Endocrine System and its glands in brief

 Endocrine System
• The endocrine system is a chemical messenger system
comprising feedback loops of hormones released by
internal glands of an organism directly into the circulatory
system, regulating distant target organs.
• In humans, the major endocrine glands are the thyroid
gland and the adrenal glands.
• In vertebrates, the hypothalamus is the neural control centre
for all endocrine systems. The study of the endocrine system
and its disorders is known as endocrinology.
1JCR - Endocrine System

2
Intercellular Chemical Signals
• Hormones: type of intercellular signal. Produced by cells of endocrine
glands, enter circulatory system, and affect distant cells; e.g., estrogen
• Autocrine: released by cells and have a local effect on same cell type
from which chemical signals released; e.g., prostaglandin
• Paracrine: released by cells and affect other cell types locally without
being transported in blood; e.g., somatostatin
• Pheromones: secreted into environment and modify behavior and
physiology; e.g., sex pheromones
• Neurohormone: produced by neurons and function like hormones; e.g.,
oxytocin
• Neurotransmitter or neuromodulator: produced by neurons and
secreted into extracellular spaces by presynaptic nerve terminals;
travels short distances; influences postsynaptic cells; e.g.,
acetylcholine.
JCR - Endocrine System

 Functional Classification of Intercellular
Chemical Signals
JCR - Endocrine System 3

4
 Functional Classification of Intercellular
Chemical Signals

 Hypothalamic Control of the
Endocrine System
• Master control center of the endocrine system
• Hypothalamus oversees most endocrine
activity:
– special cells in the hypothalamus secrete hormones
that influence the secretory activity of the anterior
pituitary gland
• called regulatory hormones
• releasing hormones (RH)
• inhibiting hormones (IH)
• Hypothalamus has indirect control over these
endocrine organs.

 Hypothalamic Control of the
Endocrine System
• Hypothalamus produces two hormones that are
transported to and stored in the posterior pituitary.
– oxytocin (paraventicular nucleus)
– antidiuretic hormone (ADH) (supraoptic nucleus)
• Hypothalamus directly oversees the stimulation and
hormone secretion of the adrenal medulla.
– An endocrine structure that secretes its hormones in response
to stimulation by the sympathetic nervous system.
• Some endocrine cells are not under direct control of
hypothalamus.

Pituitary gland

The master gland :
• The pituitary gland is called the “master gland”
because its hormones regulate other important
endocrine glands—including the adrenal, thyroid, and
reproductive glands (e.g., ovaries and testes)—and in
some cases have direct regulatory effects in major
tissues, such as those of the musculoskeletal system.

 Anatomy
Location
• Lies at the base of brain Sella turcica.
• Connected with the hypothalamus by the pituitary
stalk or hypophyseal stalk.
Division
• Anterior lobe ( adenohypophysis)
• Intermediate lobe ( not present or very small in
humans dispersed within anterior lobe)
• Posterior lobe ( neurohypophysis)

 Lobes of pituitary gland
• Anterior pituitary ( adenohypophysis)
Consists of three divisions
1. Pars distalis
2. Pars tuberalis
3. Pars intermedia
• Posterior pituitary
Consist of two parts
1.Infundibular stalks
2.Pars nervosa

Pituitary hormone secretion

Pituitary Gland (Hypophysis)
• lies inferior to the hypothalamus.
• Small, slightly oval gland housed within the
hypophyseal fossa of the sphenoid bone.
• Connected to the hypothalamus by a thin stalk, the
infundibulum.
• Partitioned both structurally and functionally into an
anterior pituitary and a posterior pituitary.
– (called anterior lobes and posterior lobes)

The pituitary gland consists of:
A) Anterior lobe (adenohypophysis): Consists of:
- Pars distalis - Pars tuberalis - Pars intermedia
B) Posterior lobe (neurohypophysis):
Consists of pars nervosa which is connected by
infundibulum (pituitary stalk) to the median
eminence (tuber cinereum) of hypothalamus.

Pars distalis is formed of:
Thick irregular cords of cells + blood sinusoids
There are 2 types of cells:
a) Chromophobes: About 50% of the cells. They are
small, found in groups and have NO GRANULES in
their cytoplasm.
b) Chromophils: The other 50% of the cells. They have
GRANULES in their cytoplasm and are larger than
the chromophobes.There are 2 types of chromophil
cells:
— ACIDOPHILS (10%): have reddish cytoplasm. They
secrete growth hormone (GH) & Prolactin
(lactogenic) H.
— BASOPHILS (40%): have bluish cytoplasm.
They secrete TSH, ACTH, FSH & LH.
In general basophils are larger in size and stain deeper
than the acidophils.

Cells and hormones of the anterior pituitary gland & their functions
Cell Hormone secreted Function
Somatotropes
(Acidophilic)
Growth H (somatotropin) Stimulates body growth
Mammotropes
(Acidophilic)
Prolactin (PRL) Stimulates milk production &
secretion
Thyrotropes
(Basophilic)
Thyroid Stimulating H (TSH) Stimulates production of thyroid H
by follicular cells
Gonadotropes
(Basophilic)
-Follicle Stimulating Hormone
(FSH)
-Luteinizing H (LH)
-Stimulates follicular cells in ovary
& spermatogenesis in testis.
- Stimulates production of estrogen
& progesterone from the ovary &
testosterone from the testis
Corticotropes
(Basophilic)
Adreno-Cortico Trophic H
(ACTH or corticotropin)
Stimulates secretion of
glucocorticoids & androgens from
adrenal cortexJCR - Endocrine System 20

Pars nervosa contains:
a) Bundles of nerve fibers.
b) Cells called pituicytes.
c) homogenous intercellular
substance: on fixation it
precipitates to form
Herring’s body.
• The bundles of nerve
fibers in the pars nervosa
arise in the hypothalamus
and descend to the
posterior lobe forming the
hypothalamo-
hypophyseal tract (HHT).
• The hormones secreted
by nerve cells in the
hypothalamus travel
down along the HHT &
accumulate at the end of
the tract in pars nervosa
as Herring’s bodies.
• It secretes Vasopressin or
ADH (Anti Diuretic H) &
Oxytocin.

 Pituitary Gland Blood Supply

 Seven Anterior Pituitary Hormones
1. Human growth hormone (hGH)
2. Thyroid-stimulating hormone (TSH)
3. Follicle-stimulating hormone (FSH)
4. Luteinizing hormone (LH)
5. Prolactin (PRL)
6. Adrenocorticotropic hormone (ACTH)
7. Melanocyte-stimulating hormone (MSH)

Posterior Pituitary

Figure : Synthesis, storage, and release of posterior pituitary hormonesJCR - Endocrine System 27

Posterior Pituitary
– Antidiuretic Hormone (ADH)
• Causes kidneys to retain more water
• Causes vasoconstriction  increases blood pressure
• Dehydration, pain, stress  increase ADH secretion
– Oxytocin causes
• Smooth muscle contraction of uterus during childbirth
• Causes “letdown” of milk from glands to ducts

 Posterior
Pituitary

 Pituitary gland disorders
Causes of disorders of pituitary gland
• Hyperactivity
• Hypoactivity
Hyperpituitarism
• Hyperfunctioning of anterior pituitary gland -
Gigantism and acromegaly
• Hyperfunctioning of posterior pituitary gland -
Inappropriate release of ADH

 Hypopituitarism
• Hypo functioning of anterior pituitary
Dwarfism.
• Hypo functioning of posterior pituitary
Diabetes insipidus

 Gigantism
Characterized signs and symptoms :
• Excess Growth of body
• Average height is approximately 7-8 feet
• Headache due to tumor of pituitary
• Hyperglycemia, visual disturbance and pituitary diabetes
mellitus.
• Cure : Gigantism can be cured by hypopituitarism ( burning
cells of anterior pituitary)

 Acromegaly
Characterized symptom & causes
• Enlargement, thickening and broadening of bones.
• Particularly extremities of the body.
• Hypersecretion of growth hormone, thyroid,
parathyroid hormone.
• Hypertension, headache and visual disturbance are
seen.
• Cure : as like as gigantism.

 Dwarfism
Deficiency of
growth hormone
in children before
growth is
completed
resulting retarded
growth.
• Short stature.

 Control of Anterior Pituitary Gland
Secretions
• Anterior pituitary gland is controlled by
regulatory hormones secreted by the
hypothalamus.
• Hormones reach the anterior pituitary via
hypothalamo- hypophyseal portal system.
– essentially a “shunt”
– takes venous blood carrying regulatory hormones
from the hypothalamus directly to the anterior
pituitary

Thyroid gland

Thyroid Gland
• Located immediately inferior to the thyroid cartilage of the larynx and
anterior to the trachea.
• Distinctive “butterfly” shape due to its left and right lobes, which are
connected at the anterior midline by a narrow isthmus.
• Both lobes of the thyroid gland are highly vascularized, giving it an intense
reddish coloration.
• Regulation of thyroid hormone secretion depends upon a complex thyroid
gland–pituitary gland negative feedback process.

