cytoplasm to form hormone receptor complex the complex enter the nucleus get incorporated with the DNA cause transcription of DNA & form mRNA-(2nd messenger mRNA –cause protein formation---form hormone action 3-Thyroid hormone (GENOMIC action): - They are very small and can pass cell membrane so they pass cell membrane & nuclear membrane - Bind to receptor in nucleus - Increase transcription of DNA to form mRNA (2nd messenger) - Increase protein formation---form hormone action 2 - Feed back control of hormones: - Def: It is the mechanism by which the ENDOCRINE system MAINTAIN the LEVEL of the HORMONE secreted by certain gland CONSTANT in blood. - Negative feed back: - If the HORMONE level INCREASE in blood ---- the HORMONE inhibit the GLAND to decrease its secretion. - Types of negative feed back: Short –short loop Short loop Long loop (Ultra short) Hormone inhibit itself Hormone inhibit its releasing Hormone inhibit hypothalamus hormone and pituitary - Positive feed back: - Increase the LEVEL of hormone -----stimulate secretion of the other hormone. - Eg increase estrogen ----- increase LH 3  Development of pituitary Pituitary gland Quizlet / Ditki / Research gate ANATOMY OF THE PITUITARY GLAND Embryological preview: It develops from two sources; Rathke’s pouch (at the roof of stomodeum or future mouth) and infundibulum (at the floor of diencephalon or future hypothalamus). Rathke’s pouch grows towards the diencephalon. The part connecting it to the stomodeum disappears, while the cranial part enlarges forming ant lobe of pituitary. An extension from the floor of diencephalon descends to meet the pouch and forms the post lobe of pituitary. The infundibulum between the diencephalon and the pituitary remains containing the nerve fibers connecting both. ❖ It is the Master of the endocrine gland, measuring 12 X 8 X 6 mm and weighting 0.5 gm ❖ The pituitary gland is connected to the hypothalamus by a stalk passing through the diaphragma sellae Relations: it lies in the pituitary fossa with the following relations: Ant: tuberculum sellae. Post: dorsum sellae. Sup: diaphragma sellae and optic chiasma Inf: sphenoid air sinuses. Lat: cavernous venous sinus. 4 - Histology of the pituitary gland A- Adenohypophysis: - Adenohypophysis: (Pars distalis, Pars tuberalis &Pars intermedia). B- Neurohypophysis: Neurohypophysis: It includes Pars nervosa, & Infundibulum. Pituitary gland I) Pars distalis - It is formed of cells classified into 2 groups: Chromophobes & Chromophils. Chromophobes (52%): - Small cells with pale cytoplasm which has mild affinity for stains. - Some cells are granular may secrete hormones. - Some cells are non granular & are considered as stem cells. Chromophils (48%) They are classified into: A) Acidophils (37%). B) Basophils(11%) A) Acidophils (37%) - They are medium sized cells between chromophobes &basophils Cell type a) Somatotrophs b) Mammotrophs Hormone - Growth hormone (If increased before closure of epiphysis, it causes gigantism, if after closure, it causes Prolactin (Milk secretion) acromegaly. - If it decreased, it causes dwarfism. L.M. - Spherical cells with central rounded Oval cells with oval nuclei & nuclei &acidophilic granules. acidophilic granules E.M. Golgi, mitochondria, rER & secretory Mitochondria, golgi, rER, granules secretory graules which enlarge during pregnancy & lactation Orange G Special (Orangeophil) Carmine (Carminophil) stain 5  B) Basophils (11%) They are the largest cells classified into 3 types: Cell type Thyrotrophs Corticotrophs Gonadotrophs Hormones TSH (Thyroid ACTH FSH LH stimulating (Adrenocorticotrphic secreting secreting hormone), T3 & T4 hormone), MSH cells cells (Melanocyte stimulating hormone) Endorphin, Lipotropic factor. L.M. Rounded cells with Oval cells with eccentric FSH rounded nuclei. nuclei. LH Rounded cells with rounded nuclei E.M. All cells have mitochondria, golgi, rER& secretory granules. II) Pars Tuberalis -Basophilic cells. -Unknwon functions, but some secrete gonadotrophins (FSH&LH) III) Pars