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Chapter – 6 Muscle

14. Different types of muscles


15. Muscle contraction

14. DIFFERENT TYPES OF MUSCLES

14.1 INTRODUCTION
14.2 SKELETAL MUSCLE
14.3 CARDIAC MUSCLE
14.4 SMOOTH MUSCLE
14.1 INTRODUCTION

Muscle (from Latin musculus "little mouse") is contractile tissue of the body and is derived from the
mesodermal layer of embryonic germ cells. It is classified as skeletal, cardiac, or smooth muscle and its
function is to produce force and cause motion, either locomotion or movement within internal organs.
Much of muscle contraction occurs without conscious thought and is necessary for survival, like the
contraction of the heart, or peristalsis (which pushes food through the digestive system).

Muscle is mainly composed of muscle cells. Within the cells are myofibrils; myofibrils contain
sarcomeres, which are composed of actin and myosin. Individual muscle fibres are surrounded by
endomysium. Muscle fibers are bound together by perimysium into bundles called fascicles; the bundles
are then grouped together to form muscle, which is enclosed in a sheath of epimysium. Muscle spindles
are distributed throughout the muscles and provide sensory feedback information to the central nervous
system.

A) Skeletal muscle
B) Cardiac muscle
C) Smooth muscle

14.2 SKELETAL MUSCLE

Skeletal muscle is a type of striated muscle,


which usually attaches to tendons. Skeletal
muscles are used to create movement, by
applying force to bones and joints; via
contraction. They generally contract
voluntarily (via somatic nerve stimulation),
although they can contract involuntarily
through reflexes. The whole muscle is wrapped in a special type of connective tissue, epimysium.

Muscle cells (also called muscle fibers) are cylindrical, and are multinucleated (in vertebrates and
insects). The nuclei of these muscles are located in the peripheral aspect of the cell, just under the
plasma membrane, which vacates the central part of the muscle fiber for myofibrils. (Conversely, when

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the nucleus is located in the center it is considered a pathologic condition known as centronuclear
myopathy.)

Skeletal muscles have one end (the "origin") attached to a bone closer to the centre of the body's axis
and the other end (the "insertion") is attached across a joint to another bone further from the body's axis.
The bones rotate about the joint and move relative to one another by contraction of the muscle.

There are several different


ways to categorize the type of
skeletal muscle fibers (see
below). One method uses the
type of protein contained in
myosin (one of the important
proteins that is responsible for
the ability of muscle to
contract). Using this
classification scheme, there are
two major types of fibers for
skeletal muscles: Type I and
Type II. Type I fibers appear
reddish. They are good for
endurance and are slow to tire
because they use oxidative
metabolism. Type II fibers are
whitish; they are used for short
bursts of speed and power, and use both oxidative metabolism and anaerobic metabolism depending on
the particular sub-type, and are therefore quicker to fatigue.

14.3 CARDIAC MUSCLE

Cardiac muscle is a type of highly


oxidative (using molecular oxygen to
generate energy) involuntary striated
muscle found in the walls of the
heart, specifically the myocardium
where they are also known as
cardiac myocytes. The cells that
comprise cardiac muscle are
sometimes seen as intermediate
between these two other types in
terms of appearance, structure,
metabolism, excitation-coupling and
mechanism of contraction.

Cardiac muscle shares similarities


with skeletal muscle with regard to
its striated appearance and contraction, with both differing significantly from smooth muscle cells.
Coordinated contraction of cardiac muscle cells in the heart propel blood from the atria and ventricles to
the blood vessels of the circulatory system. Cardiac muscle cells, like all tissues in the body, rely on an

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ample blood supply to delivery oxygen and nutrients, and to remove waste products such as carbon
dioxide. The coronary arteries fulfill this function.

14.4 SMOOTH MUSCLE

Smooth muscle is a type of non-striated muscle,


found within the tunica media layer of large and
small arteries and veins, the bladder, uterus, male
and female reproductive tracts, gastrointestinal
tract, respiratory tract, the ciliary muscle, and iris
of the eye. The glomeruli of the kidneys contain a
smooth muscle-like cell called the mesangial cell.
Smooth muscle is fundamentally different from
skeletal muscle and cardiac muscle in terms of
structure, function, excitation-contraction coupling,
and mechanism of contraction.

Smooth muscle fibers are spindle-shaped, and, like


striated muscle, can contract and relax. In the
relaxed state, each cell is spindle-shaped, 20-500
micrometers in length, and 2-10 micrometers wide.
There are two types of smooth muscle
arrangements in the body: multi-unit and single-
unit. The single-unit type, also called unitary
smooth muscle, is far more common. Whereas the former presents itself as distinct muscle fibers that are
usually activated by their own nerve fibers, the latter operate as a single unit and are arranged in sheets
or bundles.

Smooth muscle cells have, in general, single nuclei and a plethora of mitochondria. The cells are
arranged in sheets or bundles and connected by gap junctions which connect the cells chemically. In
order to contract, the cells contain actin filaments and a contractile protein called myosin.

The smooth muscle cell contains less protein than a typical striated muscle cell and much less myosin.
The actin content is similar, so the ratio of actin to myosin is ~6:1 in striated muscle and ~15:1 in
smooth muscle. Smooth muscle does not contain the protein troponin; instead calmodulin (which takes
on the regulatory role in smooth muscle), caldesmon and calponin are significant proteins expressed
within smooth muscle.

The reproductive, digestive, respiratory, and urinary tracts, skin, eye, and vasculature all contain this
muscle type. For example, contractile function of vascular smooth muscle is critical to regulating the
lumenal diameter of the small arteries-arterioles called resistance vessels. The resistance arteries
contribute significantly to setting the level of blood pressure

***

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15. MUSCLE CONTRACTION

15.1 INTRODUCTION
15.2 BIOCHEMISTRY OF MUSCLE CONTRACTION
15.3 ENERGETICS OF MUSCLE CONTRACTION

15.1 INTRODUCTION

Muscles take chemical energy in our bodies and convert it into motion. How is this accomplished?
Skeletal muscle is a striated tissue composed of numerous muscle fibers, which each contain hundreds
to thousands of myofibrils. The basic contracting unit of the myofibril is sarcomere, which consists of
about 1500 myosin filaments or thick filaments and twice as many actin or thin filaments. These
filaments slide past each other during muscular contraction due to cross-bridges between the two
filaments. The force of contracting muscles is generated by chemical reactions that cause a
conformational strain in the head of the cross-bridges.

The ratchet theory for muscle contraction was first developed by A. F. Huxley in 1957. (Huxley won a
Nobel prize for his model of the giant axon of the squid, which is seminal work in understanding action
potentials in nerves.) The cross-bridge cycle begins with the binding of ATP to the head of the cross-
bridge. A calcium ion next binds to this protein, which changes the charges and promotes binding of the
cross-bridge to the actin filament.

The ATP is hydrolyzed to ADP, which results in a conformational change in the head of the cross-
bridge and generates the force to pull the actin filament toward the center of the cell. Next the ADP is
released and binding between the filaments is broken, and the cycle is ready to begin anew with the next
binding of ATP.

15.2 BIOCHEMISTRY OF MUSCLE CONTRACTION

The "Sliding-Filament Theory of Muscle Action" explains how the movement of thick- and thin-
filaments relative to each other leads to the contraction and relaxation of whole muscles - hence
ultimately to the movement of the limbs or tissues attached to those muscles:

There are two physical units that are important for the action of muscles. They are thick filaments and
thin filaments.

Skeletal muscles contract according to the sliding-filament model:

1. An action potential originating in the CNS reaches an alpha motor neuron, which then transmits an
action potential down its own axon.

2. The action potential activates voltage-gated calcium channels on the axon, and calcium rushes in.

3. Calcium causes vesicles containing the neurotransmitter acetylcholine to fuse with the plasma
membrane, releasing acetylcholine into the synaptic cleft between the motor neuron terminal and
the motor end plate of the skeletal muscle fiber.

4. The acetylcholine diffuses across the synapse and binds to and activates nicotinic acetylcholine
receptor on the motor end plate. Activation of the nicotinic receptor opens its intrinsic
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sodium/potassium channel, causing sodium to rush in and potassium to trickle out. Because the
channel is more permeable to sodium, the muscle fiber membrane becomes more positively
charged, triggering an action potential.

5. The action potential spreads through the muscle fiber's network of T tubules, depolarizing the
inner portion of the muscle fiber.

6. The depolarization activates voltage-gated calcium channels in the T tubule membrane, which are
in close proximity to calcium-release channels in the adjacent sarcoplasmic reticulum.

7. Activated voltage-gated calcium channels physically interact with calcium-release channels to


activate them, causing the sarcoplasmic reticulum to release calcium.

8. The calcium binds to the troponin C present on the actin-containing thin filaments of the
myofibrils. The troponin then allosterically modulates the tropomyosin. Normally the tropomyosin
sterically obstructs binding sites for myosin on the thin filament; once calcium binds to the
troponin C and causes an allosteric change in the troponin protein, troponin T allows tropomyosin
to move, unblocking the binding sites.

9. Myosin (which has ADP and inorganic phosphate bound to its nucleotide binding pocket and is in
a ready state) binds to the newly uncovered binding sites on the thin filament. Myosin is now
bound to actin in the strong binding state. The release of ADP and inorganic phosphate causes the

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myosin head to turn, causing a ratchet movement (actin acts as a cofactor in the release of
inorganic phosphate, expediting the release). This will pull the Z-bands towards each other, thus
shortening the sarcomere and the I-band.

10. ATP binds myosin, allowing it to release actin and be in the weak binding state. (A lack of ATP
makes this step impossible, resulting in the rigor state characteristic of rigor mortis.) The myosin
then hydrolyzes the ATP and uses the energy to move into the "cocked back" state while releasing
ADP and inorganic phosphate. In general, evidence (predicted and in vivo) indicates that each
skeletal muscle myosin head moves 10-12 nm each power stroke, however there is also evidence
(in vitro) of variations (smaller and larger) that appear specific to the myosin isoform.

11. Steps 7 and 8 repeat as long as ATP is available and calcium is present on thin filament.

12. While the above steps are occurring, calcium is actively pumped back into the sarcoplasmic
reticulum. When calcium is no longer present on the thin filament, the tropomyosin changes
conformation back to its previous state so as to block the binding sites again. The myosin ceases
binding to the thin filament, and the contractions cease.

The calcium ions leave the troponin molecule in order to maintain the calcium ion concentration in the
sarcoplasm. The active pumping of calcium ions into the sarcoplasmic reticulum creates a deficiency in
the fluid around the myofibrils. This causes the removal of calcium ions from the troponin. Thus the
tropomyosin-troponin complex again covers the binding sites on the actin filaments.

15.3 ENERGETICS OF MUSCLE CONTRACTION AND ATP HYDROLYSIS

ATP, adenosine triphosphate (there are three phosphates in ATP), is not stored to a great degree in cells.
Once muscle contraction starts the regeneration of ATP must occur rapidly. There are three primary
sources of ATP which, in order of their utilization, are creatine phosphate (CP), anaerobic glycolysis,
and oxidative phosphorylation.

Energy from ATP derives from cleaving of the terminal phosphate of the ATP molecule. The resulting
molecule is called ADP, adenosine diphosphate. Creatine phosphate converts ADP back to ATP by
donating its phosphate in the presence of an enzyme which is called either creatine kinase (CK) or
creatine phosphokinase (CPK).

The reaction of CP with ADP to form ATP is very rapid but short lived, since the cell does not store
high amounts of CP. However during short, high intensity contractions, CP serves as the major source
of energy. This form of energy generation is often called a lactic anaerobic because it neither produces
lactate nor requires oxygen. It is of paramount importance in sports requiring bursts of speed or power
such as sprints of 10 seconds or less in duration.

As soon as muscle contraction starts, the process of anaerobic glycolysis also begins. Anaerobic
glycolysis does not contribute as large an amount of energy as CP in the short term, but its contribution
is likely to last from 30 to 60 seconds. During glycolysis, locally stored muscle glycogen and possibly
some blood born glucose, supply the substrate for energy generation. No oxygen is required so the
process is called anaerobic. Lactic acid (lactate is the salt) is formed as the end product of pure
anaerobic glycolysis. Sufficient lactic acid formation can lower the pH of the cell to the extent that
metabolism is turned off in the cell.
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The major substrate for anaerobic glycolysis is glycogen, so prior hard exercise without adequate
repletion of glycogen is going to limit further high intensity, short term work by muscles.

The final, and virtually limitless supply of energy, comes from the process of oxidative
phosphorylation. Maximum energy production rates from oxidative phosphorylation are not as high as
from glycolysis. Aerobic events like the marathon are run at a considerably slower pace than a 440
because of this fact.

The substrates for oxidative metabolism are primarily glucose and fat (free fatty acids, not cholesterol),
although protein can also act as an energy source through intermediate conversions to glucose, glucose
precursors or free fatty acids. Because fat can be metabolized aerobically, most well nourished humans
have a near limitless supply of energy for low intensity exercise. Limitation of low intensity exercise is
rarely due to substrate depletion, although depletion of muscle glycogen may also result in fatigue
during aerobic events. The reasons for this are beyond the scope of this description.

Energetics

Muscle can be regarded as a machine that converts chemical energy into work. The first and
second laws of thermodynamics apply to muscle the same way as they apply to other machines.
The first law states that the total energy remains constant when it changes from one form to
another:

427.263 kg.m = 1.000 kilocalorie = 4.184 kilojoules

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The ultimate source of our energy resides in the food that we eat. The energy values of the various
foodstuffs are known since the beginning of the 20th century: When 1.0-g of carbohydrate was
oxidized to CO2 and H2O in a bomb calorimeter 4.1 kcal was released. Values for 1.0-g fat or 1.0-
g protein were 9.1 or 4.1 kcal, respectively. Similarly, the calorie values of various substances in
the body were determined and the next job was to find the chemical substance that directly
provides the energy for muscle work.

ATP, Phosphocreatine and Glycogen Provide Energy for Muscle Contraction

The direct energy source for muscle contraction is ATP (from ATP hydrolysis). The contractile
protein, actomyosin, hydrolyzes ATP to ADP + Pi, the used ATP is quickly restored via the
Lohmann reaction during contraction (Fig. EN5a). The depleted store of PCr is restored from ATP
when the muscle is returned to the resting state.

ATP is synthesized via glycolysis in the sarcoplasm and/or via oxidative phosphorylation in the
mitochondria. Glycolysis may occur under anaerobic condition, the yield is 2 or 3 ATP/glucose.
The lactate produced from glycogen is oxidized to yield 36 ATP/glucose. Also, dismutation of 2

ADP catalyzed by adenylate kinase yields 1 ATP + 1 AMP.

It is important to realize that the ATP concentration in muscle is quite low (5-8 mmoles/g muscle),
enough only for a few contractions. The used ATP is immediately resynthesized from PCr.
However, the PCr concentration is also low (20-25 mmoles/g), enough for some additional
contractions. Glycogen offers a rapid but still limited energy store (endogenous glycogen
concentration about 75 mmoles glucose units in glycogen/g muscle), whereas oxidative
phosphorylation is the slowest and most efficient process for ATP production. For example, the
glycogen store offers energy for a runner for about 1/2 hr and oxidative phosphorylation for an
additional 2 hrs.

***

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Chapter – 7 DIGESTIVE SYSTEM

16. Organization and functions of gastrointestinal tract


17. Organization and functions of salivary glands
18. Structure and functions of liver

16. ORGANIZATION AND FUNCTIONS OF GASTROINTESTINAL TRACT

16.1 INTRODUCTION
16.2 ORGANIZATION OF GI TRACT
16.1 INTRODUCTION

The gastrointestinal (GI) tract, also known as the alimentary canal, is a long, hollow tube that begins at
the mouth and ends at the anus. The specific parts include the mouth, esophagus, stomach, small
intestine, large intestine, and rectum. The GI tract works with the assisting organs -0 the salivary
glands, liver, gallbladder ad pancreas – to turn food into small molecules that the body can absorb and
use. The GI tract has an amazing variety of functions, including:

1. Ingestion- the receipt and softening of food.


2. Transport of ingested food.
3. Secretion of digestive enzymes, acid, mucus and bile.
4. Absorption of end products of digestion.
5. Movement of undigested material, and
6. Elimination-the transport, storage, and excretion of waste products.

16.2 ORGANIZATION OF GI TRACT

GI is hollow tube, its structure is really much more complex. The gastrointestinal tract has a uniform
general histology with some differences which reflect the specialization in functional anatomy.[4] The
GI tract can be divided into 4 concentric layers:

Mucosa
Submucosa
Muscularis externa (the external muscle layer)
Adventitia or serosa

Mucosa: The mucosa is the innermost layer of the gastrointestinal tract that is surrounding the lumen,
or space within the tube. This layer comes in direct contact with the food (or bolus), and is responsible
for absorption and secretion, important processes in digestion. The mucosae are highly specialized in
each organ of the gastrointestinal tract, facing a low pH in the stomach, absorbing a multitude of
different substances in the small intestine, and also absorbing specific quantities of water in the large
intestine. Reflecting the varying needs of these organs, the structure of the mucosa can consist of
invaginations of secretory glands (e.g., gastric pits), or it can be folded in order to increase surface
area (examples include villi and plicae circulares). The mucosa can be divided into: Epithelium,
Lamina propria and Muscularis mucosae.

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Submucosa: The submucosa consists of a dense irregular layer of connective tissue with large blood
vessels, lymphatics and nerves branching into the mucosa and muscularis. It contains Meissner's
plexus, an enteric nervous plexus, situated on the inner surface of the muscularis externa.

Muscularis externa: The muscularis externa consists of an inner circular layer and a longitudinal
outer muscular layer. The circular muscle layer prevents the food from going backwards and the
longitudinal layer shortens the tract. The coordinated contractions of these layers is called peristalsis
and propels the bolus, or balled-up food, through the GI tract. Between the two muscle layers are the
myenteric or Auerbach's plexus.

Adventitia: The adventitia consists of several layers of epithelia. When the adventitia is facing the
mesentery or peritoneal fold, the adventitia is covered by a mesothelium supported by a thin
connective tissue layer, together forming a serosa, or serious membrane.

In a normal human adult male, the GI tract is approximately 6.5 meters (20 feet) long and consists of the
upper and lower GI tracts. The tract may also be divided into foregut, midgut, and hindgut, reflecting
the embryological origin of each segment of the tract. The upper GI tract consists of the mouth,
pharynx, esophagus, and stomach. The lower GI tract comprises the intestines (small intestine:
duodenum, jejunum and ileum and anus, Large intestine: Cecum, colon and rectum) and anus.

