Endocrine System

Chemical Co-ordination and Integration What are Endocrine Glands ?

. Ductless glands

. Cell secrete “hormone” into the blood stream

–Vascular system is a conduit for hormone

–May have a widespread effect • Greek word – Hormaein (Starling in 1950) - To set in motion / to spur on

Definition • Hormones are informational molecules secreted by endocrine glands in one part of the body and carried to another part of body to perform physiological actions. released from produce effect on SOURCE cells TARGET cells

receptors travel through bloodstream

Defn : A chemical messenger that is produced by one cell or a group of cells, secreted directly into the bloodstream and transported to distant target cells, in which it elicits a typical physiological response. Target Cell Hormone • Target cells will have appropriate hormone receptors in them

• Not all cells in body respond to presence of hormone. Receptor Not a target • Only target cells with cell specific receptor is "in tune" to the presence of hormone in the circulation. Endocrinology • Study of endocrine glands, their secretions and functions.

• W H Bayliss & E H Starling - Hormone first discovered - secretin - Hormone from Small intestine. Difference between Nervous and Endocrine co-ordination

Nervous Co-ordination Endocrine / chemical co- ordination

Information passes as electrical Information passes as chemical impulses along nerve fibers substances through blood and lymph

There is rapid transmission of There is slow transmission of information information

Response is immediate and short lived Response is slow and long lasting

After its physiological action ------metabolised by liver and kidney Types of Endocrine glands

Organized Endocrine gland Non- organized endocrine gland

Hormone producing cells are present Hormone producing cells are scattered in clusters

Pituitary, Pancreas, Parathyroid, Heart, liver, Kidney, GIT Penial, Thyroid, Thymus, Adrenal and Gonads Classification of Hormones CLASSIFICATION OF HORMONES

based on chemical nature

based on solubility Depending on Chemical Nature

HORMONES

Proteins and Amino acid polypeptides derivatives Steroids Hormones and their receptors

Hormone Class of hormone Location of Receptors

Amine Water-soluble Cell surface Ex: epinephrine ,Nor- epinephrine, Dopamine Amine / Iodinated Lipid soluble Intracellular Ex: thyroid hormone Peptide/protein Water soluble Cell surface Ex: hypothalamic , pituitary, insulin, glucagon, PTH Steroids - from Lipid Soluble Intracellular cholesterol Ex: Hormones of adrenal cortex, testis, ovary, placenta lipid insoluble hormone

Membrane bound extracellular receptors lipid soluble hormone

Intracellular Receptors Mechanism of action of Hormones

• Amines – catecholamines – via change in membrane permeability • Steroid & thyroid hormones – Gene expression • Peptides – second messengers

1). Adenylyl cyclase – CAMP 2). Guanyl cyclase- CGMP 3).IP3 system 4).Calcium – Calmodulin system Peptide Hormones – Second messengers

Nobel Prize Winner – EW Sutherland in 1950

1). Adenylyl cyclase – CAMP 2). Guanyl cyclase- CGMP 3).IP3 system 4).Calcium – Calmodulin system 5) Tyrosine Kinase Activation 1. Adenylyl cyclase- cyclic AMP system

1 Hormone (1st messenger) Adenylate cyclase Extracellular fluid binds receptor.

G protein (GS)

2nd messenger

5 cAMP acti- Receptor vates protein kinases. Active protein kinase GDP 2 Receptor 3 G protein 4Adenylate Inactive activates G activates cyclase protein kinase protein (G ). adenylate converts ATP S cyclase. Hormones that to cAMP (2nd act via cAMP messenger). Triggers responses of mechanisms: target cell (activates enzymes, stimulates cellular secretion, Epinephrine Glucagon opens ion channel, ACTH PTH etc.) FSH TSH LH Calcitonin Cytoplasm 2. Guanylyl cyclase- cyclic GMP system

1 Hormone (1st messenger) Guanylate cyclase Extracellular fluid binds receptor.

G protein (GS)

5 cGMP acti- cGM vates protein Receptor P kinases.

GT Active P protein kinase GDP 2 Receptor 3 G protein 4 Guanylate Inactive activates G activates cyclase protein kinase protein (G ). Guanylate converts GTP S cyclase. Hormones that to cGMP (2nd act via cGMP messenger). Triggers responses of mechanisms: target cell (activates enzymes, stimulates cellular secretion, •Nitric oxide opens ion channel, •Atrial etc.) Natriuretic Cytoplasm peptide 3. Hormone Action Via Inositol Triphosphate

Hormone + Receptor Activates G - protein

G- protein activates Phospholipase C

Releases from cell membrane Diacyl Glycerol + Inositol triphosphate

Activates Moves protein kinase C calcium out from PHYSIOLOGICAL endoplasmic ACTION reticulum 4). Calcium – Calmodulin system

Hormone + receptor Activates G- protein

Release Opens calcium calcium from channels in endoplasmi cell c reticulum membrane

Calcium binds with Physiological action Calmodulin lipid insoluble hormone

Membrane bound extracellular receptors lipid soluble hormone

Intracellular Receptors Hormones and their receptors

Hormone Class of hormone Location of Receptors

Transcription of mRNA

mRNA comes to cytoplasm & promotes ribosomes to produce proteins Steroid hormone Plasma Extracellular fluid membrane 1 The steroid hormone diffuses through the plasma membrane and Cytoplasm binds an intracellular receptor. Receptor Receptor- protein hormone complex 2 The receptor- hormone Hormone complex enters the nucleus. Nucleus response elements 3 The receptor- hormone

DNA complex binds a hormone response element (a specific DNA sequence). mRNA 4 Binding initiates transcription of the gene to mRNA.

