CHAPTER 8

ENDOCRINE SYSTEM

Endocrine System Thyroid Underactivity of Thyroid Overactivity of Thyroid Parathyroids Underactivity of Parathyroids Overactivity of Parathyroids Adrenal Cortex Underactivity of Adrenal Cortex Overaetivity of Adrenal Cortex Adrenal Medulla Adrenaline Development of Pituitary Anterior Pituitary Underactivity of Anterior Pituitary Overactivity of Pituitary Somatotroph Cells Overactivity of Pituitary Corticotroph Cells Panhypopituitarism Posterior Pituitary Oxytocin Antidiuretic Hormone (AD H) Underactivity of Posterior Pituitary Aldosterone and Antidiuretic H ormone in the Maintenance of Blood Volume Pancreas: Islets of Langerhans

194 195 196 197 198 199 200 20 1 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217

ENDOCRINE SYSTEM

ENDOCRINE SYSTEM
The DUeneSS GLANDS produce hormones ('chemical messengers') which they pass into the blood stream for general circulation to excite or inhibit the activity of other organs or tissues.

0\\ -

.-I -;.u _ - PITUITARY

::

_ HYPOTHALAMUS

ANTERIOR LOBE POSTERIOR LOBE

,,

----

_ - - THYROID

- --- -- 4 PARATHYROIDS

The glands of internal secretion are concerned w ith the control and coordination of processes wh ich are w idespread in the body - such as Metabolism Fluid balance Growth Maintenance of stability of internal environment Resistance to stress

-- ... - - Some other systems also produce hormones which are passed int o the blood stream.

__ - -

_ 2 ADRENALS Cortex Medulla

-- PANCREAS (Islets of Langerhans)

/ 2 TESTES in Male
I

(2 OVARIES in Female

,,
,

"
.'

[plus placenta in pregnancy).)

.

Sexual development and Reproduction

DIGESTIVE SYSTEM:STOMACH - GASTRIN SMALL INTESTINE

,

,1 , I
.t'

VIP (pp.75, 86, 96) GIP (p.79) Secretin Cholecystokinin (CCK)

Erythropoietin Renin 1,25-DHCC (p.198)

",
I I

, I

All have a profuse blood supply to receive their secretions

KIDNEY

Hormone molecules may be: proteins, peptides or catecholamines which act on plasma membrane receptors, or they may be steroids or iodinated tyrosine derivatives (p .195) which act on receptors in the cell membrane.

194

ENDOCR INE SYSTEM

THYROID
STRUCTURE: FUNCTION:

2 LOBES (joined by ISTHMUS) composed of lie in front of TRACHEA

Cubical epithelium extracts from the blood stream and concentrates IODIDE (iodide trapping)

! - oxidised by peroxidase
IODINE links with TYROSINE MONOIODOTYROSINE (MIT) DJlODOTYROSINE (DfT)

DIT+DIT MIT+MIT
(6'"'"
,

,0\

"",0 ,

('

'.

Blood vessels

I'-:e
'"

TRJlODO'0 "'" THYRONINE V"" .. TETRAIODO- (T3) (j THYRONINE _

t
:

THYROID Gland weighs about 25 g in adult

(T4 )

'

Stored in colloid when required linked with protein a protein-splitting THYROGLOBULIN enzyme releases

REGULATION OF SECRETION:

.,.--- .... ,...

:::..:

/'" " FALL in blood I,'" THYROID " HORMONES \

TRHfrom HYPOTHALAMUS ,

5: I
-.

pro":,otes ' ;:; I production of I a I III 7iRH d I Q:.,a: Cl ' an I ::.: lI.i 0 I thus THYROID- : '0 I STlMULA TlNG I ,/ I HORMONE (TSH) , I y, 0. I from ANTERIOR E \ PITUITARY
I

I I

RISE in blood THYROID HORMONES depresses production of 7iRH d th an us THYROID

';;;

en

III

production \ ',and release "...

from ANTERIOR : PITUITARY ; decreases " production and release

I

HORMONE (TSH or THYROTROPHIN)

T 3 and T 4 are carried by the blood to all body tissues. T 4 is usually converted in the cell cytoplasm to T 3 which binds to receptors in the nuclei. This complex binds to DNA and increases specific genes which increase mRNA and ribosomal RNA and hence protein synthesis. Oxygen consumption, heat production and metabolism are increased. Normal thyroid output is required for normal growth.
(P a r a follicula r cells secrete...calcitonin - which lowers blood calcium by suppressing calcium mobilization from bone and by increasing calcium excretion in the urine.)

of (THVROIDi of .........---HORMONES---/-1': 8.'Z1 .: ',.:.' ;.

w , .J

BODY TISSUES

THYROID GLAND

Increased O 2 consumption is due to an increase in the size and number of mitochondria, in Na + , K + - ATPase activity and the rates of glucose and fatty acid oxidation and synthesis.

195

ENDOC RINE SYSTEM

UNDERACTIVITY OF THYROID
If the thyroid shows atrophy or destruction of its secretory cells or is inadequately stimulated , the syn drome of hypothyroidism develops because of lack of thyrotrophinreleasing hormone from the hypothalamus or thyroid-stimulating hormone from the anterior pinutary.
Less (or no) Fall (or absence) THYROID of THYROID HORMONES enter blood HORMONES ,/ in blood \ , to depress \ , ' , ' activity of \ I I ' ANTERIOR ' " PITUITARY : n TSH \ rr TSH

Atrophied thyroid cells - -

Thyroglobulin

'"

,.- /

I:
-.

x 200

I.