Intermedia - Basophilic cells - Rudimentary in man, but in some species, they secrete melanocyte stimulatin hormone 6  Neurohypophysis - It is formed of two parts which are: I) Infundibulum. II) Pars Nervosa. I) Infundibulum: - It connects the hypothalamus with pars nervosa. II) Pars Nervosa: - It does not secrete hormones. - It contains: a) Pituicytes: They are supporting neuroglial cells. b) Nerve fibers (no nerve cells): - Axons of secretory cells of hypothalamus. - They carry neurosecretion to blood capillaries. c) Herring bodies: - They are acidophilic bodies containing the accumulated secretions in axon terminals of nerve fibers. - They contain two hormones: oxytocin &vasopressin. d) Fenestrated blood capillaries: - They are surrounded by Herring bodies. Functions of pars nervosa: - It is the site of storage of ADH &Oxytocin secreted by supraoptic & paraventricular nuclei of hypothalmus. - Hormones secreted by the anterior pituitary They are: 1- T.S.H. 2- A.C.T.H. 3- F.S.H. 4- L.H. 5- G.H. 6- P.R.L. 1- Thyroid stimulating hormone (TSH): - TSH release is stimulated by thyrotrophin-releasing hormone (TRH) from the hypothalamus - TSH release is inhibited by increase T3 and T4 , this is called negative feedback. - Secretion of TRH is stimulated by cold and by stress, via the CNS. - TSH acts on the thyroid gland. - It stimulates the release of thyroid hormones (T3 and T4 ). - It increases iodine uptake by the thyroid; and stimulates thyroid growth 2- Adrenocorticotropic hormone ( A.C.T.H.): - It is a Polypeptide hormone. 7  - ACTH is stimulated by corticotropin-releasing hormone (CRH) from the hypothalamus. - It is inhibited by increased glucocorticoids (cortisol hormone) --- negative feedback. - Secretion of ACTH is increased by stress. - Secretion of the A.C.T.H. is pulsatile with a diurnal rhythm (high at 7.00am, low at midnight). - It stimulates production and secretion of cortisol from the cortex of the adrenal gland. - ACTH produces some increase in adrenal sex steroids and stimulates growth of the adrenal cortex. - It stimulates Melanocyte-stimulating hormone and thus stimulates pigmentation of skin via actions on melanocytes. 3-Gonadotrophins ( L.H , F.S.H ) Luteinizing hormone (LH), follicle-stimulating hormone (FSH): - In Females: - LH and FSH control growth and development of follicles. - LH and FSH control ovulation. - LH and FSH control synthesis of sex steroids by the ovary. - LH and FSH control growth and secretion of the sex steroid progesterone by the corpus luteum - In Males: - LH controls testosterone production by the Leydig cells; - FSH stimulates the Sertoli cells and sperm production - Control: - LH and FSH release is stimulated by hourly pulses of gonadotrophin-releasing hormone (GnRH) during reproductive life - LH and FSH release is inhibited by sex steroid oestrogen --- negative feedback. - Oestrogen causes positive feedback for LH at mid ovarian cycle causing LH surge at ovulation. - In males, LH release is inhibited by negative feedback from testosterone; - In females ovarian peptides (inhibin and follistatin) inhibit FSH. - Cyclical variations in LH and FSH in menstrual cycle. 4-Growth hormone (GH) : - It stimulates long bone and soft tissue growth. - It acts via stimulating the release of Insulin growth factors ( IGFs ) from the liver and to a less extent by direct actions. - It is essential for growth after 2 years postnatally, - It only promotes growth if sufficient nutrition is available. - Growth hormone exerts complex actions on metabolism (amino acid, fatty acid, glucose). - It has insulin-like effects to promote amino acid uptake by liver and muscle and, therefore, promotes protein synthesis. - If growth hormone is chronically increased, it has anti-insulin effects. - It is one of the hormones that switches metabolism away from glucose use ( increase blood glucose – diabetogenic ) and it goes towards increased oxidation of fat (e.g. in starvation) 8 - Function of GH: Metabolic action on Metabolic action on Metabolic action