Human Physiology, Bio 12
Chapters 1, 3, 73
Review chapter 2
1
STUDY TIP:
• If you study while you are exercising, you
will remember better.
• WRITING TIP: A poorly placed comma
can make the difference in how the patient
is cared for.
•
A panda eats, shoots, and leaves.
•
A panda eats shoots and leaves.
• Meet with tutors in a public location, and
always bring another student with you.
2
Lecture outline
I. Introduction
II. Physiology vs. pathophysiology
III. Homeostasis
A. Terms of homeostasis
B. Types of correction mechanisms
C. Levels of regulation
i. Cells
ii. Tissues
iii. Organs
iv. Organ systems
D. The price of homeostasis
3
Lecture outline for
Thermoregulation
I. Body temperature throughout the day
II. Ways we lose heat
III. Reflex arc of temperature regulation- a negative
feedback mechanism
IV. Consequences of extreme core temperatures
A. Hyperthermia
B. Heat stroke
C. hypothermia
V.
VI.
Exercise induced hyperthermia
Hyperthermia from fever
A. Pyretics
B. Anti-pyretics- COX inhibitors
4
Physiology
The science that is concerned with the function
of the living organism and its parts, and of
the physical and chemical processes involved.
Pathophysiology
• The study of disordered body
function (i.e. disease)
• The basis for clinical medicine
5
• Physiology is the study of how the body
functions. In Anatomy, you learned that, with
form, comes function. You were taught how to
figure out the function of a muscle by looking at
it shape, origin, and insertion. Half of the
understanding of physiology understanding is
how the body’s physiology goes awry.
Physiology is the main component in the study
of medicine. When a patient is in a hospital, their
physiology has gone wrong.
6
• You will learn the physiology of organs, as well as their
pathophysiology. When you see a patient’s lab test that
is abnormal, you need to learn how to back-track to what
is normal; this will help you to understand what has gone
wrong. You need to use all the skills you learn this
semester on the first day of nursing school. On the first
day, they will have you evaluate a patient. On the
second day, you will meet with the nursing instructor,
who will grade you on the accuracy and quality of your
evaluation. Do your serious work here so you can enjoy
your work in nursing school!
7
A Recurrent Theme:
Homeostasis
The maintenance of a stable
“ milieu interieur”
Claude Bernard (1813 - 1878)
Why do we need a stable,
internal environment?
• Prevent denaturation of proteins
• To keep cells under optimum
conditions for function and survival
• It’s all about the plasma!
8
• Claude Bernard coined the term “homeostasis”,
or the maintenance of a stable internal
environment. He was referring to a stable
extracellular fluid compartment. Intracellular
fluid is the largest of the fluid compartments; it is
the fluid inside of all of the body’s cells. What is
extracellular fluid? It is interstitial fluid (the fluid
between cells) plus plasma (Remember, whole
blood is not the same as plasma. Whole blood
also includes blood cells).
9
• What are the other fluid compartments?
Transcellular fluid is that which is
surrounded by epithelia. Your digestive
tract is lined with epithelia, so the fluid
inside your GI tract is transcellular fluid.
The synovial joints are also transcellular
fluid.
10
• Claude Bernard especially meant that the
plasma has to be stable. The plasma is
where the interstitial fluid comes from. In
capillary beds, there are forces that
squeeze the oxygen-rich plasma through
the vessel to the extracellular space.
Other forces return the oxygen-depleted
extracellular fluid back into the circulation
(now called plasma again).
11
• When the fluid returns to the plasma, it brings
with it wastes like CO2, which is carried to the
lungs to get rid of it by exhalation. Then, you
breathe in, and the O2 dissolves into the
plasma, and the cycle continues. In the
meantime, the GI tract absorbs nutrients, and
these are also taken into the plasma and
distributed throughout the body. Thus, it is
important to maintain the plasma in a healthy
state, with not too much waste or too many
nutrients.
12
• Ions (sodium, calcium potassium,
magnesium, etc) need to be within a
stable range or dysfunction will occur in
the cells or organs. Potassium should be
in high concentration inside of each
cell, and in low concentration outside
of the cells. The opposite is true for
sodium; it should be in high
concentration outside of the cells and
low concentration inside of the cells. 13
• Potassium has to be strictly regulated so that it stays
within the range of 3-5 mili-equivalents. At 6-7 miliequivalents, doctors get worried. The final lethal injection
a prisoner on death row receives is potassium chloride. It
opens up a channel in the cells so that potassium flows
out of the cell and causes death quickly. Sodium is
regulated also, but not as much. You will learn why
during this semester.
