endocrine system - physiology
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“The endocrine system”
By
Dr. Mary A. Youssef
________________________________
Cairo University
2012
Two main control systems
1. The nervous system
2. The endocrine system
Rapid control system
Slow control system
Exocrine glands Endocrine glands
Have ducts ductless
Secrete their products to the outer surface or the
lumen of GIT
Secrete their products (hormones) into the
blood
Can not Can reach distant tissue
2. The endocrine system
hypothalamus
Gland
Hormone
(Sender)
(signal)
blood
receptor (receiver & transducer)
Hormone
Target cell
Small amount
Rate of secretion
Superadded rhythms
Effector
Opposing effects
Classification of hormones
1. According to their chemical nature
olypeptide H.protein and P. 1 Hypothalamic, pituitary, pancreatic & parathyroid H.
. Steroid H.2
Adrenocortical and gonadal H.
. Hormones derived from a.a.3
Thyroid h. & adrenal medullary h.
cortex
2. According to their origin
Hypophysiotropic hormones
1. Releasing H.
GHRH
Thyrotropin (TSH) RH (TRH)
Corticotropin RH
Gonadotropin RH
2. Inhibiting H.
Somatostatin (SS)
Prolactin inhibiting H.
Hypothalamus
Hypothalamus
Anterior pituitary
posterior pituitary
prolactin H. Thyrotropin
TSH
Thyroid G. T3&T4
Growth H. Corticotropin
ACTH
steroids
FSH & LH (gonadotropins)
gonads
Sex H.
Anti-diuretic H.
(ADH)
Oxytocin
GHIH (SS) GHRH
PIH
TRH
CRH
GnRH
Mechanisms of hormone action
What is meant by a target cell?
GH
What are the target cells of GHRH?
a. cells of the Hypothalamus
b. Anterior pituitary cells
c. Posterior pituitary cells
d. Bone cells
I. Mechanism of action of protein & polypeptide hormones:
The hormone (1ry messenger) binds to a cell membrane receptor of target cell
formation of a 2nd messenger inside the cell
changing the activity of certain enzymes
- cAMP
- Calcium-calmodulin
- DAG & IP3
Hormone
(1ry messenger)
Receptor
1. cAMP system
Change certain
enzymes activity
(2ry messenger)
2. Calcium-calmodulin system
Change certain enzymes activity
Hormone
(1ry messenger)
(2ry messenger)
calmodulin
3. Membrane phospholipid system
DAG
IP3
Hormone
(1ry messenger)
Change certain enzymes activity
(2ry messenger)
II. Mechanism of action of Steroid H.
Receptor
Increase or a decrease in the synthesis of a certain protein
III. Mechanism of action of Thyroid H.
T T
T T
T
T
Receptor
Increase in the synthesis of certain proteins in almost all cells
H. derived from a.a.
Steroid H. Protein or
polypeptide H.
Nuclear R. Cytoplasmic R. Cell membrane
R.
_ _
2ry messenger - cAMP -Ca-calmodulin
-DAG & IP3
Synthesis of new proteins
Synthesis of new proteins
Change the activity of
already present enzymes
Thyroid & adrenal
medullary h.
Adrenocortical & Gonadal h.
Hypothalamic, pituitary,
parathyroid, pancreatic
Regulation of hormone secretion
Target gland
Hypothalamus
Ant. Pituitary G.
Target gland hormone
Substrate Mineral
Mineral-hormone feedback
Substrate-hormone feedback
Hormone-hormone feedback
The pituitary gland (hypophysis)
Hypothalamo- hypophyseal portal vessels
GHIH (ss)
GHRH
PIH
TRH
CRH
GnRH
Adenohypophysis
Hypothalamic neurons
Hypothalamo-hypophyseal tract
Anterior pituitary gland hormones
The anterior pituitary produces & secretes its own hormones
Its Hormones are given the extension; tropic, tropin or trophic
It is the master for the majority of the endocrine glands
Hypothalamus
Anterior pituitary
posterior pituitary
prolactin H. Thyrotropin
TSH
Thyroid G. T3&T4
Growth H. Corticotropin
ACTH
steroids
FSH & LH (gonadotropins)
gonads
Sex H.
Anti-diuretic H.
(ADH)
Oxytocin
Anterior pituitary gland hormones
Which of these is not produced by
the anterior pituitary?
►ACTH
►follicle-stimulating hormone (FSH)
►Somatostatin (ss)
►Somatotropic H.
