1 General notions of hormones

Hormones are chemical messengers sinthetized by the endocrine glands and transported by the
blood to the target cells.

The chemical structure of hormones are of 3 types: proteins and polypeptides, derivates of
amynoacids tyrosine and steroids.

Regarding the regulation of hormones, when the blood concentracion of hormones increases, the
number of receptors expressed at the level of cells decereases.(down regulation). When the blood
concentration of hormones decreases, the number of receptors at the level of cells increases(up
regulation).

Hormones can be divided into 2 categories based on the location of the hormonal receptor:

1 hidrosoluble(proteins, peptides) which are stored in the intracellular vesicles and released when
the cell is stimulated. The position of the receptor is on the cell membrane. Transported unbound.

2 lypsosoluble(steroids and thyroid hormones) The receptor is located inside the cell. Synthesis
depends on the transefer of cholesterol esters to steroid hormone production. Transported bound.

2 Mechanism of hormone action

There are 2 types of messengers primary: hormones, neurotransmitters and secondary messengers:
cAMP, DAG, IP3 and calcium.

There are 2 types of hormones: hormones whose receptor is at the level of cell membrane and
hormones whose receptor is intracellular(cytoplasm or nucleus). The receptors that are located at
the level of cell membrane are: G protein linked hormone receptors(use cAMP as secondary
messenger or use inosithol triphosphate and diacylglycerol as secondary messenger) and enzyme
linked hormone receptors that contain tyrosine kinase or are associated with tyrosine kinase.

3 Adenohiphosisis, ACTH

It is made up of several types of cells secreting different hormones: corticotrope cells(basophiles)

which secrete ACTH, Thyrotrope cells(basophiles) which secretes TSH, Gonadotrope cells(basophiles)
which secrete FSH and LH, Somatotrope cells(acidophil) which secrete GH, Lactatrope cells(acidophil)
which secrete PRL.

ACTH is a polypeptide sinthesized as a prohormone(proopiomelanocortin=POMC which is made up

of several fragments: N-terminal fragment, joining peptide, ACTH, beta lipotropin.)

The role of ACTH is to stimulate the secretion of glucocorticoid hormones(CORTISOL).

4 Prolactin FSH, LH, TSH

TSH stimulates the synthesis and secretion of thyroid hormones and the development of the thyroid
gland. FSH plays a major role in the development of the ovarian follicles and secretion of estrogen by
the granulosa cells of follicle in women and also spermatogenesis in men. LH plays a role in
stimulating ovulation, causes maturation of follicle-in the formation of corpus luteum and in the
stimulation of Leydig cells to produce testosterone(in males). TSH, FSH and LH are made up of 2
subunits: alfa and beta. Alfa subunit is common in all of them while beta is hormone specific.

Prolactin is a polypeptide and its sinthesised by lactotroph cells. The roles of prolactin are: it
stimulates the development of mammary gland, it stimulates milk secretion, it stimulates the
synthesis of casein-beta lactoglobulin-lactalbumin-lactose and it also inhibits the secretion of
gonadotrop releasing hormone-FSH-LH. Prolactin secretion increases by effort, stress, sleep, surgery,
estrogen, TRH. Prolactin secretion decreases by: dopamine, somatostatin.

5 Roles of growth hormone in growth process

GH is a polypeptide. The rate of GH secretion is not constant throughout the day, it peaks 3,4 times a
day lasting 20-30 minutes each. All cells of the body have receptros for the growth hormone that are
associated with tyrosine kinase. The functional roles of GH is stimulating the growth of the body
increasing the size of cells and the number of mitosis. Long bones grow in length at the epiphysial
plates, the deposition of new cartilage causes elongation in the shaft of the bone and the thickness is
increased.

Stimulatory effects on growing are done directly or indirectly by means of somatomedines(A B C D).
Growth hormone stimulates the synthesis of insulin-like growth factors I II(IGF-I, IGF-II). IGF-I is called
somatomedin C is similar in structure with proinsulin and is secreted mostly by the liver.

Insulin and testosterone increases the level of IGF-I

IGF increases the synthesis of collagen, the division of chondrocytes, the synthesis of nucleic acids
and the development of growth plate and increase in length of the bone.

IGF-I is decreased by cortisol hipoproteinemia and high amounts of estrogen.

6 Metabolic effects of growth hormone and regulation of its secretion

The metabolic effects of GH influence protein metabolism by stimulating the synthesis of proteins
and nucleic acids, lipid metabolism by stimulating lipolysis, the adipous tissue breaks down into fatty
acids which end up in the circulation thus resulting in their oxidation so there is an increase of ketone
bodies(ketogenesis). Fatty acids are a source of energy for the cells during hypoglicemia/fasting. In
carbohydrate metabolism GH decreases the rate of glucose utilization of cells thus leading to
hyperglicemia(diabetogenic effect), and finally in mineral metabolism GH increases the intestinal
absorption of calcium and phosphate and decreases renal excretion of NA and K.

The secretion of GH is stimulated by a GH releasing hormone(GHRH). When it comes to post meal

stimulation of GH secretion ghrelin is the stimulant. Stress, exercise, trauma, sleep, hypoglicemia and
fasting also increase GH secretion.

IGF-I exerts a direct inhibitory action of GH secretion in the pituitary gland. Somatostatin also inhibits
the secretion of GH. Therapeutically it is used for the treatment of pituitary tumors that secrete
GH(in acromegaly).
7 Regulation of adenohypophisis secretion

Hypothalamus secretes 2 types of hormones: releasing hormones(liberins) and inhibitory

hormones(statins).

Corticotropin releasing hormone(CRH) stimulates the secretion of ACTH. Thyrotropin releasing

hormone(TRH) stimulates the secretion of thyroid stimulatin hormone(TSH). Gonadotropin releasing
hormone(GNRH) stimulates the secretion of FSH and LH. Prolactin releasing hormone(PRH)
stimulates prolactin secretion. There is also prolactin inhibiting releasing hormone(PIRH) which is
dopamine.

This hormones are secreted by hypothalamus and carried by the hypothalamic-hypophisial-portal

system to the hypophysis.

8 Antidiuretic hormone and oxytocin

Neurohypophisis stores hormones secreted by the hypothalamus.

ADH is secreted mainly by supraoptic nucleus and less by paraventricular nucleus of hypothalamus.

Oxytocin secreted mainly by paraventricular nucleus of hypothalamus.

ADH is a polypeptide. It has 3 types of receptors: RV1A: smooth muscles of blood vesels(mediates
vasoconstriction), liver(increases glycogenolysis), brain. RV1B is found in the anterior pituitary, it
increases the secretion of ACTH. RV2 is found in the distant tubule and collecting duct of nephrons, it
mediates reabsorption of water by means of AQP2.

The actions of ADH: it stimulates reabsorption of water, the secretion of ACTH and stimulates the
contraction of mesangial cells leading to the decrease of GFR(glomerular filtration rate).

Regulation of ADH secretion

The factor of regulation secretion: osmolarity of plasma, decrease of blood volume, distention of
atria, baroreceptors, cold and angiotensin 2 stimulate ADH secretion, stress, emotions, pain, nausea,
vomiting and drugs increase the secretion of ADH. Alcohol, drugs(clonidine, haloperidol) inhibit the
secretion of ADH.

Oxytocin is a polypeptide which has multiple roles: on mammary gland in woman leads to ejection of
milk by contraction of myoepithelial cells from mammary glands, regulated by positive feedback
mechanism.

On pregnant uterus causes contractions during delivery( positive feedback mechanism)

On non-pregnant uterus

In males causes the contraction of smooth muscle fibers especially in vas deferens

Synthesis and transport of thyroid hormones

The structural and functional unit of the thyroid gland is the thyroid follicle, it contains a thick jell like
substance called the colloid made up of thyro globulin which is the storage form of the thyroid
hormones. The hormones that are secreted are T3, T4 and calcitonin.

Synthesis of thyroid hormones

The steps of the synthesis are the following: the first step is the synthesis of the thyroglobulin(TG)
precursor. The following step is the uptake iodide by contransport with Na+ ( sodium iodide
symporter-NIS-1-1iodide/2Na). The third step is the formation of iodo tyrosin residues which are
catalized by thyroid peroxidise leading to monoiodo tryrosine( MIT) residue and diiodotyrosine(DIT)
residue. The next step coupling reaction – DIT + MIT = T3, DIT+ DIT = T4, MIT+ DIT= rT3. The next step
is pinocytosis of colloid droplets. The sixth step is the release of t3 and t4 into the cytosol of the
follicular cells, MIT and DIT turn into iodotyrosine deiodinase which releases iodine which is
reutilised by the follicular cell for the iodinasion of thyroglobulin. The last step is the secretion of t3
and t4 into the circulation.

The transportation of thyroid hormones is done by the blood: 70% of the t4 and 80% of the t3 is
carried by thyroxine-binding-globuline, 15-20% is carried by tansthyretin( prealbumin), 9% by
albumin and less than 1% of t3 and t4 is free.

Functional roles of thyroid hormones

The thyroid hormones increase the 02 consumption and metabolic activities of cells , the activity of
mythochondria in cells leading to ATP, the activity off Na/K -ATPase, thermogenic action/ calorigenic
effect also the development of the brain during fetal life and for the first few years of postnatal life,
body growth by stimulating the expression of GH gene in the somatotroph cells,
anabolism/catabolism of proteins. There is also an increase in the uptake of glucose by the cells, an
enhancement of gluconeogenesis and it can also be seen an increased rate of absorption of glucose
from the gastrointestinal tract thus resulting in an increase of insulin secretion, lypolisis.

Thyroid hormones also play a role in increasing the cardiac output, heart rate, systolic blood
pressure, but it decreases the diastolic blood pressure, gastrointestinal motility and digestive
secretions, they increase the rate and the force of respiratory movements, they have excitatory
effects on nervous and muscular activity(muscle tremor), thus sometimes resulting in sleep
difficulties. Thyroid hormones can influence sexual functions and they stimulate eritropoiesis.

Regulation of thyroid hormones

Thyroid hormones secretion is regulated by negative feedback. When the concentration of free T3 T4
is increased in blood, hypothalamus decreases its secretion of thyroglobulin releasing hormone thus
the secretion of adenohipophisis of TSH is decreased and also the secretion of t3 t4 is inhibited.

When the concentration of free T3 T4 in blood is decreased hypothalamus stimulates its secretion of
TRH, thus the secretion of adenohipophisis of TSH is stimulated and the secretion of T3 T4 is
increased.