on Action on growth protein carbohydrates fat 1-Anabolic 1-Diabetogenic 1-Lipolytic - Increase growth of * Increase protein (Hyperglycemic) - (increase lipolysis) soft tissue ----as it is formation *increase blood glucose - Increase fatty acid ANABOLIC on * Positive nitrogen MECHANISM: uptake by liver protein balance 1-decrease glucose - Increase ketone * Increase number of entry to cell body formation by - Increase growth of cells 2-increase liver-----may lead long bones * Increase size of cells GLYCOGENOLYSIS to ketosis Mechanism: MECHANISM: Glycogen----glucose (ketogenic) GH act on epiphyseal 1-increase amino acid cartilage of bone --- uptake indirectly through 2-increase formation SOMATOMEDINS of mRNA (insulin growth 3-increase RNA factors) translation to form GH proteins ↓ Liver somatomedins ↓ Act on bones - Somatomedins: - Protein in nature - Formed in liver - Has insulin like action: - Increase glucose uptake by cell - Inhibit lipolysis - Called sulfation factors - Has prolonged action - Control: - Secretion is increased via the hypothalamus by hypoglycaemia, stress, and exercise. - Hypothalamic factors that regulate growth hormone release are growth hormone- releasing hormone (GHRH). - Hypothalamic factors that inhibit growth hormone release is somatostatin, (GHIH) which inhibits, its release. - Systemic control is via negative feedback by growth hormone when its level increases it inhibit the release at the hypothalamus level. - GH is secreted in pulsatile pattern: Factors stimulate GH secretion Factors inhibit GH secretion 1- Decrease caloric supply as in 1- GHIH - Hypoglycemia 2- Hperglycemia - Starvation 3- Increase fatty acids - Exercise 4- Obesity - Stress 5- Cortisol hormone 2- Sleep 6- Old age 3- GHRH - Control of gh secretion is done by: 9  Hypothalamic control Feed back control - GHRH ---+++++ GH secretion - Short loop negative feed back: from anterior GH ----- on reaching normal level ----inhibits GHRH pituitary - Long loop feed back: - GHIH ---- _ _ _ GH secretion from GH anterior pituitary ↓ Liver ↓ Somatomedins (IGF-1) ↓ +++ hypothalamus to secrete SOMATOSTATIN ↓ Inhibit GH secretion - Disturbances of GH secretion: Hypofunction of GH Hyperfunction of GH Hyperfunction of GH 1- Pituitary Dwarfism: Gigantism: Acromegally: Def: Dwarf due to Def: Increase GH before Def: Increase GH after union decrease GH before union of the epyphysis of epiphysis of long puberty (before puberty) bones (after puberty) Causes: Characters: 1-Over growth of 1-Decrease GHRH 1-Symmetrical over growth HANDS,FEET,FINGERS, 2-Decrease GH of all bones (taller than 2-Over growth of skull flat 3-Inability to form normal but proportionate) bones: somatomedin C 2-Over growth of soft tissue - Box shape (Levi-Lorain dwarf) (splanchnomegally) - Prominent sheeks GH secretion is normal 3-Hyperglycemia, glucosuria, - Prominent nose but person can not form DM - Prominent super cilliary Somatomedin C 4-Hypogonadism due to ridge Features: pressure of the acidophill - Protruded lower jaw 1- Symmetrical growth cells secreting GH on (proganthism) retardation (proportionate basophil cells secreting - Separated teeth dwarf)---span = height FSH Over growth of skin of scalp 2-Retarded growth of soft cause wrinkling—(buldog tissue face 3- Mentally, sexually normal - Over growth of vertebrae---kyphosis - Over growth of musclesmuscles and viscera - This case may be due to tumor in pituitary leading to pituitary enlargement----- press on optic chiasma----visual field loss (bitemporal hemi anopia) - Hyperglycemia-----glucosuria----DM - GH is similar to PRL ----lead to Gynecomastia & milk production - 5-- Prolactin (PRL): - It is secreted by lactotroph cells. - It plays a principal role in preparation for lactation. - PRL stimulates the development and growth of secretory alveoli and milk production. in the breast - PRL also inhibits the reproductive system at the level of the gonads (inhibits the effect of FSH and LH on the ovaries) (causes ‘lactational amenorrhoea’ in women after delivery of