Npb_Endocrinology

Front 1

Define endocrinology.

Back 1

def. the study of the control of the physiological processes of systems of cells, tissues, organs, and glands that secretes hormones

Front 2

Define hormone.

Back 2

def. chemicals produced by one cell which enters the bloodstream, is transported to a different body location, and then binds to a specific receptor on a target cells, altering function of the target

Front 3

2 major control system of the human body

Back 3

1) nervous system
a. rapid, short term signaling
b. precies, direct interconnection

2) endocrine system
a. slower acting, longer lasting signal
b. diffuse, indirect connection (via the blood)

Front 4

Sequence of Endocrine Signaling

Back 4

endocrine gland -> hormone -> receptor binding -> postreceptor events -> response

Front 5

General Functions of the Endocrine System

Back 5

1) homeostasis
2) Reproduction
3) Growth & Development
4) Behavior

Front 6

2 Types of Hormones

Back 6

1) tropic hormone: stimulate and maintain their endocrine target tissues; ex TSH

2) non-tropic hormone - hormones exert effects on non-endocrine target tissues

Front 7

3 Classes of Hormones

Back 7

1) Peptides & Proteins
a. hydrophobic
b. small chains of a.a.
c. synthesized via transcription & translation
d. processed in the Golgi/ER
e. mature hormone stored in secretory granules and exocytose when matured

2) Amines
a. derived from naturally occuring a.a.

3) Steroids
a. derived from cholesterol
b. lilophilic
c. after synthesis, diffuse thru PM into blood
d. body can't degrade steroids so they can be taken orally

Front 8

Postreceptor Events Mechanism for the Classes of Hormone

Back 8

1) Peptides - G coupled protein pathway

2) Steroids - DNA txn

Front 9

Regulation of Hormone Levels

Back 9

1) negative-feedback control
2) neuroendocrine reflexes
3) circadian rhythm

Front 10

Regulation of Hormone Responsiveness

Back 10

1) down regulation of hormone receptors
2) permissiveness
3) synergism
4) antagonism

Front 11

types of endocrine disorder

Back 11

1) insufficient activity -
a. hyposecretion
b. increased removal from blood
c. abnormal target responsiveness

2) overactivity
a. hypersecretion
b. reduced plasma carriers
c. decreased removal from blood

Front 12

Features of the Pineal Gland

Back 12

- tiny structures located in the center of the brain
- releases melatonin
- works in conjunction w/SCN to entrain circadian rhythm w/external cues
- additional fx: shuts down ovulation, highly effective anti-oxidant, induces natural sleep, enhances immunity

Front 13

Circadian Rhythm

Back 13

- regular fluctuation in physiological or performance parameters that occur with a roughly 24 hour period
- rely on an endogenous generator and entrainment
- focal ablation of the SCN eliminates circadian rhythm ,
- mammalian SCN integrates mult. inputs, but light is the dominant cue for entrainment
- animals placed in cts darkness exhibit "free run' which reflects the period of endogenous generator
- phototransduction apparatus for photentrainment in mammals is located in the eye. Genetic "knockout" of specialized photoreceptors located in the retina, in combination with rods and cones, together completely abolish photoentrainment

Front 14

H-P axis; hypothalamus & Pituitary axis

Back 14

- integratin of both neural and endocrine pathway:
a. produces both tropic and non-tropic hormone
b. controls growth, dvlpmnt, reproduction, stress response, water reabsorption, lactation, contractions during childbirth
- from the hypothalamus:
a. large # input
b. integrates signals from internal and external envir. to coordinate an endocrine response
c. directly controls the pituitary

- from the pituitary
a. anterior & posterior
b. collectively secretes 8 hormones

Front 15

Hormones released by H-P axis

Back 15

1) vasopressin - enhances water retention in kidney. causes contraction of arteriolar smooth muscle

2) oxytocin - stimulates contraction of uterine smooth muscle during childbirth, influences bonding

Front 16

Hormones released by Anterior Pituitary

Back 16

1) Growth Hormone (GH)
2) Thyroid-stimulating hormone (TSH)
3) Adrenocorticotropic hormone (ACTH)
4) Follicle Stimulating Hormone (FSH)
5) Prolactin (PRL)
6) Luteinizing Hormone (LH)

Front 17

What is a hypophysiotropic hormone?