16.2.1 Structure and function of Mouth

The mouth, buccal cavity, or oral cavity is the first portion of the alimentary canal that receives food
and begins digestion by mechanically breaking up the solid food particles into smaller pieces and
mixing them with saliva. It is lined with a mucous membrane (as opposed to the exterior of the body,
which is lined with skin. The lips mark the transition from mucous membrane to skin. The mouth
contains the buccal mucosa, which contains the openings of the salivary glands; the tongue; and the
teeth.
Function: The mouth plays an important role in speech (it is part of the vocal apparatus), facial
expression, kissing, eating, drinking (especially with a straw) & breathing. Infants are born with a
sucking reflex, by which they instinctively know to suck for nourishment using their lips and jaw

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16.2.2 Structure and function of Pharynx

The pharynx (plural: pharynges) is the part of the neck and throat situated immediately posterior to
(behind) the mouth and nasal cavity, and cranial, or superior, to the oesophagus, larynx, and trachea.
The human pharynx is conventionally divided into three sections:

 Oropharynx: The oropharynx lies behind the oral cavity. The anterior wall consists of the base of
the tongue and the vallecula; the lateral wall is made up of the tonsil, tonsillar fossa, and tonsillar
(faucial) pillars; the superior wall consists of the inferior surface of the soft palate and the uvula.
 Nasopharynx: The nasopharynx lies behind the nasal cavity. Postero-superiorly this extends from
the level of the junction of the hard and soft palates to the base of skull, laterally to include the fossa
of Rosenmuller. The inferior wall consists of the superior surface of the soft palate.
 Laryngopharynx: The laryngopharynx, also known as the hypopharynx, roughly corresponds to the
levels between C4 to C6, it includes the pharyngo-esophageal junction (postcricoid area), the
piriform sinus, and the posterior pharyngeal wall.

Functions: It is part of the digestive system and respiratory system of many organisms. Because both
food and air pass through the pharynx, a flap of connective tissue called the epiglottis closes over the
trachea when food is swallowed to prevent choking or aspiration. In humans the pharynx is important
in vocalization. In persons with hayfever, oral allergy syndrome and related allergies, the pharynx is
often a reaction site to allergens, with common symptoms including burning and itching

16.2.3 Esophagus

The esophagus or oesophagus (see American and British English spelling differences), sometimes
known as the gullet, is an organ in vertebrates which consists of a muscular tube through which food
passes from the pharynx to the stomach. In humans the esophagus is continuous with the laryngeal
part of the pharynx at the level of the C6 vertebra. The esophagus passes through a hole in the thoracic
diaphragm called the esophageal hiatus. It is usually 25-30 cm long which connects the mouth to the
stomach. It is divided into cervical, thoracic, and abdominal parts.

Functions: Food is passed through the esophagus by using the process of peristalsis. Specifically, it
connects the pharynx, which is the body cavity that is common to the digestive factory and respiratory
system with the stomach, where the second stage of digestion is initiated. The esophagus is lined with
mucous membrane, and is more deeply lined with muscle that acts with peristaltic action to move
swallowed food down to the stomach.

16.2.4 Stomach

The stomach is between the esophagus and the duodenum (the first part of the small intestine). It is on
the left side of the abdominal cavity. The top of the stomach lies against the diaphragm. Lying beneath
the stomach is the pancreas, and the greater omentum which hangs from the greater curvature. Two
smooth muscle valves, or sphincters, keep the contents of the stomach contained. They are the
esophageal sphincter (found in the cardiac region) dividing the tract above, and the Pyloric sphincter
dividing the stomach from the small intestine.

In humans, the stomach has a relaxed volume of about 45 ml, it generally expands to hold about 1 liter
of food, but can hold as much as 4 liters.

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The stomach is divided into four sections, each of which has different cells and functions. The
sections are:

Cardia Where the contents of the esophagus empty into the stomach.
Fundus Formed by the upper curvature of the organ.
Body or corpus The main, central region.
Pylorus or The lower section of the organ that facilitates emptying the contents into the
antrum small intestine.

Functions: The two basic/main functions of the stomach are to: helps any bacteria ingested, break
down the food into smaller pieces to create a larger surface area for easier digestion, and to hold food
and release it at a constant rate. The stomach is a highly acidic environment due to hydrochloric acid
production and secretion which produces a luminal pH range usually between 1 and 2 depending on
the species, food intake, time of the day, drug use, and other factors. Combined with digestive
enzymes, such an environment is able to break down large molecules (such as from water) to smaller
ones so that they can eventually be absorbed from the large intestine. A zymogen called pepsinogen is
secreted by chief cells and turns into pepsin under low pH conditions and is a necessity in protein
digestion.

The human stomach can produce and secrete about 2.2 to 3 liters of gastric acid per day with basal
secretion levels being typically highest in the evening. The stomach can expand to hold between 2-4
liters of food. It is a temporary food storage area, and in the process of digestion, the food goes into
the stomach first.

Absorption of vitamin B12 from the small intestine is dependent on conjugation to a glycoprotein
called intrinsic factor which is produced by parietal cells of the stomach. Other functions include
absorbing some ions, water, and some lipid soluble compounds such as alcohol, aspirin, and caffeine.

16.2.5 Small intestine (duodenum, jejunum and ileum)

Small intestine, which has three parts:

Duodenum
Jejunum
Ileum

Duodenum: The duodenum is a hollow jointed tube about 25-30 cm (10-12 in) long connecting the
stomach to the jejunum. It is the first and shortest part of the small intestine where most chemical
digestion takes place. The functions of duodenum are follows:

The duodenum is largely responsible for the breakdown of food in the small intestine. Brunner's
glands, which secrete mucus, are found in the duodenum. The duodenum wall is composed of a very
thin layer of cells that form the muscularis mucosae. The duodenum is almost entirely
retroperitoneal. The duodenum also regulates the rate of emptying of the stomach via hormonal
pathways. Secretin and cholecystokinin are released from cells in the duodenal epithelium in
response to acidic and fatty stimuli present there when the pyloris opens and releases gastric chyme
into the duodenum for further digestion. These cause the liver and gall bladder to release bile, and

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the pancreas to release bicarbonate and digestive enzymes such as trypsin, lipase and amylase into
the duodenum as they are needed.

Jejunum: The jejunum is the central of the three divisions of the small intestine and lies between the
duodenum and the ileum. The change from the duodenum to the jejunum is usually defined as the
ligament of Treitz. In adult humans, the small intestine is usually between 5.5-6m long, 2.5m of which
is the jejunum. The pH in the jejunum is usually between 7 and 8 (neutral or slightly alkaline). The
jejunum and the ileum are suspended by mesentery which gives the bowel great mobility within the
abdomen. It also contains muscles to help move the food along. The inner surface of the jejunum, its
mucous membrane, is covered in projections called villi, which increase the surface area of tissue
available to absorb nutrients from the gut contents. The epithelial cells which line these villi possess
even larger numbers of microvilli. The transport of nutrients across epithelial cells through the
jejunum and ileum includes the passive transport of sugar fructose and the active transport of amino
acids, small peptides, vitamins, and most glucose. The villi in the jejunum are much longer than in the
duodenum or ileum. The jejunum contains very few Brunner's glands (found in the duodenum) or
Peyer's patches (found in the ileum). Instead, it has many large circular folds in its submucosa called
plicae circulares which increase the surface area for nutrient absorption.

Ileum: The ileum is the final section of the small intestine. It is about 2-4 m long in humans, follows
the duodenum and jejunum, and is separated from the cecum by the ileocecal valve (ICV). The pH in
the ileum is usually between 7 and 8 (neutral or slightly alkaline). The following are the functions of
the ileum:

Its function is mainly to absorb vitamin B12 and bile salts and whatever products of digestion were
not absorbed by the jejunum. The wall itself is made up of folds, each of which has many tiny
finger-like projections known as villi on its surface. In turn, the epithelial cells which line these villi
possess even larger numbers of microvilli. Therefore the ileum has an extremely large surface area
both for the adsorption (attachment) of enzyme molecules and for the absorption of products of
digestion.
The villi contain large numbers of capillaries which take the amino acids and glucose produced by
digestion to the hepatic portal vein and the liver.
Lacteals are small lymph vessels, and are present in villi. They absorb fatty acid and glycerol, the
products of fat digestion. Layers of circular and longitudinal smooth muscle enable the digested
food to be pushed along the ileum by waves of muscle contractions called peristalsis.

16.2.6 Large Intestine (Cecum, Colon and Rectum)

The large intestine comes after the small intestine in the digestive tract and measures approximately
1.5 meters in length. which has three parts:

Cecum (the vermiform appendix is attached to the cecum).


Colon (ascending colon, transverse colon, descending colon and sigmoid flexure)
Rectum

Cecum: The cecum or caecum is a pouch connected to the ascending colon of the large intestine and
the ileum. It is separated from the ileum by the ileocecal valve (ICV) or Bauhin's valve, and is
considered to be the beginning of the large intestine. It is also separated from the colon by the
cecocolic junction.

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Colon: The colon is the last portion of the digestive system in most vertebrates; it extracts water and
salt from solid wastes before they are eliminated from the body. In mammals, the colon consists of
four sections: the ascending colon, the transverse colon, the descending colon, and the sigmoid colon.
The colon from cecum to the splenic flexure (the junction between the transverse and descending
colon) is also known as the right colon. The remainder is known as the left colon. The following are
the functions of the colon:

The large intestine is mainly responsible for storing waste, reclaiming water, maintaining the water
balance, and absorbing some vitamins, such as vitamin K.
By the time the chyme has reached this tube, almost all nutrients and 90% of the water have been
absorbed by the body. At this point some electrolytes like sodium, magnesium, and chloride are left
as well as indigestible carbohydrates known as dietary fiber. As the chyme moves through the large
intestine, most of the remaining water is removed, while the chyme is mixed with mucus and
bacteria known as gut flora, and becomes feces.
The large intestine produces no digestive enzymes — chemical digestion is completed in the small
intestine before the chyme reaches the large intestine. The pH in the colon varies between 5.5 and 7
(slightly acidic to neutral).

Rectum: The rectum is the final straight portion of the large intestine in some mammals, and the gut
in others, terminating in the anus. The human rectum is about 12 cm long. At its commencement its
caliber is similar to that of the sigmoid colon, but near its termination it is dilated, forming the rectal
ampulla.
Functions: The rectum intestinum acts as a temporary storage facility for feces. As the rectal walls
expand due to the materials filling it from within, stretch receptors from the nervous system located in
the rectal walls stimulate the desire to defecate. If the urge is not acted upon, the material in the
rectum is often returned to the colon where more water is absorbed. If defecation is delayed for a
prolonged period, constipation and hardened feces results.

Fig. Organization of gastrointestinal tract

***
61 | P G D C B , P a p e r - I Dr. M. Estari
17 STRUCTURE AND FUNCTIONS OF SALIVARY GLANDS

17.1 INTRODUCTION
17.2 ANATOMY
17.3 CROSS SECTION OF SG
17.4 FUNCTIONS
17.1 INTRODUCTION

The salivary glands in mammals are exocrine glands that produce saliva. They also secrete a chemical
(enzymes) that breaks down starch into glucose. In other organisms such as insects, salivary glands are
often used to produce biologically important proteins like silk or glues, and fly salivary glands contain
polytene chromosomes that have been useful in genetic research.

17.2 ANATOMY

Most animals have three major pairs of salivary glands that differ in the type of secretion they produce:

parotid glands produce a serous, watery secretion


submaxillary (mandibular) glands produce a mixed serous and mucous secretion
sublingual glands secrete a saliva that is predominantly mucous in character

The parotid glands are a pair of glands located in the subcutaneous tissues of the face overlying the
mandibular ramus and anterior and inferior to the external ear. The secretion produced by the parotid
glands is serous in nature, and enters the oral cavity through the Stensen's duct after passing through the
intercalated ducts which are prominent in the gland. Despite being the largest pair of glands, only
approximately 25% of saliva is produced by the glands.

The submandibular glands are a pair of glands located beneath the floor of the mouth, superior to the
digastric muscles. The secretion produced is a mixture of both serous and mucous and enters the oral
cavity via Wharton's ducts. Approximately 70% of saliva in the oral cavity is produced by the
submandibular glands, even though they are much smaller than the parotid glands.

The sublingual glands are a pair of glands located beneath the floor of the mouth anterior to the
submandibular glands. The secretion produced is mainly mucous in nature, however it is categorized as
a mixed gland. Unlike the other two major glands, the ductal system of the sublingual glands do not
have striated ducts, and exit from 8-20 excretory ducts. Approximately 5% of saliva entering the oral
cavity come from these glands.

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17.3 CROSS SECTION OF SALIVARY GLAND

The primary salivary glands are composed of numerous clusters of 15 to 100 secretory cells arranged in
globular or tubular configurations. These clusters are called acini (singular acinus.) The acini open into
ducts, which merge to carry the saliva towards the mouth. Duct cells also transport electrolytes in and
out of saliva, and they can participate in secretory activity to a limited degree. The acini and ducts are
surrounded by myoepithelial cells, which can contract to help accelerate saliva flow.

Figure : Cross section of a non-realistic salivary gland, showing three types of acini.

Acini are composed principally of two types of secretory cells, serous and mucous, which are both
specialized for the production of large quantities of proteins. Serous cells produce a thin, watery saliva
containing the digestive enzyme α-amylase. Mucous cells produce a thicker saliva rich in mucins–a type
of glycoprotein–which help lubricate food for swallowing. The proportions of serous and mucous cells
are different in the various salivary glands, and each gland secretes a saliva that reflects the cellular
makeup of its acini. (See Table)

Table 1—Salivary Gland Secretions


Gland Type Saliva Type
Parotid, and Von Ebner’s (on the tongue) Serous
Submandibular Mixed, more serous than mucous
Sublingual Mixed, but mostly mucous
Most minor Mucous

17.4 FUNCTIONS

Lubrication and binding: the mucus in saliva is extremely effective in binding masticated food into a
slippery bolus that (usually) slides easily through the esophagus without inflicting damage to the
mucosa. Saliva also coats the oral cavity and esophagus, and food basically never directly touches the
epithelial cells of those tissues.

Solubilizes dry food: in order to be tasted, the molecules in food must be solubilized.

Oral hygiene: The oral cavity is almost constantly flushed with saliva, which floats away food debris
and keeps the mouth relatively clean. Flow of saliva diminishes considerably during sleep, allow
populations of bacteria to build up in the mouth -- the result is dragon breath in the morning. Saliva also
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contains lysozyme, an enzyme that lyses many bacteria and prevents overgrowth of oral microbial
populations.

Initiates starch digestion: in most species, the serous acinar cells secrete an alpha-amylase which can
begin to digest dietary starch into maltose. Amylase is not present, or present only in very small
quantities, in the saliva of carnivores or cattle.

Provides alkaline buffering and fluid: this is of great importance in ruminants, which have non-
secretory forestomachs.

Evaporative cooling: clearly of importance in dogs, which have very poorly developed sweat glands -
look at a dog panting after a long run and this function will be clear.

***

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18. LIVER STRUCTURE AND FUNCTIONS

18.1 INTRODUCTION
18.2 EXTERNAL STRUCTURE
18.3 INTERNAL STRUCTURE
18.4 FUNCTIONS

18.1 INTRODUCTION

The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions,
a few of which are detoxification, protein synthesis, and production of biochemicals necessary for
digestion. The liver is necessary for survival; a human can only last up to 24 hours without liver
function. The liver plays a major role in metabolism and has a number of functions in the body,
including glycogen storage, decomposition of red blood cells, plasma protein synthesis, and
detoxification. The liver is also the largest gland in the human body. It lies below the diaphragm in the
thoracic region of the abdomen. It produces bile, an alkaline compound which aids in digestion, via the
emulsification of lipids. It also performs and regulates a wide variety of high-volume biochemical
reactions requiring very specialized tissues

18.2 EXTERNAL STRUCTURE

The liver is the largest gland in the body weighing about 1.4 kg in an adult. It is situated under the
diaphragm in the upper abdominal cavity and is held in place by several ligaments.
It is a reddish-brown colour and comprises of four anatomical lobes. When viewed from the front, the
dominant left and right lobes can be seen which are separated by the falciform ligament. Situated in a
depression on the posterior surface of the liver is the gall bladder, a pear-shaped sac which stores bile
synthesised by the liver.

The liver receives a blood supply from two sources. The first is the hepatic artery which delivers
oxygenated blood from the general circulation. The second is the hepatic portal vein delivering
deoxygenated blood from the small intestine containing nutrients. The blood flows through the liver
tissue to the hepatic cells where many metabolic functions take place. The blood drains out of the liver

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via the hepatic vein. The liver tissue is not vascularised with a capillary network as with most other
organs, but consists of blood filled sinusoids surrounding the hepatic cells.

18.3 INTERNAL STRUCTURE

At the microscopic level, the liver consists of hexagonal shaped functional units called hepatic lobules.
These, in turn, are made up mostly of hepatocytes (the commonest type of liver cell) arranged in thin
layers that radiate from the central canal (central vein) to the periphery of the lobule. Between the
radiating rows of hepatocytes are small blood vessels called sinusoids. These receive oxygen-rich blood
from the hepatic artery and nutrients from the intestines via the portal vein. The oxygen and nutrients
diffuse through the capillary walls into the liver cells.

Within the sinusoids are specialized macrophages called Kupffer cells that figure prominently in the
recycling of old red blood cells. At the corners of each lobule is a complex, called the portal area,
composed of branches of the hepatic portal vein, hepatic artery, bile duct, and nerve. Bile drains from
the hepatocytes by the many small bile ducts that unite to form the main bile duct of the liver, the
hepatic duct. This joins the cystic duct, which leads from the gallbladder, to form the common bile duct,
which drains into the duodenum. The central canal is a blood vessel in the middle of each lobule which
receives blood from the hepatic portal vein and hepatic artery via the sinusoids and drains the blood into
the hepatic vein.

Fig. Structure of liver lobule


18.4 FUNCTIONS

The various functions of the liver are carried out by the liver cells or hepatocytes.

The liver produces and excretes bile (a greenish liquid) required for emulsifying fats. Some of the
bile drains directly into the duodenum, and some is stored in the gallbladder.
The liver performs several roles in carbohydrate metabolism:
o Gluconeogenesis (the synthesis of glucose from certain amino acids, lactate or glycerol)
o Glycogenolysis (the breakdown of glycogen into glucose) (muscle tissues can also do this)
o Glycogenesis (the formation of glycogen from glucose)
o The breakdown of insulin and other hormones

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o The liver is responsible for the mainstay of protein metabolism.
The liver also performs several roles in lipid metabolism:
o Cholesterol synthesis
o The production of triglycerides (fats).
The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, X and XI, as
well as protein C, protein S and antithrombin.
The liver breaks down haemoglobin, creating metabolites that are added to bile as pigment
(bilirubin and biliverdin).
The liver breaks down toxic substances and most medicinal products in a process called drug
metabolism. This sometimes results in toxication, when the metabolite is more toxic than its
precursor.
The liver converts ammonia to urea.
The liver stores a multitude of substances,
including glucose in the form of glycogen,
vitamin B12, iron, and copper.
In the first trimester fetus, the liver is the main site
of red blood cell production. By the 32nd week of
gestation, the bone marrow has almost completely
taken over that task.
The liver is responsible for immunological
effects- the reticuloendothelial system of the liver
contains many immunologically active cells,
acting as a 'sieve' for antigens carried to it via the
portal system.

