Endocrine mrmc

Human
Endocrine
Glands
• In the brain:
• Hypothalamus
• Pituitary gland
• Pineal gland
• Adrenal gland
• Pancreas
• Ovary
• Testis

Endocrine action
Endocrine system controls
physiology via chemical signals from
one part of the body to another
Target cell undergoes a biological
response

Cell to Cell Signaling
AUTOCRINE

AUTOCRINE
PARACRINE

AUTOCRINE
PARACRINE
ENDOCRINE

 Neurocrine - neural
cells that release
chemical signals into
the bloodstream

Figure 18.1
The Endocrine System

FUNCTIONS
1. Regulate metabolic processes
2. Regulate rate of chemical reactions
3. Transport of substances thru membrane
4. Regulate water and electrolyte balance, blood
pressure
5. Vital roles in reproduction, development, growth

Classification of Hormones
1. Based upon chemical nature
2. Based upon function

Chemical Nature of Hormones
Hormones are
Peptides
Steroid
Amino Acid Derivatives

Chemical Classification of Hormones
1. Amino hormones
-derived from tyrosine
2. Peptide and protein hormones
- Made up of peptide
3. Steroid hormones
– derived from cholesterol

Proteins & polypeptides
Pituitary, Pancreas, Parathyroid.
b. Steroids
Adrenal cortex and Sex hormones.
c. Amino acid derivatives
Adrenal Medulla, Thyroid hormones.
Classification of hormones

Functional classifications
1. Releasing hormones
2. tropic (or Stimulating) hormones
3. Non-tropic hormones

Hypothalamus
Pituitary gland
Releasing hormones
Peripheral endocrine glands
Stimulating hormones
Hormonal axis
Hormones
Peripheral organs
BRAIN

Hormone types
1. Polar:
• Most hormones.
• Bind to receptor protein on pm.
2.Lipophilic (nonpolar):
• Cross pm, act inside target cells.
• Steroid hormones and thyroid hormones.

Hormones
Synthesis
Secretion
In circulation

Second messengers
Second messengers include
– cAMP or cGMP
– phospholipids diacylglycerol and inositol
triphosphate (DAG and IP3)
– calcium

Lipophilic hormones
- Inside cell: bind to nuclear hormone
receptors.

Transcription factors
• Transcription:
DNA is transcribed into messenger
RNA.
This mRNA will then be translated
(by ribosomes) into proteins!

Effects of [Hormone] on Tissue
Response
1. Blood levels
2. Number of receptors on target cells
3. Affinity of receptors for hormones

Regulation of receptor
1. Down regulation (desensitization):
2. Up regulation:

Hypothalamic-Pituitary Axis
– Hypothalamic-Pituitary-Thyroid axis (HPT)
– Hypothalamic-Pituitary-Adrenal axis (HPA)
– Hypothalamic-Pituitary-Gonadal axis
(HPG)

Control of Hormone Secretion
1. Negative Feedback mechanism
2. Positive Feedback mechanism
3. Hypothalamo-hypophyseal tract.

Positive Feedback Control
Parturition and suckling
•

Hypothalamic Control of Posterior Pituitary
(ADH)
(Oxy)

Measurement of Endocrine
function
1. Most used is radioimmunoassay (RIA)
-Hormones present in nanomolar to
picomolar range
2. Radioreceptor assays (RRA)
3. Bio-assays use target cell
4. ELISA

Anterior and posterior pituitary glands.

Anterior pituitary cells and hormones
Cell type Pituitary
population
Product Target
Corticotroph 15-20% ACTH Adrenal gland
Adipocytes
Melanocytes
Thyrotroph 3-5% TSH Thyroid gland
Gonadotroph 10-15% LH, FSH Gonads
Somatotroph 40-50% GH All tissues, liver
Lactotroph 10-15% PRL Breasts
gonads

Hormones of the Anterior Pituitary
1. Growth hormone (GH)
2. Prolactin
3. Thyroid stimulating hormone (TSH)
- also called thyrotropin
- stimulates milk production
- one of the growth promoting hormones

Hormones of the Anterior Pituitary con’t
4. Adrenocorticotrophic hormone (ACTH)
5. Leutinizing hormone (LH)
6. Follicular stimulating hormone (FSH)
- stimulates follicular development
- promotes ovulation
- also called corticotropin

Hypothalamic Control of the Anterior Pituitary

GH or SomatotropinGH or Somatotropin
Secreted by somatotropesSecreted by somatotropes
Done indirectly – liver produces –Done indirectly – liver produces –
somatomedins or IGF’s – insulin growthsomatomedins or IGF’s – insulin growth
factorsfactors

Actions mediated by GH and IGF-1

GH-IGF actionsGH-IGF actions
1.Protein synthesis1.Protein synthesis
• mRNAmRNA
• GH enhances amino acid transport into cellsGH enhances amino acid transport into cells
• Ensures protein anabolismEnsures protein anabolism
• Suppresses protein catabolismSuppresses protein catabolism
• Protein sparing effectProtein sparing effect

2.Lipid metabolism2.Lipid metabolism
• Release free fatty acids and glycerolRelease free fatty acids and glycerol
• FFA’s used for energyFFA’s used for energy
• Provides energyProvides energy
• 3.Carbohydrate metabolism3.Carbohydrate metabolism
• Glucose sparing effectGlucose sparing effect

4.Electrolyte balance4.Electrolyte balance
• Na, K, ClNa, K, Cl--
retention – kidneysretention – kidneys
• EnhancesEnhances CaCa++++
absorption – small intestinesabsorption – small intestines
• These electrolytes available for tissue growthThese electrolytes available for tissue growth
5. Prolactin like action.5. Prolactin like action.