Back 17

- Hypothalamus secretes hypophysiotropic hormone to control secretion of anterior pituitary hormone

Front 18

2 feedback mechanism by target gland hormones

Back 18

- long loop negative feedback: hormones produced by the target endocrine gland feeback on either the hypothalamus or anterior pituitary

Front 19

FActors affecting growth

Back 19

1)genetic determination
2)adequate diet
3)stress-free, disease-free envir.
4) growth hormones

Front 20

Features of GH

Back 20

- promote cell growth via hyperplasia or hypertrophy
- metabolic fx: mobilize fat stores as a major energy source while conserving glc

Front 21

Factors of Bone Growth

Back 21

- epiphyseal plate cartilage: active growing region of bone
- chondrcytes cartilage cells whose hyperplasia and hypertrophy trigger long bone growth
- osteoclasts bone breakers
- osteoblasts bone formers
osteocytes entrapped osteoblasts important for Ca exchange
- some actions mediated by somatomedins
- mult factors control of GH secretion

Front 22

other hormones affecting growth

Back 22

- thyroid hormone: permissive for GH, hypothyroidism leads to stunting, hyper nothing
- insulin: bidirectional effect on growth
- androgens & estrogens: stimulate linear growth and wiegh gain & increased muscle mass, then ultimately lead to closure of epiphyseal plate

Front 23

Growth Hormone Disorder

Back 23

1) GH deficiency occuring in childhood -> dwarfism

2) excess GH in childhood -> gigantism

3) excess GH excretion after adolescence -> acromegaly, condition in which bones thicken especially in extremeties and face

Front 24

Anatomy of Thyroid Gland

Back 24

- follicular gland: secrete T4 (thyroxin) & T3 (triiodothyronine)
- colloid: thyroglobulin produced by follicular cell

Front 25

Requirement for thyroid hormone synthesis

Back 25

Tyrosin & Iodine

Front 26

Steps in Synthesis of Thyroid Hormones

Back 26

1) Thyroglobulin produced in Golgi/ER of follicular cell and then secreted into colloid
2) iodine actively transported from blood to colloid
3) in colloid, tyrosine become mono- or di-iodinated
4) tyrosine couple together while still on the thyroglobulin producing T3 & T4
5) upon stimulation, follicular cells phagocytize a piece of the colloid
6) endocytotic vesicl fuses with lysosome & lysosomal nz cleaves colloid releasing t4 & t3 into the blood
7) iodine reuptook from dit & mit

Front 27

relative percentage of release of t3 to t4

Back 27

90% t4, other t3
80% of t3 comes from t4

Front 28

what percentage of t3 and t4 are free in the blood

Back 28

1% t3; 0.1% t4

Front 29

name some carriers for t3 & t4

Back 29

- thyroxin-binding globulin
- albumin
- thyroxine-binding prealbumin

Front 30

Effects of thyroid hormone

Back 30

1) primary determinant of BMR
a. slow onset, long duration
b. calorigenic
2) permissive for GH, epinephrine, norepinephrine
a. increases receptor to increase responsiveness to catecholamines
b. stimulates GH secretion and increases effectiveness of somatomedins