***

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Chapter – 8 CARDIOVASCULAR SYSTEM

19. Structure and function of heart


20. Organization and function of the circulatory system
21. Reticuloendothelial system

19. STRUCTURE AND FUNCTIONS OF HEART

19.1 INTRODUCTION
19.2 EXTERNAL STRUCTURE
19.3 CARDIAC MUSCL
19.4 SMOOTH MUSCLE
19.1 INTRODUCTION

The cardiovascular system is sometimes called the circulatory system. It consists of the heart, which is a
muscular pumping device, and a closed system of vessels called arteries, veins, and capillaries. As the
name implies, blood contained in the circulatory system is pumped by the heart around a closed circuit of
vessels as it passes again and again through the various "circulations" of the body. The heart is the
muscular pump that is located between your lungs, slightly to the left of your breastbone. It is slightly
larger than a human fist, with a weight of between 200 to 425 grams. Everyone's heart has to beat
approximately 100,000 times each and every day.

19.2 EXTERNAL STRUCTURE OF HEART

The heart is enclosed by a sac known as the pericardium. There are three layers of tissues that form the
heart wall. The outer layer of the heart wall is the epicardium, the middle layer is the myocardium, and
the inner layer is the endocardium. The external structures of the heart include the ventricles, atria,
arteries, and veins. Arteries carry blood away from the heart while veins carry blood into the heart. The
vessels colored blue indicate the transport of blood with relatively low content of oxygen and high
content of carbon dioxide. The vessels colored red indicate the transport of blood with relatively high
content of oxygen and low content of carbon dioxide.

The heart pumps blood into the blood vessels, a series of pipes that take blood from the heart to the
organs of the body (via the arteries) and send the blood back into the heart (via the veins). The arteries
are muscular and elastic (like a rubber band) and are able to send the blood in a pulsatile form to all
organs. As the arteries enter an organ, Arteries carry oxygenated blood to all the organs except the lung.
The pulmonary artery arises from the right ventricle and carries blood deficient in oxygen into the lung.

Veins carry blood toward the heart. After blood passes through the capillaries, it enters the smallest
veins, called venules. From the venules, it flows into progressively larger and larger veins until it
reaches the heart. In the pulmonary circuit, the pulmonary veins transport blood from the lungs to the
left atrium of the heart. Systemic veins transport blood from the body tissue to the right atrium of the
heart.

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Fig. External structure of Heart

19.3 INTERNAL STRUCTURE

Heart Chambers: The heart is a four chambered structure made up of two receiving chambers called
atria and two pumping chambers called ventricles. The right atrium receives oxygen poor
blood returning from the body through the superior and inferior vena cava. The right
ventricle pushes the oxygen poor blood to the lungs through the pulmonary arteries.
The left atrium receives oxygen rich blood returning from the lungs through pulmonary veins.
The left ventricle pushes the oxygen rich blood out through the aorta, which directs the
blood to all parts of the body. The right and left atria are separated by the
interatrial septum while the right and left ventricles are separated by the interventricular septum.

Fig. Internal structure of Heart

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Heart Valves: When blood flows through the heart it follows a unidirectional pattern. It first enters both
atria and then fills both ventricles before leaving the heart. In order to prevent backflow
against this pattern there are four valves in the heart that serve this function.
Found between the atria and ventricles are two atrioventricular (A-V) valves that prevent blood from
reentering the atria. The valve that guards the right atrium is called the tricuspid valve while the valve
guarding the left atrium is called the bicuspid or mitral valve. The two remaining valves are called
semilunar valves. The valve located where the pulmonary trunk meets the right ventricle is called the
pulmonary semilunar valve. The valve found where the aorta and left ventricle meet is called the aortic
semilunar valve. Both semilunar valves prevent backflow of blood into the ventricles.

Conduction System: The conduction system of the heart explains how heart muscle has
automaticity and is able to contract without the help of outside nervous or hormonal innervation. It is
made up of specialized cardiac cells that initiate and guide myocardial contraction. The conduction
system consists of the sinoatrial node (S-A node), atrioventricular node (A-V node), atrioventricular
bundle (A-V bundle or A-V bundle of His), Purkinje fibers and bundle branches.

The S-A node is located in the posterior wall of the right atrium. It sets off impulses that trigger atrial
contraction. It discharges impulses quicker than any other part of the heart and establishes the rate
and rhythm for the entire heart. Because of this it is more commonly known as the pacemaker. The
contracted atrial cells then send the impulse to the A-V node, which is located in the atrial wall near
the interatrial septum. Once the A-V node picks up the signal, the speed of impulse transmission is
slowed down to allow the atria time to complete contraction before ventricular contraction occurs.

From the A-V node the impulse then travels to the A-V bundle (bundle of His) which is made up of
special fibers called Purkinje fibers. The A-V bundle begins at the right side of the interatrial septum
and runs down to the beginning of the interventricular septum. It then branches into right and left
bundle branches that run down the length of the interventricular septum. The bundle branches
further divide into Purkinje fibers that cover the inner surface of the ventricles. The impulses relayed
from the Purkinje fibers initiates ventricular contraction.

Fig. Conduction (Pace makers)

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19.4 FUNCTIONS

The heart is a complex organ with many functions. A primary function of the heart is to pump oxygen-
rich blood to vital organs and tissues. Oxygen is needed by every cell of the body for energy and for
life.

The main functions of the heart can be summarised as follows:

Right-Hand Side of the Heart


The right-hand side of the heart receives de-oxygenated blood from the body tissues (from the upper-
and lower-body via the Superior Vena Cava and the Inferior Vena Cava, respectively) into the right
atrium. This de-oxygenated blood passes through the tricuspid valve into the right ventricle. This
blood is then pumped under higher pressure from the right ventricle to the lungs via the pulmonary
artery

Left-Hand Side of the Heart


The left-hand side of the heart receives oxygenated blood from the lungs (via the pulmonary veins)
into the left atrium. This oxygenated blood then passes through the bicuspid valve into the left
ventricle. It is then pumped to the aorta under greater pressure (as explained below). This higher
pressure ensures that the oxygenated blood leaving the heart via the aorta is effectively delivered to
other parts of the body via the vascular system of bllod vessels (incl. arteries, arterioles, and
capillaries).
The pump action performed by the heart is achieved by a sequence of alternating contraction and
relaxation of the heart muscle).
In this context the term "systole" refers to the contraction part of the sequence and the term "diastole"
to the relaxation part of the sequence. Hence, the "systolic" and "diastolic" pressures may be measured
and recorded separately when monitoring blood pressure.
This process is directed by the nervous system, nerve impluses initiating each sequence. The whole
series of actions that cause alternating contractions and relaxations may be summarised in five stages:

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1. The vagus nerve stimulates the sinoatrial node (SAN), the pacemaker of the heart.
The sinoatrial node (SAN) is a tiny area of specialised cardiac (meaning "heart") muscle in the
upper wall of the right atrium, near the vena cava - as shown above. The fibres of the SAN
contract rhythmically approx. 70 times each minute. After each of these contractions, the impluse
is dispersed across the atrial cardiac muscle, leading to ...
2. ... simultaneous contraction of both the right and left atria. This movement of the cardiac muscle
pushes blood from the atria into the ventricles (via the tricuspid and bicuspid valves).
3. The contractions of the atria send impulses down the Purkinje fibers, which in turn stimulate the
atrioventricular node (AVN).The atrioventricular node is a mass of modified cardiac muscle
located in the lower/central part of the right atrium of the heart. The Purkinje fibres are referred
to by various names in different textbooks, so are also known as "Purkyne Fibres", "Purkynje
Fibres", and as the "Bundle of His". This/these are a bundle of modified cardiac muscle fibers
that transmit impulses from the atra, via the AVN, to the ventricles.
4. The action potential from the impulse transmitted down the Purkinje fibers reaches the right and
left branches of the Purkinje fibres - as shown in the diagram on the right. This causes the ...
5. ... ventricles to contract, which pushes blood upwards into the arteries that take the blood away
from the heart (the pulmonary artery taking blood to the lungs, and the aorta taking blood to the
body).

***

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20. ORGANIZATION AND FUNCTION OF THE CIRCULATORY SYSTEM

20.1 INTRODUCTION
20.2 PULMONARY AND SYSTEMIC CIRCULATIONS
20.3 FUNCTIONS
20.1 INTRODUCTION

The main components of the human circulatory system are the heart, the blood, and the blood vessels.
The circulatory system includes: the pulmonary circulation, a "loop" through the lungs where blood is
oxygenated; and the systemic circulation, a "loop" through the rest of the body to provide oxygenated
blood. An average adult contains five to six quarts (roughly 4.7 to 5.7 liters) of blood, which consists of
plasma, red blood cells, white blood cells, and platelets. Also, the digestive system works with the
circulatory system to provide the nutrients the system needs to keep the heart pumping.

Organization of circulatory system is explained by two important aspects, i.e. Pulmonary and Systemic
Ciruculations, Volume and Pressure distribution

20.2 PULMONARY AND SYSTEMIC CIRCULATIONS

20.2.1 Pulmonary circulation


Pulmonary circulation is the portion of the cardiovascular system which carries oxygen-depleted
blood away from the heart, to the lungs, and returns oxygenated blood back to the heart.
Course: In the pulmonary circulation, deoxygenated blood exits the heart through the pulmonary
arteries, enters the lungs and oxygenated blood comes back through pulmonary veins. The blood
moves from right ventricle of the heart to the lungs back to the left atrium.

 Right heart: Oxygen-depleted blood from the body leaves the systemic circulation when it enters
the right heart, more specifically the right atrium through the superior vena cava and inferior vena
cava. The blood is then pumped through the tricuspid valve (or right atrioventricular valve), into the
right ventricle.

 Arteries: From the right ventricle, blood is pumped through the pulmonary semilunar valve into the
pulmonary artery. This blood enters the two pulmonary arteries (one for each lung) and travels
through the lungs.

 Lungs: The pulmonary arteries carry blood to the lungs, where red blood cells release carbon
dioxide and pick up oxygen during respiration.

 Veins: The oxygenated blood then leaves the lungs through pulmonary veins, which return it to the
left heart, completing the pulmonary cycle. This blood then enters the left atrium, which pumps it
through the bicuspid valve, also called the mitral or left atrioventricular valve, into the left ventricle.
The blood is then distributed to the body through the systemic circulation before returning again to
the pulmonary circulation.

20.2.2 Systematic circulation


Systemic circulation is the portion of the cardiovascular system which carries oxygenated blood away
from the heart, to the body, and returns deoxygenated blood back to the heart.

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Course: In the systemic circulation, arteries bring oxygenated blood to the tissues. As blood circulates
through the body, oxygen diffuses from the blood into cells surrounding the capillaries, and carbon
dioxide diffuses into the blood from the capillary cells. Veins bring deoxygenated blood back to the heart.

Arteries: Oxygenated blood enters the systemic circulation when leaving the left ventricle, through
the aortic semi-lunar valve. The first part of the systemic circulation is the artery aorta, a massive and
thick-walled artery. The aorta arches and gives off major arteries to the upper body before piercing the
diaphragm in order to supply the lower parts of the body with its various branches.

Capillaries: Blood passes from arteries to arterioles and finally to capillaries, which are the thinnest
and most numerous of the blood vessels. These capillaries help to join tissue with arterioles for
transportation of nutrition to the cells, which absorb oxygen and nutrients in the blood. Peripheral
tissues do not fully deoxygenate the blood, so venous blood does have oxygen, but in a lower
concentration than in arterial blood. In addition, carbon dioxide and wastes are added.

Venules: The deoxygenated blood is then collected by venules, from where it flows first into veins,
and then into the inferior and superior venae cavae, which return it to the right heart, completing the
systemic cycle. The blood is then re-oxygenated through the pulmonary circulation before returning
again to the systemic circulation.

Veins: The relatively deoxygenated blood collects in the venous system which coalesces into two
major veins: the superior vena cava (roughly speaking from areas above the heart) and the inferior
vena cava (roughly speaking from areas below the heart). These two great vessels exit the systemic
circulation by emptying into the right atrium of the heart. The coronary sinus empties the heart's veins
themselves into the right atrium.

Fig. Pulmonary and Systematic circulation

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20.3 FUNCTIONS OF CIRCULATORY SYSTEM

The circulatory system has as main function the rapid transport of substances to cells throughout the
body, but is also involved in other processes that are essential to the normal functioning of organisms.

The basic functions of the cardiovascular system are, as follows:

In nutrition (Rapid substance transport to and from the tissues and organs of the body). This is
done by convection over the long distances and by diffusion at the cellular level. The most important
advantage convective transport has to offer is speed of transport. Oxygen, glucose, amino-acids, fatty
acids, water, vitamins, drugs are carried along blood vessels, in a stream of fluid that is pumped
through them by the heart. Oxygen is carried by the red cells of the blood, in the form of
oxyhemoglobin, a stable compound formed of oxygen and hemoglobin, the characteristic pigment that
gives red cells their colour. The circulatory system carries digested food substances to the cells of the
body. These nutrients enter the bloodstream by passing through the walls of the small intestine into
the capillaries. The blood then carries most of the nutrients to the liver.

Fig. Function in nutrition

In excretion (Rapid removal of metabolic waste) (carbon dioxide, urea, creatinine). The circulatory
system collects the metabolic waste products and delivers them to the excretory organs - e.g., the
kidneys, which then filter wastes (especially urea) from the blood and excrete them and water in urine.
CO2 is carried to the lungs by the red cells as well, through hemoglobin, which is capable of attaching
carbon dioxide as well.

Fig. Rapid removal of metabolic waste

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In respiration: From the left side of the heart, blood full of oxygen is pumped into the systemic
circulation. This blood leaves the heart through the aorta, the main artery of the body. A number of
major arteries branch off the aorta. These arteries, in turn, branch into smaller and smaller vessels,
finally emptying into the tiny capillaries. There, oxygen leaves the blood and enters the tissues
through the thin capillary walls. In a similar way, carbon dioxide leaves the tissues and enters the
blood. The blood, now carrying carbon dioxide, leaves the capillaries and flows through larger and
larger veins. Eventually, the blood enters the right side of the heart through two large veins--the
superior vena cava, which carries blood from the head and arms, and the inferior vena cava, which
carries blood from the trunk and legs.

From the right side of the heart, the blood is pumped into the pulmonary circulation. Pulmonary
arteries carry the blood that contains carbon dioxide to capillaries in the lungs. The carbon dioxide
passes through the capillary walls into the lungs and is then exhaled. Oxygen that has been inhaled
passes from the lungs into the blood in a similar way. The blood returns through the pulmonary veins
to the left side of the heart and begins its journey again.

Fig. Function in respiration

Distribution of hormones to the tissues. Hormones are secretions of the endocrine glands that have
specific effects on the functioning of other tissues/organs. The circulatory system is part of this
control system, by distributing, through blood, the hormones to their tissue/organ of destination. It is
interesting to note that the cardiovascular system also secrets some hormones of its own (e.g. the atrial
natriuretic peptide).

Immune protection. Blood circulation plays an important part in the immune system of defense
against infection. The immune system protects the body from foreign substances and pathogenic
microorganisms by producing the immune response. The circulatory system carries out its role of
protection through blood cells: leucocytes or white cells are specialized for antibody production and
destruction of toxins of microbial origin; they function by means of fagocitosis (ingestion and
destruction); thrombocytes (platelets) have a role in immune reactions, in the endocytosis of smaller
particles (engulfment of bacteria or molecules by forming a vesicle around them), as well as in wound
healing, by stimulating the growth of smooth muscle fibers. Protection against pathogens is also
carried out by means of blood clotting, process in which platelets have the essential role as well.

Temperature regulation. Through the circulatory system, that covers the entire body, heat is delivered
from the core to the peripheral areas. Temperature regulation is done by the alteration of the blood
flow through the skin. Vasodilation (dilation of arterioles and small arteries) and vasoconstriction (the
76 | P G D C B , P a p e r - I Dr. M. Estari
opposite process) determine temperature locally; the arterioles act as "taps" of the circulation,
allowing blood flow increase or turning down the blood flow, to match local needs. By contracting
hard, terminal arterioles can even prevent blood from flowing through the capillaries they feed. The
arterio-venous anastomosis also helps local temperature regulation of skin. The anastomosis
(interconnection) occurs in skin tissues and is in fact the connection of arterioles to venules directly,
bypassing the capillaries, by means of shunt vessels having a diameter of 20-135 µm.

Reproduction: The role the circulatory system in the reproductive process is to provide a mechanism
for penile erection. The male reproductive organ contains two chambers, called the corpora cavernosa,
filled with spongy tissues; this type of tissue contains smooth muscles, fibrous tissues, spaces, veins,
and arteries. Impulses from the brain and local nerves cause the muscles of the corpora cavernosa to
relax, allowing blood to flow in and fill the open spaces. The blood creates pressure in the corpora
cavernosa, making the penis expand; the surrounding membrane helps to trap the blood in the corpora
cavernosa, thereby sustaining erection. The reverse process starts when muscles in the penis contract,
stopping the inflow of blood and opening outflow channels.

***

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21. RETICULOENDOTHELIAL SYSTEM

21.1 INTRODUCTION
21.2 COMPONENTS OF RES
21.3 CLASSIFICARTION OF RES
21.4 FUNCTIONS
21.1 INTRODUCTION

The reticuloendothelial system (RES), part of the immune system, consists of the phagocytic cells
located in reticular connective tissue, primarily monocytes and macrophages. These cells accumulate in
lymph nodes and the spleen. The Kupffer cells of the liver and tissue histiocytes are also part of the
RES. The term "reticulo-endothelial system" was coined because it was formerly believed that a major
part of the blood vessel endothelial cells could perform phagocytic functions similar to those performed
by the macrophage system. It should be remembered that the reticulo-endothelial system is almost
synonymous with the tissue macrophage system.

21.2 COMPONENTS OF RES

The reticulo-endothelial system (RES) is a diffuse system consisting of phagocytic cells (Monocytes
and Macrophages). These are derived from bone marrow stem cells, which are associated with the
connective tissue framework of the liver, spleen, and lymph nodes. It consists of the combination of
mobile macrophages and fixed tissue macrophages. Macrophages are defined as mononuclear
phagocytes found in the tissues. These cells arise from stem cells in the bone marrow. They develop
into monocytes and circulate in the blood for about 40 hours.

Monocyte, are non-granular white blood cells that function as phagocytes in the blood. They are
transformed into macrophages after leaving the blood stream and moving into the connective tissues.
It is here that they undergo a magical metamorphosis increasing in size, phagocytic activity and
lysosomal enzyme content. The lysosomal sacs of these cells contain hydrolytic (digestive) enzymes
that are active in an acid pH. This is an incredibly important point if you are using enzymes to
enhance immune function. Pancreatic enzymes are not active in an acid pH environment, only in the
alkaline environments found in the blood and small intestine.

Macrophages are most frequently concentrated in the following areas:

Loose connective tissues, which are especially numerous in mucous membranes of the digestive
and respiratory tracts and in association with the lymphatics in the connective tissue of the pleura
and peritoneum;
Lining the alveoli (terminal air sacs) of the lungs;
Lining the blood sinuses of the liver (Kupfer cells) and bone marrow;
Lining the sinuses of lymph nodes and the spleen, and
Microglia of the central nervous system. Microglia are small, non-neural, interstitial cells of
mesodermal origin that form the supporting structure of the central nervous system.