Calcium and phosphorus in the body

The total amount of calcium in the human body is between 1-1.5 kg, 99% of this amount can be
found in the bones, the rest of the calcium is found in the circulation(calcemia), 9.0-10.5mg. 40-42%
of circulatory calcium can be found bound to plasma proteins(non diffusible), 50% of it is free or
ionized, and lastly 8-10% is bound to small anions such as citrate, phosphate and bicarbonate.
Regarding the distribution of phosphorus in the body 500-800 grams of total amount of phosphorus.
85-90% of the total amount can be found in bones and teeth, 10-15% intracellularly and plasma
concetration hosts 3.0-4.5mg. The daily intake of calcium is usually 1g, 1/3 of ingested calcium is
absorbed, 2/3 are excreted(90% faeces, 10% urine). The net absorption equals 10% of the ingested
amount. The absorption happens in the duodenum and a portion of the jejunum by active transport,
which is mediated by vitamin D3 and the calcium binding protein(calbinidin).

Absorption of phosphorus

The daily intake of phosphorus is 1400mg and the net absorption is 1100mg/day. The absorption
takes place in the proximal small intestine where calcium is also absorbed, as mentioned previously.
The excretion of these minerals happens through the faeces, 300mg/day. The active absorption of
phosphorus is stimulated by vitamin D3 which stimulates the synthesis of transport protein Na/Pi-
cotransporter at the luminal membrane of enterocyte.

Excretion of calcium through urine

The daily filtered amount of calcium is 10 grams, 98-99% of the total filtered amount of calcium is
reabsorbed: 60-65% in PCT, 4-9% in the distal tubule(DT) and collecting duct(CD) and the remaining
25-30% in the loop of Henle(LH). 1% of the amount that is filtered is eexcreted(100-150mg/day).
Everyday 6-7 grams of phosphate are filtered, 85-90% of filtered phosphate is reabsorbed and 10-
15% is excreted in the urine. The reabsorbtion of phosphate takes place in PCT(65-80%) and in
DT(10%). The presence of phosphate in urine acts as an important ph buffer.

Vitamin D- metabolism and functional roles

Vitamin D has 2 origins, a vegetal origin(vitamin D2=ergocalciferol) or an animal origin(vitamin

D3=cholecalciferol). The absorption of vitamin D takes place through the skin, the first biochemical
form it has in the body is 7-dehydrocholesterol which then becomes previtamin D3 and finally
vitamin D3, later 25OH cholecalciferol synthesizes in the liver which then changes into 1,25(OH)2
vitamin D3 which is equal with calcitriol(kidney-1alfahidroxylase). 1alfahidroxylase is stimulated by
PTH, estrogen, GH, prolactin, hypocalcemia and hypophosphatemia.

Transport of vitamin D3

99% of vitamin D3 is bound in plasma by transcalciferin, the receptor for vitamin D3 is at the level of
nucleus.

The functions of vitamin D

Vitamin D stimulates calcium and phosphate absorption in the gastrointestinal tract. It also increases
calcium and phosphate reabsorption in the renal tubule and by that decreases the excreted amount
of these substances in the urine. Regarding the bones it stimulates osteoblasts, thus the synthesis of
alcalinphosphatase, plasminogen activator, collagenic and noncolagenic proteins, such as
osteopontin, osteocalcin and finally it inhibits the secretion of PTH and by that the transcription of
the gene for PTH.

Paratyroid hormone

It is secreted by the chief cells of the parathyroid glands as a preprohormone. The receptor of PTH is
on the cell membrane and it is coupled with G protein which connects with the cAMP receptor on
osteoblasts, PCT and DT(renal tubule cells).
I Functional roles

PTH stimulates bone reabsorption by stimulating the activity of calcium pump from osteoblasts and
osteocytes, by that stimulation calcium moves from these cells into the blood under a few minutes,
thus resulting in a rapid rise of calcemia, this being the first phase. In the second phase(slow phase)
osteoclasts are activated, which break down the bone tissue and by that calcium gets in the blood
stream from the bones. The third phase implies the maturation of the immature osteoclasts and they
become mature osteoclasts. And in the last phase PTH inhibits the synthesis of collagen by
osteoblasts.

II Functional roles of PTH

PTH increases the reabsorption of calcium at the level of ASLH and DT and by that leading to
calciuria(100-150mg/day). 60% of the reabsorption of calcium happens in PCT, 40% in ASLH, DT and
CD.

III.

It inhibits the reabsorption of phosphates at the level of PCT and that leads to phosphaturia and later
to hypophosphatemia.

IV.

It increases the rate of reabsorption of Mg++ and H+, it decreases the reabsorption of Na, K, HCO3-
and aminoacids.

V.

PTH stimulates the synthesis/activity of 1alfahydroxilase that leading to calcitriol, thus leading to an
increase of intestinal absorption of calcium and phosphorus.

VI.

It indirectly stimulates the absorption of calcium in the gastrointestinal tract.

Regulation of PTH secretion

The secretion of PTH is regulated by calcemia which is sensed by calcium sensing receptor(CaSR)
found on the cell membrane of chief cells. A decrease of calcemia(ionized form of calcium) leads to
the secretion of PTH. An increase of calcemia leads to a decrease of the secretion of PTH. An
increased amount of phosphate stimulates PTH secretion by lowering the plasma concentration of
free ionized calcium. If PTH had increased both calcium and phosphate levels it could lead to a
precipitation in bone or soft tissues as calcium phosphate, thus the necessary increase in plasma
calcium concentration would not occur.

Magnesium is required for a normal secretion of PTH and response of target tissues of PTH.
Magnesium deficiency leads to hypocalcemia. Calcitriol inhibits the secretion of PTH by reducing
preproPTH mRNA.

Calcitonin

Calcitonin is a polypeptide synthesised by parafollicular cells of the thyroid gland.

The roles of calcitonin

It reduces the concentration of calcium and phosphate in blood, it stimulates the activity of
osteoblasts and inhibits the activity of osteoclasts and that leads to a deposit of calcium and
phosphate in the bones, it decreases the tubular reabsorption of calcium and phosphate.

Regulation of secretion

1. Calcitonin stimulation is stimulated by an increase in plasma calcium concentration and the

concentration of calcitonin also increases in pregnancy and lactation.
2. Calcitonin secretion is inhibited by hypocalcemia.

Endocrine pancreas and synthesis and secretion of insulin and insulin receptor

The structural units of the endocrine pancreas are the Langerhans islets, each islet has a few
hundred to a few thousand cells. There are 5 types of cells which secrete several hormones: Beta
cells which count for 60-70% of the cells and they secrete insulin and amylin. Next up we have the
alfa cells which represent 20-25% of the cells and they secrete glucagon. The next category are the
delta cells, they make up 1-8% of the cells and they secrete somatostatin. Next up we have the F
cells, which make up less than 2% of the total amount of cells and they secrete pancreatic
polypeptide, and finally we have epsilon cells, which secrete ghrelin.

Insulin

Insulin is a protein synthesized by the beta cells, as preproinsulin, which becomes proinsulin and
finally insulin. The secretion is biphasic. The receptors of insulin are on the cell membrane and they
are associated with tyrosine kinase. Most cells in the organism have receptors for insulin.

Insulin receptors

The receptors for insulin consist of: 2 alfa and 2 beta subunits connected by disulphide bridges. One
receptor can bind to molecules of insulin. When the concentration of insulin increseas the number of
receptors decreases. In case of starvation the number of receptors for insulin increases. When
overfeeding happens, the secretion of insulin is stimulated, continuously the number of receptors
decreases and that leads to insulin resistance.

Effects of insulin on carbohydrate metabolism

Insulin decreases glycemia by several mechanisms. First and foremost it stimulates the uptake of
glucose by cells, this process being mediated by glucose transoprters(GLUTS). It stimulates
glycogenogeneis in hepatocytes, during interdigestive periods glycogenlysis happens, which leads to
glucose being released in blood. In addition, glucose is stored in muscles in the form of glycogen that
being used to supply energy in anaerobic conditions. In case there is glucose that cant be stored in
hepatocytes as glycogen it s turned into fatty acids, which are stored as triglycerides in adipose
tissue. Furthermore, it inhibits glycogenolysis and gluconeogenesis and stimulates glycolysis.
 Effects of insulin on fat, protein and electrolyte metabolism

Lipid metabolism

Insulin has an effect on lipid metabolism by increasing the synthesis of FA in the liver, stimulating the
synthesis of TG in adipose tissue and it also increases the activity of lipoprotein lipase which leads to
lipoproteins in the blood which later break down adipose tissue into fatty acids and finally resulting
in TG and insulin also inhibits lipolysis. In case of lack of insulin such as in diabetes meillitus, TG are
broken down into free fatty acids which end up in the blood and then the liver, where betaoxydation
happens and acetyl Co-A forms keton bodies, which are released in blood and cause ketosis and
acidosis.

Protein metabolism

Insulin stimulates the transport of amino acids in cells and the synthesis of proteins in ribosomes. It
also increases the permeability of cell membranes for amino acids. It stimulates the anabolism of
proteins and inhibits their catabolism. Insluin also inhibits the synthesis of gluconeogenetic enzymes.
In case of diabetes mellitus, the catabolism of proteins is stimulated.

Insulin increases the activity of Na/K-ATPase, which leads to hypocalemia.

Regulation of insulin secretion and disturbances of insulin secretion

Glicemia

When glicemia is increased, the secretion of insulin is also increased. Glucose from beta cells is
carried via GLUT 2 transporters. Then phosphorylation happens and glucose-6-phosphate is formed,
releasing ATP, which inhibits the ATP-sensitive K channels causing the closure of K channels, thus
leading to depolarization and opening of voltage gated calcium channels, that causes an influx of
calcium and secretion of insulin by exocytosis.

Amino acids(arginine, lysine, leucin and free fatty acids)

Amino acids and free fatty acids increase intracellular levels of ATP, causing the secretion of insulin.

Glucagon + gastric inhibitory peptide + PNS/Acetylcoline increase calcium levels stimulating insulin
secretion.

Somatostatin + SNS/Norepinephrine(acting on alfa-2-adrenergic receptors) inhibit exocytosis of

insulin, this causing the stimulation of beta-2-receptors of beta cells and stimulation of insulin
secretion. Stimulation of SNS(exercise) inhibits the secretion of insulin preventing hypoglicemia and
excessive uptake of glucose by muscles and the possibility to use fats as energic substrates.

GH, ACTH, cortisol, T3, T4 stimulate the secretion of insulin.

Leptin, somatostatin and fasting decrease insulin secretion.

Disturbances of insulin secretion

Diabetes mellitus represents hyperglicemia and an increase in concentration of lipids in blood.

Diabetes mellitus can be divided into 2 categories: type 1/insulin dependant, when the beta cells are
destroyed by autoimmune mechanism. Type 2/noninsulin dependant which is more common in
obese people. The symptoms of diabetes mellitus are: polyfagia, glucosuria, polyuria, polydipsia and
dehydration.

Complications of diabetes mellitus are: atherosclerosis(stroke, myocardial infarction), diabetic

retinopathy, neuropathy and nephropathy.

