Transcript Physiology of Endocrine

Assist prof. of Medical Physiology
Excess GH
Before Union of
epiphysis
Gigantism
After Union of
epiphysis
Acromegaly
Decreased GH
In children
In adults
Dwarfism
Loss of
some body
proteins
Causes:
1. Hyperplasia or
2. Tumor of the somatotrop cells (adenoma)
Manifestations:
• The manifestations depends upon, if it occurs before or after
the union of the epiphyses.
A) Gigantism: ↑ed GH before the union of the epiphyses.
B) Acromegaly: ↑ed GH after the union of the epiphyses
or in adults
Def:
• Condition caused by excess GH before union of
epiphysis
Manifestations:
1) Marked elongation of bones but in a relative
proportion.
2) Overgrowth of soft tissues e.g. the muscles &
viscera.
Gigantism in a 36-year-old woman. Her companions are normal.
Manifestations:
3) Hyperglycemia and increased MR.
4) Hypogonadism:
• Gonads and accessory sex organs remain infantile
due to￬ed gonadotropins secretion
 GH secreting cells encroach upon the other cells.
S
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S S S S S T
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M S G
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M S
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Pituitary tumor causes compression
and atrophy of gonadotrophes
Manifestations:
5) Headache due to pressure on Sella Turcica
and visual disturbances (Bitemporal
hemianopia) due to pressure of the growing
tumor on the optic chiasma.
6) These patients are often mentally subnormal
Bitemporal hemianopia
Def:
• Condition caused by excess GH after union of epiphysis in
adults
Manifestations:
1. The bones become thicker and deformed; the ms and viscera
also enlarge
2. Generalized coarsening of the features due to:
a. Thick skin and SC tissues.
b. Enlargement of the head, hands and feet.
c. Prognathism: the lower jaw enlarged & protrudes forward,
and separated teeth.
Spade hand
Manifestations:
• 3) Kyphosis due to thickening of the vertebrae.
• 4) Hyperglycemia and glucosuria.
• 5) Raised BMR.
Manifestations:
• 6) Hypogonadism.
 7) Some patients have visual fields
defects due to pressure of the tumor on
optic chiasma.
 Increased intracranial tension lead to
headache & vomiting.
• 8) Hirsutism (increased body hair).
• 9) Gynaecomastia and may be
galactorrhea
Treatment:
• 1) Surgical: removal of tumor
• 2) Medical:
• Somatostatin or
• Somatostatin synthetic compounds e.g. Octreotide and
lanreotide
Def:
•
Condition caused by deficiency of GH in children
Manifestations:
a) Short stature due to rapid closure of the epiphyses
leading to proportionate reduction of all body sizes.
b) The growth rate of soft tissues is reduced, but mild
obesity is common.
• The patient looks much younger than his age.
Manifestations:
c) Normal Mental growth usually.
d) Low metabolic rate & episodes of hypoglycemia due to
lack of insulin antagonism by GH.
e) Normal Sexual maturation in cases of isolated GH
deficiency.
• Few dwarfs show hypogonadism and the gonads,
external sexual organs and characters remain infantile
Infantilism .
NB:
Deficiency of GH in adults has no physical signs
• 1) Cretinism: Thyroid hypofunction in infants.
• 2) Precocious puberty:
– in cases of hypergonadism in children, which leads to
early closure of the epiphyses.
• 3) Gonadal dysgenesis e.g. Turner’s syndrome where an
XO chromosomal pattern instead of XX or XY.
• 4) Bone and metabolic diseases.
• 5) Constitutional delayed growth in many cases no
evident cause for stunted growth is found.
Turner syndrome
Excess prolactin
Due to
Hypothalamic
dysfunctions
Decreased prolactin
Due to
Pituitary
tumors
Destruction
of ant.
Pituitary G.
Manifestations:
• High prolactin inhibit GnRH and pituitary gonadotropins
resulting in;
• a) In women,
1. Loss of menses (amenorrhea),
2. Anovulation and infertility.
3. Galactorrhea: lactation unassociated with
pregnancy
4. Decreased libido.
Manifestations:
• b) In men,
1) Decreased:
 testosterone secretion.
 sperm production.
 libido.
