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Endocrinology

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18 views167 pages

Endocrinology

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dipakpatra714
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Endocrinology

• The various physiological activities in our body


are controlled by substances called chemical
messengers
• These messenger substances may be
hormones or hormone like substances
Hormone
• It is a chemical substance secreted by
endocrine gland into blood or body fluid
which exerts its physiological effects on
distant organ.
• Hence it is also called as chemical messenger
Endocrine glands
• They are ductless glands which secretes
hormones, released directly into blood.
• The hormones are transported by blood to the
target organs or tissues in different parts of
the body, where the actions are executed.
Classification of hormones
A. Based on chemical structure
1. Steroid hormones – corticosteroids, sex
hormones
2. Protein hormones – hormones secreted by
pituitary gland, parathyroid glands, pancreas
and placenta
3. Derivatives of amino acid – tyrosine- thyroid
hormones and adrenal medullary hormones
B. Depending on site of action
1. Classical hormones
- Secreted by endocrine glands
- Which act on different parts of body
- Ex: GH, Insulin
2. Local hormones
- Secreted from other tissues
- Acting on near by structures
- Ex: Gastrointestinal hormones such as gastrin,
secretin, CCK-PZ
3. Target specific hormones
- Act on specific target only
- Ex: TSH, ACTH
Hormones secreted by major endocrine glands
Anterior pituitary
• Growth hormone (GH)
• Thyroid stimulating hormone (TSH)
• Adrenocorticotropic hormone (ACTH)
• Follicle stimulating hormone (FSH)
• Leuteinizing hormone (LH)
• Prolactin
Posterior pituitary
• Antidiuretic hormone (ADH)
• Oxytocin
Thyroid gland
• Thyroxine
• Triiodothyronine
Pancreas
• Insulin
• Glucogon
• Somatostatin
Adrenal cortex
Mineralocorticoids
• Aldosterone
• Deoxycorticosterone
Glucocorticoids
• Cortisol
• Corticosterone
Sex hormones
• Androgens
• Estrogen
• Progesterone
Adrenal medulla
• Adrenaline (epinephrine)
• Noradrenaline (norepinephrine)
• Dopamine
Hormones secreted by gonads
Testes
• Testosterone
• Dihydrotestosterone
• Androstenedion
Ovary
• Estrogen
• Progesterone
Hormones secreted by other organs
Pineal gland
• Melatonin
Thymus
• Thymosin
• Thymin
Placenta
• Human chorionic gonadotropin (hCG)
• Human chorionic somatomammotropin (hCSM)
• Placental estrogen
• Placental progesterone
General functions of hormone
• Promotes physical, mental and sexual growth.
Physical growth involves skeletal, muscular,
visceral and soft tissue growth
• Helps in metabolism
• Helps in reproduction
• Maintenance of homeostasis
Stress hormone
• Any disturbance in homeostasis caused by
physical injury, mental stress, disease, change
in body temperature, acid-base balance or
changes in blood pressure is called stress
• The hormones which are released because of
stress are called stress hormone
• They are ADH, GH, Cortisole, Adrenaline,
Noradrenaline, Thyroxine
Regulations of hormones
1.Hypothalamus
• Secretes releasing and inhibiting hormones
which control anterior pituitary gland
2.Anterior pituitary gland
• It is called master of endocrine orchestra
because they secretes hormones which
controls the activity of other endocrine glands
3.Stress or disturbance in homeostasis
• Is important stimulus for secretion of
hormones
4.Circadian rhythm
• Hormone secretion can vary in different parts
of day. Ex1 – peak secretion of cortisol takes
place at early morning and minimum at
evening. Ex2 – peak secretion of thyroxin at
mid night, minimum secretion at evening
5.Negative feedback
• For ex – TSH secreted by ant.pituitary gland
stimulate secretion of T3 & T4 by thyroid
gland. When levels of T3 & T4 increases, T3&
T4 exert an inhibitory effect on ant.pituitary
gland causing inhibition of TSH secretion
Pituitary gland
• Synonym – hypophysis
• Diameter – 1cm
• Weight – 0.5- 1 gm
• It is situated at sella turcica, which is hollowed
out area of sphenoid bone
• Physiologically divided into 2 parts
1. Anterior pituitary / adenohypophysis
2. Posterior pituitary / neurohypophysis
Anterior pituitary / adenohypophysis
• Cut section of anterior lobe shows the
presence of gland cells of blood vessel hence
called adenohypophysis
• There is vascular connection between
hypothalamus and anterior pituitary called
hypothalamo hypophysial portal system
• Through which the releasing and inhibiting
hormones secreted by hypothalamus reach
the ant.pituitary
Cells and hormones secreted
• Somatotropes – somatotropin / GH
• Lactotropes – lactotropin / prolactin
• Thyrotropes – thyrotropin / TSH
• Corticotropes – corticotropin / ACTH
• Gonadotropes – gonadotropin - FSH & LH
Somatotropin/ Growth hormone (GH)
• Secreted by somatropes
• Chemical structure – polypetide hormone

