Download L 2 parathyroid and calcium homeostasis 25th september 2012

Endocrine System
Lecture 2
Parathyroid hormone, calcium homeostasis
and suprarenal hormones
Asso. Professor Dr Than Kyaw
24 September 2012
PARATHYROID GLAND
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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 Gland
2. Parathyroid Gland
3. Parathyroid Gland
4. Enlarged Thyroid Gland
PARATHYROID GLAND
Parathormone
• Polypeptide hormone
• Secreted in response to low serum Ca & phosphorus levels
• Regulate calcium and phosphorus metabolism
Precursor PTH
In RER
Formation of
active PTH
In Golgi
Stored in
Secretory
vesicles
Secretion by
exocytosis
PARATHYROID GLAND
Parathormone
Organs 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
Parathormone
Increase
Ca absorption
(Distal convoluted
tubules of kidney)
Decrease phosphate
reabsorption
(Proximal convoluted
tubules of kidney
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
PTH
Promotes production of
enzyme α1-hydroxylase
needed for
Vitamin D
- Skin
(ultra violet light)
- diets
Metabolized to
2nd precursors
in the liver
Further
metabolized in
kidneys
1st precursors
inactive form
2nd precursors
inactive form
active form
1,25 dihydroxycholecalciferol
(calcitriole)
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
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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
HYPOPARATHYROIDISM
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
HYPERPARATHYROIDISM
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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)
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Sex hormones
Androgens, estrogens
Rate of secretion very low
Not necessary for normal reproductive behaviour and function
Adrenal glands
Adrenal gland
Cap 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.
2.
3.
4.
Corticosterone
Cortisol
Cortisone
11-dehydrocorticosterone
1. 11- deoxycorticosterone
2. 17-hydroxy -11-deoxycorticosterone
3. Aldosterone
Glucocorticoids
Mineralocorticoids
Structure of principle adrenocortical hormones
Role of glucocorticoids
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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
Renin - secreted by
juxtaglomerula
cells of the kidney
Circulating blood globulin,
angiotensinogen to form
Angiotensin I
Vascular
endothelium
form Angiotensin II
Low blood pressure
- Systemic arteriolar vasoconstriction
- Increase systemic blood pressure
Aldosterone
secretion
(Zona glomerulosa)
Promote Na reabsorption
And retention of water
Mechanism of corticotropin (ACTH) on adrenocortical steroidogenesis.
1. Stimulation of the uptake of low-density lipoproteins (LDL), which are further
processed to free cholesterol
2. Stimulation of the hydrolysis of stored cholesterol esters to generate free cholesterol
3. Stimulation of the transport of cholesterol into mitochondria, where cleavage of the
cholesterol side chain occurs
4. 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
Adrenal medulla (inner part)
– 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
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
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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 animals
Vomiting
Diarrhoea,
Lethargy
Lack of appetite,
Tremors or shaking,
Muscle weakness,
Low body temperature,
Collapse,
Low heart rate, and
Pain in the hind quarters
Adrenal Insufficiency
Sex hormone deficiency
• Loss of body hair
• Loss of libido or importancy
• Menstrual and fertility disorders in women
Adrenal Insufficiency
Cushing’s syndrome
Cause:
- Sustained over-production of glucocorticoids by adrenal
gland from ACTH by pituitary tumour
- Excessive glucocorticoid administration
• HYPOTENSION
Sex
Steroids
• 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, Corticotropinreleasing hormone.
ADRENAL GLAND
HORMONE
FUNCTION
Aldosterone
Renal : Na & Cl reabsorption; K
excretion
GI : Na absorption
Increase serum glucose by
gluconeogenesis & glycogenolysis esp.
during Stress
Blocks inflammation
Counteracts effect of histamine
Physiologically insignificant
Becomes useful during menopause in
women
Glucocorticoids
Sex hormone
END OF LECTURE