Less functional I , "... " tissue to respond '.. , to THYROID --- 6_" --.- STIMULATING HORMONE

,'"

,
I

Body Tissues

Slowing up of all bodily processes

Insufficient hormonal secretion released to blood stream. Tissue oxidations are depressed, l.e, rate at which cells use energy is reduced. The basal metabolic rate falls. Less heat is produced. Body temperature falls (and person feels cold). Energy units are stored w ith water. Skin - Thick, leathery, puffy, yellow (due to circulating carotene). Blood cholesterol increases. Appetite is reduced; weight increases. Gut movements sluggish ..... constipation. Heart and respiratory rates and blood pressure reduced. Thought processes slow down ..... lethargy; apathy; somnolence. Hair - brittle, sparse, dry. Slow, husky voice. Bone marrow suppressed ..... anaemia

In the CHILD - e.g. congenital absence of the gland

I CRETINISM
A child who

IS

Gross dwarfing

hypothyroid from birth is a CRETIN

Failure of skeletal sexual mental

growth and development

NB: Protruding tongue and pot belly.

All 'milestones' of babyhood are delayed.

196

THYROXINE (taken by mouth) restores individuals to normal.

ENDOCR INE SYSTEM

OVERACTIVITY OF THYROID
Commonest form is Graves' disease. Produces increased thyroid hormone secretion (t h y r ot oxicosis), enlarged thyroid (goit r e) and protrusion of eyeballs (exop h t h a lm os). The disease is caused by production of antibodies against the person's own thyroid cells (i.e. an autoimmune disease). These antibodies, thyroid-stimulating immunoglobulins ( T S I) , act like thyroid-stimulating hormone ( T SHy and release thyroid hormones (T 3 and T 4)'
Great RISE in blood THYROID HORMONES .... Lacunae Hyperplasia of thyroid - cells
x 200

.....- .. , " ,"

\

depresses 1" \ . .... production : Formation \ of I of Thyroid, TSH by , Stimulating I M ANTERIOR :/mmunoglobulinst _ PITUITARY I (TSI) , , I but TSH \ stimulates : does not " greater I affect . ,TSI action \ production --, and release ",,-, ......< d_.-":;: _ ,-f' ' . -., , 0f &.;:. "

... ......_-

Body Tissues

":;.i.".y .\1"":

.,..

THYROID GLAND takes up more IODINE [N .B. If the excess thyroxine is formed by tumour tissue th is is outside the negative feedback control of TSH. Similarly TSI are not suppressed by l Thyroxine.] Speeding up of all bodily processes

Excess thyroid hormones are distributed by blood stream to the tissues of the body. ----> Speed up oxidations in the cells. i.e. rate at which all cells use energy. The basal metabolic rate is raised, more heat is produced ----> rise in body temperature (person feels warm). Skin hot and flushed. Profuse sweating. Energy stores of body (i.e. glycogen and fat) are depleted. Appetite increases but weight falls. Movements of digestive tract are increased ----> diarrhoea. Heart and respiratory rates rise. Blood pressure is raised. A fine muscular tremor and nervousness are marked. Person becomes excitable, irritable and apprehensive.

....... .- ...
.f

CVS symptoms very important. T3 and T4 increase cAMP and number of p adrenergic receptors in heart, thus increase heart's sensitivity to adrenaline. Blocked by p-receptor blocking agents.

Goitre

[Exophthalmos (p rotrusion of eyeballs) may be due to an action of an antibody against a protein of the extraocular muscles and the connective tissue behind the eye which causes these tissues to swell. It is not due to an excess of thyroid hormones.]
197

Surgical removal of part or all of the overactive gland or destruction by radioactive iodine reduces the thyroid activity.

ENDOC RINE SYSTEM

PARATHYROIDS
Four small glands composed of cords of chief cells which secrete a peptide \ parathyroid hormone - parathormone or PTH
\

,-.

\\

'

1
!

--,GLANDS

CAPILLARIES

General circulation to all tissues of the body

Situated behind THYROID /

-, -,
I',",

OESOPHAGUS

2: :, --:.l I"...Each weighs from

20-50 mg in Adult

,,
\

But not all tissues are sensitive to It. It plays an important role in calcium and phosphate metabolism.

OXYPHIL CELLS with eosinophilic granules function unknown.

Three hormones, parathormone, 1, 25-dihydroxycholecalclferol (1,25-DHCC) and calcitonin act on kidney and gut to keep blood ionized calcium constant (n ecessary for normal nerve and muscle excitability, blood coagulation and formation of bone and teeth).
PARATHYROIDS

BONE

PTH
KIDNEY Increases

SKIN

-,

,,- ,

Vitamin D metabolites converted by liver and kidney to hormone 1 25-DHCC , ".....

Ii,
i ll ' /(,

Stimulates mobilization _ ,oq.1, of ,/9 Ca and " '9"& pol- Inhibited by Calcitonin

!/o

01)&

and I '<-, ,\. \ tubular secretion of P0 4 3 -

BLOOD STREAM Increases Ca in Blood

'3\\0(\
CO
'3- \(\
A

,.,

,....

Increases excretion of pol- in urine GUT '..' f

'3S0S
,

'O\Oou

BLOOD C 2+ a LEVELS:

't,flo"'III, l b ' sorption

..

