physiology chapter 19: Peripheral endocrine glands

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the thyroid gland consists of two left and right lobed joined by what in the middle?

isthmus

bone mass diminish when

movement is limited and inactive life style is carried out

the two main cells types in parathyroid glands include....

oxyphil cells and chief cells

chief cells secrete what

parathyroid hormone

Parathyroid hormone acts to increase

plasma level of Ca2+

Parathyroid hormone utilizes bone as a bank for withdrawing Ca2+ when overall calcium level falls in the body. By two mechanisms:

1) Transfer Ca2+ from bone fluid into plasma (Immediate) 2) Transfer by stimulating bone dissolution (slow)

action of parathyroid hormone

1. Parathyroid hormone withdraw Ca2+ from bone fluid through PTH-activated Ca2+ pumps located in the osteocytic-osteoblastic bone membrane 2. Parathyroid hormone activates osteoclasts (bone dissolving cells that breakdown bones) and Ca2+ content of the bone is released and is diffused into the plasma.

Triiodothyroxine (T3): contains how many atoms of iodine?

3

Thyroxine (T4): contains how many atoms of iodine?

4

myxedema

A condition where edema occurs due to high production of glucosaminoglycan, a water retaining carbohydrate, that infiltrate the skin. puffy appearance of the face, hands, and feet, known as

Glucagon increases blood glucose level-Just opposite of insulin

Action on carbohydrate: Increase blood glucose level Hepatic production of glucose and release into blood Convert Glycogen into glucose in liver Action on fat: Promotes break down of stored fat (triglycerides) and inhibits its synthesis. Action on protein: Increase amino acid level in blood Inhibits hepatic protein synthesis and promotes degradation of hepatic protein. Stimulates gluconeogenesis. Glucagon secretion is high during post-absorptive (fasting, in between meals)

adrenalcortical hypersecretion

Addison's disease: Primary adrenocortical insufficiency where all layer of adrenal cortex is undersecreting. Both aldosterone and cortisol are deficient. Due to autoimmune attack by erroneous antibodies against adrenal cortex. Symptoms: Hyperkalemia (K+ retention) and hyponatremia (Na+ depletion) Poor response to stress in cortisol deficiency, which is due to hypoglycemia (low blood glucose)

Adrenal sex hormone: Androgen and estrogen

Adrenal cortex secretes both Androgen and Estrogen in male and female Most biologically relevant hormone is dehydroepiandrosterone (DHEA) It is physiologically not relevant in male due to more dominant testosterone but is important in female DHEA exerts androgenic function in female such as: growth of (armpit) hair enhancement of the pubertal growth, development and maintenance of female sex drive DHEA secretion peaks at puberty and declines with aging ACTH control adrenal androgen secretion

Androgen Hypersecretion

Adrenogenital syndrome: effect of excessive sex hormones on genitalia and associated sexual characteristics. Hirsutism: Female develop male pattern body hair, deepening voice, and more muscular arms and legs. Female characteristics diminish (shrinkage of breasts, suppression of menstrual cycle, etc) Pseudohermaphroditism: a female who have ovaries but develops external genitalia like man. Precocious pseudopuberty: Young boys prematurely develop male secondary sexual characteristics such as deep voice, beard, enlarged penis, and sex drive. Excess adrenal androgen has no effect in adult males because effect of weak DHEA is dominated by testosterone.

Mineralcorticosteroids

Aldosterone is important in electrolyte balance by regulating the Na+ and K+ balance in the body and control blood pressure. ... Acts on distal and collecting tubules of Kidney Promotes Na+ retention and K+ elimination Na+ retention indirectly retains H20 through osmotic gradient Increase ECF/Plasma volume and provides long-term regulation of blood pressure. In the absence of Aldosterone , a person can die due to circulatory shock (rapid fall in plasma volume). Secretion is controlled by RAAS mechanism in response to fall in Na+ and plasma volume and direct secretion by rise in plasma K+ Not regulated by Anterior Pituitary gland.

graves disease

An autoimmune diseases in which body produces antibodies (Thyroid stimulating immunoglobulin, TSI) that stimulate thyroid cells by targeting TSH receptors. result in bulging of eyes (exophthalmos) due to inflammation of eye muscles

fuel metabolism

Anabolism/Catabolism Glycogenesis Glycogenolysis Gluconeogenesis Protein synthesis Protein degradation Fat synthesis Fat breakdown

sex hormones

Androgen, a sex hormone involved in reproductive activity

bone remodeling

Bone is composed of hydroxyapatite crystals consisting of precipitated calcium phosphate salts in the bone matrix. Osteoblast cells deposit bone matrix for crystallization of Ca2+

Consequences of PTH hypersecretion

Ca2+ blocks sodium channels and increases depolarization threshold Muscle weakness and neurologic disorders (reduced muscle excitability), decreased alertness, poor memory, and depression Thinning of bone leads to skeletal deformities Calcium containing kidney stones can impair kidney function

adrenal medulla

Catecholamines (epinephrine and norepinephrine)

thyroglobulin

Chief substance in colloid that incorporate thyroid hormone during its synthesis.