Thyroid Gland
• Follicle cells:
– Produce and secrete thyroid hormone
– Precursor is stored in colloid
• Thyroid hormone
– Increases metabolic rate
– Important in growth and development.
• Parafollicular cells
– Produce and secrete calcitonin
• Calcitonin
– Secreted in response to elevated calcium levels
– Reduces blood calcium levels
– Acts on osteoblasts.

The thyroid gland produces 3 major hormones:
• Calcitonin: Reduce the concentration of calcium ions in the
blood by aiding the absorption of calcium into the matrix of
bones.
• Triiodothyronine (T3)
• Thyroxine (T4)
The hormones T3 and T4 work together to regulate the body’s
metabolic rate. Increased levels of T3 and T4 lead to increased
cellular activity and energy usage in the body.

 Thyroid Hormone Synthesis
There are six steps in the synthesis of thyroid hormone-
• Active transport of Iodide into the follicular cell via
Sodium-Iodide Symporter (NIS). This is actually secondary
active transport, and the sodium gradient driving it is
maintained by a Sodium-Potassium ATPase.
• Thyroglobulin (Tg), a large protein rich in Tyrosine, is
formed in follicular ribosomes and placed into secretory
vesicles.
• Exocytosis of Thyroglobulin into follicle lumen, where it is
stored as colloid. Thyroglobulin is the scaffold upon which
thyroid hormone is synthesised.

• Iodination of the Thyroglobulin. Iodide is made reactive by
the enzyme thyroid peroxidase. Iodide binds to the benzene
ring on Tyrosine residues of Thyroglobulin. First formed is
monoiodotyrosine (MIT) then diiodotyrosine (DIT).
• Coupling of MIT and DIT to give Triiodothyronine (T3)
hormone and coupling of DIT and DIT to give
Tetraiodothyronine (T4) hormone, also known as
Thyroxine.
• Endocytosis of iodinated thyroglobulin back into the
follicular cell. Thyroglobulin undergoes proteolysis in
lysosomes to cleave the iodinated tyrosine residues from the
larger protein. Free T3 or T4 is then released, and the
Thyroglobulin scaffold is recycled.

 Secretion of thyroid hormone-
• Thyroid hormones are released as part of a hypothalamic-
pituitary-thyroid axis. The Hypothalamus detects a low
plasma concentration of thyroid hormone and releases
Thyrotropin-Releasing Hormone (TRH) into the
hypophyseal portal system.
• TRH binds to receptors found on thyrotrophic cells of the
anterior pituitary gland, causing them to release Thyroid
Stimulating Hormone (TSH) into the systemic circulation.
TSH binds to TSH receptors on the basolateral membrane of
thyroid follicular cells and induces the synthesis and release
of thyroid hormone.

 Function
The thyroid gland is one of the main regulators of metabolism.
T3 and T4 typically act via nuclear receptors in target tissues
and initiate a variety of metabolic pathways. High levels of
them typically cause these processes to occur faster or more
frequently.
Metabolic processes increased by thyroid hormones include:
• Basal Metabolic Rate
• Gluconeogenesis
• Glycogenolysis
• Protein synthesis
• Lipogenesis
• Thermogenesis

 Thyroid Conditions-
• Goiter: A general term for thyroid swelling. Goiters can be
harmless, or can represent iodine deficiency or a condition
associated with thyroid inflammation called Hashimoto’s
thyroiditis.
• Thyroiditis: Inflammation of the thyroid, usually from a
viral infection or autoimmune condition. Thyroiditis can be
painful, or have no symptoms at all.
• Hyperthyroidism: Excessive thyroid hormone production.
Hyperthyroidism is most often caused by Graves disease or
an overactive thyroid nodule.
• Hypothyroidism: Low production of thyroid hormone.
Thyroid damage caused by autoimmune disease is the most
common cause of hypothyroidism . 52JCR - Endocrine System

• Graves disease: An autoimmune condition in which the
thyroid is overstimulated, causing hyperthyroidism.
• Thyroid cancer: An uncommon form of cancer, thyroid
cancer is usually curable. Surgery, radiation, and hormone
treatments may be used to treat thyroid cancer.
• Thyroid nodule: A small abnormal mass or lump in the
thyroid gland. Thyroid nodules are extremely common. Few
are cancerous. They may secrete excess hormones, causing
hyperthyroidism, or cause no problems.
• Thyroid storm: A rare form of hyperthyroidism in which
extremely high thyroid hormone levels cause severe illness

 Thyroid function tests-
• Thyroid function tests are a series of blood tests
used to measure how well your thyroid gland is
working. Available tests include the T3, T3RU, T4,
and TSH.

 T4 & TSH results-
• The T4 test and the TSH test are the two most common
thyroid function tests. They’re usually ordered together.
• The T4 test is known as the thyroxine test. A high level of
T4 indicates an overactive thyroid (hyperthyroidism).
Symptoms include anxiety, unplanned weight loss, tremors,
and diarrhea. Most of the T4 in your body is bound to
protein. A small portion of T4 is not and this is called free
T4. Free T4 is the form that is readily available for your
body to use. Sometimes a free T4 level is also checked
along with the T4 test.
• The TSH test measures the level of thyroid-stimulating
hormone in your blood. The TSH has a normal test range
between 0.4 and 4.0 milli-international units of hormone per
liter of blood (mIU/L). 55JCR - Endocrine System

 T3 result-
• The T3 test checks for levels of the hormone
triiodothyronine. It’s usually ordered if T4 tests and TSH
tests suggest hyperthyroidism. The T3 test may also be
ordered if you’re showing signs of an overactive thyroid
gland and your T4 and TSH aren’t elevated.
• The normal range for the T3 is 100–200 nanograms of
hormone per deciliter of blood (ng/dL). Abnormally high
levels most commonly indicate a condition called Grave’s
disease. This is an autoimmune disorder associated with
hyperthyroidism.

 Parathyroid Gland

 Structure
• 4 tiny parathyroid glands, in the neck, on the posterior
surface
of the thyroid gland. Have 2 superiorly & 2 inferiorly.
• Small in size, measuring about 6 mm long,
3 mm wide and 2 mm thick with dark brown color

 Histology
• Made up of chief cells & oxyphil cells
Chief cells
• Secrete parathormone
Oxyphil cells
• Degenerated chief cells and their function is
unknown.
• May secrete parathormone during physiological
condition called parathyroid adenoma.

 Parathormone
• Secreted by the chief cells of the parathyroid glands.
• Essential for the maintenance of blood calcium
level within a very narrow critical level.
• Maintenance of blood calcium level is necessary
because calcium is an inorganic ion for many
physiological functions.

Chemistry
• Parathormone is protein in nature, having 84 amino acids.
• It’s Molecular weight in 9,500.
Half life & Plasma level
• Parathormone has a half-life of 10 minutes.
• Normal plasma level of PTH is about 1.5-5.5 mg/dL.

 Actions of PTH on Blood Calcium Level
• Primary action of the PTH is to maintain the blood calcium
level within the critical range of 9-11 mg/dL
• PTH control blood calcium level by
1. Reabsorption of Ca from Bones
2. Reabsorption of Ca from renal tubules (Kidney)
3. Absorption of Ca from Gastrointestinal tract

On bones
• PTH enhances the reabsorption of Ca from the bones by
acting on osteoblasts and osteoclasts of the bone.
• Increases the number and activity of osteoclasts (bone
destroying cells).
• Increases collagen synthesis.
• Increases alkaline phosphatase activity.
• Increases local growth factors: IGF and transforming
factors.

On Kidney
• PTH increases the reabsorption of Ca from the renal tubules
along with magnesium ions and hydrogen ions Increases
Ca reabsorption mainly from distal convoluted tubule
and proximal part of collecting duct.
• PTH also increases the formation of 1, 25-di-
hydroxycholecalciferol (activated form of vitamin D) from
25-hydroxycholecalciferol in kidneys.
• Decreased phosphate, sodium and bicarbonate reabsorption
from the proximal tubule.

On Gastrointestinal Tract
• PTH increases the absorption of Ca ions from the GI tract
indirectly.
• The activated vitamin D is very essential for the absorption
of Ca from the GI tract.
• PTH also increase the absorption of PO4 & mg.

 Disorders of
Parathyroid Gland

 Tetany
Manifested by neuromuscular excitability due to plasma
ionized Ca2+
Causes:
a)Hypoparathyroidism
b)Alkalemia :Decrease the solubility product of Ca2+& PO4
and leads to reduced ionized Ca2+ & precipitation of CaPO4
c)Decreased Ca2+ absorption from the intestine:
1.Low calcium intake and Excess intake of antacids (peptic
ulcer) lead to Ca2+ precipitation and decreased absorption.