Functions
A. Growth – responsible for physical growth and
has no effects on mental & sexual growth
.
On physical growth GH is responsible for -
a. Skeletal growth – before puberty GH causes
proliferation of epiphyseal cartilage of long
bones, hence it is responsible for increasing
the longitudinal length of long bones. After
puberty (epiphyseal cartilage undergo
ossification) GH increases thickness of bones
b. Increases cartilaginous growth
c. Increases muscular growth
d. Increases soft tissue growth
e. Increases visceral growth
B.Effect over metabolism
• Anabolic effect on protein metabolism, i.e. it
increases the synthesis of proteins and nucleic
acid
• Catabolic effect over carbohydrate mechanism,
i.e. it causes breakdown of glycogen and
increases blood glucose level. Hence GH is
called Diabetogenic hormone
• Catabolic effect on fat metabolism, it causes
break down of fats and production of fatty acids
• Increases the absorption of minerals such as
calcium, sodium, potassium from small
intestine
C.Miscellaneous
• It has a minor role in erythropoiesis
• It has major role in galactopoiesis,
maintenance of breast milk during period of
lactation
Control of GH
• Hypothalamus secretes GHRH & GHIH
Stimulating factors
• Anxiety
• Exercise
• Sleep
• Hypoglycemia
• Thyroxine
• Testosterone
Inhibiting factors
• Estrogen
• Cortisol
• Progesterone
Applied physiology
Gigantism
• Condition characterised by increase in secretion of
GH before puberty
• Commonly due to tumor of ant.pituitary
Clinical features
• Person is tall more than 7 or 8 feet
• The limbs are disproportionately long
• Bulky muscles
• Increased soft tissue
• Enlarged viscera
• Increased basal metabolic rate
• Hyperglycemia even glycosuria
Acromegaly
• Condition characterised by increase in
secretion of GH after puberty
• Due to tumor of ant.pituitary
Clinical feature
• Acromegalic or gorilla face – protrusion of
supraorbital ridges, broadening of nose,
thickening of lips, thickening and wrinkles
formation on forehead and protrusion of lower
jaw
• Enlarged tongue (macroglossia)
• Increased thickness of skin and subcutaneous
tissues
• Bulky muscles
• Enlarged viscera
• Increased basal metabolic rate
• Hyperglycemia and glycosuria resulting in DM
• Visual disturbances due to compression of
optic chiasma
Dwarfism
Due to decreased secretion of GH before puberty

Clinical features
• Short stature less than 3-4 feet
• Normal intelligence
• Sexual growth is normal
Prolactin
Functions
• Stimulating the secretion of breast milk after
child birth (lacto genesis)
• Responsible for enlargement of mammary
gland during pregnancy
• Control
• Hypothalamus secretes PLRH & PLIH
• Estrogen increases secretion of prolactin
• Progesterone decreases secretion of prolactin
Applied physiology
Gynacomastia
• Long term use of Dopamine antagonists (anti
psychotics) causes enlargement of breasts in
men
TSH (Thyroid stimulating hormone)
• Secreted by thyrotropes
• Chemical structure – polypeptide hormone
Functions
• Stimulates growth of thyroid gland
• Responsible for biosynthesis of T3 & T4
Control
• Hypothalamus through TSHRH
• Negative feedback balance
• Circadian rhythm – Peak secretion at midnight
and lowest at evening
ACTH – adrenocorticotropic hormone

• Secreted by corticotropes
• It is polypeptide hormone

Functions
• It acts on zona fasciculata & zona reticularis of
adrenal cotex to stimulate the secretion of
glucocorticoids and adrenal androgens
• It stimulates the melanocytes of skin to
secrete a pigment melanin
Control
• Hypothalamus through ACTHRH
• Negative feedback mechanism
• Circadian rhythm – peak secretion at early
morning & lowest at evening
Applied physiology
• Cushing’s disease – due to increased secretion
of ACTH by a tumor of ant.pituitary
Gonadotropin
• FSH & LH
• Secreted by gonadaotropes
• Structure – polypeptide hormone
Functions of FSH
In males
• After puberty FSH is responsible for
spermatogenesis
In females
• After puberty FSH stimulates maturation of
graphian follicle
• Stimulates the estrogen by graphian follicle
Functions of LH
In males
• Stimulates the interstitial cells of Leydig to
secrete a hormone – Testosterone
In females
• Responsible for ovulation
• Responsible for conversion of graafian follicles
into corpus luteum after ovulation
• Secretion of progesterone by corpus luteum
Control
• Hypothalamus through gonadotropin RH
• Negative feedback mechanism
Posterior pituitary/ Neurohypophysis
• It is made up of nerve cells & nerve fibers
hence known as neurohypophysis
• It does not have any gland cells
• It does not secrete any hormone
• There are some neuro endocrine cells of
hypothalamus which secrete – ADH & oxytocin
• They are transported into posterior
hypothalamus through a tract called
hypothalamo hypophysial tract
• Hormones are stored their & released into
blood when ever body requires
Anti diuretic hormone (ADH) / Vasopressin
• Secreted by neuro endocrine cells of
hypothalamus
• Stored in the post.pituitary gland
Functions
• Increases reabsorption of water by DCT (distal
convoluted tubule) by process called facultative
reabsorption (collecting duct become more
permeable hence water reabsorbed by
osmosis)
• Causes vasoconstriction of blood vessel and
increases PVR – thus play important role in
regulation of BP
Control
• Special receptors – Osmo receptors – receptors
present in the hypothalamus which are sensitive
to water content of the blood. Decrease in the
water content of blood stimulates osmo
receptors which in turn responsible for secretion
of ADH
• Hemorrhage – decrease in blood volume
stimulates secretion of ADH
• Stimulation by decrease in BP
• Stress stimulates the secretion
• Hypoxia stimulates secretion
Applied physiology
Diabetes insipidus
• Condition characterised by polyurea and
polydypsia due to deficiency of ADH
• Polyurea – secretion of large volume of urine
with less specific gravity
• Polydypsia – excessive thirst
Types
• Central diabetes insipidus
• Nephrogenic diabetes insipidus
• Central diabetes insipidus – due to failure of
secretion of ADH by neuro endocrine cells of
hypothalamus

