GENERAL MEDICINE – 1ST YEAR – ENGLISH MODULE

PHYSIOLOGY
Semester I
Summary of exam topics
2014/2015
CONTENTS

PHYSIOLOGY LECTURES

Semester I, 2014/2015

I. Body water, introduction to physiology 2

II. Saliva 16
III. Stomach, gastric juice 26
IV. Pancreas, pancreatic juice 36
V. Liver, bile 44
VI. Intestinal absorption 50
VII. Motility 58
VIII. Endocrine system, introduction 71
IX. Hypothalamus and hypophysis 77
X. Surplus* will be published as a free pdf

***

The material in this paper has been written using the following sources:

1. Lectures given by Dr. Papacocea in the first semester of the first pre-clinical year of
general medicine at Carol Davila (English module);
2. Accompanying textbook “Lecture Notes of Clinical Physiology” by Dr. Papacocea;
3. Additional information from: Hall, J.E. “Guyton and Hall Textbook of Medical
Physiology”, 12th edition, Saunders, Philadelphia: 2011

While great care has been taken to ensure that the material presented herein is complete and
accurate, it must be stressed that this paper is by no means meant to be used as a single source
of study for exams. Please use this work as a guide for your own study of the primary sources
mentioned above. No responsibility will be taken for any error, omission or otherwise
incorrect information.

This work is not affiliated, associated, authorized, endorsed by, or in any way officially
connected with UMF Carol Davila.

1
I BODY WATER / INTRODUCTION TO PHYSIOLOGY

1.1 Introduction

In the human body, water represents a structural building block. It acts as a solvent, reaction
medium and reactant. It carries nutrients as well as waste products, helping the body get rid of
them (for example through urine formation). Water is also involved in thermoregulation,
lubrication and shock absorbing.1

When speaking of body water – and many things in physiology – we always have to take
variations into account. For example, two of these variations may be normal (physiological)
and abnormal (pathological) conditions. Other variations include gender, age, weight/height
ratio, muscle/fat ratio, and so on. Due to such variations, the amount of body water and its
composition will differ per individual.

Generally, however, body water represents about 60% of one’s body weight. Men will
typically have more body water than women, on account of the higher amount of skeletal
muscle tissue in men (contains more water) and the higher adipose tissue in women (water
repellent). It follows thus that an overweight person – male or female – would generally be
more “dehydrated” than a lean individual, as there would be more water repellent adipose
tissue and therefore a relative low water to weight ratio.

Total body water variations with age:

Embryo – 97%
Phoetus – 85-90%
Young child – 70-80%
Adult: 60%
Elderly: 55%2

1.2 Properties of water

The special properties of water are mostly the result of the hydrogen bonds: each H atom is
covalently bonded to the oxygen via a shared pair of electrons.

1. High polarity

High polarity means water has a high solubility. High solubility is vital for an increased
chemical reactivity.

Water basically acts like a magnet, having two poles: negative and positive. Water is therefore
a dipole.

Water is seen as a universal solvent since it can dissolve so many substances. Molecules can
be hydrophilic (dissolve in water) or hydrophobic (cannot dissolve; does not form hydrogen

1
For example in the brain
2
The decline in body water is directly related to muscle loss; aging has a catabolic (protein destroying) process

2
bonds with water).3 Most of these latter compounds do dissolve in oils and are therefore
known as lipophilic. They tend to be electrically neutral and non-polar.

2. High specific heat4

Water’s specific heat is 1 calorie/gram degrees Celsius5 -- higher than any other common
substance. The water molecule is thus able to “absorb” a great amount of heat, playing a main
role in thermoregulation, especially in preventing hyperthermia.6

3. High heat of vaporization

Another thermoregulating property. The high heat of vaporization of water makes it an

effective coolant for the human body via evaporation of perspiration, extending the range of
temperatures in which humans can exist. Because of heat absorbtion, evaporation has a
cooling effect on the surface exposed to this process: sweat evaporation cools the skin.

4. High thermal conductivity

Water transfers heat rather fast, making tissue that is rich in water poor insulators for the
body. By contrast, fatty tissue, being water repellent, is an efficient body insulator.

5. High surface tension (cohesion/adhesion)

Cohesion, otherwise known as water's attraction to other water molecules, is one of the major
properties of water. Water's polarity lends it to be attracted to other water molecules – this is
responsible for the phenomenon known as surface tension.7

The molecules at the surface do not have other water molecules on all sides of them and
consequently they cohere more strongly to those “next” to them on the surface. This forms a
surface "film" which makes it more difficult to move an object through the surface.

1.3 Water sources

Sources of water gain can be divided in exogenous and endogenous8 sources.

Exogenous sources are of course water ingestion through drinking (1500 ml/day) and food
(500 ml/day).

Endogenous water mostly comes from cell metabolism (200 ml/day).

3
Compounds containing C and H atoms. Eg. fats, oils, parafins, etc.
4
Amount of heat/g required to increase t by 1 degree Celsius
5
Or 4.186 Joule/g
6
Elevated body temperature due to failed thermoregulation that occurs when a body produces or absorbs
more heat than it dissipates
7
It is exactly this that enables some insects to walk on water.
8
Exo: from outside, endo: inside

3
1.4 Body water compartments

In a healthy adult, body water is roughly 60% of total body weight. This water is stored in
several compartments within the body.

- 40% of body weight (or, 2/3 of total body water) makes up intracellular fluid9
- 20% of body weight (or, 1/3 of TBW) makes up the extracellular fluid10, of which:
o 15% is interstitial fluid11
o 5% is intravascular fluid

The composition of electrolytes differs in each compartment, due to the selective permeability
of the membranes.

The exchange of electrolytes and other compounds between cells and capillary vessels takes
place in the interstitium.12

There is a third ‘compartment’ loosely known as transcellular fluid. This is basically all the
rest fluids:

- Cerebral spinal fuild (central nervous system)

- Aqueous humor and vitreous body (fluid of the eyes)
- All gastrointestinal tract fluids
- Perilymph and endolymph fluid (inner ear)
- Pleural fluid (membrane covering lungs)
- Pericardic fluid (membrane around heart)
- Peritonic fluid (around digestive organs)
- Synovial fluid (the lubricating fluid around cartilage at synovial joints (knees, elbows,
wrists, etc))

1.5 Electrolytes

Electrolytes in the body fulfil a variety of roles:

- They control osmosis

- Maintain acid-base balance
- Carry electrical current13
- Control some hormones and neurotransmitters

9
Fluid in the cells (intra = in), rich in K and proteins; poor in Na
10
Fluid outside the cells (extra = out), rich in Na, poor in K and proteins
11
Place between the cells themselves and between cells and capillaries (inter = between)
12
Arteries have thick walls and cannot exchange nutrients and other large compounds. Capillary walls can.
13
Necessary for action potential generation.

4
Some important electrolytes:

Sodium (Na+)

- Most abundant extracellular ion

- Necessary for electroimpulse transmission (and thus excitability)
- Needed for muscle contraction
- Regulates fluid and electrolyte balance by creating most of the osmotic pressure in the
extracellular fluid
o Sodium is mainly controlled by aldosterone.

Potassium (K+)

- Most abundant cation14 in intracellular fluid

- Responsible for rest membrane potential generation
- Regulates cellular excitability
- Modulates muscle contraction
- Regulates blood pH
o Mainly controlled by aldosterone

Calcium (Ca+2)

- Mostly an extracellular ion

- Building block for bones and teeth
- Part of the mechanism of blood clotting
- Enables neurotransmitter release
- Needed for maintenance of muscle tone
- Regulates excitability of nervous and muscle tissue
o Regulated by calcitonin and parathyroid

Magnesium (Mg+2)

- Intracellular cation
- Activates enzymes for protein digestion
- Needed for neuromuscular activity
- Has myocardial15 function
o Regulated by parathyroid

14
An anion (−) from the Greek word ἄνω (ánō), meaning "up", is an ion with more electrons than protons,
giving it a net negative charge (since electrons are negatively charged and protons are positively charged).
A cation (+) from the Greek word κατά (katá), meaning "down", is an ion with fewer electrons than protons,
giving it a positive charge.
15
Myocardium = muscular tissue of the heart

5
1.6 Diffusion, osmosis and filtration

Water exchange between body compartments is mostly passive, that is to say, “down-the-hill”
transport, necessitating no energy to move to one place to another.16

There are in the body three types of passive transport:

A. Diffusion17
B. Osmosis
C. Filtration

1.6.1 Diffusion

The process in the illustration above is simple diffusion, where particles move through a semi-
permeable membrane towards the area with lower particle concentration. In other words, a
substance is moved by the concentration gradient.18 The higher the gradient (so the more
difference in concentrations), the more diffusion will take place.

1.6.2 Osmosis

In osmosis we have a semi-permeable membrane that blocks particle (eg. electrolyte)

molecules but admits water to pass through. Diffusion cannot take place as particles cannot
travel from one area to another. Water, however, can, and it will go from the compartment
with the low particle concentration to the one with high particle concentration (see picture
below).

16
Active transport requires transporters such as ionic pumps (ATP-ases, proteins that break down ATP) or so-
called co-transporters that do not break down ATP but profit from the energy released by ATP-ase: free-riders.
17
Can be simple or facilitated. Facilitated means that the substance travels through the membrane carried by a
carrier-protein.
18
Concentration difference

6
Properly put, osmosis is the spontaneous net movement of solvent molecules through a
partially permeable membrane into a region of higher solute concentration, in the direction
that tends to equalize the solute concentrations on the two sides.

In other words, in osmosis it is the solvent (water) making the move, while in diffusion it is
the solute (dissolved compound; an atom, ion, or molecule) moving.

In the body, most substances have osmotic activity. In other words, they attract water to move
towards them. The normal osmotic pressure in humans (π) is about 300 milli-osmols/L.

1.6.3 Osmolarity, osmolality, osmotic pressure and tonicity: a paranthesis

Osmolarity is a measure of the osmoles of solute per liter of solution. A capital letter M is
used to abbreviate units of mol/L. Since the volume of solution changes with the amount of
solute added as well as with changes in temperature and pressure, osmolarity is difficult to
determine.

Osmolality is a measure of the moles (or osmoles) of solute per kilogram of solvent expressed
as (mol/kg, molal, or m). Since the amount of solvent will remain constant regardless of
changes in temperature and pressure, osmolality is easier to evaluate and is more commonly
used, and often preferred.

Osmotic pressure is the pressure of a solution against a semipermeable membrane to prevent

water from flowing inward across the membrane. Tonicity is the measure of this pressure. If

7
the concentration of solutes on both sides of the membrane is equal, then there is no tendency
for water to move across the membrane and no osmotic pressure. The solutions are isotonic
with respect to each other.

1.6.4 Filtration

Blood entering the capillary at its arterial end19 it has some remaining pressure from being
pumped out by the heart. That pressure is the hydrostatic capillary pressure or simply Pc. It is
a pro-filtration force: it pushes the blood not only through the capillary but also forces out a
bit of water through the thin capillary walls.

In plasma there is also an anti-filtration force, known as colloid osmotic pressure. 20 It is

provided by blood proteins which basically “attract” water to them through osmotic pressure,
carrying it forward towards the vein. This is noted as πc.

The water is filtered out of the capillary into the interstitium, where two similar forces are also
at work: a hydrostatic interstitial pressure Pi and a colloid osmotic pressure πi. The two
forces are anti- and pro-filtration forces respectively. They are known as the Starling forces.

The Starling forces can be put in a simple formula giving us the Starling equation:21

NFP = (Pc + πi) – (Pi + πc), where NFP = net filtration pressure.

Together, the four forces exchange water but at the same time maintain a balance by pumping
out as much as is being pumped back in.

19
Capillaries “begin” with an arterial end (from an artery) and “end” with the connection to the veins, so a
venal end
20
Also known as oncotic pressure
21
Simplified, ie. without the reflection coefficient.

8
In the beginning (arteriolar end) of a capillary, there is a positive net driving force outwards
from the capillary. In the end (venular end), on the other hand, there is a negative net driving
force. This roughly means that on average, about 20 L of water is being filtered out of
capillaries a day by the Pc and πi forces, but only about 17 L filtered back in thanks to the Pi
and πc forces. What happens with the remaining 3 L?22

The power of Pi is lessened in a way by lymph vessels which act almost like a vacuum23 and
take some of the interstitial fluid away in them.24 This translates to the equation as the value
for pi will be slightly negative: (pc + πi) – (-pi + πc).

This draining by lymph vessels happens for a reason. The lymphatic system has four main
functions:25

1. it ensures constant communication between plasma and interstitial fluid

2. it distributes nutrients, hormones and dissolved gases to tissues
3. it transports insoluble substances that cannot cross capillary walls
4. it flushes bacterial toxins and other chemicals towards immune-system tissues

In the end, the lymph vessels bring the fluid back into the blood stream, and balance is once
again restored.