baby). Normal level of prolactin is 5 ng/ml in male & 8 ng/ml in females 10  - Control: - Secretion of PRL is increased by suckling. - PRL release is inhibited by dopamine from the hypothalamus. - PRL synthesis is stimulated by circulating oestrogen. - Chlorpromazine drug stimulates PRL secretion. - Physiologic variation of PRL in plasma: Sleep Pregnancy Parturaition Suckling Stress Rise at onset of - Rise gradually After parturition - It forms - Physical or sleep during pregnancy PRL level returns SURGE (sharp mental stress - Reach peak at to its normal rise) increase PRL parturition level 8 ng/ml secretion - Disturbances of PRL secretion Hypoprolactinemia Hyperprolactinemia (increase PRL secretion) - Rare Causes: - Occur if pituitary is damaged 1- Tumor of anterior pituitary - The female may not lactate 2- Intake of DOPAMINE blocking drugs as CHLORPROMAZINE after labor Effects: In males: Increased PRL has inhibitory effect on FSH on testes this leads to: - Sterility - Infertility - Impotence - Gynaecomastia (enlarged male breast) - Decrease libido In females: 1-The high level of PRL------ INHIBIT the action of GONADOTROPINE (FSH) on the ovaries leading to ↓ No maturation of ova ↓ Ammenorrhea ( no monthly period) ↓ Infertility ↓ Sterility 2-Galactorrhea (increase milk production in non lactating females) Hormones secreted by the posterior pituitary - ADH (vasopressin) = pressophysin - Actions: - It increases water reabsorption by acting on collecting ducts of kidney through (V2 receptor). - It has a vascular pressor effects to constricting peripheral arterioles and veins through (V1 receptors) - ADH acts on receptors in the glomerular mesangium to increase formation of the (PGE2) --- which is a vasodilator 11  - The action of the (PGE2) as a vasodilator antagonizes the vasoconstrictor action of the ADH on the renal tissue - It acts through V3 receptors In anterior pituitary (Corticotrope cells) = cells which secrete ACTH - Control of ADH: Stimuli inhibit ADH secretion Stimuli increase ADH secretion 1- Cold weather 1- Increase plasma osmolarity ( increase osmotic pressure in 2- Alcohol plasma) 1% 3- Hypervolemia ↓ 4- Decrease osmotic pressure in Stimulate osmoreceptors in hypothalamus plasma (plasma osmolarity) ↓ 5- Alpha agonists Increase ADH secretion ↓ Increase water REABSORPTION in DISTAL tubules in kidney (FACULTATIVE) ↓ Return plasma osmolarity to normal 2- Hypovolemia: Decrease blood volume by 10% Decrease blood pressure +++ Carotid sinus baroreceptors +++ Atrial receptors ↓ ↓ +++ Vasomotor center +++ Vagus nerve ↓ ↓ +++ secretion of ADH +++ ADH +++ BP (weak ) ↓ Vasoconstrition , increase blood pressure 3- Stress increases ADH secretion as the it stimulates the release of CRH and the it is co-secreted with the ADH 4- Drugs (morphine nicotine) 5- Nausea (it stimulates the release of the ADH by an unknown cause ) 6- Hot weather (as there will be more sweat so the ADH will decrease the urine output to preserve the water and blood volume ) - Diabetes insipidus: Def: Caused due to defeciency of ADH Causes: 1- Lesion in supraoptic nucleus ----(central diabetes insipidus) 2- Congenital defect in V2 receptors in kidney kidney does not respond to ADH (nephrogenic diabetes insipidus) - Manifestation of diabetes insipidus (D.I.): * Polyuria ----- increase volume of urine up to 10 liters /day-----specific gravity of urine ---very low (1002-1004) - Loss of water soluble vitamins - Loss of electrolytes 12  * Polydepsia: drink large volume of water * Increased BMR as more volume of water is heated - Oxytocin ( oxyphysin ): - Actions: It causes contraction of uterine myometrium in childbirth and contraction of breast myoepithelium to eject milk. - Control: - The hormone release is stimulated by stretch of cervix/vagina during parturition (the Ferguson refl ex) - The hormone release is stimulated by suckling—stimulation of the nipple causes the milk ejection. 