0\ (,'0

'0

(\6
TOTAL 2.4 mrnol/l. PROTEIN BOUND 1.2 mmol/l. ACTIVE IONIZED Ca 2 + 1.2 mmol/l.

dietary Ca and P0 4 and 2+ ' ... ....,reduces loss of Ca In faeces

198

In bones and kidneys PTH activates adenylate cyclase, thus increasing cAMP. Osteoblast cells are responsible for bone formation and differentiate into osteocytes (p.19). PTH inhibits synthesis of new bone by osteoblasts: osteoclasts resorb (break down) bone. Calcium ions in extracellular fluid control parathyroid activity. j Ca2 + depresses PTH secretion. ! Ca2 + increases PTH secretion.

ENDOC RINE SYSTE M

UNDERACTIVITY OF PARATHYROIDS
Atrophy or removal of parathyroid tissue causes a fall in blood calcium level and increased excitability of neuromuscular tissue. This leads to. severe convulsive disorder - tetany.
CHVOSTEK'S SIGN

PARATHYROID GLANDS

Inadequate production of

PTH
I
I

Usual manifestations:twitchings, nervousness, occasional spasms of facial, li mb and laryngeal muscles (can cause fatal asphyxia)

'",

<z: '.

TROUSSEAU'S SIGN
;'

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."

I
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I I

"" "" ... "

".

I I
I

"" , "

--"'"
TETANY

KIDNEY

"

If concentration of ionized Ca 2 + in blood falls below about 1mmol/l . (Hyperventilation can also produce low Ca 2 +.) Fall in concentration of

[Note the inverse relationship between plasma calcium and inorganic phosphate]

Symptoms are relieved by injection of large doses of calcium and a Vit.D compound.

199

ENDOCR INE SYSTEM

OVERACTIVITY OF PARATHYROIDS
Overactivity of the parathyroids (due often to tumour) leads to rise in blood calcium level which may produce renal stones, kidney damage and perhaps osteitis fibrosa cystica.

1 -

PARATHYROID GLANDS

Overproduction of PTH

BONE

...."""" "" -

UV LIGHT SKIN Vitamin D metabolites

(After case by Ashhurst.J OSTEITIS FIBROSA CYSTICA

Eventual softening and deformity of bones Multiple bone cysts.

! !

KIDNEY
, t.

Greatly increased } tubular ./ reabsorption of Ca 2 + - and tubular secretion of P0 43 T 1.25-DHCC Great loss of P0 43 and Ca 2 + in Urine

-',

II

GUT .Great increase in ... absorption of " . " ' dietary Ca 2 + ,,,,,.,

..

Great increase in concentration of Ca 2 + in Blood (Plasm a Ca 2+ may be over 4 mmol/l Increased Viscosity of Plasma.) Deposition of calcium in unusual sites e.g. kidney. Signs of toxicity (nausea, vomiting, loss of appetite, etc.)

200

The increased level of blood calcium eventually leads to excessive loss of calcium in urine (in spite of i reabsorption) and also of water since the salts are excreted in solution. Polyuria, dehydration and thirst result. Most cases are diagnosed before bone disease develops. Excision of the overactive parathyroid tissue abolishes syndrome.

ENDOC RINE SYSTEM

ADRENAL CORTEX
The adrenal cortex is essential for life. It plays an important role in states of stress.
There are TWO adrenal glands. They lie close to the kidneys. Each has an outer CORTEX and an inner : MEDU LLA I

"

..:r:'::-.

RIGHT KIDNEY

LEFT KIDNEY

1. MINERALOCORTICOIDS Especia lly aldosterone but also deoxycorticosterone. - ch ief action on kidney tubules.

Secret ion from the adrenal cortex is under the cont rol of adreno-eorticotrophic hormone fACTH, corticotrophin) from the anterior pituitary (AP). Stress acts via HYPOTHALAMUS
FA LL in blood CORTICOIDS
I

,
.

x 80

J' . .
t::
(J:::f:r.::;, 0

RISE in blood CORTICOIDS

0!i

.8
o '"'
,.. +

2. GLUCOCORTICOIDS
00;:

11

I
I

"

promotes \ production ,

depresses

{J

lit,;:::

Especially cortisol (hydrocortisone) but also . LIVER

corticosterone causes protein catabolism Amino acids

I I
,

of
ACTH

'

,'

stimulates \ production and release \\ of

, ,
I

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production If This of reciprocal 0 c ACTH ,,:.:: relationship ,, tw A .. - (5 De een and adrenal

'tl
!'ow ;'.

'...

- - GLAND ADRENAL
_.". ...: / 1

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CORT/COIDS , -- -- . - -- . '. t, .'=' ' \

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., "'--

"8

cortex leads to ' balanced effects

,l. f .v
#

0'

f l

'

so formed are used to make

on.

Secretion of aldosterone from the zona glomerulosa is controlled not only by ACTH but also by (a ) Angiotensin II released by the renin-angiotensin system (page 183) following blood or fluid loss and (b) increase in plasma potassium.

glucose in liver. v'" Increases blood sugar. They also have anti-insulin, anti-inflammatory and anti-allergic actions; are necessary for noradrenaline and adrenaline actions; reduce circulating eosinophils. 3. ANDROGENS (sex hormones) Especially dehydroepiandrosterone but also androstenedione (Oestrogen produced from this in the circulation.) Promote protein anabolism and growth (anabolic steroids). Have minor effects on reproductive 201 function.

