Endocrine System

Lecture 2Parathyroid hormone, calcium homeostasis

and suprarenal hormones

Asso. Professor Dr Than Kyaw24 September 2012

PARATHYROID GLAND• How many parathyroid glands in animals?• Located within or near thyroid gland• 2 pairs in most domestic animals, 2 on each side• External or internal (burried inside) parathyroids• Commonly one pairs is visible outside the thyroid gland• Pigs and birds – lack of internal parathyroids

2 cell types - Chief cells

- produce parathyroid hormone (PTH)/parathormone- Oxyphil cells

- larger, less numerous (found in horse, cattle and man) - function unknown

Left thyroid and parathyroid glands 1. Normal Thyroid Gland2. Parathyroid Gland3. Parathyroid Gland4. Enlarged Thyroid Gland

PARATHYROID GLANDParathormone• Polypeptide hormone• Secreted in response to low serum Ca & phosphorus levels• Regulate calcium and phosphorus metabolism

Precursor PTHIn RER

Formation of active PTH

In Golgi

Stored in Secretoryvesicles

Secretion byexocytosis

PARATHYROID GLAND

ParathormoneOrgans affected

• primary effect of PTH is to increase Ca and decrease Phosphate concentrations in extracellular fluids

• Bones – bone resorption- osteocytes maintenance and turnover of the mineral content of the bone - release of calcium and phosphate from bone - bone formation by osteoblasts is inhibited- Osteoclasts – bone resorption, removal of bone matrix

PARATHYROID GLAND

On kidney

Increase Ca absorption

(Distal convoluted tubules of kidney)

Decrease phosphate reabsorption(Proximal convoluted tubules of kidney

Parathormone

Promote the formation of

active Vit D by the kidney

- Overall result of parathormone action on bone and kidney - increase in blood calcium and phosphorus

Parathormone and Vitamin D

Vitamin D- Skin (ultra violet light)- diets

Furthermetabolized in

kidneys

1st precursorsinactive form

Metabolized to 2nd precursors

in the liver

2nd precursorsinactive form

active form1,25 dihydroxycholecalciferol

(calcitriole)

PTHPromotes production ofenzyme α1-hydroxylase

needed for

Vitamin D- Increases the rate of Ca and P absorption from GIT- Reduce loss of Ca in the urine

Parathormone is more important in the regulation of Calcium and Phosphorus than

calcitonin.

Relationships of parathyroid hormones and other organs

HYPO-PARATHYROIDISM• Decreased PTH production• Rare both in animals and man• Hypocalcemia• Calcium is:

– Deposited in the bones – Excreted in urine

Cause:• Heredity• Idiopathic• Surgical removal of thyroid gland

Hypocalcemia in animals (Tetany/eclampsia)

• Most common Ca metabolism disturbance occurs at the time of parturition.

• Most frequent in dairy cows (milk fever) and dogs. • Affected animals

- severe hypocalcemia- often severe neuromuscular dysfunction- recumbent (cow) and involuntary muscular spasm (dog) referred to tetany or eclampsia

• The problem arises from sudden demand of Ca needed for milk production so that serum Ca concentration is no longer maintained within homeostatic limit.

Hypocalcemia in animals (Tetany/eclampsia)

Cause• Cause of milk fever – complex one• It does not seem to involve a failure of PTH secretion

- It may be due to impaired responsiveness of PTH target tissues (receptor expression)- impaired Vit D activation

Treatment- infusion of glucose and calcium (calcium borogluconate)- the animal usually recover after the treatment

Signs in man• Acute hypocalcemia

– Tingling of the fingers• Chronic hypocalcemia

– Fatigue, weakness– Personality changes– Loss of tooth enamel, dry scaly skin– Cardiac arrhythmia– Cataract

HYPOPARATHYROIDISM

MANAGEMENT:• Ca supplement• Vit D supplement – LIQ FORM: WITH WATER, JUICE OR MILK

• Ca-gluconate

HYPOPARATHYROIDISM

HYPERPARATHYROIDISM

• Increased PTH production• HYPERCALCEMIA• HYPOPHOSPHATEMIA• Primary cause – Tumour or hyperplasia of the parathyroid

gland• Secondary – Compensatory oversecretion of PTH in

response to hypocalcemia from:– Chronic renal disease– Rickets– Malabsorption syndrome– Osteomalacia

Dietary Ca deficiency and hyperthyroidism

• Insufficient Ca in diets - common in domestic animals• Especially diets formulated primarily on grain products• Chronically low intake of dietary Ca - stimulates increased

secretion of PTH to keep blood Ca level for nerve and muscle function.

• Ca is removed from bone matrix - bone decalcification- bone deformities- osteoporosis

• k/s - Nutritional 2° hyperthyroidism• Rickets in young• Bran disease or big-head disease in horse

PARATHYROID DIAGNOSTIC TESTS:• Hematological

– Serum calcium– Serum phosphorus– Serum alkaline phosphatase

• Urinary studies– Urinary calcium– Urinary phosphate – tubular reabsorption of

phosphate

Adrenal Gland (Suprarenal gland)

Adrenal Gland (Suprarenal gland)• Adrenal gland located atop kidney• Shape, size and exact location vary depending on the species• Generally stimulated by ACTH

Adrenal cortex (outer part)– Zona glomerulosa– Mineralocorticoids (mainly aldosterone)– Na and K balance– Control loss of Na and K in the urine– Mineralocorticoids are not regulated by ACTH (regulated by renin-

angiotensin system)