5 The mRNA directs protein New protein synthesis. Amines – change in membrane permeability • Hormone + receptor

• Conformational change in receptor proteins Hormone s • Opening / closing of ion channels

• Influx /efflux of ions

• Expected functions of hormones Hypothalamus Pineal gland Pituitary gland Organs containing Thyroid gland endocrine cells: Parathyroid glands Thymus Heart

Liver Adrenal glands Stomach

Testes Pancreas Kidney Kidney Small intestine Ovaries Hypothalamus

• Base of fore brain / Diencephalon • Ectodermal origin • Neurosecretory cells • Controls secretions of pituitary gland Hypothalamus • co-ordinator of Hormone release. • Controls anterior & posterior pituitary. • Secretes Releasing & inhibitory hormones • Hormones:

SR PRH H Hypothalamus

Melanocyte stimulating Melanocyte stimulating hormone hormone releasing hormone Inhibiting hormone

Controls Anterior Pituitary SKIN MSH Skin Pigmentation Pituitary Gland / Hypophysis

It was called as master gland of the endocrine system. It controls the functions of the other endocrine glands . Connected to Hypothalamus via pituitary stalk.  Ovoid, flattened organ,0.5X1X1cm, 0.5g in weight.

 situated in a socket of sphenoid bone, called sella turcica

• Lobes : 2

Anterior Posterior Pituitary

• Length – 1 cm • Width – 1-1.5cm • • Thick – 0.5cm • Weight – 0.5gm

• Origin • Ant pit – roof of mouth - Rathke’s pouch • Post pit – Floor of diencephalon - downward growth

Pituitary Gland

Anatomical division

Pars Nervosa Pars Dorsalis Posterior lobe Anterior lobe Pars Intermedia Intermediate lobe Pituitary Gland

Functional Division

Adenohypophysis / Neurohypophysis / Anterior pituitary Posterior pituitary

Ectodermal- Rathkes Neuro ectodermal- pouch- buccal cavity outgrowth of Hypothalamus Hypothalamus --- anterior pituitary

• Hypothalamus secretes hormones through axons.

• Axons terminates on portal blood vessels.

• Endocrine cells of Anterior pituitary releases corresponding hormone. Hypothalamus --- Posterior Pituitary

• Axons from hypothalamus

• Terminates on blood vessels of posterior Pituitary.

• No specific endocrine cells from posterior pituitary. Adenohypophysis Neurohypophysis

Hypothalamo - hypopyseal Hypothalamo-hypophyseal Portal System Tract Histology of Anterior Pituitary

Pars Distalis Cells

Chromophils Chromophobes a)Acidophils - 40% b)Basophils - 10% Somatotrophes-30%( GH) Gonadotrophes-10-20% (LH,FSH) Mamotrophes- 10% Prolactin Thyrotrophes-3-5% (TSH) Corticotrophs- (ACTH Hormones secreted by Anterior Pituitary Growth Hormone

• STH (Somatotropin Hormone) • Protein Hormone • 188 Amino acids • Promotes growth - Whole body - Elongation of bones - Growth of muscle and cartilage - Mitosis and cell proliferation in visceral organs Effect of Growth hormone on metabolism

• On Carbohydrates – GH decreases uptake of glucose from blood into cells causing hyperglycemia --- Thus called diabetogenic Hormone.

• On Proteins – GH increases amino acid uptake from blood to liver and skeletal muscles increasing protein synthesis – thus called anabolic hormone.

• On Fats – GH increases lipolysis (breakdown of fat) and utilises it for ATP production. Abnormalities in GH Secretion

1)Hyposecretion: Before Puberty : Dwarfism After Puberty : Acromicria

2)Hypersecretion: Before Puberty : Gigantism After Puberty : Acromegaly DWARFISM • GH hypo secretion

• Premature arrest of skeletal development

• stunted physical growth

• Maximum height at adult age is only 3 feet

• No mental retardation GigGantism  GH hypersecretion  before puberty

 before epiphysial closure) Due to tumor of acidophil cells

•Characteristic features Tall stature-above 8 ft Limbs are dispropotionately long Acromegaly  hypersecretion of GH in adults  overgrowth of bones of Face, hands & feet Increased thickness of lower jaw

Gonadotrophic Hormones

FSH & LH

Testes Ovary Follicle Stimulating Hormone

• Protein Hormone (204 AA) • Basophilic cells of Pars Distalis • Function : • Females : Growth of ovarian follicles

• Males : Development of Seminiferous Tubules - Maintains Spermatogenisis Primary Secondary Follicle Follicle

Antral Follicle Graffian Follicle • Granulosa cells of the growing follicles

Release Hormone Estrogen Luteinizing Hormone

• Females – For Ovulation, LH surge • Ovulation-- occurs 9 hrs after peak rise in LH Luteinizing Hormone

• Stimulates Interstitial cells Leydig cells of testis

secretes

Testosterone

ICSH – Interstitial cell stimulating hormone

Prolactin

• Acidophilic cells of anterior pituitary. • Protein with 198 Amino acids. • Function: - Mammary gland development - Stimulates milk secretion after delivery.