Note that in a capillary, blood is filtered out at the arterial end (beginning) and filtered in at
the venal end. At the arterial end, pHc is high, whereas at the venal end, this force is low.

1.6.5 Clinical view: Edemata

An edema (pl. edemata) is a swelling of a tissue resulting from excessive accumulation of

interstitial fluid. There could be several causes for such a swelling:

- increased pHc (for example with heart failure, venous stasis, venous obstruction)
- decreased oncotic pressure (for example during hypoalbumenia or hypoproteinemia26)
- increased capillary permeability (for example caused by inflammatory substances such
as histamines, or through damage to capillary integrity (wound, burn))
- lymphatic obstruction (filarosis; inflammation of lymph vessels. Mostly at extremities
(limbs and facial features), extreme enlargement of affected area (elephantiasis))

22 th
Numbers from Guyton & Hall Textbook of Medical Physiology, 12 ed.
23
In fact exert a subatomic pressure
24
Once that fluid enters the lymph vessel, it is known simply as “lymph”
25
Not relevant for the exam
26
Caused by for example kidney or liver disease; proteins are synthesized here

9
1.7 Reflex arc

The reflex arc is a physiological phenomenon that is the same for every reflex. It is the path
that neural messages travel in order to effect a reaction to a stimulus. That path is represented
as follows:

1. Receptors
2. Afferent fibers (sensory neurons)
3. Regulatory nervous center (spinal cord, central nervous system)
4. Efferent fibers (motor neurons)
5. Effector

It is a rather straightforward model. Suppose you burn your hand on a hot plate. The receptors
in this case would be in your skin: they sense the heat/pain and send a message through the
sensory neurons (afferent) which is received by the central nervous system. The nervous
center then sends a message back, through the motor neurons (efferent), effecting some
motoric action – in our burn example, this message would be received by the muscles of the
arm (effectors) which contract to move the hand away from the heat source. See the following
picture:

The same model applies to the body’s water regulation system. The receptors in this instance
are various types:

- Osmoreceptors
o Specialized cells in the hypothalamus27
o Respond to extracellular tonicity changes (especially in Na+)28
- Low pressure baroreceptors (aka Volume receptors)
o Located in the right atrium and the great veins
o Respond to transmural pressure in the walls of these vessels (thus transmit
when blood volume (and pressure) drops drastically)

27
More specifically, in the so-called AV3V region (anteroventral 3d ventricle)
28
Basically detects changes in osmotic pressure in extracellular fluid

10
 - High pressure baroreceptors
o Located in the carotid sinus
o Respond to changes (up/down) in mean arterial blood pressure

1.8 Water intake regulation

Thirst can be described as the subjective sensation that is the driving force behind the
physiological impulse to ingest water (in other words, to drink). Its stimulus is a drop in body
water volume of about 10% or a rise in hypertonicity29 of 1-2%.

1.8.1 Stimuli: Four elements

The osmolarity of plasma is roughly 300 mOsm/liter. If the extracellular fluid is isotonic, it
has the same osmolarity as blood. If it is hypertonic, the concentration of electrolytes is
higher, and if it is hypotonic, the concentration of electrolytes is lower than plasma.

There are four elements which can trigger the sensation of thirst.

1. Hypertonicity
This basically is cellular dehydration. If the extracellular fluid has a high concentration
of electrolytes (therefore a high osmolality), the cells will give up the water from their
fluid to restore the balance. The cells then shrink, which is not good, as they need
water for their basic chemical reactions. This stimulates the osmoreceptors in the
hypothalamus.
2. Hypovolemia
When blood volume drops, the low pressure baroreceptors in the great veins and
atrium signal the CNS that something is wrong.
3. Hypotension
At low blood pressure, the so-called high pressure baroreceptors alarm the CNS to
motivate you to drink.
4. Angiotensin II
This is a substance produced in the kidney response to renal hypoxia. It is a potent
dipsogen30, acts as a vasoconstrictor31 and stimulates aldosterone secretion.

1.9 Water elimination

Water elimination takes place mostly through diuresis (secretion of urine by the kidneys).
Normal amounts are about 1.5 to 2 L per day. Water is also lost through sweat, insensible
perspiration and feces.

29
Higher concentration of osmotic active particles in extracellular fluid
30
Thirst stimulator
31
The narrowing of blood vessels

11
Kidney and nephron anatomy

One kidney contains about 1 million nephrons (see pictures above).

Nephron anatomy and urine formation path is as follows:

Bowman’s capsule proximal convolute tubule loop of henle distal convolute tubule
collector tube

The bowman capsule contains many glomerular capillaries where glomerular filtration takes
place and the collector tube is made up of cells called nephrocytes.

Glomerular filtration is the first step in urine formation. In glomerular filtration, a lot of the
blood plasma spills out of the capillaries into Bowman’s capsule (similar to what we saw
earlier with systemic capillaries). Electrolytes, wastes and small hormones could all pass
through in this filtration process. Blood cells and plasma proteins, however, cannot. Most of
the electrolytes and other nutrients filtered out will be re-absorbed at the level of the distal
convolute tubule.

The distal tubule is partly responsible for the regulation of potassium, sodium, calcium, and
pH. It is the primary site for the kidneys' hormone based regulation of calcium.

- It regulates pH by absorbing bicarbonate and secreting protons (H+) into the filtrate,
or by absorbing protons and secreting bicarbonate into the filtrate.
12
 - Sodium and potassium levels are controlled by secreting K+ and absorbing Na+.
Sodium absorption by the distal tubule is mediated by the hormone aldosterone.
Aldosterone increases sodium reabsorption.
- It also participates in calcium regulation by reabsorbing Ca2+ in response to
parathyroid hormone.

Anti-diuretic hormone (ADH) increases water re-absorption from the urine back into the
blood. This action takes place at the level of the distal tube. It reduces urine volume and
increases its concentration, while increasing blood volume and reducing its concentration.

ADH in high doses is also known as vasopressin since it acts as a vasoconstrictor. It is

stimulated by a drop of blood volume level (ca. 10%) or a change in blood osmotic pressure
(ca. 1-2%). ADH is a peptide hormone synthesized in the hypothalamus. In fact, the
hypothalamus uses ADH as a neurotransmitter. ADH can also be stimulated by pain or stress,
as well as by morphine, nicotine and barbiturics.

ADH inhibitors could be hypervolemia, hypotonicity and alcohol.

1.9.1 Renin-angiotensin aldosterone system: a paranthesis32

When renal33 blood flow is reduced, renin34 is secreted directly into the circulation. Plasma
renin then carries out the conversion of angiotensinogen released by the liver to angiotensin I.
Angiotensin I is subsequently converted to angiotensin II. Angiotensin II is a potent
vasoconstrictor that causes blood vessels to constrict, resulting in increased blood pressure.
Angiotensin II also stimulates the secretion of the hormone aldosterone from the adrenal
cortex. Aldosterone causes the tubules of the kidneys to increase the reabsorption of sodium
and water into the blood. This increases the volume of fluid in the body, which also increases
blood pressure.35

32
More information than you’ll need for the test.
33
Kidney
34
Not to be confused with rennin, a peptide acting on milk proteins (casein).
35
If the renin-angiotensin-aldosterone system is abnormally active, blood pressure will be too high. There are
many drugs that interrupt different steps in this system to lower blood pressure. These drugs are one of the
main ways to control high blood pressure (hypertension), heart failure, kidney failure, and harmful effects of
diabetes.

13
Aldosterone36 is a steroid hormone (mineralocorticoid family) produced by the adrenal gland.
It plays a central role in the regulation of blood pressure mainly by acting on the distal tubules
and collecting ducts of the nephron, increasing reabsorption of ions and water in the kidney,
to cause the conservation of sodium, secretion of potassium, increased water retention37, and
increased blood pressure.

1.9.2 Disorders of water balance

To end the body water chapter, we will sum up some consequences of disruption of water
balance. If you’ve understood the material so far, most of these should follow logically.

- Isotonic fluid
o excess: extracellular hyperhydration (too much water)
o lack: extracellular dehydration
- Hypertonic fluid38
o Excess:
extracellular hyperhydration
intracellular dehydration
• Cells give up water due to osmosis to restore balance in
extracellular fluid
o Lack:
Intracellular hyperhydration
Extracellular dehydration

36
Stimulators: decrease of the Na/K ratio, ACTH, angiotensin II (see above), prostaglandin E1 and E2. Inhibitors:
Pg, F1 and F2α
37
Water follows sodium due to osmotic pressure
38
Maximum C% NaCl

14
 - Hypotonic fluid39
o Excess:
extracellular hyperhydration
intracellular hyperhydration
o Lack:
Intracellular dehydration
Extracellular dehydration

***

39
Pure water

15
II SALIVA

2.1 Introduction

The digestive system consists of a gastrointestinal tract and accessory glands.

Its roles40 are:

1. Secretion of digestive juices

2. Digestion of food
3. Movement of food
4. Absorption of digestive products
5. Excretion
6. Endocrine function41

The anatomical order of the digestive tract:

1. Mouth (oral cavity)42

2. Pharynx
3. Esophagus
4. Stomach
5. Small intestine (bowel)
a. Duodenum
b. Jejunum
c. Ileum
6. Large intestine (bowel)
a. Cecum
b. Colon
i. Ascendant
ii. Transverse
iii. Descendent
7. Sigmoid Colon43
8. Rectum
a. Anal sphincter

Accessory glands:

1. Salivary gland
2. Pancreas
3. Liver

40
One could argue there is an “accessory” role of information: it tells the body what is or isn’t good to eat.
41
The endocrine system refers to the collection of glands of an organism that secrete hormones directly into
the circulatory system to be carried towards a distant target organ. Conversely, exocrine refers to any gland or
cell releasing substances into a tube, a cavity or outside the body.
42
Oral or buccal are adjectives relating to the mouth.
43
Some medical sources consider the sigmoid colon, the rectum and the anal canal to be part of the large
intestine. On Dr. Papacocea’s slides, however, they were presented as separate parts.

16
2.1.1 Digestive tube layers

From outside to inside:

1. Serosa
2. Longtitudinal muscle layer
3. Circular muscle layer
4. Submucosa
5. Mucosa

The submucosa contains the so-called Meissner plexus: thousands of networked neurons
comprising the local nervous plexus.

17
The muscularis also contains the Auerbach plexus (not pictured) which controls muscle
contraction (for example to move the food down the tract).

2.1.2 Digestive secretions

Secretions occur in most places along the digestive tract. These secretions consist of mixtures
of varying content and concentrations. Generally, enzymes, mucus, ions and other substances
can be found. Regulation of secretion is normally both nervous and humoral.44 It is mainly
parasympathetic45, but can sometimes also be conditioned.46

Secretion can depend on certain variables: quantity (eg. more saliva is secreted when eating),
quality (the type of food will dictate the content of secretion) and biorhythm (persons with a
strict regular diet can get conditioned to secrete in anticipation even if no food is yet present).

44
From, with or by hormones
45
Unconscious, “rest-and-digest”. The opposite is sympathetic, together they form the autonomous nervous
system.
46
See Pavlov’s dog.

18
2.2 Saliva

The target cell in salivary secretion is an exocrine cell, located in one of the salivary glands.
The salivary glands are the parotid, submandibular and sublingual glands, as well as some
smaller buccal glands.47

The secretory or exocrine cells in such gland consist of acini48 which contain both serous49
cells and mucus cells. The secretion is then excreted in the oral cavity through the ducts,
which are made from striated cells and are myoepithelial.50

Depending on the gland, acini are serous in the parotid gland, mucous in the sublingual gland
and both in the submandibular gland.

47
These secrete mostly mucus.
48
Clustered cells resembling a raspberry, sg. acinus
49
Secreting a body fluid that is not mucus
50
Cells usually found in glandular epithelium as a thin layer above the basement membrane but generally
beneath the cells in the lumen.

19
20
The exocrine cells pictured above are typical cells found in salivary glands. They have an
apical pole (at the level of secretion), rich in granules containing enzymes, and a basal pole
which is in contact with the blood vessel.

2.2.1 Primary saliva

Saliva secretion actually happens in two steps. Primary saliva is produced in the acini by an
active secretion done by ionic pumps. This primary secretion contains ptyalin and mucin in a
solution of ions in concentrations not too different from plasma – it is (nearly) isotonic.

2.2.2 Secondary or Final saliva

Primary saliva is not left untouched by the gland: in the salivary ducts, it is adapted and
reformed: the final composition of saliva is altered.

The striate cells of the duct actively reabsorb Na and secrete K instead.51 This process is
regulated by aldosterone. Also, Cl is reabsorbed (passively) and exchanged for HCO3
(bicarbonate). The result is that the final saliva is hypotonic52 and has a pH that is very
slightly acidic (6.8-7).53

In conclusion: the first stage involves the acini, and the second, the ducts.