• Nephrogenic diabetes insipidus – ADH is


secretion is normal but target cells of DCT are
not responding to the action of ADH
Oxytocin
• Secreted by neuro endocrine cells of
hypothalamus
• Stored in the post.pituitary gland
Functions
• Responsible for contraction of smooth muscles
of uterus during labuor. Thus it facilitates the
child birth
• Responsible for milk ejection – it causes
contraction of myo epithelium cells present in
lactiferous ducts of mammillary gland thus it
helps in the expulsion breast milk
Control
• Stretching of the cervix and vagina during
labor stimulates release of labor
• Milk ejection reflex
• During the process of breast feeding the
sucking of the nipple stimulates the special
receptor which are present around the nipple.
The information carried to hypothalamus,
which in turn secretes 2 hormones
-Oxytocin
-PLRH (prolactin releasing hormone)
• PLRH causes the secretion of prolactin from
ant.pituitary gland.
• Prolactin reaches the mammary gland through
blood stream to cause secretion of milk called
Lactogenesis
• Oxytocin reaches the mammary gland through
blood causes contraction of lactiferous duct &
helps in the process of expulsion of breast
milk
Therapeutic uses of oxytocin
• Oxytocin injections are given during labour to
increase the strength of uterine contractions
and facilitate child birth
• After child birth oxytocin injections are given
to prevent bleeding ( post partum
hemorrhage)
Thyroid gland
• Present in front of neck covering the trachea
• Enclosed by pre tracheal fascia
• Consists of two lobes , joined by isthmus
• Isthmus is related to 3,4,5 tracheal rings
• Behind the upper lobe of thyroid gland there
are a pair of superior parathyroid glands
• Behind the lower lobe of thyroid gland there
are a pair of inferior parthyroid glands
• A cut section of thyroid gland shows the
presence of follicles
• The follicles are made up of
- Follicular cells - secretes T3 & T4
- Para follicular cells - secretes Calcitonin
T3 – Triiodothyronine & T4- Triidothyronine
• Secreted by follicular cells of thyroid gland
• Chemical structure – thyroxine derivative
Synthesis
• Iodine & tyrosine are essential for the
formation
• Daily requirement of iodine – 100-200 micro
grams/day
Sources of iodine
• Fish, vegetables of Brassica family – cabbage,
cauliflower, radish, turnip & soya
Sources of tyrosine
• Soy products, chicken, fish, peanuts, almonds,
avocados, bananas, milk, cheese & yogurt
Steps of Biosynthesis
• In GIT iodine is converted into iodide and
absorbed to blood
• Through blood iodide reaches thyroid gland
• Thyroid gland takes up iodide by the process
called iodide trapping, it is an active process
takes place in the presence of TSH
• After entering the thyroid gland iodide is
oxidized to iodine in the presence enzyme
peroxidase
• Iodine combines with thyrosine (an amino acid)
to form
- Mono iodo thyrosine (MIT)
- Di iodo thyrosine (DIT)
• Coupling – in the presence of TSH
- 1 MIT+ 1 DIT – T3 (Tri iodo thyronine)
- 1 DIT + 1 DIT – T4 (Thyroxine)
• T3 &T4 are stored in the thyroid follicles in the
form of Thyroglobulin
• Whenever the body requires T3 & T4
thyroglobulin breaks down to release T3 & T4
• T3 & T4 circulate in blood mainly bound to
a plasma protein albumin
• 99% of T3 & T4 circulates bound to albumin, 1 %
circulates freely
Functions
• Helps in growth – physical, mental & sexual
Hence deficiency of T3 & T4 in children causes
retardation of physical, mental & sexual
growth
• Metabolism
-General metabolism – increases basal
metabolic rate. Increases oxygen consumption
by target cell because of break down of ATP
and release of energy , this will result in
thermo genesis. Hence T3 & T4 play important
role in body temperature regulation
-Vitamin metabolism – T3 & T4 helps in
conversion of inactive vit A (beta carotene) to
active vit A
-Mineral metabolism – T3 & T4 in high
concentration increases the activity of
osteoclasts and causes bone resorption, break
down of bone matrix hence bones undergo
osteoporosis
-Carbohydrate, protein and fat metabolism
In normal concentration T3 & T4 have
anabolic effect, in high concentration it has
catabolic effect
Carbohydrate metabolism -
• @normal level – increases synthesis of
glycogen
• @High level – breakdown of glycogen &
increase in blood glucose
Fat metabolism -
• @ normal level – increase in the synthesis of fat
• @ high level – break down of fat (lipolysis)
Protein metabolism -
• @ normal level – increase protein synthesis
• @ high level – break down of protein
(proteolysis)
• Effect over Individual system
Cardiovascular system
• T3 & T4 increases sympathetic activity hence
increase of HR & BP
Central nervous system
• T3 & T4 are essential for growth and myelination
of nerves
GIT
• T3 & T4 are responsible for motility of GIT
Miscellaneous
• It has minor role in erythropoiesis
• Major role in galactopoiesis
Control
• Hypothalamus – through TSHRH
• Pituitary – through TSH
• Stress – any disturbances in the thermostasis
release T3 & T4
• Negative feedback mechanism
• Circadian rhythm – peak secretion – midnight,
less secretion - evening
Applied physiology