Front 31

Regulation of thyroid hormone

Back 31

- hpothalamus-pituitary-thyroid axis
- activated by stress, cold in infants

Front 32

Abnormalies of thyroid Function

Back 32

1) Hypothyroidism
- Caused by failure of thyroid gland, failure of H-P axis, or lack of dietary iodine.
- Leads to myxedema in adults, cretinism in children.
- Treatment is replacement therapy with exogenous thyroid hormone or iodine.
2) Hyperthyroidism
- Caused by autoimmunity (Graves disease Figure 19-4), excess in H-P axis, or thyroid tumor.
- Graves disease often accompanied by exopthalmos (bulging eyes Figure 19-5).
- Treatment is partial removal of oversecreting thyroid, radioactive iodine, or antithyroid drugs.
3) Goiter can occur with either hypo- or hyper-thyroidism, depending on the etiology

Front 33

Anatomy of the Adrenal Gland

Back 33

- Adrenal cortex - zonas glomerulosa, fasciculate and reticularis. Secretes steroids (below).
- Adrenal medulla - secretes catecholamines

Front 34

Cortisol (glucocorticoids)

Back 34

- Metabolic effects of cortisol:
a) increase blood glucose by decreasing uptake everywhere except the brain and by increasing
hepatic gluconeogenesis.
b) increase free fatty acids (lipolysis).
c) increase blood amino acids (proteolysis).
- Permissive for catecholamines to induce vasoconstriction.
- Stress adaptation.
- Anti-inflammatory and immunosuppressive
- Regulated by hypothalamus-pituitary-adrenal cortex axis (CRH, ACTH) (Figure 19-8)
- Cortisol hypersecretion: Cushing’s syndrome

Front 35

DHEA

Back 35

- Weak masculinizing hormone
- In males, more abundant but weaker than testosterone
- In females, significant role in pubertal growth spurt, sex drive
- Hypersecretion in childhood results in adrenogenital syndrome (Figure 19-10; 19-11)
males: precocious pseudopuberty (no sperm production)
females: pseudohermaphroditism

Front 36

Abnormalities of adrenal cortex

Back 36

1) Aldosterone hypersecretion
- Conn’s syndrome, caused by tumor
- hypernatremia, hypokalemia, high blood pressure

2) Cortisol hypersecretion
- Cushing’s syndrome, caused by tumor or excess CRH/ACTH
- hyperglycemia, muscle weakness, hippocampal atrophy

3) DHEA hypersecretion
- Adrenogenital syndrome, caused by defect in cortisol pathway
- masculinization, sterility, symptoms of cortisol deficiency

4) Adrenocortical hyposecretion
- Addison’s disease, caused by autoimmune destruction of adrenal cortex
- aldosterone symptoms: hyperkalemia, hyponatremia, low blood pressure
- cortisol symptoms: hypoglycemia, poor stress response

Front 37

Catecholamines

Back 37

1) Secreted by adrenal medulla under influence of sympathetic nervous system (Figure 7-4)

2) Effects of catechoamines
- reinforce sympathetic response “fight or flight”
- increased cardiac output
- generalized vasoconstriction
- vasodilation of vessels supplying heart, muscles and lungs
- increased glucose and fatty acids in blood
- increased alertness

3) Secretion is part of a generalized stress response (Figure 19-11; 19-12)

Front 38

Reaction in fuel metabolism

Back 38

- glycogensis: glucose is stored as glycogen, blood glucose goes down
- glycogenolysis: glycogen is broken down to glucose, blood glucose goes up
- gluconeogenesis: amino acids are interconverted to glucose, blood glucose goes up
- protein synthesis and degradation
- fat synthesis and degradation

Front 39

Major pathways in fuel metabolism

Back 39

Food intake -> digestion -> absorbable units -> usable metabolic pool in body <-> storage

Front 40

Absorptive state (fed)

Back 40

- preferred fuel (glucose) is plentiful, used by most cells
- rapid anabolism of absorbed fuel subunits
- lasts about 4 hours following a mea

Front 41

Postabsorptive state (fasting)

Back 41

- glucose sparing at non-neural tissue
- gluconeogenesis is activated
- anabolism of amino acids and fatty acids is curtailed

Front 42

Pancreatic hormones insulin and glucagon regulate fuel metabolism

Back 42

islets of Langerhans:
- beta cell secretes insulin
- alpha cell secretes glucagon