ENDOCRINE SYSTE M

UNDERACTIVITY OF ADRE AL CORTEX

Atrophy of the adrenal cortex can be caused by autoimmune disease or destruction by tuberculosis or cancer. Total absence of adrenal hormones is rapidly fatal. Reduced production of all corticoids gives 1 'MI ERAlOCORTICOID' EFFECT Incomplete destruction of glands produces ADDISON'S DISEASE

,
.'. .
.
. " ' .' '..

I I

Inadequate reabsorption of sodium and ;: water .. ;. and ". Reduced , . tubular : secretion . of potassium . and hydrogen
- '.

-"

Blood sodium level falls (hyponatraemia) Hydrogen retention Potassium retention (Increase in blood urea eventually) Excessive loss of sodium and water in urine (polyuria) Potassium level in urine falls.

- -- - l ..

body fluid volume decreases (dehydration) Blood volume falls

1 1

blood pressure falls I (hypotension) i risk of circulatory failure

'--_ metabolic acidosis

' - - - . Potassium intoxication 1 (hyperkalaemia) Muscular weakness and wasting 1 'ADRENAL A DROGEN' EFFECT: Females show loss of pubic and axillary hair.

. ..' '- .

'.

1 'GLUCOCORTICOID' EFFECT
I
I
.

- .. . .'.'.
'

".

- - --

.' . ,

.'

GLUCOSE formation from PROTEIN is depressed / ; 9/

_ .. Fasting blood sugar level low (hypoglycaemia) . . . may be fatal. Reduced mobilization of proteins and fat causes lack of energy for metabolism. great mu eular we kness and wasting, great loss of weight, 10 s of ppetite, hypotension vomiting and abdominal pain, anaemi II RBC formation), pigmentation of exposed and pressure areas of skin (due to rise in ACTH which has melanophore-stimulating properties), 1 resistance to stress and infections increased eosinophilsand lymphocytes in blood.

.'.c:

., .. .. : . .. . .-.

'. ,

. ..

Patients show M inor stress can produce a sudden collapse (Addisonian crisis). If untreated can be fatal.

202

Administration of cortisol, a synthetic mineralocorticoid, and sodium chloride restores individual to normal.

ENDOCR IN E SYSTEM

OVERACTIVITV OF ADRENAL CORTEX

O v eractivity or tumour of adrenal cortex may give excess secretion of any or all of the cor ticoid s:

e.g. ALDOSTERONE - -- - - - - . " PRIMARY ALDOSTERONISM (Conn's Syndrome) i TUBULAR SECRETION of K+ " Signs of potassium depletion and H+ predominate ... (lost with water) -----... ! ' ALKALOSIS MUSCLE / Excessive i Blood sodium --..... WEAKNESS reabsorption - I Expanded ECF ! of Sodium "\ volume Occasional periods and \ HYPERTENSION of muscular paralysis \ " ..... ', ! loss of Na" i BP due to nerve blocks '..".' i of K+ and W In urine Overproduction of CORTISOL and/or " CUSHING'S SYNDROME (see also CORTICOSTERONE - -- " i RBC --+ polycythaemia --+ florid complexion p.210)
Excess glucose : fo rmation from . protein

............

viscosity of blood --+ i BP ! Tissue protein ! Connective tissue

l< ,

!
High blood sugar -....,... Obesity especially Lipolysis i Glucose in urine diabetes mellitus ! Free fatty acids in blood of face and trunk

Altered res istance to stress

Overproduction of ADRENAL ANDROGENS - - - - - -- - - - - - " ADRENOGENITAL SYNDROME (Frequently excess production of androgens) Virilism in In CHILDREN ADU LT precocrous woman development of secondary , ...".. sex characteristics and secondary Muscular sex organs hypertrophy in 6-year-old boy , , , - -.> ' Pocket Hercules' Virilism in (After a 9-year-old (After a case girl case by Kepler et al.) by Guthrie)

--" ..

--

Administration of cortisone depresses pituitary secretion of A CTH -+ inhibits production of the abnormal steroids. R emoval of the over -secreting tissue or tumour restores individual. In secondary h yp eraldost eronism excess aldosterone i s the r esult of increased renin and angiotensin II secretion.

203

ENDOC RIN E SYSTEM

ADRENAL MEDULLA
The adrenal medulla arises from the same primitive tissue as the postganglionic cells of the sym pathetic nervous system. .
The cells contain granules HO which stain brown with H H ;) C - C HO salts of chromic acid. 90% \\"--..!J 0 H of the cells containing H these chromaffin granules --secrete ._ - - . --+ ADRENALINE and HO HO 10% of these cells secrete x 200 H C H C H H C H N '" ... H H " N H CH 3

0
H
-+

----.

NORADRENALINE

Richly supplied by a plexus of preganglionic sympathetic nerve fibres (p.31S). Secretion of the adrenal medulla is under control of the SYMPATHETIC NERVOUS SYSTEM (p.321). In times of stress or fear

released to Capillaries General circulation Body tissues

Frontal lobes stimulate one area of HYPOTHALAMUS Centre in MEDULLA OBLONGATA sends impulses along preganglionic sympathetic nerves (greater splanchnic) which cause liberation of adrenaline by adrenal medullae into blood stream

Adrenaline reinforces action of sympathetic nervous system in preparing the various systems of the body to react efficiently in emergencies and stress (p.205).

There is some evidence to suggest that adrena line and noradrenaline are released separately, e.g. stimulation of another part of the hypothalamus apparently leads to release of noradrena line into blood stream general vasoconstriction

204

Acetylcholine (ACh) transm its the nerve impulse from the preganglionic nerve endings to the adrenal medullary cells.

rise in blood pressure.