• Acids and bases also have to be regulated. If you
accumulate too much waste, the cells become
compromised, but why? You will learn about that, this
semester.
14
• What converts glucose into usable
energy? What makes sure potassium
concentrations stays high inside of the
cells? Proteins! They are also responsible
for replicating, transcribing, and translating
DNA. Proteins do the work in the body.
They need to be translated and configured
correctly, or they may not do their job
correctly.
15
• What are the monomers (building blocks)
of proteins? Amino acids (AA). Two AA’s
are linked by dehydration synthesis (water
is lost) to form a dimer (two amino acids).
To break the peptide apart, bring back the
water by hydrolysis.
16
• Proteins have different levels of structure.
The primary structure of a protein is the
basic string of amino acids. The
secondary structure of a protein is when
this string folds into beta pleats. The
tertiary structure of a protein is when the
protein folds onto itself and forms links to
keep it in that shape. The quaternary
structure of a protein is when more than
one proteins link to each other.
17
• A protein is said to become denatured
when it loses these bonds; a denatured
protein loses its function. What denatures
a protein? Mainly heat, but acids and
bases can also cause problems. It is so
important to keep the proteins from
overheating, that the body has protective
mechanisms. For instance, the fluid in the
pericardial cavity (lines the heart) is there
to prevent heat build-up during cardiac 18
• Cold does not denature proteins, so you
can freeze chicken and take it out later
and make it twitch with an electrode. While
proteins are too cold, they do not work
because they have been slowed, but they
are not denatured, because they will return
to function when they are warmed up.
19
• When a patient goes to a doctor in illness or for a checkup, we want to measure anything that is measurable in
the body. Blood and urine tests reflect important things,
such as liver and kidney function. There are many
variables in the body to be measured. Examples of
variables are levels of calcium, glucose, hormones, and
things such as how hard your heart contracts. All
variables in the body have a set point, (an optimal range)
that assures proper function of the body. If a variable
goes beyond the accepted range, it has deviated. The
body must be able to detect variables that have
deviated, elicit a response, and recruit corrective
measures.
20
• For example, if you set your thermostat at
home to 65°C. It may work at +- 2°C and
still be considered as functioning normally.
Thus, our temperature in the room may be
63-67°C. When it gets dark outside, the
room may cool off to 64°C, but the
thermostat does not turn on until 62.9°C,
and it will stay on until it gets to 67.1°C.
21
• So, there is a set point, but there is an
acceptable range. This is what happens
in your body. When the deviation is too
great, the body has to detect it first, and
then correct it. There are two ways to
correct deviations that are outside of the
acceptable range: Negative and Positive
feedback.
22
Key Terms
• Variable- anything that changes
and can be measured (ex. temp,
pH, BP, [Na+], plasma glu)
• Set-point-value that is optimal
• Deviation-a change from set
point
• Correction- compensation-how
much depends on how great the
deviation is!
23
Negative Feedback-promotes stability
1.
When the variable deviates from set-point, the sensor
detects the deviation.
2. The input signal is compared to the set-point, forming
a “difference signal” (deviation).
3. A preprogrammed correction is triggered (That’s the
physiology! Understanding how a system corrects!)
4. The output signal activates an effector mechanism. In
NEG feedback: the correction is opposite in direction
to the deviation!
5. Result: Returns the variable toward setpoint
Dev
Corr
Setpoint
24
• Negative Feedback is when the deviation and
correction go in opposite directions. The home
thermostat is an example of this. Too cold?
Make it hotter. Too hot? Make it colder. When
you eat sweets, you increase you blood glucose
level beyond the normal range in the blood.
Insulin is released, drags the sugar into cells for
storage. Cells have proteins that can be inserted
into their cell membrane to act as glucose
receptors so that glucose can be drawn in.
25
• If you are hungry, your blood sugar is low.
In the liver, stored glucose is in the form of
glucagon. When the blood sugar is low,
the pancreas releases a substance to tell
the liver to chop up its glucagon into its
components (glucose) and take the
glucose into the bloodstream. Most of the
corrective mechanisms in the body are
negative feedback.
26
Positive Feedback promotes a
change in one direction,
instability, disease
• Deviation from
the setpoint
• Correction
• Result???