Physiological function of GH (somatotropin) :
↑Plasma FFA
↑Plasma glucose
↓Plasma amino acids
↓ Plasma urea
Metabolism
Condrocytes
↑Amino acid uptake
↑Protein synthesis
↑DNA,RNA synthesis
↑Chondroitin sulfate
↑Cell size and number
↑Linear growth
Muscle
↓ Glucose uptake
↑Amino acid uptake
↑ Protein synthesis
↑Lean body mass
Adipose tissue
↓Glucose uptake
↑Lipolysis
↓ adiposity
Kidney, pancreas, intestine, islets,
parathyroids, connective tissue,
bone, heart, lungs
↑Protein synthesis
↑DNA,RNA synthesis
↑Cell size and number
↑Organ size
↑Organ function
Growth
hormone

Control of GH secretion
SS GHRH
GH
IGF-1
Target tissue
⊕○-
⊕
⊕
-○
Somatostatin: SS
Somatotropin: GH
Somatomedin: IGF-1

Regulation of Growth HormoneRegulation of Growth Hormone
SecretionSecretion
• GH secretion controlled primarily byGH secretion controlled primarily by
hypothalamic GHRH stimulation andhypothalamic GHRH stimulation and
somatostatin inhibitionsomatostatin inhibition

Regulation of GH releaseRegulation of GH release
Augment GH Inhibit GH
Neurogenic Stage 3 and 4 sleep
Stress
Alpha agonists
Beta antagonists
REM sleep
Emotional deprivation
Metabolic Hypoglycaemia
Fasting
Amino acids
Hyperglycaemia
High FFA
Obesity
Hormonal GHrH
Low IGF-1
Oestrogens
Glucagon
GHRPs
Somatostatin
High IGF-1
Hypothyroidism
High GC levels

Abnormalities of GH secretion :
Dwarfism
Acromegaly
Gigantism

– Pituitary dwarfsPituitary dwarfs are a result ofare a result of
hyposecretionhyposecretion
– GigantismGigantism results from juvenileresults from juvenile
hypersecretionhypersecretion
– AcromegalyAcromegaly results from adultresults from adult
hypersecretion of GHhypersecretion of GH

• ExcessiveExcessive
Production duringProduction during
childhoodchildhood

Growth Hormone Excess
• in childhood leads to GIGANTISM

GigantismGigantism
Identical twins, 22 years old, excess GH secretion

Features :
 Tall stature
Bilateral gynecomastia
 Large hands & feets
 Coarse facial features
 Loss of libido

• HandsHands
• FeetFeet
• JawsJaws

Growth Hormone Excess
• in adulthood leads to ACROMEGALY

• Progression of untreated acromeglyProgression of untreated acromegly
Prior
Early
Onset
Full
Development

Features :
 Elongation and widening of mandible
 Enlargement of sinuses causing prominent
brow
 Thickening of skin & coarsening of the facial
features.
 Kyphosis & Scoliosis.
 Hypertrophy of body soft tissue

• With the life cycle
the rate of growth
is not even.
• Infancy has the
highest rate
decreasing until of
spurt of growth
caused by sexual
maturity.

• Growth Rates differ according to
the time of the life cycle.
• Growth hormone and Thyroxine
are the most active.
• Sex hormones govern growth
spurt at sexual maturity.

Posterior lobe
• Produces No Hormones .
• Stores and releases OT and ADH

Posterior pituitary
• Stores and releases 2 hormones that are
produced in the hypothalamus:
1. - Antidiuretic hormone (ADH)
2. - Oxytocin

posterior lobe (neurohypophysis)
 Neurons of the supraoptic nucleus manufacture
antidiuretic hormone (ADH)
1. Decreases the amount of water lost at the kidneys
2. Elevates blood pressure

posterior lobe (neurohypophysis)
 Neurons of the paraventricular nucleus
manufacture oxytocin
1. Stimulates contractile cells in mammary glands
2. Stimulates smooth muscle cells in uterus

Structures of ADH and oxytocin

Antidiuretic hormone (ADH):
• aka vasopressin ( 1000:1)
• Synthesis
• Transport
• Release

Physiological effects of ADH :
1. The retention of water in excess of
solute by the kidney
2. In large doses, vasopressin elevates
arterial blood pressure

ADH (antidiuretic hormone):
• Stimulates fusion of aquaporin (water channel)
vesicles in the collecting duct.
• Results in (increased permeability to H20 and )
increased reabsorption of water.

Mechanism of Vasopressin Action
Figure 20-6: The mechanism of action of vasopressin

ADH increases renal tubular
absorption of water

• Administration of (sodium) cause ADH
release.
• Urea - ???
• Changes of 1-2%
Secretion of ADH–osmolality control

• decrease in blood volume, cardiac output, or
blood pressure.
• Hemorrhage
Secretion of ADH—hemodynamic
control

• Hypovolemia
• Normally, pressure receptors tonically
inhibit ADH release.
• 5 to 10% change in volume
Secretion of ADH

Feedback Loop for ADH
Negative feedback

• The two major stimuli of ADH secretion
interact.
1. Changes in volume
2. changes Plasma osmolar.
• Hypovolemia sensitizes the ADH response
to hyperosmolarity.
Secretion of ADH

Regulators
of
Vasopressin
Release

Neuroendocrine reflexes
• release hormones – nervous system signal
1. ADH – dehydration > osmolarity of blood –
osmoreceptors detect – ADH released = water
conservation
2. >BP –stimulates stretch receptors in heart & certain
arteries – inhibits ADH release, > urine output, < BP

Regulation/Stimuli:
- Blood (or ECF) osmolality/osmoreceptor
- Blood volume
- Others: alcohol, nicotine, barbiturates, etc.