51
Antiport mechanism
52
Up to 10 times less Na and 7 times more K concentration than plasma.
53
Enables ptyalin to do its work in optimal conditions

21
Daily secretion of saliva is about 1000 to 1500 ml per day, but this can vary:

Increased flow with:

- Pregnancy
- Psychological disorders (eg schizophrenia)
- Nervous diseases (eg Parkinson’s)

Decreased flow with:

- Age
- Dehydration
- Sleep
- Stress

2.3 Saliva composition

You now know that final saliva will contain water, mucus and various ions. There is, of
course, more. Thanks to Burger and Emmelin and their experiment, we know that saliva also
contains some other organic substances such as urea54 and ptyalin.55

54
CO(NH2)2 -- Urea serves an important role in the metabolism of nitrogen-containing compounds by animals
and is the main nitrogen-containing substance in the urine of mammals.
55
Salivary amylase

22
2.4 Roles of saliva

Saliva has digestive and non-digestive roles.

Digestive roles:

1. Moistens dry food and so increases solubilisation of food particles

2. Allows mastication, swallowing, helps stimulate taste buds and olfactory receptors56
3. Hydrolyses starch with ptyalin, generating dextrines and finally maltose
4. Lubricates and washes buccal cavity
5. Protects against mechanical injuries

Non-digestive roles:

1. Talking
2. Excretion of viruses, heavy metals, ions
3. Promotes oral hygiene by excreting bacteria
4. Antiseptic role through thiocyanate57 ions, lysosime, IgA58
5. thermoregulation59
6. endocrine role: secretes EGF60 and NGF61

56
Olfactory receptors are responsible for the detection of odor molecules.
57
Technically an anion. Thiocyanate is an important part in the biosynthesis of hypothiocyanite by a
lactoperoxidase. Thus the absence of thiocyanate in the human body, (e.g., cystic fibrosis) is damaging to the
human host defense system.
58
Immunoglobuline A (antibody) – generally protects mucosa (also in the nasal cavity)
59
Not in humans, not really, but in dogs and rats – fun to know.
60
Epidermal growth factor or EGF is a growth factor that stimulates cell growth, proliferation, and
differentiation: involved in wound healing.
61
Nerve growth factor (NGF) is a small secreted protein that is important for the growth, maintenance, and
survival of certain target neurons (nerve cells).

23
2.5 Regulation

In the previous chapter on body water we talked about the reflex arc. Salivary regulation
works much in the same way as it is a reflex that is regulated by both nervous and humoral
stimuli.

To recap, the reflex arc consists of:

- receptors
- sensory fibers (afferent)
- nervous center
- motor fibers (efferent)
- effectors

2.5.1 Nervous regulation

In the case of saliva, the nervous regulation consists of both parasympathetic and sympathetic
reflexes.

Parasympathetic reflexes (picked up by receptors 5, 7, 9 and 10) stimulate a very watery

salivary secretion that is low in enzymes and mucus. The sympathetic reflex, controlled by
fibers originating in the cervical ganglia, stimulate62 the secretion of a saliva rich in mucus
and ptyalin.

There is a conditioned part to this reflex, too. A smell, sight, remembrance or even thought of
a favorite food can stimulate the appetite area located in the anterior part of the hypothalamus.
This in turn stimulates salivary centers as if food were actually ingested.

We will discuss this mechanism in more detail in the next chapter on gastric secretion.

62
Via sympathetic nerves.

24
2.5.2 Humoral regulation

The hormones that affect salivary secretion are:

Increase secretion: 63

1. Bradikynin
2. VIP64

Decrease secretion:65

1. Angiotensin II
2. Substance P
3. Oxytocin

***

63
These are generally vasodilators, so they widen blood vessels and increase blood flow
64
Vasoactive intestinal peptide
65
Vasoconstrictors – decrease blood flow

25
III THE STOMACH: Gastric juice

3.1 Introduction

In this part we will discuss gastric juice, its composition and secretion mechanism. Gastric
juice is the body fluid found and secreted by cells in the stomach.

The stomach has a vertical and a horizontal part. The horizontal part is represented by the
cardial sphincter, the fundus and the body (corpus). The vertical part consists of the antrum,
the pyloric channel.

In previous chapters we discussed the various layers of the gastrointestinal tract, and we saw
that it is roughly the same throughout the tract. The stomach, then, also consists of the same
layers, as can be seen on the picture below – serosa, muscularis, submucosa, mucosa.

26
In addition to mucus-secreting cells that line the entire surface of the stomach, the stomach
mucosa has two important types of tubular glands: oxyntic glands66 and pyloric glands.67 The
oxyntic glands secrete hydrochloric acid, pepsinogen, intrinsic factor and mucus. The pyloric
glands secrete mainly mucus for protection of the mucosa from the acid. They also secrete the
hormone gastrin.

3.2 Secretory glands

Oxyntic glands have 3 types of cells:

1. Mucous neck cells

a. Mucus producing cells which cover the inside of the stomach, protecting it
from the corrosive nature of gastric acid. It prevents the stomach digesting
itself.
2. Oxyntic or Parietal cells
a. These secrete gastric acid (HCl, KCl, NaCl) and intrinsic factor.68
3. Peptic or Chief cells
a. cells in the stomach that release mainly pepsinogen – the precursor of pepsin.

Pyloric glands secrete mainly mucus to protect themselves and the stomach wall from HCl.
They also have specialized cells called gastrin cells, or G-cells, which produce the hormone
gastrin. Gastrin, as we will see later, plays an important role in stimulation of acid secretion.

66
Found in the fundus and the corpus
67
In the pyloric antrum
68
a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12
(cobalamin) later on in the small intestine (less acidic area).

27
3.3 Gastric juice composition

28
The composition of gastric juice is fairly straightforward and consists, like many other bodily
secretions, mainly of water with a small amount of organic and inorganic substances. We will
discuss the secretion of these substances in the next paragraphs.

- HCO3 = bicarbonate, Na = sodium, K = potassium

- Enzymes: digestive enzymes pepsin and rennin
o Pepsin69 converts proteins into simpler, more easily absorbed substances
o Hydrochloric acid provides the acid environment in which pepsin is most
effective.
o Rennin aids the digestion of milk proteins.70

- Mucus secreted by the gastric glands helps protect the stomach lining from the action
of the acid.

3.4 Regulation of gastric juice secretion

The secretion of gastric juice follows a similar reflex arc as discussed in the previous chapters
on body water and saliva. For gastric juice, however, one may distinguish three separate

69
Activated form of pepsinogen
70
Namely casein.

29
phases of secretion: cephalic, gastric and intestinal (see picture above). The regulation is also
both nervous and humoral.

3.4.1 The three phases

As mentioned, the three phases of gastric juice secretion are:

- Cephalic71 phase
- Gastric phase
- Intestinal phase

Note that each of these phases depends on the position of the food. Sometimes food does not
have to be present at all to stimulate secretion; indeed, we can say secretion starts in the head.

Cephalic Phase

- Before food even enters stomach

- Sight, smell, taste, thought of food can be a stimulus
- Cerebral cortex sends nervous impulse (using acetylcholine, or Ach) through (the
dorsal nuclei of) the vagus nerve72 stimulating the stomach (parasympathetic process,
accounts for 30% of gastric secretion while eating).
- Increases hydrochloric acid (HCl) & pepsin73 secretion
- Acetylcholine further stimulates gastrin, which is secreted by the endocrine G-cells
and travels the bloodstream until it reaches the stomach again and stimulates yet more
HCl secretion

Gastric Phase

- Food reaches and distends the stomach

- Nervous mechanism
o Distension receptors from the gastric wall transmit impulses to the dorsal
motor nuclei of the vagus nerve, which, through acetylcholine:
stimulate an increase in HCl, pepsin, histamine and gastrin.
The latter two further stimulate secretion HCl & pepsin during several
hours
- Humoral mechanism
o When the stomach mucosa comes into contact with proteins and peptides, G-
cells are triggered to release gastrin, thus increasing HCl and pepsin secretion.
- Accounts for 60% of secretion

Intestinal Phase

- Nervous mechanism

71
Greek Kefalos = head
72
Also known as nerve X, or nerve 10
73
Peptide acting on proteins

30
 o Distension receptors from the duodenum transmit impulses to the dorsal motor
nuclei of the vagus nerve, releasing acetylcholine to
Local enteric nervous system (plexi) and then to
Gastric glands; effecintg:
• DIRECTLY: HCl and pepsin increase
• INDIRECTLY: Histamine increase, thus increasing HCl and
pepsin
- Humoral mechanism
o If proteins reach duodenum: Further secretion of gastrin from G-cells (thus
more HCl en pepsin; stimulatory effect).
o If lipids and sugars reach duodenum: inhibitory hormones74 release from
intestinal endocrine cells, inhibiting gastric secretion.

3.4.2 Inhibitory hormones

Secretin is a hormone that regulates water homeostasis throughout the body, and influences
the environment of the duodenum by regulating secretions in the stomach and pancreas.
Secretin is produced in the S cells of the duodenum.

Secretin’s role is to help regulate the pH of the duodenum by:

- inhibiting the secretion of gastric acid from the parietal cells of the stomach;
- stimulating the production of bicarbonate from the centroacinar cells and intercalated
ducts of the pancreas.75

Somatostatin (also known as growth hormone-inhibiting hormone (GHIH)) is a peptide

hormone that regulates the endocrine system and affects neurotransmission. Its main role is to
inhibit a number of hormones, but for our purpose it is important to know it inhibits gastrin
secretion.

3.4.3 Secretion of hydrochloric acid (HCl)

Hydrochloric acid is secreted solely by the parietal cells, which synthesize HCl
extracellularly. This occurs in several steps:

- First, H2O is dissociated inside the cell cytoplasm into H and OH

o H is then actively secreted into the canaliculi76 in exchange for K, thanks to
H/K ATP-ase (an ionic pump).
- Pumping out H by H/K/ ATP-ase results in OH accumulation
o OH then forms HCO3 with CO2, which was acquired from plasma
o HCO3 is then exchanged for Cl from extracellular fluid and Cl is secreted in
the canaliculi

74
Secretin, glucagon, somatostatin, CCK, GIP, VIP
75
See chapter IV
76
“Canals” formed by the cells where HCl is stored until secretion; important to realize this is extracellular

31
 o In the canaliculi there is now a potent concentration of hydrochloric acid (HCl)
at a pH of about 1-1.5 which finally is secreted through the open end of the
canaliculus into the lumen of the gland

To produce such a concentration of H ions requires minimal back leak into the mucosa. This
is achieved first by the thin layer of alkaline mucus forming a barrier, but also thanks to the
very tight junctions between the cells themselves.

3.4.4 Pepsinogen and pepsin

Peptic or chief cells are mainly responsible for the secretion of pepsinogen. When pepsinogen
comes in contact with HCl, it is activated to form pepsin. Pepsin, vital for protein digestion in
the stomach, only functions in a highly acid environment. This environment is provided by
the hydrochloric acid. It works on proteins by attacking the molecular chain inside the protein
molecule.

3.4.5 Intrinsic factor

The substance intrinsic facto is a glycoprotein and is essential for the absorption of vitamin
B12 in the ileum. It is secreted by the parietal cells along with HCl. Without this factor
vitamin B12 would not be absorbed and anemia could develop, because red blood cells cannot
mature without this vitamin.

3.4.6 Mucus

Gastric mucus exists in three types:

1. Free mucus – dissolved in gastric juice

2. Attached to the gastric epithelium – loosely attached at that, as it could be washed
away
3. Dense mucus layer, not detachable, important in protection of the stomach. It is made
up of neutral mucopolisaccharides.

Mucus synthesis is stimulated by prostaglandins, but inhibited by every-day factors such as

smoking, aspirin, adrenalin, cortisol, and so on. If mucus is chronically inhibited, there will be
a high risk of ulcer development.

3.4.7 Histamine and gastrin

As stated earlier, HCl secretion is under continuous control by both nervous signals and
humoral mechanisms (or, in other words, endocrine signals). Histamine plays an important
role in the humoral system. Parietal cells operate in close association with so-called ECL cells
(enterochromaffin-like cells), whose primary function is the secretion of histamine.

Histamine is a chemical mediator and since the ECL cells lie deep in the oxyntic gland,
histamine will make direct contact with the parietal cells. The rate and amount of HCl

32
secretion by parietal cells is directly related to histamine release: this is a paracrine77
mechanism. In fact, it is these cells that are stimulated by gastrin to in turn stimulate HCl
release!

When certain foods – mostly proteins – come into the antral end of the stomach, gastrin cells
in the pyloric glands are stimulated to release gastrin into the blood. It then reaches the ECL
cells in the corpus of the stomach, causing histamine release which acts quickly to stimulate
HCl secretion. So: food gastrin circulatory system ECL cells histamine parietal
cells HCl!

3.4.8 Other gastric enzymes

Gastric lipase is a weak lipase acting only on pre-emulsified fats. Rennin (also known as
labferment) breaks down casein (milk proteins).