• Further deviation
from the setpoint!
So, in which situations are we wired to use positive
feedback?
To amplify an effect rapidly…. (avalanche!)
27
• Positive feedback is rare, and this
mechanism is always used carefully.
Positive feedback mechanisms are
associated with illness. All positive
feedback mechanisms have to
eventually be stopped with a negative
feedback mechanism. Positive feedback
goes in the same direction as the deviated
variable, and eventually both become too
high.
28
• An example of positive feedback is pregnancy. The
“parasite” gets bigger, so the uterus expands to
accommodate it. This growth continues until it reaches
critical mass, then the negative feedback mechanism
kicks in…birth. When birthing, the more that smooth
muscle is stretched, the more calcium is pushed into the
muscle cells, causing contractions of greater force.
When the head of the Parasite rams the cervix, the
hypothalamus is stimulated to release oxytocin, which
makes contractions increase more. Contractions
increase in frequency and strength until negative
feedback (delivery) occurs.
29
• Then another positive feedback kicks in…delivery of the
afterbirth. When the placenta separates from the uterus,
the spiral arteries in the lining of the uterus are torn,
causing a lot of bleeding. This phase is very dangerous
since excess bleeding can occur, so the nurses jump on
the woman and push against the uterus to reduce the
amount of bleeding. The most dangerous complication is
disseminated intervascular coagulation (DIC). In this
condition, all of the clotting factors in the body are all
used up in the effort to stop the bleeding, yet there are
even more torn vessels. Since there are not enough
clotting factors left in the body, she bleeds out. Clotting
is a positive feedback mechanism. Luteinizing
30
hormone is another positive feedback mechanism.
• Which feedback mechanism is
associated with the greatest health?
Negative.
• Which needs to be carefully controlled?
Positive.
31
• All of the body’s variables need to be maintained
in their homeostatic level. Where is their
regulation occurring? You will learn that this
semester. There is a lot of redundancy in
corrective mechanisms; many are synergistic,
some are antagonistic (work against each
other). Which of these competing mechanisms is
the stronger one depends on where the
deviation is. The greater the deviation, the
greater the compensation.
• Your set point can vary throughout the day. For
example, picture your set point as the desire to
pull your car into your garage. As you are driving
down the street towards your house, you are
getting closer to the set point. But as you get
close, do you floor the gas pedal? No, you ease
up on the gas, then use the break as you are
just entering the garage. When variable
deviation is great, the compensation is great.
When there is less deviation, less compensation
needed. The mechanisms constantly overshoot
33
and undershoot the set points in the body.
How do all the organ systems (kidney, lungs, heart, liver, GI, musculoskeletal,
nervous, endocrine) help maintain homeostasis of the extracellular fluid?
• The kidneys filter, secrete, and excrete. Kidneys are
also endocrine glands. They are the crankiest organs in
the body. They have a sensor for anything that goes
wrong. If they don’t have enough blood (reduced
perfusion), they sense that the O2 levels have dropped
(hypoxia), and they also detect that the blood vessels
are not stretching. If this condition were to continue, the
O2 levels would become completely depleted (anoxia),
cellular metabolism would shut down, and tissue would
die. If the kidney is not happy with current conditions
(such as low O2 levels), it triggers a series of events,
including a cascade of hormones, erythropoesis
(production of new red blood cells), and an increase in 34
the amount of salt retained.
• The respiratory system is best friends with the kidneys.
Both maintain the acid-base balance in plasma. Kidneys
get rid of organic acids. Lungs get rid of dissolved acid
gases.
•
• The heart generates the force to eject the blood. Arteries
expand and recoil and put pressure on the flow of blood,
maintaining the driving force to push the blood forward,
so the blood reaches capillaries and leaks out.
35
• The liver detoxifies blood, removes dead or
dying RBCs. It has over 500 functions. Why
does an alcoholic have a big belly (ascites) from
liver damage? The liver is supposed to make
albumin (a protein), but since the hepatocytes
are damaged, they can’t make albumin. Albumin
is essential for maintaining the osmotic pressure
needed for proper distribution of body fluids
between intravascular compartments and body
tissues. Without albumin, water accumulates in
abdominal cavity.
36
• The GI system absorbs food, gets rid of
waste.
•
• Musculoskeletal system participates in
maintaining homeostasis of the
extracellular fluid during shivering,
sweating, pumping the veins, and muscles
are needed to physically put food in your
mouth and to eliminate waste.