Pituitary - Diabetes Insipidus

1. Diabetes insipidus
2. Nephrogenic diabetes insipidus
(receptor disease)
Clinical implications:

Diabetes Insipidus - clinical features:
• polyuria- 3-15 L/day
• SG < 1.005
• urine osmolality <200 mOsm/kg
• plasma osmolality > 287 mOsm/kg
• polydipsia

1.In uterus during parturition
2.In mammary gland during lactation
Oxytocin

“Positive feedback loop”
Oxytocin↑
Uterine
contraction
Cervix
dilation
Labor
Oxytocin receptor
↑x100
Estradiol
⊕
⊕

Oxytocin secretion is stimulated by
nursing

Oxytocin
1. Childbirth – labor contractions – smooth muscle –
uterus
2. Lactating mothers – milk let-down effect
3. Surges –sexual arousal and orgasm – m & f
4. Feelings sexual satisfaction and emotional bonding

Control of oxytocin secretion
• Stimuli:
• Stimulation of the “touch receptor”
1. Around the nipples Milk let-down or
“milk ejection reflex”
2. Genital tract stimulation
• Inhibition:

Neuroendocrine reflexes
• Infant suckling – hypothalamus – release OT = milk
ejection
• Cerebral cortex – trigger neuroendocrine reflexes
• Examples – lactating mother hears baby cry = milk
ejection reflex

Thyroid Gland
 First endocrine gland to be recognized.
Weighs about 15-25gm &has rich blood
supply (4-6ml/gm/min).
Made up of multiple acini / follicles.
 Between follicles “C cells/parafollicular cells ”
are present Calcitonin.

 Each follicle contains proteinaceous material
called colloid which contains Thyroglobulin.
Follicular cells secrete T4 & T3.

i. Synthesis of thyroglobulin on ribosomes of ER.
ii. Iodide trapping.
 T/P iodide ratio = 20-50:1
Trapping is brought by active transport
(Iodide pump) which depends on
Na+/k+ATPase.
TSH stimulates both iodide pump &
Na+/k+ATPase.
Inhibited by Perchlorate, Thiocyanate.

iii. Oxidation of iodide ion:
Iodide converted to oxidised form of iodine ,
either nascent iodine (Io
) or I3
-
.
I-
Io
or I3
-
.
Peroxidase H202

iv. Iodination of tyrosine & formation of thyroid
hormones .
Binding of iodide with thyroglobulin is called
“organification of thyroglobulin”.
Tyrosine
Iodinase
MIT & DIT
MIT + DIT  T3 + Alanine.
DIT + DIT  T4 + Alanine.
DIT + MIT  rT3+ Alanine.
Coupling
reactions
Thyroid peroxidase is probably involved in coupling
& Iodination.

Storage of thyroglobulin (Tg):
Tg  30 T4 + few T3 molecules.
Large amount of thyroid hormones are stored in
this form which is sufficient for 2-3 months.

Secretion of Thyroid Hormones
 Stimulated by TSH
 Endocytosis of colloid on apical membrane
 Coupling of MIT & DIT residues
 Catalyzed by TPO
 MIT + DIT = T3
 DIT + DIT = T4
 Hydrolysis of Thyroglobulin
 Release of T3, T4
 Release inhibited by Lithium

Transport of thyroid hormones
 Majority of circulating hormone is T4
 98.5% T4
 1.5% T3
 Total Hormone load is influenced by serum
binding proteins (TBG, Albumin, TBPA)
 Thyroid Binding Globulin (TBG) 70%
 Albumin 15%
 Thyroid Binding PreAlbumin (TBPA) 10%
 Regulation is based on the free component of
thyroid hormone

Metabolism of Thyroid hormones

Actions of Thyroid hormones
♪ Metabolic actions.
♪On various systems.
♪On Growth.
♪ Interaction with Catecholamines.

1. Metabolic Actions :
A. Calorigenic
 Increases O2 consumption & heat production by
stimulating Na+
-K+
-ATPase (except in brain,spleen,
testes, uterus & Ant.pituitary).
 Increases BMR.
 Heat sensitivity inHyperthyroidism.
 Some of calorigenic actions are due to lipolytic effect

BMR
K+
excretion
N2 excretion.
Vitamin deficiency
Uric acid & Urinary hexosamine
excretion

B. Carbohydrate Metabolism :
Hyperglycemic.
Increase rate of reabsorption of glucose from GIT
Increases glycogenolysis in liver, muscle.
Increase gluconeogenesis.
Reduces secretion of insulin & accelerates its
breakdown.
 promotes Diabetes.

C. Fat metabolism :
Promotes cholesterol synthesis , but also promotes
hepatic breakdown & biliary excretion of cholesterol.
Increases fecal excretion of cholesterol.
Reduction in plasma cholesterol levels.
Causes lipolysis, promotes fatty acid oxidation
by the cells.
i.e. breakdown > synthesis.
 Therapeutically used to lower cholesterol levels

D. Protein metabolism :
 Physiological doses stimulate both structural and
functional protein synthesis.
Hyperthyroidismprotein catabolism.
 Hypo  decreased protein synthesis.

F. Electrolyte & water metabolism :
Hyper+ve Mg++
,-ve Ca2+
,-ve Po4
-
balance.
Hypo -ve Mg++,+ve Ca2+,+ve Po4- balance
E. Vitamin metabolism :
Converts ß carotenes to vit-A.
Hypo ß carotene accumulationyellowish skin.
Increases demand for coenzymes & vitamins.

2. On Various systems :
a.Blood :
Stimulates erythropoiesis.
Hyperpolycythemia.
Hypo Normocytic normochromic &
Megaloblastic anemia.

c. Respiration :
Rate of metabolism
Utilization of O2 & formation of Co2
Rate & Depth of respiration.

d. GIT :
Increases appetite & food intake.
Increases motility & secretions.
 Hyper food intake motility  Diarrhoea.
 Hypo food intake motility  Constipation.

e. Reproduction :
Required for normal sexual & gonadal function.
In men :
Lack of TH’sloss of libido,oligospermia,sterility
Excess TH’s sometimes impotency.
In women :
Lack of TH’s  Menorrhagia, polymenorrhoea,
loss of libido, reduced fertility.
Helps in maintainence of milk secretion during lactation.

f. Skeletal muscle :
 Muscular weakness in both hyper &
hypothyroidism
 Hypogeneralised depression of metabolism.
 Hyper  due to thyrotoxic myopathy which is due
to
I. Excess TH’s break muscle proteins.
II. Excretion of creatine,  less CP.
III. Heightened irritability of CNS.

g. On Sleep :
Hyper  constant tiredness & difficulty to sleep.
Hypo  extreme somnolence with sleep
sometimes lasting for 12 – 14 hours.

h. On Skin :
Hyper  Excess heat
Sweat production.
Cutaneous vasodilation.
Skin is soft , warm & wet.
Hypo skin is coarse, dry, scaly, cold & puffy.
Hypersensitive to cold.

i. On CNS :
Essential for normal development &growth of CNS.
In adult brain TH’s stimulate :
Branching of dendrites.
Myelination.
Increases no. of synapses.
In fetus & newborn stimulate growth of brain.