How is plasma calcium level balanced in the body?

Controlled at three levels: Absorption (intestine) Excretion (Kidney) Reservoir (Bone)

Glucocorticoids

Cortisol plays important role in glucose metabolism, protein metabolism, and lipid metabolism to adapt to stress. ...... Metabolic effect: Increase blood glucose level (to feed the brain) at the expense of proteins and fats Cortisol stimulates gluconeogenesis (liver) Cortisol inhibits glucose uptake by tissues except brain Stimulates protein metabolism in muscle Stimulates lipolysis in adipose tissue Catecholamine require cortisol action for their vasoconstriction action (Permissiveness) Adaptation to stress: Cortisol increases pool of glucose, amino acids, and fatty acid for use during stress. Anti-inflammatory and immunosuppressive effects: Cortisol suppress immune responses by interfering every step of inflammation and with antibody production by lymphocytes. ACTH from anterior pituitary enhances secretion of cortisol from adrenal cortex.

cortisol hypersecretion

Cushing's syndrome Due to excessive secretion of ACTH Too much glucose production, extra glucose deposits in face and other places Loss of muscle proteins due to excessive amino acids mobilization

Regulation of thyroid hormone synthesis

Falling TH levels stimulate TSH release from pituitary High TH levels feed back to hypothalamus hypothalamus eventually decreasing TSH levels. Controlled by conditions which require greater energy output (pregnancy, cold, stress) stimulate the hypothalamus to secrete thyrotropin-releasing hormone (TRH), which triggers TSH release. TRH can override negative feedback controls.

Ca2+ metabolism disorders

Due to abnormal levels of: 1) PTH 2) Vitamin D PTH hypersecretion and hyposecretion hyperparathyroidism: hypercalcemia and hypophosphatemia Hypoparathyroidism: hypocalcemia and hyperphosphatemia

aldosterone hypersecretion

Due to abnormality in adrenal (tumor) that increases aldosterone secreting cells (Primary hyperaldosteronism or Conn's syndrome) Abnormally high activity of RAAS (secondary hyperaldosteronism) Leads to increase blood pressure

thyroid hormone process

Follicular cells synthesizes tyrosine and binds with thyroglobulin Tyrosine containing thyroglobulin is then transported to colloid space by exocytosis Since thyroid hormone synthesis require iodine, iodine is exported into follicular cells from plasma by Na-I symporters in the follicular cells Iodine is then oxidized to active form by TPO at the luminal membrane of follicular cells Iodine channels present in the luminal membrane exports active iodine into colloid space Exported iodine subsequently binds to tyrosine to form MIT (1 iodine binding) and DIT (2 iodine binding) T3 is formed by coupling of 1 DIT and 1 MIT T4 is formed by coupling Two DITs.

Importance of Maintenance of Plasma Calcium Level

Function in neuromuscular excitability Excitation-contraction of cardiac and smooth muscle Stimulation of secretory cells Maintenance of tight junction Clotting of blood Intracellular function as second messenger

Hypothyroid conditions:

Goiter Myxedema Cretenism

calcitonin

Hormone important in Ca2+ metabolism but not related to thyroid hormone production or secretion.

Consequences of PTH Hyposecretion

Increase neuromuscular excitability leads to muscle cramps and twitches Increases irritability and paranoia Complete absence can lead to death.

action of parathyroid hormone in intestine

Indirectly promote absorption PTH activate vitamin D Vitamin D promotes Ca2+ and PO43- absorption in small intestine

Insulin: Action on carbohydrates

Inhibits blood glucose level Facilitates glucose transport into most cells Recruits glucose transporters (GLUT) to cell surface in the plasma membrane Stimulates glycogenesis Conversion of glucose to glycogen in liver and muscle Inhibits glycogenolysis Suppress conversion of glycogen to glucose Inhibits gluconeogenesis Suppress conversion of amino acids and fatty acids into glucose

Pancreatic endocrine secretions regulate fuel metabolism

Insulin (beta cells) Decrease blood glucose level Pass glucose from blood to cells Glucagon (alpha cells) Increase blood glucose level Pass glucose from storage to circulation Somatostatin (Delta cells) Inhibits digestion and nutrient absorption and decrease plasma nutrient level

Insulin: Action on proteins

Lower blood amino acids and enhance protein synthesis Promotes active transport of amino acids into cells Enhances protein synthesizing machinery Inhibits protein degradation By building protein, insulin is essential for normal growth.