ENDOCRINE SYSTE M

ADRENALINE
Under quiet resting conditions the blood contains very little adrenaline. During excitement or circumstances which demand special efforts adrenaline is released into the blood stream, and is responsible for the following actions summed up as the 'fight or flight' function of the adrenal medullae. These actions are produced via 0( and Padrenergic receptors although adrenaline has a greater affinity for P receptors than IX receptors.
It constricts smooth muscle of skin -+

hairs 'stand on end'; 'Gooseflesh' . Dilates pupil of eye to admit more light.

Constricts smooth muscle of abdominal blood vessels and cutaneous blood vessels -+ pallor with fright. Dilates smooth muscle in arterioles of skeletal muscles. Excites cardiac muscle
[ Rate and force of contraction

L..-

,
\'

T Cardiac output T In local metabolites

1
1

Dilates coronary arteries Relaxes smooth muscle in wall of bronchioles -+ better supply of air to alveoli. Stimulates respiration. Inhibits movements of digestive tract. \ Contracts sphincters of gut. ..... Inhibits wall of urinary bladder. Contracts ureters and sphincter of I urinary bladder. , Mobilizes muscle and liver glycogen ,, I .,1 -+ increase in blood sugar, and mobilizes depot fat -+ 1 free fatty acid. Stimulates metabolism -+ T BMR Exerts favourable effect on contracting " skeletal muscle -+ fatigues less readily. Increases coagulability of blood. -Most of these effects can also be produced by stimulating sympathetic nerve fibres . The adrenal medullae are not essential to life - but without them the body is less able to face emergencies and conditions of stress.

'''''

/
, ,

I"

205

ENDOC RINE SYSTE M

DEVELOPMENT OF PITUITARY
The pituitary gland consists of anterior, intermediate and posterior parts which differ in origin, structure and function.
3rd VENTRICLE

'. ..,,",, i ;: ,, .: from roof of ,. . .../' primitive ./' mouth cavity .

ANTERIOR PART, arises as upgrowth

. /

POUCH
';\ ":,,;,,,;,

forms vesicle and. "; can nection with mouth -'," ' a-...... , cavity disappears .. :!:

'. ...tJ

--

--- -

POSTERIOR _ PART . anses as downgrowth from floor of primitive brain

Connection with base of brain persists

The two parts meet and fuse

I

I I

HYPOTHALAMUS ANTERIOR LOBE POSTERIOR LOBE

"ffJ"ij/

"'.,.,...::-;:'. ,-, . . . . " . .. . .: ...... ' . ' ..... 1.-. " . " .........:'" - . . . ." ,. ...O:Vt

-.

--

Part of Rathke's Pouch '" ... .' - - MEDIAN extends upwards to PARS base of brain to form - - - - - ... TUBERALlS ....- ,- - - -9;:. -_ EMINENCE , , INFUNDIBULAR - Cavity of Rathke's Pouch STEM is reduced to narrow spaces _ - - PARS Anterior of Rathke's \ - - - .. POSTERIOR Pouch thickens to form - . - -- PARS

,,

r. )

"Posterior wall of Rathke's Pouch thins down (After Garven) to form

..

,.'. -,

ANTERIOR

- - - - - -- PARS INTERMEDIA

Pars tuberalis + infundibular stem = infundibulum or pituitary stalk. Neurohypophysis = pars posterior (posterior or neural lobe) + infundibular stem + median eminence. Adenohypophysis = pars anterior (pars distalis or glandularis) + pars tuberalis (pars intermedia is also sometimes included). The adult pituitary (hypophysis) is a small (8 x 12 mm) oval gland which lies in the Sella Turcica - a small cavity in the bone at the base of the skull. It weighs only 500 mg but, along with the adjacent hypothalamus, it exerts a major control over endocrine function. Their close interdependence has resulted in the adoption of the term ' h yp ot hala m o- h y p op h ysia l system'.

206

ENDOCR INE SYSTEM

ANTERIOR PITUITARY
This is the master gland of the endocrine system. It regulates the activity of other endocrine glands, including the gonads, and influences all metabolic processes including growth. HYPOTHALAMUS
'/ . k-

Many parts of brain

STRESS : . - - - NERVOUS REFLEXES SUPERIOR Nerves from hypothalamus .. _ HYPOPHYSEAL synthesize hypothalamic ",,/ ,........ ARTERY =:::.:.:,; releasing and inhibiting"" by which hormones ,I . : " hormones and release them from the other ! ' , ' , into MEDIAN EMINENCE. This endocrine glands ., -, " FIRST CAPILLARY PLEXUS exert feedback ,--,"",-'" carries these hormones control of the ". ,down the LONG secretion of PORTAL VEINS to a hormones _ SECOND CAPILLARY from .' ) PLEXUS which surrounds the .; anterior pituitary cells anterior where they stimulate or pituitary inhibit release of trophic and hormones. hypothalamus HYPOPHYSEAL VEIN by which trophic hormones reach, influence and stimulate tissues

"'

: l,; :\.

--

.- -

From hypothalamus Thyrotrophinreleasing hormone. Corticotrophinreleasing hormone. Gonadotrophinreleasing hormone. Growth hormonereleasing hormone. Growth hormoneinhibiting hormone. (somatostatin). Prolactin-inhibiting hormone i.e. dopamine. Prolactin-releasing hormone.

THYROTROPHIN (TSH) GONADOTROPHINS ADRENOstimulate activity of CORTlCOGONADS. TROPHIC Testes in male. HORMONE Ovaries in female. (ACTH) FOLLICLE-STIMULA TlNG / HORMONE (FSH) ./ LUTEINIZING HORMONE (LH) ....