To assess function of CNS, reflex time is
measured :
•Hyper Reflex time is shortened.
•Hypo Reflex time is prolonged.
 wave frequency in EEG is reduced in Hypo &
increased in Hyperthyroidism.
Some of effects on brain are probably 20
to increase
responsiveness to catecholaminesstimulate RAS.

Growth & development of CNS :
Thyroid & Ant.pituitary TSH system begins to
function in fetus at about11weeks.
Deficiency of TH’s during fetal & post natal life leads to
“cretinism”.
Cretinism :
Failure of normal growth & development of CNS.
Delayed occurance of normal stages of child development
like holding head up, sitting, walking, speech.
Anatomically brain is small & underdeveloped.
Marked reduction in cerebral vascular bed.
Decreased myelination, dendrite branching & decreased
number of synapses.
Deaf mutism & rigidity.
Dwarfed, mentally retarded, pot bellies, protruding tongue

Hyperthyroidism
Increased excitability
Becomes irritable,
emotional, unstable,
restless & anxious.
Easily fatiguable.
Fine rhythmic tremors
in hands, tongue or
eyeballs.
Hypothyroidism
Mental function is less.
Memory power is low.
Somnolence.
Slowness of thought &
speech.
Slow cerebration.
Fatigue, depression.
Coma on exposure to
cold.

3. On growth :
Required for normal growth & differentiation
from the 1st
day of newborn.
GH requires thyroxine to exert its full effect.
T3 has direct growth promoting effect .
4. Interaction with Catecholamines :
 TH’s sensitizes the tissues to catecholamines
by increasing no. of receptors on cells.

TRH
 Produced by Hypothalamus
 Release is pulsatile, circadian
 Downregulated by T4, T3
 Travels through portal venous system to
adenohypophysis
 Stimulates TSH formation

TSH
 Produced by Adenohypophysis Thyrotrophs
 Upregulated by TRH
 Downregulated by T4, T3
 Travels through portal venous system to
cavernous sinus, body.
 Stimulates several processes
 Iodine uptake
 Colloid endocytosis
 Growth of thyroid gland

Thyroid Function Tests
 Radio Active Iodine Uptake (RAIU).
 Estimation of serum total TH conc.
 TRH Levels.
 TSH Levels.
 BMR normal ±15%
 Serum Cholesterol Estimation.
 Reflex time.
 Biopsy & Scanning of thyroid gland.

Wolff-Chaikoff Effect
 Increasing doses of I-
increase hormone synthesis
initially but higher doses cause cessation of
hormone formation.
 This effect is countered by the Iodide leak from
normal thyroid tissue.

Jod-Basedow effect
 Aberration of the Wolff-Chaikoff effect
 Excessive iodine loads induce
hyperthyroidism
 Observed in several disease processes
 Graves’ disease
 Multinodular goiter

Hypothyroidism
 Symptoms – fatigability, coldness, weight gain,
constipation, low voice
 Signs – Cool skin, dry skin, swelling of
face/hands/legs, slow reflexes, myxedema
 Newborn – Retardation, short stature, swelling of
face/hands, possible deafness
 Types of Hypothyroidism
 Primary – Thyroid gland failure
 Secondary – Pituitary failure
 Tertiary – Hypothalamic failure

Causes :
1.Congenital deficiency of the gland.
2. Iodine deficiency in mother during
pregnancy.
3. Administration of Anti-Thyroid drugs
during pregnancy.
Cretinism

Features :
Periorbital puffiness
Nose broad &flattened
Eyes widely placed
Tongue is large & protruding.
Pot belly, sparse hair, umbilical hernia.
Dwarf stature.
Mentally retarded.
IQ is very much less.
Hypogonadism.

Myxedema :Features :
Goiter
Puffiness of face.
Periorbital swelling.
Loss of hair.
Ptosis.
Dry thick & rough & yellow skin.
Low BMR.
Hypersensitive to cold.
Coarseness of eyes.
Memory loss.
Increase in serum cholesterol levels.

Hyperthyroid
 Symptoms – Palpitations, nervousness, fatigue,
diarrhea, sweating, heat intolerance
 Signs – Thyroid enlargement (?), tremor
 Lab workup
 TSH
 FT4
 RAIU

Features :
•Exopthalmosis.
•Goiter .
•Increased BMR.
•Heat intolerance.
•Thyrotoxic myopathy.
•Easy fatiguability.
•Osteoporosis.
•Skin warm, moist & soft.
•Tachycardia.
•Scanty periods.
•Thyroid diabetis.

Graves
 Most common cause of hyperthyroidism
 Result of anti-TSH receptor antibodies
 Diagnosis
 Symptoms of hyperthyroidism
 Clinical exopthalmos and goiter
 Low TSH, normal/high FT4, anti-TSH Ab (Optional)
 Treatments
 Medical – Propothyouracil, Methimazole, Propranolol
 Surgical – Subtotal Thyroidectomy
 Radiation

Calcium RegulationCalcium Regulation
ParathyroidParathyroid

CalciumCalcium
 Required for muscle contraction,
intracellular messenger systems, cardiac
repolarization, hemostasis, membrane
excitation, stabilisation of membrane,
excitation secretion process of hormone &
enzymes.
 Exists in free (ionised) and bound states
 Albumin (40% total calcium)
 Phosphate and Citrate (10% total calcium)
 Concentration of Ca2+
mediated by
 Parathyroid gland
 Parafollicular C cells
 Kidney & Bone.