Hyperinsulinism means the hyper secretion of insulin due to an insulinoma. When glicemia
decreases it leads to tremor, nervousness, sweating, tahycardia, increased blood pressure, dizziness,
speaking disturbances. The symptoms are due to the lack of glucose at the level of the neurons and
the stimulation of the simphatetic nervous system. If not treated immediately it can lead to
convulsions, unconciusness, and in extreme cases to hypoglycemic coma.

Glucagon and regulation of its secretion

Glucagon is a polypeptide. It is synthesised by alfa cells of the pancreas from its precurscor,
preproglucagon and by the upper gastrointestinal tract(stomach and intestine). The receptor is
coupled with G protein, forming cAMP. The roles of glucagon are: firstly it increases glicemia.
Glicogenolisis in liver. Gluconeogenesis, glucagon increases the transport of amino acids into
hepatocytes leading to the synthesis of glucose. Secondly, it stimulates lypolisis, leading to the
mobilization of fatty acids, causing ketogenesis. Ketones are the source of fuel for muscle cells and
heart cells during starvation, sparing blood, glucose for other tissues that are obligatory glucose
users(CNS). Lastly, glucagon stimulates the secretion of insulin by acting on beta cells.

Regulation of glucagon secretion

The ingestion of proteins acts as a major stimulus for the secretion of glucagon. Regulation of
glucagon secretion is also done by the level of glicemia. When glicemia decreases, the secretion of
glucagon is stimulated. Secretion is also stimulated by SNS, PNS, a diet rich in proteins, CCK, gastrin,
starvation, stress and exercise. Secretion is inhibited by SNS(alfa R), high level of
exogenous/endogenous FFA, ketons, insulin, somatostatin and secretin.

Somatostatin and pancreatic polypeptide

Somatostatin is secreted by delta cells of the pancreas, hypothalamus, digestive tract. Somatostatin
synthesized as preprosomatostatin. Factors that stimulate it s secretion: hyperglicemia, glucagon,
increased amino acids(arginin and leucin), increased fatty acids, CCK.

The roles of somatostatin

Somatostatin inhibits the secretion of: insulin, glucagon and pancreatic polypeptide, GH and TSH,
gastrin, CCK, GIP, VIP.

It decreases the motility of digestive tract, reduces gastric and piliary secrertion and gallbladder
motility. The principal role of somatostatin is to extend the period of time over which the food
nutrients are assimilated into the blood, preventing rapid exhaustion of the food, making it available
over a longer period of time.

Pancreatic polypeptide
It is synthesized by F cells of the pancreas. The roles of pancreatic polypeptide are the following: they
increase glucagon secretion from alfa cells, they reduce the exocrine secretion of the pancreas, they
also reduce gastric acids secretion and the emptying of it and upper intestinal motility. Pancreatic
polypeptides have a decreasing effect on the absorption of food. The secretion is increased by:
hypoglicemia, the presence of chyme containing proteins in the small intestine. Somatostatin can
decrease its secretion.

Classification, synthesis and transport of adrenal hormones

Adrenal glands

The adrenal glands consist of 2 parts: a cortex and a medulla. The cortex has 3 layers: zona
glomerulosa, which makes up 15% of the cortex and it s the place of secretio of mineralocorticoids.
The next layer is zona fasciculata(75%) and here are secreted glucocorticoids. And the last layer is
zone reticularis(10%) and it secretes adrenal sex hormones. The activity of zona glomerulosa is not
under the control of ACTH, but under angiotensin II. Adrenal hormones are synthesized form
cholesterol that fact making them steroid hormones. Cholesterol can be found in blood in the form
of LDL, and acetate is produced in the adrenal gland cells. Adrenal corticotrope hormone(ACTH)
stimulates the uptake of cholesterol by the adrenal cells. Cholesterol is esterified and stored inside
the plasm as lipid droplets.

Esterified cholesterol turns into free cholesterol and then because of the influence of cholesterol
desmolase it becomes pregnenolone. The enzyme dehydrogenase turns pregnenolone into
progesterone and after arriving in the zona glomerulosa it finally gains the shape of aldosterone and
cortisol and sex hormones(zona fasciculata and zona reticularis).

Transport of adrenal hormones

Adrenal gland hormones are not hidrosoluble, thus they are transported in plasma bound by
proteins.

Glucocorticoid hormones(cortisol), 90% of it, is transported in blood by corticosteroid-binding

globulin(alfa 2 globulin synteshized by liver). 7% of it by albumin and lastly 3-4% is free in plasma.
Corticosteron is transported by transcortin and albumin. 60% of aldosterone is transported by
plasma proteins such as transcortin and albumin and 40% of it is free in plasma, thus having a
shorter lifespan. Sex hormones are transported by sex hormone binding globulin.

Glucocorticoid hormones- functional roles, regulation of secretion

Glucocorticoid hormones(zona fasciculata) are cortisol, corticosteron, cortizon. Cortisol is considered

the physiologically important glucocorticoid in humans. Cortisol is liposoluble, that means that it
diffuses through the cell membrane, that s why the receptor is in the cytoplasm and the hormone
receptor complex interacts with specific regulatory DNA sequences(glucocorticoid response
elements).

Funtional roles of glucocorticoids

An effect of cortisol is hyperglicemia because it stimulates gluconeogenesis in the liver by activating
the enzymes required to convert amino acids into glucose, the mobilization of amino acids from the
extra hepatic tissues mainly from muscles and it also inhibits glucose uptake and its utilization by
peripheral cells.

Cortisol decreases the synthesis of proteins in extra hepatic tissues by depressing amino acid
transport into muscle cells and other extrahepatic tissues, also by mobilizing amin oacids from the
nonhepatic tissues, thus it diminishes the tissue stores of protein. Cortisol has an effect on liver
proteins, they become enhanced by the increasing amount of amino acids that are transported into
hepatic cells.

Functional roles of glucocorticoids

Cortisol mobilizes fatty acids from the adipose tissue, as a result of that there is an increase in the
amount of FFA in the plasma, thus their utilization for energy also increases. It also stimulates the
oxidation of fatty acids in the cells and that leads to ketogenesis. It has an effect on Na retention and
on the increase of K excretion. It also stimulates the activity of osteoclasts(bone reabsorption) and it
inhibits the osteoblastic ability(bone formation and mineralization) and that can lead to
osteoporosis. It maintains the vascular tonus and increases the force of contraction of the heart by
increasing the response of smooth muscle cells to catecholamines.

Glucocorticoids are required for a normal response of vascular smooth muscles to vasoconstriction
action of noradrenaline and angiotensin II. It maintains plasma volume by increasing the movement
of fluid from interstitial space into the vessels. It inhibits the secretion of GH, ADH, TSH and the
conversion of T4 into T3. Cortisol also stimulates the secretion of hydrochloric acid(HCL) and pepsine
and it inhibits the synthesis of prostaglandins and that can lead to peptic ulcer.

The negative effects of cortisol surplus are: eosinophenia, basophenia, limfocitophenia, neutrophilia,
thrombocytosis and imunosupression. It can have an inhibitory effect on the morphology and
function of the nervous system. In adults the hyper secretion of glucocorticoid hormones can lead to:
emotional disturbances, EEG abnormalities and an increase of taste and olfactory sensitivities.

A major negative factor is stress because it leads to an increased amount of CRH(corticotropin

releasing hormone), which then leads to a abnormal amount of ACTH being released, which impacts
cortisol secretion, thus leading to vasoconstriction in skin and vasodilatation in muscles, because of
the improper distribution of blood flow the muscles suffer from a constant fight or flight reaction.
Glucocorticoids secretion rises during stress, fever, burns, bleeding, hypoglicemia, hypotension. In
conclusion cortisol is a life-protecting hormone because it helps withstand the stress and trauma.

Regulation of glucocorticoid secretion

The regulation is done by negative feedback mechanism(corticotropin releasing hormone leads to

ACTH being released, thus it results in large amounts of cortisol). The receptors for CRH are G
proteins that bind with cAMP and by that leading to exocytosis of ACTH. ATH also stimulates ACTH
secretion in stressful conditions and ACTH further stimulates all steps of synthesis of cortisol under a
few seconds. Chronic stimulation with ACTH can be caused by Cushing disease and chronic stress, in
these situations the weight of the adrenal glands increases with several folds. Glucocorticoid therapy
must be done gradually because patients that are treated with large doses of cortisol can suffer from
prolonged suppression of ACTH.
 Mineralocorticoids- functional roles, regulation of their secretion

Mineralocorticoids are aldosterone, deoxycorticosterone, corticosterone(zona glomerulosa).

Aldosterone binds with intracelular receptors, thus activating the trasncription of specific genes
related to the Na and K transport mediated by Na/K-ATP-ase.

The roles of aldosterone

It controls the blood volume by regulating the amount of Na is excreted, by that it regulates blood
pressure and it stimulates the reabsorption of Na+ in DT and CT together with the secretion of K+
and H+ ions. The secretion of H+ ions in exchange for K in the intercalated cells of the cortical
collecting tubules, by that it decreases the H+ concentration in the extracellular fluid, that leading to
alkalosis. The reabsorption of Na+ happens in the salivary glands, sweat glands and gastrointestinal
mucosa. Aldosterone enhances Na+ absorption by the intestine(colon), thus preventing the loss of
Na in the stool. In the absence of aldosterone, diarrhea may occur and that leads to loss of salt from
the body.

Aldosterone secretion stimulation

Angiotensin II reacts with the cell membrane of glomerulosa cells by binding with the AT1 receptors,
thus leading to the activation of PLC(phosphorylase C) and by that sending secondary messengers
diacylglycerol(DAG) and inositholtriphosphate(IP3), which further increase the secretion of
aldosterone. Increased calemia is caused by depolarization of cell membrane which causes Ca2+
channels to open thus activating the conversion of cholesterol into aldosterone. Aldosterone is also
stimulated by decreased natremia, decreased ECF volume and less by ACTH.

Male reproductive system- spermatogenesis

Testes have 2 functions: gamatogetic(spermatogenesis) and endoncrine(synthesis of androgens).

Spermatogenesis starts at puberty and it is a continuous process that takes place in seminiferous
tubules, that declines at old age. It has several stages: 1. Spermatogonia(46 chromosomes) that
divide mitotically at puberty and they become 2.primary spermatocytes(46 chromosomes), these
undergo the first meiotic division forming 3.secondary spermatocytes(23 two chromatid
chromosomes), then begins the second meiotic division which leads to 4.spermatids and finally to
5.spermatozoa .

Semen

The production o semen goes through the following anatomical structures: seminiferous tubules-
rete testes- vas deferens- epididimus.