Hyperthyroidism (Thyrotoxicosis)
• Due to increased secretion of T3 & T4 by thyroid
gland
Clinical features
• Presence of goitre ( enlargement of thyroid
gland)
• Exopthalmus – outward protrusion of eye ball
• Effect of increased T3& T4 on
-CVS – tachycardia, hypertension, palpitation
-CNS – increased activity of nerves, anxiety,
restlessness, tremors
-GIT – diarrhea
-Skeletal system – osteoporosis
-General metabolism – hyperglycemia, increased
body temperature causing heat intolerance
Hypothyroidism
• Due to reduced secretion of T3 & T4 by
thyroid gland

• It is of 2 types
1. Childhood hypothyroidism ( Cretinism)
2. Adult hypothyroidism ( Myxedema)
Chidhood hypothyroidism (Cretinism)
• Short stature
• Deformities in bone & teeth
• Muscular growth – pot belly due to weakness
of abdominal muscles
• Mental retardation, deafness, mutism
• Delayed milestones such as neck holding,
creeping, crawling, sitting, standing
• Delayed sexual growth
• Face – bloated idiotic look, thick lips,
protruded tongue, dribbling of saliva, broad
flat nose
• Skin – thick, rough with scanty hairs
• Constipation
• Hypoglycemia
• Low body temperature hence cold intolerance
• Decrease in resistance so child is susceptible
for infections
Myxedema / adult hypothyroidism
• More common in females