3.5 Roles of hydrochloric acid

- Digestive roles
o Protein denaturation (changing, or rather simplifying the structure of the
molecules, making them ready for pepsin action)
o Activating of pepsinogen to pepsin
o Creating and maintaining an optimal pH for pepsin
- Non-digestive roles
o Antimicrobial (antiseptic protection due to destruction of microorganisms)
o Chemical and mechanical protection due to mucus and HCO3 barrier
o Antianemic role
By secreting intrinsic factor along with HCl, it prevents anemia caused
by B12 deficiency – pernicious anemia.78
It converts Fe3 to Fe2, the only absorbable form for the body, thus
preventing anemia caused by iron deficiency

3.6 Receptors of parietal (oxyntic) cells

By now we have learned that a variety of messengers and substances target oxyntic cells to
secrete gastric acid and other substances. The three important ones are gastrin, histamine and
the neurotransmitter acetylcholine. The oxyntic cell has receptors for all three:

77
Only stimulates neighboring cells
78
This can appear due to absence of intrinsic factor or during atrophic gastritis, whereby parietal cells are
destroyed.

33
 - H2 receptors for histamine
o Blockers: ranitidine, cimetidine, famotidine
o Prevents histamine from binding, reduces acid secretion
- M3 receptor for acetylcholine
o Blockers: atropine et al.
- CCK-B Gastrin receptor
o Blocker: proglumid
If no blockers help, a H-pump blocker may be prescribed (omeprazole),
which blocks H-secretion altogether

3.7 Pathology: ulcers

Ulcers represent a pathological state where there is a disturbance in the equilibrium between

- Aggression factors: HCl and pepsin

- Protection factors:
o Gastric epithelium integrity
o Gastric mucus
o Gastric microcirculation
o Cytoprotective prostaglandins

Every time aggression factors increase or protection factors decrease (or both), the risk of
ulcers rises.

34
3.7.1 Ulcer types

Normally, the stomach produces enough mucus to protect the mucosa against HCl and pepsin
action. Moreover, in the duodenum, pancreatic bicarbonate creates a pH of 7.5 at the luminal
membrane of the mucosa. Still, mucosa ulceration may occur due to various causes.

- Gastric ulcer
o Decrease of protective factors
o Aggression factors low, normal or high
- Duodenal ulcer
o Increase of aggression factors
o Protective factors normal or low

3.7.2 Other risk factors

HCl and pepsin secretion can be increased by caffeine, anti-inflammatory drugs,

hyperparathyroidism, gastrin producing tumors (Zollinger-Ellison syndrome, tumor mostly
located in pancreas).

Aspirin and other drugs alike can decrease the protective factor of the mucosa as it depletes it
of prostaglandins. Alcohol can damage the mucus barrier and further stimulate acid secretion.

Addendum: HCl synthesis and secretion

***

35
IV PANCREAS

4.1 Introduction

The pancreas is an abdominal organ and one of the accessory glands of the digestive system.
It is a mixed gland, meaning that it has both exocrine and endocrine functions. In this chapter,
we will focus on the exocrine secretions of the pancreas.79

The pancreas is situated inferior and parallel to the stomach. It is a large, compound gland
with a structure that is similar to salivary glands. The pancreatic secretion is called pancreatic
juice and is released into the lumen of the duodenum via a duct (the Wirsung duct or
channel).80

The pancreatic juice secreted in the duodenum will contain HCO3 (bicarbonate) to counter the
acidity of gastric juice, as well as many digestive enzymes. These enzymes are secreted by the
acini.81 So-called centroacinar cells are responsible for fluid and electrolyte secretion. Duct
cells will finally modify this secretion by adding HCO3.

The exocrine glandular tissue mass comprises around 80% to 90% of the total mass of the
pancreas.

We will now have an in-depth look at the exocrine pancreatic secretion.

79
Endocrine secretions of the pancreas are glucagon and insulin (by the Lagerhans islets) into the blood.
80
Note that the pancreatic head is situated in the duodenal concavity
81
Much like the ones in salivary glands, see chapter 2

36
4.2 Pancreatic Juice

The pancreas secretes digestive enzymes together with large volumes of HCO3 solution. The
precise contents and characteristics of the juice are to some extent determined by the type of
nutrients in the chyme.82 In other words: it adapts its secretion depending on what you just
ate.

4.2.1 Pancreatic Juice: composition and secretion

Pancreatic secretion is 98% water and 2% dry substances. We saw earlier that pancreatic juice
content can vary depending on the type of food you eat. This is thanks to the duodenal
mucosa which contains a large variety of endocrine cells (much like G-cells in the stomach)
which release various substances into the blood when triggered by certain nutrients.

For example, starch from bread will stimulate S-cells, which release secretin, which in turn
“tells” the pancreas to release pancreatic amylase. Proteins trigger CCK-cells, which release
CCK into the blood, causing the pancreas to release proteases.

82
Chyme (/kaɪm/; from Greek χυμός khymos, "juice") is the semifluid mass of partly digested food expelled by
the stomach into the duodenum.

37
4.2.1.1 Pancreatic juice composition: digestive enzymes

Note that there are enzymes to digest just about anything: protelolytic enzymes for proteins,
lipolytic enzymes for fats, glycolytic enzymes for sugars. The enzymes are synthesized in the
endoplasmic reticulum of the acinar cells and packaged in the zymogen granules.

The glycolytic enzyme is pancreatic amylase, which we remember from saliva. The
pancreatic variety is much stronger than the ptyalin found in saliva. Unlike the other
pancreatic enzymes, amylase is released in active form.83 Pancreatic amylase hydrolyzes
starches, glycogen and most other carbohydrates to form mostly disaccharides,84
oligosaccharides85 and a few trisaccharides.86 It functions optimally at a pH of 7

Pancreatic lipase is responsible for the digestion of lipids. 87 It acts together with a co-factor
(co-lipase) to attack and break the bonds of triglycerides, resulting in monoglycerides and free
fatty acids, and sometimes free glycerol and fatty acids.88 Free glycerol is readily absorbed

Finally, the pancreatic enzymes for digesting proteins are trypsin, chymotrypsin and
carboxypolypeptidase. These are released in inactive form, as they would otherwise digest the
pancreas itself (as we will see, this happens with acute pancreatitis).

4.2.1.2 Protease activation

Trypsin, chymotrypsin and carboxypolypeptidase are secreted as trypsinogen,

chymotrypsinogen and procarboxypolypeptidase respectively. These inactive forms become
activated only after they are secreted into the duodenum.

Trypsinogen is the first to be activated by enterokinase, an enzyme released from duodenal

mucosa when chyme comes in contact with the mucosa.89

Trypsin then activates all the other proteases. 90

4.2.2 Secretion

The pancreatic digestive enzymes are released by the pancreatic acini. Large volumes of
sodiumbicarbonate solution are secreted by cells in the small ducts leading from the acini.
This mixture then travels through the pancreatic duct (Wirsung duct) and joins the common

83
It does not form a danger to pancreatic tissue
84
Eg. maltose (2 glucose)
85
Dextrins
86
Eg. maltotriose
87
Other enzymes for fat digestion that were not mentioned in the lecture are cholesterol esterase, which
hydrolyzes cholesterol esters; and phospholipase, which splits fatty acids from phospholipids.
88
Guyton & Hall make no mention of free glycerol + fatty acids, though it is mentioned in Dr. Papacocea’s book.
I have found no other source confirming or disproving this, but as was also discussed in the Biochemistry
lectures, lipase can in principle only cleave two fatty acids off a triglyceride, resulting in a monoglyceride + 2
free FA.
89
Trypsinogen may also be activated by previously formed trypsin still found in the duodenum: autocatalytic
90
Two other proteases are collagenase and elastase (digesting collagen and elastic proteins resp.); they are
released and activated in a similar manner.

38
bile duct (or hepatic duct) before it empties in the duodenum through the papilla of Vater,
surrounded by the sphincter of Oddi.

The main (Wirsung) duct runs the entire length of the pancreas. An accessory duct, known as
the Santorini duct, empties from the superior part of the pancreatic head either directly into
the duodenum or in the Wirsung duct.

As previously stated, the pancreatic juice is collected in the acinar ducts before being
transported through a network of branches to the Wirsung duct.

39
4.3 Regulation of pancreatic secretion

Not unlike salivary and gastric secretion, pancreatic secretion is regulated by both a nervous
and a hormonal mechanism. The nervous mechanism consists of a parasympathetic
mechanism, with the vagus nerve releasing acetylcholine. The hormonal part is represented by
CCK, Secretin, VIP, GIP91 and somatostatin and enteroglucagon.

4.3.1 Stimuli causing secretion

The basic stimuli causing pancreatic secretion are:

1. Acetylcholine
i. Representing the nervous parasympathetic mechanism, it is released
from the vagus nerve endings and other nerves in the enteric nervous
system
2. Cholecystokinin (CCK) 92
i. Secreted by the duodenal mucosa when food93 enters the small
intestine. It stimulates a pancreatic secretion rich in enzymes.
3. Secretin94
i. Secreted by duodenal mucosa in response to highly acid chyme. It
stimulates a watery, alkaline95 secretion.

Another stimulus is VIP (vasoactive intestinal peptide), a hormone which stimulates secretion
of water and electrolytes. It also stimulates contraction of enteric smooth muscle, dilating
peripheral blood vessels, pancreatic bicarbonate secretion, and inhibits gastrin-stimulated
gastric acid secretion.

Acetylcholine and CCK both stimulate a secretion rich in pancreatic enzymes but with
relatively small quantities of water and electrolytes. Most of the enzymes remain in the acinar
ducts until the watery secretion, stimulated by secretin, washes them out.

4.3.2 Phases of pancreatic secretion

Pancreatic secretion occurs in three phases which are the same for gastric secretion: the
cephalic phase, gastric phase and the intestinal phase.

91
In Dr. Papacocea’s book this hormone is listed as a stimulus, however it is now believed that the (sole)
function of GIP is to induce insulin secretion.
92
CCK, like secretin, passes through the circulatory system to the pancreas, but unlike secretin, CCK causes
secretion of pancreatic enzymes by the zymogen granules of the acinar cells. This effect is similar to the
nervous, vagal stimulation, but is actually stronger.
93
Mostly fats and proteins; to a lesser extent glucose.
94
Secretin is mainly responsible for the watery secretion in the duodenum.. At the level of the stomach, it
inhibits the secretion of gastric acid from the parietal cells.
95
Large volumes of HCO3

40
 - Cephalic phase
o Before food enters stomach
o 10% of total secretion
o Sight, smell, taste, thought of food can be a stimulus (conditioned reflex)
o Cerebral cortex sends a nervous impulse, releasing acetylcholine from the
vagal nerve endings in the pancreas
o Unconditioned reflex: oral cavity receptors release impulses transmitted by
afferent nerves V, VII, IX and X (vagus). These impulses reach the pancreatic
center of the medulla oblongata. The efferent (or motor) fibers are vagal (X)
and they release acetylcholine, stimulating pancreatic secretion and gastrin
secretion in the stomach
o Hormonal: gastrin can stimulate acinar cells (zymogen granules) as well, via
the CCK receptor.
- Gastric phase
o Food is in the stomach
o Nervous stimulation continues
o <20% of total secretion
o Vago-vagal loops and gastrin (as in cephalic)
- Intestinal phase
o As chyme leaves the stomach and enters the duodenum, pancreatic secretion
increases greatly, due to secretin
o 70% of secretion
o Most important and most complex secretion
o Large quantity of fluid with large quantities of bicarbonate, neutralizing the
gastric acid

4.3.3 Inhibitors of secretion

Somatostatin and enteroglucagon are the inhibitory hormones in pancreatic secretion

regulation.

Somatostatin suppresses the release of gastrointestinal hormones such as gastrin, CCK,

secretin, VIP and GIP.

Enteroglucagon is released when fats and glucose are present in the small intestine, which
decrease the motility to allow sufficient time for these nutrients to be absorbed.

4.4 Bicarbonate and water secretion

Unlike the pancreatic enzymes which are secreted entirely by the acini, bicarbonate ions and
water (the other two major components of pancreatic juice) are secreted mainly by epithelial
duct cells leading from the acini.

The role of the alkaline bicarbonate is to neutralize the HCl emptied into the duodenum from
the stomach.

The HCO3 and H2O secretion works as follows:

41
 - CO2 diffuses from the blood into the cell
- Carbonic anhydrase (an enzyme) makes it combine with H2O to form carbonic acid
(H2CO3)
- The carbonic acid then dissociates into HCO3 and H
- Through active transport, the HCO3 ions are brought into the lumen of the duct, in
association with Na ions
- The H ions formed by disassociation in step 3 are exchanged for Na, and the overall
movement of Na and HCO3 causes an osmotic pressure gradient that attracts water
into the pancreatic duct

What you need to remember is that HCO3 is formed from carbonic acid thanks to the enzyme
carbonic anhydrase.

Major stimulants for this are secretin, CCK, acetylcholine and gastrin; while inhibitors are
atropine, somatostatin, pancreatic polypeptide and glucagon.