13 Pineal Body (Epiphysis Cerebri) - It is a cone shaped neuroendocrine gland. - It is derived from neuroectoderm. - It is formed of: - Pinealocytes. - Astrocytes. - Fenestrated blood capillaries. - Brain sand (psammoma bodies). 1) Pinealocytes: - Structure: - They are large branched cells with long tortuous processes which end by dilations on blood capillaries in the vascular septa. - The nuclei are large pale with clear nucleolus. - The cytoplasm is basophilic. - By E.M:they are rich in mitochondria,golgi apparatus,rER& secretory granules. - Functions: They secrete: - Serotonin (at day time). - Melatonin (at night): * Regulates gonadal function to prevent precocious puberty. * Antioxidant(protection of body cells). * Regulation of sleep rhythm. 2) Astrocytes: - They are neuroglial supporting cells. - They are presented between pinealocytes. - The nuclei are darker. - They have long processes. - They have many intermediate filaments. 3) Fenestrated blood capillaries. 4) Brain sand (Psammoma bodies,corpora aranacea): - They are calcified secretory products in concentric layers. - They increase with age. - They are land mark in x-ray to localize any mass in the brain,which may displaces its position. 14 Pineal body 15  Development of thyroid Thyroid (ant view) Thyroid (transverse section) Weebly / Teachmeanatomy 16  ANATOMY OF THYROID GLAND Embryological preview: The endoderm of 1st pharyngeal arch develops into the mucous membrane of the ant 2/3 of tongue. While the endoderm of 3rd and 4th arches develops into the mucous membrane of the post 1/3 of tongue. The line between the ant 2/3 and post 1/3 of the mucous membrane of the tongue is called sulcus terminalis and it shows foramen cecum at its middle. From foramen cecum arises a thyroglossal duct which migrates caudally to reach the thyroid cartilage and forms the thyroid gland acini. the connective tissue and vessels arise from surrounding mesoderm. The duct connecting the thyroid to the tongue forms the pyramidal lobe above the isthmus and the rest disappears. Congenital anomalies: Aplasia or hypoplasia of thyroid: due to failure of development of thyroid acini. Lingual thyroid: due to failure of extension of thyroglossal duct. Mediastinal thyroid: the thyroglossal duct continue its migration to the thorax.. Thyroglossal cyst: persistence of part of thyroglossal duct with cyst formation. This cyst moves with the protrusion of tongue. Relations: the thyroid gland has two lobes connected by an isthmus. Lobe: pyramidal in shape, tracheal ring. It has: Apex: at the C5 vertebra. Base: at the level of T1vertebra (6th tracheal ring). Ant border Post border: related to parathyroid gland. Lat (superficial) surface: related to skin, superficial fascia (containing platysma), deep investing fascia and sternohyoid, sternothyroid, omohyoid and sternomastoid muscles. Posterolateral surface: related to carotid sheath. Med surface: related to: larynx and pharynx (between C5-C6 vertebrae), trachea and esophagus (between C6 and T1 vertebra). External laryngeal nerve is related to the upper part of this surface and the recurrent laryngeal nerve is related to its lower part. Isthmus: it has: Upper border: presents a small pyramidal lobe. Inferior border. Anterior surface: related to skin, superficial fascia (containing platysma), deep investing fascia, and sternohyoid and sternothyroid muscles. Posterior surface: related to tracheal rings 2-4. Capsules of the gland: Inner (true) capsule: formed of connective tissue. Outer false capsule: derived from the pretracheal fascia and attached to larynx. 