Causes
• Iodine deficiency
• Pituitary disorder – decreased secretion of TSH
• After thyroidectomy
• Auto immune disorders
Clinical features
• Person has puffy ( swollen) edematous
appearance due to deposition of myxomatous
tissue (connective tissue components). Hence
called as myxedema
• Sluggish reflex
• Hoarness of voice due to deposition of
myxomatous tissues in vocal cord
• Skin – rough, thick, dry
• Loss of hair from axilla, pubic region, eyebrows
• Loss of memory
• Excessive drowsiness
• Constipation
• Hypoglycemia
• Decreased immunity
• Reduced body temperature causing
intolerance to cold
Goiter
• Means enlargement of the thyroid gland
• Can occur both in hypothyroidism &
hyperthyroidism
Goiter in hypothyroidism – Toxic goiter
• Due to the tumor of thyroid gland
• The size of the gland increases because of
increase in the number of hormone secreting
cells
• The hormone level increases to a very great
extent
Goiter in hypothyroidism – Nontoxic goiter
• Enlargement of the gland but secretion of
hormones reduced
• Based on the cause non toxic goiter is
classified into two types
1. Endemic colloid goiter
2. Idiopathic Nontoxic goiter
Endemic colloid goiter
• It is also called iodine deficiency goiter
• In certain areas of world like Kashmir valley,
the soil does not contain enough Iodine,
therefore the foodstuffs also donot contain
iodine
• Occurs when iodine intake is less than 50
microgram
• By lack of iodine there is no formation of
hormones
• By feed back mechanism hypothalamus and
anterior pituitary stimulated as a result TRH &
TSH secreted more
• TSH causes secretion of tremendous amount
of thyroglobulin which get accumulated in
follicles of the gland
• Thus size of the gland increases
Idiopathic non toxic goiter
• Enlargement of gland occurs even without
iodine deficiency
• The exact cause is not known
• In some, abnormal enzyme system leads to
goitre , like deficiency of enzyme peroxidase,
iodinase and deiodinase which required for
thyroid hormone synthesis
• Vegetables like cabbage, turnip & soybean
contain goiterogenic substances, they
suppress the synthesis of thyroid hormone
• Patients first affected by thyroiditis which
reduces the synthesis of T3&T4
• Therefore the secretion of TSH increases
causing increase in the size of the gland
Goitre Grade 1
Goitre Grade 2
Goitre Grade 3
Multi nodular goitre
Calcium metabolism
Distribution
• 99% of calcium in the bone and teeth
• 1% of calcium in plasma, lymph, intercellular
fluid, CSF, aqueous humor, digestive juices
• Normal plasma calcium level – 9-11mgm/100ml
• Less than 9 mgm/ 100 ml – Hypocalcemia
• More than 11 mgm/ 100ml- Hypercalcemia
• There is dynamic equilibrium between plasma
calcium and bone calcium
• Whenever the plasma calcium increases excess
calcium is deposited in bone
• When plasma calcium level decreases there is
bone resorption (breakdown of bone matrix by
osteoclast) and release of calcium into blood
Sources
• Milk
• Cheese
• Eggs
• Green leafy vegetables
• Fish & meat
Daily requirement – 0.5- 0.8 gms / day
• Requirement of calcium increases in certain
age like in children, pregnancy, lactation,
old age
Functions
• Responsible for hardness of bone and teeth
• Required for contraction of skeletal, cardiac & smooth
muscles
• An important coagulating factor
• It acts as 2nd messenger for some hormones
• Helps in activation of digestive enzymes like
pancreatic & intestinal lipase
• Responsible for neuro muscular excitability
- Decrease in calcium will increase neuro muscular
excitability
- Increase in calcium will decrease neuro muscular
excitability
Hormones which play important role in calcium
metabolism
• Calcitonin
• Parathormone
• 1,25 - Dihydroxycholecalciferol
( calcitriol – active form of vitamin D)
Calcitonin
• Secreted by parafollicular cells of thyroid
gland
• Chemical structure –polypeptide hormone
Functions
• It reduces serum calcium level of blood by
inhibiting the activity of osteoclast
• Hence it is regarded as serum calcium
decreasing hormone
Control
• Hypercalcemia stimulates the secretion
Applied physiology
Pagets disease
• Is a disease of bone in which excess of activity
of osteoclast which cause the weakening of
bone
• Calcitonin is used in this disease because it
inhibits activity of osteoclast
Paratharmone (PTH)
• Secreted by parathyroid glands
• Chemical structure – polypeptide hormone
Functions
• Increases activity of osteoclast and thus
increases serum calcium
• Decreases the excretion of calcium through
kidney
• Increases absorption of calcium from the GI
tract
• It helps in conversion of 25
hydroxycholecalciferol to its active form 1,25-
dihydroxycholecalciferol in kidney
• It plays important role in bone remodelling ,
which is the combination of breakdown of
bone with new bone synthesis
Control
• Hypocalcemia stimulates secretion
Applied physiology
Hyperparathyroidism
• Due to increased paratharmone
Features
-Bone resorption Osteoporosis
Pathological fractures
-Hypercalcemia Decreased neuromuscular
excitability Calculus in urinary tract &
gallbladder
Hypoparathyroidism
Decreased PTH secretion hypocalcemia
neuromuscular excitability TETANY
Clinical features of Tetany
• Convulsions
• Chvostek sign – tapping the facial nerve near
angle of jaw causes contraction of epsilateral
(same side) facial muscle
Chvostek sign
• Carpopedal spasm
Increasing pressure of the upper arm cause
Flexion of elbow
Flexion of wrist
Flexion of metacarpo phalangeal joints
Extension of inter phalangeal joint
Thumb in opposition with finger tips
Carpopedal spasm
Carpopedal spasm
Calcitriol
• It is steroid hormone derived from cholesterol
Sources
o Dietary source – milk, egg yolk, fish liver oil
o Sunlight
• Daily requirement of Vit D- 100 IU/ day
• Requirement is increased in growing children,
pregnancy, lactation
• When UV rays of sunlight fall on skin, a
substance called 7- Dehydrocholesterol is
converted into cholecalciferol (Vit D3)
• Cholecalciferol reaches liver, converted into
25- hydroxycholecalciferol
• In kidney, in presence of PTH,
25- hydroxycholecalciferol converted into
1,25-dihydroxycholecalciferol, which is active
form of Vit D/ Calcitriol
Functions
• Helps in absorption of calcium from GIT to
blood
• Helps in deposition calcium ions into bone
matrix
• In PCT of nephron, Vit D helps in re absorption
of calcium ions into blood
Control
• Vit D synthesis increases whenever there is
hypocalcemia
Applied physiology
Rickets
• Vitamin D deficiency in children
Causes
• Inadequate intake of Vit D in diet
• Inadequate exposure to sunlight
• Decrease in absorption of Vit D in small
intestine
• Diseases of liver & kidney
Clinical features
• Soft bones
• Hypocalcemia
• Bone deformities like
Rickety rosary -
enlarged costochondral junctions of the ribs
resembling a string of rosary beads
Pigeon chest/Pectus carinatum is a term used to
describe a spectrum of protrusion abnormalities
of the anterior chest wall.
Bending of weight bearing bones like femur