Parathyroid
Parathyroid glands contains chief cells which
secrete parathyroid hormone (PTH).
Its primary function is to keep the Ca2+
conc. In
ECF & ICF constantly.

Actions :
1.On Bones :
Increases plasma calcium & decreases plasma
phosphate conc. by osteolytic effect.
Increases cAMPCa2+
entry into cell lactic acid
& citric acid accumulates solubilises the bone
Ca2+
is released.
cAMP itself causes resorption of Ca2+.
increases Osteoclast size, no. of osteoclast nuclei
& osteoclast proliferation.
Hydrolyzes the organic bone matrix.

2. On Kidneys :
Increases Ca2+
reabsorption from DCT.
Decreases Ca2+
excretion in urine.
Decreases reabsorption of phosphate from PCT &
increases its excretion in DCT.
Promotes conversion of 25 HCC to 1,25 DHCC by
activating 1 hydroxylase.
Increases urinary excretion of Na+
,K+
,HCO3
-
, &
decreases excretion of NH4
+
& H+
causing metabolic
acidosis.

3. On GIT :
Enhances both Ca2+
& PO4
-
absorption by
increasing production of 1,25 DHCC.
Decreases Ca2+
conc. in milk, sweat, & GI fluids.

Regulation :
Stimulation of parathyroid
PTH
Mobilisation of Ca2+
from bones
Normal serum Ca2+
Serum Ca2+1.

2. Serum phosphate
PTH
Serum Ca2+
3. 1,25 DHCC  1/PTH Secretion

calcitonin
•Secreted from “C cells/ parafollicular cells” of
thyroid gland.

Actions :
 Decreases plasma Ca2+
& PO4
-
conc.
 Inhibits Osteoclast activity& its number.
 Decreases renal formation of 1,25 DHCC.
 Inhibits intestinal absorption of Ca2+
& PO4
-
.
 Effect is greater in children than adults.

Vitamin-D
Plasma PO4
-
concentration

HypoparatHyroiDism
Removal of parathyroid gland during thyroidectomy
Decreased serum ionised Ca2+
conc. which results
in tetany.

tetany
Features :
•Neuromuscular hyper excitability.
•Facial irritability (chovstek’s sign)
•Carpopedal spasm (Trousseaus sign)
•Visceral manifestations
•ECG changesST segment prolonged with
abnormal T wave.
•Precipitate cataract formation.

Hyper paratHyroiDismHyper paratHyroiDism
 Primary  tumours of parathyroid gland
 Secondary  as a compensation for
hypocalcemia.

Features :Features :
 Weakness, lassitude, Hypotonia, thirst, Polyuria,
Anorexia, Nausea, Vomitting, Constipation
 Nephrocalcinosis.
 Demineralisation of bones producing painful bones
 Multiple bone cysts (Osteitis fibrosa cystica) .
 Increased plasma Alkaline Phosphatase conc.

rickets
•Result of Vit-D deficiency.
•Causes : Inadequate intake of vit-D, Inadequate
exposure to sun, kidney failure, liver dysfunction,
defect in target cell receptors.
•Pathology : Deficiency in deposition of Ca2+
salts in
bones, process of Ossification is abnormal.

Features :
Deformed bones & bow legs.
Thickening of wrists & ankles.
Retarded growth, shortness of stature.
Delayed dentition.
Widening & cupping of epiphyseal cartilagenous
plate.
Hypocalcemia, Hypotonia, Myopathy, Prominence
of costochondral junction, Frontal bossing.

osteomalaciaosteomalacia
Adult rickets.
Inadequate absorption of Ca2+
due to
deficiency of vit-D & Ca2+
in diet.
 Serum Ca2+
is low , 6-7mgs%.
 Mostly seen in females after multiple
pregnancies.

Features :Features :
 Bone pain & tenderness.
 Fractures may occur.
 Proximal Myopathy.

Adrenal Glands
Paired
organs that
cap the
kidneys.
Each: outer
cortex and
inner
medulla.

Adrenal cortex
Adrenal cortex:
- stimulated by ACTH.
- secretes corticosteroids
- different regions secrete different hormones.
- all made from cholesterol.

Adrenal Cortex
Corticosteroids include:
- mineralocorticoids:
- glucocorticoids
- gonadocorticoids

Adrenal Cortex
Mineralocorticoids:
- aldosterone
- targets kidneys
- affects Na+
and K+
balance
- stimulates transcription of Na+/K+ ATPase
pump!
- more aldosterone -> more Na+, water in body
- stress -> CRH -> ACTH -> aldosterone ->
retain fluid -> high blood pressure!

Adrenal Cortex
Glucocorticoids (gc)
- cortisol (aka hydrocortisone)
- metabolism, more glucose in blood
- stress -> large increase in gc
- pharmacologically: suppress inflammation,
asthma, rheumatoid arthitis

Adrenal Cortex
Gonadocorticoids:
-sex steroids
- include DHEA (precursor for estrogen,
testosterone)
- not well understood

Aldosterone
Corticosterone
Deoxycorticosterone
18 OH Corticosterone
Progesterone
∆5 Pregnolone
Cholesterol
17 OH Pregnolone
17 OH Progesterone
Deoxycortisol
Cortisol
20,22 desmolase
DHEA
Androstenedione
Oestrone
Dihydrotestosteone
Androstenediol
Testosterone
Oestrodiol
5α Reductase

Cortisol Actions :
 Metabolic actions.
On various systems.
Anti-inflammatory & Anti-immunity.
Stress adaptation.
Anti-growth effects.
Permissive actions.