ACTH • Adrenocorticotrophic Hormone

• Secreted by Basophilic cells

• Polypeptide with 39 AA

• Stimulates Adrenal cortex Parts of Adrenal Gland

 2 distinct parts 1. Cortex 2. Medulla

 Both differ in their structure and function Adrenal Cortex

• Exhibits three distinct zones: 1. Zona Glomerulosa - Aldosterone

2. Zona Fasciculata - Cortisol

3. Zona Reticularis - Adrenal androgens Deficiency of ACTH a) Acute Psoriasis - Excess skin proliferation - Itchy & dry skin b) Dermatitis - Skin inflammation Hypersecretion of ACTH

• Cushing’s Syndrome

- Centripetal obesity - Skin pigmentation - Excessive facial hair - Bone demineralisation Centripetal obesity • Abnormal fat deposition in • Face – “ moon face” • Chest & abdomen • Buffalo hump • Purple striae

TSH • Thyroid stimulating hormone • Secreted by Basophilic cells

• Stimulates Thyroid gland LPH • Lipotropin / Lipolytic Hormone

• Function: - Stimulates fat breakdown in adipose tissues

FFA Triglycerides Hyposecretion : obesity Hypersecretion : Emaciation Pars Intermedia

– From Rathke’s Pouch – Prismatic granular cells – MSH (Melanocyte stimulating Hormone ) Secretes

Melanin

Synthesis and dispersal of melanin pigment in skin More effective in lower vertebrates MSH

• Metachrosis - Ability to change the skin colour. - By melanin pigment distribution below skin - Amphibians , reptiles

• Simmond’s disease - Degeneration of ant pituitary - Dry & wrinkled facial skin - Premature ageing.

Adenohypophysis Neurohypophysis

Hypothalamo - hypopyseal Hypothalamo-hypophyseal Portal System Tract Neurohypophysis

• Pars Nervosa • Cells of post pituitary

Pituicytes

• Hypothalamo-hypophyseal Tract Mechanism Of Secretion  Are peptide hormones

 Stored in secretory granules – Herring bodies

 Action potential in nerve terminals --- Exocytosis

 Hormones are taken up by adjacent capillaries Hormones of Posterior pituitary

 2 Hormones :

Hormone Synthesis

ADH supraoptic nucleus

paraventricular OXYTOCIN nucleus

 Cell bodies of the nucleus secretes these hormones. Actions of Oxytocin • Acts primarily on

I. Mammary Gland – milk ejection

II. Uterus – PARTURITION Delivery/ Labour Milk Ejection Reflex Milk Ejection reflex

 Stimulus - Suckling  Receptors - Touch receptors  Afferent – Sensory Nerves ( Spinothalamic Pathway) Center - Paraventricular nucleus  Efferent - Hormonal (oxytocin)  MOA - calcium- calmodulin system  Effect - contraction of myoepithelial cells of alveoli of mammary gland. ( Milk Ejection) PARTURITION REFLEX

PARTURITION REFLEX

• stimulus - movement of babies head causing stretch of cervix • Receptors - Stretch receptors in cervix • Nerves - sensory nerves (pelvic Nerves) • Center - Para-ventricular Nucleus • Efferent – Hormonal (Oxytocin) • MOA – calcium calmodulin system • Effect - contraction of myometrium (Parturition ) Hormones of Posterior pituitary

 2 Hormones :

Hormone Synthesis

OXYTOCIN paraventricular nucleus

ADH supraoptic nucleus

 Cell bodies of the nucleus secretes these hormones. Antidiuretic Hormone (ADH)

 Source :supraoptic nuclei of hypothalamus

Functions :

- Water reabsorption in DCT & CT of nephron - Vasoconstriction in high doses

Vasopressin / Pitressin Regulation Of ADH Secretion

 Controlled by 2 important stimuli :

1. Plasma osmolality (concentration of blood )

2. Blood Volume Osmotic stimuli

Normal plasma osmolality 300mosm/kg

If plasma osmolality300-350mosm/kg

Sensed by osmoreceptors near Supraoptic nuclei

ADH secretion ↑ Blood volume

• 10-15% ↓ in blood volume. • Baroreceptors & atrial stretch receptors

Mechanism : blood volume reduced Blood Pressure

Baroreceptors & atrial stretch receptors

Signals to SON – ADH secretion

Applied Aspect

 Diffeciency of ADH

 Reduced water reabsorption

 excessive excretion of dilute urine

 Diabetes Insipidus Diabetes Insipidus

Central D I Nephrogenic D I

Failure of ADH secretion Inability of kidney to respond to ADH

CAUSE : head injury, V2 receptor Infections congenital unresponsiveness

Inability of renal tubule to reabsorb H20

large volume of dilute urine > 15 L/day Hypothalamus Pineal gland Pituitary gland Organs containing Thyroid gland endocrine cells: Parathyroid glands Thymus Heart

Liver Adrenal glands Stomach

Testes Pancreas Kidney Kidney Small intestine Ovaries Pancreas

• Behind the stomach • Close to concavity of duodenum.