4.5 Pathology

In healthy individuals, the pancreas is protected against autodigestion by the fact that most
enzymes are secreted in their inactive form. Moreover, antitrypsin (another enzyme) binds
and neutralizes trypsin once its work is done, further protecting against harmful effects.

Sometimes, however, premature activation occurs, leading to unpleasant situations.

4.5.1 Acute pancreatitis

Acute pancreatitis is the acute inflammation of the pancreatic tissue due to auto-activation of
pancreatic enzymes in the organ itself.

When the pancreas gets damaged or when a duct becomes blocked, large quantities of
pancreatic secretion may get pooled in the damaged areas. Under these condition, trypsin may
auto-activate (and will in turn activate all others) and can digest the pancreas in a matter of
hours.

While trypsin is usually the prime suspect in such cases, it is likely that all digestive enzymes
play their part in the destruction. Elastase, for example, can digest blood vessel walls.96

The typical patient is male, around 40 years old, very fat or obese, after a meal rich in fats and
proteins accompanied by high alcohol intake.

The onset is sudden with unbearable abdominal pain, which may in some cases be so intense
that it can lead to a shock or even death.

The condition is sometimes lethal because of pain and/or accompanying circulatory shock, but
even if not, can lead to chronic pancreatic insufficiency.

96
If the enzymes enter the blood stream, other organs may be affected such as liver, heart and even the brain.

42
4.5.2 Chronic pancreatitis

Pancreatic (exocrine) insufficiency occurs when approximately 80% of the functioning

pancreas is destroyed. As mentioned above, this may be a lasting effect of having survided
(one or more cases of) acute pancreatitis.

Digestion of carbohydrates, proteins and fats will be severely impaired and unabsorbed fat
will appear in the stool.97 Absorption of food will be insufficient and often weight loss occurs.

***

97
Steatorrhea; can also occur due to insufficient pancreatic lipase

43
V LIVER & BILE

5.1 Introduction

In this part we will have a look at the liver, its secretion (bile) and the gall bladder.

Producing and secreting bile is one of the liver’s main functions, as bile salts are essential for
a complete digestion: bile acts as a detergent to facilitate digestion and absorption of lipids.
Bile is produced continuously, and when not needed for use, stored in the gall bladder.

The chapter will end with a brief discussion of various pathological states.

5.2 The liver

The liver is the largest gland in the human body. Located in the upper right corner of the
abdominal cavity, it weighs about 1.5kg and is divided by fissures into four lobes: right, left,
quadrate and caudate.

The liver lobes are made up of tiny units called lobules, which in turn consist of plates of liver
cells. At the edge of the lobules are sinusoids, the most permeable capillaries in the body.

5.2.1 Roles of the liver

The liver fulfils various roles in the body:

1. Production of bile
2. Processing and storing of nutrients, iron, vitamins
3. Synthesis of blood proteins and coagulation factors
4. Detoxification and inactivation of drugs and other toxic substances
5. Participation in iron metabolism
6. Metabolism of some hormones
7. Phagocytosis98 of bacteria and other debris

98
The process of “eating” a cell by another, specialized cell

44
5.2.2 Liver vasculature

Blood containing oxygen is supplied by the hepatic artery, which follows directly from the
aorta. This oxygenated blood is brought via branches and finaly hepatic capillaries to the left
and right lobes.

Blood is also supplied from the digestive tube (stomach, intestines) containing absorbed
substances.99 This mix is collected by a network of venules and brought into a larger vein: the
hepatic portal vein.100 Branches of this vein terminate in the sinusoids, between the lobules.

Both the blood from the hepatic artery as from the hepatic portal vein is eventually collected
in just one vein: the central vein.101

As you can see in the image above, the bile duct, portal vein and the hepatic artery cluster
together. They are therefore collectively called portal triad. In reality, the triad part is a
misnomer, as the bundle includes lymphatic vessels and a branch of the vagus nerve as well.

99
Nutrients but also toxins
100
Blood containing CO2
101
Not pictured in the image on this page

45
The blood leaves the liver via a central vein contained in each lobule. These small branches
form the right, middle and left hepatic veins and lead directly to the inferior vena cava,
draining blood from the liver.

Note the hexagonal shape of the lobule, the plates of hepatocytes (liver cells) and the portal
triad.

46
5.3 Bile

Bile is the secretion produced by the liver. Its production is a continuous process, and excess
bile is drained in the hepatic duct and stored in the gall bladder. Production volume is
approximately 1500 ml per day.

5.3.1 Bile composition

98% H2O; 2% dry substances:

• Inorganic substances
o HCO3, Na, K, Cl
In similar concentrations to plasma contents
• Organic substances
o Cholesterol
o Phospholipids
o Bile acids
o Bile pigments
o Proteins (mainly albumin and IgA)

Note that bile does not contain any enzyme!

Bile composition also differs slightly depending on where it is. Hepatic bile is of a yellow-
golden color, clear, isotonic and alkaline (pH 8). In the gall bladder, bile is dark yellow to
greenish, viscous, more concentrated and has a pH of around 7.5.

5.3.2 Bile acids

Bile acids are synthesized by hepatocytes from cholesterol and come in two forms: cholic
acid and deoxycholic acid. These are known as primary bile acids.

Most bile acids are then conjugated with either taurine or glycine102; they are then known as
bile salts.103

They are then secreted into the small intestine104 where local bacteria105 convert a portion of
the primary bile acids to secondary bile acids (deoxycholic acid and litocholic acid).

Most bile acids (around 95%) are reabsorbed in the distal part of the ileum106 and transported
back to the liver through the portal vein. This phenomenon is known as the hepato-
enterohepatic recirculation107.

A small part of bile acids is excreted with feces. In this case, resynthesis occurs to replace as
many bile salts as needed.
102
Cholic acid, for example, would form taurocholic and glycocholic acid respectively.
103
They are also complexed with sodium
104
Through the common bile duct; enters through sphincter of Oddi
105
Largely in the jejunum and ileum
106
Thanks to a Na/Bile co-transporter (secondary active transporter).
107
Lit.: liver-intestine-liver recirculation

47
During interdigestive periods, the sphincter of Oddi will close and the gall bladder will relax,
so that bile will flow to and be stored there. As a result of reabsorption of solutes and water,
bile will generally be concentrated.

5.3.3 Secretion stimuli

Gastrointestinal agents that stimulate the flow of bile into the duodenum are called
cholagogues. The main cholagogues are:

- Acetylcholine
- Secretin

Those that stimulate the production of bile by the liver are choleretic substances and are:

- Acetylcholine
- Cholecystokinin
- Lipid

5.3.4 Bile acid roles

1. Lipid emulsification108
a. Bile acids are amphipathic: they have both hydrophilic and hydrophobic poles,
acting like a detergent. It emulsifies fat into small droplets.109
2. Forming micelles
a. Again because of their amphipathic trait, bile salts form, together with lipds,
so-called micelles: small physical complexes of lipids that remain suspended in
water and are semi-soluble because of bile salt electrical charges. In this way,
lipids can be “ferried” through the mucosa and be absorbed.
3. Choleretic role
a. Stimulate bile secretion (but not synthesis
4. Transport and absorption of fat-soluble vitamins

5.4 Bile pigments

Bile has two pigments: bilirubin (yellow) and biliverdin (green). These pigments both stem
from the hemoglobin from erythrocytes (red blood cells).

The lifespan of a erythrocyte is about 120 days, after which it will be catabolized by
macrophages110 from the liver. The cytoplasm of erythrocytes is rich in hemoglobin, an iron-
containing biomolecule that is responsible for the red color of the cells. Macrophages further

108
Triglycerides, phospholipids and cholesterol
109
A physical, not a chemical process; not hydrolysis.
110
Macrophages (lit. “big eaters”, from Gr. makros + phagein), are a type of white blood cell that engulf and
digest cellular debris, foreign substances, microbes, and cancer cells by phagocytosis.

48
break the heme from hemoglobin down to biliverdin, which normally quickly reduces to
bilirubin.111

Bilirubin is transported to the liver by albumin. Before it reaches the liver it is also called pre-
hepatic. Pre-hepatic bilirubin is unconjugated (indirect), not soluble in water and bound to the
albumin molecule. Once in the liver, it is post-hepatic, free (no longer bound to albumin),
conjugated (direct).

Though most bile acid is resorbed in the terminal ileum to participate in enterohepatic
circulation, conjugated bilirubin is not absorbed and instead passes into the colon.

Under normal conditions, bilirubin concentration in plasma should be 1mg/dl, most of this
(0.9 mg) being conjugated. An excess of bilirubin (3mg or more) in plasma is known as
jaundice,112 which may point to liver disease, hemolysis or obstructions of the bile ducts.113

***

111
This process is sometimes seen in bruises, where fresh bruises have a greenish color which later turns to
yellowish. Bilirubin is also responsible for the yellow color of urine, as it is excreted in it.
112
Due to the skin obtaining a yellow color
113
Obstruction may be due to gallstones, which may form due to overstimulation of the gall bladder by fats.
Most of the time, gallstones are solidified cholesterol. They may or may not cause discomfort, but when they
do, one often feels pain in the right upper abdomen or upper back; nausea and vomiting (sometimes vomiting
bitter bile), bloating, indigestion etc.

49
VI Intestinal Absorption

6.1 Introduction

In chapter II we briefly introduced the intestinal structure. In this chapter, we will focus on the
small intestine, which as you now know, consists of three parts:

- Duodenum
- Jejunum
- Ileum

The duodenum is about 25 cm long and is the primary site of digestion in the intestine. The
jejunum follows with 120 cm in length, some digestion takes place here. Lastly, there is the
ileum, coming in at 150 cm it is the longest part, but little to no digestion happens in this part.

The layers of the digestive tract were (from inside out):

- Mucosa
- Submucosa (with the Meissner plexus)
- Muscularis (circular and longitudinal; with Auerbach plexus)
- Serosa (covered by peritoneum: a double membrane covering organs)

Let’s take a closer look at the structure of these layers and how they work together to absorb
nutrients from our food.

6.2 Layer structure

50
The small intestine is the site of the completion of digestion and absorption of nutrients. In
fact, most of the digestion and absorption happens here (around 70%).

The gut mucosa consists of:

- Epithelium with villi and microvilli

- Lamina propria
- Muscularis mucosa

Thanks to the various cells found in mucosa villi, it fulfils three functions:

- Barrier / protection
- Absorption
- Secretion

6.3 Mucosa and the crypts of Lieberkühn

In the first few centimeters of the duodenum (close to the pyloric sphincter) one can find a
great many mucous glands called Brunner’s glands. Their function is to secrete large amounts
of alkaline mucus in response to either irritating stimuli (for example from gastric juice),
vagal stimulation (which causes increased mucus secretion parallel with increased gastric
secretion) and/or hormones, especially secretin.

51
The function of this mucus is to protect the duodenal wall from the digestive action of gastric
juice. In addition, the mucus’ alkaline nature aids the pancreatic secretion and liver bile in
neutralizing the hydrochloric acid.

The small intestine can also secrete some digestive juices. These are secreted by the so-called
crypts of Lieberkühn, which are located all over the surface of the small intestine, between the
villi (see picture on previous page; “intestinal crypt”).

The surface of both crypt and villi are covered by an epithelium containing number of cells:

(1) Goblet cells

a. These cells secrete mucus that protects and lubricates the surface.
(2) Enterocytes / absorptive cells
a. In the crypts, these cells secrete large volumes of water with electrolytes, and
when found in villi, they reabsorb water and electrolytes as well as any
nutrients.

Remarkably, in the lower parts of the crypt, there are stem cells that continuously regenerate
the structure of the epithelium. This process is needed as the villi are degraded by the
digestive action of enzymes and gastric juice entering the duodenum. The stem cells are
therefore also known as enterocyte percursors.

Other cells are enteroendocrine cells which secrete some hormones, and Paneth cells which
have an antimicrobial function by secreting lysozyme – not unlike saliva. These cells are to a
certain extent also capable of phagocytosis.

52
6.4 Absorption area

The absorption area in the intestine is many times greater than one may expect. This is in part
thanks to the folds114 of the intestines, but it doesn’t stop here.

As can be seen on the image above, the relative surface is increased over 600 times thanks to
(1) the aforementioned circular folds, (2) the villi, which add another layer of folds on top of
the folds, and (3) the microvilli, which form a so-called brush border and are mainly
responsible for the massive surface area increase.

6.5 Intestinal secretion and digestive enzymes

Secretion in the small intestine is pale yellow, watery, isotonic and alkaline. It consists of
99% water and 1% dry substances:

Inorganic: Na, K, HCO3, Cl

Organic: Mucus

Note that intestinal secretion doesn’t contain any digestive enzyme whatsoever. Instead,
certain enzymes are found in the membranes of the microvilli that form the brush border of
the enterocytes that line the villi of the small intestine.