37
• The Nervous and endocrine systems
communicate between themselves and with
other systems, and they coordinate their actions.
This coordination helps to regulate and
modulate their activity. The endocrine system
acts indirectly, the nervous system acts directly.
Both use a chemical. Neurotransmitters and
hormones are chemicals. Cells need functional
receptors to respond to these chemicals.
Diabetics may have receptors but they do not
bind insulin as much as they should.
38
• The nervous and endocrine systems communicate to the same
effectors. The nervous system is faster. The nervous and endocrine
systems can either work together or be antagonistic to each other.
Nerves are quick but not long lasting. Hormones are slow but
their effects last longer. For example, the nerves can only provide
short-term blood pressure control. There are pressure receptors
(Baroreceptors) in the aortic arch and carotid artery. When a
greater volume of blood is ejected from the heart, the arteries stretch
more. The greater the stretch, the faster the action potential is sent
from the Baroreceptors to the brain. The brain integrates this
information, and sends a message through the Vagus nerve to the
heart, telling the heart to slow down, so the very next beat is less
forceful.
39
• Do you feel your BP changing now? No, but it is
constantly being regulated. That’s why you need to run
an EKG until you get several peaks, to get an average. If
BP is increased from hardened arteries, the
baroreceptors fire, but the situation cannot be corrected
because it is the artery that is damaged. Eventually, the
nervous system stops trying to maintain blood pressure
at its set point of 120/80. The body then resets the
optimum blood pressure to 140/90. The nervous system
cannot maintain long term blood pressure control; you
need the kidneys for that. The blood pressure set point
keeps going up with time. Long-term high blood pressure
can lead to an aneurism. The underlying cause is
something that is broken (arteries have hardened), and
can’t be fixed.
40
Proper function requires
Regulation and Integration
• Exists at all levels of organization
• within Cells: e.g., genes, operons, repressor
proteins, transcription factors, membrane transport
(gene expression will be discussed during special topics session)
•Tissues: e.g., autacoids (acts on same cell),
paracrines (acts on other cells)
• within and between Organ systems: e.g., nervous
41
and endocrine systems
Each body system
has a job
•
•
•
•
•
Renal
Respiratory
Cardiovascular
GI tract/ Liver
Musculoskeletal system
• Nervous and Endocrine:
regulate body functions
How are these different from each other?
42
Nervous
vs.
• Neurons/neurotransmitters
• Electrical impulses and
neurotransmitters
• Synapses on specific
target cells
• Local effects
• Quick (1-10 msec).
• Stops quickly when
stimulus stops
Endocrine Systems
• Glands/ Hormones
• Exposure throughout
body
• Sometimes general
effects, sometimes
specific
• Slower- seconds to
days
• Effects continue long
after stimulus stops
43
•
The
Nervous
System
Sensor- detects
state of body and
surroundings
•
Integrator- brain
and spinal cord
•
Effector-motor
output and involves
voluntary and
involuntary effectors
44
• The peripheral nervous system needs a
way to sense these problems, convey that
info into CNS. Action potentials going into
the CNS are afferent fibers. Outgoing
action potentials are efferent; they elicit a
response from effectors organs. Many
feedback systems are redundant, just to
be sure the job gets done.
45
• A knockout mouse is when you destroy a
mouse’s gene so no protein can come from that
gene. Babies born of this mouse might show
some abnormality, but many times there
appears to be no difference in the babies. This is
because there is so much redundancy in
protective mechanisms that something else has
taken over the defective functions. Some genes
are so important that a new mouse can’t even be
formed.
46
• As stated, mechanisms can be synergistic
and/or antagonistic. The ultimate price
for homeostasis is cellular energy,
ATP. Don’t use the word equilibrium
instead of homeostasis…equilibrium
causes death. Equilibrium means that
potassium is the same on both sides of the
cell membrane.
47
The price of Homeostasis
• A single feedback loop does
not work in isolation
• Feedback mechanisms can
work synergistically or
antagonistically (e.g. insulin
vs epinephrine or cortisol).
• Redundancy (that explains
why some K.O. mice fail)
• Competition and hierarchy of
loops
• ENERGY is the price!
• Variable NOT at equilibrium
rather the variable is in a
steady state.