Once in the connective tissues, the macrophages become powerful scavengers, even more powerful
than neutrophils. They have the ability to engulf not only much larger particles but also larger
quantities than the neutrophils. Macrophages are capable of ingesting four times as much material as
neutrophils before dying. They can even phagocytize whole red blood cells and malarial parasites,
whereas -- neutrophils are not capable of phagocytizing particles much larger than bacteria. Also,
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macrophages have much greater ability to phagocytize necrotic tissue. When these cells come in
contact with extraneous particulate matter, either in the tissues or in the blood stream, the
phenomenon of phagocytosis takes place extremely rapidly, the particle passing through the cell
membrane to the inside of the phagocyte within a few hundredths of a second.

The phagocytic cells within this system comprise the mononuclear phagocyte system (MPS), and the
macrophage is the major differentiated cell in the MPS. The MPS also consists of bone marrow
monoblasts and pro-monocytes, peripheral blood monocytes and tissue macrophages. Cells of the
RES and MPS, particularly the liver macrophage or Kupfer cells, are known to be important in the
clearance of particles from the bloodstream. Negatively charged particles, in particular, are avidly
scavenged by macrophages. The Kupfer cell is one of the most important cells in the MPS. These are
highly phagocytic cells located in the sinusoid wall, usually on the endothelial surface, of the liver.
They have a number of functions, but one of the most important is their ability to endocytose and
remove from the blood potentially harmful materials and particulate matter such as bacterial
endotoxins, micro-organisms, immune-complexes and tumour cells. The recognition of these
materials is mediate by an array of cell surface receptors that include receptors for IgG, IgA,
complement components, galactose, mannose, CD4 and the carcino- embryonic antigen. Other
receptors include the scavenger receptor, transferrin and DNA-binding receptors

Fig. Components of Reticuloendothelial system

21.3 CLASSIFICATION OF RETICULOENDOTHELIAL SYSTEM

The reticuloendothelial system is divided into primary and secondary lymphoid organs.

21.3.1 Primary (or "central") lymphoid organs

The sites where the cells of the RES are produced. The cells of the RES are produced in the bone
marrow. The thymus is also included as it is the required site for T cell maturation.

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Bone marrow: All cells of the blood orginate from pluripotent stem cells in the bone marrow.
Animals including humans will die when given high dose radiation because stem cells will be
destroyed. Theoretically 1 stem cell can reconstitute the animal. In addition Bone Marrow serves as
site of maturation of B lymphocytes in most mammals studied to date. Because there is not a discrete
site, the process is very difficult to study. There is known to be a selection process. Stromal cells in
the bone marrow very important in this process. Soluble factors are not as well characterized in the
bone marrow but IL-7 is known to be an important signal. Many pre-B cells die in the bone marrow.
If they do not form functional Ig molecules or if they possess Ig molecules which recognize and bind
to self antigens. B cells that survive this selection process leave the bone marrow through efferent
blood vessels.

Thymus: Flat, bilobed organ situated above the heart and below the thyroid gland. Each lobe is
surrounded by a capsule and is divided into lobules, which are separated from each other by strands
of connective tissue called trabeculae. Each lobule is organized into two compartments: the cortex
(outer compartment) the medulla (inner compartment). Cortex and Medulla are both crisscrossed by a
3D network of stromal cells composed of: loosely packed epithelial cells and interdigitating dendritic
cells. The thymus is at its largest relative size at birth and its largest actual size is at puberty.
Following puberty the thymus begins to shrink. In elderly individuals hardly any of it left.
Relationship between aging and a decline in immune responsiveness. Stress can also result in
shrinkage of the thymus.

Macrophages physically interact with the developing T cells as well as secreting soluble factors
which influence T cell maturation. In cortex, network is densely packed with thymocytes and less
dense in medulla. In medulla, the epithelial cells are more visible and you also find HASSAL's
Corpuscles. Function Unknown.

Fig. Location structure of thymus gland

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21.3.2 Secondary (or "peripheral") lymphoid organs:

The sites where the cells of the RES function. This includes the lymph nodes, tonsils, spleen, and
"MALT" (mucosa-associated lymphoid tissue).

i) Lymph nodes: Encapsulated bean-shaped structures (normally <1 cm in diameter) containing a


reticular network packed with lymphocytes, macrophages, and dendritic cells. They are present at
the junctions of lymphatic vessels. Serve as the first organized structures to encounter most
antigens. The major function of the lymph nodes is to filter antigen from the lymph. 3 regions to
the lymph node:

Cortex (outermost layer- contains mostly B lymphocytes, follicular dendritic cells and
macrophages arranged in clusters called primary follicles). Following antigenic stimulation
they primary follicles become secondary follicles consisting of concentric rings of densely
packed lymphocytes and central lymphocytes, macrophages, and dendritic cells. The GCs
(germinal centers) contain large proliferating B lymphocytes and plasma cells interspersed
with macrophages and dendritic cells. The GC is a site of intense B-Cell activation and
differentiation into plasma cells and memory cells.
Paracortex - layer just beneath the cortex
It is an area populated with T lymphocytes and also interdigitating dendritic cells. It is an
important site for T cell activation by these APCs.
Medulla- inner most layer, more sparsely populated

Many of the cells are plasma cells so there is a fairly high concentration of immunoglobulin at this
site.

ii) Spleen: The spleen is a large, oval secondary lymphoid organ positioned high in the left
abdominal cavity. Spleen is adapted to filter the blood, it responds therefore to systemic infections.
It is surrounded by a capsule, which sends trabeculae into the interior to form a compartmentalized
structure. Two types of compartments with a Marginal Zone in between:

Red Pulp- Network of sinusoids populated with macrophages and numerous erythrocytes. Site
where old RBCs are destroyed and removed.
White Pulp- Surrounds the splenic arteries, forming a periarteriolar lymphoid sheath (PALS)
populated mainly by T lymphocytes. Clusters of B lymphocytes in the PALS form primary
follicles occupying a more peripheral position. Upon antigenic challenge, these primary
follicles develop into characteristic secondary follicles containing germinal centers.

iii) Mucosal-Associated Lymphoid Tissue (MALT): A variety of lymphoid tissues are found at
various locations along mucous membrane surfaces [digestive system, respiratory system and
urogenital system]. Major role appears to be as secondary lymphoid tissue. Probably most antigens
enter the body through this route so incredibly important and previously under-emphasized.

GALT gut associated lymphoid tissue – dispersed


BALT bronchus associated lymphoid tissue – dispersed
There are also organized clusters: tonsils, appendix, Peyer's patches
3 tonsil groups: lingual at base of tongue, palatine at side of back of mouth, nasopharyngeal in
the roof of the nasopharynx [adenoids]

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Antigens are delivered across the epithelial cell boundary of the mucosa by M cells. The M
cells have broad membrane processes on the lumen side and a deep pocket in basolateral
plasma membrane for clusters of B cells, T cells, and macrophages.

Fig. Secondary lymphoid organs

iv) Tonsils: The tonsils are areas of lymphoid tissue on either side of the throat. An infection of the
tonsils is called tonsillitis. Most commonly, the term "tonsils" refers to the palatine tonsils that can
be seen in the back of the throat. Like other organs of the lymphatic system, the tonsils act as part of
the immune system to help protect against infection. In particular, they are believed to be involved
in helping fight off pharyngeal and upper respiratory tract infections. Tonsils tend to reach their
largest size near puberty, and they gradually undergo atrophy thereafter.

21.4 FUNCTIONS OF RES

The secondary lymphoid structures function to survey all entering or circulating antigen and to mobilize
an immune response against foreign antigen upon its discovery. The GALT and BALT are privy to a
myriad of antigen entering the gastrointestinal and respiratory tracts, respectively. All extracellular fluid
must filter through lymph nodes as it traverses the lymphatics on its way back to the systemic
circulation. Antigen residing in the interstitium is thus swept to the lymph nodes for processing. Finally,
the spleen filters the blood in search of antigen. Upon the discovery of foreign antigen, all of these
tissues react in a similar manner to amass an appropriate and multifaceted immune response.

***

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Chapter – 9 KIDNEY

22. Structure and functions of kidney

22. STURCURE AND FUNCTIONS OF KIDNEY

22.1 INTRODUCTION
22.2 STRUCTURE
22.3 FUNCTIONS

22.1 INTRODUCTION

In humans, the kidneys are located in the posterior part of the abdomen. There is one on each side of the
spine; the right kidney sits just below the liver, the left below the diaphragm and adjacent to the spleen.
Above each kidney is an adrenal gland (also called the suprarenal gland). The asymmetry within the
abdominal cavity caused by the liver results in the right kidney being slightly lower than the left one
while the left kidney is located slightly more medial.

In a normal human adult, each kidney is about 10 cm long, 5.5 cm in width and about 3 cm thick,
weighing 150 grams. Together, kidneys weigh about 0.5% of a person's total body weight. The kidneys
are "bean-shaped" organs, and have a concave side facing inwards (medially).

22.2 STRUCTURE OF KIDNEY

Each kidney is about 4-5 inches long and about two inches thick in the average adult. Because of the
presence of many blood vessels, the kidneys are colored a dark reddish-brown. The kidney is divided
into an outer cortex, middle medulla and inner pelvis, 20% of blood pumped by heart goes through
kidneys.

The following are the main functional structures of kidneys:

Renal hilus:
The renal hilus is an indentation near to the centre of the concave area of the kidney. This is the
area of the kidney through which the ureter leaves the kidney and the other structures including
blood vessels (illustrated), lymphatic vessels, and nerves enter/leave the kidney.
Renal capsule:
The renal capsule is a smooth, transparent, fibrous membrane that surrounds, encloses, and
protects the kidney. Each kidney has it's own renal capsule (outer layer), which helps to
maintain the shape of the kidney as well as protecting it from damage. The renal capsule is itself
surrounded by a mass of fatty tissue that also helps to protect the kidney by damage by
cushioning it in cases of impact or sudden movement.
Renal cortex:
The renal cortex is the outer part of the kidney and has a reddish colour (shown as very pale
brown above). It has a smooth texture and is the location of the Bowman's Capsules and the
glomeruli, in addition to the proximal and distal convoluted tubules and their associated blood
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supplies (these structures are part of the kidney nephrons - described in further detail on the
page about kidney nephrons).
Renal medulla:
The renal medulla is the inner part of the kidney. "Medulla" means "inner portion". This area is
a striated (striped) red-brown colour.
Renal pyramids:
There are approx. 5 - 18 striated triangular structures called "Renal Pyramids" within the renal
medulla of each kidney. The apperance of striations is due to many straight tubules and blood
vessels within the renal pyramids.
Renal pelvis:
The renal pelvis is the funnel-shaped basin (cavity) that receives the urine drained from the
kidney nephrons via the collecting ducts and then the (larger) papillary ducts..
Renal artery:
The renal vein delivers oxygenated blood to the kidney. This main artery divides into many
smaller branches as it enters the kidney via the renal hilus. These smaller arteries divide into
vessels such as the segmental artery, the interlobar artery, the arcuate artery and the interlobular
artery. These eventually seperate into afferent arterioles, one of which serves each nephron in
the kidney.

Renal vein:
The renal artery receives deoxygenated blood from the peritubular veins within the kidney. These
merge into the interlobular, arcuate, interlobar and segmental veins, which, in turn, deliver
deoxygenated blood to the renal vein, through which it is returned to the systemic blood circulation
system.
Interlobular artery:
The interlobular artery delivers oxygenated blood at high pressure to the glomerular capillaries.

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Interlobular vein:
The interlobular vein receives deoxygenated blood (at lower pressure) that it drains away from the
glomerular filteration units and from the Loops of Henle.
Kidney nephron:
Kidney nephrons are the functional units of the kidneys. That this, it is the kidney nephrons that
actually perform the kidney's main functions. There are approx. a million nephrons within each kidney.

Fig. Structure of nephron

About one million nephrons are in the cortex of each kidney, and each one consists of a renal
corpuscle and a renal tubule which carry out the functions of the nephron. The renal tubule consists of
the convoluted tubule and the loop of Henley.

The nephron is part of the homeostatic mechanism of your body. This system helps regulate the
amount of water, salts, glucose, urea and other minerals in your body. The nephron is a filtration
system located in your kidney that is responsible for the reabsorption of water, salts. This is where
glucose eventually is absorbed in your body. One side note, diabetics have trouble reabsorbing the
glucose in their body and hence a lot of it comes out in the urine - hence the name "diabetic" or "sweet
urine." But that's another topic.

The Loop of Henley is the part of the nephron that contains the basic pathway for liquid. The liquid
begins at the Bowman's capsule (upper left) and then flows through the proximal convoluted tubule
(that mess of tangled stuff up top). It is here that Sodium, water, amino acids, and glucose get
reabsorbed. The filtrate then flows down the descending limb and then back up. On the way it passes a
major bend called the Loop Of Henle. This is located in the medulla of the kidney. As it approaches
the top again, hydrogen ions (waste) flow into the tube and down the collecting duct.

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Collecting Duct (Kidney):
The collecting duct labelled in the diagram above is part of the kidney nephron (shown much enlarged).
The distal convoluted tubules* (term explain on the page about kidney nephrons) of many nephrons
empty into a single collecting duct. Many such collecting ducts unite to drain urine extracted by the
kidney into papillary ducts, then into a minor calyx, then the major calyx (at the centre of the kidney),
and finally into the ureter through which the urine leaves the kidney en-route to the urinary bladder.
Ureter:
The ureter is the structure through which urine is conveyed from the kidney to the urinary bladder.

22.3 FUNCTIONS OF THE KIDNEY

The nephron is the functional unit of the kidney. The functions of the kidney can be divided into two
groups: secretion of hormones, and extracellular homeostasis.

22.3.1 Secretion of hormones

The kidneys secrete a variety of hormones, including erythropoietin, urodilatin, and vitamin D.
Secretion of erythropoietin, which regulates red blood cell production in the bone marrow.
Secretion of renin, which is a key part of the renin-angiotensin-aldosterone system.
Secretion of the active form of vitamin D, calcitriol, and prostaglandins.

22.3.2 Extracellular homeostasis

The kidney is responsible for maintaining a balance of several substances: Blood Filtering by
filtration, reabsorption and secretion. First, the blood enters through the glomerulus.

Filtration and Reabsorbtion During progress through the nephron, some solutes like sodium
chloride, potassium and glucose are reabsorbed, along with water, back into the bloodstream. This
maintains a correct balance of these chemicals within the blood, assisting blood pressure regulation,
for example. The filtration and reabsorbtion of glucose within the kidneys also helps to maintain
correct levels of vital blood sugars. When this regulation breaks down very serious health
consequences can follow.

Urea and uric acid are nitrogen containing waste products from metabolic processes in the body.
These substances are potentially toxic and are partially excreted by the kidneys to maintain good
health. Interestingly, of the filtrate which enters each nephron from the blood, only about 1%
actually leaves the body as urine because of the various reabsorbtion mechanisms driven by
osmosis, diffusion, and active transport.

Tubular Secretion in the Kidneys Another, less familiar, mechanism for urine production in the
kidneys is tubular secretion. Specialised cells move solutes directly from the blood into the tubular
fluid. For example, hydrogen and potassium ions are secreted directly into the tubular fluid. This
process is ―coupled‖ or balanced by the re-uptake of sodium ions back into the blood.

Tubular secretion of hydrogen ions, augmented by control of bicarbonate levels, is important in


maintaining correct blood pH. When the blood is too acidic (acidosis) more hydrogen ions are
secreted. If the blood becomes too alkaline (alkalosis), hydrogen secretion is reduced. In

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maintaining blood pH within normal limits (about 7.35–7.45) the kidney can produce urine with pH
as low as that of acid rain or as alkaline as baking soda!

Excretion of waste products: The kidneys excrete a variety of waste products produced by
metabolism, including the nitrogenous wastes: urea (from protein catabolism) and uric acid (from
nucleic acid metabolism) and water.

Homeostasis: The kidney is one of the major organs involved in whole-body homeostasis. Among
its homeostatic functions are acid-base balance, regulation of electrolyte concentrations, control of
blood volume, and regulation of blood pressure. The kidneys accomplish these homeostatic
functions independently and through coordination with other organs, particularly those of the
endocrine system. The kidney communicates with these organs through hormones secreted into the
bloodstream.

Acid-base balance: The kidneys regulate the pH of blood by adjusting H+ ion levels, referred as
augmentation of mineral ion concentration, as well as water composition of the blood.

Blood pressure: The renin-angiotensin system (RAS) or the renin-angiotensin-aldosterone system


(RAAS) is a hormone system that regulates blood pressure and water (fluid) balance. When blood
pressure is low, the kidneys secrete renin. Renin stimulates the production of angiotensin.
Angiotensin causes blood vessels to constrict resulting in increased blood pressure. Angiotensin also
stimulates the secretion of the hormone aldosterone from the adrenal cortex. Aldosterone causes the
tubules of the kidneys to retain sodium and water. This increases the volume of fluid in the body,
which also increases blood pressure.

Plasma volume: Any significant rise or drop in plasma osmolarity is detected by the hypothalamus,
which communicates directly with the posterior pituitary gland. A rise in osmolarity causes the
gland to secrete antidiuretic hormone, resulting in water reabsorption by the kidney and an increase
in urine concentration. The two factors work together to return the plasma osmolarity to its normal
levels.

***

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Chapter – 10 SKELETEL SYSTEM

23. Organization of skeletal system


24. Osteocyte and their functions
25. Bone marrow and its role

23. ORGANIZATION OF SKELETAL SYSTEM

23.1 INTRODUCTION
23.2 AXIAL SKELETON
23.3 APPENDICULAR SKELETON

23.1 INTRODUCTION

The human skeleton consists of both fused and individual bones supported and supplemented by
ligaments, tendons, muscles and cartilage. It serves as a scaffold which supports organs, anchors
muscles, and protects organs such as the brain, lungs and heart. The longest and heaviest bone in the
body is the femur and the smallest is the stapes bone in the middle ear. In an adult, the skeleton
comprises around 13% of the total body weight, and half of this weight is water. Fused bones include
those of the pelvis and the cranium. Not all bones are interconnected directly:

There are six bones in the middle ear called the ossicles (three on each side) that articulate only with
each other. The hyoid bone, which is located in the neck and serves as the point of attachment for the
tongue, does not articulate with any other bones in the body, being supported by muscles and ligaments.

Much of the human skeleton maintains the ancient segmental pattern present in all vertebrates
(mammals, birds, fish, reptiles and amphibians) with basic units being repeated. This segmental pattern
is particularly evident in the vertebral column and in the ribcage.

There are 206 bones in the adult human skeleton, a number which varies between individuals and with
age - newborn babies have 270 bones some of which fuse together. These bones are organized into a
longitudinal axis, the axial skeleton, to which the appendicular skeleton is attached.