114
Like the brain folds, or gyri, to fit more brain in our tiny skulls

53
6.5.1 Digestion of peptides

The microvilli membranes contain multiple peptidases that protrude through the membranes
to the exterior, where they come into contact with intestinal fluids.

At this level of digestion, only peptides remain of digested proteins, so that proteases are not
found in the microvilli. Many types of peptidases exist in order to ensure that finally, more
than 99% of polypeptidases are digested to the final stage to form single amino acids. These
then pass on through the other side of the enterocyte and from there into the blood.

6.5.2 Other digestive enzymes

The first step in fat digestion is emulsification and the increasing of solubility of fat by bile
acids. Then, pancreatic lipase can digest all triglycerides it can reach, splitting them into
monoglycerides and two free fatty acids.115

Lastly, bile salts strike again, by forming micelles and basically “smuggle” the
monoglycerides and free fatty acids to the brush border, where they are absorbed into the
blood.

The enterocytes lining the villi contain additional enzymes – disaccharidases – that can digest
lactose, sucrose and maltose, plus some other small glucose polymers into monosaccharides.

Their names are self-explanatory:

- Maltase hydrolyzes maltose to glucose;

- Sucrose hydrolyzes sucrose to glucose and fructose;
- Lactase hydrolyzes lactose to galactose and glucose.

All this digestive action results in final absorption of:

- Monosaccharides
- Amino acids, di- and tripeptides
- Free fatty acids
- Glycerol (monoglycerides)
- Vitamins (both water and fat soluble)

6.6 Absorption

Absorption can be:

- Passive
- Facilitated
- Active
- Endocytosis116

115
Enterocytes contain some lipase, known as enteric lipase, but this is generally not needed.

54
Most absorption in the small gut is by way of co-transportation. Have a look at the images of
the villi structure presented in this chapter. Notice the capillary network inside the villi – it is
here that substances are absorbed.

Various co-transporters (also known as secondary active transporters) carry substances from
the lumen of the villi into the enterocyte’s apical pole and thence into the capillaries (situated
at the cell’s basal pole).

Glucose, for example, is carried by Sodium-dependent Glucose Transporter, or SGLT1.

Like any co-transporter, in feeds on the energy of a primary pump – in this case the Na+/K+
ATPase pump. The SGLT proteins use this energy to transport glucose across the apical
membrane against an uphill glucose gradient. Therefore, these co-transporters are an example
of secondary active transport.117

Similar sodium-dependent transporters also exist for the transport of amino acids. Small
peptides are absorbed into the small intestinal epithelial cell by cotransport with H ions via a
transporter called PepT1.118

6.6.1 Absorption of fats

Let’s again review the absorption of fat from the moment of entering the intestine to being
taken up into the blood.

Glycerol molecules (ie. without fatty acids attached to them) is readily absorbed and enters
the capillaries directly thanks to passive diffusion.119 Free fatty acids can also directly pass
into the blood if they are so-called small chain fatty acids, ie. consisting of 10 carbons or less.

Large chain fatty acids (more than 10 C atoms) cannot directly enter the enterocyte membrane
– it is for such fats that bile salts offer the micelle solution.120 Since the hydrophilic parts of
the micelles are “sticking out”, they will make contact with the membrane and the membrane
will allow them to pass through.

Now, here’s the interesting part.

Once inside the cell, the free fatty acids come into contact with their respective glycerol (or
monoglycerides) molecules again. Together, they again form the triglycerides they originally

116
Endocytosis is an energy-using process by which cells absorb molecules (such as proteins) by engulfing
them. It is used by all cells of the body because most substances important to them are large polar molecules
that cannot pass through the hydrophobic plasma or cell membrane. The opposite process is exocytosis.
117
Both SGLT1 and SGLT2 are known as symporters, since both sodium ions and glucose are transported in the
same direction across the membrane.
118
You do not need to remember the transporter names for the control test.
119
Remember though that gastric / pancreatic lipase can in principle only split fatty acids from triglycerides at
the 1st and 3d position, so mostly you will have monoglycerides + 2 free fatty acids. Hormone sensitive lipase
nd
can however also break the 2 position, resulting in glycerol + 3 free fatty acids. This detailed information is
however not necessary for the physiology test, but was given in biochemistry.
120
Solution here meaning outcome, not chemical solution.

55
were. Note then, that the only reason triglycerides are hydrolyzed and split is for them to be
transported into the cell.

Still in the enterocyte, they are thrown together on a heap with other lipids, fatty vitamins and
various proteins, forming a ball-shaped compound. This compound, called a lipoprotein or
more specifically a chylomicron, will transport to and deposit the contents in adipose tissue,
cardiac or skeletal muscle.

6.6.2 Absorption of ions

Sodium is actively transported through the intestinal membrane. Remember the secondary
active transport with glucose, SLGT? That’s the one. There are several other co-transporters,
like sodium-amino acid co-transporter etc. Remember that co-transporters, being active
transporters, require energy. Being secondary transporters, they don’t create energy
themselves but feed on energy released by various ATP-ases in the cell membrane.

Water is transported through osmosis. Each time when the osmolality121 in blood is greater
than in the intestine, water goes into the blood due to the osmotic pressure gradient. (more on
that in chapter 8).

Chloride absorption occurs mainly by diffusion and takes place in the upper part of the small
intestine. When sodium is absorbed through the epitelium, the chyme will be electronegative
while the spaces between epithelial cells will be electropositive. Cl ions move along (diffuse)
this electrical gradient (basically, they “follow” the Na ions).

Large quantities of bicarbonate ions are reabsorbed in the duodenum and jejunum. However,
the epithelial cells on the surface of the villi in the ileum, have a special capacity of secreting
HCO3 in exchange for absorption of Cl ions. This furthermore provides alkaline HCO3 to
neutralize the acid products formed by bacteria in the large intestine.

121
Basically meaning, concentration of salt in blood.

56
Calcium is actively absorbed into the blood especially from the duodenum. The amount of
absorption is exactly controlled to supply the body’s daily Ca need. The most important
mechanisms here are parathyroid hormone and vitamin D. The former activates the latter, and
vitamin D greatly enhances Ca absorption.

Fe (iron) ions are also actively absorbed by the enterocytes of the small intestine. These cells
have special molecules that allow them to move iron into the body. To be absorbed, dietary
iron must be reduced from Fe3+ to Fe2+. An enzyme on the enterocyte’s brush border does
just that. A protein which transports all kinds of divalent metals into the body, then transports
the iron across the enterocyte's cell membrane into the cell.

These intestinal lining cells can then either store the iron as ferritin (in which case the iron
will leave the body when the cell dies and is sloughed off into feces) or the cell can move it
into the body, using a protein called ferroportin. The body regulates iron levels by regulating
each of these steps.122

***

122
Not necessarily relevant to know in detail for the control test.

57
VII MOTILITY

7.1 Introduction

The last chapter on the digestive system will cover motility123 of the digestive tract. We can,
in broad terms, distinguish between mastication (chewing), deglutition (swallowing), the
motor functions of the stomach, the small intestine and the large intestine. All these processes
work together to get your food from your plate to your stomach, intestine, and beyond.

7.2 Mastication

Mastication is a repetitive sequence of opening and closing of the jaw, enabled by a voluntary
motor reflex which brings the occlusal surfaces124 of the teeth into intermittent contact. In
other words, mastication or chewing is the process by which food is crushed and ground by
teeth.

As chewing continues, the food is made softer and warmer, and the enzymes in saliva begin to
break down carbohydrates in the food. After chewing, the food (mixed with saliva, now called
a bolus) is swallowed.

The grinding is very important, as it increases the surface area of the food. Digestive enzymes
only act on the surface of food, so the rate of digestion by intestinal secretions is highly
dependent on the surface area.125

Grinding the food to a fine consistency also increases the ease with which food is emptied
from the stomach and brought further down the intestinal tract.

There are active and passive elements involved in mastication. During mastication –
performed by the masticatory muscles – the food is positioned by the cheek and tongue
between the teeth for grinding. These three are active.

Passive elements are the jaw, maxillae126 and the teeth.

The teeth’s function is two-fold: the incisors have a strong cutting action, while the molars
perform the grinding. Both functions are effected by the jaw muscles, which have enormous
strength: they can exert a force of 250 kg. In fact, the closing muscles are so powerful that
they need to be inhibited during depression (opening) of the mouth.

7.2.1 Masticatory muscles

The following muscles are involved in chewing:

123
Motor function
124
Occlusal surface is the biting surface of a tooth. In dentistry, occlusion simply means the contact between
teeth. More technically, it is the relationship between the maxillary (upper) and mandibular (lower) teeth when
they approach each other, as occurs during chewing or at rest.
125
Think of breaking a piece of wood: it’s much easier if the wood is flat, thin and long, as opposed to a thick,
solid log.
126
The two maxilla bones forming the upper jaw and palate of the mouth

58
 • The masseter (composed of the superficial and deep head)
• The temporalis
• The medial pterygoid127
• The lateral pterygoid128
• The buccinators

All of these primary muscles are paired, which each side of the mandible129 containing one.
The muscles of mastication are all innervated by the trigeminal nerve (or CN V).130

Jaw closing (elevator muscles): masseter, temporal and medial pterygoid muscles. Jaw
opening (depressor muscles): submandibulary and lateral pterygoid muscles.

7.2.2 Roles of mastication

We’ve already touched upon a few chewing roles (increasing surface area, facilitating
digestion) but there are several others:

• Decreasing food size

• Lubricating food
• Preventing excoriation131 of the mouth, esophagus and stomach
• Facilitating smell and taste by mixing food with saliva
• Facilitating digestion by increasing surface area exposed to digestive enzymes
• Activates the ascending reticular activating system (ARAS)132

7.2.3 The tongue

The eight muscles of the human tongue are classified as either intrinsic or extrinsic.

- The intrinsic muscles act to change the shape of the tongue.

- The extrinsic muscles are responsible for protrusion and retrusion; in other words, they
act to change the position of the tongue.
Innervation:
o Sensitive: sensory fibers of nerve V
o Sensation of tase: gustatory fibers of nerve VII (the facial nerve), IX and X
(vagus)
o Motor: somatic fibers of nerve XII

127
Also called internal pterygoid
128
Also called external pterygoid
129
Jawbone
130
More specifically, they are innervated by the mandibular branch, or V3, but for the test you only need to
know nerve V.
131
A scratch or abrasion of the epithelium.
132
In my opinion not relevant for the exam, and also slightly confusing. Action of the ARAS, or ascending
reticular activating system on the cerebral cortex is responsible for achievement of consciousness. It regulates
the sleep-wake cycle. The related descending reticular system is responsible for motor functions coordination,
for example while walking, but also for chewing and swallowing. At any rate, this neurological phenomenon
goes well beyond what we need to know now.

59
7.2.4 Jaw opening reflex

The jaw opening reflex basically enables you to open your mouth, and keeps you from
crushing your teeth against each other all the time. Remember we said the jaw closing force is
so strong, the muscles need to be inhibited in order to open your mouth? That’s the opening
reflex.

It is a polysynaptic process.133 Forces applied to the teeth slightly dislocate them in their
sockets, thus stimulating the periodontal mechanoreceptors.

They send a signal through the afferent fibers of nerve V134 and the motor response is initiated
by the motor nucleus of CN V.135

Result:

- Stimulation of the depressor muscles, together with:

- Relaxation of elevator muscles

7.2.5 Jaw closing reflex

Now your mouth is open, it must also close again. This is the jaw closing reflex. Remember
the reflex arch? Receptors, afferent (sensory) fibers, nervous center, efferent (motor) fibers?

The receptors in this case are muscle spindles, which are stimulated by muscle stretching
(opening of your mouth). Afferent and efferent fibers are again of nerve V, and the nervous
center is located in the pons.136 The result is muscle contraction, and now your mouth is
closed, you look smart again.137

During movement, this reflex likely also helps to maintain the position of the mandible
relative to the maxilla, as well as the postural stability of the mandible.

7.2.5.1 Jaw-jerk-reflex138

The jaw jerk reflex or the masseter reflex is a stretch reflex used to test the status of a patient's
trigeminal nerve (CN V). The mandible—or lower jaw—is tapped at a downward angle just
below the lips at the chin while the mouth is held slightly open. In response, the masseter
muscles will jerk the mandible upwards. Normally this reflex is absent or very slight.
However in individuals with upper motor neuron lesions the jaw jerk reflex can be quite
pronounced.

133
Pertaining to a nervous process or system of nerve cells requiring a series of synapses.
134
Specifically: the trigeminal ganglion (or Gasserian, or Gasser's ganglion), the sensory ganglion of the
trigeminal nerve (CN V).
135
CN stands for cranial nerve, so CN V = Cranial Nerve 5.
136
The pons is part of the brainstem.
137
But seriously, this reflex also keeps your mouth shut during sleep.
138
http://tinyurl.com/mtgtao4 see this link for video example

60
7.2.6 Neural regulation during mastication

The control and regulation of mastication is a fine-tuned and delicate process of interaction of
reflexes with voluntary movement.