Growth hormone
(somatotropic hormone)
It is a protein hormone that stimulates growth
1. On bone growth
Actions of growth hormone
GH
somatomedin
2. On protein metabolism
It is an anabolic hormone
mRNA
a.a. a.a.
1. Rate of DNA transcription
2. a.a. transport into the cell
3. On carbohydrate metabolism
It increases blood glucose level (diabetogenic action)
glucose Glucose 6-PO4
Glycogen
Glycogen synthase
phosphorylase
Insulin R.
Glucose transporter pyruvate
2 X Glycolysis
1
4. On lipid metabolism
Fat (T.G.)
GH Lipolysis
FA Glycerol
FFA
Factors affecting GH secretion
GH secretion is increased by GHRH Low blood glucose and FFA Protein meal Emotional stress Deep sleep
GH secretion is Decreased by somatostatin High blood glucose and FFA treatment with corticosteroids
Disorders of GH secretion
A. Growth hormone deficiency (dwarfism)
Decrease in the size of the trunk & extremities
Normal mental & sexual development
GH Gonadotropins
Pituitary infantilism
Failure of:
Physical development
Sexual development
B. Growth hormone Excess Before closure of epiphyses Gigantism
taller than normal
After closure of epiphysis Acromegaly
Main features of acromegaly
No linear growth of bones
1.Bones of hands and feet
2.Bones of the face
3.Mandible
4.The spine
5.Diabetes
Excess Deficiency Actions Hormone
:Gigantism
Before closure of epiphysis
Acromegaly
After closure of epiphysis
Pituitary dwarfism:
Only failure of physical develop.
Pituitary infantilism:
Failure of physical &
sexual develop.
On bone linear growth (via
somatomedin)
On protein Anabolic
On CHO
Diabetogenic
On lipid lipolysis
Growth H.
(Ant. (Pituitary
Growth hormone
A. directly stimulates growth of cartilage and bone.
B. enhances protein breakdown in nonvital muscles.
C. levels are subnormal in Gigantism.
D. promotes lipolysis in adipose tissue.
Posterior pituitary gland hormones
Antidiuretic hormone (ADH)
(Vasopressin)
It is a protein hormone
Formed in supraoptic n. of the hypothalamus and secreted from the posterior pituitary
Actions of ADH (vasopressin)
1. On Kidney
Anti-diuresis (retention of water)
2. On blood vessels
Pressor effect
3. On smooth muscles
Contraction of the smooth muscles
Antidiuretic H.
Summary of the actions of ADH
Antidiuretic hormone
Blood volume Vascular resistance
Arterial blood pressure
Regulation of ADH secretion
ADH secretion is increased by osmotic pressure of ECF blood volume (e.g. Hge) Stress Drugs (e.g. morphine & nicotine)
osmoreceptors
H2o
Na+ +
-
Baroreceptors & low pressure R
Hypovolaemia
Disorders of ADH secretion
ADH deficiency
Diabetes insipidus
1. Polyuria
2. Polydipsia
3. Loss of water
soluble vitamins
Oxytocin
It is a protein hormone
Formed in paraventricular n. of the hypothalamus and secreted from the posterior pituitary
Actions of Oxytocin
1.Uterine contraction during delivery
2.Milk ejection action during suckling
3.Mild antidiuretic action
The Thyroid gland
Histology
1.Follicles
Lined with a single layer of epithelial cells
Its centre is filled with colloid
2. Parafollicular cells
Hormones secreted from the thyroid gland
From parafollicular cells
From thyroid follicle cells
Thyrocalcitonin (calcitonin)
Thyroid Hormones
T3 (tri-iodothyronine)
T4 (tetra-iodothyronine, thyroxine)
It affects Ca homeostasis
It affects body metabolism
Actions of Thyroid hormones
T T
T T
T
T
Synthesis of new protein
Receptor
mRNA
Proteins for growth &
maturation
Enzymes & transport
ptns
of oNmitochondria
O2
substrate
GIT
Metabolism Calorigenic
effect
2
3
4
5 Respiration 1
6 CVS
blood glucose
blood FFA (lipolysis) CNS 7
Physical
mental
Sexual O2 consumption Metabolic rate
Regulation of thyroid hormones
Thyroid h. secretion is regulated by :
