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Endocrine System. Lecture 2 Parathyroid hormone, calcium homeostasis and suprarenal hormones. Asso . Professor Dr Than Kyaw 24 September 2012. PARATHYROID GLAND. How many parathyroid glands in animals? Located within or near thyroid gland

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slide1

Endocrine System

Lecture 2

Parathyroid hormone, calcium homeostasis and suprarenal hormones

Asso. Professor Dr Than Kyaw

24 September 2012

parathyroid gland
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
slide3

Left thyroid and parathyroid glands

1. Normal Thyroid Gland2. Parathyroid Gland3. Parathyroid Gland4. Enlarged Thyroid Gland

slide5

PARATHYROID GLAND

  • Parathormone
  • Polypeptide hormone
  • Secreted in response to low serum Ca & phosphorus levels
  • Regulate calcium and phosphorus metabolism
  • Stored in
  • Secretory
  • vesicles
  • Formation of
  • active PTH
  • In Golgi
  • Precursor PTH
  • In RER
  • Secretion by
  • exocytosis
slide6

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 osteoblastsis inhibited
  • - Osteoclasts – bone resorption, removal of bone matrix
slide7

PARATHYROID GLAND

  • On kidney
  • Parathormone
  • Promote the formation of activeVitD by the kidney
  • Increase
  • Ca absorption
  • (Distal convoluted tubules of kidney)
  • Decrease phosphate reabsorption
  • (Proximal convoluted tubules of kidney
  • - Overall result of parathormone action on bone and kidney - increase in blood calcium and phosphorus
slide8

Parathormone and Vitamin D

PTH

Promotes production of

enzyme α1-hydroxylase

needed for

  • Vitamin D
  • Skin
  • (ultra violet light)
  • - diets
  • Further
  • metabolized in
  • kidneys

Metabolized to 2nd precursors

in the liver

active form

1,25 dihydroxycholecalciferol

(calcitriole)

  • 1st precursors
  • inactive form
  • 2nd precursors
  • inactive form
  • Vitamin D
  • Increases the rate of Ca and P absorption from GIT
  • Reduce loss of Ca in the urine
hypo parathyroidism
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
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 eclampsia1
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
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
hypoparathyroidism1
HYPOPARATHYROIDISM

MANAGEMENT:

  • Ca supplement
  • VitD supplement – LIQ FORM: WITH WATER, JUICE OR MILK
  • Ca-gluconate
hyperparathyroidism
HYPERPARATHYROIDISM
  • Increased PTH production
  • HYPERCALCEMIA
  • HYPOPHOSPHATEMIA
  • Primary cause – Tumour orhyperplasia 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
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
  • Ricketsin young
  • Bran disease or big-head disease in horse
parathyroid
PARATHYROID

DIAGNOSTIC TESTS:

  • Hematological
    • Serum calcium
    • Serum phosphorus
    • Serum alkaline phosphatase
  • Urinary studies
    • Urinary calcium
    • Urinary phosphate – tubular reabsorption of phosphate
adrenal gland suprarenal gland1
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)

    • Zonaglomerulosa
    • 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
slide22

Adrenal gland

Cap capsule

C cortex

Fzonafasciculata

Gzonaglomerulosa

M medulla

Rzonareticularis

Ttrabeculae

V vein

slide23

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

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

adrenal gland
Adrenal Gland
  • Glucocorticoids (cortisol and corticosterone)
  • - secreted by zonafasciulataand zonareticularis
  • - regulated by ACTH
  • - Stress ACTH glucocorticoids secretion
  • - absence of ACTH – atrophy of zonafasciulata and zonareticularis but not zonaglomerulosa
seven adrenocortical hormones
Seven adrenocortical hormones
  • Corticosterone
  • Cortisol
  • Cortisone
  • 11-dehydrocorticosterone
  • Glucocorticoids
  • 11- deoxycorticosterone
  • 17-hydroxy -11-deoxycorticosterone
  • Aldosterone
  • Mineralocorticoids
role of glucocorticoids
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
Mineralocorticoids (Aldosterone)
  • Secretion is regulated by
  • Renin-angiotensin system
  • Increased plasma concentration of potasium (hyperkalemia)
  • ACTH sitmulation (minor)
renin angiotensin system
Renin-angiotensin system

Renin - secreted by juxtaglomerula cells of the kidney

Vascular endothelium

form AngiotensinII

Circulating blood globulin, angiotensinogen to form AngiotensinI

Low blood pressure

Aldosterone

secretion

(Zonaglomerulosa)

- Systemic arteriolar vasoconstriction

- Increase systemic blood pressure

Promote Na reabsorption

And retention of water

slide30

Mechanism of corticotropin (ACTH) on adrenocorticalsteroidogenesis.

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

Promotion of the binding of cholesterol to the enzyme.

AC, Adenylcyclase; ATP, adenosine triphosphate;

cAMP, cyclic adenosine monophosphate; R, recaptor.

mineralocorticoids aldosterone1
Mineralocorticoids (Aldosterone)
  • Actions
  • Increase sodium reabsorptionand potassium excretion from the kidney
  • Membrane transport in sweat glands, salivary glands, and intestinal mucosa
  • They also have some glucocorticoid activity
slide32

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
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
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
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

slide36

Adrenal Insufficiency

Sex hormone deficiency

  • Loss of body hair
  • Loss of libido or importancy
  • Menstrual and fertility disorders in women
slide37

Adrenal Insufficiency

  • Cushing’s syndrome
  • Cause:
  • - Sustained over-production of glucocorticoids by adrenal gland from ACTH by pituitary tumour
  • - Excessive glucocorticoid administration
sex steroids
Sex Steroids
  • HYPOTENSION
  • FLUID LOSS
  • HYPONATREMIA

LAB:

  • Serum electrolytes: Decreased Na

Increased K

  • Serum glucose
  • Adrenal hormone assay
  • Hydroxycorticoid & 17- ketosteroid in urine
slide39

Regulation of cortisol secretion by the hypothalamopituitary axis.

Plus signs indicate stimulation; minus signs indicate inhibition.

CRH, Corticotropin­releasing hormone.