In the epididymis spermatozoa are stored, they are not motile at head level, they move with the
tail(due to the activation of protein CatSper). From the epididymis spermatozoa pass into vas
deferens from there to prostate gland. The secretion of seminal vesicles(seminal fluid) happens
through the ampula of vas deferens, then the ejaculatory duct and before reaching the internal
urethra it also goes through the prostate. The seminal fluid is mucoid, viscous, slightly alkaline. The
seminal vesicles contribute to about 60% of the semen volume. It contains fructose, prostaglandins,
fibrinogen. The prostate secretion is milky and alkaline, rich in phosphates, and it contains citrate and
coagulation factors. The clotting enzymes turn fibrinogen into fibrin. Phosphates and citrates have
the role of neutralizing the acidic ph of vagina and assure the survival of sperm. The maturation of
spermatozoon takes 74 days. The volume of semen ejaculated once is of 2-5 ml. 1ML OF SEMEN HAS
100-150 MILLON SPERMATOZOA!!!!!!! When the number of spermatozoa is less than 20 million/ml is
called oligospermia, which means infertility. The semen volume is 5-10% spermatozoa, 60% seminal
vesicle secretion, 30% prostate secretion, 5% bulbo urethral secretion. 100 million spermatozoa are
produced daily.

Spermatozoon

It consists of 4 parts: head, neck, body and tail.

Head

The head has a nucleus and an acrosome, a protein filled vesicle containing several
enzymes(proteolytic enzymes, mucoplysacharides), it plays a role in the penetration of the egg.

Neck

It s made up of anterior and posterior and knobs.

Body

It has an axial filament covered by cytoplasmic capsule, the axial filament is the central core, the axial
filament is surrounded by the spiral filament made up of mitochondrias which provide the energy for
the movement.

Tail

It has 2 pieces: main piece of tail which has an axial thread and a terminal piece. The tail is a
flagellum which produces whip-like movements.

Sertoli cells(Italian)

Sertoli cells are tall and large and they have a supporting role. They also have receptors for FSH and
testosterone. Blood-testes barrier is formed by tight junctions between the adiacent Sertoli cells near
the basement membrane of the seminiferous tubules. The barrier impedes the penetration of
proteins and macromolecules from interstitial space into seminiferous tubules. If the blood-testes
barrier is damaged antibodies might attack the sperm, thus leading to infertility.

Leydig cells(Norway)

Leydig cells lie in the small connective tissue space between the seminiferous tubule. They do not
have FSH receptors. FSH stimulates the production of growth stimulators from Sertoli cells, thus
enhancing the growth of the Leydig cells. Growth factors from Sertoli cells increase the number of
speratogonia, spermatocytes, spermatis in the testes, thus increasing the fertility potential of sperm.
Androgens stimulate the proliferation of developing Leydig cells. Estrogen receptors are present on
Leydig cells, but estrogen reduces the proliferation and activity of these cells, Leydig cells also have
LH receptors and LH stimulates testosterone secretion. LEYDIG CELLS SECRETE TESTOSTERONE,
DEHYDROTESTOSTERONE AND ANDROSTENEDION!!!!!!! BETWEEN SERTOLI AND LEYDIG CELLS ARE
BIDIRECTIONAL INTERACTIONS.

Regulation of spermatogenesis

Spermatogenesis is regulated by several hormones: FHS, LH, testosterone, estrogen, GH, inhibin,
activin.
FSH plays a role in the initiation of spermatogenesis by inducing the proliferation of spermatogonia.
It stimulates the production of ABP(androgen binding protein) and plasminogen activator. It
increases the secretion of inhibin and it influences the conversion of androgens into estrogens.

Testosterone influences the growth, maturation and transformation of spermatogonia maintenance

of spermatogenesis(spermatogenesis requires high levels of testosterone).

Even though estrogen decreases testosterone levels in Sertoli cells it is necessary in the
transformation of spermatides into sperm together with testosterone. Estrogen in males arises from
secretion done by the testes in small amounts and from conversion of androgens into
estrogen(notiably in adipose tisuue).

LH is essential for the secretion of testosterone from Leydig cells.

GH is necessary for the metabolic processes in testes and for proliferation of spermatogonia, for
example in pituitary dwarves the spermatogenesis is severely affected.

Inhibin secreted by Sertoli cells and it inhibits FSH secretion by negative feedback mechanisms.

Activin is secreted by Sertoli and Leydig cells, it increases the secretion of FSH and speeds up
spermatogenesis.

Endocrine role of testes and testosterone secretion

Testes secrete male sex hormones(androgens) such as testosterone, dihydrotestosterone and

androstenedione. Testosterone is secreted by Leydig cells. Receptors for LH are coupled with G
protein(cAMP). LH stimulates steroidogenesis by phosphorylation of cholesterol esterase which
releases cholesterol from its intracellular storages(1) and activation of cholesterol side chain cleavage
enzyme(2). Leydig cells have receptors for prolactin and estrogen, estrogen reduces the proliferation
and activity of these cells. Hyperprolactinemia in men leads to a decreased testosterone level and
decreased LH secretion.

Testosterone has intracellular receptors. The normal plasma concentration of testosterone in men is
3-10-ng/ml, in females it s less than 1 ng/ml.

Transport-wise 97% of the testosterone is bound with albumin and with beta-globulin called sex
hormone binding globulin(SHBG), 3% is free.

In many target tissues(prostate, scrotum, penis) testosterone takes up the form of

dihydrotestosterone which is the most active androgen. In adipose tissue, liver, CNS testosterone
takes up the form of estradiol(by aromatization). T is metabolised in liver and kidney from where it s
excreted either into the intestine by the bile or into urine.

Regulation of testosterone secretion and functional roles

Hypothalamic neurons produce gonadotropin releasing hormone(GnRH) which stimulates the

production of LH and FSH.(the release of GnRH is pulsatile) GnrH ends up in the hypothalamic-
pituitary portal system and binds to the receptors on gonadotrops, thus stimulating FSH and LH
secretion into the blood. LH and FSH are also released into a pulsatile fashion. Sertoli cells regulate
the production of estradiol. Activin stimulates the secretion of FSH. Estradiol has an inhibitory effect
on GnRH secretion.
Roles of testosterone in adult life

Testosterone is required to initiate spermatogenesis, it decreases GnRH via an action on the

hypothalamus, it inhibits LH secretion, induces diferenciation of male accessory reproductive organs
and maintains their function, induces secondary male sex characteristics, stimulates protein
anabolism required for sex drive.

Gametogenetic functions of the ovary

The female reproductive system has 2 funcitons: gametogenesis(oogenesis) and endocrine

function(synthesis of estrogen and progesterone). In the intrauterine life the cortex of ovary is made
up of germinal epithelium, this epithelium contains the primordial ova. The ovum is surrounded by a
layer of spindle cells from the ovarian stroma named granulosa cells. The primordial ovum along with
granulosa cells forms the primordial follicle. At the 7-8th month of pregnancy, 6 million primordial
follicles are found in ovaries. At the moment of birth there are only 1-2 million primordial follicles
left. At the puberty only 300-400 thousand primordial follicles remain active but only 400 are
destined to ovulate and all the others degenerate. The degeneration of follicles is called atresia and
the degenerated follicle is known as atretic follicle. During early uterine development oogonia goes
through mitotic division and around the 3rd month of conception the oogonia is divided into oocites.
Oogonia contains primary oocites which then begin the first meiotic division. All the eggs present at
birth are primary oocites, containing 46 chromosomes, each with 2 chromatides. Only those primary
oocites destined for ovulation will complete the first meiotic division. During this division each
daughter cell receives 33 chromosomes, 1 of the daughter retains virtually all the cytoplasm(the
ovum) and the other cell(first polar body) is very small and non functional. The second meiotic
division occurs in uterine tube after ovulation but only if the second oocite is fertilized, thus each
daughter cell receives 33 chromosomes, each with a single chromatid. The net result of oogenesis is
that from each primary oocite results only one ovum. In the ovaries, the eggs exist in structures
known as follicles. Follicles begin as primordial follicles which consist of one primary oocite
surrounded by a single layer of cells(granulosa cells). The next step in development from the
primordial follicle is increasing in size of the oocite proliferation of the granulosa cell into multiple
layers and the separation of the oocite from the inner granulosa cells by a thick layer of
material(zona pellucida).

Menstrual cycle

After puberty, the female reproductive system is subjected to clinical changes, meaning a period of
preparation for fertilization and pregnancy, called menstrual cycle. The duration of the cycle is 20-40
days, average duration being 28 days. The most conspicuous of these changes is the vaginal
bleeding(menstruation), the first day of menstrual cycle. At the beginning of each menstrual cycle, 6-
12 of preantral and early antral follicles develop into larger antral follicles, one of them becoming the
dominant follicle. At the time of ovulation, the egg emerges from meiotic arrest and completes it s
first meiotic division, turning into secondary oocite. The graafian follicle becomes very large and it
succumbs to ovulation. Ovulation occurs on approximately day 14 of menstrual cycle. After the
graafian follicle discharges its antral fluid and egg, it becomes corpus luteum, which secretes
estrogen, progesterone and inhibin. If the discharged egg is not fertilized, the corpus luteum
degenerates by apoptosis. The ovarian cycle may be divided in 2 phases: the follicular phase, during
which a single mature follicle and secondary oocite develop and the luteal phase that begins after
ovulation and lasts until the demise of corpus luteum.

Estrogen-functional roles

The estrogen promotes tissue growth in the genital organs. On the ovarian follicle stimulates the
proliferation of the follicular cells and increases the secretary activity of theca cells. On uterus, it
stimulates the proliferation of endometrial cells,increasing the size of uterus twice comparative to its
childhood size. Proliferation and dilatation of blood vessels and glands on endometrium cause the
blood vessels to become more tortuous(coiling). It increases blood supply and the contractility of
miometrum due to the sensitivity to oxytocin.

The secretion of cervix mucus is alkaline, abandoned and thin under the action of estrogen.

On the vagina it changes the cuboidal epithelium(before puberty) to a stratified type(after puberty)
which is more resistant to infection and traumatisms. The ph of vagina is 3,5-4,5.

It has an effect on secondary sexual characteristics such as the distribution of hair in the pubic region
and axila.

The skin becomes softer and smoother with increased vascularisation. The secretion of sebaceous
glands becomes less viscous and it reduces the tendency to acne.

The way the fats are distributed create the characteristic shape of a females body(proeminent
breasts and buttocks), the shoulders become narrow, hips broadens, the tighs converge and the arms
diverge. The pelvis becomes round shaped.

In bones the activity of osteoblasts is stimulated, estrogen increases the growth rate but also an early
closure of the epiphysial plates. After menopause the lack of estrogen may lead to osteoporosis, thus
creating a higher chance for fractures.

The effects of estrogen on metabolism are the following: Na and water retention by the renal
tubules, anabolic effect on the protein metabolism, antagonizing effect on the action of insulin and it
helps deposit fats in the subcutaneous tissue, buttocks, breasts and tighs. It decreases the level of
cholesterol in blood.