1.Metabolic actions :
Carbohydrate metabolism :
Carbohydrate sparing hormone, anti-insulin
effects.
Increases hepatic glycogenesis 6-10 fold.
Decreases rate of glucose utilization.
 Adrenal Diabetis.
Impaired insulin action on tissues is due to its
lipolytic effect.

Fat metabolism :
Lipolytic .
Increases plasma FFA by promoting mobilisation
of fatty acids from adipose tissue.
Enhances oxidation of fatty acids in the cells.
Protein metabolism :
catabolic.
Reduces protein stores in all cells except in liver.
Increases liver & plasma proteins

Electrolyte & H20 metabolism :
Actions similar to Aldosterone, less potent.
Retention of Na+
& Cl-
.
Excretion of K+
.
Maintains ECF volume, provides adequate GFR
Promotes diuresis by antagonising actions of
ADH by destroying it.

2. On various Systems :
1.Blood :
 Lack of cortisol leads to Lymphocytosis,
Eosinophilia, Neutropenia, Anaemia.
Increases platelet count & shortens blood clotting
time.
2.CVS :
Required for maintenance of normal BP.
Improves myocardial performance by blocking Na+
-
Ca++
exchanger.
Permissive action to catecholamines & A-II

3. Renal :
Increases GFR by decreasing preglomerular
resistance & by increasing RPF.
Essential for rapid excretion of water load.
Increases Ca++
& P04
–
excretion.
Generates NH4
+
from glutamate in response to
acid loads.
4.GIT :
Promotes peptic ulcer formation.
Promotes absorption of water insoluble fats .

5.Muscle :
Maintains the contractility & work performance of
skeletal and cardiac muscle.
Increases ß adrenergic receptors in myocardium.
6. Connective tissue :
Inhibits collagen synthesis and produces thinning
of skin and walls of capillaries.
7. CNS :
Modulates excitability & behaviour.
Required for initiation & maintainence of REM
sleep and accompanying easy arousability.

8.Bone :
Increases bone resorption .
 Decreases the systemic &local generation of
IGF-1 molecules.
Antagonizes the action of Vit-D.
9. On Foetus :
Facilitates inutero maturation of CNS, retina, skin,
GIT & lungs.
Increases rate of development of alveoli, flattening
of lining cells, increases surfactant ynthesis.

3. Anti-inflammatory & anti-immunity action :

4. Stress adaptation :
Stress  ACTH  Cortisol
5. Permissive actions :
Permissive actions of cortisol include
1.Glucagon & catecholamines to exert calorigenic
effects.
2.Catecholamines to exert lipolytic effects.
3.Catecholamines to produce pressor respones &
bronchodilation.

6. Anti-growth Effect :
Large doses of vit-D antagonize action of vit-D
1.Decreases Ca++
reabsorption.
2.Inhibit mitosis of fibroblasts.
3.Cause degradation of collagen.
Osteoporosis
Delays wound healing
Large doses leads to muscular weakness &
atrophy.

Regulation of Cortisol secretion :

Cushing syndrome
Hypercortisolism.
It is a clinical disorder which results from
the exposure of body tissues to sustained
supraphysiological blood levels of
corticosteroids, either endogenous in origin
or iatrogenically produced.

Causes :
1. ACTH dependent causes
Bilateral adrenocortical hyperplasia.
Benign or malignant ACTH secreting
tumours.
Iatrogenic treatment with ACT
2. Non-ACTH dependent causes :
Adenomas or carcinomas of adrenal cortex.
Iatrogenic pharmacological doses of
corticosteroids.

Cushing’s SyndromeCushing’s Syndrome
– Central obesity
– Moon face
– Buffalo hump
– Thin skin, easy bruising
– Osteoporosis
– Diabetes
– Excess hair growth
– Irregular periods
– Problems conceiving
– Impotence
– High blood pressure
– Fluid retention
 changes in protein and
fat metabolism
 changes in sex
hormones
 salt and water retention

TreatmentTreatment
• Aminoglutethimide
• Metyrapone
• Ketoconazole
• Etomidate
• Trilostane
• Octreotide

Aldosterone
Corticosterone
Deoxycorticosterone
Progesterone
∆5 Pregnolone
Cholesterol
17 OH Pregnolone
17 OH Progesterone
Deoxycortisol
Cortisol
DHEA
Androstenedione
Oestrone
Dihydrotestosteone
Androstenediol
Testosterone
Oestrodiol
20,22 desmolase
17αOH
21 OH 21 OH
11β OH
18 OH
18 Oxidase
11β OH
17βHSO
3β HSD
5α Reductase
17,20,
desmolase
17βHSO
3β HSD3β HSD3β HSD
Aminoglutethimide
Metyrapone
Ketoconazole
Trilostane
Etomidate

AldosteroneAldosterone
Produced in the zona glomerulosa
of the adrenal cortex
Acts on the kidney via receptor
binds glucocorticoids with equal
affinity

Progesterone
∆5 Pregnolone
Cholesterol
17 OH Pregnolone
17 OH Progesterone
Cortisol
Androgens
Oestrogens
20,22 desmolase
17αOH
3β HSD
17,20,
desmolase
3β HSD
Aldosterone
Corticosterone
Deoxycorticosterone
21 OH
11β OH
18 OH
18 Oxidase

Aldosterone actions
1.Na+
& H2O reabsorption  on CD & late DCT.
2. K+
secretion with Na+
reaborption.
3. H+
secretion with Na+
reaborption.
4. NH4
+
excretion .
5. Stimulates Mg++
excretion.
6. Infusion of small doses causes increase BP.
7. Enhances Na+
absorption especially in colon,
which prevents loss of Na+
in stools.