 Manifestation of Tetany
• These depend on the degree of red blood Ca2+ level:
1. Manifest tetany:
– Blood Ca2+ level is below 7 mg% (N 9-11 mg%).
– Muscular spasms in the hands and feet (Carpo-pedal
spasm).
2. Latent tetany:
– Blood Ca2+ level is at 7-9 mg%. 69JCR - Endocrine System

 Treatment of Tetany
1.IV injection of Ca2+ gluconate during spasm. Stops
immediately the tetanic spasms.
2. Calcium level is then maintained by giving vitamin D and
administration of oral calcium.
3.Acidifying salts as ammonium chloride help Ca2+ absorption
as they increase the ionization of Ca2+.

 Islets of Langerhans
of
Pancreas

 Pancreas
• A triangular gland, which has both exocrine and endocrine
cells, located behind the stomach
• Strategic location
• Acinar cells produce an enzyme-rich juice used for
digestion (exocrine product)
• Pancreatic islets (islets of Langerhans) produce hormones
involved in regulating fuel storage and use.

 Islets of Langerhans
• 1 Million islets
• 1-2% of the pancreatic mass
• Beta (β) cells produce insulin
• Alpha (α) cells produce glucagon
• Delta (δ) cells produce somatostatin
• F cells produce pancreatic polypeptide

 Insulin
• Hormone of nutrient abundance
• A protein hormone consisting of two amino acid chains
linked by disulfide bonds
• Synthesized as part of proinsulin (86 AA) and then excised
by enzymes, releasing functional insulin (51 AA) and C
peptide (29 AA).

 Insulin Structure
1- Large polypeptide 51 AA (MW 6000)
2- Tow chains linked by disulfide bonds.
A chain (21 AA)
B chain (30 AA)
3- Disulfide bonds.

 Insulin Action on Cells
• Insulin is the hormone of abundance.
• The major targets for insulin are:
– liver
– Skeletal muscle
– adipose tissue
• The net result is fuel storage

 Insulin Action on Carbohydrate
Metabolism
Liver:
• Stimulates glucose oxidation
• Promotes glucose storage as glycogen
• Inhibits glycogenolysis
• Inhibits gluconeogenesis
Muscle:
• Stimulates glucose uptake (GLUT4)
• Promotes glucose storage as glycogen

 Glucagon
• A 29-amino-acid polypeptide hormone that is a potent
hyperglycemic agent
• Produced by α cells in the pancreas
• Its major target is the liver, where it promotes:
– Glycogenolysis – the breakdown of glycogen to
glucose
– Gluconeogenesis – synthesis of glucose from lactic
acid and noncarbohydrates
– Release of glucose to the blood from liver cells

 Physiological Action of Glucagon
• Stimulates glycogenolysis, gluconeogenesis &
inhabits glycogenesis
• Promotes lipolysis & ketogenesis
• Increases calorigenesis

 Somatostatin
• Secreted from D cells of pancreas
• Also secreted from hypothalamus & GIT
• A peptide hormones with 2 forms, one with
14 AAs & the other with 28 Aas
Functions
➤ Inhibits secretion of insulin & glucagon
➤ Inhibits GI motility & GI secretions
➤ Regulates feedback control of gastric emptying

 Diabetes Mellitus (DM)
• A serious disorder of carbohydrate metabolism
• Results from hyposecretion or hypoactivity of insulin
• The three cardinal signs of DM are:
– Polyuria – huge urine output
– Polydipsia – excessive thirst
– Polyphagia – excessive hunger and food consumption

 Diabetes Mellitus Type l
Type 1: beta cells destroyed- no insulin produced chronic
fasted state, "melting flesh", ketosis, acidosis,
glucosuria, diuresis & coma
Diabetes Mellitus Type ll
• Over 15 million diabetics in USA- 10% type I, 90% type II
• More common is some ethnic groups
• Insulin resistance keeps blood glucose too high
• Chronic complications: atherosclerosis, renal failure&
blindness

 Symptoms of Diabetes Mellitus
➤ Hyperglycemia
➤ Polyuria
➤ Polydipsia
➤ Polyphagia
➤ Ketoacidosis
➤ Hyperlipidemia
➤ Muscle wasting
➤ Electrolyte depletion

 Diagnosis
• Demonstrating persistence hyperglycemia & glycosuria
• Glucose Tolerance Test (GTT) – oral is preferred
• Estimation of Fasting Blood Glucose (FBG)
• FBS more than 126 mg% in more than
two occasions confirms DM
Treatment
• Insulin therapy
• Oral hypoglycemic agents
• Life style modifications

Adrenal Glands

Our body has two adrenal (suprarenal) glands, each located
on the superior pole of each kidney. Each adrenal gland is
Structurally and functionally differentiated into two regions
or zones:
1.Adrenal Cortex
2. Adrenal medulla

 Adrenal Cortex
This is the outer or peripheral zone of the adrenal
gland, which makes up the bulk of the gland.
The adrenal cortex is divided into three zones. Each
zone has a different cellular arrangements and secrets
different groups of steroid hormones.

 Layers of Adrenal Cortex
1. Zona-glomerulosa
2. Zona-fasciculata
3. Zona-reticulata
Zona-glomerulosa:
• This is the outermost layer of the adrenal cortex
which secrets mineralocorticoid hormones.
• Immediately beneath the capsule.
• Columnar or pyramidal cells
• Arranged in closely packed, rounded, arched cords or
small clumps.
• Occupy 15% of the adrenal cortex. 93JCR - Endocrine System

 Zona-fasciculata
:
• This is the middle zone of the adrenal cortex which
secrets glucocorticoids hormone.
• Occupy 65% of the adrenal cortex.
• Polyhedral, often binucleated cells with lipid droplets in
their cytoplasm.
• Cells are also called spongyocytes due to vacuolization.

 Zona-reticularis
• This is the innermost layer of the adrenal cortex
which secrets androgen but in small quantities.
• Occupy 7% of the adrenal cortex.
• Smaller cells disposed in irregular cords forming
anastomosing network.
• Presence of lipofuscin pigment granules –large and
numerous.

 Hormones of the Adrenal cortex
The adrenocortical hormones and their functions in the body
are classified into three groups:
1. Mineralocorticoids
2. Glucocorticoids
3. Adrenal androgens.
Biosynthesis of adrenal hormones:

 Mineralocorticoids
Mineralocorticoids:
– secreted from the adrenal cortex-zona glomerulosa.
– Main secreted hormone is aldosterone.
– It also secrets deoxy-corticosterone,9-alpha
flourocortisol, cortisol, cortisone.
Functions:
– Maintain balance of electrolytes content of the body
fluid.
– Increased tubular reabsorption of Na+ ions in the
exchange for K+ and H+ ions.

 Mineralocorticoids
– Act mainly on the distal kidney tubules, salivary glands
and sweat glands.
– Increase blood volume and cardiac output.
– Increase blood pressure.
Regulations of aldosterone secretion :
– Increased of K+ ions.
– Decreased of Na+ ions.
– Undefined pituitary factors.
– ACTH
– Hypotension
– Increased renin angiotensin 99JCR - Endocrine System

 Glucocorticoids
Secreted from adrenal cortex-zona fasciculata.
Main secreted hormones are:
• Cortisol
• Prednisone & methyl
prednisone
• Corticosterone
• Cortisone

 Functions
Effects in the metabolism of carbohydrates, proteins and
lipids.
• Stimulation of gluconeogenesis.
• Mobilization of amino acids from extra
hepatic tissues.
• Inhibition of glucose uptake in muscles
and adipose tissues.
• Stimulation of fat breakdown. .

 Functions
• Suppress immune response.
• Destroying circulating
lymphocytes.
• Inhibiting mitotic activity.
• Controlling secretion of
cytokines.
– Promotes maturation of lungs and production of
surfactants in fetal development

 Androgen
• Secreted from the adrenal cortex-zona reticularis.
• Exhibit actions similar to testosterone.
Functions :
• Responsible for the development and maintenance of
reproductive functions.
• Stimulation of secondary sex characteristic.
• Stimulates the production of skeletal muscles and bones
and RBC.

104
• Regulations of androgen:
1. Controlled by luteinizing hormone (LH) and follicle
stimulating hormone(FHS).
2. Prolactin shows an inhibitory effects on androgen
secretion.
• Adrenal glands disorders :
1. Tumors including pheochromocytomas. Infections
2. Genetic mutations.
3. Cushing's syndrome.
4. Addison’s disease.
5. A problem in another gland, such as pituitary.
6. Hyperaldosteronism.

 Adrenal Medulla
• Structure
• Biosynthesis of hormones
• Functions and regulations
• Disorder of adrenal medulla

Introduction
• The adrenal medulla is part of the adrenal gland it is
located at the center of the gland. It is surrounded by
adrenal cortex. It is the innermost part of the adrenal gland
and it has such type of cells that secrete epinephrine also
known as adrenaline and norepinephrine which is known
as noradrenaline. It also secretes dopamine at a small
amount in response to stimulation by sympathetic
preganglionic neurons.
• In general adrenal medulla is a less common site of
chemically induced degenerative lesions.