Progesteron-functional roles

On ovi ducts it stimulates the secretory activity of the mucosa that is lining the tubes.

In the uterus it increases the number and size of the endometrium cells. It also increases the size of
the uterine glands and their secretion. It has a stimulating effect on fat and glycogen in the stromal
cells of endometrium, thus helping these elements with their deposition. It increases the blood
supply by making blood vessels larger and dilatation(baso-dilatation).

In the cervix it promotes a reduced mucous secretion.

On the lining of the vagina it makes the vaginal epithelium thicker and infiltrated with white blood
cells, the mucous secretion is also thicker.

In the mammary glands it stimulates the development of lobules and alveoli, and also the secretory
activity of this gland.

Progesterone also has an overall influence on the way body temperature changes since in time of
ovulation body temperature raises with about 0.5 degrees Celsius, it also stimulates the respiratory
center and electrolyte balance.

Regulation of menstrual cycle

The menstrual cycle is regulated by hypothalamo-pituitary-ovarian axis. Hypothalamus releases

GnRH every 2 hours, thus leading to the production of FSH and LH. Epinephrine and norepinephrine
stimulate the secretion of GnRH, dopamine and serotonine inhibits the secretion of GnRH. The
hypothalamus is affected by the plasma levels of sex hormones by negative feedback mechanisms.

FSH has an effect on the recruitment and development of immature follicles. It also increases the
activity of aromatase from granulose cells. FSH stimulates lutein cells to secrete inhibin which inhibits
FSH secretion, it also maintains the secretory activity of corpus luteum.

LH has an effect on ovulation and sustains corpus luteum, it helps with the synthesis of androgens
from theca cells of follicle. LH stimulates the secretion of progesterone.

After ovulation LH transforms granulosa cells into lutein cells, thus promoting the production of
estrogen and progesterone. The secretion of LH is reduced during the follicular phase.

Estrogen exercises a double feedback control on GnRH: 1. Estrogen in low plasma concentration
inhibits GnRH secretion and decreases FSH and LH secretion(negative feedback). 2. Estrogen in high
plasma concentration stimulates the secretion of GnRH, thus leading to a high secretion of FSH and
LH(positive feedback). Estrogen increases the number of receptors for FSH and LH on granulosa cells.

NERVOUS SYSTEM

Somatic sensitivity

Somesthesia means the consciuous sensitivity from skin, muscles and joints. Unconsciuous sensitivity
is transmitted through spino-cerebelar pathways. Visceral sensitivity is transmitted through all the
afferent pathways that come from the internal organs. Sensorial sensitivity comes from the sense
organs.

Somesthesia includes touch sensitivity, pain sensitivity, temperature sensitivity and

proprioceptive(conscious) signals. The receptors for somatic sensitivity are located in skin, muscles,
joints and ligaments.
From pilogenetic point of view somesthesia is divided in 2 types: 1.the older type, protopathic
sensitivity(pain, temperature and crude touch signlas). 2.The newer type, epicritic sensitivity, which
conducts the fine touch signals and the profound signals from muscles and joints(proprioception).

Proprioceptive sensitivity

Proprioceptors can be found in joints, muscles, tendons, ligaments(deep structures in general), they
provide information about the position of the body/limbs, force and speed of muscle contraction,
the feedback from these receptors is necessary for the control of movements. They give a conscious
picture of the position of the body.

In skeletal muscles the proprioreceptors are: muscle spindles(MS), golgi tenton organs(GTO), free
nerve endings and Pacinian corpuscles.

In joints we have: Ruffini endings(joint angle), Pacini endings, free nerve endings. The joint capsule
contains free nerve endings.

In ligaments there s golgi endings(joint torque).

Proprioceptive sense has 2 subtypes: 1.Static position sense, which refers to a conscious perception
of the orientation of the different parts of the body regarding one another. 2.Rate of movement
sense(kinesthesia or dynamic proprioception). The Pacinian corpuscles and muscle spindles are
especially adapted for detecting rapid rates of change so they can provide the feedback that is
necessary for the control of movements.

Epicritic sensitivity-dorsal column-lemniscla pathway

Signals from touch and proprioceptors go through the dorsal column-lemniscal pathway formed by 3
neurons.

The primary order neuron comes from posterior root ganglia, it has a long axon, which enters the
spinal cord and ascends through the posterior white column(Goll/Gracilis and Burdach/Cuneatus
tracts), myelinated fibers. Fasciculus gracilis consists of fibers from the lower extremities and lower
parts of the body(sacral, lumbar and lower thoracic ganglia). Fasciculus cuneatus consists of fibers
from the upper part of the body(upper thoracic and cervical ganglia of posterior nerve root).

The secondary order neuron goes through medulla oblongata then nucleus gracilis and cuneatus and
after it passes the sensory decussation it forms the medial lemniscus that ascends to ventral postero-
lateral nucleus of thalamus, where the third neuron is located. The axon of the third neuron is
projected in the post-central gyrus.

Fine touch sensitivity

Fine touch sensitivity is transmitted through Goll and burdach tracts. The touch receptors in the
hairless skin are:free nerve endings, found everywhere in the skin and other tissues being slow
adapting and they detect touch and pressure; Meissner corpuscles are elongated, found in fingertips
and lips, they are fast adapting receptors and they detect movement of objects over the surface of
skin and low frequency vibrations; Merkel discs are slow adapting receptors located under the
epidermis, they detect continuous touch of objects against the skin pressure; Pacinian corpuscles are
very fast adapting receptors located in deep dermis, they sense pressure and vibrations and
determine the position of joints; Ruffini and organs are located in dermis, they adapt very slow and
detect continuous states of deformations of skin. In the hairy skins there are the following receptors:
free nerve endings, Iggo dome receptors, Merkel discs, Ruffini endings, Pacinian corpuscles and hair
and organs which are fast adapting receptors that detect movement of objects on the surface of
skins or initial contact with the body.

Crude touch sensitivity

Protopatic sensitivity represents the crude touch sensitivity, pressure sensation, pain and
temperature sensation, itch tickle sensations and sexual sensations. It is transmitted to cerebral
cortex by spino-thalamic tracts(ant and lat). Anterior spino-thalamic tract transmits crude touch
pressure, itch and tickle sensation. The first neuron is located in the posterior nerve root ganglia. The
impulses come from the free nerve endings; it has a short axon that goes to the posterior horn of
spinal cord. The axon of the secondary order neuron crosses the midline in the white commissure
and forms the anterior spinotalamic tract, goes to the anterior white column of the opposite side and
the fibres ascend through other segments off spinal cord and brain stem and reach thalamus. The
third order neuron is located in the ventral-postero-lateral nucleus of thalamus and its axon goes to
the postcentral gyrus in the sensory cortex. Lateral spino-thalamic tract transmits pain and
temperature sensations. The first neuron is located in the posterios nerve root ganglia. Its axon
makes sinapses with the second order neuron that is located in the marginal nucleus and substantia
gelatinosa of Rolando. Axons from these structures cross to the opposite sides and reach the lateral
column of the same segment, then they go to the brain stem. The third order neuron is located in the
ventral postero-lateral nucleus of thalamus and its axon reaches the somatosensitve cortex. Some of
the fibres emit collaterals to the reticular formation of the brainstem and impulses that participate to
the awakeness state of the cortex and maintain muscle tone. Fibres that convey the pain sensation
are located superficially and fibres for the temperature signlas are located deeper.

Pain-receptors, stimulation of pain receptors

Pain receptors are called algo-receptors or noci-receptors and are represented by the free nerve
endings that are spread in most tissues except viscera and they do not adapt or they adapt very little.
In deeper structures, pain receptors are found in capsules or vessels. The number of pain receptors
in skin is 10 times higher than that of touch receptors. The benefits are: giving warning signals about
the existence of a problem, preventing further damage of tissues by causing the reflex of withdrawal
of the body, making the person reduce the activity or to take the required treatment. Factors that
stimulate pain receptors are external or exogenous that can be divided in physical(thermical,
electrical, mechanical) and chemical(basic, acid substances, hypotonic hypertonic solutions). The
endogenous internal stimuli are chemical( HCL in peptic ulcers). Chemical substances that can
stimulate pain receptors are: bradichinin, histamine, acids, serotonin, K, proteases, prostaglandins,
substance P.

Cutaneus pain. Itching

After stimulation of the skin by painful stimulus, pain appears in 2 variants. Fast pain is sharp, well
localized, persists when the stimulus is on the skin, felt within 0.1 seconds after the stimulus is
applied. The tract is formed from 3 neurons: first neuron is located in the ganglion on the posterior
root of spinal nerve, second neuron is located in the marginal nucleus of the posterior horn of the
spinal cord, third neuron is located in the ventral postero-lateral nucleus of thalamus. Slow pain
appears after a latency of 0.5-1 s, it is diffused and unpleasant and produced by protheasis, released
from the destroyed tissues. The first neuron is located in the ganglion of the posterior root of the
spinal nerve. The second neuron is located in the substantia gelationsa of Rolando from the posterior
horn of spinal cord. And the third neuron is located in the ventral postero-lateral nucleus of
thalamus. Pain is transmitted through the lateral spino-thalamic tract: 75-90% of fibres are
unmielnated(paleo-spino-thalamic pathway) and 10-25% are mieliniated fibres(neo-spino-thalamic
pathway).

Deep pain

Deep pain is felt by the stimulation of pain pain receptors from muscles, joints, ligaments,
periosteum. This type of pain is not very well localised, it sometimes associates with BP
variations(hypotension) and contractions of the muscles around the stimulated area. The damage of
bones, joints and tendons is associated with a reflex of muscle spasms.

Contraction of the muscles stimulates mechanically pain receptors and compresses the vessels thus
leading to ischemia and metabolities that accumulate locally ( e.g. P-substance, bradykinin) and they
lead to pain.

When the muscles relax the blood washes away the metabolities and the pain disappears.

Visceral Pain

The viscera has no pain receptors. Pain receptors are present only in the capsule or serosa of organs,
e.g. peritoneum, pleura, pericardium etc.

Visceral pain is not well localised(its diffused) and may be associated with 1.autonomic
reactions( nausea, hypotension) 2. Muscle spasms and 3.Radiated pain(referred pain)

Causes of visceral pain.

1.ischemia: the decrease of blood supply to an organ that leads to an accumulation of subsances
locally( lactic acid,bradykinin, enzymes) that stimulate pain receptors of viscera.

2.spasm of hollow organs: spastic contraction of smooth muscles from the wall of different hollow
organs(digestive tract, urinary pathwys) cause pain by mechanical stimulation of pain receptors

3.overdistention of hollow organs: strectching of hollow viscera is painful because overstretching

compresses the vessels and induces ischemia

4. chemical stimuli: gastric juice or other digestive juices that may leak from the digestive tract into
the peritoneal cavity and stimulate pain receptors.