• Length- 15cm • Width- 2.5cm • Weight- 85gm Parts of Pancreas

Exocrine Endocrine Cells of Islet

1. α cell ( 25%)- glucagon

2. β cell (60%)- insulin

3. δ cell ( 10%)- somatostatin

4. PP cell – Pancreatic polypeptide • Discovered by – Benting & Best • Molecular structure given by – A.F. Sanger (Nobel Prize) with the help of Bowine (cow’s) insulin • Term insulin given by - A.F. Sanger • Artificial insulin synthesized by- Tsan

• One molecule of insulin – 51 amino acid • Alpha chain – 21 amino acids • Beta chain – 30 amino acids • Normal blood glucose concentration 80 – 120 mg/ 100 ml of blood

Hormone Insulin ---- decreases blood glucose

Hormone Glucagon ----- Increases blood glucose Insulin Blood glucose level

Gluconeogenisis Glycolysis Glycogen formation in liver

Conversion of converts glucose to fat & stores in Oxidation of glucose to adipose tissue glucose in glycogen & tissues stored in liver

Target Tissues Protein Metabolism Insulin

Protein synthesis & storage Proteolysis

Amino Acids

mRNA translation

New proteins Insulin Lipolysis

By inhibiting enzyme

Hormone sensitive Lipase Deficiency of Insulin

Ketosis FFA in liver ,blood

B-Hydroxy butyric + Acetone Activation of Carnitine transport Enters system circulation FFA

Condenses Mitochondria Acetoacetic Acetyl coA acid for β-oxidation Diabetes Mellitus

• Clinical syndrome of Hyperglycemia . • (blood glucose > 140mg/dl) Insulin • Cause :

- Lack of insulin Insulin receptor - Sensitivity of tissues to insulin TYPES

Type I Type II IDDM NIDDM

Sensitivity of tissues / Insulin secretion Insulin resistance

1. Viral infection 1. Insulin receptors 2. Auto immune disorder 2. Unresponsiveness of 3. Hereditary factor receptors to insulin

Onset : 12-15 yrs 35 - 60yrs Juvenile onset Adult onset Diabetes Mellitus • Cause : - Lack of insulin • Features: • Hyperglycemia (blood glucose > 140mg/dl) • Unable to convert glucose to glycogen Insulin • Glycosuria --- glucose in urine • Polyuria – excess urination Insulin receptor • Polydypsia • Polyphagia • Ketosis – due to fat oxidation Glycosuria Diabetes Mellitus

• Weight loss: - Reduced uptake of glucose to cells - Reduced glycolysis

Lipolysis occurs for ATP production In the process Gluconeogenisis occurs (new glucose molecules are produced) Diabetes Mellitus

• Treatment: • Oral Hypoglycemic drugs - tolbutamide, orinase, sulphonylurease

• Insulin Hormone injection

• Sugar free diet Over secretion of Insulin

• Hypoglycemia • Fasting hypoglycemia

• Features: • Hunger • Increased Heart rate • Tremors • Weakness • Nervousness • Sweating Actions of Glucagon

• Hyperglycemic Hormone • Increases blood glucose level • Glycogenolysis • Gluconeogenisis from proteins & fats • Lypolysis ---- Free fatty acids + glycerol

Beta oxidation Gluconeogenesis

Release ketone bodies Somatostatin • δ cells of pancreas

• 14 AA • Functions: - Inhibits insulin & Glucagon secretion - Slows absorption of nutrients from GIT Synergestic Hormone

• Two or more hormones complement the functions of each other and all are needed together for the full expression of hormone effect.. • Example: Insulin, Growth hormone, thyroid hormone – synergestic for body growth.

• Antagonistc hormone : when two hormones oppose the function of each other. • Example : Insulin & glucagon - Calcitonin Parathyroid hormone - MSH & melatonin Thyroid Gland Introduction

• Largest of the glands

• Weight: 15-20gms

• Endodermal origin

• Lies over the trachea just below the larynx.

• Two lobes connected by isthmus.

110

• Thyroid gland is composed of:

• Follicles – lined by cuboidal epithelial cells

• Parafollicular cells / ‘C ‘ cells

• Stromal / interstitial tissue. Structure of thyroid follicle - 3 million follicles – Functional unit - Lined by Cuboidal Epithelial cells - Lumen – colloid – thyroglobulin (Tg) - contains Thyroid hormones

Thyroglobulin Basal membrane of epithelial cells Apical membrane of epithelial cells

Thyroid C-cell

Capillary (Rich blood supply)

Cuboidal epithelial cells

Basement membrane Biosynthesis of thyroid hormone

• Ingredients required: o Tyrosine – amino acid synthesized in the body and attached to thyroglobulin in follicular colloid - Not a dietary essential

o Iodine – obtained from dietary intake

I2 - sea food , bread , dairy products , iodized salt

- Requirement of Iodine – 120 - 150µg/ day Principle Hormones

 Follicular Cells  T4 / THYROXINE – 90%

 T3 / TRIIODOTHYRONINE - 10%

 REVERSE T3 - < 1%

T4 secretion is more than T3 but T3 is four times effective than T4. Therefore on reaching tissues T4 is converted to T3 . Para Follicular C cells  CALCITONIN  3 Iodine --- 3,5,3’ Triiodothyronine (T3)

 4 Iodine ----3,5,3’,5’ Tetraiodothyronine (T4)

• T3 is more potent than T4 • Gudernatsch – 1912- Effect of thyroxine in tadpole

• Kendall (1914) – Isolated Thyroxin crystals in humans

• Harrington & Barger (1927)- molecular structure of thyroxine. • Kendall (1914) – isolated thyroxine hormone • Harrington & Barger (1927)- molecular structure of thyroxine. • Gudernatsch (1912) – effect of thyroxine in tadpole. Mechanism of hormone action Functions of Thyroid Hormone 1) Regulates Basal Metabolic Rate - rate of oxidation and heat production

2) Controls Body temperature

3) Physical & Mental development

4) Enhances Lipolysis Cellular metabolic activity • Known to increase metabolic activity