2) Stimulation of breast enlargement
(Gynaecomastia) & Galactorrhea is rare.
• Diagnosis :
 by a high prolactin blood level.
• Treatment:
by:
A) Surgical removal of the tumor or
B) Dopaminergic drugs to reduce prolactin
secretion
 In women produces inability to lactate.
 No other clinical consequences are known.
Results from destruction of the ant pituitary, leads to:
– Severe deficiency of its hormones and
– Atrophy of the thyroid and adrenal glands and of the gonads.
Manifestations:
1. In children: lead to infantilism.
– failure of growth and of sexual maturity.
2. In adults, the lack of trophic hormones results in
– hypofunction of the target endocrine glands with relative
hyperinsulinism.
Manifestations:
• a) Thyroid gland (Myxoedema)
• b) Adrenal cortex (hypocorticism or ‘Addison’s
disease) → leading to ms weakness, loss of
weight, hypoglycaemia and dehydration.
• c) The gonads (hypogonadism).
Manifestations:
d) Loss of weight and severe wasting of muscles
(cachexia) due to:
– loss of appetite (anorexia) and absence of anabolic effect of
GH and androgens.
e) Premature senility:
– dry skin and wrinkled with early graying of hair
– so the patient looks older than his age.
Manifestations:
f) Hypoglycaemia due to:
– relative increase insulin level
– lack the effects of antagonistic hormones.
g) Skin colour becomes lighter due to:
– anaemia and
– deficiency of ACTH and beta-MSH.
• Thousands of nerve fibres connect the hypothalamus,
(supra-optic & para-ventricular nuclei), with the post
pituitary.
• The crude extract of the post lobe is called pituitrin
that contains 2 hormones:
1). Antidiuretic hormone (ADH), also called vasopressin or
pitressin.
2). Oxytocin (or pitocin) hormone.
Synthesis and Storage:
• Oxytocin & ADH, are synthesized in the hypothalamus
and stored in granules with a binding protein
(neurophysin)
1. Neurophysin-1 for oxytocin
2. Neurophysin-2 for antidiuretic hormone.
• Granules pass down the axons through hypophyseal
tracts to the nerve endings in post pituitary.
• The terminal swellings of nerve endings are called
‘Herring bodies’.
• When a nerve impulse is transmitted from the cell
body in hypothalamus down the axon:
1. Depolarizes the terminal Herring body.
2. Ca+ influx into the Herring body induce hormone release
by exostosis, and enters the adjacent capillary.
Source:
• Mainly from supraoptic
hypothalamic nucleus
Chemistry:
• Peptide hormone 9 a.a.
1. Reabsorption of water from
renal tubules (major action)
2. Vasoconstriction of blood
vessels (in large dose)
3.As CRH on pituitary gland
• Is the major action of ADH
• Reabsorption of free water from the tubular fluid.
• Target site of action:
1. Distal convoluted tubules
2. Collecting ducts
• In large doses
• ADH causes vascular smooth muscles contraction
leading to:
1. Elevation of the blood pressure
2. Coronary vasoconstriction
3. Intense splanchnic vasoconstriction.
• This effect used clinically in controlling, serious GIT
bleeding.
ADH Used in treatment of GIT bleeding
• Some of ADH pass to the ant pituitary via its portal veins
where it act as CRH → Increase ACTH.
Regulation of vasopressin secretion.
1. Osmotic regulation
2. Blood volume
3. Other factors (stimulators and
inhibitors)
• Hypothalamic supraoptic nuclei contain very sensitive
osmoreceptors.
• Rise in plasma osmolarity (1%) → loss of intracellular water
from osmoreceptor neurons → ADH secretion.
• ADH produces reabsorption of free water (without
electrolytes) from tubular fluid→ dilutes the plasma→ return
of osmolarity to its normal value.
• Normal plasma osmolarity is 290 m osm/liter.
Causes of increase plasma osmolarity:
1) Dehydration (Water deprivation), either due to:
 Decreased water intake or
 Excessive loss.
2) Administration of solutes: which do not rapidly penetrate
the cell membrane, such as Na+.
– Substances that enter cells rapidly, as urea do not stimulate
ADH secretion, because they do not produce osmotic
dysequilibrium between ECF and ICF.