Thermic sensitivity

The skin has cold, warmth and pain receptors. Thermo receptors have nerve endings connected with
myelinated and unmyelinated fibres.

Cold receptors(Krauses and Bulb) are connected with A delta fibres and C fibres. The 1 st neuron is in
the ganglia in posterior root on the spinal nerve and forms sinapses with the 2 nd order neuron in the
dorsal horn of spinal cord.
Warmth receptors(Ruffini and Bulb) are connected with C fibres. Thermic sensitivity goes through the
lateral spino-thalamic tract – 20-40 degrees Celsius. Warmth receptors are stimulated. 10-35 degrees
Celsius the cold receptors are stimulated. At temperatures above and below these the receptors do
not adapt. Cold pain is induced by: something cold swallowed quickly, peripheral neuropathy and
chemotherapy. Very high skin temperatures lead to paradoxical cold, caused by activavtion of a part
of the cold receptor population.

Thalamus-fucntions and disorders

Thalamus is a mass of grey matter, placed bilaterally in the encephalum and its made up of several
nuclei. It receives afferent signals from parietal and occipital lobes, hypothalasmus, reticular
formation, auditory and optic tract, globus pallidus, red nuclei, cerebellum and lateral and medial
lemniscus. In addition thalamus sends efferents to parietal and occipital lobes, prefrontal cortex,
hypothalamus, auditory and visual cortex, limbic cortex and basal ganglia. The thalamus sends
signals to cerebral cortex, which receives signals from thalamic radiation and they contain both
thalamocortical and cortico-thalamic fibres. Thalamic radiations are divided into 4 groups: anterior,
superior, posterior and inferior.

Functions of Thalamus

1.Relay centers for sensations

It represents the major center for processing the sensory information. The relay nuclei are 1.the
ventral postero-lateral nucleus, from medial lemniscus and spino-thalamic tratcs, 2. The ventro-
medial nuclei(taste and smell), 3.Geniculate bodies(visual and hearing information).

Spino-thalamic system is in connection with right and left thalamus. Medial lemniscal system is in
connection with contra-lateral thalamus.

All the peripheral sensory information reaching thalamus are selected, integrated and modified
before being sent to specific areas of cerebral cortex.

2.Relay for effector/motor reactions

The ventro-lateral nucleus receives information from cerebellum, the ventro-anterior and ventro-
lateral nuclei from basal ganglia, the anterior nuclei of thalamus from the mamillary bodies of
hypothalamus, the anterior nuclei are in connection with the limbic system(mamilo-thalamo-limbic
circuit, which is involved with memory and emotions).

3.Thalamus participates in the association reactions

3 thalamic nuclei are involved: the pulvinar(parietal and temporal cortex), postero-lateral
nucleus(parietal cortex), dorso-median nucleus(frontal cortex). The association regions play a role in
language.

4.Thalamus modulates cerebral cortex activity

The signals from thalamus maintain the cortex awake, and influence the electrical activity in the
brain.

Disturbances of thalamus

Thalamic lesions can form from thrombosis in the thalamo-geniculate artery(branch of posterior
cerebral artery.) In this case the postero-ventral nuclei are affected.
THALAMIC SYNDORME involves contra-lateral anasthesia, astereognosia(the ability to recognise an
object by touch with closed eyes), ataxia(incoordination of complex voluntary movements). It can
also cause involuntary movements: athetosis, chorea, intention tremor, thalamic hand(moderate
flexion at wrist and hyperextension of fingers), hyperalgesia(painful stimuli).

Somatosensitive cortex

Somatosensory cortex is placed at the level of parietal lobe(post central gyrus). Parietal lobe is
divided into three functional areas: 1.Somatosensory area 1(S1), 2.Somatosensry area 2(S2),
3.Somatosensry association area(SAA).

S1 is located in the anterior part of post central gyrus(Broddmans area 3, 1, 2) it is also called primary
somestetic area. Neurons of S1 send their axons to S2, adiacent areas of the parietal lobe, cortical
motor areas, brainstem, spinal cord.

S2 is located posterior and inferior to S1 and forms the superior wall of the fissure of Sylvius.

SAA is situated posteriorly to post central gyrus, above the auditory cortex and in front of visual
cortex(area 5 and 7 of Broddmans).

The projection from in S1 have some characteristics: 1.The projection of different parts of the body is
upside down(the face is at the bottom, the foot is in the upper part of parietal cortex), the mapping
of sensitive homunculus, WHICH IS A MAP OF YOUR BODY IN YOUR BRAIN. Each lateral side of the
cortex receives sensory information from the opposite side of the body. 2.The cortical areas do not
correspond with the body surface(the lips, face, thumb, the larynx are very well represented, but the
trunk and lower segments are represented by small areas). The size of areas in the cortex are
directly proportional to the density of receptors in each respective peripheral area of the body. 3.S1
has a high degree of localization of different parts of the body. 4.Cortical projections of somestetic
sensitivity have plasticity.

Functions of S1

S1 plays a role in perception and integration of cutaneus and kinestetic sensations, receives sensory
signals from cutaneus receptors(touch, pressure, vibration, pain, temperature) and proprioreceptors
from the opposite side of the body, recognition of discriminative features of sensations(spatial
recognition, recognition of intensity of stimuli).

Functions of S2

S2 has a smaller surface than S1 and the projection is more symmetrical(the size of body segments is
proportional with their projection in the cortex). The neurons in S2 are stimulated by moving of an
object on the skin.

Lesions in S2 cause deficits in learning by object manipulation and in recognizing the texture and size
of hand-held objects, thus touch discrimination is lost so a person can not learn by touching. S1 and
S2 are connected, signlas are first processed in S1 and then in S2.

SAA plays a role in the synthesis of various sensations perceived by S1 and deciphering their deeper
meanings. SAA is located in the superior parietal lobe, which is posterior to S1.
SAA is the center of stereognosis. The neurons in SAA are responsive to somatosensory and visual
stimuli, they have large somatic receptive fields in which responsiveness is based on the context of
the stimulus.

When SAA is removed on one side of the brain it leads to astereognosis, amorphosynthesis(the
person recognizes only one side of the object).

Cortical control of movements

The execution, planning, coordination and adjustments of the movements of the body is under the
control of different parts of the nervous system(somato-motor system). The coordination and the
control of movements is dependant on 2 factors: 1.Feedback signals from the proprioreceptors,
2.Interaction between different parts of nervous system. The cortical areas concerned with the origin
of motor signals are: 1.Primary motor area, 2.Premotor area, 3.Supplementary motor area, 4.Sensory
area.

Somatomotor cortex

Functions of primary motor cortex(MI) are: encoding the capability to control mucle force, muscle
length, joint movement and position; it is concerned with initiation of voluntary movements and
speech; activates the lower motor neuron in the anterior horn of spinal cord through the cortico-
spinal tracts; MI does not generally control individual muscles correctly.

Alfa motor neurons in the spinal cord encode the force of contraction of individual muscles and
groups of muscle fibres. Unilateral lesions of area 4 leads to paralysis in the contralateral side of the
body, area 4S is named supressor area, it is placed anterior to area 4(it has the role to supress the
extra impulses produced by area 4).

MI exerts its influence over muscles by a varitety of descending routes: the cortico-rubral tract allows
the cortex to modulate the rubro-spinal tract. The cortico-tectal tract allows cortex to modulate the
tecto-spinal tract. The cortico-reticular tract allows the cortex to modulate the reticulo-spinal tracts.
The cortico-striated tract allows the cortex to modulate caudate nucleus and putamen.

Premotor cortex

The premotor cortex is placed anterior to the MI, extending inferiorly into the Sylvian fissure and
superiorly into the longitudinal fissure. It includes 4 areas: 6, 8, 44, 45.

The most anterior part of the premotor area first develops a motor image of the total muscle
movement that is to be performed. In the posterior premotor cortex this image excites each
successive pattern of muscle activity required to achieve the image. They go through the basal
ganglia and thalamus and then back to the primary motor cortex.

The premotor area is concerned with control of postural movements by sending motor signals to the
axial muscles, the premotor cortex appears to be involved in the selection of appropriate motor
plans for voluntary movements, but MI is involved in the execution of these voluntary movements.

Area 6 gives origin to some of the pyramidal tract fibres, its functions are coordination of
movements, initiated by area 4, it is also the cortical center of extrapyramidal system.

In case of lesions of area 6 there s a loss of skilled movements(apraxia).

Area 8 is situated anteriorly to area 6, it is concerned with conjugate movements of eyeballs and
control of eyelids(blinking).

Lesions of area 8 lead to loss of voluntary movements of the eyes.

Area 44 and 45(Broca s area)

It is the motor area for speech, it is situated in the left hemisphere(dominant hemisphere for right
handed people). Broca’s area is found in inferior frontal gyrus, in pars triangularis(area 44) and pars
opercularis(area 45). Broca’s area helps the movements off tongue, lips, larynx.

Lesions of Broca’s area lead to aphasia(loss/defect of language).

Role of gamma motor neurons

The roles of gamma motor neurons are to maintain muscle tone, it is maintained continuously and
regulated by supraspinal centers located in different parts of the brain. Some of these centers
increase the muscle tone by sending facilitatory impulses while other centers decrease the muscle
tone by inhibitory impulses.

SUPRASPINAL FACILITATORY CENTERS THAT INCREASE MUSCLE TONE ARE: area 4 of motor cortex,
cerebellum, red nucleus and vestibular nucleus.

SUPRASPINAL INHIBITORY CENTERS THAT DECREASE MUSCLE TONE ARE: suppressor areas of
cerebral cortex, basal ganglia and descending inhibitory reticular system.

Muscle spindle

Motor inervation of muscle spindle(MS)

It is the only receptor having a motor innervation. Motor supply is done by A-gamma type fibres
located on the ends of the spindle.

There are 2 types of motor fibres: 1.Gamma 1 fibres that innervate the nuclear backfibres, thus the
neuromuscular motor end plates, functionally it is knows as the dynamic gamma efferent nerve fibre,
it has a very fast reaction. 2.Gamma 2 fibres primarily on nuclear chain fibres, but also on the nuclear
back fibres. Their stimulation is very slow, functionally it is know as the static gamma efferent nerve
fibres. On the gamma motor neurons from spinal cord act 3 systems: cortico-spinal, vestibulo-spinal
and reticulo-spinal.

The functions of muscle spindle

The passive stretching of MS or the active contraction of the ends of intrafusal fibres leads to the
stretching of the central area of intrafusal fibres, thus leading to the stimulation of the annulo-spiral
and Flower spray endings.

There are 2 mechanisms that control the contraction of the skeletal muscle: 1.Impulses from the
spinal alfa motor neurons(unlimited contractions with maximum magnitude), 2.Gamma motor
neurons indirectly initiate the contraction, thus shortening the ends of intrafusal fibres and by that
stimulating the annulo-spiral receptors then the alfa motor neurons in the anterior horn of the spinal
cord and finally leading to the contraction of the skeletal muscle.