48
• Potassium is always highly concentrated
inside of the cell, so that means it
constantly wants to get out. There has to
be a protein in the cell membrane to push
it back in, against its own concentration
gradient, and that takes energy.
49
• Are we locked into our set points? No, we
vacillate around it. Our body temperature
is set around 37°C , but it is not always at
that exact point. When you are hot, you
sweat and you don’t feel like moving
around much; when you are cold, you
shiver and curl up to conserve heat.
50
Are we really locked at our set points?
sweat
Average
Set point
37°C
shiver
sweat
sweat
Normal
range
shiver
Let’s continue this story on temperature.....
51
Poikilotherms vs. Homeotherms
Difference is the ability to regulate body temperature
Body temperature depends on
•time of day (low between 3-6am and high between 3-6 pm)
•physical activity
•menstrual cycle (0.5° C higher after ovulation)
•Age (newborns are more like poikilotherms (no shivering or
sweating and they have a greater surface-to-mass ratio.
52
• Humans have a reflex arc to maintain body
temperature. That means you are a
homeotherm (can regulate one’s own body
temperature). Lizards and other reptiles are
poikiloterms; they need sunlight to warm up
better. They are so cold in the morning, it is
difficult for them to move much. Newborn human
babies look like lizards and act like them, too!
Babies do not regulate their body temperature
as well as adults, so they get cold easier. Just
because you are hot does not mean that the
53
baby is hot… he might be cold!
• Where do you make heat? Heat is a
byproduct of metabolism. Converting
food into cellular energy is not 100%
efficient, so there is a byproduct: heat.
There are four main ways to lose heat:
radiative, conductive, convective, and
evaporative heat losses.
54
Ways we passively
lose heat
• radiative heat loss-60%
of heat lost
• Conductive heat loss
(normally minimal)
• convective heat loss
• evaporative heat loss
55
• Radiative heat loss is when your body
loses heat into the cooler environment
around you. Most excess heat is lost by
this method. Infrared detectors pick up
this type of heat.
56
• Conductive heat loss is from your body
to a solid object that you are touching. A
metal toilet seat is cold during the night!
The second person gets a warmer seat
because the first person has warmed it up.
They warmed it up because of conductive
heat loss. You also have conductive heat
loss from your ear to your cell phone,
which warms from being at your ear for 20
minutes.
57
• Convective heat loss is from your body to a fluid around your
body (humidity in air or if you are in water). If you put your hand
above your arm, it will warm the air between your hand and your
arm. The warmed air will rise and leave the area, while cool air will
fill in the gap and make you colder. If you are in water, especially
cold water, you will lose a lot of heat. (NOTE: if you are in water
hotter than your body temperature, you will not lose heat, you will
gain it). Even with a wet suit it is cold. The water comes into the suit,
your body has to take time to heat that water, but the heated water
is not quickly replaced since the suit holds the warm water against
your body for quite a while. The wet suit eventually allows you to
stay warmer in cold water than if you did not have a suit, but the
effect takes a while. Most people who are stranded in the ocean do
not die from drowning. They die from hypothermia. This type of heat
loss is convection.
58
• Evaporation is when water on skin surface that
becomes a gas; it leaves the body and goes into
the air, pulling off more water off with it by
cohesion. The result is that you become cooler.
If you are in the desert, you can get heat stroke.
This condition is especially common when the
air is humid as well as hot. If there is too much
water in the air from the humidity, you won’t
evaporate the sweat as much, so you won’t lose
excess heat as much. This leads to heat stroke.
59
• Being out in the open on a hot, humid day, or
immersed in cold water are both main causes of
thermal deaths. One thermal extreme is
hyperthermia, the other is hypothermia.
• Number one environmental cause of
hyperthermia is from prolonged exposure to
heat and high humidity
• Number one environmental cause of
hypothermia is prolonged immersion in cold
water
60
• The CNS has to make an appropriate scan
of the body conditions, and evoke an
appropriate response. There are
peripheral and central thermal receptors.
Peripheral (skin) receptors detect
changes in coldness only; they fire more
when cold. The central thermal
receptors are in the hypothalamus, and
can detect cold as well as hot.