17  Blood supply of thyroid Wikimedia Blood supply of the thyroid gland: Arteries: Rt and Lt sup thyroid As (of ECA): supplies the apex and anterior aspect of the gland. the two arteries anastomose at the upper border of the isthmus. Rt and Lt inf thyroid As (of thyrocervical trunk of subclavian A): supplies the base and the posterior aspect of the gland. Thyroidea ima artery (of aortic arch): supplies the isthmus. Veins: Rt and Lt sup thyroid Vs: emerges from the apex of the thyroid lobe and usually drains to IJV. Rt and Lt middle thyroid Vs: emerges from the middle of the lobe and drains to IJV. Rt and Lt inf thyroid Vs: emerges from the base of the thyroid lobe. They unite forming a single vein and drains to Lt brachiocephalic V. Applied anatomy: Due to the enclosement of thyroid gland within the pretracheal fascia connecting it to the larynx, the thyroid gland moves during swallowing. Enlargement of the thyroid gland may cause pressure symptoms on trachea and esophagus (difficulty in breathing and swallowing). The sup thyroid A is closely related to the external laryngeal N away from the gland, while the inf thyroid A is closely related to the recurrent laryngeal nerve near the gland. To avoid the nerve injuries during thyroidectomy the sup thyroid artery should be ligated near the apex. While the inf thyroid artery should be ligated away from the gland. Injury of external laryngeal nerve causes paralysis of cricothyroid muscle of larynx leading to loss of of high pitched voice. Injury of RLN causes paralysis to other muscles of larynx leading to hoarseness of voice. 18 - Histology of the thyroid gland It is formed of stroma & parenchyma. I) Stroma: - Capsule: Two capsules (True& False): True capsule: Inner capsule, firmly adherent to the gland. - False: Outer capsule, formed of pretracheal fascia. - Trabeculae: Thin,divide the gland into lobes &lobules &carry blood vessels. - Reticular C.T: reticular cells &fibers in the background, stained with Ag(silver). II) Parenchyma: -It is formed of Thyroid follicles &Inter follicular tissue. A) Thyroid follicles: - The structural & functional units of the gland. - Shape: oval or rounded. - Lined with cubical epithelium, resting on thin basement membrane. - Surrounding a lumen filled with acidophilic colloidal material called (iodinated glycoprotein). - They are lined with two types of cells: 1) Follicular cells (98%): - By L.M: Cubical cells with basophilic cytoplasm& central rounded nuclei. - By E.M: The cells have: - Apical micro villi. - Tight junctions between adjacent cells. - Mitochondria, supranuclear golgi apparatus, ribosomes, lysosomes &apical secretory vesicles. Functions: Secretion of thyroid hormones (T3 & T4) under control of TSH. 2) Parafollicular (c-cells) (2%): - By L.M: - They are larger cells with paler cytoplasm, so called clear cells , stained with Ag. - They are presented between the basement membrane & follicular cells. - They don’t reach the lumen of the follicle. - By E.M: -Mitochondria, rER, Golgi apparatus& basal secretory granules. Functions: They secrete Thyrocalcitonin which decreases blood calcium. B) Interfollicular Tissue: - It is in between thyroid follicles. - It contains; reticular C.T., interfollicular cells, C-cells & fenestrated blood capillaries. - Hormones of the thyroid gland - They are: 1-Thyroxine T4,T3 19  2-Calcitonin ----from para follicular cells - Formation of the thyroid hormones: - Iodide trapping: active iodide uptake by thyroid gland. - Oxidation of iodide to iodine - Binding of iodinated tyrosine with the glycoprotein( thyroglobulin). - Iodination of tyrosine to form monoiodotyrosine( MIT),diiodotyrosine( DIT). - Coupling of 2( DIT) to form T4 and 1( MIT) +1( DIT) to form T3. - Release of thyroid hormones. - Normal level of T4, T3: T4 T3 Total 8-12 ug/dl 0.15 ug/dl Bound 99.98% 99.8% Free 1- 6 ng/dl 0.3ng/dl - Function of thyroid hormones: Effect on Effect on Effect on Effect on Effect on Effect on metabolism metabolism metabolism metabolism metabolism metabolism Calorigenic Carbohydrate Fat metabolism Protein Vitamin Basal metabolic metabolism metabolism metabolism rate - Increase O2 - Increase - Lipolysis--- - Anabolic--- - Increase body - Increase BMR consumption absorption of mobilize lipids increase protein needs for - Responsible for - Increase heat glucose by from stores formation (in vitamins as normal BMR production intestine - Deplete fat normal dose) thyroid hormone - Increase size & - Increase stores - On large dose --- act as coenzymes number of gluconeogenesis - Decrease -catabolic - Help