• ADH release is stimulated by a 5% to 10% decrease in
circulating blood volume, or cardiac output.
– Haemorrhage decreases blood volume,
– Standing & positive pressure breathing reduce cardiac
output.
• Hypovolemia is perceived by pressure sensors :
a. Arterial baroreceptors in carotid sinus and aortic arch
b. Stretch receptors in the walls of left atrium &
pulmonary veins.
• Pressure receptors normally maintain tonic inhibition
of ADH secretion, so hypovolemia decreases the flow
of these inhibitory impulses  increases ADH
secretion.
c. Juxtaglomerular apparatus is stimulated by
hypovolemia & secrete Renin which generate
angiotensin II
• Angiotensin II directly stimulate thirst & stimulate ADH
secretion.
Juxtaglomerular
apparatus
Renin
Angiotensin II
↓ Plasma Volume
(Hypovolemia)
ADH secretion
↑ Plasma Volume
Stretch receptors and
baroreceptors
1. Inhibitors
a) Diuretics
b) Water loading
c) Prostaglandin E
d) Cortisol, and
e) K+ deficiency
f) Ca+ excess
g) -adrenergic agonists
h) Cold weather,
i) Ethanol
2. Stimulators
a) Sulfonylureas
b) Nicotine
c) opiates
d) Hot weather
e) -adrenergic agents
f) oestrogens, &
progesterone
Excess Secretion
Decreased Secretion
Syndrome of
inappropriate
ADH secretion
(SIADH)
Diabetes Inspidus
Causes:
1. Deficiency of ADH secretion (neurogenic DI)
2. Inability of the kidney to respond to ADH
(nephrogenic type).
Symptoms :
1) Polyuria: (urine volume reach 25
liters/day)
• Due to failure of the facultative
water reabsorption by the distal
tubules.
• Very low urine specific gravity
(1001-1003).
2) Polydepsia:
• drinking large amount of water
due to intense thirst 2ry to
polyuria.
3) Anorexia and general weakness due
to loss of important substances in
urine as vitamins.
• Treated by:
•
By Administration of ADH except Nephrogenic’ type as
there is a congenital defect in the renal tubules.
 Cause:
• Increased ADH than predicted by plasma volume or tonicity
 Manifestations:
a) Hyponatremia (serum sodium 100 - 115 mEq/L).
• Results in headache, drowsiness, nausea and often coma.
b) High urine osmolality.
c) Slight increase in ECF volume.
d) Excess renal sodium excretion despite the low serum sodium
due to;
• Elevated levels of atrial natriuretic factors caused by the
expanded plasma volume.
Source:
• Mainly from paraventricular
hypothalamic nucleus
Chemistry:
• Peptide hormone 9 a.a.
Mechanism of action:
• Bind to specific cell membrane receptors
• Exerts its effects by increasing intracellular Ca++
content.
1. Milk Ejection
2. Uterine contraction during labour
3. Transport of sperms in female genital
tract
4. Transport of sperms in male genital tract
5. Stimulation of apocrine sweat glands
Mechanism:
 Stimulate contraction of the myoepithelial cells of the alveoli
of the mammary glands.
 This forces milk into the ducts.
 This action of oxytocin is:
 Potentiated by oestrogen
 Inhibited by catecholamines.
• Suckling-reflex:
– Suckling stimulates touch receptors at the nipple
and areola which send afferent impulses to the
hypothalamus to release both oxytocin and
prolactin hormones.
• Lower the threshold for membrane depolarization of the
myometrial ms.
• This effect is:
1. Potentiated by oestrogen
2. Inhibited by progesterone.
• Oxytocin has minimal effect in initiating labour
• But plays an important role in the sustained post-partum uterine
contractions that help to :
1. Maintain haemostasis after evacuation of the placenta,
2. Involution of the uterus after delivery.
3. In females:
• Transport of the sperms into the uterus during intercourse.
– By the end of intercourse, oxytocin is secreted & induce
rhythmic uterine contractions which suck, the sperms into
the uterus & giving the orgasm sensation.
4. In males,
– help the discharge of sperms from the semineferous tubules
and epididymis to vas deferens. During ejaculation
5. Stimulation of apocrine sweat secretion
– at the axillae, nipples, groins and perineum that produce sex
attraction in animals.