Structure of adrenal medulla
• The adrenal medulla consists of irregularly shaped cells
grouped around blood vessels. These cells are intimately
connected with the sympathetic division of the autonomic
nervous system(ANS).
• The cells of the adrenal medulla are derived from the neural
crest in contrast to the mesodermal origin of the adrenal
cortex. The secretory cells of the adrenal medulla are called
chromaffin cells because of the formation of colored
polymers of catecholamines after exposure to oxidizing
agents such as chromate.
• In fact these adrenal medullary cells are modified
postganglionic neurons and preganglionic autonomic nerve
fibers lead to them directly from the central nervous system.107JCR - Endocrine System

Structure of adrenal medulla

Functions of adrenal medulla
• Biosynthesis of hormones:
The adrenal medulla is the principal site of the conversion
of the amino acid tyrosine into the catecholamines
epinephrine, norepinephrine and dopamine.
• Stimulation of the sympathetic nerves to the adrenal
medullae causes large quantities of epinephrine and
norepinephrine to be released into the circulating blood,
and these two hormones in turn are carried in the blood to
all tissues of the body. On average, about 80 percent of the
secretion is epinephrine and 20 percent is
norepinephrine.

Functions of adrenal medulla
• The circulating epinephrine and norepinephrine have almost
the same effects on the different organs as the effects
caused by direct sympathetic stimulation, except that the
effects last 5 to 10 times as long because both of these
hormones are removed from the blood slowly over a period
of 2 to 4 minutes.
• The circulating norepinephrine causes constriction of most
of the blood vessels of the body; it also causes increased
activity of the heart, inhibition of the gastrointestinal
tract, dilation of the pupils of the eyes, and so forth.

Regulatory activity of adrenal
medulla
• Adrenal medulla is the part of the sympathetic system and
is important for the regulation of blood pressure .
Catecholamines released from the adrenal medulla also
have metabolic effects . The following are the most
important effects of catecholamines:
• They increase blood pressure , skeletal muscle blood flow,
skeletal contractility, heart rate, blood glucose, lipolysis.
• They decrease visceral blood flow ,gastrointestinal
contractility ,urinary output.

Disorder of the adrenal medulla
• Pathology within the adrenal medulla and the autonomic
nervous system is primarily because of neoplasms. The
most common tumour, called pheochromocytoma when
located in the adrenal medulla, originates from chromaffin
cells and excretes catecholamines.
• Those tumours found in extra-adrenal chromaffin cells are
sometimes referred to as secreting paragangliomas.
Neoplasms may also be of neuronal lineage, such as
neuroblastomas and ganglioneuromas.

Pheochromocytoma
• Pheochromocytoma is a chromaffin cell neoplasm that
typically causes symptoms and signs from episodic
catecholamine release, including paroxysmal
hypertension.
• In population-based cancer studies, its frequency is
approximately two cases per million of the population. The
diagnosis of pheochromocytoma is typically made in the
fourth or fifth decade of life without gender differences.

Paragangliomas
• Extra-adrenal pheochromocytomas can be referred to as
paragangliomas. They arise from paraganglionic
chromaffin cells in association with sympathetic nerves,
and are found in the organ of Zuckerkandl, urinary bladder,
chest, neck and at the base of the skull.
• They are more common in children than in adults, and are
more frequently malignant. As discussed earlier, mutations
in the SDH family may predispose to head and neck
paragangliomas and pheochromocytoma.

Paragangliomas

Neuroblastomas
• Neuroblastomas and ganglioneuromas are tumours of the
primitive neuroblast cells from the sympathetic nervous
system in ganglia and the adrenal medulla. They may
represent a continuum of neuronal maturation and are the
most common malignancy found in children, representing
7–10% of all childhood cancers.
• Because of their more mature ganglion cells which are
histologically benign, ganglioneuromas are often
metabolically inactive and asymptomatic. They are found
incidentally or with compressive symptoms mostly in the
posterior mediastinum or retroperitoneum.

Neuroblastoma

Nervous System 1
Nervous System
• Nervous system is the most important organization which control and
integrates the different body functions and maintains the constancy
of internal environment.
• A network of billions of nerve cells linked together in a highly
organized fashion to form the rapid control center of the body.
• Primarily, the nervous system is divided into two parts:
(1) Central nervous system (2) Peripheral nervous system
JCR/Human Physiology

Nervous System 2
Division of nervous system

Nervous System 3
Division of nervous system

Nervous System 4
Neuron
• Defined as the structural and functional unit of the nervous system
• It is otherwise called nerve cell.
• Neuron is different from other cells by two ways:
(i) neuron has branches or process called axon and dendrites
(ii) neuron does not have centrosome so it cannot undergo division

Nervous System 5
Neuron: structure
The neuron is made up of three parts:
(1) Nerve cell body or soma
(2) Dendrites
(3) Axon

JCR/Human Physiology Nervous System 6
Neuron: structure
Nerve cell body
• The nerve cell body is irregular in shape and is constituted by a mass of
cytoplasm called neuroplasm.
• The cytoplasm contains a large nucleus, nissl bodies, neurofibrils,
mitochondria and golgi apparatus.
• The nucleus does not contain centrosome, so they cannot multiply like other
cells.
• Nissl bodies are present in the soma but not in axon.
• Presence of neurofibrils is a characteristic feature of the neurons.
Neurofibrils are thread like structures present in the soma.

Neuron: structure
Dendrites
• It is the branched process of the
neuron and it is branched repeatedly.
• It is conductive in nature.
• It transmits impulses towards the
nerve cell body.
• Usually dendrites are shorter than
axon.
• Number varies from nil to numerous.

Neuron: structure
Axon
• It is the longer process of the nerve cell.
• Arises from axon hillock of the nerve cell
body.
• Devoid of Nissl granules.
• Extends for a long distance away from the
nerve cell body.
• The length of the longest axon is about one
meter.

Neuron: Myelin sheath
• In a myelinated nerve fiber, the axis cylinder is
covered by a thick tubular sheath called myelin
sheath.
• Does not form a continuous sheath and is absent at
regular interval.
• The area where the myelin sheath is absent is called
node of Ranvier.
• Myelin sheath is responsible for the white color of
the nerve fibers.

Myelin sheath: Functions
1. Myelin sheath is responsible for faster
conduction of impulse through the nerve
fibers.
2. Myelin sheath has a high insulating capacity.
Because of this quality, the myelin sheath
restricts the nerve impulse within the single
nerve fiber, and prevents the stimulation of
neighboring nerve fibers.

Myelinogenesis
• Myelin sheath is formed from wrapping of Schwann cell around the axis
cylinder in many concentric layers.
• The process of the formation of myelin sheath is called the myelinogenesis.
• In the peripheral nerve, the myelinogenesis starts at 4th month of
intrauterine life. It is completed only in the second year after birth.
• The axon is first enveloped completely by Schwann cell membrane.
• The Schwann cell membrane then gives several turns leaving the axon
surrounded by many concentric layers.

Myelinogenesis

Myelinogenesis
• During this repeated wrapping, more and more cytoplasm is pushed to the
periphery of the Schwann cell.
• When the myelination process is completed, the Schwann cell covers the
axon with many layers of plasma membranes. This covering is called a myelin
sheath.
• The Schwann cell cytoplasm outside the myelin sheath contains the cell
nucleus and referred to as the neurolema.

Classification of Neurons
A. Based on the number of processes that emanate from their cell body, neurons can be
classified as:
1. Apolar (have no process)
• Apolar neurons are type of neuron which contain only one protoplasmic process extends from
cell body.
• Such neurons are common in insects.
• Apolar neurons are specific to the cerebellum and granule region of the dorsal cochlear nucleus.
2. Unipolar (only axon, i.e., 5th cranial nerve)
• A unipolar neurons is a type of neuron in which only one protoplasmic process (neurite) extends
from the cell body.
• Most neurons are multipolar, generating several dendrites and an axon and there are also
many bipolar neurons.
• Unipolar neurons that begin as bipolar neurons during development are known
as pseudounipolar neurons.
• Typically these have special structures for transducing some type of physical stimulus (light,
sound, temperature, etc.) into electrical activity, no dendrites, and a single axon that conveys the
resulting signals into the spinal cord or brain.

3. Bipolar (both axon and dendrite, i.e., retina)
• A bipolar neurone or bipolar cell, is a type of neuron which has two extensions (one axon and
one dendrite).
• Bipolar cells are specialized sensory neurons for the transmission of special senses.
• As such, they are part of the sensory pathways
for smell, sight, taste, hearing and vestibular functions.
4. Pseudounipolar
• cell body in one side, T-shaped, one branch of T being the dendrite and another branch is
axon, found in all spinal ganglia.
• A pseudounipolar neuron (pseudo – false, uni – one) is a kind of sensory neuron in the
peripheral nervous system.
5. Multipolar
• A multipolar neuron is a type of neuron that possesses a single axon and many dendrites,
allowing for the integration of a great deal of information from other neurons.
• These processes are projections from the nerve cell body.
• Multipolar neurons constitute the majority of neurons in the central nervous system.
• They include motor neurons and interneurons are most commonly found in the cortex of
the brain, the spinal cord, and also in the autonomic ganglia.