conversion mitochondria Change amino cholesterol in of carotein to - Increase ATP acid----glucose plasma vitamin A formation - Increase glucose - Increase - Increase Na+ K+ uptake by cells oxidation of fatty ATPase enzyme - Increase insulin acids - On Body system: On GIT On CVS On CNS - +++ motility of GIT - Increase HR: - Increase myelination and - +++ secretion of GIT - Thyroid hormone stimulates SAN growth of neurones - +++ absorption of GIT - Thyroid hormone has direct effect on excitability - Increase synaptic transmission - Increase CO-- due to (needed for wakfulness ) - Increase metabolism - Stimulate Beta adrenergic receptors - Increase heat production - Increase pulse pressure Systolic – Diastolic - Increase systolic pressure due to increase CO - Decrease diastolic pressure due to peripheral vasodilation - Increase force of contraction – enzyme activity - Effect on growth: - Essential for MENTAL development during first year post natal - Needed for PHYSICAL linear growth , maturation of growth centers and eruption of teeth - Needed for SEXUAL growth & maturation. 20 - Abnormalities of thyroid gland function: - Hypothyroidism: - Causes of hypothyroidism: 1- Causes in the thyroid gland. (primary ) Causes in pituitary origin (secondary ) Causes in hypothalamus (tertiary ) - Congenital absence of thyroid gland - Chronic iodine defeciency - Chronic thyroiditis - Excessive antithyroid drugs - Surgical removal of thyroid gland 2- Decrease TSH of the anterior pituitary Decrease TRH of the hypothalamus Hypothyroidism (adult)-(Myxoedema) Hypothyroidism (infant)-(cretenism) Characters: - Delay in all normal growth milestones 1- BMR---Decreased to about 50% leading to: - Retarded physical , and mental , and sexual - Increase body weight growth - Can not tolerate cold weather 1- Physical growth: - Coarse & sparse hair - Dwarf (short) - Skin: Cold - Disproportionate –as span is retarded more Dry: No sweat than height as vertebrae not retarded Puffy: Accumulate complex proteins - Umbilicus not central water retention: Puffy skin - Obese: Why: Because the skeletal growth Yellow: Why is more inhibited than soft tissue growth - Delay eruption of teeth Liver need thyroid hormone to transfer - Delay close fontanels Carotene: Vitamin A - Delay sitting and walking - Increase body weight As the thyroid hormone is decreased carotene - Increase plasma cholesterol will not be transferred to vitamin A and remain - Decrease activity of all body systems under skin giving it the yellow color - Decrease metabolic rate, body temperature 21  Hypothyroidism (adult)-(Myxoedema) Hypothyroidism (infant)-(cretenism) 2- CNS: Facial features: - Slow mentation - Ugly face - Poor memory - Swolen eye lid - Hypersomnia - Depressed nose , wide nostril - Hyporeflexia - Enlarged protruded tongue - Thick dry skin deposit fat in supraorbital 3- CVS: Decrease HR, CO region Atherosclerosis - Pot belly abdomen due to enlarged liver Low voltage ECG and spleen Mental development: He is mentally retarded 4- GIT: Constipation Loss of appetite Sexual development: Delayed sexual development 5- Blood: Increase serum cholesterol level 6- Non pitting oedema: Due to accumulation of the myxoedematous tissue 7- Decrease respiratory rate (decrease ventilation) 8- Eye: Puffiness Swelling face Night blindness---decrease vitamin A 9- Metabolism: - Decrease glucose absorption - Increase glycogen in liver & muscle - Non pitting oedema—myxoedematous accumulate Difference between GH dwarf and thyroid dwarf Thyroid dwarf GH dwarf - Lack of thyroid hormone - Lack of GH - Disproportionate dwarf - Proportionate dwarf - Idiot - Normal mentality - Impotent - Infantile shape - Ugly - Normal sexually - Hyperthyroidism (thyrotoxicosis): Excessive secretion of thyroid hormone - Causes: 1-Acute thyroiditis---inflammation of thyroid---lead to increase secretion of the thyroid hormone 2-Tumor in thyroid gland 3-Graves disease---antibodies present against TSH receptors on the thyroid gland ----produce excess T3, T4----while they have no