Control of AldosteroneControl of Aldosterone
ReleaseRelease
ADRENAL CORTEX
Aldosterone
ECV
 K+
Renin
Renin Substrate
(Angiotensinogen)
Angiotensin I
Angiotensin II
decrease BP
 Δ Na+
Macula
Densa
SNS Activity
ACE
ACTH
 K+

Aldosterone SyndromesAldosterone Syndromes
Over production
 Conn’s Syndrome
Underproduction
 Addison’s Syndrome
 Congenital Adrenal
Hyperplasia

Primary Aldosteronism :Conn’s Syndrome
 It is a condition in which there is prolonged
excessive secretion of aldosterone from an
adrenocortical adenoma .
Features :
Hypernatremia, Hypokalemia, Hypervolemia,
Hypertension.
Polyuria, Polydypsia.
Absence of edema, Alkalosis, Muscular
weakness.

Secondary Aldosteronism :
 It is a condition in which oversecretion of
Aldosterone is brought about by extra adrenal
factors.
 Features are same as primary aldosteronism
except that edema is present.
Treatment :
Spironolactones.
ACE inhibitors.
Amiloride diuretic.

Adrenogenital syndrome or Virilism :
• Adrenocortical tumors secreting excessive
quantities of androgens that cause intense
musculinizing effects throughout the body.
•In females develops virile characters.
• Occasionally adrenal tumors secrete
Estrogens to produce feminization in males ,
with enlargement of breasts, atrophy of testes
and diminished sexual interest in woman.

Adrenal cortex Insufficiency
 Destruction of adrenal cortex
Eg: Addison disease.
 Diminished secretion of ACTH due to
Adenohypophyseal or Hypothalamic failure
 Congenital failure of Cortisol secretion due
to defects in the enzymes responsible for its
synthesis.

Addison’s disease :
• Chronic deficiency of both Mineralocorticoids
and Glucocorticoids due to destruction of
adrenal cortex.

Features :
Muscular weakness.
Hypoglycemia, Hypovolemia, Hypotension.
Anemia.
Resistance to stress &infection
Disturbed electrolyte balance.
Anorexia, Nausea, Vomiting, & Weight loss.
Sometimes Vitiligo, change in pigmentation
of skin.

Treatment :
 Replacement therapy with both Gluco &
Mineralocorticoids.
 Dexamethasone , Betamethasone,
Prednisolone, Fludrocortisone.

Adrenal Medulla
Adrenal medulla:
Derived from embryonic neural crest
ectoderm (same tissue that produces the
sympathetic ganglia).
Controlled by preganglionic sympathetic
innervation
(is like a postganglionic neuron!)
Secretes adrenaline (aka epenephrine)
(also secretes norepenephrine)

Actions :
1.Intracellular actions :
• Adrenaline & NA produce different effects
depending on type of Adrenergic receptors
alpha & beta.
Effector organ Receptor Response
1.Eyeradial muscle  contraction
Ciliary muscle ß Relaxation.

2. Metabolic actions :
•Both stimulates Gluconeogenesis,
Glycogenolysis, Muscle Glycogenolysis i.e.
Hyperglycemic. Adrenaline is more potent than NA.
•Both are lipolytic . NA is more potent than
adrenaline.

3. On CVS :
•Both increase force & rate of contraction of isolated
heart.
•Increases myocardial excitability.
•NA produces vasoconstriction in most organs but
Adrenaline dilates blood vessels in skeletal muscles
& liver.
•When NA is infused slowly causes increase in both
SBP &DBP, Pulse pressure, peripheral resistance
and decreases heart rate & Cardiac output.
•Adrenaline causes increase in SBP, Pulse
pressure,Heart rate & Cardiac output & Decreases
DBP & peripheral resistance.

4. On CNS :
•Produces Anxiety, Apprehension, initial
stimulation of breathing, Coarse tremors of
extremities.
•Do not cross blood brain barrier.
5. On BMR :
•Increases BMR by 7-15%, also increases non
shivering thermogenesis and diet induced
thermogenesis.
•Epinephrine is important part of response to cold
exposure& helps to regulate overall energy
balance and energy stores.

6. On Blood :
•Increases RBC & Hb levels due to shift of stored
RBC to circulating pool.
•WBC count increases due to shift of marginated
pool to circulating pool.
7. On Skeletal muscle :
•Adrenaline increases muscular blood flow.
•Has Anticurare effect.
•Increases force of contraction.

8. Other effects :
•Inhibits GI motor activity.
•Relaxation of bronchioles to improve gas exchange.
•Dilatation of pupils.
•Increases renin release from kidneys.
•Enhances thyroid hormone secretion.
•Adrenaline stimulates influx of potassium into muscle
cells.

Actions of Dopamine
•Causes vasodilation of renal & Splanchnic vessels
and vasoconstriction in other areas.
•Positive Ionotrophic effect on heart.
•Moderate doses increase SBP and no change in
DBP.
•Causes Natriuresis and may exert this effect by
inhibiting renal Na+
-K+
ATPase.

Hyposecretion
•Occurs during TB &malignant destruction of
adrenal glands following Adrenalectomy.
•Produces probably no symptoms or other clinical
features.
Parkinsonism :
•Due to deficiency of Dopamine.

Hypersecretion
Phaeochromocytoma :
•A tumor consisting of Adrenal medullary tissue is
called Phaeochromocytoma.
•Occurs in less than 1% of all cases of arterial
hypertension, their diagnosis is important because they
produce a type of hypertension which can be cured by
surgery.

Physical features of Patient :
 Looks Anxious .
Skin is pale , cool, moist.
Pupils dilated.
Increase heart rate, but in some patients Bradycardia
 Occurance of extrasystoles.
Increased BP, Occasionally 300/200mmHg.
Body temperature rised, Hyperglycemia, Increased
BMR.

Treatment :
Surgical removal of adrenomedullary tumor.
-receptor blocking drugs Ergot
alkaloids, Phentolamine,
Phenoxybenzamine.
ß-receptor blockers Propanolol
Reserpine  depletes tissues of their
stores of 5-HT & Catecholamines.