61
Negative feedback for
thermoregulation
• Thermoreceptors (Sensory)
– Peripheral in skin
- Mainly detect cold and cool
temperatures
- Function to prevent hypothermia
– Central
- Preoptic area and anterior
hypothalamus
- Heat sensitive and cold sensitive
neurons
• AFFERENT nerve fibers
• Integration in posterior hypothalamus
- Receives input from anterior hypothalamus
and peripheral temp receptors to elicit
mainly heat producing and heat conserving
reactions
•EFFERENT nerve
fibers to effectorsskeletal muscle, sweat
glands, etc
62
• During a fever, the brain resets the set point of the core
body temperature. Instead of 37°C, something wants the
body to be at a higher temperature. The new set point is
made within the hypothalamus. Normal body temp is
now deviated from new set point, and the person will
shiver, even though the skin might be warm. Fevers are
particularly dangerous in children since their CNS is not
fully developed. It takes Tylenol 20 minutes to be
absorbed and have the effect of lowering the set point in
the hypothalamus back to normal. In the meantime, a hot
brain can be denaturing the brain proteins. Use a cold
compress or a cool bath (but not too cold) while you wait
for the Tylenol to work. If the bath is too cold, they might63
shiver and wind up getting warmer!
Temperature Effectors: cutaneous circulation, sweat
glands, skeletal muscle
Increase Temp
• Vasoconstriction – Impedes heat transfer to
skin
• Increased heat production
– Shivering
– “fetal” position
Decrease Temp
• Vasodilation - transfers
heat to skin
• Sweating - evaporative
heat loss and sprawled
position
• Decreased heat production
– Shivering inhibited
– Less movement in general
64
• If you are too cold and you want to get
warm, you shiver, curl up, and
vasoconstriction occurs, which shunts
blood away from the skin and toward the
organs. If you are too hot and you want to
cool down, you sweat, sprawl out, and
vasodilatation occurs, to shunt more blood
(and heat) to the skin for radiative heat
loss.
65
Consequences of Deviations in
Body Temperature
Temperature ° C
Consequence
40-44
Heat stroke with multiple organ
failure and brain lesions
38-40
Hyperthermia (fever or exercise)
36-38
Normal range
34-36
Mild hypothermia
30-34
Impairment of temperature
regulation
27-29
Cardiac fibrillation
66
When the environment overwhelms
the body’s ability to regulate
•
•
Number one environmental cause
of hyperthermia is from prolonged
exposure to heat and high
humidity
Heat stroke- core temperature
rises,
– excessive vasodilation
– Decrease brain and heart
perfusion
– Loss of consciousness
– Disseminated intravascular
coagulation
– Rhabdomyolysis- skeletal muscle
release contents
– Hepatic, renal insufficiency
•
Number one environmental
cause of hypothermia is
prolonged immersion in cold
water
What, exactly, killed most of
the Titanic passengers?
67
• When the body is too hot, excess
vasodilatation causes a drop in blood
pressure. This leads to hypoxia, then
anoxia, in the brain, heart, and kidneys.
This leads to organ failure and death by
heat stroke.
68
Exercise induced
hyperthermia
• Exercise raises heat
production, followed by a
matching rise in heat
loss, but at the cost of a
steady-state
hyperthermia of exercise.
• This hyperthermia is NOT
from a change in the set
point!
• Exercise hyperthermia is
from the initial imbalance
between heat production
and heat loss (time delay
for cooling).
69
Exercise vs. Fever-induced Hyperthermia
• Exercise Hyperthermia
• Exercise uses muscles, heat gain occurs, and you
sweat. The body temperature has deviated (is higher)
from the set point. Why don’t your body’s corrective
measures bring you back to a normal body temperature
while you are still working out? There is a time delay. It
takes a while for nervous reflex arc to catch up enough.
You don’t keep getting hotter and hotter while you work
out, it reaches a peak level. Someone with no sweat
glands can get a heat stroke while exercising, but a
normal person should be okay (as long as they are
properly hydrated).
70
• When you stop working out, you continue to sweat for a
while as the corrective measures continue toward the set
point. Was the hypothalamus set point changed? No,
it was the same; you just gained heat, and the negative
feedback kicked in with a time delay. Too much sweat
after exercising might cause too much cooling, causing
coldness and shivering. If it takes too long for you to start
sweating while working out, you can get too warm too
fast, a condition called exercise hypothermia. By the
way, if you go swimming in icy water, go in without
clothes, get out and dry off with snow first, to wipe off the
water before putting clothes on. You will warm up faster
because you have eliminated the evaporative cooling. 71
• Fever-Induced Hyperthermia
• This condition is actually called Fever Hyperpyrexia. In
this condition, the set point in the hypothalamus is
reset. Anything that resets the thermal set point is called
a pyrogen (“heat generator”). When WBCs come into
contact with an antigen, they release cytokines, a
chemical that recruits other WBCs (chemotaxis).