• Increase in BMR

• Mechanism : • Increase in number and activity of mitochondria

– Power house of the cell

– oxygen consumption & ATP generation

– Increases cellular activity Functions of Thyroid Hormone

1) Regulates Basal Metabolic Rate - rate of oxidation and heat production

2) Controls Body temperature

3) Physical & Mental development

On metabolism Protein Metabolism

Thyroid Hormone

Maintains growth of Stimulates Protein skeletal, muscular & synthesis nervous system

Carbohydrate Metabolism

Reduces glucose uptake from Blood to cells resulting in hyperglycemia – thus called diabetogenic hormone Fat metabolism • Thyroid Hormone Lipolysis

• FFA Glycerol

β - oxidation Gluconeogenisis

ATP generation Cardiovascular system

• Increased Heart rate – SA node activity

• Increases force of contraction

• Increases Cardiac output RESPIRATION • ↑ rate of metabolism

• ↑ oxygen utilization

• ↑ co2, metabolites in blood

• stimulates respiratory center

• ↑ rate and force of respiration Gastro Intestinal tract: – Increases the appetite & rate of secretion of digestive juices.

– Enhances Gastric motility • Hyperthyroidism Hypothyroidsm Diarrhea constipation Central Nervous System • Essential for normal fetal & neonatal brain development • Regulates : - Proliferation of axons - Myelinogenesis - synaptic connections, dendrite formation - Alertness & responsiveness to stimuli - Thought process , speech, Memory Thyroxine Excess • Grave’s Disease / Exophthalmic goiter

Toxic Nodular Goiter Hyperthyroidism Causes : 1. Graves diseases • Cause : autoimmune disease -Thyroid stimulating immunoglobulins are produced • activates TSH receptors on thyroid • Increased secretion of thyroid hormone. 2. TSH secreting tumor in the anterior pituitary Features of Hyperthyroidism

• Elevated BMR • Increased heat production ,sweating • Heat intolerance • Enlarged Thyroid • Heart Beat

• Shortness of breath • Exophthalmus (protrusion of eye ball) Exophthalamus - Protrusion of the eyeballs - edematous swelling of retro orbital tissues

- Cause : (TSI)antibodies attack the soft tissue & muscles behind eyes . - edema of these tissues pushes eyeballs out from bony orbit Toxic Nodular Goiter

• Plummer’s disease.

• Nodules developed on thyroid gland.

• Excess Thyroid hormone synthesis by nodules. Deficiency of Thyroxine

1. In children - Cretinism

2. In Adults – Myxoedema

3. Simple Goiter Cretinism

• Hyposecretion of thyroid hormone • In children • Features : - Stunted physical & sexual growth. - Mental retardation - Rough, dry , wrinkled skin - Pot belly, umbilical hernia Myxoedema / Gull’s disease

• Hyposecretion of thyroxine • In adults Features : - Swelling of face, hands, feet (protein bound chondroitin sulphate + hyaluronic acid in tissue spaces - Reduced BMR - Obesity - Sluggishness activities - Coarse skin , hair fall Goiter • Enlarged Thyroid gland • Cause: - Iodine deficiency in food - Excess TRH & TSH

• Pathology : - Increased TSH ---Constant stimulation of Thyroid hyper activity & hyperplasia of Follicular cells Regulation of secretion

• Controlled by hypothalamic hypophysial – thyroid axis

• TRH – Thyrotrophin Releasing Hormone - Released from Hypothalamus

• TSH – Thyroid stimulating Hormone - by Tyrotrophes of ant Pituitary - stimulates Thyroid Hormone release

• ↑ T3 , T4 in blood exerts Negative feed back effect 138 1 2

Hypothalamic / Graves Pituitary Tumor Disease

Thyroid stimulating Immunoglobulins Excess TSH Over stimulation of Thyroid Over stimulation of Thyroid

Goiter Endemic Colloid Goiter

• Cause : Dietary deficiency of Iodine • - If intake < 10µg/day

(daily req:100-200µg/day) Deficiency of T3 and T4 in blood

Increases TSH levels

Stimulates Thyroid Gland Increasing its size & activity Calcitonin/ Thyrocalcitonin (TCT) • Synthesized by parafollicular cells (C cells) of thyroid gland

• Function : 2+ 3- • Reduces blood Ca & Po4 levels • Site of action : Bone Kidney

• Action opposite to PTH and Vit D Clacitonin – Mechanism of Action • Decreases Plasma Ca2+ levels • Bones : - Inhibits osteoclast activity - Decreases bone resorption - Increases bone deposition - Moves Ca2+ from plasma to bone

• Kidney : Inhibits Inhibits - Inhibits tubular reabsorption tubular Osteoclasts - Increases urinary excretion of reabsorption Ca2+ & Po43-

Total Body Calcium = 1100mg/dl

99 % in Bones 0.9 % in ICF 0.1% in ECF & teeth (plasma + interstitium)

Normal Plasma Calcium = 9.4mg/dl (9 –11 mg/dl )

0.4 mg/dl - 4mg/dl – protein 5mg/dl – complex calcium bound ionized form Metabolically Metabolically inactive active Role of Calcium in ECF

145 Calcium Homeostasis

• Maintaining a constant level of ionic calcium blood is calcium homeostasis.