There is coordination between sensory feedback from peripheral organs, brain stem nuclei,
jaw reflexes and various other basic oral activities.

All this requires integration by brain stem cranial nerve nuclei of reflex inputs and commands
from other central nervous system nuclei. A current conceptual model for understanding
control of rhythmic oral motor activity postulates the existence of a central pattern generator,
which produces the sequence of movements common to many oral functional activities.139

7.3 Deglutition

Swallowing, or deglutition, is the process by which food is transported from the mouth to the
stomach. It is a reflex coordinated in the medulla and consists of three phases:

• Oral (or voluntary) phase

o Food is forced posteriorly into the pharynx by pressure of the tongue
o The food bolus stimulates swallowing through the sensory fibers of CN V, VII,
IX and X, which carry the impulses to the brain stem, leading to the:
• Pharyngeal phase (nerves V, IX, X, XII)
o The food bolus stimulates swallowing through the sensory fibers of CN V, VII,
IX and X; automatic contractions; swallowing occurs
o The soft palate140 closes the posterior nares141 and nasopharynx

139
According to this model, the output of the generator can be influenced by activity in cranial nerve afferents
or modified by signals from other central nuclei. The central control model predicts that the threshold for reflex
responses will change during the jaw opening and closing phases of mastication so that the effect of sensory
stimulation will vary with the concurrent activity of the muscular and central nervous systems. [this note is not
relevant for the exam, but in case you were interested]
140
The soft palate the soft tissue constituting the back of the roof of the mouth. The soft palate is distinguished
from the hard palate at the front of the mouth in that it does not contain bone.

61
 o The oropharynx is closed by the tongue
o palato-pharyngeal folds are pulled medially to form a Sagittal slit.
o the epiglottis moves back and forth to prevent the passage of food and liquids
into the lungs. The usual upright position of the epiglottis allows air to flow
into the lungs and the larynx. When you swallow, the larynx is pulled upwards,
causing the epiglottis to flatten backward to cover the entrance to your larynx
and prevent food from entering the trachea.142 This causes the trachea to be
closed off and the food to be diverted into the esophagus. The epiglottis returns
to its usual position after swallowing.

o The upward movement of the larynx enlarge the opening of the esophagus and
the pharyngo-esophageal sphincter relaxes, while the pharynx’s muscular wall
contracts, propelling the food into the esophagus.

141
Singular: naris. A pair of posterior internal openings in the nasal cavity connecting it with the nasopharynx
and allowing the inhalation and exhalation of air. The soft palate blocks this so food can’t go back into your
nose.
142
Windpipe

62
 • Esophageal phase (nerve X and local plexus)
o a fast peristaltic143 wave originating in the pharynx forces the bolus into the
esophagus
primary peristalsis
• continuation of the peristaltic waves that began in the pharynx
• vago-vagal mechanism; controlled by swallowing pattern
generator in the brainstem (see 7.2.6).
• once activated, neurons from this generator send patterned
charges of inhibition and excitation to the motor nuclei of the
cranial nerves
o remember: always activated by the pharyngeal
swallowing
secondary peristalsis
• appears if the first waves fail to move all the food that has
entered the esophagus to the stomach
• executed entirely by local plexi – Meissner / Auerbach

7.3.1 Lower esophageal sphincter

The lower esophageal sphincter is located just above the cardial sphincter of the stomach. In
its normal state, it is constricted and relaxes only when food passes through the esophagus, in
order to let the food into the stomach.

This is in order to prevent gastro-esophageal reflux (backflow of food into esophagus).

When the sphincter is too relaxed, there can be a gastro-esophageal reflow disorder (food
keeps flowing back). When the sphincter contracts too much, so that food cannot enter, we
speak of achalasia. The solution is to surgically cut the sphincter.

7.4 Motor function of the stomach

Three main functions:

- gastric filling (let food enter the stomach)

- mixing food with gastric juice (like a cocktail shaker, if you will)
- gastric emptying (into intestine)

7.4.1 Gastric filling

When the stomach is empty, so-called hunger contractions can occur. They last 15 minutes
and our brain makes us feel a sense of hunger. The contractions are intensified by
hypoglycemia.

If you do not eat, the contractions will stop after 15 minutes, but after about 90 minutes will
reoccur.

143
A symmetrical contraction and relaxation of muscles that propagates in a wave down a tube, in an
anterograde direction.

63
When food finally enters the stomach, it will not contract, but rather relax to let food in. This
is called receptive relaxation. This reflex is brought about by the vagus nerve, with VIP and
nitric oxide (NO) acting as neurotransmitters.

Plasticity is the property of the cells of the smooth muscle of the stomach to stretch – within
limits – without any change in tension. In this way, the stomach, which has an empty volume
of 50 ml, can expand to a whopping 1l or even more.

7.4.2 Mixing movements

The stomach’s mixing movements are represented by peristaltic waves over the entire
stomach body.

In the distal two thirds of the stomach, smooth muscle exhibits myoelectric activity with a
very regular pattern. A specialized network of cells, known as the interstitial cells of Cajal,
generate slow electrical waves in the stomach. These cells are electrically coupled to smooth
muscle cells in the gastric wall. The slow waves therefore cause depolarization of the stomach
muscle cells, calcium144 entry and thus contractions.

In summary, slow electrical waves initiate a basic rhythm, but do not cause contractions.
Rather, they effect changes in rest membrane potential of the smooth muscle cells.

7.4.2.1 Spike potential and contractions145

All cells have a resting potential: an electrical charge across the plasma membrane, with the
interior of the cell negative with respect to the exterior. The size of the resting potential
varies, but in excitable cells runs about −90 millivolts (mv).146

144
Calcium is the most important ion in muscle contraction
145
This won’t be an exam question, but merely serves as theoretical background to better understand the rest
146
Actually, according to most other sources, it should be -70 mV, but I’m going here with the figures given by
Dr. Papacocea in her lecture

64
In the process of depolarization, the negative internal charge of the cell becomes positive for a
very brief period of time. This shift from a negative to a positive internal cellular environment
allows for the transmission of electrical impulses both within a cell and, in certain instances,
between cells. Depolarization is caused by the opening of Na / Ca channels.

In smooth muscle, rest potential is not constant, but oscillates slightly and randomly,
generating tiny action potentials here and there. However, a contraction will only occur if
there is a so-called spike potential – a true action potential. This only occurs if a certain
stimulus reduces the potential to the threshold voltage (about −50mv). It is typically
stimulated by acetylcholine (through nerve X) and / or muscle stretching.

Action potential passing the -50 threshold = true action potential

7.4.2.2 Antral mill

In the antral portion of the stomach, the contractions become exceedingly strong, violently
throwing the food around and back (retropulsion) as if it was in a wrestling ring.

7.4.3 Gastric emptying

The violent waves during the antral mill stage also help to push the food further down into the
intestinal tract. But before food can be completely emptied into the duodenum, it must be:

- homogenous
- isothermal (it must be 37 degrees Celcius)
- isotonic (must have similar osmotic pressure to plasma)
65
7.4.4 Pyloric valve

The pyloric sphincter acts like a valve through which food is released. It thus not only
regulates stomach emptying, but also prevents regurgitation of duodenal contents.

Pyloric relaxation lets food pass through. To let food in, VIP and NO are released from the
vagal nerve to inhibit the pyloric sphincter, which, as a consequence, relaxes. This relaxation
is further stimulated by gastrin and an increased volume of chyme (distention). Increased
fluidity also allows for more rapid emptying.

Pyloric constriction is brought about by cholinergic vagal fibers, sympathetic nerves and
several hormones:

- Cholecystokinin
- Gastric inhibitory peptide
- Secretin

It is also stimulated by acidity hitting the duodenal wall, other irritation, fats and sugars (the
latter two representing gastro-enteric reflexes).

7.5 Intestinal motility

One can distinguish three types of motility in the small intestine, divided as follows:

1. Segmentary
a. Localized rings of contraction
2. Peristaltic
a. One unique ring of contraction which advances like a wave; propulsive
movement. It takes about three hours for chyme to pass from the pylorus to the
ileo-cecal valve.147
3. Migrating myoelectric complex (MMC)
a. Waves of activity that slowly sweep through the intestines in a regular cycle
during a fasting state. It takes about one hour per contraction.
b. It advances all food content from stomach to colon
c. Removes fluid accumulation from digestive tube and moves it towards colon
where most of it is reabsorbed
d. When one MMC wave reaches the ileum, a new one starts in the stomach.

Neural control starts with gastro-enteric reflex: increase in gastric distension and gut
contractions. Hormonal regulation is mediated by:

- Gastrin, CCK, insulin, serotonin (stimulatory)

- Secretin, glucagon (inhibitory)

147
Sphincter muscle valve that separates the small intestine and the large intestine

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7.5.1 Emptying of the ileum

Similarly as gastric emptying, a sphincter is the main barrier through which the contents must
pass. This ileo-cecal sphincter is normally closed, but short-range peristalsis and some
distension in the ileum relaxes it. A little chyme will be squirted out of the ileum into the
cecum, which will distend and cause the sphincter to contract again. However, after eating,
gastro-ileal reflex will enhance emptying of the ileum, as gastrin will relax the sphincter
again.

7.5.2 Functions of the colon

The colon is responsible for:

- Water and ion reabsorption

- HCO3 secretion
- Storage and subsequent elimination of feces
- Vitamin and amine synthesis

Motility of the colon consists of:

- Haustration (very similar to segmentary contraction in the small intestine; localized

rings contract)
- Antipropulsion (reverse peristalsis)
- Mass movement

7.6 Defecation

Defacation is no laughing matter, as it is a complex behavior involving integration of

voluntary action and reflexes.

Under normal conditions, the rectum is free of feces, as the tactile and mechanoreceptors are
very sensitive to even the smallest distension, and continuous presence of feces in the rectum
is therefore not tolerated.

Fecal matter is stored in the sigmoid colon until a mass contraction pushes it into the rectum.

The internal (smooth muscle) and external (striated muscle)148 anal sphincters prevent the
continuous dribble of feces.

The defecation reflex is parasympathetic. The reflex arch is as follows:

• Receptors: tactile and mechanoreceptors from rectal wall

• Afferent nerves: sensory fibers from pelvic nerves
• Neural center: S2-S4 (parasymp.); inhibitory center: L4-L5149
• Efferent nervers: parasymp. motor fibers from pelvic nerves

148
Smooth (or visceral) muscle = involuntary regulation, while striated (or skeletal) muscle = voluntary
regulation
149
Activated when conditions do not permit defecation

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 • Effector: rectal muscle layer and internal anal sphincter
o Note that the external anal sphincter is controlled voluntarily and forms no part
of this reflex arch.

In newborns, but also in persons who, through accident or otherwise, have a transected spinal
cord, automatic (uncontrollable) emptying of the rectum occurs.

7.7 Regulation

As you by now undoubtedly know, the gastrointestinal tract is characterized by semi-

autonomous nervous systems in the gastro-intestinal walls: the Meissner and Auerbach plexi.

Auerbach is a myenteric plexus (situated in the muscle layer) while Meissner is the
submucosal one.

Also known as “the little brain in the gut”, together with a major network of ganglia150 and
interconnecting neurons, they form the enteric nervous system.

150
In anatomy, a ganglion is a nerve cell cluster or a group of nerve cell bodies located in the peripheral
nervous system.

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Appendix: list of hormones and their actions in the gastro-intestinal tract

69
70
VIII ENDOCRINE SYSTEM: INTRODUCTION

8.1 Introduction and definitions

Other sources of hormones are the brain, kidneys, the skin and the digestive tube.

71
The endocrine system refers to the collection of glands of an organism that secrete hormones
directly into the circulatory system to be carried towards a distant target organ. It is literally
vital to humans and other mammals and as it is a condition for adaptation, and therefore
survival.

Adaption is an integrated system consisting of:

• Central Nervous System

o Neural, fast acting and short-term adaptation (reflexes)
• Endocrine system
o Slow acting, long-term adaptation by use of hormones

Endocrine glands are glands of the endocrine system that secrete their products, hormones,
directly into the blood or the lymphatic system rather than through a duct.

The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas,
ovaries, testes, thyroid gland, parathyroid gland, hypothalamus and adrenal glands.151

Local chemical messengers, not generally considered part of the endocrine system, include:

- Autocrine, which act on the same cells that secrete them,

- Paracrine, which acts on neighboring cells, and
- Juxtacrine, which, like paracrine acts on a nearby cell, but this time a specific one

Hormones are a class of signaling molecules (or chemical messengers) secreted by specialized
cells which may or may not be organized in glands. A hormone is transported by the
circulatory system to target distant organs to regulate physiology and behavior, metabolism
and morphology.

It is very important to realize that hormones do not initiate new processes; they merely
regulate pre-existing fundamental biological reactions.