Classification of Neurons
B. According to function:
1. Sensory Neuron (Afferent):
convey information from tissues and organs into the central nervous system.
2. Motor Neuron (Efferent):
transmit signals from the central nervous system to the effector cells/tissue.
3. Interneurons:
connect neurons within specific regions of the central nervous system.

Nerve fibers
• A nerve fiber is a threadlike extension of a
nerve cell and consists of an axon
(microfilament + microtubule) and myelin
sheath (if present) in the nervous system.

Classification of nerve fiber
Nerve fibers are classified by six methods:
(1) Depending upon structure
(2) Depending upon distribution
(3) Depending upon origin
(4) Depending upon function
(5) Depending upon the secretion of neurotrnsmittter
(6) Depending upon diameter and conduction

Classification of nerve fibers
(1) Based on the structure, the nerve fibers
are classified into two ways:
1. Myelinated nerve fibers: covered by
myelin sheath
2. Non-myelinated nerve fibers: do not
have myelin sheath.

(2) Based on distribution, the nerve fibers are classified into two ways:
1. Somatic nerve fibers: supply the skeletal muscle of the body.
2. Autonomic or Visceral nerve fibers: supply the various internal organs of
the body.
(3) Based on origin, the nerve fibers are classified into two ways:
1. Cranial nerve fibers: arising from the brain.
2. Spinal nerve fibers: arising from the spinal cord.

(4) Based on function, the nerve fibers are classified into two ways:
1. Motor or Efferent nerve fibers: carry motor impulses from CNS to PNS.
2. Sensory or Afferent nerve fibers: carry sensory impulses from PNS to
CNS.
(5) Based on secretion of neurotransmitter, the nerve fibers are classified into
two ways:
1. Adrenergic nerve fibers: secrete noradrenaline or norepinephrine.
2. Cholinergic nerve fibers: secrete achetylcholine.

(6) Based on diameter and conduction, the nerve fibers are classified into three
major types:
1. Type A nerve fibers: further classified into (i) Type A alpha (ii) Type A beta
(iii) Type A gamma and (iv) Type B delta
2. Type B nerve fibers
3. Type C nerve fibers
• The diameter (thickness) of the nerve fibers: Type A alpha (12 to 24 μ)>
Type A beta> Type A gamma > Type A delta> Type B> Type C (<1.5 μ)
• The velocity of conductance of the nerve fibers: Type A alpha (70 to 120
m/s)> Type A beta> Type A gamma > Type A delta> Type B> Type C (0.5 to 2
m/s)

Properties of nerve fibers
(1) Excitability: The nerve can be stimulated or excited by a suitable
stimulus, which may be:
-mechanical
-thermal
-chemical
-electrical
The stimulus must be adequate to produce the action potential, which is
propagated.
• Excitability depends upon the following factors:
(a) Strength of stimulus
(b) Duration of stimulus
(c) Frequency of stimulus
(d) Injury

(2) Conductivity: Conductivity of nerve fiber shows the following
characteristics:
(i) Impulse is propagated along a nerve in both directions [but under
normal conditions the nerve impulse travels in one direction only-in the
motor nerve towards the responding organ; in sensory nerve toward the
center]
(ii) The nerve impulse is propagated with a definite speed. The conduction
velocity depends upon the diameter of the nerve fibers, the thicker
fibers showing higher velocity. The velocity also depends on the
myelination and on temperature.

3. All-or-none law:
-When a nerve is stimulated by a stimulus with sub-threshold strength,
action potential does not develop. If the strength of stimulus is above the
sub-threshold level, action potential will develop and response will take
place.
-If the strength or duration of the stimulus be further increased, no
alteration in the response will take place. The action potential remains the
same.
4. Refractory period:
When the nerve fiber is once excited, it will not respond to a second
stimulus for a brief period. This period is called refractory period.

5. Summation:
When one subliminal stimulus is applied, it does not produce any response
in the nerve fiber. However, if two or more subliminal stimuli are applied
within a short interval, the response is produced. It is because the subliminal
stimuli are summed up together.
6. Adaptation:
While stimulating a nerve fiber continuously, the excitability of the nerve
fiber is maximum in the beginning. Later the response decreases slowly and
finally the nerve fiber does not show any response at all. This phenomenon is
known as adaptation.

7. Accommodation:
If a stimulus even in stronger strength is applied very slowly to a nerve,
then there may have no response only due to lack of attaining the
threshold strength. This phenomenon is called accommodation.
8. Indefatigability:
A nerve fiber cannot be fatigued, even if it is stimulated continuously for a
long time. The reason for this is the nerve fiber can conduct only one
action potential at a time. At that time, it is completely refractory and does
not conduct another action potential.

Neuroglia
• Neuroglia or glia is the supporting cell of the nervous system.
• They are non excitable and do not transmit nerve impulse.
• Compared to the number of neurons, the number of glial cells is 10 to 15 times greater.
Classification:
(1) Central neuroglial cells
(a) Astrocytes
(b) Microglia
(c) Oligodendrocytes
(2) Peripheral neuroglial cells
(a) Schwann cell
(b) Satellite cell

Central neuroglial cells : Astrocytes
• Star shaped cells present in all parts of the
brain.
• Two types: (i) Fibrous astrocytes and (ii)
Protoplasmic astrocytes
• Fibrous Astrocytes:
• Occupy mainly the white matter.
• Processes of these cells cover the nerve cells
and synapses.
• Form the Blood Brain Barrier (BBB)
• Protoplasmic Astrocytes:
• Present mainly in gray matter.

Central neuroglial cells : Astrocytes
Functions of Astrocytes:
• Form supporting network in brain and spinal
cord.
• From BBB thereby regulate the entry of
substances from blood into brain tissues.
• Provide calcium and potassium and regulate
neurotransmitter level in synapse.
• Regulate recycling of neurotransmitter during
synaptic transmission.

Central neuroglial cells : Microglia
• Derived from monocytes
• Enter the tissues of nervous system
from blood
• Engulf and destroy the microorganisms
and cellular debris by phagocytosis

Central neuroglial cells : Oligodendrocytes
• Cells forming myelin sheath around the
nerve fibers in CNS.
• Provide support to the CNS by forming a
semi-stiff connective tissue between the
neurons.

Peripheral neuroglial cell: Schwann cell
• Major glial cells in PNS.
• Provide myelination around the nerve fibers in PNS.
• Play important role in nerve regeneration.
• Remove cellular debris by their phagocytic activity.

Peripheral neuroglial cell : Satellite cells
• Present in the exterior surface of PNS neurons.
• Provide physical support to the PNS neurons.

Action Potential
• When two electrodes are connected through a suitable
amplifier and placed on the surface of a single axon, no
potential difference is observed.
• However, if one electrode is inserted into the interior of the
cell, a constant potential difference is observed, with the
inside negative relative to the outside of the cell at rest.
• A membrane potential results from separation of positive and negative
charges across the cell membrane.
• In resting cell the surface is positively charged and the interior is
negatively charged.
• In neurons, the resting membrane potential is usually about –70 mV

Stages of Action Potential
Resting stage:
• This is the resting membrane potential before the action potential begins.
• The membrane is said to be “polarized” during this stage because of the –70
millivolts negative membrane potential that is present.
Depolarization stage:
• At this time, the membrane suddenly becomes very permeable to sodium ions,
allowing tremendous numbers of positively charged sodium ions to diffuse to the
interior of the axon.
• The normal polarized stage is immediately neutralized by the inflowing positively
charged sodium ions, with the potential rising rapidly in the positive direction. This is
called depolarization.

Repolarization Stage
• After depolarization stage when the sodium channels begin to close and the
potassium channels open more than normal.
• Then, rapid diffusion of potassium ions to the exterior re-establishes the
normal negative resting membrane potential. This is called repolarization of
the membrane.
• In the last part of repolarisation the rate of fall is being abruptly slowed. This
slower fall is known as negative after-potential.

Repolarization Stage
• After reaching the basal level the wave overshoots slightly but slowly in the
hyperpolarisation direction. This is known as positive after potential.
• The Absolute Refractory Period:
Just after the neuron has generated an action potential, it cannot generate another
one. Many sodium channels are inactive and will not open, no matter what voltage
is applied to the membrane. Most potassium channels are open. This period is
called the absolute refractory period.
The neuron cannot generate an action potential because sodium cannot move in
through inactive channels and because potassium continues to move out through
open voltage-gated channels. A neuron cannot generate an action potential during
the absolute refractory period.