1. TRH
2. TSH
3. Feedback
Mechanism
4. Cold
5. Stress
Ant. pituitary
Hypothalamus
Thyroid
++
--
--
Cold & emotional
stress
+
Iodine deficiency
++
Disorders of thyroid hormone secretion
A. Hypothyroidism
1. BMR & calorigenesis
2.Generalized decrease in activity of all body systems
3.Myxoedematous tissue CVS: Heart rate & Cardiac output
GIT: intestinal motility (constipation)
CNS: slow mentation & sluggish reactions, S
In adults Myxoedema
Since birth Cretinism
Delayed physically: Dwarf, teeth erupt later than normal
Delayed mentally
Delayed sexually
Special features:
Depressed nasal bridge
Wide nostrils
Protruding tongue
Protuberant abdomen
B. Hyperthyroidism (thyrotoxicosis)
One of its types is Grave’s disease (exophthalmic
goitre)
Autoimmune disease
TSH-R(stim) Ab
TSH-R (stim) Ab
Characters of hyperthyroidism
1. BMR & calorigenesis
2.Generalized increase in activity of all body systems
3.Loss of weight in spite of increased food intake
CVS: Heart rate & Cardiac output
GIT: intestinal motility (diarrhea)
CNS: tremors, irritability, insomnia
Calcium homeostasis
The adult human body contains 1 Kg of calcium
Functions of calcium:
1.Mineralization of bones & teeth
2.Blood clotting
3.Neuromuscular excitability
4.Muscle contraction & relaxation
5.Release of neurotransmitters
6.Hormonal secretion & act as a 2ry messenger
8
Diet 1g
Extracellular fluid 1g
175 mg
1 Kg
1% exchangable in bone fluid
99% stable in mineralized
bone
10 g filtered/day
175 mg
Plasma calcium:
Its concentration is about 10mg/dl 1. Ionized 50%
2. Bound to protein 40%
3. Complex & diffusible form 10%
Solubility product:
[Ca2+] x [PO43-] = constant
Bone
Bone tissue is formed of:
1. Organic matrix (formed mainly of collagen)
2. Crystalline salts (mainly hydroxyapatite crystals & calcium phosphate)
3. Bone cells
A. Osteoblast
B. Osteocyte
C. Osteoclasts
Ca hydroxide
Ca phosphate
hydroxyapatite
Bone matrix proteins
Alkaline phosphatase
Bone forming
cells
Secrete H+ that dissolve hydroxyapatite
Acid protease that dissolve collagen
Bone eating cells
Secrete
Phosphate ester phosphate
Ca phosphate
Outer surface of the bone
Osteoblasts
Osteocytes
10 mg/dl Ca++
Ca bound to ptn Complex form
Bone fluids
Hydroxy-apatite crystals
Hormonal control of plasma Ca level
3 hormones play a role in the control of plasma Ca level
1. Parathormone hormone (PTH) : Parathyroid glandSource
:Actions
1. On bones
A.Rapid phase
B.Slow Phase
2. On kidney
3. On GIT
PTH
Ca++
Ca++
Ca++
Ca++
Ca++
Hydroxyapatite crystals
Ca++
2. On kidney
PCT
DCT Ca++
PO4
+
-
Ca++ reabsorption
Phosphate reabsorption
Ca++ absorption
ECF Ca++
ECF PO43-
3. Vitamin D2
Skin Source:
25-hydroxy-cholecalcife
rol
1, 25-dihydroxy cholecalciferol
ECF Ca++
ECF PO43-
. Calcitonin3
: parafollicular cellsSource
:Actions
1. On Bone (inhibits activity of osteoclats)
2. On kidney
ECF Ca++
ECF PO43-
Ca++
PO4
-
-
Tetany It is a state of increased neuromuscular excitability due to decreased ionized calcium
Causes
Types:
Latent tetany: when the total plasma Ca is between 9 and 7 mg/dl. Its manifestations do not appear during rest
Manifest tetany: when the total plasma Ca
drops below 7mg%. The patient is presented by spasmodic contractions
Hypoparathyroidism Vitamin D deficiency Renal disease Akalemia
The adrenal glands
Each adrenal gland consists of two endocrine organs
1. Adrenal cortex
Secretes steroid hormones
2. Adrenal medulla
Secretes catecholamines
cortex
C
ort
ex
Medulla
Zona glomerulosa
Zona Fasciculata
Zona Reticularis
Mineralocorticoids
Glucocorticoids
Sex Hormones
Aldosterone
cortisol
Androgens & estrogen
A. Glucocorticoids
Cortisol = 95% of total glucocorticoid activity.