8.2 Classification of hormones according to their origin

• Neurohormones
o Hormones produced and released by neurons
o TRH, GnRH152, CRH, OTC, ADH153, noradrenalin
• Glandular hormones
o Hormones produced and released by glands
o EG, PG, MLT, Insulin, DHEA154, Adrenalin
• Other
o Gastrin, secretin, and other GI hormones; ANF, calcitriol, etc

151
The hypothalamus and pituitary gland are neuroendocrine organs.
152
Gonadotropin-releasing hormone (aka luteinizing hormone releasing hormone)
153
Antidiuretic hormone (vasopressin)
154
Natural steroid produced by adrenal glands

72
8.3 Classification of hormones according to their structure

- proteic hormones (ADH, FSH, prolactin)

- amine hormones (adrenaline155 and noradrenaline, thyroid hormones)

- steroid hormones (corticoids, sexual hormones)

8.4 Receptors

All hormones act on receptors.

A receptor is a proteic molecule with specific bindings, able to activate and create chain
reactions inducing the hormone’s effect.

Receptors may or may not be exposed to receiving hormones; this depends mostly on
hormone concertration. For example, if there is an excess of a certain hormone, the number of
available receptors will be reduced. Conversely, if more hormone action is needed but there is
insufficient hormone circulating, more receptors will expose themselves.

8.4.1 Receptor types

• Membrane receptors
o Used by proteic / peptidic hormones and catecholamines156
Because proteic molecules cannot pass through the membrane and enter
the cell, the receptor is positioned on the membrane
A second messenger is used,157 common ones include:
• cAMP for adrenaline, glucagon, ADH, angiotensin II,
luteinizing hormone
• calcium – inositol triphosphate (IP3) for ADH, adrenaline
• Unknown for insulin

As seen, calcium ions are also important intracellular messengers. In fact, calcium ions are
probably the most widely used intracellular messengers.

In response to many different signals, a rise in the concentration of Ca2+ in the cytosol
triggers many types of events such as:

- muscle contraction;
- exocytosis, e.g., release of neurotransmitters at synapses
- secretion of hormones like insulin
-

155
Another name for adrenaline and noradrenaline is epinephrine and norepinephrine respectively.
156
Adrenaline and noradrenaline
157
Second messengers are molecules that relay signals received at receptors on the cell surface — such as the
arrival of protein hormones, growth factors, etc. — to target molecules in the cytosol and/or nucleus.

73
 • Cytoplasmic receptors
o Used by steroid hormones
They can pass through the membranes and reach the receptors in the
cytoplasm (in the cell)
• Nuclear receptors
o Used by thyroid hormones
Easily pass through cell to reach nucleus

8.5 Circulation

Hormones can circulate in either free forms or bound forms. Some hormones (peptidic
hormones) exclusively travel in free form. The advantage of this is that it allows quicker
access to target cells.

When a hormone is bound, it is not active. It is a sort of physiological storing mechanism,

with adapted release regulation, with a gradual hormone distribution according to the body’s
need. This is for example the case with the thyroid hormone. Most of the thyroid hormone
circulating in the blood is bound to transport proteins. Only a very small fraction of the
circulating hormone is free (unbound) and biologically active.

8.6 General characteristics

74
8.7 Hormone regulation

Regulation of hormone balance happens at the level of the hypothalamus and hypophysis158
(more detail in next chapter).

The rate of hormone biosynthesis and secretion is often regulated by a homeostatic negative
feedback control mechanism. Such a mechanism depends on factors that influence the
metabolism and excretion of hormones. Thus, higher hormone concentration alone cannot
trigger the negative feedback mechanism. Negative feedback must be triggered by
overproduction of an "effect" of the hormone.

Negative feedback is self-limiting. The usefulness of negative feedback inhibition is that it

results in hormonal homeostasis, that is, the maintenance of hormone levels within a
particular appropriate physiological range. Positive feedback is rare, explosive and self-
reinforcing.159

Example of a negative feedback loop

8.8 Biorhythm

Hormones aren’t just secreted at random. There is an inborn modulation of hormone secretion
that is controlled by a biological clock. There are different clocks and different corresponding

158
Also known as pituitary gland
159
A notable example of positive feedback is contractions at birth; they reinforce themselves and get more
intense as a result thereof. Inactivation of the feedback loop is birth of the child itself.

75
patterns, for example pulsation in the case of GnRH 160and GhRH161 (respectively 1h and 5h),
or adhering to a daily biorhythm, such as in the case of cortisol (secretion is maximal in the
morning).

It is therefore extremely important that in the administering of external hormones and/or

drugs, these patterns are taken into consideration. To do this means not only to increase the
drug’s efficacy, but to also minimize possible adverse effects of hormone administration
contrary to one’s biological pattern.

8.9 Hormone inactivation – not required for the control test

Depending on the type of hormone, there are different ways of inactivating them. Peptidic
hormones, for example, are disposed of intracellularly by phagocytosis – they literally get
eaten – while in the extracellular space they are hydrolyzed by certain enzymes.

Hormones deriving from aminoacid are oxidized, while steroid hormones are conjugated or
dehydrogenated.

***

160
Gonadotrophin-releasing hormone
161
Growth hormone-releasing hormone

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IX HYPOTHALAMUS & HYPOPHYSIS

9.1 Introduction

The hypothalamus is a portion of the brain that contains many small secretory nuclei with a
variety of functions. One of the most important functions of the hypothalamus is to link the
nervous system to the endocrine system via the hypophysis (pituitary gland).

The hypothalamus is responsible for certain metabolic processes and other activities of the
autonomic nervous system. It synthesizes and secretes certain hormones and these in turn
stimulate or inhibit the secretion of pituitary hormones.

The hypothalamus controls body temperature, hunger, important aspects of parenting and
attachment behaviors, thirst, fatigue, sleep, and circadian rhythms.

For this chapter we are especially interested in the anterior and median nuclei of the
hypothalamus, as herein lies its endocrine function.

9.2 Hypothalamic hormones

Hormones secreted by the hypothalamus come in three varieties:

1. Neurohormones
2. Neuromodulators
3. Neurotransmitters

Neuromodulators regulate pain, sometimes pleasure (endorphins); neurotransmitter is a

substance which enables communication between synapses (chemical or electrical).

77
78
9.3 Hypothalamic–pituitary axis

First described by Grigore T. Popa and Una Fielding in 1930, the hypothalamic-pituitary axis
is a complex set of direct influences and feedback interactions among two162 endocrine
glands: the hypothalamus and the pituitary gland.

The two glands are connected to one another by way of the so-called hypothalamo-neural
stalk,163 connecting the hypothalamus to the posterior pituitary.

Through this connection, two important hormones are synthesized and released: ADH164 and
oxytocin.

Both of these hormones are produced in the anterior nuclei165 of the hypothalamus,
transported through the hypothalamo-neural stalk and are stored (and secreted) by the
posterior pituitary gland.

9.4 ADH and oxytocin

These two hormones have a similar peptide structure,166 this may explain why some of their
actions may overlap.

162
In other sources it is presented as the hypothalamic-pituitary-adrenal axis, which features the adrenal gland
as the third gland involved in the complex. In dr. Papacocea’s lecture however, only the hypothalamus and
pituitary gland were named.
163
Also known as hypothalamo-hypophyseal tract or pituitary stalk
164
Antidiuretic hormone, aka vasopressin
165
ADH in the paraventricular nuclei and oxytocin in the supraoptic nuclei

79
Hypothalamus, pituitary gland and the pituitary stalk (hypothalamo-hypophyseal tract)

9.4.1 ADH

Its two primary functions are to retain water in the body167 and to constrict blood vessels.

Most of it is stored in the posterior pituitary to be released into the bloodstream. However,
some ADH may also be released directly into the brain, and accumulating evidence suggests it
plays an important role in social behavior, learning and memory. It may also play a part in
stress, as it is a stimulator of ACTH.168

ADH is secreted from the posterior pituitary gland in response to:

166
Nine peptides; nonapeptides.
167
By making the kidneys reabsorb water, see chapter I
168
Adrenocorticotropic hormone (ACTH), also known as corticotropin, is a polypeptide tropic hormone
produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-
pituitary-adrenal axis and is often produced in response to biological stress (along with its precursor
corticotropin-releasing hormone from the hypothalamus). Its principal effects are increased production and
release of corticosteroids.

80
 - reductions in plasma volume,
- increases in the plasma osmolality,
- cholecystokinin (CCK) secreted by the small intestine.

Secretion in response to reduced plasma volume is activated by pressure receptors in the

veins, atria, and carotid sinuses.169

Secretion in response to increases in plasma osmotic pressure is mediated by osmoreceptors

in the hypothalamus.

It acts on three types of receptors: V1, V2 and V3.170

• V1
o Location
vascular smooth muscle, platelet, hepatocytes, myometrium
o Signal pathways
Second messenger; G protein-coupled, phosphatidylinositol/calcium
o Function
vasoconstriction, myocardial hypertrophy, platelet aggregation,
glycogenolysis, uterine contraction
increases blood pressure
• V2
o Location
basolateral membrane of collecting duct (kidney)
o Signal pathways
Adenylyl cyclase/cAMP
o Function
Increased production of Aquaporin-2 (AQP-2)171
Vasodilation
• V3
o Location
anterior pituitary gland
o Signal pathwways
G protein-coupled, phosphatidylinositol/calcium
o Function
releases ACT
endorphins

ADH has an important cardiovascular role as it increases peripheral vascular resistance

(vasoconstriction) and thus increases arterial blood pressure. This effect appears small in
healthy individuals; however it becomes an important compensatory mechanism for restoring
blood pressure in hypovolemic shock such as that which occurs during hemorrhage.

169
See also chapter I
170
V for Vasopressin
171
Aquaporins are membrane proteins that form pores in the membrane of biological cells.

81
Aquaporins are "the plumbing system for cells." Water in a cell moves through it in a very
organized way. The process occurs rapidly in tissues that have these aquaporins or water
channels.

Aquaporins selectively conduct water molecules in and out of the cell, while preventing the
passage of ions and other solutes.

Ten human aquaporins have been identified, of which the first four are important in kidney
functions:

AQP1

- Present in both apical and basolateral membrane172 of the proximal tubule and loop of
Henle in the kidney173

AQP2

- On the luminal surface of cells in the collecting duct

- Responsible for water transport from lumen of nephron into collecting duct cells
o Pro-formation of urine

AQP 3 & AQP4

- Basolateral membrane of collecting duct cells

- Facilitate water movement from cells into interstitium
o Anti-formation of urine; pro-reabsorption

Keeping in mind this other function of ADH – increased production of aquaporins – we may
now summarize its roles as follows:

• Increases kidney ducts permeability to water

• Increases water absorption
• Increases blood volume
• Increases blood pressure
• Decreases urine volume
• Increases urine concentration

And its stimuli / inhibitors:

Stimuli: high blood osmolality,174 low blood volume / pressure; stress, nicotine

Inhibitors: low blood osmolality, high blood volume / pressure; alcohol

172
Basolateral: at the side of the capillary (where exchange takes place); apical: the other side
173
See chapter I for kidney anatomy
174
Increased osmotic pressure due to presence of salts

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9.4.2 Oxytocin

A nonapeptide, just like ADH, it plays an important role in the neuroanatomy of intimacy,
specifically in sexual reproduction of both sexes, in particular during and after childbirth.

Oxytocin is released in large amounts after distension of the cervix and uterus during labor,
facilitating birth, maternal bonding, and, after stimulation of the nipples, lactation. Both
childbirth and milk ejection result from positive feedback mechanisms: it is oxytocin that is
responsible for the contractions during birth that we discussed earlier.

Recent studies have begun to investigate oxytocin's role in various behaviors, including social
recognition, pair bonding and maternal behaviors. For this reason, it is sometimes referred to
as the "bonding hormone".

Interestingly, oxytocin is also capable of generating higher levels of trust and generosity. It
furthermore has a positive effect on behaviors such as altruism, compassion and empathy.175

Some researchers, however, have argued oxytocin has a general enhancing effect on all social
emotions, since some tests showed that intranasal administration of oxytocin also increases
envy and Schadenfreude.176

A lack of oxytocin is associated with aggressive behavior.

Similar effects have been observed with ADH.

ADH is released into the brain in a circadian rhythm. ADH may be involved in aggression
behaviors, pregnancy and lactation regulation.

Studies suggest ADH may also play a role in pair bonding, and may also have pain reducing
effects.

***

Appendix: biochemistry cross-over

For those of you who haven’t had enough after this, here’s a chance to practice for the
biochemistry exam:

The systematic name of oxytocin is:

cysteine-tyrosine-isoleucine-glutamine-asparagine-cysteine-proline-leucine-glycine-amide.

Practice by writing the structure of oxytocin.

175
These last three were mentioned by Dr. Papacocea in the lecture, but are contested by some other sources.
176
An untranslatable German term meaning the feeling of joy or pleasure when one sees another fail or suffer
misfortune. The related Dutch word is leedvermaak. Absolutely not relevant for the exam since we are not
studying linguistics.

83