1

Homeostasis and Thermal Regulation

2

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

3

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

4

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

• Physiology is the study of how the body functions. In Anatomy, you learn that, with form, comes function. 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.

5

Pathophysiology

• 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!

6

7

A Recurrent Theme: Homeostasis

The maintenance of a stableInternal environment

• 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?

Homeostasis

• Claude Bernard coined the term “homeostasis”, or the maintenance of a stable internal environment.

• He was referring to a stable extracellular fluid compartment.

8

9

I ntracellular Fluid (I CF) comprises 2/3 of the body's water. I f your body has 60% water, ICF is about 40% of your weight.

Extracellular Fluid (ECF) is the remaining 1/3 of your body's water. ECF is about 20% of your weight. The ECF is further subdivided into three subcompartments:

I nterstitial Fluid (I SF) surrounds the cells, but does not circulate. I t comprises about 3/4 of the ECF. Plasma circulates as the extracellular component of blood. I t makes up about 1/4 of the ECF. Transcellular fluid is a set of fluids that are outside of the normal compartments. These 1-2 liters of fluid make up the CSF, Digestive J uices, Mucus, etc.

Body Fluid Compartments

Interstitial Fluid Comes From Plasma

• 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).

10

Importance of stable plasma

• 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 few nutrients.

11

Potassium and Sodium• Ions are things with a positive or negative charge,

such as sodium (Na+), calcium (Ca++), potassium (K+), magnesium (Mg++), chloride (Cl-). They 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.

12

Homeostasis

• 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.

13

Proteins• 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.

14

Amino Acids

• 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.

15

Protein Structure• Proteins have different levels of structure. The

primary structure of a protein is the sequence of amino acids, like beads on a necklace.

• The secondary structure of a protein is when this string folds into beta pleats (looks like stairs) or an alpha helix (winding coil).

• 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 two or more proteins link to each other.

16

17

Denatured Protein

• A protein is said to become denatured when it loses these bonds; a denatured protein changes shape without those bonds; then it 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.

18

Denatured Proteins

• 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

Variables in Optimum Range

• 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 from the set point, and perform corrective measures.

20

Set Point and Acceptable Range

• 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

Set Point and Acceptable Range

• 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

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

SetpointDev Corr

Negative Feedback

• 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.

24

Negative Feedback

• If you are hungry, your blood sugar is low. In the liver, stored glucose is in the form of glycogen. When the blood sugar is low, the pancreas releases a substance to tell the liver to chop up its glycogen into its components (glucose) and take the glucose into the bloodstream. Most of the corrective mechanisms in the body are negative feedback.

25

26

Positive Feedback promotes a change in one direction,

instability, disease

• Initial deviation from the setpoint

• Results in further deviation from the setpoint!

So, in which situations are we wired to use positive feedback?

To amplify an effect rapidly…. (avalanche!)

Positive Feedback

• There are three events in the body where positive feedback is normal:

• Pregnancy

• Blood Clotting

• Ovulation

27

Positive feedback• Positive feedback is a vicious cycle because it leads to

progressive instability and sometimes death.• Positive feedback is rare, and this mechanism is always

used carefully. • Most 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

Positive feedback

• 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

Positive feedback

• Then another positive feedback kicks in…delivery of the afterbirth. When the placenta separates from the uterus, the 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 encourage vasoconstriction to reduce the amount of bleeding.

30

Positive feedback

• The most dangerous complication of childbirth 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 from the placenta ripping away from the uterus, yet there are even more torn vessels.

• Since there are not enough clotting factors left in the body, she bleeds out.

• Clotting of blood is a positive feedback mechanism.

31

Positive feedback• There is another positive feedback mechanism that is not

associated with ill health:

• Luteinizing hormone is released from the pituitary gland.

• It causes fluid to rush into a follicle in the ovary. The excess fluid in the follicle stimulates the pituitary to release more luteinizing hormone, so more fluid rushes into the follicle (positive feedback).

• Eventually, so much fluid enters that follicle, it pops like a balloon, and the egg (ovum) is spit out of the ovary and enters the fallopian tube. This process is called ovulation.

• Once the ovum is released, it signals luteinizing hormone to turn off (negative feedback). All positive feedback mechanisms eventually have to be turned off by a negative feedback mechanism.

