Assist prof. of Medical Physiology. Excess GH Decreased GH Before Union of epiphysis Gigantism After Union of epiphysis Acromegaly In children Dwarfism.

Assist prof. of Medical Physiology

Excess GH

Decreased GH

Before Union of epiphysis

Gigantism

After Union of epiphysis

Acromegaly

In children

Dwarfism

In adults

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.

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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 syndromeTurner syndrome

Excess prolactin

Decreased prolactin Due to

Hypothalamic

dysfunctions

Pituitary tumors

Due to

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.

• 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 oxytocin2. 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.

• 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 pressure2. Coronary vasoconstriction3. 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.

• 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.

↓ Plasma Volume (Hypovolemia)

↓ Plasma Volume (Hypovolemia) Stretch receptors

and baroreceptors

Stretch receptors and

baroreceptors Juxtaglomerular

apparatus Juxtaglomerular

apparatus

ADH secretion

ADH secretion Reni

n Reni

n

Angiotensin IIAngiotensin II↑ Plasma Volume ↑ Plasma Volume

1. Inhibitorsa) 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. Stimulatorsa) Sulfonylureas

b) Nicotine

c) opiates

d) Hot weather

e) -adrenergic agents

f) oestrogens, & progesterone

Excess Secretion

Syndrome of inappropriate ADH secretion

(SIADH)

Decreased Secretion

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.

• 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 oestrogen2. 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.