• Tendency of pathological fracture
Rickety rosary
Rickety rosary
Pigeon chest
Osteomalacia
• Vitamin D deficiency in adults
Causes – same as Rickets
Clinical features
• Hypocalcemia
• Osteoporosis
• Tendencies for pathological fractures
• Joint pain & back ache
Endocrine pancreas
• It is made up of Islets of Langerhans/ islands
of Langerhans (irregularly shaped patches of
endocrine tissue located within pancreas)
• There are 4 types
o Alpha cells – Glucagon
o Beta cells – Insulin
o Delta cells – Somatostatin
o F cells – Pancreatic polypeptide
• These hormones regulate one another’s
secretion
Insulin
• Secreted by Beta cells of Islets of Langerhans
• It is isolated by Panting and Best at 1921
Chemical structure
• Polypeptide hormone, made up of 2 polypeptide
chains
• One polypeptide chain has 21 amino acids , other
has 30 amino acids
• 2 polypeptide chains are connected by disulphide
bonds
Mechanism of action
• Binds to receptors in the target cell membrane and
increases permeability of target cell membrane
Pro insulin
Insulin
Functions
Insulin increases permeability of target cells to
o Glucose, thus it increases utilization of glucose
by target cells
o Fatty acids, amino acids, potassium ions
Metabolism
Carbohydrate metabolism
o Insulin reduces blood glucose in the following
ways
o It increases utilization of glucose by target cell
o It converts glucose into glycogen which is
stored in liver and skeletal muscles
o It prevents gluconeogenesis – synthesis of
glucose from non carbohydrate sources like
fats and protein
o It prevents glycogenolysis – break down of
glycogen
o Hence when there is deficiency of insulin,
blood glucose levels increases
Protein metabolism
o Insulin increases protein synthesis
o It inhibits the breakdown of protein
Fat metabolism
o Insulin increases lipogenesis
o Inhibits lypolysis
o Inhibits production of ketone bodies
Nucleic acid metabolism
o Insulin increases synthesis of DNA & RNA
Short note on Ketone bodies
• Ketone bodies are intermediate products
found during oxidation of fatty acids to
glucose.
• There are 3 ketone bodies, namely Acetone,
Acetoacetic acid & beta –Hydroxybutyric acid.
Insulin prevents gluconeogenesis, thus it
prevents formation of ketone bodies.
• When there is lack of insulin, ketone bodies
concentration in the blood increases
– Keto acidosis & excretion of ketone bodies in
urine - Ketonuria
Regulation
Blood glucose level
• Hyperglycemia will stimulate secretion of
insulin
Diabetogenic hormones like GH, Thyroxin,
Glucogon, Cortisol, Estrogen, Adrenaline
stimuates secretion of insulin
Gastrointestinal hormones like Gastrin
stimulate secretion of insulin
Autonomic nerves
o Sympathetic stimulation increases secretion of
insulin
o Parasympathetic stimulation decreases
secretion of insulin
Applied physiology
Insulinoma
• It is a tumor of beta cells of pancreas which
increases secretion of insulin resulting
hypoglycemia
DIABETES MELLITUS
 Disease caused by deficiency of insulin in
which there is hyperglycemia associated with
glycosuria
Types
1.Primary DM
There is pathology in the pancreas
2.Secondary DM
Due to other endocrine disorders. E.X.
Acromegaly, Hyperthyroidism, Cushing’s
syndrome
Secondary to use of drugs ( e.x. Steroids)
Primary DM – 2 types
-IDDM- Insulin dependent DM
-NIDDM – Non insulin dependent DM
IDDM
• Commonly seen in children & young adults,
hence also called as Juvenile DM
• Treatment depends on insulin injections
 Mechanism
• It is an auto immune disease where antibodies
are produced by immune system against beta
cells of pancreas. Hence there is deficiency of
insulin
NIDDM
• Seen in middle aged persons hence called
maturity onset DM
• Treatment does not depend upon insulin
 Mechanism
• Insulin secretion is normal but the number
insulin receptors are decreased or the target
cells are not responding to insulin
Symptoms of DM – ‘3Ps’/ Triads
• Polyurea – increased voidance of urine>2.5ltr/d
• Polydypsia – excessive thirst
• Polyphagia – excessive hunger
Pathophysiology
 Insulin deficiency hyperglycemia exceeding
renal threshold glycosuria osmotic diuresis
polyurea
 Polydypsia – excessive thirst in order to
compensate for loss of water in urine
 Polyphagia – excessive hunger because
glucose in the blood can not be utilized by
target cells. This will stimulate glucoreceptors
in hypothalamus which will cause feeling of
hunger
Complications
• Delayed wound healing
• Ketoacidosis – due to increased ketone bodies
in blood leading into Diabetic coma
• Diabetic nephropathy- renal failure
• Diabetic neuropathy – degeneration of
sensory and autonomic nerve fibers
• Diabetic retinopathy – cataract & retinal
detachment
Glucogon
• Secreted by alpha cells of Islets of langerhans
• Structure – polypeptide hormone
Functions
• Decreases utilization of glucose by target cell
• Reduces glycogenesis ( formation of glycogen)
• Increases breakdown of glycogen –
glucogenolysis
• Increases gluconeogenesis
 Thus it increases blood glucose level,
hence known as a Diabetogenic hormone
Somatostatin
• Secreted by Delta cells of Islets of Langerhans
Functions
• It inhibits
Secretion of insulin
Secretion of GH
Secretion of HCL in the stomach
Regulation of blood glucose
o Normal fasting blood glucose–70-100mg/100ml
o Normal post prandial blood glucose (2 hours
after food) – 100 -140 mg/100 ml
• It is important to maintain blood glucose level
because all the cells in the body need glucose for
nutrition
BG < 70mg/100ml – Hypoglycemia
BG > 140mg/ 100ml - Hyperglycemia
Mechanisms which maintain BG level
 Endocrine glands
• When BG level <70 mg/dl, diabetogenic
hormones are secreted which increases BG
• When BG level > 140 mg/dl, insulin will be
secreted which decreases BG
 Liver & muscles
• When ever BG level increases, excess of glucose
is converted into glycogen & stored in to liver &
muscles
• When ever BG level decreases, liver & muscle
glycogen breaks down to release glucose into
blood
 Kidney
• The reabsorption of glucose in PCT of Nephron
depends on renal threshold. It is the value of BG
beyond which glucose starts appearing in urine.
Normal value of renal threshold is 180 mg/ dl
• When the BG above renal threshold, PCT stops
reabsorbing glucose, hence the excess glucose
is excreted in urine - Glycosuria
 Gastrointestinal tract
• Normal gastric emptying time is 3-4 hours
• When carbohydrate rich meal is consumed
there will be delay in gastric emptying. This
prevents sudden increase of BG during
absorption in small intestine
 Autonomic nervous system
• During stress there is stimulation of
sympathetic nervous system. This will cause
secretion of adrenalin & noradrenalin by
adrenal medulla. They are diabetogenic
hormones which increases the blood glucose
 Skin
• When BG increases, the excess of glucose is
stored in skin, hence skin infections are very
common in DM
• When skin becomes rich in glucose, acts as a
cultured medium medium for growth of
microorganisms
Adrenal gland