Insulin: Action on Fats

Lower blood fatty acid level and promote triglyceride storage in adipose tissue Transport glucose into adipose tissue by recruiting GLUT-4 Enhances chemical reaction to convert fatty acid and glucose into triglyceride synthesis Blocks lipolysis (breakdown of fats into fatty acid) and release of fatty acid into blood Ultimately, removes fatty acid and glucose from blood and promote storage as triglycerides.

colloid

Lumen of follicle is filled with this substance useful for storage of secreted thyroid hormone.

follicle

Made up of single layer of follicular cells that form ring like structure.

follicular cells

Major secretory cells of thyroid gland that are organized into follicle.

cretenism

Sever hypothyroidism in children characterized by dwarfism and mental retardation. This is due to lack of proper thyroid hormone stimulation of growth and CNS development.

functions of epinephrine

Norepinephrine exerts similar response as epinephrine through ⍺1 receptor Vasoconstriction Epinephrine exert unique effect through exclusive β2 receptors (heart and skeletal muscles) Eg. Vasodilation Sympathetic nervous system control stimulation of epinephrine, so epinephrine reinforces activity of sympathetic nervous system .. Catecholamines function through second messenger pathways (cAMP, IP3, and DAG). .... Influence body's metabolic activity to prepare for "fight or flight" situations. Increases cardiac output (increase the rate and strength of cardiac contraction) Increase arterial blood pressure Dilation of respiratory airways Reduce digestive activity Inhibit bladder emptying ... Influence body's metabolic activity to prepare for "fight or flight" situations. Metabolic adjustments Make more energy available Increase tissue metabolism Increase blood glucose level by various mechanisms Stimulates gluconeogenesis Inhibits glycogenolysis Increases arousal and alertness Prepare for quick thinking Increases sweating to get rid of body heat

thyroid hormone secretion

Once formed in colloid, thyroid hormone is engulfed by the follicular cells through phagocytosis Bound thyroglobulin is then split and iodinated thyroid hormone is freed Thyroid hormone is diffused into the blood stream for distribution into the body tissues

adrenal cortex

Outer cortex: Zona glomerulosa (Minerolcorticoids) Inner cortex: Zona fasciculata, zona reticularis (Glucocorticoids, Sex hormone)

action of parathyroid hormone in kidney

PTH promotes Ca2+ reabsorption and PO43- elimination PTH action in kidney simultaneously increases plasma Ca2+ and reduced plasma PO43- Urinary excretion of PO43- is important to prevent reprecipitation in bone, which would decrease plasma Ca2+ level.

Insulin and glucagon balances

blood glucose and fatty acid level

Consequences of Vitamin D deficiency

Reduced absorption of Ca2+ in intestine leads to low plasma Ca2+ level Low plasma Ca2+ level triggers PTH secretion PTH increase plasma Ca2+ at the expense of bones Lack of Ca2+ in bone leads to demineralization and weakening of bone, which can lead to bone deformation in children. This condition is known as Rickets.

What regulates thyroid hormone secretion from thyroid gland?

Released from thyroid gland in response to TSH TSH are released from adenohypophysis (anterior pituitary glands), which is activated by thyroid releasing hormone (TRH) produced by hypothalamus Therefore, thyroid hormone secretion is controlled by hypothalamus-pituitary regulatory axis TSH also regulate the production of colloid and iodine transport into follicular cells

Integrated stress response

Role of sympathetic nervous system and epinephrine Role of cortisol Role of other hormones: Less insulin and more glucagon secretion Increased RAAS and Vasopressin to maintain high blood volume and high blood pressure

Adrenal Medulla: Norepinephrine and Epinephrine

Secretes two hormones commonly called catecholamines Norepinephrine and Epinephrine Modified postganglionic sympathetic neuron cells called Chromaffin cells in adrenal medulla are the adrenomedullary hormone secreting cells Adrenal medulla predominantly secrete epinephrine (80%) and secretes norepinephrine in small amount .... Norepinephrine is secreted predominantly by sympathetic neurons Hormones are stored in chromaffin granules to protect against cytoplasmic enzymes before secretion Hormones secreted by exocytosis of chromaffin granules Norepinephrine and Epinephrine are structurally similar except that epinephrine has a methyl group. Also have differing affinities for adrenergic receptors

Control of insulin secretion

Secretion of insulin is controlled by increase blood glucose level

c cells (also called parafollicular cells):

Secretory cells found in the interstitial space between the follicular cells that secrete hormone calcitonin.