Regulation of Adrenomedullary secretion :

pancreas
 Located in the curve of duodenum.
Has both Exocrine & Endocrine function.
Secretes major hormones Insulin & Glucagon
and Amylin, Pancreastatin, Somatostatin,
Pancreatic polypeptide minor role.
Four types of cells, ß, D, F cells.

  cells Glucagon
 ß cells  Insulin
 Delta cells  Somatostatin.
 F or PP cells Pancreatic polypeptide.

Insulin
•Polypeptide containing two chains ( &ß)
linked by disulfide bridges.
•A chain21aa’s & B chain 30aa’s.
•Biological activity resides in B chain.

Biosynthesis :
• Synthesized in ER of ß cells.
•Pre proinsulin Pro insulinInsulin

Insulin secretion :
Increased Decreased
•D-glucose .
•Proteins.
•Keto acids , FFA.
•K+
, Ca++
•Glucagon.
•Gastric Inhibitory Peptide.
•Secretin, Cholecystokinin.
•Vagal activity, Ach.
•Sulfonyl urea drugs.
•Fasting.
•Exercise
•Somatostatin.
•Galanin.
•Pancreastatin, Leptins.
•Prostaglandin E2
•K+
depletion.
•Thiazide diuretics.
•Insulin.

Actions :
1.Metabolic actions : Carbohydrate metabolism
On liver On muscle On adipose
tissue
•Promotes
glycogenesis &
glycolysis.
•Inhibits
glycogenolysis &
gluconeogenesis
•Stimulates
transport of glucose
into cells.
•Stimulates
glycogenesis.
•Increase muscle
blood flow
•Stimulates
transport of glucose
into adipose tissue.
•Glucose is
converted into
glycerophosphate
& fatty acids
(minor)

Fat metabolism :
On liver On muscle On adipose tissue
•Lipogenic & Anti-
ketogenic.
•Glucose converted
to fatty acids
•Favours Cholesterol
synthesis
•Decreases
Apolipoprotein-B
synthesis.
•Suppresses
lipoprotein
lipase
•Inhibits
lipolysis.
•Inhibits FFA
uptake,
Oxidation.
•Inhibits
Hormone
Sensitive Lipase.
•Stimulates use
of keto acids
•Promotes
deposition of fat
into adipose
tissue.

Protein metabolism :
•Anabolic hormone.
•Stimulates Na+
dependent transport of
neutral aa’s across cell membrane in muscle.
•Increases gene transcription.
•Contributes to body growth by stimulating
synthesis of macromolecules in bone,
cartilage & stimulates transcription of growth
factors such as IGF-I

Electrolyte metabolism :
•Stimulates uptake of K+
, Po4
-
, Mg++
by cells.
•Regulates K+
balance.
•Increases renal reabsorption of K+
, Po4
-
, Mg++
.

2. On CNS :
Selected areas of brain (hypothalamus)
requires insulin.
Injection of insulin into cerebral ventricles
decreases food intake.
Continuous insulin excess increase body
wt.& adipose mass  increase leptin levels 
induces satiety.

3. On blood vessels :
 Overall vasodilator effect  mediated by
increase in NO synthesis.
4. Autocrine effects :
ß cells also possess insulin receptors.
Essential for development of normal size islets
and for glucose stimulated insulin release.

5. On Growth :
• Essential for growth of an animal as GH is.
•Insulin & GH acts synergistically to promote
growth, each performing a specific function.

Regulation of Insulin secretion
1. Substrate stimulation :by a feedback
relationship with exogenous nutrient supply.

2. Hormonal control :
 GI hormones  Glucagon, Secretin, CCK,
GIP,GLP-I.
 Glucagon.
 Growth hormone.
 Cortisol.
 Thyroid hormones.
 Human Placental Lactogen.

3. Electrolytes :
 K+
& Ca++
.
 Mg++
has a modulatory effect.
4. Neural control :
 Parasympathetic Increases secretion.
 Sympathetic  Decreases secretion.

5. Oral Hypoglycemic agents :
• Tolbutamide.
• Sulfonylurea drugs ( Glipizide, Glyburide,
Tolazamide).
• Biguanides Penformin, metformin  acts in
absence of insulin.

Diabetes
mellitus
A clinical state which is associated
with flow of sugar in urine which is due
to deficiency of Insulin .

Causes :
Insulin deficiency.
Increase in levels of antagonistic hormones
(GH, Glucagon, Catecholamines, Cortisol).
Hereditary, Age, Obesity, Drugs like Alloxan,
Streptozoticin etc…

Signs & Symptoms :
•Hyperglycemia.
•Glycosuria.
•Polyuria.
•Polydipsia.
•Polyphagia.
•Dehydration.
•Loss of weight.
•Ketonuria.
•Poor resistance to infections.

Complications :
 Atherosclerosis.
 Microangiopathy :
 Neuropathy
 Retinopathy
 Nephropathy
 Dermatopathy.

glucagon
 Promotes mobilisation rather than storage of
fuels, especially glucose.
Actions opposite to insulin.

Actions :
Have no influence on glucose uptake by
peripheral tissues.
Increases glycogenolysis & gluconeogenesis
in liver.
Lipolytic & Ketogenic hormone.
Inhibits storage of Tg’s in liver.
Have calorigenic action.
Glucagon in very high conc. Causes +ve
ionotrophic effect, increase blood flow to
tissues, inhibits gastric acid secretion,
enhances bile secretion.

 causes natriuresis.
Has a role in appetite.
Stimulates secretion of Insulin, GH,
Pancreatic somatostatin.

Regulation of Glucagon secretion

Stimulators Inhibitors
•Amino acids
(Glucogenic).
•CCK, Gastrin.
•Cortisol
•Exercise
•Beta adrenergic
stimulators.
•Theophylline.
•Acetyl choline.
•Glucose.
•Somatostatin
•Secretin
•FFA, Ketones.
•Insulin.
•GABA
•Alpha adrenergic
stimulators
Glucagon secretion

Endocrine mrmc

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