The dynamic stretch reflex is a monosynaptic reflex with a short latency. Muscle spindle gives
response to change in the length of a muscle, it detects how much the muscle is strectched and
sends information to central nervous system for the determination of the position of different parts
of the body. Muscle spindle plays an important role in preventing the overstretching of the muscle
and maintaining muscle tone.

Impulses from the Annulospiral receptors thick nerve fibers (Aα) alpha motor N from anterior horn of
spinal cord. In clinic, the dynamic component of the stretch reflexes is tested by tapping tendon of
the muscle with a reflex hammer. The static stretch reflex due to Flower-spray receptors keeps the
muscle contraction all the period when the muscle is excessively stretched.

Golgi tendon organ

The Golgi tendon organ (GTO) is a small encapsulated receptor, located in the tendons, at the site
where each tendon unites with the muscle fibers. GTO consists of a netlike collection of knobby
nerve endings. About 20 -25 muscle fibers are usually connected to a GTO. GTO is stimulated when
this small bundle of muscle fibers is tensed by contracting or stretching the muscle. GTO detects
muscle tension as reflected by the tension in itself.

GTO receptors for the inverse stretch reflex and the lengthening reaction prevents damage of muscle
due to overstretching. GTO is stimulated both by passive stretch of muscle and active contraction of
muscles. GOT provides the nervous system with instantaneous information on the degree of tension
or force in each small segment of each muscle. Signals from the GTO go to (A alpha) nerve fibers
and then spinal cord and finally cerebellum by spinocerebellar tracts.

When GTO is stimulated by increased tension in the connecting muscle the impulse goes through the
spinal cord then the inhibition of muscle leads to the relaxation of muscle. Those fibers that exert
excess tension become inhibited by the reflex, whereas those that exert too little tension become
more excited because of absence of reflex inhibition it spreads the muscle load over all the fibers
and prevents damage in isolated areas of a muscle where small number of fibers might be
overloaded. The impulses from GTO stimulate the inhibitory interneuron inhibits the alpha motor
neuron. The force generated by the own contraction of the muscles is the stimulus for the own
relaxation. In patients with hypertonic/spastic paralysis due to injuries of central motor neurons, the
passive flexion of the elbow meets immediate resistance. Further flexion is followed by a sudden
decrease in resistance and flexion is possible = Clasp Knife effect - due to the intervention of GTO
which are stimulated only by a certain level of tension inhibit the α-motor neuron which is
responsible for the spastic muscle contraction. Clonus = repetitive contraction and relaxation of a
muscle in an oscillating fashion every second, in response to a single stimulus. Ankle clonus -
initiated by fast dorsiflexion of foot  rhythmic plantar flexion of ankle, due to repetitive successive
contractions which are produced without the discharge of GTOs. The spindles of the tested muscle
are hyperactive and the bursts of impulses from spindles discharge all the motor N suplying the
muscle at once. As soon as the muscle relaxes  it is again stretched spindle is stimulated

The Inverse Myotatic Reflex is the active contraction of a muscle that leads to reflex inhibition of the
contraction.

Active muscle contraction stimulates GTO and type Ib afferent axons and finally inhibitory intern
that influence homonymous and heteronymous motor neurons and on excitatory interneurons that
influence motor neurons of antagonists. The function of the inverse myotatic reflex is a tension
feedback system that can adjust the strength of contraction during sustained activity. Reciprocal
inhibition acts primarily on the antagonist, while the inverse myotatic reflex acts on the agonist. The
inverse myotatic reflex, like the myotatic reflex, has a more potent influence on the extensor muscles
than on the flexor muscles, suggesting that the two reflexes act together to maintain optimal
responses in the antigravity muscles during postural adjustments.

STRETCH/MYOTHATIC REFLEX

Stretch reflexes/myotatic reflexes are proprioceptive reflexes caused by stretching of skeletal

muscles. Stretching of the muscle leads to contraction of the muscle being stretched.

The receptor (R) of reflex is the muscle spindle

Proprioceptors are the muscle spindle, Golgi tendon organ, Ruffini-type organ, Golgi tendon-like
organ, Pacini-type endings, free nerve endings provide information about : muscle lenght, speed of
muscle contraction, muscle tension, joint movement, joint angle, joint position.

Conscious proprioception means conscious body position, body movement (transmitted through the
dorsal column system).

Unconscious proprioception are transmitted through the spinocerebellar tracts cerebellum; the
information is not consciously processed. It is used for regulation of muscle tone and posture .

Skeletal muscles have muscle spindles, Golgi tendon organs, free nerve endings, Pacinian corpuscles

Joints have Ruffini endings and Pacinian corpuscles

int capsules contain free nerve endings

Ligaments have contain Golgi tendon-like organs

Information from proprioreceptors is feedback necessary for the control of movements.

The Inverse Myotatic Reflex

The Inverse Myotatic Reflex Involves Sensors of Muscle Force in the Tendon. Stretch receptors called
Golgi tendon organs are found within the collagen fibers of tendons and within joint capsules. They
are generally located in series with the muscle rather than the parallel arrangement of the intrafusal
muscle fibers.

Mechanism of the Inverse Myotatic Reflex:

The inverse myotatic reflex involves the reciprocal activation of muscle groups and relies on sensory
receptors called Golgi tendon organs (GTOs). These specialized receptors are located within the
tendons near the muscle-tendon junctions. When a muscle is stretched, the GTOs are activated and
transmit signals to the spinal cord.

The afferent fibers of the GTOs synapse with inhibitory interneurons in the spinal cord. These
interneurons, in turn, inhibit the motor neurons that innervate the same muscle experiencing
tension. As a result, the muscle relaxes and prevents further stretching or potential damage. This
process occurs almost instantaneously, ensuring quick response and protection.
The inverse myotatic reflex is vital for maintaining balance and coordination during various physical
activities. It prevents muscles from being overstretched, which could lead to strains or tears. For
example, during weightlifting exercises, when excessive load is applied to a muscle, the reflex is
triggered to prevent overextension and potential muscle damage.

Sympato-adrenal system

ADRENERGIC RECEPTORS

Adrenergic receptors are ligand gated, G protein-linked type, on the cell membrane of target cells

alpha R and beta R consist of alpha-1 and alpha-2 R; beta-1, beta-2 and beta-3 R

Norepinephrine stimulates mainly alpha R, but excites the beta R to a lesser extent as well.
Epinephrine stimulates both types of R approximately equally. Effects of norepinephrine and
epinephrine on different effector organs are linked types of R in the organs

alpha 1 R activates phospholipase C increases the intracellular concentration of DAG and IP3 and
further of Ca2+ . alpha 2 R inhibits adenylyl cyclase beta R stimulates adenylyl cyclase and increases
cAMP. Beta R are blocked by Propranolol

Alpha- 1 R - smooth muscle of blood vessels, eye, uterus, digestive tract, pilomotor muscle, salivary
glands. Norepinephrine reacts with these R the smooth muscles contract vasoconstriction and
reduction of blood flow. Alpha- 2 R - presynaptic and postsynaptic R. Are found in smooth muscles,
CNS, coronary arteries, skin, salivary glands, veins. Beta- 1 R - skeletal muscles increase the
metabolic activity. In the heart increase the rate and force of contraction of myocardium. Beta 1 R -
also found in digestive tract, adipose tissue, atria, ventricles, AV node, Purkinje fibers. Beta- 2 R -
smooth muscle of the bronchi, blood vessels, intestine, uterus, bladder, heart. Beta- 3 R - adipose
tissue, gall bladder, urinary bladder. They are involved in the regulation of lipolysis and
thermogenesis

EFFECTS OF STIMULATION OF SNS

Adrenaline : - cardiac stimulation (acting on beta 1 R) lowers Noradrenaline thus leading to

vasodilation in striated muscles and liver (by beta 2 R) increases BP by increasing CO

Noradrenaline:

- increases the total peripheral resistance, due to vasoconstriction (mediated by alpha 1 R) increases
myocardium excitability tachyarrhytmias - increase oxidation reactions increases the BMR -
glycogenolysis in the liver and muscles - increases mobilization of FFA from adipose tissue -
increases glycemia – bronchodilation

When SNS begins the fight-or-flight response all resources are mobilized:

- HR and BP increase - blood flow to the skeletal muscles, heart, and brain increase - the liver
releases glucose (glycogenolysis) - dilation of pupils (mydriasis) - the activity of the GIT and blood
flow to the skin – decrease

ADRENAL MEDULLA
The adrenal medulla - is a sympathetic ganglion. It receives preganglionic sympathetic fibers (from
lesser splanchnic nerve) originating in the lower thoracic spinal cord (T12). The cells of the adrenal
medulla are postganglionic N that have lost their axons; neurotransmitters are secreted directly into
the bloodstream ( adrenaline (epinephrine) and noradrenaline (norepinephrine)).

The organs are stimulated in two ways: : 1) directly - by the sympathetic nerves 2) indirectly - by the
adrenal medullary hormones The hormones secreted by adrenal medulla are not removed very fast
thus the blood and most tissue have relatively low concentration of the enzymes necessary for their
inactivation.

PARASYMPATHETIC NERVOUS SYSTEM

The preganglionic fibers arise from the cranial and sacral parts of the nervous system, its called
craniosacral outflow.

The parasympathetic division is distributed to : - head (cranial component) , oculomotor (III), facial
(VII), and glossopharyngeal (IX) cranial nerves. - thorax and upper abdomen vagus (X) - pelvic organs
pelvic branches of sacral spinal nerves S2-S4 The preganglionic fibers from the cranial and sacral
region synapse with postganglionic N, located close to or in the target organs that they supply. A
presynaptic parasympathetic N synapses with 15 to 20 postsynaptic N. The lacrimal muscle (tear
gland), ciliary muscle (for accommodation for near vision) and the sublingual salivary gland are
innervated exclusively by parasympathetic nerves

Withdrawal reflex
Is a nociceptive reflex and it occurs in response to noxious stimuli. It is a
polisinaptic reflex and its stimulated by touch pressure heath cold or tissue
damage( cutaneous stimulation ). Flexor withdrawal reflex represents the
contraction of flexors and relaxation of extensors in stimulated limbs. The action
may be accompanied by a contraction of the extensor of the contralateral side.
The axons of cutaneous sensory receptors synapse on interneurons in the dorsal
horn where it excites the motor neurone of the flexor muscles and inhibits those
of the extensor muscles. Collaterals of interneurons cross the midline to excite
the contralateral extensor motoneurons and in habit flexors. The characteristic of
reflexes are: they have a long latency period, a weak stimulus to one foot
producers a minimal localised flexion response but stronger stimuli produce
progressively greater flexion of the entire limb, the duration of the reflex is longer
than the time of the stimulation.