23.1 AXIAL SKELETON

The axial skeleton (80 bones) is formed by the vertebral column (26), the thoracic cage (12 pairs of ribs
and the sternum), and the skull (22 bones and 7 associated bones). The axial skeleton transmits the
weight from the head, the trunk, and the upper extremities down to the lower extremities at the hip
joints, and is therefore responsible for the upright position of the human body.

Most of the body weight is located in front of the spinal column which therefore have the erector spinae
muscles and a large amount of ligaments attached to it resulting in the curved shape of the spine. The
240 skeletal muscles acting on the axial skeleton position the spine, allowing for small movements in
the thoracic cage for breathing, and the head, where they control the minute and complex facial
movements.

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23.2 APPENDICULAR SKELETON

The appendicular skeleton (126 bones) is subdivided into the upper and lower extremities: The axial
skeleton is connected to the upper extremity (60) through the pectoral girdle (4) and to the lower
extremity (60) through the pelvic girdle (2). Some 300 muscles attach to the appendicular skeleton.

The only joint between the pectoral girdle and the thorax is between the clavicle and the sternum (i.e.
the sternoclavicular joint), the scapula instead being controlled by muscles. The humerus articulates to
the scapula at the shoulder joint and to the two parallel bones of forearm, the radius and ulna, in the
elbow joints (humeroulnar, humeroradial, and radioulnar). The distal ends of the forearm bones form the
wrist joints with the hand. In the hand, eight carpal bones arranged in two rows articulate with the
metacarpal bones of the palm which articulate with the 14 finger bones (the phalanges).

The pelvic girdle is a composite structure which includes bones from both the axial skeleton, the sacrum
and the coccyx, and the lower extremities, the two hip bones. Because the lower limbs have to bear the
weight of the human body — reaction forces at the feet can be 5-10 times the body weight during
sprinting and jumping — the bones of the pelvic girdle, the thigh, and the lower leg are massive and
have a network of fibers and many strong muscles to maximize strength and stability. Similarly, and in
contrast to the elbow, in the knee the kneecap, a sesamoid bone formed in the tendon of the large
quadriceps muscles of the thigh, protects the knee from damage while helping the muscles in extending
the knee. In each ankle there are 7 tarsal bones, including the heel bone, and in each foot 5 metatarsal
bones and 14 phalanges.

Fig. Organization of human skeletal system

***

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TABLE : Axial Skeleton Bones (80 Bones)
General Description Name of Bone No. of Bones Additional Information
cranium (8) frontal 1
parletal 2
temporal 2
sphenoid 1
ethmoid 1
occipital 1
facial bones (14) mandible 1 lower jawbone
maxilla 2 upper jawbone
zygomatic bone 2 cheek bones
nasal bone 2
lacrimal bone 2
palatine 2
inferior nasal concha 2
vomer 1
hyoid hyoid 1
ear ossicles malleus, incus, stapes 6 2 each
vertebral column (26) cervical vertebrae 7 C1-C7
thoracic vertebrae 12 T1-T12
lumbar vertebrae 5 L1-L5
sacrum 1 5 fused S1 - S5
coccyx 1 4 fused
thorax (thoracic cage or bony thorax) sternum 1
true ribs (7 pair) 14 vertebrosternal
false ribs (3 pair) 6 vertebrochondral
false ribs (floating ribs) 4 vertebral ribs

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TABLE : Appendicular Skeleton Bones (126 Bones)

General Description Name of Bone No. of Bones Additional Information

pectoral girdle clavicle 2 collarbone

(shoulder girdle) scapula 2 shoulder blade

upper limb (60) humerus 2 1 per arm

ulna 2 1 per forearm

radius 2 8 per wrist

carpals (16)

1. scaphoid 2

2. trapezium 2

3. capitate 2

4. trapezoid 2

5. lunate 2

6. triquetrum 2

7. pisiform 2

8. hamate 2

metacarpals 10 5 in each arm

phalanges 28 3 per digit (pollex has 2)

pelvic girdle coxal bones (os coxae) 2 hip bones

(hip) (2) 1. ilium

2. ischium (3 fused pairs)

3. pubis

lower limb (60) femur 2

patella 2

tibia 2

fibula 2

lower limb (60) tarsal (14)

1. talus 2

2. calcaneus 2

3. cuboid 2

4. navicular 2

5. medial cuneiform 2

6. interm. cuneiform 2

7. lateral cuneiform 2

lower limb (60) metatarsals 2 5 per foot

phalanges 2 3 per toe (hallux has 2)

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24. OSTEOCYTE AND THEIR FUNCTIONS

An osteocyte, a star-shaped cell, is the most abundant cell found compact bone. Cells contain a nucleus
and a thin ring of cytoplasm. When osteoblasts become trapped in the matrix they secrete, they become
osteocytes. Osteocytes are networked to each other via long cytoplasmic extensions that occupy tiny
canals called canaliculi, which are used for exchange of nutrients and waste. The space that an osteocyte
occupies is called a lacuna.

Although osteocytes have reduced synthetic activity and, like osteoblasts are not capable of mitotic
division, they are actively involved in the routine turnover of bony matrix, through various
mechanosensory mechanisms. They destroy bone through a rapid, transient (relative to osteoclasts)
mechanism called osteocytic osteolysis. Osteoblasts/osteocytes develop in mesenchyme.
Hydroxyapatite, calcium carbonate and calcium phosphate is deposited around the cell.

Fig. Structure of Osteocyte

FUNCTIONS:

Special features of osteocytes.

Osteocyte are actively involved in bone turnover;


The osteocyte network is through its large cell-matrix contact surface involved in ion exchange; and
Osteocytes are the mechanosensory cells of bone and play a pivotal role in functional adaptation of
bone.

The osteocyte is capable of bone deposition and resorption. It also is involved in bone remodeling by
transmitting signals to other osteocytes in response to even slight deformations of bone caused by
muscular activity. In this way, bone becomes stronger if additional stress is placed on it (for example,
by frequent exercise or physical exertion) and weaker if it is relieved of stress (for example, by
inactivity). The osteocyte may aid in calcium removal from bone when the body’s calcium level drops
too low.

***

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25. BONE MARROW AND ITS ROLE

25.1 INTRODUCTION
25.2 ANATOMY
25.3 FUNCTION OF BONE MARROW
25.1 INTRODUCTION

Bone marrow is a special, spongy, fatty tissue that houses stem cells, located inside a few large bones.
These stem cells transform themselves into white and red blood cells and platelets, essential for
immunity and circulation. Anemia, leukemia, and other lymphoma cancers can compromise the
resilience of bone marrow. Bone marrow transplants are a growing treatment for these conditions of the
lymphatic system that can't be otherwise cured.

Our skull, sternum, ribs, pelvis, and femur bones all contain bone marrow, but other smaller bones do
not. Inside this special tissue, immature stems cells reside, along with extra iron. While they are
undifferentiated, the stem cells wait until unhealthy, weakened, or damaged cells need to be replaced. A
stem cell can turn itself into a platelet, a white blood cell like a T-cell, or a red blood cell. This is the
only way such cells get replaced to keep our body healthy.

25.2 ANATOMY

Bone marrow is the flexible tissue found in the hollow interior of bones. In adults, marrow in large
bones produces new blood cells. It constitutes 4%[1] of total body weight, i.e. approximately 2.6 kg (5.7
lbs.) in adults.

25.2.1 Marrow types

Section through the femur head, showing the cortex, the red bone marrow and a spot of yellow bone
marrow. The white bar represents 1 centimeter.

There are two types of bone marrow: red marrow (consisting mainly of myeloid tissue) and yellow
marrow (consisting mainly of fat cells). Red blood cells, platelets and most white blood cells arise in
red marrow; some white blood cells develop in yellow marrow. Both types of bone marrow contain
numerous blood vessels and capillaries.

At birth, all bone marrow is red. With age, more and more of it is converted to the yellow type. About
half of the bone marrow is red. Red marrow is found mainly in the flat bones, such as the hip bone,
breast bone, skull, ribs, vertebrae and shoulder blades, and in the cancellous ("spongy") material at the
epiphyseal ends of the long bones such as the femur and humerus. Yellow marrow is found in the
hollow interior of the middle portion of long bones.

In cases of severe blood loss, the body can convert yellow marrow back to red marrow in order to
increase blood cell production.

25.2.2 Stroma

The stroma of the bone marrow is all tissue that isn't directly involved in the primary function of
hematopoiesis. The yellow bone marrow belongs here, and makes the majority of the bone marrow
stroma, in addition to stromal cells located in the red bone marrow.
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Still, the stroma is indirectly
involved in hematopoiesis,
since it provides the
hematopoietic
microenvironment that
facilitates hematopoiesis by the
parenchymal cells. For
instance, they generate colony
stimulating factors, affecting
hematopoiesis. Cells that
constitute the bone marrow
stroma are:

fibroblasts (reticular
connective tissue)
macrophages
adipocytes
osteoblasts
blood vessels (sinusoid) Fig. Cross section of Bone marrow

Bone marrow barrier: The blood vessels constitute a barrier, inhibiting immature blood cells from
leaving the bone marrow. Only mature blood cells contain the membrane proteins required to attach to
and pass the blood vessel endothelium. Hematopoietic stem cells may also cross the bone marrow
barrier, and may thus be harvested from blood.

Stem cells: The bone marrow stroma contain mesenchymal stem cells (also called marrow stromal
cells). These cells are multipotent stem cells that can differentiate into a variety of cell types. Cell
types that MSCs have been shown to differentiate into in vitro or in vivo include osteoblasts,
chondrocytes, myocytes, adipocytes, and, as described lately, beta-pancreatic islets cells. They can
also transdifferentiate into neuronal cells. Bone marrow contains three types of stem cells:

Hematopoietic stem cells give rise to the three classes of blood cells that are found in the
circulation: white blood cells (leukocytes), red blood cells (erythrocytes), and platelets
(thrombocytes).
Mesenchymal stem cells are found arrayed around the central sinus in the bone marrow. They have
the capability to differentiate into osteoblasts, chondrocytes, myocytes, and many other types of
cells. They also function as "gatekeeper" cells of the bone marrow.
Endothelial stem cells

25.2.3 Compartmentalization
There is biologic compartmentalization in the bone marrow, in that certain cell types tend to aggregate
in specific areas. For instance, erythrocytes, macrophages and their precursors tend to gather around
blood vessels, while granulocytes gather at the borders of the bone marrow.

25.3 FUNCTIONS

Hematopoietic stem cells from bone marrow are the most studied and used for clinical applications in
restoring various blood and immune components to the bone marrow via transplantation. There are at
least two other populations of adult stem cells that have been identified from bone marrow and blood.

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Their primary functions are to maintain the steady state functioning of a cell—called homeostasis—and,
with limitations, to replace cells that die because of injury or disease. For example, only an estimated 1
in 10,000 to 15,000 cells in the bone marrow is a hematopoietic (bloodforming) stem cell (HSC).

Gut epithelial stem cells (or precursors) occur at the bases of crypts—deep invaginations between the
mature, differentiated epithelial cells that line the lumen of the intestine. These epithelial crypt cells
divide fairly often, but remain part of the stationary group of cells they generate.

Unlike embryonic stem cells, which are defined by their origin (the inner cell mass of the blastocyst),
adult stem cells share no such definitive means of characterization. In fact, no one knows the origin of
adult stem cells in any mature tissue. Some have proposed that stem cells are somehow set aside during
fetal development and restrained from differentiating.

Fig. Role of Bone marrow

Definitions of adult stem cells vary in the scientific literature range from a simple description of the
cells to a rigorous set of experimental criteria that must be met before characterizing a particular cell as
an adult stem cell. Most of the information about adult stem cells comes from studies of mice. The list
of adult tissues reported to contain stem cells is growing and includes bone marrow, peripheral blood,

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brain, spinal cord, dental pulp, blood vessels, skeletal muscle, epithelia of the skin and digestive system,
cornea, retina, liver, and pancreas.

In order to be classified as an adult stem cell, the cell should be capable of self-renewal for the lifetime
of the organism. This criterion, although fundamental to the nature of a stem cell, is difficult to prove in
vivo. It is nearly impossible, in an organism as complex as a human, to design an experiment that will
allow the fate of candidate adult stem cells to be identified in vivo and tracked over an individual's entire
lifetime. Ideally, adult stem cells should also be clonogenic.

Adult stem cells may assume the characteristics of cells that have developed from the same primary
germ layer or a different germ layer. For example, many plasticity experiments involve stem cells
derived from bone marrow, which is a mesodermal derivative. The bone marrow stem cells may then
differentiate into another mesodermally derived tissue such as skeletal muscle, cardiac muscle or liver.

Alternatively, adult stem cells may differentiate into a tissue that—during normal embryonic
development—would arise from a different germ layer. For example, bone marrow-derived cells may
differentiate into neural tissue, which is derived from embryonic ectoderm. And—reciprocally—neural
stem cell lines cultured from adult brain tissue may differentiate to form hematopoietic cells , or even
give rise to many different cell types in a chimeric embryo .

One population of bone marrow cells, the hematopoietic stem cells (HSCs), is responsible for forming
all of the types of blood cells in the body. HSCs were recognized as a stem cells more than 40 years ago.
Bone marrow stromal cells—a mixed cell population that generates bone, cartilage, fat, fibrous
connective tissue, and the reticular network that supports blood cell formation—were described shortly
after the discovery of HSCs.

Bone marrow adipocytes and myelosupportive stromal cells—both of which are derived from BM
stromal cells—may be regarded as interchangeable phenotypes. Adipocytes do not develop until
postnatal life, as the bones enlarge and the marrow space increases to accommodate enhanced
hematopoiesis.

***

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Chapter – 11 NERVOUS SYSTEM

26. Organization of nervous system


27. Chemical transmitters

26. ORGANIZATION OF NERVOUS SYSTEM

26.1 INTRODUCTION
26.2 CENTRAL NERVOUS SYSTEM
26.3 PERIPHERAL NERVOUS SYSTEM
26.4 AUTONOMOUS NERVOUS SYSTEM
26.1 INTRODUCTION
The nervous system is the most intricate and delicate system in the human body. It is a highly
specialized set of nerve cells that are responsible for monitoring and directing a vast array of crucial
elements such as the five senses, the involuntary and voluntary functions (for example, coordination,
balance and blood pressure), as well as the capacity for deliberate thought and reasoning.

The nervous system is divided into two categories: the central and the peripheral nervous systems. The
central nervous system is the larger of the two and consists of the brain (located within the skull) and
the spinal cord (located within the vertebral column.) It is in charge of controlling how a person receives
and processes data, how a person moves, as well as how well the senses function.

The peripheral nervous system consists of the nerve cells that exist outside of the central nervous system
(such as those used for extremities and organs) and are used to transmit data from the body to the brain
and vice versa. The system is divided into two categories: the somatic and the autonomic nervous
systems. The autonomic nervous system is further broken down into three categories: the sympathetic,
the parasympathetic and the enteric.

Fig. Organization of Nervous system

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26.2 CENTRAL NERVOUS SYSTEM ORGANIZATION

In vertebrates, the central nervous system (CNS) is the part of the nervous system which is enclosed in
the meninges. It contains the majority of the nervous system and consists of the brain (in vertebrates
which have them), and the spinal cord. he CNS is contained within the dorsal cavity, with the brain in
the cranial cavity and the spinal cord in the spinal cavity. The brain is protected by the skull, while the
spinal cord is protected by the vertebrae.

Rhinencephalon, Amygdala,
Telencephalon Hippocampus, Neocortex, Lateral
ventricles
Prosencephalon
Epithalamus, Thalamus, Hypothalamus,
Diencephalon Subthalamus, Pituitary gland, Pineal
Central Brain gland, Third ventricle
nervous Tectum, Cerebral peduncle, Pretectum,
Mesencephalon
system Mesencephalic duct
Pons,
Brain stem Metencephalon
Cerebellum,
Rhombencephalon
Medulla
Myelencephalon
oblongata
Spinal cord

26.2.1 Brain

The adult human brain is a 1.3-kg (3-lb) mass of pinkish-gray jellylike tissue made up of
approximately 100 billion nerve cells, or neurons; neuroglia (supporting-tissue) cells; and vascular
(blood-carrying) and other tissues. Between the brain and the cranium—the part of the skull that
directly covers the brain—are three protective membranes, or meninges. The outermost membrane,
the dura mater, is the toughest and thickest. Below the dura mater is a middle membrane, called the
arachnoid layer. The innermost membrane, the pia mater, consists mainly of small blood vessels
and follows the contours of the surface of the brain.

A clear liquid, the cerebrospinal fluid, bathes the entire brain and fills a series of four cavities, called
ventricles, near the center of the brain. The cerebrospinal fluid protects the internal portion of the
brain from varying pressures and transports chemical substances within the nervous system.

The brain is made of three main parts: the forebrain, midbrain, and hindbrain. The forebrain
consists of the cerebrum, thalamus, and hypothalamus (part of the limbic system). The midbrain
consists of the tectum and tegmentum. The hindbrain is made of the cerebellum, pons and medulla.
Often the midbrain, pons, and medulla are referred to together as the brainstem.

i) Forebrain (cerebrum, thalamus, and hypothalamus):


The forebrain, or prosencephalon as it is also known, develops in the adult to form the following
components:

cerebrum (cerebral cortex + basal ganglia)


Diencephalon (hypothalamus and thalamus

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The Cerebrum: The cerebrum or cortex is the largest part of the human brain, associated with
higher brain function such as thought and action. It consists of two cerebral hemispheres. These
hemispheres have an outer convoluted layer of gray matter – the cerebral coretx – and an inner
layer of white matter. The two halves are linked by the corpus callosum. Each hemisphere of the
cerebrum (cerebral cortex ) is subdivided into four lobes visible from the outside. They are the
frontal, parietal, occipital, and temporal lobes.

Frontal Lobe- associated with reasoning, planning, parts of speech, movement, emotions,
and problem solving
Parietal Lobe- associated with movement, orientation, recognition, perception of stimuli
Occipital Lobe- associated with visual processing
Temporal Lobe- associated with perception and recognition of auditory stimuli, memory,
and speech

Diencephalon: The Diencephalon is composed of two structures: the thalamus and the
hypothalamus. Thalamus- a large mass of gray matter deeply situated in the forebrain at the
topmost portion of the diencephalon. The structure has sensory and motor functions. Almost all
sensory information enters this structure where neurons send that information to the overlying
cortex. Axons from every sensory system (except olfaction) synapse here as the last relay site
before the information reaches the cerebral cortex. Hypothalamus- part of the diencephalon,
ventral to the thalamus. The structure is involved in functions including homeostasis, emotion,
thirst, hunger, circadian rhythms, and control of the autonomic nervous system. In addition, it
controls the pituitary.

The limbic system, often referred to as the "emotional brain", is found buried within the
cerebrum. This system contains the thalamus, hypothalamus, amygdala, and hippocampus.

Fig. Internal parts of human brain

ii) Midbrain (tectum and tegmentum)


Midbrain or Mesencephalon-the rostral part of the brain stem, which includes the tectum and
tegmentum. It is involved in functions such as vision, hearing, eyemovement, and body
movement. The anterior part has the cerebral peduncle, which is a huge bundle of axons traveling
from the cerebral cortex through the brain stem and these fibers (along with other structures) are
important for voluntary motor function.