• The Relative Refractory Period:
Immediately after the absolute refractory period, the cell can generate an action potential, but
only if it is depolarized to a value more positive than normal threshold. This is true because
some sodium channels are still inactive and some potassium channels are still open. This is
called the relative refractory period.
The cell has to be depolarized to a more positive membrane potential than normal threshold
to open enough sodium channels to begin the positive feedback loop. The lengths of the
absolute and relative refractory periods are important because they determine how fast
neurons can generate action potentials.
• Resting state:
Resting state is when membrane potential returns to the resting voltage that occurred before
the stimulus occurred

Propagation of action potential
• Conduction of nerve impulse through a myelinated nerve fiber is about 50
times faster than through a nonmyelinated fiber.
• This is because the action potential jumps from one node to another node of
Ranvier.
• This type of jumping of action potential from one node to another is called
SALTATORY CONDUCTION.

Conduction of nerve impulse

Propagation of action potential
• The myelin sheath is not permeable to ions. So, the entry of sodium from
extracellular fluid into nerve occurs only in the node of Ranvier, where the
myelin sheath is absent.
• It causes depolarization in the node, and not in the internode. Thus, the
depolarization occurs at seccessive nodes.
• So, the action potential jumps from one node to another. Hence, it is called
SALTATORY CONDUCTION.

Synapse
• The junction between the two neurons is called synapse.
• It is the physiological continuity between two nerve cells.

The synapse consists of:
a presynaptic ending that contains neurotransmitters,
mitochondria and other cell organelles,
a postsynaptic ending that contains receptor sites for
neurotransmitters and,
a synaptic cleft or space between the presynaptic and
postsynaptic endings. It is about 20nm wide.

Types of synapse
According to the nature of synapse formation:
(1) Electrical synapses
(2) Chemical synapses
According to the nature of connections:
(1) Axosomatic
(2) Axodendritic
(3) Axo-axonic

JCR/Human Physiology Nervous System
50
Electrical Synapses
• Pre- and postsynaptic neurons joined by gap junctions
• Allow local current to flow between adjacent cells.
• Rare in CNS or PNS
• Found in cardiac muscle and many types of smooth muscle.

Chemical synapse
• The transfer of information across the synapse are brought about by
chemical process.
• Neurotransmitter is released from presynaptic neuron which travels the
synaptic cleft and bind with the receptors on the postsynaptic neuron
which facilitates ion channels opening and produces action potentials.

Chemical Synapse

Types of synapse
• Axosomatic: The presynaptic terminal of the axon ends in the cell body
(soma) of the neuron.

Types of synapse
Axodendritic synapse
• The presynaptic fibers of any axon
end in the dendrites of the
postsynaptic cell.
Axo-axonic synapse
• The presynaptic axon form synapse
with the axon of post synaptic cells.
• Rare synapse.

Mechanism of synaptic transmission
1. Arrival of action potential on presynaptic neuron opens volage-
gated Ca++ channels.
2. Ca2+ influx into presynaptic terminal.
3. Ca2+ acts as intracellular messenger stimulating synaptic
vesicles to fuse with membrane and release Neurotransmitter
(NT) via exocytosis.
4. NT diffuses across synaptic cleft and binds to receptor on
postsynaptic membrane.

5. Receptor changes shape of ion channel opening it and changing
membrane potential.
6. Opening of all types of ion channels causes a localized
depolarization of the membrane and produces an excitatory
postsynaptic potential (EPSP).
7. Selective opening of only the smaller ions like K+ and Chloride ions,
causing hyperpolarization of the membrane and that constitutes the
inhibitory postsynaptic potential (IPSP).

9. If the EPSP exceeds threshold value, it initiates the propagated
action potential in the postsynaptic neuron or muscle action
potential (MAP) in most skeletal and cardiac muscle.
10. During the development of the EPSP, simultaneously IPSP may
be developed at the same site by incoming action potential from
other sources. The propagation of nerve impulse by EPSP is
dependent upon the intensity of the postsynaptic potential.
11. NT is quickly destroyed by enzymes or taken back up by
astrocytes or presynaptic membrane.

Properties of synapse
(1) Law of forward conduction/One way conduction:
• An impulse is allowed to pass through a synapse in one direction only, i.e., from
presynaptic neuron to postsynaptic neuron.
(2) Synaptic delay:
• During the transmission of impulse via synapse, there is a short delay in
transmission. It is called synaptic delay. Synaptic delay in chemical synapse is less
than 0.5 millisecond.
• The synaptic delay is due to:
• Release of neurotransmitter
• Movement of neurotransmitter from axon terminal to postsynaptic
membrane
• Action of neurotransmitter to open the ionic channels in postsynaptic
membrane

(3) Fatigue:
• The synaptic fatigue is due to exhaustion of transmitter materials from the synaptic
vesicles following repeated presynaptic stimulation at faster rate.
(4) Summation:
• If the stimulus be subminimal, the released neurotransmitter will produce EPSP
which will not be sufficient to produce discharge of impulse in the postsynaptic
neuron. But if a number of subminimal stimuli be applied, their effects will be
summated together and the EPSP will be sufficient to discharge a impulse.
• Summation is of two types:
• (a) Spatial summation: when many presynaptic terminals are stimulated simultaneously.
• (b) Temporal summation: when one presynaptic terminal is stimulated repeatedly.

(5) Inhibition:
(A) Postsynaptic inhibition:
• The postsynaptic inhibition is due to release of inhibitory NT.
• This inhibitory NT change of permeability of the membrane which cause
hyperpolarization of the postsynaptic membrane and consequently, the action
potential elicited by the excitatory stimulus will fail to occur.
(B) Presynaptic inhibition:
• Inhibition of a stimulatory neuron before it synapses, by inhibiting Ca2+ entry and
blocking downstream processes, preventing neurotransmitter release, and
therefore preventing the neuron generating and EPSP post-synaptically.

(6) Synaptic block:
• The inhibitory neurotransmitter may be blocked at the synaptic junction producing
convulsion.
• Strychnine (pesticide) blocks the inhibitory activity and causes reduction or abolition
of the IPSP in most of the synaptic junctions.
• Tetanus toxin also has got similar effects and produces convulsion by blocking the
inhibitory neurotransmitter.

Neurotransmitter
• Neurotransmitters are endogenous chemicals that act as the mediator for
the transmission of nerve impulse from one neuron to another neuron
through a synapse.
• Neurotransmitters are packaged into synaptic vesicles and are released into
the synaptic cleft, where they bind to receptors in the membrane on the
postsynaptic side of the synapse.
• Release of neurotransmitters usually follows arrival of an action potential
at the synapse.

Types of neurotransmitter
(1) According to the nature (chemistry) of NT
(a) Amino acids:
• NT of this group are involved fast synaptic transmission and are inhibitory and
excitatory in aciton
• Examples:
• γ-aminobutyric acid (GABA) [inhibitory]
• Glutamate (glutamic acid) [excitatory]
• Aspartate (aspartic acid) [excitatory]
• Glycine [inhibitory]
(b) Monoamines:
• NT of this group involve in slow synaptic transmission and may be inhibitory
and excitatory in action.
• Acetylcholine (excitatory and inhibitory)
• Serotonin (inhibitory)

(1) According to the nature (chemistry) of NT
(c) Catecholamines:
• Dopamine (inhibitory)
• Epinephrine (Adrenaline) [excitatory & inhibitory]
• Norepinephrine (Noradrenaline) [excitatory & inhibitory]
(d) Others:
• Nitric oxide (excitatory)
• Histamine [excitatory]

(2) Based on the activity on postsynaptic neuron
(a) Excitatory NT
• Responsible for the conduction of impulse from presynaptic neuron to the post
synaptic neuron.
• Causes depolarization in the postsynaptic neuron.
• Causes development of EPSP.
• Example:
• Acetylcholine
• Aspartate
• Histamine
• Glutamate

(b) Inhibitory NT
• Inhibit the conduction of impulse from presynaptic neuron to the post synaptic
neuron.
• Causes hyperpolarization in the postsynaptic neuron.
• Causes development of IPSP
• Example:
• GABA
• Dopamine
• Serotonin
• Glycine

Transport and release of NT
• The NT is produced in the cell body of neuron and is transported through the axon.
• At the axon terminal, the NT is stored in small packets called vesicles.
• Under the influence of a stimulus, these vesicles open and release the NT into the synaptic cleft.
• It binds to specific receptors on the surface of the postsynaptic neuron.
• The receptors are G proteins, protein kinase or ligand gated receptors.

Inactivation of NT
• After the execution of the action, neurotransmitter is inactivated by following
mechanisms:
• (1) It diffuses out of synaptic cleft to the area where it has no action
• (2) It is destroyed or disintegrated by specific enzymes
• (3) It is engulfed and removed by astrocytes
• (4) It is removed by reuptake process, i.e. the neurotransmitter is taken
back into the axon terminal from where it was released.

Functions of Neurotransmitters
1. Acetylcholine:
This neurotransmitter was discovered in the year 1921, by Otto Loewi. It is
mainly responsible for stimulating muscles. It activates the motor neurons that
control the skeletal muscles. It is also concerned with regulating the activities
in certain areas of the brain, which are associated with attention, arousal,
learning, and memory. People with Alzheimer's disease are usually found to
have a substantially low level of acetylcholine.
2. Dopamine:
Dopamine is the neurotransmitter that controls voluntary movements of the
body, and is associated with the reward mechanism of the brain. In other
words, dopamine regulates the pleasurable emotions.
Drugs like cocaine, heroin, nicotine, opium, and even alcohol increase the level
of this neurotransmitter. A significantly low level of dopamine is associated
with Parkinson's disease, while the patients of schizophrenia are usually found
to have excess dopamine in the frontal lobes of their brain.