• Plasma Ca2+ = 9.4mg/dl (9 – 11 mg/dl )

Each 100ml of blood contains 12mg of Ca2+ -source Allen Hormones primarily concerned with calcium homeostatsis:

1. Parathyroid hormone (PTH) 2. 1,25-Dihydroxycholecalciferol Clacitrophes 3. Calcitonin PARATHYROID HORMONE (PTH) PARATHYROID HORMONE (PTH) PARATHYROID GLANDS • small pealike organs • Location: posterior surface of the thyroid • Four in number

• 2 types of cells  chief cells  oxyphil cells

• Chief cells secrete parathyroid hormone (PTH) – Collip’s Hormone • From Endoderm • As epithelial buds from 3rd & 4th pharyngeal pouches

• PTH increases the blood calcium concentration Calcium exchange between bone, intestine , kidney and blood PARATHYROID HORMONE

• Fnt : Plasma Ca2+ concentration 3- Plasma Po4 concentration

• Target organs : 1. Bones Directly 2. Kidney 3. Intestine Indirectly

Collip’s Hormone Action on bone • PTH activates osteoclasts PT H • Acidic secretions of osteoclasts dissolves bone matrix

2+ 3- • Moves Ca & Po4 from bone to plasma

2+ 3- • Both Ca & Po4 are released into blood. Action on Kidney

• PTH reabsorption of Ca2+

• From late distal tubules & collecting ducts • Epithelial Ca2+ channels - apical surface • Calbindin moves it apex – base • Basolateral membrane 3 Na – Ca antiporter & Ca ATPase

3- • Inhibits Po4 reabsorption from PCT Action on GIT

• Indirect Action

• PTH stimulates Kidney

to activate Vitamin D

( 1,25 – (OH)2D3 = Calcitriol)

3- Po4 3- Po4 • Increases absorption of Ca2+ 3- & Po4 from intestine Formation of active VITAMIN D3 / Calcitriol

Inactive form

25 hydroxylase

1 α hydroxylase Functions of PTH – Increase Plasma Ca2+ Reduces Phosphate level by excreting it in urine • PTH

• Excretes phosphate in urine.

• Hypercalcemic & Hypophosphatemic hormone Hyperparathyroidism

• Parathormone excess

• Features: • Excess blood calcium • Bone demineralization • Osteoporosis • Calcification of kidney, arteries, stomach, lungs Bone cyst

Metastasis Hypoparathyroidism

• Deficiency of Parathormone

• No calcium Reabsorption

• × • Reduced blood calcium × × (hypocalcemia) Hypoparathyroidism Tetany

Involuntary contraction of muscle or group of muscles. Features of Tetany

• Hyperexcitibility of nerves & muscles

• Muscle spasm

• Cramps Hypocalcemia – excites Nervous system

Plasma Ca2+ 6mg/dl Plasma Ca2+ 6- 5mg/dl

Neuronal permeability increases to Na+ ions Super excited nerve fibers

Initiates AP even for a Spontaneous impulse subthreshold stimulus discharge to skeletal muscle

Muscle contraction Tetanic muscle contraction Paraesthesia • Tingling sensations in toes , feet , perioral area

• Muscle cramps Contraction of larynx Hormones primarily concerned with regulation of calcium metabolism

1. Parathyroid hormone (PTH) 2. 1,25-Dihydroxycholecalciferol Clacitrophes 3. Calcitonin Calcitonin • Synthesized by parafollicular cells (C cells) of thyroid gland

• Function : 2+ 3- • Reduces blood Ca & Po4 levels • Site of action : Bone Kidney

• Kidney : Inhibits Inhibits - Inhibits tubular reabsorption tubular Osteoclasts - Increases urinary excretion of reabsorption Ca2+ & Po43- ADRENAL Gland Parts of Adrenal Gland

Length : 4 cm Width: 3 cm  2 distinct parts 1. Cortex 2. Medulla

 Both differ in their structure and function • Cortex – Mesodermal

• Medulla – Ectodermal

Adrenal Cortex

• Exhibits three distinct zones: 1. Zona Glomerulosa - Aldosterone

2. Zona Fasciculata - Cortisol

3. Zona Reticularis - Adrenal androgens 1. Zona Glomerulosa

• Outermost layer of cortex • Main site for production of mineralocorticoids

Aldosterone Regulates Electrolyte balance Aldosterone • Function: - Na+ absorption & K+ , H+ secretion

• Target organs: DCT , CT of Salivary Sweat Colon nephrons glands glands Addison Disease • Cause : • Deficiency of Aldosterone

• Features : 1. Low sodium in blood 2. Increased loss of Na+ & water in urine 3. Decreased blood volume , Hypotension 4. Diarrhea 5. Weight loss , nausea, vomiting, weakness 6. Hyper pigmentation – excess ACTH Aldosteronism

• Conn’s Disease • Cause: - Excess Aldosterone secretion • Features: • High sodium in blood • High blood pressure • Edema 2. Zona Fasiculata

• Central layer of Cortex • Main site for production of Glucocorticoids

Cortisol cortisone corticosterone Glucocorticoids

• Cortisol, Cortisone Called Stress hormone / Life saving hormone • Functions • Stress hormone • Increases blood glucose level -Gluconeogenesis -Lipolysis -Proteolysis

• Anti inflammatory action Hyperglycemic effect of Cortisol

Glycogen ------Glucose Fat ------Glucose Anti inflammatory Action • Tissue injury --- inflammation – Cortisol – a) blocks stages of inflammation b) fastens healing process 1. Inhibits secretion of histamine , proteolytic enzymes from injured tissues 2. Reduces capillary permeability Decreases migration of WBC 3.Decreases output of T cells and antibodies --- reduces tissue reactions 4. Helps in rapid healing – provides amino acids for tissue repair Glucocorticoids (steroids) areanti inflammatory and immuno-suppressive ( that is they reduce immune reactions by antibodies)