What regulates the PTH secretion?

Since the primary effect of PTH is to raise Ca2+ level in plasma, its secretion is dependent upon plasma level of Ca2+ Chief cells in parathyroid glands are sensitive to plasma level of Ca2+ Plasma Ca2+ regulate PTH secretion in a negative feedback loop mechanism

Mode of Action of Steroid Hormones

Steroid hormones are lipophilic Can easily diffuse out from secreting cells and get access to blood In the blood, it is carried bound to the plasma proteins In the target cell, binds to cytoplasmic receptor Mineralocorticoid receptor (MR) Glucocorticoid receptor (GR) Androgen receptor (AR) .... Steroid hormone-receptor complex moves to nucleus Binds to Hormone response element (HRE) in DNA Upon binding to DNA, it activates transcription of Hormone target proteins Effector proteins carry out hormone specific functions.

function of thyroid hormone in the body

TH has its function in virtually all cells in our body with some exceptions: Brain, spleen, testes, uterus, and thyroid gland itself Increases basal metabolic rate Regulates heat production (Calorigenic effect) by stimulating glycolysis enzymes Participates in the regulation of blood pressure by controlling adrenergic receptors Regulates tissue growth and development (especially skeletal muscle, nervous system, and reproductive systems).

T4, Thyroxine (tetraiodothyronine) and T3 (Tri-iodothyronine

Two iodine-containing hormones produced by follicular cells

Unwanted Stress Response can be harmful

Wanted stress response against stressor such as: Physical (trauma, surgery, intense heat or cold) Chemical (reduced O2 supply, acid-base imbalance) Physiologic (heavy exercise, hemorrhagic shock, pain) Infectious (bacterial invasion) Unwanted and harmful response to psychological or emotional stressors such as: Anxiety, fear, sorrow, Personal conflicts, change in lifestyle This can lead to high blood pressure

hyperthyroidism

access TH secretion Marked by increased metabolic rate, sweating, rapid heartbeat, nervousness, and weight loss.

oxyphill cells

appear at the onset of puberty but theur exact function is inknown

goiter

can also accompany hyperthyroidism due to excess secretion of TSH due to hypothalamus or anterior pituitary defect, which can overstimulate thyroid gland and simultaneous produce too much of T3 and T4.

hypothyroidism

deficient in TH secretion due to.... 1)primary failure of the thyroid gland 2) Secondary deficiency in TRH, TSH or both 3) From inadequate dietary iodine Marked by low metabolism, cold, lethargy, and mental sluggishness Less active thyroid hormone in circulation ceases negative feedback inhibition of anterior pituitary or hypothalamus. Increase in TSH secretion stimulates increases size and number of follicular cells to increase thyroid hormone secretion, which leads to enlarged thyroid gland, which is goiter.

adrenal glands

embedded above kidney secrete.... Steroid hormones Mineralocorticoids (Aldosterone) Glucocorticoids (Cortisol) Sex hormones (Dehydroepiandrosterone) Catecholamines Epinephrine Norepinephrine

in hypothyroidism Thyroid hormone suppress production of

glycosaminoglycans by connective tissue and when it is deficient there is overproduction and results in edema.

hyperthyroid conditions

grave's disease

The most common cause of hyperthyroidism is

graves disease

T4 is secreted in ______________ quantity, but has _______________ active than T3

greater, less

movement and mechanical stress enhance bone

growth and bone deposition pathway

T3 has ____________ affinity for receptors and is significantly ____________ active than T4

higher, more

Problems due to homeostatic imbalance in Thyroid hormone include.....

hypothyroidism hyperthyroidism

where are parathyroid glands located?

in the posterior surface of the thyroid glands

osteoporosis

reduction in bone mass

aging triggers bone

resorption more than bone deposition

osteoclasts cells

secreted Hcl and dissolve the organic matrix to dissolve the Calcium phosphate matrix to release Ca2+ and phoshpates.

Bone Fluid that lies between bone membrane and the adjacent bone contains

the pool of Ca2+

T4, Thyroxine (tetraiodothyronine) and T3 (Tri-iodothyronine: these two hormones are collectively called

thyroid hormone

parathyroid hormone

together with calcitonin and vitamin D, is a major hormone controlling blood Ca2+ levels.


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