Front 43

Effects of insulin on cho's, fat, and pro's

Back 43

carbohydrate: insulin lowers blood glucose levels
- facilitates glucose transport into most cells
- stimulates glycogenesis, inhibits glycogenolysis, inhibits gluconeogenesis
fat: insulin lowers blood fatty acid levels and promotes triglyceride storage
protein: insulin lowers blood amino acid levels and enhances protein synthesis

Front 44

Factors controlling insulin secretion

Back 44

- major factor: negative feedback between beta cells and plasma glucose level
- amino acid levels in blood
- gastrointestinal hormones (feedforward control)
- autonomic nervous system

Front 45

Diabetes mellitus (too little insulin activity)

Back 45

Most common endocrine disorder
Results from inadequate insulin action
Most prominent feature is elevated blood glucose levels, leading to “sweetened” urine
Type I: lack of insulin secretion
- childhood onset
- treated with insulin injections
Type II: normal or increased insulin secretion but reduced sensitivity of target tissue
- adult onset
- treated with diet control
Short-term consequences of insulin deficiency
- hyperglycemia causes dehydration, can lead to renal and/or circulatory failure
- switch to fats as main energy source, can lead to ketosis and acidosis
Long-term consequences
- on average, reduced life span due to degenerative disorders of the vasculature and nervous system
- heart disease, stroke, kidney and retinal lesions, neuropathies and circulatory problems, sometimes
requiring amputation

Front 46

Effect of glucagon on cho's, fats, and pro's

Back 46

carbohydrate: increase blood glucose levels
- inhibits glycogenesis
- stimulates glycogenolysis
- stimulates gluconeogenesis
fat: increase blood fatty acid levels
protein: promotes protein catabolism, but little effect on blood amino acid levels

Front 47

Fuel metabolism following a high protein meal

Back 47

The effects of insulin and glucaogon counteract one another to keep blood glucose levels within normal
range

Front 48

Calcium in the body

Back 48

99% in bone, 0.9% inside cells, <0.1% in ECF

Front 49

The concentration of freely diffusible calcium found in ECF is critical for:

Back 49

Neuromuscular excitability
Excitation-contraction coupling in cardiac and smooth muscle
Stimulus-secretion coupling
Maintenance of tight junctions between cells
Clotting of blood

Front 50

ECF [Ca] is regulated by hormonal control of Ca exchange between the ECF and
three compartments: bone, kidney and intestine. Involves

Back 50

Calcium homeostasis
- maintenance of constant ECF [Ca] on minute-to-minute basis
- primarily accomplished by exchange with bone
Calcium balance
- maintenance of constant total amount of Ca in body
- balances intake with excretion over long term (months)

Front 51

ACtion of parathyroid hormone on ECF [Ca]

Back 51

1) raises ECF [Ca]
Actions on bone
- “bone bank” consists of Ca stored in hydroxyapatite crystals
- PTH induces fast Ca efflux into ECF from the small labile Ca pool in bone fluid
- PTH promotes a slow transfer of Ca (and phosphate) to the ECF (bone resorption)
- osteoporosis involves an altered balance of osteoclast/osteoblast activity.
Actions on kidneys: stimulates Ca conservation
Action on the intestine: indirect, by stimulating kidney enzymes that activate vitamin D
Negative feedback regulation of PTH by ECF [Ca]
PTH hypersecretion – hypercalcemia - “bones, stones and abdominal groans”
PTH hyposecretion – hypocalcemia - accidental removal of parathyroid leads to death

Front 52

Action of CAlcitonin of ECF [Ca]

Back 52

Calcitonin lowers ECF [Ca] by decreasing Ca efflux into ECF, decreasing bone resorption

Front 53

Interxn of PTH & Vit D

Back 53

Vitamin D increases Ca absorption in the intestine
Vitmain D deficiency - demineralized bone (Rickets)