• Theraputically used in: 1. Rheumatoid Arthritis 2. Skin Allergies 3. Organ transplantation Cushing's Syndrome • Hypersecretion of cortisol. • Causes • Over secretion of CRH, ACTH or both • Adrenal tumors • Features - Centripetal obesity - Limb muscle wasting - Skin pigmentation - High Blood sugar - Excessive facial hair Centripetal obesity • Abnormal fat deposition in • Face – “ moon face” • Chest & abdomen • Buffalo hump • Purple striae Hyposecretion of cortisol

• Crashing during stress • Hypoglycemia 3. Zona Reticularis • Interior Layer of Cortex • Responsible for production of small amount of sex hormones Gonadocorticoids

 Androgen – male hormone Major androgen secreted by adrenal gland is DHEA (dehydroepiandrostenedione )  Estrogen – female hormone

These hormones are secreted in both males & females Hypersecretion of sex corticoids

• Adrenogenital Syndrome / Adrenal virilism • Cause : congenital adrenal hyperplasia • Features : • In Females : masculine features

• In prepubertal Males : - Rapid development of male secondary sexual characters Adrenal medulla

Catecholamines Adrenaline ---- 80% Epinephrine

Nor-adrenaline---- 20% Nor - Epinephrine • Half life – 1-3 min Dopamine ----- < 1% • Degraded : Liver ,kidney • Adrenal Medulla consists Of strands of chromaffin cells. • Each cell stores catecholamines in vesicles Synthesis of Catecholamines Actions of Epinephrine

• Helps to face stress

• Flight or Flight hormone

• Increase blood supply to muscles • Decreases to visceral organs . • Increases blood glucose Hyperglycemic effect of Adrenaline

Fat is broken down to Glycogen is converted to glycerol and converted to Glucose Glucose Thus adrenaline increases blood glucose concentration Actions of Epinephrine

• Heart Rate & respiration • Blood Pressure

• Relaxes smooth muscles of GIT • Thus stops peristalsis

• Relaxes Bronchi • Dilates pupil • Adrenal Glands

Glands of emergency

Adrenal medulla – Triple F gland Adrenaline – 3F hormone – Fight, fright, flight Adrenal Gland

• Is called 4 - S gland

S – Sugar metabolism S – Salt retaining action S – Sex hormones S – Stress reactions Thymus gland

• Origin: from third pharyngeal pouch - Enodermal

• Location: Between pericardium & sternum Thymus gland - Connective tissue capsule • Outer Cortex - Proliferating T- lymphocytes

• Inner Medulla - Lymphocytes - Macrophages - Hassall’s corpus (groups of epithelial cells) Thymus gland

• Function : - Secretes Thymosin

Stimulates development of T- lymphocytes

Thymus gland is called “ Throne of Immunity”, “ Training school of T- Lymphocytes”.

• Atrophies from adolescence to old age Functions of Thymus

• Secretes hormone Thymosine • Functions: - Increases cell division - Promotes growth - Development & differentiation of T- lymphocytes - Resistance to infection - Provides cell mediated immunity

Pineal Gland

• Between 2 cerebral hemispheres

• Below corpus callosum

• Arising from roof of diencephalon

• Reddish – grey, vascular structure

• 150gm

Origin of Pineal gland - ectoderm

Maximum development till 7 years of age later undergoes involution. CaPo4 deposits in pineal gland is called Brain sand or “ Aceruvili” Pineal Calcification

• Starts at puberty

• Cause: - Excess calcium - Excess Flouride deposits

• Also called as Brain sand Pineal Gland • Secretes

- Melatonin - Seretonin - Adrenoglomerulotrophin

Melatonin

• Amino acid hormone – Tryptophan • Action : - Regulates working of gonads - Regulates sleep wake cycle - Maintains biological clock (circadian/ diurnal rhythm) - Controls the secretion of other hormones. - Stimulates immune system • Melatonin • Stimulates the aggregation of melanin in melanocyte.

• Penial gland also secretes - Antigonadal hormone - Controla sexual behavior in mammals

Seretonin

• 5 – hydroxy Tryptamine

• Functions: • Potent vasoconstrictor • Increases blood Pressure

Adrenoglomerulotrophin

• Adrenoglomerulotrophin secreted by pineal gland

• Stimulates Zona Glomerulosa

• To secrete hormone Aldosterone Gonadal Hormones

Testes Ovary

Oestrogen Testosterone Progesterone Relaxin Heterocrine glands Testis

• Parts:

• Seminiferous Tubules

• Interstitial tissue Testis • Interstitial cells

secretes

Testosterone

Controlled by LH of ant pituitary Testosterone

1) Develops external and internal male genitalia

2) Male secondary sexual characters Ovary

• Female gonad • Located in abdomen

• Consists of • Ovarion follicles

• Stromal tissue Estrogen • FSH stimulates follicular development in ovary.