-=rii:ii:i"--::===============:::=J

:c a:

MAINLY CORTISOL OESTROGEN

PROLACTIN _ stimulates production of milk after parturition (At other times HYPOTHALAMIC PROLACTlNINHIBITING HORMONE prevents its release) I<-- GROWTH HORMONE (GH) (SOMATOTROPHIN) stimulates growth; acts via somatomedins IGF-1 (somatomedin C) and IGF-2; promotes retention of Nitrogen; influences protein. fat and carbohydrate metabolism: major anabolic action SOMATOSTATIN inhibits GH release. PROGESTERONE TESTOSTERONE in male

PIH or PRH "':"";":':"';""---1

The anterior pituitary cell population consists of 15-20% corticotrophs, 3-5% thyrotrophs, 10-15% gonadotrophs, 40-50% somatotrophs, 10-25% mammotrophs; identified by immunohistochemistry. (lGF-l = insulin-like growth factor l).

207

END OCRINE SYSTE M

UNDERACTIVITY OF ANTERIOR PITUITARY

D eficiency or absence of somatotroph cells Destructive disease of part of anterior pituitary (usually with damage to posterior pituitary and/or hypothalamus)

!
Underproduction of growth hormone ( somatotrophin)

!
Underproduction of growth and other endocrine- trophic hormones

! PITUITARY DWARF
( L orain Dwarf) Delayed skeletal growth and retarded sexual development but alert, intelligent, well proportioned child.

FROHLICH'S DWARF
Stunting of growth, obesity (large appetite for sugar); arrested sexual development; lethargic; somnolent; mentally subnormal.

..
" '.

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:::. ;c:. ;'.;_;,:.:

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.

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. v . . . . . _

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}n

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If atrophy of other endocrine glands

., (
:,:,.
'.

!
Signs of deficiency of their hormones.

"

.!
, ,
.';

':.-.:::: ' . '.' ;. ,

":::: :.;.-

AGE 13

208

Replacement therapy restores growth and development pattern to normal. Short stature of Pygmies is due to a genetic defect which prevents IGF-l being produced by growth hormone. In the LARON syndrome GH levels are normal but IGF-l levels are low.

NORMAL CHILD AGE 13

AGE 13
A similar condition occurs in adults without dwarfing but with suppression of sex functions and regression of secondary sex characteristics. Growth and gonadotrophic hormones aid in restoring patient to normal.

ENDOCR INE SYSTEM

OVERACTIVITY OF PITUITARY SOMATOTROPH CELLS

Functional overactivity (or tumour) chiefly of the SOMATOTROPH cells of the anterior pituitary leads to GIANTISM in the CHILD: ACROMEGALY in the ADULT. Overproduction of growth Hormone

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i IGF-1 (somatomedin

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Overgrowth of all body tissues

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Onset before bony epiphyses have closed at puberty Bones thicken especially of

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Onset after puberty

Stimulates protein synthesis. Influences carbohydrate and fat metabolism and mitosis of ALL CELLS of the body

-Long bones

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grow in length and feet (Height 7-8 feet) Overgrowth of I ... MUSCLES oJ , I Overgrowth of_ i'. SOFT TISSUES - -. . Coarse thick . I and / SKIN . ., INTERNAL ORGANS ./ r (e.g. Heart, ....."':;..i.'.:-;".;,c.,., . \ , :' .,'h. .';',' Sp Ieen, / v, Stomach, etc.)

face, jaw, _ _ nose, hands

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NORMAL CHILD AGE 13

AGE 13

Destruction of the overactive tissue - usually by surgery or radiation therapy - prevents progress of the condition.

209

ENDOCRI NE SYSTEM

OVERACTIVITY OF PITUITARY CORTICOTROPH CELLS

Overactivity (often due to tumour) of the corticotroph cells of the anterior pituitary gives [ ab sorption of Ca 2 + from gut -+ osteoporosis (rarefaction of bones) leads Cushing's to collapse of vertebrae syndrome and fractures. I Overproduction especially excess protein breakdown of ADRENOCOR TICO TROPHIC muscle wasting-weakness: HORMONE atrophied skin -+ purple striae ( A C T H or [ connective tissue corticotrophin) 1 FFA high blood sugar -+ obesity / sugar 10 unne I "" polyuria thirst 1Glucocorticoid effect Overstimulation, hypertrophy and 1 red blood count BP overacnviry polycythaemia of florid complexion ADRENAL - ----;.. T Mineralocorticoid effect CORTEX - - .... Excess (of cortisol and corticosterone) Corticoids is corrected by the body's adjustments to aldosterone secretion Via renm-angiotensin system Excess Androgens
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and anti-allergic effects: altered resistance to stress infections spread rapidly due to decreased inflammatory response; wounds heal slowly; fibroblastic activity is inhibited; normal allergic reactions are prevented since histamine release is hindered.

1 Anti-inflammatory

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Hirsutism and suppression of menstrual cycle

This condition is usually indistinguishable clinically from that seen in primary overactivity or tumour of the adrenal cortex itself. It can be produced by administration of large doses of glucocorticoids. The syndrome is shown here in the adult woman. 210 Overproduction of thyroid stimulating hormone
-+

Overactivity of thyroid gland.