– Sex hormones– Androgens, estrogens– Rate of secretion very low– Not necessary for normal reproductive behaviour and function

Adrenal glands

Adrenal glandCap capsule C cortex F zona fasciculata G zona glomerulosa M medulla R zona reticularis T trabeculae V vein

A) Cross section of the adrenal gland showing the contrasting appearance of the cortex and medulla

B) Magnification of boxed-I area in A that shows the different cell types associated with the the three zones of the cortex

Adrenal Gland

• Glucocorticoids (cortisol and corticosterone)- secreted by zona fasciulata and zona reticularis- regulated by ACTH- Stress ACTH glucocorticoids secretion

- absence of ACTH – atrophy of zona fasciulata and zona reticularis but not zona glomerulosa

Seven adrenocortical hormones

1. Corticosterone2. Cortisol3. Cortisone4. 11-dehydrocorticosterone

Glucocorticoids

1. 11- deoxycorticosterone2. 17-hydroxy -11-deoxycorticosterone3. Aldosterone

Mineralocorticoids

Structure of principle adrenocortical hormones

Role of glucocorticoids

• Carbohydrate metabolism• Gluconeogenesis• From non-carbohydrate sources – protein and fat• Other two hormones – glucagon and epinephrine

- increases blood glucose level by glycolysis of liver glycogen

Use of glucocorticoids- treatment of bovine ketosis- anti-inflammatory activity- ophthalmic preparation, ear-drops, skin ointment

Mineralocorticoids (Aldosterone)

Secretion is regulated by– Renin-angiotensin system– Increased plasma concentration of potasium (hyperkalemia)– ACTH sitmulation (minor)

Renin-angiotensin system

Circulating blood globulin, angiotensinogen to form

Angiotensin I

Renin - secreted by juxtaglomerula

cells of the kidney

Vascular endothelium

form Angiotensin II

Aldosteronesecretion

(Zona glomerulosa)

Promote Na reabsorptionAnd retention of water

Low blood pressure

- Systemic arteriolar vasoconstriction- Increase systemic blood pressure

Mechanism of corticotropin (ACTH) on adrenocortical steroidogenesis.1. Stimulation of the uptake of low-density lipoproteins (LDL), which are further processed to free cholesterol2. Stimulation of the hydrolysis of stored cholesterol esters to generate free cholesterol 3. Stimulation of the transport of cholesterol into mitochondria, where cleavage of thecholesterol side chain occurs4. Promotion of the binding of cholesterol to the enzyme.

AC, Adenyl cyclase; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; R, recaptor.

Mineralocorticoids (Aldosterone)

Actions– Increase sodium reabsorption and potassium excretion

from the kidney– Membrane transport in sweat glands, salivary glands, and

intestinal mucosa– They also have some glucocorticoid activity

– Chromaffin cells– Secrete amine hormones (catecholamines)

- Epinephrine & norepinephrine (fight –fright-flight)- More epinephrine is secreted by adrenal medulla than norepinephrine- Norepinephrine is also secreted by postganglionic sympathetic neurons

- Activation of catecholamines – very fast- half life of epinephrine - 20 to 40 seconds

- Medullary secretion – a continuous process and increases dramatically during an emergency

Adrenal medulla (inner part)

Catecholamines

• Actions of epinephrine and norepinephrine are the similar• Differences depend on receptors• Adrenergic receptors

- alpha receptors (stimulatory, but not intestinal mucosa)- beta receptors (inhibitory, but not cardiac muscle)

- In addition to fight-fright-flight reactions of catecholamines, they have pronounced metabolic effect.- hyperglycemia, lypolysis, - calorigenic effect – increased muscle activity

Adrenal Insufficiency in man

• Addison’s disease--hyposecretion of cortisol• Chronic adrenal insufficiency• Not common in man• Darkened skin (pigmentation)• Weight loss, • Hypoglycemia, increased K• Low BP• Metabolic acidosis• Inability to handle stress (impaired stress tolerance)• Dehydration and hypotension shock

Addison’ disease in animals

Common in canines, not found in other animalsVomitingDiarrhoea,Lethargy Lack of appetite, Tremors or shaking, Muscle weakness, Low body temperature,Collapse, Low heart rate, and Pain in the hind quarters

Sex hormone deficiency

• Loss of body hair• Loss of libido or importancy• Menstrual and fertility disorders in women

Adrenal Insufficiency

Adrenal Insufficiency

Cushing’s syndromeCause:- Sustained over-production of glucocorticoids by adrenal gland from ACTH by pituitary tumour

- Excessive glucocorticoid administration

Sex Steroids• HYPOTENSION• FLUID LOSS• HYPONATREMIA

LAB:• Serum electrolytes: Decreased Na

Increased K • Serum glucose • Adrenal hormone assay

Hydroxycorticoid & 17- ketosteroid in urine

Regulation of cortisol secretion by the hypothalamopituitary axis.Plus signs indicate stimulation; minus signs indicate inhibition.CRH, Corticotropin releasing hormone.

ADRENAL GLANDHORMONE FUNCTIONAldosterone Renal : Na & Cl reabsorption; K

excretion GI : Na absorption

Glucocorticoids Increase serum glucose by gluconeogenesis & glycogenolysis esp. during Stress

Blocks inflammation Counteracts effect of histamine

Sex hormone Physiologically insignificant Becomes useful during menopause in

women

END OF LECTURE