Actions of cortisol depends on its plasma level:
1. Permissive Actions
2. Physiological Actions
3. Pharmacological Actions
its presence even at small amounts permits certain processes to occur
Effects of the normally present hormone levels in plasma
Effects of the high levels of hormone in plasma
It means that cortisol does not initiate the changes, but its presence even at small amounts permits certain processes
1. Permissive Actions
Glucagon & catecholamines
Glycogenolysis
Catecholamines Arteriolar V.C. response &
bronchodilatation
2. physiological Actions
I. Effect on metabolism
Glucose
Gluconeogenesis
glycogen
glucose Glucose 6-PO4
Glycogen Glycogen synthase
phosphorylase
pyruvate
3 Glycolysis
2
Blood glucose
protein Fat (T.G.)
Lipolysis
FA Glycerol
Blood FFA
1
a.a.
II. Effect on CNS
Required for normal EEG pattern
III. Weak mineralocorticoid effect
IV. Anti-stress effect
I. Effect on metabolism
V.C. catecholamines
Permissive action
Blood glucose Plasma a.a. Plasma FFA
3. pharmacological Actions
I. Anti-allergic effect
II. Anti-inflammatory effect
Mast cell
Local redness
Local heat
Local swelling
V.D.
Capillary permeability
Phospholipids
PGs
Local pain
Loss of function
Destruction of cells
Lysosomes
White blood cells Eosinophils
Basophils
Phagocytic cells
Walling off of infections
Fibroblasts
1
2
3
4
5
Control of glucocorticoid secretion
1
2
3
4 5
hypothalamus
B. Mineralocorticoids
Actions:
DCT
Collecting duct
Na+
K+
Aldosterone actions H2O
ECFV
Cushing’s syndrome 1.cause: Hypersecretion of cortisol + excess androgen
. Features2
I. Excess cortisol
1.CHO metabolism (DM)
2.Excess protein catabolism
3.Disturbed fat deposition
II. Mineralocorticoid effect
III. Excess Androgens
Moon face
Buffalo hump
Purple striae
Disorders of adrenocortical hormones
Addison’s syndrome
1.cause:
Hyposecretion of adrenocortical hormones
. Features2
I. Mineralocorticoid deficiency
1. Hypotension
2. Polyuria & polydipsia
3. Hyperkalemia
B. Mineraloco
rticoids
Actions:
Na+
K+
Aldosterone actions
H2O
ECFV
II. Glucocorticoid deficiency
Depression of many metabolic functions
hypoglycemia
1. Metabolism
- CHO metabolism
Decreased resistance to stress 3. During stress
ACTH skin pigmentation 4. ACTH
Loss of appetite weight loss 2. Appetite
Control of glucocorticoid secretion
hypothalamus
1
The Pancreas
Actions of insulin I. On CHO metabolism:
glucose Glucose 6-PO4
Glycogen
Glycogen synthase
phosphorylase
Insulin R.
Glucose transporter pyruvate
Glycolysis
In skeletal m., cardiac m. & adipose tissue
Glucose
Glucose
Glucose 6 P
+
Glycogen
Glycogenesis +
Glycogenolysis -
gluconeogensis -
1. Indirectly facilitates glucose entery
2. Promotes glycogenesis
3. Inhibits glycogenolysis
4. Inhibits gluconeogensis
In the liver
II. On lipid metabolism: lipogenesis
III. On protein metabolism: (Anabolic)
mRNA
a.a. a.a.
1. Rate of DNA transcription
2. a.a. transport into the cell
IV. On Growth
Actions of Glucagon
Glucagon Insulin
glycogenolysis
gluconeogenesis
glycogenolysis
gluconeogenesis
On CHO metabolism
Lipolysis Lipogenesis On lipid metabolism
Catabolic Anabolic On protein metabolism
hypoglycemia hyperglycemia Stimulus
Diabetes mellitus
Signs & symptoms
urine Blood Response Organ/tissue
Polyuria
dehydration
glucosuria
Hyperglycemia
Decreased glucose uptake
Polydipsia Osmotic diuresis
Hyperglycemia
Glycogenolysis
Gluconeo-genesis
Weight loss
Polyphagia
(Hyperphagia)
Protein catabolism
Glucose Homeostasis
The importance to maintain a normal blood glucose concentration
Body response to ingestion of a meal (high glucose)
100
120
140
1h 2h 3h 4h
Insulin returns blood glucose level back to control level
Mechanisms controlling blood glucose concentration
1. Glucostatic function of the liver
Glycogenesis (after meals) Glycogenolysis (between meals) Gluconeogenesis (during fasting)
2. Hormonal Mechanism
Both insulin & glucagon function as important feedback control systems to maintain a normal blood glucose level
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