• Develops into Graffian Follicle. Primary Secondary Follicle Follicle

Antral Follicle Graffian Follicle • Granulosa cells of Graffian follicle

Estrogen

• Female secondary sexual characters • Development of reproductive organs. • Menarche • After release of ovum from Graffian follicle

Process --- Ovulation

• Follicle is converted to corpus Luteum secretes Progesterone Proliferative Phase Secretory Phase

Range – 21 – 35 days Follicular Phase Luteal Phase

Bleeding Proliferatory Secretory phase Phase Phase If fertilization takes place resulting embryo is implanted in thick uterine endometrium Functions of Progesterone

• Uterine endometrial growth • Implantation of fertilized ovum in uterus • Development of placenta in pregnancy. Mammary Gland Estrogen Progesterone

• Proliferation of ducts • development of lobules and • development of stromal alveoli. tissues • fat deposition in breast • Supports secretory function • Pigmentation of areola of breast during lactation. Relaxin

• From Corpus luteum

• Function:

• relaxes uterus • inhibits uterine contractions during pregnancy. Relaxin

• At term – from placenta

• Function:

• relaxes pubic symphysis and other pelvic joints in parturition. Endocrine Function • Synthesizes hormones like: - human chorionic gonadotrophin (HCG) - human chorionic somatotrophin - Estrogen - Progesterone - Inhibin / Activin

Human Chorionic Gonadotrophin

1. Prevent involution of the corpus luteum in pregnancy. 2. Causes corpus luteum to secrete large quantity of progesterone for few months. 3. HCG in urine indicates pregnancy. Human chorionic somatomammotrophin

• Human placental lactogen (HPL)

• FUNCTIONS: 1) Promotes growth of mammary gland & stimulates production of milk . Inhibin / Activin

• Source: - Corpus Luteum, Placenta , Testis

• Function • Inhibits or activates Gonadotrophic activity of Hypothalamus & pituitary.

Eunnuchoidism

• Reduced secretion of testosterone.

• Underdeveloped secondary sexual characteristics.

• Non functional gonads.

• Gynecomastia Precocious puberty

• Boys - Excess testosterone before 10 years age.

• Girls - Excess oestrogen before 9 years Gynaecomastia

• Development of mammary tissue in males

• Cause : Hormonal imbalance • Low androgen levels • Androgen resistance • Hyper prolactinemia • Fetal exposure to high levels of female hormones Atrial Natriuretic Factor

• Hormone secreted by atrial wall.

• Function: - Reduces Blood pressure - Vasodilation - Natriuresis & diuresis Reabsorption of Na+ , Excess Aldosterone Water

Venous Return BP

Release of Atrial Stretching ANP Atrial natriuretic peptide Normal BP Natriuresis & Diuresis

Hormones of Kidney

• Renin

• Erythropoietin

• Vitamin D activation Renin

• Secretion – JG cells of Juxtglomerular apparatus

• stimulus : Reduced blood pressure • Function : Increases blood pressure Renin Angiotensin System

Renin released from ↓ BP JG apparatus

Angiotensin Angiotensin I

ACE

Vasoconstriction Angiotensin II 1 3 2 Release aldosterone Retention of salt & Stimulates water thirst center ↑BP Blood volume Erythropoietin

• Secretion : cells of Peritubular capillaries • Blood vessels of nephron

• Function: - Stimulates Erythropoeisis Early Intermediate Late

PPSC Proerythrobla Normobla Reticulocyt RBC st st e 248 Formation of active VITAMIN D3 / Calcitriol

Inactive form

25 hydroxylase

1 α hydroxylase • Cells of Proximal Convoluted tubule

• Has an Enzyme

1 α hydroxylase

• Gives another OH group to 25- OH D3

• Results in 1,25- OH D3 – active form of vitamin D HORMONES SOURCE ACTIONS

- Increases GASTRIN G – Cells in stomach - Gastric juice - Gastric motility

CCK –PZ – Cells of duodenum , - Succus entericus I - enzyme rich pancreatic jejunum juice - contraction of gall bladder to release bile - intestinal motility

- Alkaline watery pancreatic SECRETIN S – Cells of duodenum , & bile secretion jejunum - gastric secretion GIP mucosa of - gastric motility (gastric inhibitory duodenum , polypeptide ) jejunum

VIP Jejunum in response - Intestinal secretions (vasoactive intestinal to fatty meals - inhibits gastric polypeptide ) juice - dialates blood vessels Duocrinin cells of duodenum - Intestinal secretions (Brunners gland)

Enterocrinin small intestinal - Succus entericus epithelium - Somatostatin delta cells of Islets of - insulin , glucagon Langerhans from pancreas Local Hormones 1) Histamine

Function : - Inflammatory , allergic reactions - Vasodilation 2) Prostaglandin

• Secretion : Fatty acids in cell membrane of various tissues

• Functions - Induces uterine contractions - Constriction of bronchioles 3) Leukotrines

• Secretion : - Mast cells

- Function: - In allergic , inflammatory reactions - Attracts neutrophils, eosinophils to the site of allergen

4) Thromboxane

• Secretion: - Activated Platelets

• Functions: • Vasoconstriction • Platelet aggregation • blood coagulation

5)Pheromones

• Odoriferous secretions by an individual into environment which produces response in other member of same species. Can attract male moth from a distance of 3 – 4 km 6) Cytokines

• Interleukins & interferrons

• Secretion: - Macrophages - Lymphocytes - infected cells • Functions: - Intercommunication & stimulation of T cells 7) Kinins

• Chemicals secreted by all organs of the body at times of chemical change in ECF. • Functions: - Dilates blood vessels - Reduce BP - Reduce clotting time This chemical is called “ First aid hormone” Negative Feedback Positive Feedback uterine contraction at onset of labour

Releases Oxytocin

Intensifies uterine contractions Further oxytocin release stops only after the birth process