 Hormones of adrenal cortex


Mineralocorticoids
Glucocorticoids
Adrenal adrogens
Mineralocorticoids
• They are hormones secreted by outer layer of
adrenal cortex namely Zona glomerulosa
Ex. Aldosteron
• Act on the metabolism of electrolytes or
minerals, especially sodium & potassium
Aldersteron
Chemical structure
• Steroid hormone derived from cholesterol
Functions
• Usually called as life saving hormone
• It is responsible for reabsorption of salt (NaCl)
and water in the DCT of Nephron. Hence it
increases blood volume, cardiac output & BP
• Reabsorption of salt & water in DCT take place
in exchange for K+ and H+ ions. Thus it
maintains plasma potassium level and acid
base balance of the body
Regulation
Renin – Angiotensin
• Decrease in BP stimulates secretion of an
enzyme, renin by juxta glomerular apparatus of
kidney. Renin converts angiotensinogen (which is
produced in the liver) to the hormone
angiotensin1. An enzyme known as ACE
(angiotensin converting enzyme) found in
vascular endothelium of lungs, metabolizes
angiotensin1 into angiotensin2. Angiotensin2
causes constriction of blood vessels thus
increases BP
• Angiotensin2 stimulates release of hormone
aldosterone in the adrenal gland
Plasma potassium –hyperkalemia stimulates
secretion of aldosterone which will cause
excretion of K + ions. When there is
hypokalemia there is decrease in secretion of
aldosterone

pH of blood
• When there is acidosis secretion of
aldosterone increases which causes excretion
of H + ions. Alkalosis inhibits secretion of
aldosterone
Applied physiology
CONN’S syndrome
• It is a condition in which there is excess of
secretion of aldosterone by adrenal cortex
Clinical features
• Hypertension
• Hypernatremia
• Hypokalemia
• Alkalosis
Glucocorticoids
• They act on glucose metabolism hence they
named as glucocorticoids
• Secreted by Zona fasciculata of adrenal cortex
• Cortisol and corticosterone are glucocorticoids
• Cortisol / hydrocortisone is more potent
Cortisol

Chemical structure
• Steroid hormone derived from cholesterol

Is a life protecting hormone because it


helps to withstand the stress and trauma
Functions
Anti inflammatory function
• Cortisol inhibits the action of neutrophils and
prevents inflammation
• It inhibits the T- lymphocytes and decreases
immunity
• It inhibits secretion of histamine by mast cells
& protects body from allergy
Antistress
• Stress increases stimulation of cortisol, which
helps in fighting against the stress
Metabolism
o Carbohydrate metabolism
• It increases glycogenolysis and
gluconeogenesis
• Thus it increases blood glucose, hence cortisol
is diabetogenic hormone
o Protein metabolism
• In high concentrations, it causes breakdown of
proteins in skin, bone and muscles
o Fat metabolism
• In high concentration it causes redistribution
of fat into face, neck & trunk
o Mineral metabolism
• It reduces absorption of ca ions in small
intestine
On individual system
CVS – cortisol increases reabsorption of salt
and hydrogen ions (minerlo corticoid effect)
• Hence it increases blood volume, CO & BP
RS- it helps in synthesis of surfactant during IUL
CNS – it regulates emotions and behavior of a
person
• High level of cartisol causes Psychosis
• Low level of cartisol causes mental depression
Digestive system – in high concentration causes
increased secretion of HCl and causes peptic
ulcers
Blood- in high concentration causes
polycythemia, neutropenia, eosinopenia,
lymphocytopenia
Regulation