Usually in humans are explored several withdrawal reflexes: cutaneous

abdominal reflexes,cremasteric reflex and plantar reflex.

Crossed extensor reflex is a part of withdrawal reflex and has a latency of 200-
500 ms. When a strong noxious stimulus is applied to a limb, it causes the flexion
and withdrawal of the limb and extension of opposite limb. After the noxious
stimulus is removed the crossed extensor reflex persists for a longer time and the
flexor reflex helping organism to get away from the noxious stimulus
BASAL GANGLIA
Is represented by caudate nucleus ,putamen, globes palidus, subtalamic nucleus, subtantia nigra (compacta and
reticulate). Corpus striatum is formed by caudate nucleus , putamen and globes palidus.
Caudate nucleus and putamen form striatum; putamen and globes palidus form lenticular nucleus.

Afferent connections are the main input to the basal ganglia terminate in the striatum and subtalamic
nucleus.Stritum receives afferents from excitatory corticostriatum pathway from m1 and premotor cortex, and
also from intralaminar nuclei of talamus. Putamen receives afferents from. Sensory motor areas and subtalamus
receives afferents from cortical area concerned with motor function including eye movement and globus palidus.
Substancia nigra receives impulses from putamen, frontal cortex, maxillary bodies, head nucleus, medial and
lateral lemniscus.

Domanigergic nigrostraiatal projection from the sub. Nigra is connected with striatum. GABAergic projection
from the striatum is connected with the sub. Nigra and striatum is connected with GPe and GPi

GPi via the talamic fasciculus emits efferents to the ventral lateral, ventral anterior and centromedial nuclei of
talamus which arrives in the prefrontal and premotor cortex. GPi also sends efferents to the midbrain
extrapyramidal area which then goes to the neurons of the reticulospinal tract. Sub. Nigra emits efferents to the
superior coliculus of mezenchephalon, involved in eye movement.

Bazal ganglia have functions in control of muscle tone (inhibits the muscle tone) , control of motor activity by
regulations of voluntary movements, regulations of conscious and subconscious movements; control of reflex
motor activity by integrating and coordinating of impulses for the visual and labyrinthine reflexes; control of
automatic associated movements ( swing of the arms while walking); role in arousal mechanism

Disorders of basal ganglia are movement disorders. Hyperkinesia is represented by abnormal excessive
movement and hypokinesia is represented by akinesia and bradikinesia.
Cerebellum
Is formed by vermis and two lateral hemispheres. Its has 3 lobes: anterior,
posterior and floculonodular lobe, and contains 3 pairs of intrinsic nuclei:
fastigial, interpositus and dentate.

From the phylogenetic and functional pov the cerebellum is divided into 3 parts .
Arhicerebellum ( floculonodular lobe) which is connected with the vestibular
aparatus, it is involved in the maintainance of echilibrium and eye movement. It
receives inputs from the vestibular apparatus in the inner ear and visual areas
and gives outputs to the vestibular nuclei. Paleoc erebvellum ( vermis and medial
part of hemispheres) receives inputs from proprioceptors through spinocerebelar
tracts from the visual and auditory receptors and from vestibular system and the
cerebral cortex. The vermis gives outputs to the fastigial nuclei, the info arriving
in the inferior cerebellar peduncle to the vestibular nuclei and reticular formation
of the ponce and medulla, than through vestibular spinal and reticulospinal tracts
it arrives in the spinal cords. The intermediate zones send outputs to the red
nucleus and through the rubrospinal tract it arrived to the spinal cord .
Neurocerebellum ( lateral parts of hemispheres) it is involved in the planning and
timing of movements , in the cognitive functions of cerebellum. It receives inputs
exclusively from the cerebral cortex relaied trough the middle cerebellar
peduncles of the pons and it gives outputs to the dentate nuclei and via the
ventrolateral talamus the info arrives in the motor and premotor cortex.

Cerebellar cortex is organised in 3 layers: The molecular layer/plexiform layer is

the most external and is formed by many parallel fibres stelates and basket cells.
The medial layer / purkinje layer contains purkinje cells that have the dendrites
between the parallel fibres while the axons end is on deep cerebellar nuclei and
vestibular nuclei of brain stem. The innermost layer is the granular layer that
contains granule cells, Golgi cells and many nerve fibres.
The cerebellum receives info from cerebral cortex via the cerebro-ponto-
cerebellar tract which passes into the cereblllllllum through the middle
peduncles, basal ganglia, brain stem, vestibular nucleus, reticular nuclei, olivary
nuclei and proprioceptors. The efferent fibres are included into circuits. The first
one is represented by the fibres from the celebellllum that go into the red nuclei
then in thalamus and finally in the motor cortex. The second circuit is
represented by the fibres that pass to the vestibular nuclei and reticular nuclei
thhen to spinal cord.

Motor commands are not initiated in the cerebellum but it modifies the motor
commands of the descending pathways to make the movements more adaptive
and accurate. The roles of cerebellum are: timing of motor activities, rapid ,
smooth progression from one muscle movements to the next, it controls intensity
of muscle contraction when its load changes, controls necessary instantaneous
interplay between agonist and antagonist muscle groups. The cerebellum
compares the motor plan with what isn actually happening and smoothes and
coordinates the movement by sending impulses to the motor cortex and nuclei
in the brainstem. The cerebellum compares cerebral cortex programming and
movements with the performance, cerebellum being permanently informed about
the position of the body and calculating the speed of the movements and the
moment when the movement will reach the target. It also integrates the visual
and auditory impulses with movement calculating the speed with which the body
comes near an object. In addition cerebellum has a role in coordination of
different muscles, the force and duration of contraction of them and the moment
of initiation of contraction. it also has a role in maintenance of balance and
posture.
Reticular formation
Is a diffused mass of small neurons located in central portion of brain stem and it is a multisinaptic relay system.
The afferents received by reticular formation are: optic, olf, auditory, taste pathways, spinotalamic tract, medial
lemniscus, cerebral cortex, Cerebellum, talamus and corpus striatum. Reticular formations emit efferents to:
cerebral cortex, talamus, hypothalamus, red nuclei, tectum, sub nigra, cerebellum, spinal cord.

Ascending activating reticular system starts from medulla then goes to the pons then to mezencephlum, talamus
and arrives in cerebral cortex. The projection is in two ways via thalamus and subtalamus.
Ascending reticular system is concerned with alertness, maintainance of attention and wakefulness. The specific
sensory pathways transmit impulses from the receptors to the cerebral cortex via talamus, the projection is in a
specific localised area of cortex and causes perception of only a particular sensation, involving 3 or 4 synapses.
The nonspecific sensory pathways are all the sensory pathways that send collateral to the ARAS and the
projection of the cortex is the diffusely and is located also in the other parts of the brain.

Descending facilitatory reticular system is placed in upper and lateral formation and facilitates the somatomotor
activities maintaining the muscle tone by stimulation of gamma motor neurone from ant horn of spinal cord. It
also facilitates the autonomic function being the centre of cardiac function, blood pressure, respiration,
gastrointestinal function and body temperature. Descending inhibitory reticular system is placed in the lower
and medial part of reticular formation and controls somatomotor activities by receiving fibres from basal ganglia
and inhibiting the gamma motor neurone from spinal cord. It also controls the autonomic function being the
centre for inhibition for cardiac function, bp, respiration, gi function and body temperature.
Function of hypothalamus
Stimulation of the posterior hypothalamus causes rage reactions: tahicardia, increased bp, tahipnea, increased
catecolamin secretion and the level of glucocortocoizi, acth secretion and hyperglycaemia.

If the anterior hypothalamus is destroyed , the same reactions are going to appear as by stimulation of the
posterior hypothalamus. Cerebral cortex has and inhibitory influence on hypothalamus causing sham rage due to
the inhibitory influence of cortical control. Reward centre is located in the ventromedial nucleus of
hypothalamus and is responsible for pleasure or satisfaction in animals. Punishment centre is located in the
posterior and lateral nuclei of hypothalamus and is responsible for pain, fear, and defence reaction.
Hypothalamus has role in sleep awake rhythm, mamilarhry bodies being the wakefulness centre. The
stimulation is the result of wakefulness and the sleep is due to its lesion. Hypothalamus has a role in circadian
rhythm which is the regular recurrence of physiological processes with a periodicity of 24 hours. Circadian
rhythm takes place in response to alternation of daylight and darkness and the sulprachismatic nucleus sets the
biological clock. The damage of suprachiasmatic nucleus gives the disturbances in sleep awake rhythm, feeding
rhythm and hormone secretion of acth and gh but the temperature regulation remains constant

When the posterior hypothalamus isn stimulated the vessels in the muscles dilate and those in the skin and git
contract. Hypothalamus changes the cardio vascular reaction during the feeding period thus vessels in the git
dilate while those in the muscles contract. It also regulates bp and hr by acting on the vasomotor center of
medulla oblongata.

The intrauterine sexual differentiation depends on the presence of hormones at the level of hypotalamus. The
lack of testosterone in hypothalamus is the result of female caracteristic developed in fetus.

Hypotalamus has satiety centre and feeding centre. Distraction of satiety centre increase the food intake and
obesity, the lesions and the level of hunger centre result in adipsia.

The water balance is also regulated by hipotalamus because in the anterior part is found the thirst centre. It also
regulates the metabolism of energy substances, the autonomic nervous system activity, termoregul,ationand it
has a role in behaviour and emotional changes
Autonomic nervous system
Has a role in regulation of the activity of internal organs and is organised on the
basis of reflex arch. The visceral afferent neurons have origin in the spinal ganglia
and the extranevraxial cerebral ganglia and its dendrites reach the receptor from
the internal organs and blood vessels while the axons penetrates into cns coming
into contact with the vegetative centre. The preganglionic neurone synapses with
the postganglionic neurone and the efferent fibres go to the visceral electors
inhibiting or stimulatimh them. The efferent pathway has 2 neurons. The first
neurone is the pregamglionic neurone from the ins and its axon make synapse
with postganglionic neutrons that inervates the effector.

Autonomic nervous system has 2 divisions: the sympathetic and parasympathetic

nervous system. Sympathetic nervous system ganglia lie close to the spinal cord
and form the 2 chains of ganglia one on each side of the cord called sympathetic
paravertebral chain. The pre vertebral or collateral ganglia are located in the
abdominal cavity closer to the inervated organs.

At the level of some organs there are mixed vegetative plexuses sympatetic-
parasimpatetic and most of the organs receive double and antagonic inervations.
In some organs the two divisions work synergistically ( salivary secretion); in
spleen, skin, and blood vessels receive only sympathetic nervous system
enervation , their activity being regulated by increase or decrease in the baseline
firing rate of the sympathetic nerves. Gastric and pancreatic nerves receive only
parasympathetic inervation.