negative feed back 4-Excessive adminstration of thyroid hormones 5-Pituitary tumor - Characters: 1-BMR---Increase BMR to 100% Not tolerate hot weather Warm flushed sweaty skin 22  2-CNS---Irritable. Tremors , insomnia , hyperreflexia Increased excitability of nervous tissue 3-CVS---Tachycardia due to -Direct stimulation of SAN -Increase senstivity of the SAN to catecholamines 4-blood pressure: -Increase systolic –due to increase SV, CO -Decrease diastolic—due to peripheral VD -Increase pulse pressure *Eyes: Exophthalmus Antibodies against extra ocular muscles Cause hypertrophy of the muscles Push eye ball forward Press on optic nerve causing atrophy, blind *GIT---Diarrhea, hyperphagia *Blood:---Hyperglycemia Decrease cholesterol level Increase pulmonary ventilation Shift O2 dissociation curve to right On metabolism: Increase catabolism of protein of protein Hyperglycemia Decrease cholesterol level in blood - GOITRE - Def: enlarged thyroid ( non inflammatory non neoplasmic) - It may be associated with - With normal , decreased or increased thyroid activity - It is of three types 1- Physiologic: - During puberty - During pregnancy - Thyroid gland enlarges to form more thyroid hormone to meet the increased needs for thyroid hormone 2- Hypothyroidism: - In case of iodine deficiency (colloid goitre) - Thyroid follicles filled with - Thyroglobulin - Thyroid hormones not formed 3- Hyperthyroid: - In TUMOR adenoma (parenchymatous goitre) - Graves disease Thyroid cells increase in size & number 23 - Goitergenic substances are : Drugs block iodide trapping Drugs block of iodine Natural goitergens - Monovalent anions: - Thioria - They are carrots, cabbage & turnips 1- Perchlorate, nitrate iodate - Thiouracil - They contain progoitrin --- & its Compete with iodine - Thiocarbmide converter is heat labile & Uptaken to follicles They compete with tyrosine - The converter is heat labile 2- Thiocynate Prevent formation of MIT, DIT - The progoitrin is converted to Compete with iodine goitrin even if the food is cooked but Decrease thyroid hormones due to presence of bacteria activator They are not uptaken to follicles Increase TSH in the intestine act as converter They lead to: - Decrease thyroid hormones - Increased TSH 24  Parathyroid glands Medicocrazy ANATOMY OF THE PARATHYROID GLANDS ❖ They are four small glands embedded in the posterior aspect of thyroid lobes. ❖ The sup parathyroid lies at the middle of the posterior border of thyroid lobe, while the inf parathyroid lies close to the inferior pole of thyroid lobe. Embryological preview: the superior parathyroid develops from the 4th pharyngeal pouch while the inferior parathyroid develops from the 3rd pharyngeal pouch Blood supply: inf thyroid As. Applied anatomy: during thyroidectomy, its post part should be preserved to maintain the parathyroid glands. - Histology of the parathyroid gland - They are four small endocrine glands at the back of the thyroid gland. - They are formed of stroma & parenchyma. A) Stroma: - Capsule: Thin, formed of C.T cells & fibers. - Trabeculae: Thin, formed of C.T cells & fibers divide the gland into incomplete lobules, carry blood vessels. - Reticular C.T.: Reticular cells & fibers, in the background ,stained with Ag. B) Parenchyma: Two types of cells. - Chief (Principal) cells - Oxyphil cells. a) Chief cells b) Oxyphil cells Small & more numerous. Larger & less numerous, but No. increases with age. Polygonal cells with central rounded nuclei. Oval or rounded cells with eccentric nuclei. Basophilic cytoplasm Acidophilic cytoplasm Fine granules Acidophilic granules By E.M: Mitochondria, rER, golgi & secretory Mitochondria granules. 25 Functions: Secretion of parathyroid hormone Un known function. (parathormone) which increase blood calcium. Thyroid & parathyroid gland 26 Calcium homeostasis Ca2+ has very important extracellular effects as - Its effect on excitability of tissues - Its effect on blood clotting - It is an essential component of bone. The condition Hypocalcaemia (i.e. total Ca2+