3. Serotonin:
Serotonin is an important inhibitory neurotransmitter, which can have a profound
effect on emotion, mood, and anxiety. It is involved in regulating sleep,
wakefulness, and eating. It plays a role in perception as well. The hallucinogenic
drugs like LSD actually bind to the serotonin receptor sites, and thereby block the
transmission of nerve impulses, in order to alter sensory experiences.
4. Gamma-aminobutyric Acid (GABA):
GABA is an inhibitory neurotransmitter that slows down the activities of the
neurons, in order to prevent them from getting over excited. When neurons get
over excited, it can lead to anxiety. GABA can thus help prevent anxiety.
GABA is a non-essential amino acid, that is produced by the body from glutamate.
A low level of GABA can have an association with anxiety disorders. Drugs like
Valium work by increasing the level of this neurotransmitter. Alcohol and
barbiturates can also influence GABA receptors.

5. Glutamate:
Glutamate is an excitatory neurotransmitter that was discovered in 1907 by
Kikunae Ikeda of Tokay Imperial University. It is the most commonly found
neurotransmitter in the central nervous system. Glutamate is mainly associated
with functions like learning and memory. An excess of glutamate is however, toxic
for the neurons. An excessive production of glutamate may be related to the
disease, known as amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease.
6. Epinephrine and Norepinephrine:
Epinephrine (also known as adrenaline) is an excitatory neurotransmitter, that
controls attention, arousal, cognition, and mental focus. Norepinephrine is also an
excitatory neurotransmitter, and it regulates mood and physical and mental
arousal. An increased secretion of norepinephrine raises the heart rate and blood
pressure.

7. Endorphins:
Endorphins are the neurotransmitters that resemble opioid compounds, like
opium, morphine, and heroin in structure. The effects of endorphins on the body
are also quite similar to the effects produced by the opioid compounds. In fact, the
name 'endorphin' is actually the short form for 'endogenous morphine'.
Like opioids, endorphins can reduce pain, stress, and promote calmness and
serenity. The opioid drugs produce similar effects by attaching themselves to the
endorphin receptor sites. Endorphins enable some animals to hibernate by slowing
down their rate of metabolism, respiration, and heart rate.
8. Melatonin:
It is the hormone produced by the pineal gland that also acts as a
neurotransmitter. It basically controls the sleep-wake cycle. It is also
associated with controlling mood and sexual behavior. The production
of melatonin is dependent on light. Light to the retina inhibits the
production of melatonin, while darkness has a stimulating effect on its
production.

• 9.
Nitric Oxide:
It is a gas that acts both as a hormone and neurotransmitter,
depending on the specific requirement. It can cause the blood vessels
to dilate, besides preventing the formation of clots. This in turn, can
promote the circulation of blood. Nitric oxide can increase the level of
oxygen in the body, and improve memory, learning, alertness, and
concentration. It is also responsible for causing the smooth
gastrointestinal muscles to relax.
To sum up, neurotransmitters are chemicals that allow the nerves to
communicate with each other, and thus, regulate the various
functions of the body. A substantially high or low level of these
chemicals can alter the functions of the entire nervous system.

 Reflex-
• A reflex action, also known as a reflex, is an
involuntary and nearly instantaneous
movement in response to a stimulus.
• When a person accidentally touches a hot
object, they automatically jerk their hand away
without thinking.
• A reflex does not require any thought input.

 Classification of reflexes-
Reflexes
Clinical
Classification
Superficial
Deep
Visceral
Pathological
Anatomic
Classification
Segmental
Intersegmental
Suprasegmental
No . of
Synapses
Asynaptic
Monosynaptic
Polysynaptic
Bisynaptic
Functional
Classification
Flexor
Extensor
Righting
Postural
Withdrawal
Conditioned
Unconditioned

 Clinical Classification-
• Superficial- stimulating superficial structures.
• Deep- stimulating receptors deep in muscle.
• Visceral- stimulating receptors in viscera.
• Pathological- present only during abnormality.

 Anatomic Classification-
• Segmental- reflex arc pass through one anatomic segment
Example- knee jerk
• Intersegmental- involve> one segment
Example- crossed extensor response
• Suprasegmental- involve interaction with suprasegmental
components
Example- postural reflexes (head-limb)

 Number of synapses-
• Asynaptic- axon reflex
• Monosynaptic- stretch reflex
• Bisynaptic- reciprocal innervation
• Polysynaptic- superficial reflex

 Functional Classification-
• Flexor reflexes
• Extensor reflexes
• Righting reflexes
• Postural reflexes
• Withdrawal reflexes

 Others-
• Unconditioned reflexes- inborn or inherent reflexes.
• Conditioned reflexes- acquired reflexes.
Secretion of saliva when food is kept in mouth is
unconditioned reflex.
secretion even with thought is conditioned reflex.

 Reflex arc
• The neural pathway that controls the reflexes occurs
through the reflex arc.
• It acts on an impulse even before it reaches the brain.
• There are some stimuli that require an automatic,
instantaneous response without the need of conscious
thought.
The following diagram shows the reflex arc pathway-

Reflex arc: composition
(1) Receptor:
It is the end organ, which receives the stimulus.
(2) Afferent nerve:
Afferent or sensory nerve transmits sensory impulses from the receptor to
the center.
Composition:
A simple reflex arc includes five components:
(1) Receptors
(2) Afferent/sensory nerve
(3) Center
(4) Efferent/motor nerve
(5) Effector ogran

Reflex arc: composition
(3) Center:
• The center is located in the brain or spinal cord.
• The center receives the sensory impulses via afferent nerve fibers and in
return, it generates appropriate motor impulses.
• Afferent and efferent are connected here by interneurons.
(4) Efferent nerve:
Efferent or motor nerve transmits motor impulses from the center to the effector
organ.
(5) Effector organ:
The effector organ such as the muscle or gland shows the response to the stimulus.

Types of reflex arc
(1) Monosynaptic reflex arc:
Has only two neurons, i.e, only one synapse.

Types of reflex arc
(2) Polysynaptic reflex arc:
Consists of several neurons and two or more synapses.

Types of reflex arc
(3) Complex or conditioned reflex arc:
• This type of reflex involves the brain.
• Salivation on smelling one's favorite food is
an example of conditional reflex. The
individual recognizes the smell and based on
a previous experience, the response
(salivation) occurs.
• The ringing of the bell is called the
conditioned stimulus. The dog had, thus,
'learnt' to associate the sound of the bell to
food and this made it salivate at the sound of
the bell.

Types of reflex arc
(4) Asynaptic reflex or Axon reflex arc:
• The reflex arc has neither an integration center nor
any synapse.
• Axon reflexes are important in a lot of physiological
and physiopathological processes from regulation
of skin blood flow and sweating to inflammation
and pain, from itch to asthma bronchiale and
allergic rhinitis.
• This is not a true reflex arc.

Properties of reflexes
(1) One way conduction:
• During any reflex activity, the impulses are transmitted in only one direction
through the reflex arc.
• The impulse pass from receptors to the center and then from center to effector
organ.
(2) Reaction time/ synaptic delay:
• There is a short interval between the application of stimulus and the onset of
reflex response.
• This time is lost in crossing the number of synapses in the central nervous
system.

(3) Summation:
Both spatial summation and temporal summation play an important role in the
facilitation of response during the reflex activity.
(i) Spatial summation: when two afferent nerve fibers supplying a muscle are
stimulated separately with subminimal stimulus, there is no response. But, if both
the nerve fibers are stimulated together with same strength of stimulus, the muscle
contracts. It is called spatial summation.
(ii) Temporal summation: When one nerve fiber is stimulated repeatedly with
subminimal stimuli, these stimuli are summed up to give response in the muscle. It
is called temporal summation.

(4) Occlusion:
• When a reflex contraction is produced by simultaneous stimulation of two afferent
nerves, the amount of tension (T) in the muscle is less that the sumtotal of the
tensions (t1+t2) setup in the same muscle when the two afferent nerves are
separately stimulated (i.e., T<t1+t2).
• Occlusion is due to the overlapping of the nerve fibers during the distribution.
(5) Facilitation:
• The passage of a reflex impulse facilitates the transmission of the next impulse (by
reducing synaptic resistance).
• Each subsequent stimulus seems to exert a better effect than the previous one and
makes the passage of the next impulse easier.

(6) Fatigue:
• When a reflex activity is continuously elicited for a long time, the response is
reduced slowly and at one stage, the response does not occur. This type of failure to
give response to the stimulus is called fatigue.
(7) After discharge:
• After reflex contracton, if the stimulation is discontinued, the muscle does not
completely relax at once. It relax gradually. This is due to the fact that the center go
on discharging motor impulses for a brief period, even after the sensory stimuli are
stopped. So, even after cessation of afferent stimulation, these impulses travel for
certain periods.