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The tectum is a region of the brain, specifically the dorsal part of the mesencephalon (midbrain).
The tegmentum is the part of the midbrain extending from the substantia nigra to the cerebral
aqueduct in a horizontal section of the midbrain. It forms the floor of the midbrain which
surrounds the cerebral aqueduct.

iii) Hindbrain (cerebellum, pons and medulla)


Also known as the rhombencephalon, one of the three sections of the brain of a vertebrate
embryo, the others being the forebrain and midbrain. The hindbrain develops to form the
cerebellum, pons, and medulla oblongata, which coordinate complex muscular movements
(cerebellum) and control and coordinate fundamental physiological processes, including
breathing and blood circulation.

Cerebellum: The cerebellum is a rounded structure with a convoluted surface, similar in


appearance to the cerebrum. It is located behind the brainstem and connected to it by thick
nerve tracts. Outwardly, the cerebellum consists of two hemispheres flanking the vermis,
which is a small protrusion from the brainstem. The cortex (outer part) of the hemispheres
consists of numerous parallel ridges separated by deep fissures, so that only one sixth of the
surface is visible. From the inner side of hemisphere, three nerve fiber stalks, or peduncles,
arise; these link up with different parts of the brainstem. All the signals between the
cerebellum and the rest of the brain travel along these nerve tracts.

Under the microscope, a cross-section of the cerebellum shows the nerve fibers from these
tracts fanning out toward the convoluted cortical surface. The cortex itself consists of gray
matter (interconnected nerve cells) arranged in three main layers. Prominent in the middle
layer are large cells called Purkinje's cells, each of which may interconnect with as many as
100,000 other cells.

Function of the cerebellum: Via its connections to the brainstem, the cerebellum receives
information from organs such as muscle tendons and the balance organ of the inner ear.
Much of this information concerns the body's posture and the state of contraction or
relaxation of its muscles. Using this information, the cerebellum, working in concert with the
basal ganglia, fine-tunes the orders sent to muscles from the motor cortex in the cerebrum,
resulting in smoothly coordinated movements and balance.

Pons: One of the structures located in the lower brainstem just above the spinal cord. It
consists of a thick bundle of nerve fibers that links the medulla oblongata to the midbrain. The
pons serves as a major pathway for motor and sensory information between the body and
higher level brain functioning.

Medulla: The lowest part of the brainstem. The medulla oblongata looks like a swelling at the
tip of the spinal cord; it is continuous with the spinal cord above the level of the foramen
magnum of the occipital bone. The medulla oblongata regulates the reflex responses that
control breathing, heart beat, blood pressure, and other essential involuntary functions. It also
contains part of the reticular formation that plays a role in arousal states, such as wakefulness
and attention, and it gives rise to many of the cranial nerves. General anesthesia probably
works by depressing medulla activity.

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26.2.2 Spinal Cord

A thick, whitish cylinder of nerve tissue that runs down the central canal of the spinal column. The
spinal cord is an extension of the brain, and together with the brain forms the central nervous
system. The spinal cord originates at the lower (inferior) end of the medulla oblongata, at the bottom
of the brainstem. It leaves the skull via a large opening called the foramen magnum, and extends
about two-thirds of the way down the spine, as far as the first lumbar vertebra.

The spinal cord is unique to the nervous system of vertebrates. In an adult human it is about 45 cm
(18 in.) long and roughly as thick as a finger. Spinal nerves from the spinal cord branch off to
various parts of the body.

Fig. Transverse section of spinal cord

Structurally, the spinal cord is a double-layered tube, roughly cylindrical in cross section, though the
diameter varies at different vertebral levels. The outer layer of the spinal cord consists of white
matter, i.e., myelin-sheathed nerve fibers. These are bundled into specialized tracts that conduct
impulses triggered by pressure, pain, heat, and other sensory stimuli or conduct motor impulses
activating muscles and glands.

The inner layer, or gray matter, has a butterfly-shaped cross-section and is mainly composed of
nerve cell bodies. Within the gray matter, running the length of the cord and extending into the
brain, lies the central canal through which the cerebrospinal fluid circulates. Three protective
membranes, known as the meninges, wrap the spinal cord and cover the brain – the pia mater is the
innermost layer, the arachnoid lies in the middle, and the dura mater is the outside layer, to which
the spinal nerves are attached.

Connecting with the cord are 31 pairs of these spinal nerves, which feed sensory impulses into the
spinal cord, which in turn relays them to the brain. Conversely, motor impulses generated in the
brain are relayed by the spinal cord to the spinal nerves, which pass the impulses to muscles and

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glands. The spinal cord mediates the reflex responses to some sensory impulses directly, i.e.,
without recourse to the brain, as when a person's leg is tapped producing the knee jerk reflex.

26.3 PERIPHERAL NERVOUS SYSTEM

There are two types of cells in the peripheral nervous system. These cells carry information to (sensory
nervous cells) and from (motor nervous cells) the central nervous system (CNS). Cells of the sensory
nervous system send information to the CNS from internal organs or from external stimuli.

Motor nervous system cells carry information from the CNS to organs, muscles, and glands. The motor
nervous system is divided into the somatic nervous system and the autonomic nervous system. The
somatic nervous system controls skeletal muscle as well as external sensory organs such as the skin.
This system is said to be voluntary because the responses can be controlled consciously. Reflex
reactions of skeletal muscle however are an exception. These are involuntary reactions to external
stimuli.

The Sensory-Somatic Nervous System: The sensory-somatic system consists of


12 pairs of cranial nerves and
31 pairs of spinal nerves.

The Cranial Nerves:


Nerves Type Function
I Olfactory sensory olfaction (smell)
vision
II Optic sensory
(Contain 38% of all the axons connecting to the brain.)
III Oculomotor motor* eyelid and eyeball muscles
IV Trochlear motor* eyeball muscles
Sensory: facial and mouth sensation
V Trigeminal mixed
Motor: chewing
VI Abducens motor* eyeball movement
Sensory: taste
VII Facial mixed Motor: facial muscles and
salivary glands
VIII Auditory sensory hearing and balance
Sensory: taste
IX Glossopharyngeal mixed
Motor: swallowing
main nerve of the
X Vagus mixed
parasympathetic nervous system (PNS)
XI Accessory motor swallowing; moving head and shoulder
XII Hypoglossal motor* tongue muscles

The Spinal Nerves: All of the spinal nerves are "mixed"; that is, they contain both sensory and motor
neurons. All our conscious awareness of the external environment and all our motor activity to cope
with it operate through the sensory-somatic division of the PNS.

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26.4 AUTONOMOUS NERVOUS SYSTEM

The autonomic nervous system (ANS) (or visceral nervous system) is the part of the peripheral nervous
system that acts as a control system, maintaining homeostasis in the body. These activities are generally
performed without conscious control or sensation. The ANS affects heart rate, digestion, respiration
rate, salivation, perspiration, diameter of the pupils, micturition (urination), and sexual arousal. Whereas
most of its actions are involuntary, some, such as breathing, work in tandem with the conscious mind.
Its main components are its sensory system, motor system (comprised of the parasympathetic nervous
system and sympathetic nervous system), and the enteric nervous system.

26.4.1 Sympathetic Nervous System

Like other parts of the nervous system, the sympathetic nervous system operates through a series of
interconnected neurons. Sympathetic neurons are frequently considered part of the peripheral nervous
system (PNS), although many lie within the central nervous system (CNS). Sympathetic neurons of
the spinal cord (which is part of the CNS) communicate with peripheral sympathetic neurons via a
series of sympathetic ganglia.

Within the ganglia, spinal cord sympathetic neurons join peripheral sympathetic neurons through
chemical synapses. Spinal cord sympathetic neurons are therefore called presynaptic (or
preganglionic) neurons, while peripheral sympathetic neurons are called postsynaptic (or
postganglionic) neurons....The preganglionic motor neurons of the sympathetic system arise in the
spinal cord. They pass into sympathetic ganglia which are organized into two chains that run parallel
to and on either side of the spinal cord.

The preganglionic neuron may do one of three things in the sympathetic ganglion:

synapse with postganglionic neurons which then reenter the spinal nerve and ultimately pass out to
the sweat glands and the walls of blood vessels near the surface of the body.
pass up or down the sympathetic chain and finally synapse with postganglionic neurons in a higher
or lower ganglion
leave the ganglion by way of a cord leading to special ganglia (e.g. the solar plexus) in the viscera.
Here it may synapse with postganglionic sympathetic neurons running to the smooth muscular
walls of the viscera.

The neurotransmitter of the preganglionic sympathetic neurons is acetylcholine (ACh). It stimulates


action potentials in the postganglionic neurons. The neurotransmitter released by the postganglionic
neurons is noradrenaline (also called norepinephrine). The action of noradrenaline on a particular
gland or muscle is excitatory is some cases, inhibitory in others. (At excitatory terminals, ATP may be
released along with noradrenaline.)

The release of noradrenaline


stimulates heartbeat
raises blood pressure
dilates the pupils
dilates the trachea and bronchi
stimulates the conversion of liver glycogen into glucose
shunts blood away from the skin and viscera to the skeletal muscles, brain, and heart
inhibits peristalsis in the gastrointestinal (GI) tract

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inhibits contraction of the bladder and rectum
and, at least in rats and mice, increases the number of AMPA receptors in the hippocampus and
thus increases long-term potentiation (LTP).

26.4.2 Parasympathetic Nervous System

The parasympathetic nervous system (PSNS) is a division of the autonomic nervous system, along
with the sympathetic nervous system (SNS) and enteric nervous system (ENS or "bowels NS"). The
main nerves of the parasympathetic system are the tenth cranial nerves, the vagus nerves. They
originate in the medulla oblongata. Other preganglionic parasympathetic neurons also extend from the
brain as well as from the lower tip of the spinal cord.

Each preganglionic parasympathetic neuron synapses with just a few postganglionic neurons, which
are located near - or in - the effector organ, a muscle or gland. Acetylcholine (ACh) is the
neurotransmitter at all the pre- and many of the postganglionic neurons of the parasympathetic system.
However, some of the postganglionic neurons release nitric oxide (NO) as their neurotransmitter.

Parasympathetic stimulation causes


slowing down of the heartbeat
lowering of blood pressure
constriction of the pupils
increased blood flow to the skin and viscera
peristalsis of the GI tract

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In short, the parasympathetic system returns the body functions to normal after they have been altered
by sympathetic stimulation. In times of danger, the sympathetic system prepares the body for violent
activity. The parasympathetic system reverses these changes when the danger is over. The vagus
nerves also help keep inflammation under control. Inflammation stimulates nearby sensory neurons of
the vagus. When these nerve impulses reach the medulla oblongata, they are relayed back along motor
fibers to the inflamed area. The acetylcholine from the motor neurons suppresses the release of
inflammatory cytokines, e.g., tumor necrosis factor (TNF), from macrophages in the inflamed tissue.

***

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27. CHEMICAL TRANSMITTERS (NEUROTRANSMITTERS)

27.1 INTRODUCTION
27.2 CHEMICAL TRANSMITTERS MECHANISM OF ACTION
27.3 TYPES OF CHEMICAL TRANSMITTERS

27.1 INTRODUCTION

Multicellular organisms, however, have evolved a more complex system that responds to external
stimuli through the use of specialized sense organs and the communication of the information from
these sensors to other parts of the organism. This type of communication falls into two categories. The
first category is the transmission of chemical messengers between one tissue and another. The second is
a more multifarious mechanism that involves the generation and transmission of impulses through the
central nervous system.

In higher organisms, the chief unit of the central nervous system is a highly specialized cell termed a
neuron, which serves to transmit impulses. In the human brain there are approximately 10 billion
neurons, each with its own identity and function. The communication processes carried out among such
a large body of cells is complex and the basic cellular structure for neurons differs radically from that of
different types of cells. Most neurons have a cell body somewhat like that found in other somatic cells,
however, they also exhibit a variety of projections (or processes) called dendrites and axons.

Dendrites are branched protoplasmic extensions that receive neural signals from adjacent cells and
conduct them inwards toward the body of the neuron. A single neuron may feature multiple dendrites.
Typically, however, neurons each only possess a single long, threadlike axon, which carries signals
away from the cell body and is capable of transmitting them to a dendrite on an adjacent cell. The
connection between the axon terminals of one cell and the dendrites of an adjacent cell is called a
synapse. The transmission of signals across a synapse is initiated by the presence of an electrical
impulse and is accomplished by the use of small chemical messengers that are termed
neurotransmitters.

There are more than 300 known neurotransmitters, including chemicals such as acetylcholine ,
norepinephrine , adenosine triphosphate , Dopamine, GABA, Serotonin and the endorphins, and gases,
such as nitric oxide .

27.2 MECHANISM OF ACTION OF CHEMICAL TRANSMITTERS

Neurotransmitters are formed in a presynaptic neuron and stored in small membrane-bound sacks,
called vesicles, inside this neuron. When this neuron is activated, these intracellular vesicles fuse with
the cell membrane and release their contents into the synapse, a process called exocytosis.

Once the neurotransmitter is in the synapse, several events may occur. It may (1) diffuse across the
synapse and bind to a receptor on the postsynaptic membrane, (2) diffuse back to the presynaptic
neuron and bind to a presynaptic receptor causing modulation of neurotransmitter release, (3) be
chemically altered by an enzyme in the synapse, or (4) be transported into a nearby cell. For the
chemical message to be passed to another cell, however, the neurotransmitter must bind to its protein
receptor on the postsynaptic side. The binding of a neurotransmitter to its receptor is a key event in the
action of all neurotransmitters.

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Fast-acting neurotransmitter: Some neurotransmitters are referred to as fast-acting since their cellular
effects occur milliseconds after the neurotransmitter binds to its receptor. These neurotransmitters exert
direct control of ion channels by inducing a conformational change in the receptor, creating a passage
through which ions can flow. These receptors are often called ligand-gated ion channels since the
channel opens only when the ligand is bound correctly.

When the channel opens, it allows for ions to pass through from their side of highest concentration to
their side of lowest concentration. The net result is depolarization if there is a net influx of positively
charged ions or hyperpolarization if there is a net inward movement of negatively charged ions.
Depolarization results in a continuation of the nerve impulse, whereas hyperpolarization makes it less
likely that the nerve impulse will continue to be transmitted.

Ach, Glycine and γ-aminobutyric acid (GABA) acts as fast-acting neurotransmitters.]

Slower-acting neurotransmitters act by binding to proteins that are sometimes called G-protein-
coupled receptors (GPCRs). These receptors do not form ion channels upon activation and have a very
different architecture than the ion channels. However, the timescale for activation is often relatively fast,
on the order of seconds. The slightly longer time frame than that for fast-acting neurotransmitters is
necessary due to additional molecular interactions that must occur for the postsynaptic cell to become
depolarized or hyperpolarized. The protein structure of a GPCR is one protein subunit folded so that it
transverses the membrane seven times. These receptors are referred to as G-coupled protein receptors
because they function through an interaction with a GTP-binding protein, called G-protein for short.

Termination of Transmission:For proper control of neuronal signaling, there must be a means of


terminating the nerve impulse. In all cases, once the neurotransmitter dissociates from the receptor, the
signal ends. For a few neurotransmitters, there are enzymes in the synapse that serve to chemically alter
the neurotransmitter, making it nonfunctional. For instance, the enzyme acetylcholinesterase hydrolyzes
acetylcholine. Other neurotransmitters, such as catecholamines and glutamate, undergo a process called
reuptake. In this process, the neurotransmitter is removed from the synapse via a transporter protein.
These proteins are located in presynaptic neurons or other nearby cells.

Fig. Action of chemical transmitters

27.3 TYPES OF NEUROTRANSMITTERS

There are many different ways to classify neurotransmitters. The three major categories of substances
that act as neurotransmitters are
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(1) amino acids (primarily glutamic acid, GABA, aspartic acid & glycine),
(2) peptides (vasopressin, somatostatin, neurotensin, etc.) and
(3) monoamines (norepinephrine, dopamine & serotonin) plus acetylcholine.

27.3.1 Amino Acids (primarily glutamic acid, GABA, aspartic acid & glycine),

Glycine: Glycine is the simplest of amino acids, consisting of an amino group and a carboxyl (acidic)
group attached to a carbon atom. Glycine's function as a neurotransmitter is also fairly simple. When
released into a synapse, glycine binds to a receptor which makes the post-synaptic membrane more
permeable to Cl- ion. This hyperpolarizes the membrane, making it less likely to depolarize. Thus,
glycine is an inhibitory neurotransmitter. It is de-activated in the synapse by a simple process of
reabsorption by active transport back into the pre-synaptic membrane. Glycine is a neurotransmitter
only in vertebrate animals.

Aspartic acid: Like glycine, apartate is primarily localized to the ventral spinal cord. Like glycine,
aspartate opens an ion-channel and is inactivated by reabsorption into the pre-synaptic membrane.
Unlike glycine, however, apartate is an excitatory neurotransmitter, which increases the likelihood of
depolarization in the postsynaptic membrane. Aspartate & glycine form an excitatory/inhibitory pair
in the ventral spinal cord comparable to the excitatory/inhibitory pair formed by glutamate & GABA
in the brain. Interestingly, the two exitatory amino acids -- glutamic acid & aspartic acid -- are the two
acidic amino acids found in proteins, insofar as both have two carboxyl groups rather than one.

Glutamate: Glutamate is the most common neurotransmitter


in the brain. It is always excitatory, usually due to simple
receptors that increase the flow of positive ions by opening
ion-channels. Glutamate stimulation is terminated by a
(chloride-independent) membrane transport system that is
only used for re-absorbing glutamate & aspartate across the
pre-synaptic membrane. Glutamate & aspartate re-enter the
cell by a transporter driven by the high extracellular
concentrations of Na+ and the high intracellular
concentrations of K+. Soduim enters the cell along with the
amino acids and potassium leaves the cell -- much the way a
pulley couples the lifting of a light weight with the fall of a
heavier weight. Thus, glutamate/asparate entry is indirectly
powered by the ATP-driven Na+-K+-ase (sodium pump)
which creates the high ion concentration gradients. Glutamate
released into synapses is either reabsorbed directly into neurons by the ion-exchange transport system
described above, or is soaked-up by astrocytes (glial cells) which convert the glutamate into glutamine
(a molecule which cannot cause excitotoxicity).

GABA: GABA is the major inhibitory neurotransmitter of the brain, occurring in 30-40% of all
synapses (second only to glutamate as a major brain neurotransmitter). It is most highly concentrated
in the substantia nigra & globus pallidus nuclei of the basal ganglia, followed by the hypothalamus,
the periaqueductal grey matter ("central grey") and the hippocampus. The GABA concentration in the
brain is 200-1000 times greater than that of the monoamines or acetylcholine.