ENDOCRINE SYSTEM

PAN HYPO PITUITARISM

Complete atrophy (or insufficiency) of all secreting cells of anterior pituitary in adult produces SIMMOND'S DISEASE Failure to produce Features usually any hormones - - - -... associated with very old age Appearance of premature senility

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Lack of growth hormone Grave upset in tissue metabolism - ..

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Hair grey, sparse: loss of body hair. Skin dry, sallow, wrinkled. Body emaciated (great loss of weight) Bones frail Sex organs atrophy. Menstruation ceases. Reproductive cycle stops. Secondary sex characteristics gradually regress.

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Lack of gonadotrophins

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This patient is only 42 years of age

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Lack of other endocrine-trophic - -.... All endocrines atrophy hormones and show depressed secretion of their hormones

After Zotuiek, Diseases of the Endoctrine Glands.

_.. Basal metabolism depressed Body temperature depressed, Heart rate low. Blood pressure low. Blood sugar low. Electrolytic upset.

T SH lack ACTH lack

Subject may die due to lack of control of metabolism. If less severe, symptoms of lack of only one or two pituitary hormones may predominate. Anterior pituitary hormones may relieve the condition but rarely succeed in completely restoring the patient to normal.

211

ENDOCRINE SYSTEM

POSTERIOR PITUITARY
NEURONS of the ,. s - : PARAVENTRICULAR HYPOTHALAMUS and ... .......... SUPRA-OPTIC NUCLEI , secrete .:> ANTIDIURETIC / HORMONES <"" Hormone (ADH or Vasopressin) " which m igrate " OXYTOCIN MAINLY attached to carrier ADH / peptide (neurophysin) along the nerve fibres in the SUPRAOPTICOHYPOPHYSEAL and I PARAVENTRICULOHYPOPHYSEAL / TRACTS to POSTERIOR PITUITARY for storage in / /' f Nerve fibres bulbous nerve endings r I' ", ... " '''' containing ........ I '. accumulations of I secretory I - - ,.. I I /;,, '. ' 01 / granules I (Herring bodies) , < .: 'e.'" i ! .,;- ... . I :;" ;...J , {e' .$,:) . and release into I '6> 1#.'1 I <::,oi!;"'* ..... J;; capillaries .... . . ,." .. x 500 Pituicytes (supporting GENERAL CIRCULATION cells)

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Nerve cells which synthesize hormones - - -

SUPRA-OPTIC __ ARTERY - - - - --Iloo(: Osmotic pressure of blood acts on osmoreceptors in hypothalamus. Influences rate of secretion and .' release of

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hormone (p.2'4)
ANTERIOR PITUITARY

3 main effects:VEIN Antidiuretic effect .... reduces output of urine by action on renal tubules via cAMP. Vasopressor effect .... constricts smooth muscle of blood vessels in response to haemorrhage .... raises arterial blood pressure. Oxytocic effect __ contraction of smooth muscle of uterus after childbirth and of myoepithelial cells in lactating mammary glands.

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ENDOCRIN E SYSTEM

OXYTOCIN
Secretion of hormone, OXYTOCIN, seems to depend on afferent (sensory) nerve im pulse - - - via sp inal cord -+ spinothalamic tract and midbrain from
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Nerve cells of the --- - - PARAVENTRICULAR NUCLEUS send impulses along axons of PARAVENTRICULOHYPOPHYSEAL - . NIPPLES - TRACTto of BREASTS POSTERIOR PITUITARY (during SUCKLING ) to discharge OXYTOCIC HORMONE LACTATING into BLOOD STREAM MAMMARY for GLANDS on Stimulates myoepithelial cells in ducts to contract

VULVA (during childbirth and coitus)

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Rapid expression of preformed milk from secreting alveoli to ducts -+ mouth of infant (galactagogue action or 'Let-down' of milk)
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Oxytocin Increases int racell ular Ca 2 + levels

Oxytocin is used therapeutically to induce labour and [0 decrease postpartum bleeding. Its function in the male is unknown.

UTERUS Lowers threshold for depolarization of muscle membrane. Reinforces contractions of uterine smooth muscle during and after chi ldbirth.

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Keeps uterus contracted after placenta is expelled, thus helps haemostasis.

213

ENDOC RINE SYSTEM

ANTIDIURETIC HORMONE (ADH)

Increased concentration of plasma sodium due to lack of dietary water or to loss of body water from sweat glands (in sweat) lungs (in expired air) gut (in faeces) Stimuli from external environment (e.g. painful . stimuli) and emotional stress Carotid. aortic baroreceptors ?nd receptors In L. atrium

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excess dietary salt results in Increased osmotic pressure of blood shrinks stimulates osmoreceptors Diminished concentration of plasma sodium due to e.g. excess intake of water Dilution of blood stream Stimulate

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Nerve cells transmit '" impulses along axons of . -. SUPRAOPTICOHYPOPHYSEAL TRACT to ---. POSTERIOR PITUITARY to cause discharge of ANTIDIURETIC HORMONE (ADH) into BLOOD STREAM for direct action on CELLS LINING DISTAL and COLLECTING TUBULES of KIDNEY NEPHRON ADH increases their permeability to water

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Diminished osmotic pressure Fall in activity of the osmoreceptors Fall in output of ADH Diminished reabsorption of water Increased output of dilute urine

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Augments reabsorption of " water from glomerular " , filtrate in ',DISTAL CONVOLUTED TUBULE and in COLLECTING TUBULES Reduces output of urine to balance and restore osmotic pressure

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Restores osmotic pressure relationships to normal. maintain fluid equilibrium

214

ADH binds to V 2 receptors on capillary side of duct cells -+ activates adenylate cyclase -+ increases cyclic AMP -> activates a protein kinase on luminal side of cell which results in the insertion of vesicles containing water channels into the apical membrane of the cell -> provides a rapid mechanism for increasing permeability of cell membrane to water.

