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Human Physiology, Bio 12

Chapters 1, 3, 73

Review chapter 2

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

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Lecture outline

I. IntroductionII. Physiology vs. pathophysiologyIII. Homeostasis

A. Terms of homeostasisB. Types of correction mechanismsC. Levels of regulation

i. Cellsii. Tissuesiii. Organs iv. Organ systems

D. The price of homeostasis

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Lecture outline for Thermoregulation

I. Body temperature throughout the dayII. Ways we lose heatIII. Reflex arc of temperature regulation- a negative

feedback mechanismIV. Consequences of extreme core temperatures

A. HyperthermiaB. Heat strokeC. hypothermia

V. Exercise induced hyperthermiaVI. Hyperthermia from fever

A. PyreticsB. Anti-pyretics- COX inhibitors

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Physiology

The science that is concerned with the functionof the living organism and its parts, and of the physical and chemical processes involved.

• The study of disordered body function (i.e. disease)• The basis for clinical medicine

Pathophysiology

• 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.

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• 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!

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A Recurrent Theme: Homeostasis

The maintenance of a stable“ milieu interieur”

Claude Bernard (1813 - 1878)

• Prevent denaturation of proteins• To keep cells under optimum

conditions for function and survival• It’s all about the plasma!

Why do we need a stable, internal environment?

• 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).

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• 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.

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• 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).

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• 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.

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• 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.

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• Potassium has to be strictly regulated so that it stays within the range of 3-5 mili-equivalents. At 6-7 mili-equivalents, 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.

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• 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.

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• 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.

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• 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.

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• 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 contractions.

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• 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.

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• When a patient goes to a doctor in illness or for a check-up, 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.

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• 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.

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• 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.

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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!

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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

SetpointDev Corr

• 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.

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• 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.

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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!)

• 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.

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• 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.

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• 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 hormone is another positive feedback mechanism.

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• Which feedback mechanism is associated with the greatest health? Negative.

• Which needs to be carefully controlled? Positive.

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• 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 and undershoot the set points in the body.

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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 the amount of salt retained.

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• 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.

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• 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.

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• The GI system absorbs food, gets rid of waste.

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• 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.

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• 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.

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• 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.

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• 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.

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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 and endocrine systems

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Each body system has a job

• Renal• Respiratory• Cardiovascular• GI tract/ Liver• Musculoskeletal system

• Nervous and Endocrine: regulate body functionsregulate body functions

How are these different from each other?How are these different from each other?

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Nervous vs. Endocrine Systems

• Neurons/neurotransmitters

• Electrical impulses and neurotransmitters

• Synapses on specific target cells

• Local effects

• Quick (1-10 msec).

• Stops quickly when stimulus stops

• Glands/ Hormones• Exposure throughout

body• Sometimes general

effects, sometimes specific

• Slower- seconds to days

• Effects continue long after stimulus stops

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The Nervous System• Sensor- detects state

of body and

surroundings

• Integrator- brain and

spinal cord

• Effector-motor output

and involves

voluntary and

involuntary effectors

• 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.

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• 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.

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• 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.

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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.

• 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.

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• 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.

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Are we really locked at our set points?

AverageSet point37°C

Normalrange

sweat sweat sweat

shiver shiver

Let’s continue this story on temperature.....

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Poikilotherms vs. Homeotherms

Difference is the ability to regulate body temperatureBody 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.

• 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 baby is hot… he might be cold!

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• 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.

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Ways we passively lose heat

• radiative heat loss-60% of heat lost

• Conductive heat loss (normally minimal)

• convective heat loss• evaporative heat loss

• 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.

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• 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.

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• 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.

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• 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.

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• 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

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• 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.

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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 effectors- skeletal muscle, sweat glands, etc

• 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 might shiver and wind up getting warmer!

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Temperature Effectors: cutaneous circulation, sweat glands, skeletal muscle

Increase Temp Decrease Temp

• Vasoconstriction - – Impedes heat transfer to

skin

• Increased heat production– Shivering– “fetal” position

• Vasodilation - transfers heat to skin

• Sweating - evaporative heat loss and sprawled position

• Decreased heat production – Shivering inhibited– Less movement in general

• 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.

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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

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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?

• 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.

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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).

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).

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• 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.

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• 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

• 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 Anti-Inflammatory 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

Figure 73-11; Guyton & Hall

“flush”- face is red due to vasodilation everywhere and sweating occurs…..”fever is breaking”

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Try drawing the exercise induced hyperthermia graph

HINT: Remember, the set point in the hypothalamus is not changed.

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.

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