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27.3.2 Peptides (vasopressin, somatostatin, neurotensin)

Peptides are the most common neurotransmitters in the hypothalamus. Their complex structure can
allow for high receptor specificity. They are all synthesized on ribosomes and are all inactivated by
hydrolysis at the synapse (rather than by re-uptake). Peptides are far more potent than other
neurotransmitters, requiring only very small amounts to produce a profound effect. Even very minute
amounts of somatostatin can inhibit growth hormone release.

Cholecystokinin (CCK) seems to function in the production of satiety. Injection of small quantities of
this peptide into the ventricles or the paraventricular nucleus can inhibit feeding. CCK is associated
with dopamine synapses in some limbic areas, and appears to modulate dopamine release. Such
peptide synergy with other transmitters is common. For example, GABA is often associated with
somatostatin and serotonin with Substance P.

Low doses of the peptide vasopressin have been shown to enhance learning in laboratory animals.
However, humans with vasopressin deficiency show no signs of memory impairment. Because
vasopressin is potent in increasing blood pressure, its use by humans should be approached with
caution. Safer analogues may yet be found

27.3.4 Monoamines (norepinephrine, dopamine & serotonin plus acetylcholine).

Dopamine: The primary monoamine neurotransmitters are dopamine, norepinephrine and serotonin.
Dopamine and norepinephrine are catecholeamines, whereas serotonin is an indolamine. The amino
acid tyrosine is not an essential amino acid because it can be synthesized in the liver from
phenylalanine by the enzyme phenylalanine hydroxylase. But it cannot be synthesized in the brain,
and therefore must enter the brain by the large neutral amino acid transporter, which also transports
phenylalanine, tryptophan, methionine and the branch-chained amino acids. These amino acids all
compete for the transporter, so a large quantity of one of the other amino acids in the blood stream
could greatly limit the amount of tyrosine entering the brain. One case in which this occurs is when
there is a liver deficiency of phenylalanine hydroxylase. In that case, Phenylalanine reaches high
concentrations in the blood and monopolizes the large neutral amino acid transporter, producing the
mental retardation of phenylketonuria.

Once in the brain, tyrosine can be converted to DihydrOxyPhenylAlanine (DOPA) by the tyrosine
hydroxylase enzyme using oxygen, iron and TetraHydroBiopterin (THB) as co-factors. High
concentrations of dopamine inhibit tyrosine hydroxylase activity through an influence on the THB co-
factor. DOPA is converted to dopamine by Aromatic Amino Acid Decarboxylase (which is fairly
nonspecific insofar as it will decarboxylate any aromatic amino acid) using PyridoxaL Phosphate
(PLP) as a co-factor. This reaction is virtually instantaneous unless there is a Vitamin B6 deficiency.

Dopamine & epinephrine are primarily inhibitory neurotransmitters that produce arousal. This may
sound paradoxical, but the most likely explanation for this effect is that the postsynaptic cells for
catecholamines themselves are inhibitory.

Norepinephrine: Norepinephrine (along with acetylcholine) is one of the two neurotransmitters in the
peripheral nervous system. Norepinephrine is synthesized from dopamine by means of the enzyme
Dopamine Beta-Hydroxylase (DBH), with oxygen, copper and Vitamin C as co-factors. Dopamine is
synthesized in the cytoplasm, but norepinephrine is synthesized in the neurotransmitter storage
vesicles. Cells that use norepinephrine for formation of epinephrine use SAMe (S-AdenylMethionine)

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as a methyl group donor. Levels of epinephrine in the CNS are only about 10% of the levels of
norepinephrine.

The most prominent noradrenergic (ie, norepinephrine-containing) nucleus is the locus ceruleus in the
pons, which account for over 40% of noradrenergic neurons in the rat brain. Most of the other
noradrenergic neurons are clustered in a region described as the lateral tegmental area. The
neocortex, hippocampus, and cerebellum receive noradrenergic stimulation exclusively from the locus
ceruleus. Most of the dopaminergic innervation of the hypothalamus comes from the lateral tegmental
nuclei.

Serotonin: Serotonin was isolated from the blood serum as a substance causing powerful smooth
muscle contraction. Only later was it demonstrated to be tryptamine with a hydroxyl group at the 5-
position. Only 1-2% of the serotonin in the body is in the brain, insofar as serotonin is widely
distributed in platelets, mast cells, etc. But there is no equilibration between body serotonin and brain
serotonin -- the serotonin in the brain is independently synthesized from tryptophan transported across
the blood-brain barrier.

Serotonin synthesis is a 2-step process, the first step of which requires the enzyme tryptophan
hydroxylase with oxygen, iron and THB as co-factors. Neither the enzyme nor the co-factors are rate-
limiting for either step of these reactions -- virtually all brain tryptophan is converted to serotonin.
Serotonin concentration in the brain is far more sensitive to the effects of diet than any other
monoamine neurotransmitter -- and can be increased up to 10-fold by dietary supplementation in
laboratory animals.

Acetylcholine: Acetylcholine was the first neurotransmitter discovered and is the major
neurotransmitter in the peripheral nervous system (the only other peripheral neurotransmitter being
norepinephrine). Acetylcholine is usually (but not always) an exitatory neurotransmitter -- in contrast
to the monoamine neurotransmitters, which are nearly always (with a few exceptions) inhibitory.

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Acetylcholine in the brain is produced from acetyl-CoA, resulting from glucose metabolism, and from
choline, which is actively transported across the blood-brain barrier. Most dietary choline comes from
phosphatidyl choline, the major phospholipid in the membranes of plants&animals (but not bacteria).
The acetyl-CoA & choline are independently synthesized in the neuron cell body and independently
transported along the axon to the synapse where they are conjugated into acetylcholine.

There are comparatively few acetylcholine receptors in the brain, but outside the brain acetylcholine is
the major neurotransmitter controlling the muscles. Body muscles can be divided into the skeletal
muscles system (under voluntary control) and the smooth muscles of the autonomic nervous system
(controlling heart, stomach, etc. -- not under voluntary control).

Fig. Acetylcholine as a neurotransmitter

***

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Chapter – 12 ENDOCRINES

28. ORGANIZATION & FUNCTIONS OF ENDOCRINE GLANDS


29. REPRODUCTIVE HORMONES (FSH, LH AND HCG)

28. ORGANIZATION & FUNCTIONS OF ENDOCRINE GLANDS

28.1 INTRODUCTION
28.2 PITUITARY GLAND
28.3 PINEAL GLAND
28.4 THYROID GLAND
28.5 PARATHYROID GLAND
28.6 PANCREAS
28.7 ADRENAL GLAND
28.8 TESTES
29.9 OVARY

28.1 INTRODUCTION

Endocrine glands are glands that secrete their product, (hormones), directly into the blood rather than
through a duct. This group contains the glands of the Endocrine system. The main Endocrine glands
include the pituitary gland, the pancreas, the ovaries, the testes, the thyroid gland and the adrenal glands.
Other organs which are not so well known for their endocrine activity include the stomach, which
produces such hormones as ghrelin.

Fig. The major endocrine glands.


1. Pineal gland 2. Pituitary gland 3. Thyroid gland 4.
Thymus 5. Adrenal gland 6. Pancreas 7. Ovary 8. Testes

The pituitary gland hangs from the base of the brain by a


stalk and is enclosed by bone. It consists of a hormone-
producing glandular portion (anterior pituitary) and a
neural portion (posterior pituitary), which is an
extension of the hypothalamus.

Endocrine organs are ductless, well-vascularized glands


that release hormones directly into the blood or lymph.
They are small and widely separated in the body.The
major endocrine organs are the pituitary, thyroid,
parathyroid, adrenal, pineal, and thymus glands, as well
as the pancreas and gonads. The hypothalamus is a
neuroendocrine organ.

Local chemical messengers, not generally considered


part of the endocrine system, include autocrines, which
act on the cells that secrete them, and paracrines, which
act on a different cell type nearby.

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28.2 PITUITARY GLAND ORGANIZATION AND FUNCTIONS

The pituitary gland, or hypophysis, is an endocrine gland about the size of a pea. It is a protrusion off
the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity (sella turcica)
covered by a dural fold (diaphragma sellae). The pituitary fossa, in which the pituitary gland sits, is
situated in the sphenoid bone in the middle cranial fossa at the base of the brain.

The pituitary is divided into two functionally distinct tissues:

1. The anterior pituitary (adenohypophysis) is composed of the pars distalis, pars intermedia, and
the pars tuberalis. During development it originates as an out pocketing of ectoderm from the
roof of the mouth known as Rathke’s pouch.
2. The posterior pituitary (neurohypophysis) is composed of the pars nervosa, infundibular stalk,
and median eminence. During development it originates from the embryonic brain and this
connection to the hypothalamus is maintained in the adult.

The anterior pituitary is a community of six distinct hormone-producing cells that are categorized
based upon their staining:

1. The somatotrophs that produce growth hormone (GH)


Acidophils:
2. The mammotrophs that secrete prolactin (PRL)
3. The thyrotrophs that produce thyroid-stimulating hormone (TSH)
4. The gonadotrophs that produce both luteinizing hormone (LH) and
follicle stimulating hormone (FSH).
Basophils: 5. The corticotrophs produce either corticotropin (ACTH) in the pars
distalis or melanocyte stimulating hormone (MSH) in the pars intermedia
through alternative processing of the pro-opiomelanocortin (POMC)
precursor protein.
6. Poorly staining cells that may include supportive cells
Chromophobes:
(folliculostellate cells) and precursors to the endocrine cells.

There are regional subdivisions of the anterior pituitary:

1. The pars distalis is the main body of the anterior pituitary and contains all six cell types.
2. The pars intermedia forms the border of the anterior and posterior pituitary and contains
predominately basophilic corticotrophs that produce melanocyte-stimulating hormone (MSH)
from the POMC precursor.
3. The pars tuberalis forms a sleeve of cells that surround the infundibulum that are typically
gonadotrophs producing LH and FSH.

The synthesis and release of the anterior pituitary hormones are tightly controlled by hypothalamic
releasing and inhibitory factors and by feedback signals from peripheral organs. These factors are
released by neurons that originate in the hypothalamus and terminate in a plexus of capillaries in the
infundibular stalk that feed into the hypophyseal portal system.

The hypophyseal portal system supplies blood to the endocrine cells of the anterior pituitary and plays a
critical role in delivering the hypothalamic factors that regulate hormone synthesis and release. The
pituitary receives blood via two paired arteries that originate from the internal carotid that empty into
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the hypophyseal portal system. There is little direct arterial blood supply to the anterior pituitary, and
the pituitary lies outside the blood-brain barrier.

Fig. Structure of pituitary Fig. Functions of pituitary gland

The posterior pituitary consists of unmyelinated fibers and nerve endings of secretory neurons whose
cell bodies lie within the hypothalamus. A highly branched glial cell known as the pituicyte is the only
resident cell in the posterior lobe. The neurons of the posterior pituitary release two different hormones:

1. Vasopressin (antidiuretic hormone, ADH) increases water reabsorption in kidney collecting ducts
and promotes vascular smooth muscle contraction; the release coupled with dehydration detected
by osmoreceptors.
2. Oxytocin stimulates contraction of uterine smooth muscle, and myoepithelial cells of mammary
gland, and its release coupled with parturition and suckling.

The following table shows the functions of pituitary hormones

POSTERIOR PITUITARY
Hormone Secreted Main Functions
stimulates uterine contraction (labor contractions)
Oxytocin
stimulates milk let-down reflex
stimulates water retention by renal collecting ducts in kidneys
Antidiuretic hormone inhibits sweat glands in skin
stimulates vasoconstriction in skin (hence name "vasopressin")

ANTERIOR PITUITARY
Hormone Secreted Main Functions
growth of skeletal muscle, bone, cartilage
Growth hormone
increase protein synthesis

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stimulates lipolysis for ATP production
reduces glucose use for ATP production
increase release of stored glucose from liver
raises blood glucose level (diabetogenic effect)
triggers thyroid hormone release from thyroid
Thyroid-stimulating hormone
indirectly enhances basal metabolism of cells via thyroid activation
Adrenocorticotropin stimulates glucocorticoid (cortisol) secretion from adrenal cortex
hormone indirectly enhances "stress-response" via adrenal activation
Prolactin promotes milk production by mammary glands
induces spermatogenesis in testes of males after onset of puberty
induces 2o oocyte development in ovaries of females after onset of
Follicle-stimulating hormone puberty
stimulates growth of ovarian follicles (granulosa cells)
stimulates estrogen production from ovaries
enhances 2o oocyte maturation in ovaries
induces ovulation
Luteinizing hormone
maintains corpus luteum for first two weeks after ovulation
stimulates testosterone production from testes

28.3 PINEAL GLAND ORGANIZATION AND FUNCTIONS

The pineal gland is a reddish-gray body about the size of a pea (8 mm in


humans), located just rostro-dorsal to the superior colliculus and behind
and beneath the stria medullaris, between the laterally positioned thalamic
bodies. It is part of the epithalamus.

The pineal gland is a midline structure, and is often seen in plain skull X-
rays, as it is often calcified. The pineal body consists in humans of a
lobular parenchyma of pinealocytes surrounded by connective tissue spaces. The gland's surface is
covered by a pial capsule. The pineal gland consists mainly of pinealocytes, but four other cell types
have been identified. The pineal gland was originally believed to be a "vestigial remnant" of a larger
organ (much as the appendix was thought to be a vestigial digestive organ). Melatonin is a derivative of
the amino acid tryptophan, which also has other functions in the central nervous system. The production
of melatonin by the pineal gland is stimulated by darkness and inhibited by light.

The pineal gland is large in children, but shrinks at puberty. It appears to play a major role in sexual
development, hibernation in animals, metabolism, and seasonal breeding. The abundant melatonin
levels in children is believed to inhibit sexual development, and pineal tumors have been linked with
precocious puberty. When puberty arrives, melatonin production is reduced. Calcification of the pineal
gland is typical in adults.

28.4 THYROID GLAND ORGANIZATION AND FUNCTIONS

The thyroid gland is located in front of the upper trachea, and is enclosed in a connective tissue capsule.
It is one of the largest endocrine organs, weighing about 20 g in North American adults. In certain
pathological conditions, such as goiters resulting from iodine deficiency, the gland may weigh more
than 200 g. There is two types of hormone producing cells in the thyroid:
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Target
Cell Type Hormone Regulator Function
Tissue
Regulates basal metabolic
Thyroid
rate and has important
Follicular cells Hormones TSH all tissues
influences on growth and
(T3,T4)
maturation.
Regulates blood Ca++
levels in concert with
Parafollicular parathyroid hormone.
Calcitonin Calcitonin Bone
(C) Cells Calcitonin lowers Ca++
by inhibiting
decalcification of bone.

The structural unit of the thyroid gland is the follicle that is formed by a sphere of cuboidal epithelial
cells. These hormone-producing cells surround a lumen that is filled with colloid, and each follicle is
enmeshed in a capillary network.

Fig. Thyroid gland structure and histology

The thyroid gland is unique in that it stores large amounts of hormone as inactive precursor in an
extracellularl lumen formed by the follicles.

The steps in thyroid hormone are:

1. Follicular cells synthesize, glycosylate, and package a large glycoprotein (670 kD) called
thyroglobulin (TG), and then release it into the lumen by exocytosis.
2. Follicular cells concentrate iodide from the blood using an iodide pump in the basal plasma
membrane that is driven by a transmembrane Na+ gradient. This pump is efficient maintaining
plasma concentrations of iodide at 0.15 mM. The thyroid adapts to low dietary intake of iodine by
increasing uptake of I-.
3. The iodide is used in organification, the iodination of tyrosyl residues on newly synthesized TG.
The enzyme thyroid peroxidase mediates this and is on the apical membrane of the follicular cell.
TG contains 115 tyrosyl residues, but only about 10% become iodinated. Iodinated TG is stored in
the lumen until needed; in humans, there is as much as a three-month supply of stored TG.

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4. Pituitary thyroid stimulating hormone (TSH) stimulates many steps in the synthesis of thyroid
hormones (T3, T4). TSH increases iodine uptake, stimulates thyroglobulin synthesis and increases
organification. TSH also stimulates follicular cells to take up TG from the lumen by endocytosis.
The endocytic vesicles fuse with lysosomes and TG is degraded by proteases, liberating 1 to 3
thyronine molecules (T4, T3) per molecule of TG. The free T3 and T4 cross the cell membrane and
enter the blood where they are selectively bound by carrier proteins.
5. Most of the thyroid hormone is released as T4. However, because of differences in carrier protein
binding, free plasma T3 concentrations approach that of free T4. Further, T3 is also derived by
deiodination of T4 in the liver and kidney. Thus, T3 contributes substantially to the metabolic
effect.

The follicular cells will appear either flattened (large amount of TG stored in lumen) or cuboidal (active
mobilization of TG) depending on the TSH stimulation.. There is a negative feedback loop regulating
pituitary TSH secretion; high [T3] inhibits TRH-stimulated TSH secretion. Parafollicular cells are
located singly or as groups of cells between the follicles. There is no known endocrine or paracrine
interactions between follicular and parafollicular cells.

1. Parafollicular cells synthesize and release calcitonin in response to increases in serum calcium
levels. Calcitonin acts coordinately with parathyroid hormone (described below) and vitamin D to
regulate serum calcium levels.
2. Calcitonin acts by inhibiting bone resorption and increase renal calcium excretion.
3. Detection of excessive serum calcitonin is an important clinical marker for a hereditary C cell
cancer, medullary carcinoma.

28.5 PARATHYROID GLAND ORGANIZATION AND FUNCTIONS

There are usually 4 parathyroid glands (two upper and two lower) located within the thyroid capsule.
They are embedded in the thyroid parenchyma and separated by a thin layer of connective tissue. This
location is a major concern during radiation therapy for thyroid disease. The parathyroid glands derive
from the same embryonic endoderm as the thymus, and form densely packed cords of cells around a
capillary network. They consist of two major cell types:

1. Principal or Chief cell: secrete parathyroid hormone (PTH).


2. Oxyphilic cell: unknown function, increase in number with age and may represent degenerative
form of chief cell.

PTH is synthesized as a precursor protein that is processed and stored by the principal cells. There is a
limited reserve of PTH stored in secretory granules. PTH functions to regulate blood calcium levels in
the normal range of 2.4 mM. PTH acts in collaboration with calcitonin from parafollicular C cells, and
vitamin D (a steroid hormone synthesized in the kidney). Normal or elevated Ca2+ levels inhibit PTH
secretion by activating a calcium sensing receptor on the principal cell surface.

In serum, PTH is further processed, and the C-terminal fragment (amino acids 35-84) is the bioactive
form of the hormone. PTH stimulates osteoblasts to release a paracrine factor that activates osteoclasts
that function in bone resorption. PTH also promotes renal calcium resorption and promotes vitamin D
synthesis in the kidney proximal tubule. Vitamin D stimulates calcium uptake in the small intestine.

Normal or elevated Ca++ levels inhibit PTH secretion by activating a calcium sensing receptor on the
principal cell surface. In serum, PTH is further processed, and the C-terminal fragment (amino acids 35-
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84) is the bioactive form of the hormone. PTH stimulates osteoblasts to release a paracrine factor that
activates osteoclasts that function in bone resorption. PTH also promotes renal calcium resorption and
promotes vitamin D synthesis in the kidney proximal tubule. Vitamin D stimulates calcium uptake in
the small intestine.