ENDOCRINE SYSTEM

UNDERACTIVITY OF POSTERIOR PITUITARY

Damage. by injury or disease to ----- - HYPOTHALAMUS or to ---_ SUPRAOPTICOHYPOPHYSEAL TRACT If pituitary gland alone is removed ADH continues to be secreted from cut axons.

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causes DIABETES INSIPIDUS characterized by excessive production of dilute urine (polyuria) and excessive thirst (polydipsia)

Absence from blood stream of ANTIDIURETIC HORMONE (ADH)

Diminished reabsorption of water - - - from - - - Normal glomerular filtrate - of about 180 litres per day. REABSORPTION - - - - of - - - - about 140 litres of glomerular filtrate water from 'PROXIMAL CONVOLUTED is outside the influence of ADH. TUBULE and loop of HENLE REABSORPTION - - - - of - - - - about 40 Iitres per day from DISTAL CONVOLUTED TUBULE and COLLECTING - - - - - normally under ADH control. DUCT is reduced. (Cells lining collecting duct remain impermeable to water) Increased elimination ,/ofwater .; Urinary volume rises - - Usually 4-6 Iitres but can be 12-15 litres of pale dilute urine excreted/day (about 200 mOsm!l) instead of normal Iitres straw coloured more concentrated fluid (1000-1400 mOsmfl) Constant thirst occurs

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Replacement of ADH restores the elimination of water and symptoms of thirst to normal.

215

ENDOCRINE SYSTEM

ALDOSTERONE AND ANTIDIURETIC HORMONE (ADH) IN THE MAINTENANCE OF BLOOD VOLUME

A reduction in the total volume of extracellular fluid (e.g. after haemorrhage or loss of isotonic secretions from the gut in vomiting or diarrhoea) leads to chain of compensatory mechanisms in which aldosterone plays an important role. See pages 183 and 185.
e.g.

HYPOTHALAMUS

increases formation of ADH and its release from POSTERIOR

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Vasoconstriction :.-"""-'<1

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rerun release

reabsorption of H20

promotes retention of Na" w ith H20 by distal tubules

Converting enzyme in lung -

ANGIOTENSIN I
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ALDOSTERONE

Vasoconstrictor

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Decreased pressure in atria decreases release of atrial natriuretic peptide from the atria, thus decreasing excretion of Na" .

These measures serve to maintain blood volume till the long term replacement of the lost RBC, plasma proteins and electrolytes can be achieved.

216

ENDOC RINE SYSTEM

PANCREAS: ISLETS OF LANGERHANS

ISLETS OF LANGERHANS make up 1-2 % of pancreatic tissue. Consist of four cell types: A(oc) secrete glucagon, B(P) secrete insulin, D (c5) secrete somatostatin, F secrete pancreatic polypeptide (regulates release of digestive enzymes of pancreas).
ACTIONS A cells secrete GLUCAGON - - - TBLOOD GLUCOSE when it falls below normal. _ " (25%) CONTROL ! !BLOOD GLUCOSE Promotes conversion in liver (fasting = 5 mmolfl). glycogen TBLOOD -+ glucose lactic acid ! GLUCOSE TGLUCAGON amino acids ! i.e. protects against ! ! GLUCA GON \ Breakdown of hypoglycaemia. x \ GLYCOGEN " ACTIONS B cells (50-75%) secrete INSULIN - - ! BLOOD SUGAR CONTROL is by 'negative feedback' with BLOOD Accelerates: glucose into skeletal GLUCOSE muscle; synthesis of proteins. Converts: glucose -+ glycogen T BLOOD GLUCOSE !BLOOD (glycogenesis); glucose etc. -+ ....- GLUCOSE after a meal fatty acids (lipogenesis). ! ! Decrease in liver: glycogen -+ glucose lINSULlN TINSULIN . (glycogenolysis) other nutrients -+ glucose (gluconeogenesis). ATROPHY of ISLETS _ ABSENCE OF INSULIN DIABETES MELLITUS / !! rate of glucose transport across cell membranes TT UTILIZATION of GLUCOSE by MUSCLE MOBILIZATION and UTILIZATION of DEPOT FAT instead of glucose

:::::=== inhibits GLUCOSE UTILIZATION : promotes FAT UTILIZATION _ ==

BLOOD SUGAR (may reach ! 28 mmolfl) Renal threshold exceeded GLUCOSE in URINE (lost in ! solution with H20) Polyuria and polyphagia \... THIRST++ -> polydipsia KETONE BODIES in URINE

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FAT STORES depleted

Free fatty acids and ketone bodies in blood ! pH (acidosis)

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FAT DEPOSITS in BLOOD VESSELS (atherosclerosis) TT GLUCONEOGENESIS -+DEPLETION of BODY PROTEIN

muscle wasting and loss of weight; fatigue readily.

If untreated

-+

progressive drowsiness

-+

coma

->

death .

Excess insulin (h y p e rinsulinis m) -- low blood sugar (hypoglycaemia) -- irritability; sweating; hunger. If untreated -- reduction of metabolism of nervous tissues ..... giddiness -coma -- death. Somatostatin prevents excessive levels of nutrients in plasma by reducing rate of food digestion and absorption - Inhibits insulin and glucagon secretion.

217