o Hypothalamus – secretes ACTHRH


o Anterior pituitary gland – secretes ACTH
o Circadian rhythm – maximum secretion is at early
morning and least at evening
o Stress – stimulates secretion of cortisol
o Feed back mechanism
• +ve feed back – decrease in plasma
concentration level of cartisol stimulate
anterior pituitary to secret ACTH, which will
stimulate secretion of cartisol
• -ve feed back – increase in plasma
concentration level of cartisol inhibits
secretion of ACTH, hence reduced secretion of
cartisol from adrenal cortex
Applied physiology
Cushing’s syndrome
• It is a condition in which there is increased
secretion of cartisol by adrenal cortex
Causes
• A tumor of adrenal cortex
• Increased secretion of ACTH by anterior
pituitary which is called as Cushing’s disease
• Prolonged treatment with steroid drugs
Clinical features
• Moon face
• Buffalo hump
– due to excess fat deposition in face and back of
neck
• Excess of fat deposition in trunk sparing
extremities
• Thinning of skin , purple striae in skin of
abdomen & thighs
• Weakness of muscles
• Osteoporosis
• Decrease in immunity
Cushing face
Buffalo hump
Purple striae over skin
• Secondary diabetes mellitus
• Hypertension
• Psychosis
• Peptic ulcer
• Polycythemia
• Neutropenia
• Eosinopenia
• Lymphocytopenia
Addison’s disease
• It is a condition in which there is decreased
secretion of cortisol
Causes
• Lesion of adrenal cortex
• Lesion of anterior pituitary causing decrease in
ACTH secretion
Features
• Hypotension
• Hypoglycemia
• Mental depression
• Inability to fight stress
Adrenal androgens
• These are weak androgens which have
musculinisng properties
• Secreted by Zona reticularis of adrenal cortex
Chemical structure – steroid hormone
Functions
• At puberty in males they are responsible for
development of male secondary sexual
characters
• It increases activity of sebacious glands. In high
concentration it can cause Acne vulgaris (pimple)
• It increases libido (sexual desire)
Regulation
• Controlled by ACTH secreted by anterior
pituitary
Applied physiology

Adrenogenital syndrome
• Due to increased secretion adrenal androgens
Cause
• Due to tumor of zona reticularis of adrenal
cortex
Pathology
• Under normal conditions, the androgens from
adrenal cortex are secreted in small
quantities. So they don’t have significant
effect on sex organs or on sexual functions
• However, when adrenal androgens are
secreted in abnormal quantities some
androgens are converted into testosterone
and responsible for androgenic activity in
androgenital syndrome
Features
• Characterized by the tendency for the
development of secondary sexual character of
opposite sex
o Symptoms in females
• Masculinization due to increased muscular
growth
• Deepening of voice
• Amenorrhea
• Enlargement of clitoris
• Male type hair growth
o Symptoms in males
• Feminization
• Enlargement of breast- gynecomastia
• Atrophy of testis
• Loss of interest in women
Hormones of adrenal medulla
Adrenaline or epinephrine
Noradrenaline or norepinephrine
Dopamine
Chemical structure
• They are the amines derived from catechol,
hormones called as catecholamines (class of
aromatic amines)
o The circulating adrenaline and noradrenaline
exert same effect as that of sympathetic
stimulation, but the effect of hormones is
prolonged 10 times more than sympathetic
stimulation
Functions of Adrenaline
o Known as ‘Fight or flight hormone’ since it
helps to respond in times of stress by vigorous
and sudden action
o Effect on metabolism
• It increases oxygen consumption and carbon
dioxide removal
• Increases basal metabolic rate, so said as
calorigenic hormone
• Increases blood glucose level by glycogenolysis
• It mobilizes free fatty acids from adipose tissues
in the presence of cortisol
o Effect on blood
• It reduces blood coagulation time
• Increases RBC count and hemoglobin content
in blood by causing contraction of spleen
o Effect on heart
• Increases overall activity of heart, i.e. heart
rate, force of contraction and excitability of
heart muscle
o Effect on blood pressure
• Increases systolic blood pressure by increasing
the force of contraction and cardiac output
• Decreases diastolic blood pressure by
reducing peripheral resistance (by dilatation of
blood vessels in skeletal muscle, liver and
heart)
o Effect on respiration
• Increases rate and force of respiration
o Effect on skeletal muscle
• Causes severe contraction and quick fatigue of
skeletal muscle
o Effect on brain – increases the activity of brain
o Effect on skin – causes contraction of arrector
pili results in goose bumps, increases
secretion of sweat
Functions of Noadrenaline
• It causes constriction of blood vessels
throughout the body, hence called as General
vasoconstrictor
• Increases diastolic pressure by increasing
peripheral resistance
Regulation of adrenaline & noradrenaline
During stress they secrete in large quantities &
small quantities at rest
Exposure to cold
• They secrete in large quantities and increase
the muscular activity, shivering so that body
temperature is increased
Hypoglycemia
• Causes release of these hormones inducing
glycogenolysis
Dopamine
• Secreted by adrenal medulla
• Also secreted by dopaminergic neurons of brain
• In brain, this hormone acts as neurotransmitter
• The other physiological functions of circulating
dopamine are not known
Effects of injected dopamine
• Vasoconstriction by releasing noradrenaline
• Vasodilatation of in mesentery
• Increase of heart rate
• Increase in systolic blood pressure
• Deficiency of dopamine in basal ganglia
produces nervous disorder called
PARKINSONISM
Applied physiology
Pheochromocytoma – Tumor of adrenal gland
• Condition in which there is excessive secretion of
catecholamines- Dopamine, noradrenaline and adrenaline
Symptoms
Signs
Anxiety
Hypertension
Headache
Tachycardia
Palpitation
Hyperglycemia
Nausea Glycosuria
Vomiting Other metabolic
Polyurea disorders
Chest pain
Loss of weight

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