There are many cytokines with names like interleukon-1
(IL-1), interleukon-2, etc. The IL1 cytokine travels to the
third ventricle of the brain, where there is a leaky Blood
Brain Barrier (BBB), and it can get to hypothalamus.
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Fever/ hyperpyrexia –elevated core
temperature reflects resetting the Set-point T°
•
Pyrogens (circulating cytokines)
– Polypeptides produced by the immune
system
– Interleukin-1 begins the cascade and is released
from macrophages following phagocytosis of
blood-borne pyrogens
- IL-1 raises set-point by interacting with a
“leaky” portion of the blood-brain barrier that
lies in the wall of the third ventricle (above the
optic chiasm).
- IL-1 causes endothelial cells to increase
prostaglandin production (mainly E2) from
arachidonic acid
- PGE2 causes the hypothalamus to elevate the Tset
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• Remember, cell membranes are made of phospholipids.
One phospholipid is arachidonic acid. In the cell is an
enzyme called cyclo-oxygenase (COX), which cuts
the arachidonic acid into pieces called
prostaglandins. Prostaglandins have many different
functions. Some cause blood to clot, some cause blood
to thin. PGE2 causes a chemical in the hypothalamus
to alter the set point of the body temperature. Thus,
WBC’s release IL-1 to attract more WBC’s to fight the
infection, and IL-1 causes prostaglandin production to
increase, and the body temperature increases.
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• To get from the old set point to the new one, your body
has been tricked into thinking it is cold. Therefore, you
will shiver, and the blood vessels will constrict. This is
fever induced hyperthermia. A low fever is beneficial
during an infection because it increases metabolism,
helps WBC’s work harder. A high fever is detrimental.
Some bacteria have lipopolysaccharides (LPS) that
can get through BBB and cause the set point to go
up too high, causing a high fever. That would be an
exogenous pyrogen, not a good situation.
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• If you want to stop this cascade by
designing a medicine that can break a
fever (an antipyretic medicine), where do
you stop the cascade? Inhibit
prostaglandin synthesis by making a COX
inhibitor. Therefore, a good antipyretic
medicine is a COX inhibitor (I’m not
talking about a condom!). Examples of
COX inhibitors are Non-Steroidal AntiInflammatory Drugs (NSAIDs).
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•
•
•
•
•
Common NSAIDs
Aspirin (Bayer, Bufferin)
Acetaminophen (Tylenol)
Ibuprophen (Advil, Motrin, Nuprin)
Naproxen (Aleve, Naprosyn)
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• NSAIDs can do three things: decrease a fever,
decrease pain, and decrease inflammation. If all
you have is a fever, you can take aspirin or
Tylenol (but aspirin causes a reflex increase in
temperature in children, so should not be used
under the age of 12). If you have pain and
inflammation (from sprained ankle, etc) it is
better to take a Non-Steroidal Anti-Inflammatory
Drug (NSAID) that is stronger than aspirin and
Tylenol. The stronger NSAIDs for inflammation
are Ibuprophen (Advil, Motrin) and Naproxen
(Aleve, Naprosyn).
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Antipyretics/ “cox inhibitors”
• Cyclooxygenase- enzyme that cleaves
arachidonic acid (phospholipid in cell
membrane) and generates E2 prostaglandin.
• Antipyretics/”cox inhibitors” block this action.
• Different types of Cox enzymes; Different types
of antipyretics (NSAIDS; acetaminophen; etc.)
• Advantages of fever?
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Time Course of Fever
“flush”- face is
red due to
vasodilation
everywhere and
sweating
occurs…..”fever
is breaking”
Figure 73-11; Guyton & Hall
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Try drawing the exercise induced
hyperthermia graph
HINT: Remember, the set point in the hypothalamus is not changed.
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ANSWER:
• You would draw a horizontal blue line (set
point of normal body temperature) that is
level from left to right, and low to the axis.
Then draw a red line (actual body
temperature) that starts with the blue line
on the left, but then increases, levels off at
a plateau, then gradually decreases until it
returns to the blue line. The blue line is not
elevated in exercise-induced hyperthermia
because the set point does not change. 84