Fig. Structure and Histology of parathyroid gland

28.6 THYMUS GLAND ORGANIZATION AND FUNCTIONS

The primary lymphatic organ in the body; it is located over the


heart and/or in the neck area, anterior to the ascending aorta and
posterior to the sternum. The thymus consists of two lobes
enclosed in a capsule and is further divided internally by cross
walls into many lobules, called thymic lobules.

The primary function of the thymus is the processing and


maturation of special lymphocytes (white blood cells) called T-
lymphocytes or T-cells, which are associated with antibody
production. T-lymphocytes migrate from the bone marrow to
the thymus, where they mature and differentiate until activated.
While in the thymus, the lymphocytes do not respond to
pathogens and foreign agents. After the lymphocytes have
matured, they enter the blood and go to other lymphatic organs
where they help provide defense against disease. The thymus also produces a hormone, thymosin,
which stimulates the maturation of lymphocytes in other lymphatic organs.

The thymus is relatively large in infants and children but after puberty it begins to decrease in size so
that in older adults it is quite small. Athymic individuals (people who have no thymus) lack T-cells.

28.7 ADRENAL GLAND ORGANIZATION AND FUNCTIONS

The adrenal (or suprarenal) glands are triangular glands positioned at the cranial pole of each kidney
and normally weigh about 4 g. Adrenal tissue can develop in ectopic sites. Each adrenal consists of two
functionally distinct endocrine glands within a single capsule. These are derived from different
embryonic tissues:

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1. The cortex develops from coelomic mesoderm and can be functionally divided into different three
regions of cells that synthesize the adrenal steroid hormones. The cortex is subdivided into three
functional layers:
 zona glomerulosa consisting of clusters (glomeruli) of cells producing mineralocorticoids.
zona fasciculata (bracketed in picture) containing cords (fascicles) of cells producing
glucocorticoids.
Zona reticularis is a cell network adjacent to the medulla that produces glucocorticoids and
minor androgens.

2. The medulla results from invasion of the cortex by neural crest cells during development. It consists
of cords of cells that secrete catecholamines and peptide hormones.

Steroid hormones are synthesized from cholesterol ester by enzymes found in the smooth ER and
mitochondria and passively diffuse across the membrane; thus, regulation of release occurs at the
synthetic enzymes. Collectively the cells in all three zones of the cortex have characteristics of steroid
production:

3. They have extensive smooth ER;


4. Numerous mitochondria with unusually amplified inner membranes,
5. Lipid droplets rich in cholesterol esters which is the precursor for steroids;
6. Accumulated lipofuscin (insoluble degradation product of organelle turnover) is
prominent in Z. reticularis.

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The following table summarizes the steroids secreted by the cortex, regulation and their actions:

Cortical cell Steroid Regulation Major action


Electrolyte and water
Angiotensin II, Plasma [K+],
Z. Glomerulosa Aldosterone balance, stimulate absorption
ACTH (minor)
of Na+
Glucocorticoids Regulation of carbohydrate,
Z. Fasciculata ACTH
(cortisol) protein, and fat metabolism
Minor androgens are not
ACTH;
Glucocorticoid, effective, but can be
Z. Reticularis cortical androgen-stimulating
androgen converted to Testosterone by
hormone
peripheral tissues

The adrenals are exceedingly well vascularized, receiving arterial blood from branches of the aorta,
renal and phrenic arteries which enter the subcapsular plexus. From here arteries supply both a
sinusoidal network in the cortex, and the medulla directly. Vessels from the sinusoidal network form
veins that traverse the medulla and empty into the central vein. This arrangement of vascular supply to
the medulla allows the direct action of glucocorticoids from cortical cells in regulating medullary cell
catecholamine production.

The chromaffin cells of the adrenal medulla synthesize and store the catecholamines epinephrine or
norepinephrine in an extensive population of secretory granules. Catecholamine synthesis is regulated at
the first enzymatic step, tyrosine hydroxylase. A proton pump (H+ ATPase) drives the accumulation of
catecholamines in secretory granules.

Other substances are packaged along with the catecholamines, including peptide hormones such as
neuropeptide Y, substance P, and enkephalin, the chromogranins which are involved in packaging of
catecholamines, the enzyme dopamine b-hydroxylase, ATP and ascorbic acid, an important cofactor in
catecholamine synthesis.

The catecholamines from chromaffin cells mediate the alarm (fright-fight or flight) response in times
of fear or stress. The release of adrenal medulla catecholamines is stimulated by sympathoadrenal
system of preganglionic sympathetic neurons (Ach) and function to increase heart rate and blood flow,
and to stimulate the release of glucose from the liver.

28.8 PANCREAS GLAND ORGANIZATION AND FUNCTIONS

The pancreas is a gland organ in the digestive and endocrine system of vertebrates. A long, soft organ
that lies transversely along the back of the abdominal wall, behind the stomach, and extends from the
region of the duodenum to the spleen. It is both an endocrine gland (producing several important
hormones, including insulin, glucagon, and somatostatin), as well as an exocrine gland, secreting
pancreatic juice containing digestive enzymes that pass to the small intestine. These enzymes help in the
further breakdown of the carbohydrates, protein, and fat in the chyme.

Under a microscope, stained sections of the pancreas reveal two different types of parenchymal tissue.[2]
Lightly staining clusters of cells are called islets of Langerhans, which produce hormones that underlie

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the endocrine functions of the pancreas. Darker staining cells form acini connected to ducts. Acinar cells
belong to the exocrine pancreas and secrete digestive enzymes into the gut via a system of ducts.

Fig. Anatomy of pancreas

Fig. T.S of pancreas


Appearance Function
Structure
Islets of Lightly staining, large, spherical Hormone production and secretion (endocrine
Langerhans clusters pancreas)
Darker staining, small, berry-like Digestive enzyme production and secretion
Pancreatic acini
clusters (exocrine pancreas)

The pancreas is a dual-function gland, having features of both endocrine and exocrine glands.

Endocrine: The part of the pancreas with endocrine function is made up of a million cell clusters called
islets of Langerhans. There are four main cell types in the islets. They are relatively difficult to
distinguish using standard staining techniques, but they can be classified by their secretion: α cells
secrete glucagon, β cells secrete insulin, δ cells secrete somatostatin, and PP cells secrete pancreatic
polypeptide. The islets are a compact collection of endocrine cells arranged in clusters and cords and are
crisscrossed by a dense network of capillaries. The capillaries of the islets are lined by layers of
endocrine cells in direct contact with vessels, and most endocrine cells are in direct contact with blood
vessels, by either cytoplasmic processes or by direct apposition. According to the volume The Body, by
Alan E. Nourse, the islets are "busily manufacturing their hormone and generally disregarding the
pancreatic cells all around them, as though they were located in some completely different part of the
body."
Exocrine: In contrast to the endocrine pancreas, which secretes hormones into the blood, the exocrine
pancreas produces digestive enzymes and an alkaline fluid, and secretes them into the small intestine
through a system of exocrine ducts in response to the small intestine hormones secretin and
cholecystokinin. Digestive enzymes include trypsin, chymotrypsin, pancreatic lipase, and pancreatic
amylase, and are produced and secreted by acinar cells of the exocrine pancreas. Specific cells that line
the pancreatic ducts, called centroacinar cells, secrete a bicarbonate- and salt-rich solution into the small
intestine.

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28.9 OVARY AND TESTES GLAND ORGANIZATION AND FUNCTIONS

28.9.1 Organization Of Ovary

The primary female reproductive organs, or gonads, are the two ovaries. Each ovary is a solid, ovoid
structure about the size and shape of an almond, about 3.5 cm in length, 2 cm wide, and 1 cm thick.
The ovaries are located in shallow depressions, called ovarian fossae, one on each side of the uterus,
in the lateral walls of the pelvic cavity. They are held loosely in place by peritoneal ligaments.
The ovaries are covered on the outside by a layer of simple cuboidal epithelium called germinal
(ovarian) epithelium. This is actually the visceral peritoneum that envelops the ovaries. Underneath
this layer there is a dense connective tissue capsule, the tunica albuginea. The substance of the ovaries
is distinctly divided into an outer cortex and an inner medulla. The cortex appears more dense and
granular due to the presence of numerous ovarian follicles in various stages of development. Each of
the follicles contains an oocyte, a female germ cell. The medulla is loose connective tissue with
abundant blood vessels, lymphatic vessels, and nerve fibers.

The outermost layer is called the germinal epithelium.


The tunica albuginea covers the cortex.
The ovarian cortex consists of ovarian follicles and stroma in between them. Included in the
follicles are the cumulus oophorus, membrana granulosa (and the granulosa cells inside it), corona
radiata, zona pellucida, and primary oocyte. The zona pellucida, theca of follicle, antrum and
liquor folliculi are also contained in the follicle. Also in the cortex is the corpus luteum derived
from the follicles.
The innermost layer is the ovarian medulla. It can be hard to distinguish between the cortex and
medulla, but follicles are usually not found in the medulla.

Fig. Ovary structure

28.9.2 Organization Of Testes

Part of the male reproductive system. The male gonads, testes, or testicles, begin their development
high in the abdominal cavity, near the kidneys. During the last two months before birth, or shortly
after birth, they descend through the inguinal canal into the scrotum, a pouch that extends below the
abdomen, posterior to the penis. Although this location of the testes, outside the abdominal cavity,
may seem to make them vulnerable to injury, it provides a temperature about 3°C below normal body
temperature. This lower temperature is necessary for the production of viable sperm. The scrotum
consists of skin and subcutaneous tissue. A vertical septum, or partition, of subcutaneous tissue in the

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center divides it into two parts, each containing one testis. Smooth muscle fibers, called the dartos
muscle, in the subcutaneous tissue contract to give the scrotum its wrinkled appearance. When these
fibers are relaxed, the scrotum is smooth. Another muscle, the cremaster muscle, consists of skeletal
muscle fibers and controls the position of the scrotum and testes. When it is cold or a man is sexually
aroused, this muscle contracts to pull the testes closer to the body for warmth.

Fig. Sagital section of testes Fig. Histology of Testis (T.S)

Each testis is an oval structure about 5 cm long and 3 cm in diameter. A tough, white fibrous
connective tissue capsule, the tunica albuginea, surrounds each testis and extends inward to form septa
that partition the organ into lobules. Under a tough membraneous shell, the tunica albuginea, the testis
contains very fine coiled tubes called the seminiferous tubules. The tubes are lined with a layer of
cells that, from puberty into old-age, produce sperm cells. There are about 250 lobules in each testis.
Each lobule contains 1 to 4 highly coiled seminiferous tubules that converge to form a single straight
tubule.

The sperm travel from the seminiferous tubules to the rete testis located in the mediastinum testis, to
the efferent ducts, and then to the epididymis where newly-created sperm cells mature (see
spermatogenesis). The sperm move into the vas deferens, and are eventually expelled through the
urethra and out of the urethral orifice through muscular contractions. Between the seminiferous
tubules are special cells called Leydig cells (or "interstitial cells") where testosterone and other
androgens are formed.

Like the ovaries (to which they are homologous), testicles are components of both the reproductive
system (being gonads) and the endocrine system (being endocrine glands). The respective functions of
the testicles are;

producing sperm (spermatozoa)


producing male sex hormones of which testosterone is the best-known
Both functions of the testicle, sperm-forming and endocrine, are under control of gonadotropic
hormones produced by the anterior pituitary:
luteinizing hormone (LH)
follicle-stimulating hormone (FSH)

***

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29. REPRODUCTIVE HORMONES (FSH, LH and HCG)

29.1 INTRODUCTION
29.2 FSH
29.3 LH
29.4 HCG

29.1 INTRODUCTION

Sex hormones are steroids (fat soluble compounds) that control sexual maturity and reproduction. These
hormones are produced mainly by the endocrine glands. The endocrine glands in females are ovaries
and those in males are testes. While both males and females have all types of hormones present in their
bodies, females produce the majority of two types of hormones, estrogens and progesterone, while
males produce mainly androgens such as testosterone. Most androgens produced by females are
converted to estrogens and some androgens in males are also converted to estrogens. Sex hormones are
synthesized from cholesterol (a fatty acid) and other compounds and secreted throughout a person's
lifetime at different levels. Their production increases at puberty and normally decreases in old age.

The production of hormones is a complex process. At puberty, the brain's hypothalamus gland produces
increased amounts of gonadotropin-releasing hormone. This hormone stimulates the nearby pituitary
gland to release two other hormones: follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
Finally, these two hormones signal the sex glands (gonads) to produce the sex hormones.

29.2 FSH

Follicle-stimulating hormone (FSH) is a hormone synthesized and secreted by gonadotropes in the


anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive
processes of the human body. FSH and Luteinizing hormone (LH) act synergistically in reproduction:

FSH is a glycoprotein. Each monomeric unit is a protein molecule with a sugar attached to it; two of
these make the full, functional protein. Its structure is similar to those of LH, TSH, and hCG. The
protein dimer contains 2 polypeptide units, labeled alpha and beta subunits. The alpha subunits of LH,
FSH, TSH, and hCG are identical, and contain 92 amino acids. The beta subunits vary. FSH has a beta
subunit of 118 amino acids (FSHB), which confers its specific biologic action and is responsible for
interaction with the FSH-receptor. The sugar part of the hormone is composed of fucose, galactose,
mannose, galactosamine, glucosamine, and sialic acid, the latter being critical for its biologic half-life.
The half-life of FSH is 3-4 hours. Its molecular wt is 30000.

FSH regulates the development, growth, pubertal maturation, and reproductive processes of the human
body.

In both males and females, FSH stimulates the maturation of germ cells.
In males, FSH induces sertoli cells to secrete inhibin and stimulates the formation of sertoli-sertoli
tight junctions (zonula occludens).
In females, FSH initiates follicular growth, specifically affecting granulosa cells. With the
concomitant rise in inhibin B, FSH levels then decline in the late follicular phase. This seems to be
critical in selecting only the most advanced follicle to proceed to ovulation. At the end of the luteal
phase, there is a slight rise in FSH that seems to be of importance to start the next ovulatory cycle.

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29.3 LH

Luteinizing hormone (LH, also known as lutropin[1]) is a hormone produced by the anterior pituitary
gland. LH is a glycoprotein. Each monomeric unit is a sugar-like protein molecule; two of these make
the full, functional protein.

Its structure is similar to the other glycoproteins, follicle-stimulating hormone (FSH), thyroid-
stimulating hormone (TSH), and human chorionic gonadotropin (hCG). The protein dimer contains 2
polypeptide units, labeled alpha and beta subunits that are connected by two disulfide bridges:

The alpha subunits of LH, FSH, TSH, and hCG are identical, and contain 92 amino acids.
The beta subunits vary. LH has a beta subunit of 121 amino acids (LHB) that confers its specific
biologic action and is responsible for interaction with the LH receptor. This beta subunit contains
the same amino acids in sequence as the beta sub unit of hCG and both stimulate the same
receptor, however, the hCG beta subunit contains an additional 24 amino acids, and both
hormones differ in the composition of their sugar moieties.

The different composition of these oligosaccharides affects bioactivity and speed of degradation. The
biologic half-life of LH is 20 minutes, shorter than that of FSH (3-4 hours) or hCG (24 hours).

In both males and females, LH is essential for reproduction.

In females, at the time of menstruation,


FSH initiates follicular growth,
specifically affecting granulosa cells.
With the rise in estrogens, LH receptors
are also expressed on the maturing
follicle that produces an increasing
amount of estradiol. Eventually at the
time of the maturation of the follicle, the
estrogen rise leads via the hypothalamic
interface to the ―positive feed-back‖
effect, a release of LH over a 24-48 hour
period. This 'LH surge' triggers ovulation
hereby not only releasing the egg, but
also initiating the conversion of the
residual follicle into a corpus luteum that,
in turn, produces progesterone to prepare
the endometrium for a possible implantation. LH is necessary to maintain luteal function for the
first two weeks. In case of a pregnancy luteal function will be further maintained by the action of
hCG (a hormone very similar to LH) from the newly established pregnancy. LH supports thecal
cells in the ovary that provide androgens and hormonal precursors for estradiol production.
In the male, LH acts upon the Leydig cells of the testis and is responsible for the production of
testosterone, an androgen that exerts both endocrine activity and intratesticular activity such as
spermatogenesis.

The release of LH at the pituitary gland is controlled by pulses of gonadotropin-releasing hormone


(GnRH) from the hypothalamus. Those pulses, in turn, are subject to the estrogen feedback from the
gonads.

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29.4 HCG

Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced in pregnancy that is made
by the embryo soon after conception and later by the syncytiotrophoblast (part of the placenta). Its role
is to prevent the disintegration of the corpus luteum of the ovary and thereby maintain progesterone
production that is critical for a pregnancy in humans. hCG may have additional functions; for instance,
it is thought that hCG affects the immune tolerance of the pregnancy.

Human chorionic gonadotropin is a glycoprotein composed of 244 amino acids with a molecular mass
of 36.7 kDa. Its total dimensions are 75×35×30 angstroms (7.5×3.5×3 nanometers). It is heterodimeric,
with an α (alpha) subunit identical to that of luteinizing hormone (LH), follicle-stimulating hormone
(FSH), thyroid-stimulating hormone (TSH), and β (beta) subunit that is unique to hCG.

The α (alpha) subunit is 92 amino acids long and has dimensions 60×25×15 angstroms (6×2.5×1.5
nm).
The beta subunit of human chorionic gonadotropin is encoded by six highly-homologous genes
that are arranged in tandem and inverted pairs on chromosome 19q13.3 - CGB (1, 2, 3, 5, 7, 8).

The two subunits create a small hydrophobic core surrounded by a high surface area-to-volume ratio:
2.8 times that of a sphere. The vast majority of the outer amino acids are hydrophilic.

Human chorionic gonadotropin interacts with the LHCG receptor and promotes the maintenance of the
corpus luteum during the beginning of pregnancy, causing it to secrete the hormone progesterone.
Progesterone enriches the uterus with a thick lining of blood vessels and capillaries so that it can sustain
the growing fetus. Due to its highly-negative charge, hCG may repel the immune cells of the mother,
protecting the fetus during the first trimester. It has also been hypothesized that hCG may be a placental
link for the development of local maternal immunotolerance.

For example, hCG-treated endometrial cells induce an increase in T cell apoptosis (dissolution of T-
cells). These results suggest that hCG may be a link in the development of peritrophoblastic immune
tolerance, and may facilitate the trophoblast invasion, which is known to expedite fetal development in
the endometrium. It has also been suggested that hCG levels are linked to the severity of morning
sickness in pregnant women.

Because of its similarity to LH, hCG can also be used clinically to induce ovulation in the ovaries as
well as testosterone production in the testes. As the most abundant biological source is women who are
presently pregnant, some organizations collect urine from pregnant women to extract hCG for use in
fertility treatment. Human chorionic gonadotropin also plays a role in cellular
differentiation/proliferation and may activate apoptosis.

***

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