(8) Rebound phenomenon
• The reflex activities can be inhibited by some methods during certain
period. But, when the inhibition is suddenly removed, the reflex activity
becomes more forceful than the force before inhibition. It is called rebound
phenomenon.

Nerve endings/Receptors
• Receptors are the sensory nerve endings that terminate in the periphery
as bare unmyelinated endings or in the form of specialized capsulated
structures.
• The receptors give response to the stimulus.
• Receptor converts the stimulus in the environment into action potentials
in the nerve fiber.

Classification of receptors
• Generally, the receptors are classified into two types:
• (1) Exteroceptors: which give response to stimuli arising from outside the body
• (a) Cutaneous receptors
• (b) Chemorecepots
• (c) Telereceptors
• (2) Interoceptors: which give response to stimuli arising from within the body
• (a) Visceroceptors
• (b) Proprioceptors

Exteroceptors
1. Cutaneous receptors:
• The receptors situated in the skin are called cutaneous receptors.
• They are also called mechanoceptors because of their response to mechanical
stimuli such as touch, pressure and pain.
2. Chemoreceptors:
• The receptors, which give response to chemical stimuli, are called the
chemoreceptors.
3. Telereceptors:
• Telereceptors give response to stimuli arising away from the body. These receptors
are also called the distance receptos.

Exteroceptors
1. Cutaneous receptors:
• The receptors situated in the skin are
called cutaneous receptors.
• They are also called mechanoceptors
because of their response to
mechanical stimuli.
• Ruffini’s corpuscles: sense heat
• Pacini’s corpuscles: sense pressure
• Merkeis disks: sense touch
• Krause’s bulbs: sense cold
• Free nerve ending/nociceptors: sense
pain

Exteroceptors
2. Chemoreceptors:
• The receptors, which give response to chemical stimuli, are called the
chemoreceptors.
• The sensation of taste and smell is mediated by these receptors
3. Telereceptors:
• Telereceptors give response to stimuli arising away from the body.
• These receptors are also called the distance receptos.
• Vision and Hearing is mediated by these receptors

Interoceptors
1. Visceroceptors:
• The receptors situated in the viscera are called visceroceptors.
• Stretch receptors: in heart
• Baroreceptors: in blood vessels
• Chemoreceptors: in the GI tract
• Osmoreceptors: in the urinary tract
2. Proprioceptors:
• Proprioceptors give response to change in the position of different parts of the
body.
• Receptors are situated in muscle, tendon, ligament, joints, labyrinthine
apparatus

Sensations
• Sensations are FEELINGS aroused by change of environment.
• The different ways by which the body may be aware of its surroundings are called
SENSATIONS.
Sensation mechanism:
For each sensation the following mechanism is involved:
• (a) An appropriate stimulus
• (b) A specific nerve ending-selectively sensitive to that stimulus
• (c) The sensory pathway-carries the impulse to the central nervous system
• (d) The nerve center-the impulse is finally interpreted as a particular sensation
• (e) Psychical center-the ‘meaning’ of the sensation is analyzed and understood.

Properties of sensation
(1) Modality:
-The ability to distinguish the characteristic of a sensation from all other sensations is
known as modality.
(2) Quality:
-Quality means the nature of sensation.
-Sensations of the same modality may vary in quality. For instance, some individuals
cannot distinguish between red and green (color blindness).
(3) Intensity:
-Stronger the stimulus, higher will be frequency and more intense will be the
sensation.
-Two sensation of same quality may differ in intensity. A warm object delivers little
energy and a hot object delivers mush energy to the receptors.

Properties of sensation
(4) Adaptation:
-The structure of muscles and nerve adapt to a constant stimulus.
-The frequency of impulse gradually decreases due to adaptation.
(5) Extent:
-It indicates the area from which the sensation arises.
-Depends upon the number of receptors simultaneously stimulated.
(6) Duration:
-The duration of a sensation may be shorter that that of a stimulation due to
adaptation.
-On the other hand, sensations may outlast the period of stimulation and thereby give
rise to after-sensation.
(7) Localization or projection:
-It is the ability to locate the exact spot from which the sensation arises.
-Sensations are invariably projected either to some part of our own body or to some
part of the environment.

 The nervous system can be divided
into:
• The central nervous system (CNS): Consisting
of brain and spinal cord
• The peripheral nervous system (PNS):
Consisting all the nerves outside brain and
spinal cord

 The Peripheral nervous system(PNS):
• The peripheral nervous system (PNS) consists of
paired cranial and sacral nerves.
• Some of these nerves are sensory (afferent).
 i.e. transmit impulses to the CNS.
• Some are motor nerves (efferent).
 i.e. transmit impulses from the CNS. Some others
are mixed.

 The central nervous system(CNS):
• The central nervous system receives sensory
information through afferent nerves.
• It then processes this information and responds
appropriately by sending impulses through motor
nerves to the effector organs.
• For example, responses to changes in the internal
environment regulate important functions such as
respiration and blood pressure.

 Types of Nerves
• Sensory Nerves – These send messages to the brain
from all the sensory organs.
• Motor Nerves – They carry messages from the brain to
the muscles in the body.
• Mixed Nerves – They carry the sensory and motor
nerves. They help in conducting the incoming sensory
information and also the outgoing information to the
muscle cells.

 Based on which part the nerves connect to the Central Nervous System, they are
classified as:
 Cranial Nerves –
• They start from the brain
and carry messages from
the brain to the rest of
the body.
• Certain nerves are
sensory nerves while
some are mixed nerves.
• The brain communicates
with the body through
the spinal cord and
twelve pairs of cranial
nerves.
Number Name Function
1 olfactory smell
2 optic sight
3 oculomotor Moves eye,pupil
4 trochlear Moves eye
5 trigeminal Face sensation
6 abducens Moves eye
7 facial Moves eye,salivate
8 vestibulocochlear hearing, balance
9 glossopharyngeal taste, swallow
10 vagus heart rate,
digestion
11 accessory moves head
12 hypoglossal moves tongue

 Spinal Nerves
• These nerves originate from the Spinal
Cord.
• They carry messages to and from the
central nervous system.
• They consist of mixed nerves.
Central nervous system
The central nervous system consists of-
• The brain
• The spinal cord.
 Forebrain:
• The cerebrum.
• Hypothalamus.
• Thalamus.
 Midbrain:
• The tectum.
• Tegmentum.
 Hindbrain:
• The cerebellum.
• Medulla.
• Pons.

Temporal lobe
• Understanding language (Wernicke’s area)
• Memory
• Hearing
• Sequencing and organization
Occipital lobe
• Interprets vision (color, light, movement)
• Housing the visual cortex.
Parietal lobe
• Interprets language, words
• Sense of touch, pain, temperature (sensory strip)
• Interprets signals from vision, hearing, motor,
sensory and memory
• Spatial and visual perception
Frontal lobe
• Personality, behavior, emotions
• Judgment, planning, problem solving
• Speech: speaking and writing
• Body movement
• Intelligence, concentration, self awareness
 The brain is roughly split into four lobes:

The cerebellum
The cerebellum is the second largest part of the brain which is
located in the posterior portion of the medulla and pons.
Functions-
 Transfer of information.
 Fine control of the voluntary body movements.
 The cerebellum is responsible for coordinating eye
movements.
 It predicts the future position of the body during a
particular movement.
 The cerebellum is also essential for making fine adjustments
to motor actions.

The Medulla oblongata
The medulla oblongata is a small and the lowest region of the
brain that is enclosed and well protected.
Functions-
• It helps in controlling the involuntary functions of both
respiratory and cardiovascular centers.
• It is involved in regulating life-sustaining functions such as
coughing, sneezing, swallowing, vomiting, salvation,
hiccups, etc.

The Pons
The pons is the major structure of the brain stem present
between the midbrain and medulla oblongata.
Functions-
• It is involved in transferring information between the
cerebellum and motor cortex.
• It controls the magnitude and frequency of the respiration.
• It is also involved in controlling the sleep cycles.
• In addition, the pons is involved in sensations such as the
sense of taste, hearing, and balance.

 Difference between sympathetic and parasympathetic nervous system
Topic Parasympathetic nervous system Sympathetic nervous system
Introduction The parasympathetic nervous system is one of the
two main divisions of the autonomic nervous system
(ANS). Its general function is to control homeostasis
and the body's rest-and-digest response.
The sympathetic nervous system (SNS) is one
of two main divisions of the autonomic
nervous system (ANS). Its general action is to
mobilize the body's fight-or-flight response.
Function Control the body's response while at rest. Control the body's response during perceived
threat.
Activate
response of
Rest and digest. Fight-or-flight.
Heart rate Decreases heart rate. Increases contraction , heart rate.
Salivary gland Saliva production increases. Saliva production decreases.

Endocrine System and its glands in brief

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