32

Positive and Negative Feedback

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

• Which needs to be carefully controlled? Positive.

33

Homeostasis

• 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 (work with each other), 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.

Compensation for Deviation in Set Point

• 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.

• But if you are 100 miles away from your home, you drive fast. 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.

35

All the organ systems help maintain homeostasis of the extracellular fluid

• Kidneys• Lungs• Heart• Liver• Gastrointestinal (GI) system • Musculoskeletal system• Nervous system• Endocrine (hormone) system

36

Homeostasis Requires Energy

• 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 levels are the same on both sides of the cell membrane.

37

THERMOREGULA

TION

38

Thermoregulation

• 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.

39

40

Are we really locked at our set points?

AverageSet point37°C

Normalrange

sweat sweat sweat

shiver shiver

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

Poikilotherms vs. Homeotherms

• 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 poikilotherms; 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!

41

42

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).

Heat

• 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.

43

44

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

• 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.

45

Conductive Heat Loss

• 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.

46

Convective Heat Loss

• 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 the ocean 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.

47

Evaporation• 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.

• Evaporation occurs when the air temperature is high but humidity is low (less than 10%).

• 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.

48

Hyper and Hypothermia• 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

• Of course, if you are immersed in hot water, you gain heat, not lose it.

49

Thermal Receptors

• 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.

50

Fever• During a fever, the set point of the core body temperature is

changed (set at a higher point). Instead of 37°C, something wants the body to be at a higher temperature. The new set point is made within the hypothalamus region of the brain.

• 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 40 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!

51

52

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

Thermal Compensations

• 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.

53

54

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

55

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?

Heat Stroke

• When the body is too hot, excess vasodilatation causes a drop in blood pressure.

• This leads to hypoxia (low oxygen), then anoxia (no oxygen), in the brain, heart, and kidneys.

• This leads to organ failure and death by heat stroke.

56

57

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).

58

Exercise Hyperthermia• 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 pathogenic exercise hyperthermia. 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. 59

Fever-Induced Hyperthermia• This condition is actually called Fever Hyperpyrexia. In

this condition, the set point in the hypothalamus is reset so it is greater than the body temperature. When this happens, sweating is DECREASED. This is usually caused by a bacterial infection or a chemical agent.

• Anything that resets the thermal set point to a higher temperature is called a pyrogen (“heat generator”).

• An antipyretic medicine is one that changes the set point back to normal. Note: exercise-induced hyperthermia does not change the hypothalamic set-point temperature.

60

Prostaglandins

• Cell membranes are made of phospholipids. One type of phospholipid is arachidonic acid.

• In the cell is an enzyme called cyclo-oxygenase (COX), which cuts the arachidonic acid into pieces called prostaglandins.

• Prostaglandins (PG) have many different functions. Some cause blood to clot, some cause blood to thin.

• PG-E2 causes a chemical in the hypothalamus to alter the set point of the body temperature. Thus, WBC’s release a substance called interleukon 1 (IL-1) to attract more WBC’s to fight the infection, and IL-1 causes prostaglandin production to increase, and the body temperature increases

61

62

Fever Induced Hyperthermia

• To get from the old set point to the new one, your body has been tricked by the invading bacteria 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.

63

Fever Medicines

• 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), such as Tylenol.

64

Common NSAIDs

• Aspirin (Bayer, Bufferin)

• Acetaminophen (Tylenol)

• Ibuprophen (Advil, Motrin, Nuprin)

• Naproxen (Aleve, Naprosyn)

65

NSAIDs• 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).

66

Advantages of Fever

– Increased metabolism – Increased vasodilation (more blood flow)– Increased T-cell proliferation

67

68

69

Time Course of Fever

Figure 73-11; Guyton & Hall

Induction phase: core temperature is rising. Patient has shivering and cutaneous vasoconstriction

70

Time Course of Fever

Figure 73-11; Guyton & Hall

“fever breaking” is when cutaneous vasodilation and sweating occurs.This means the core temperature is falling.

Vasodilation causes the red “flush” face.

71

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.

72

• Hydration and exercise: How to get it right

• http://fxn.ws/PUjNMc

• Your body heat can power electronic devices

• http://fxn.ws/N5knnw

73