WEEK11 - module 4. Physiological examples of homeostasis

Learning objectives

-Briefly explain why control over body temperature is crucial, and describe the normal range in core body temperature during the day.

 

Our body function is on enzyme activities and they are highly dependent on temperature. Too high body temperature can destroy cellular proteins including enzymes and depress neurons.

Normal core body temperature is around 36.2-37.5 celcius.

 

-A large number of components are involved in control over body temperature – illustrate these in some detail, using a flow diagram, and describe those responses that are crucial to counter rising core body temperatures, and those employed to correct a falling body temperature.

Body temperature flow diagram

Body temperature is detected by nerve endings in our skin (shell-integumentary system) and hypothalamus (core-brain). They sense the temperature and send the signal to the control center which is hypothalamus. 

For the effectors, to lower the heat, sweat glands(release sweat) and smooth muscles in blood vessels (dilated) are involved. Also skeletal muscles are relaxed and our conscious decision, such as getting away from the sun and drink water, occurs. To increase the heat, skeletal muscles are constricted and shivers, erector pilli muscle in the hair follicle constricted to make the insulating air layer on our skin, and blood vessels are constricted to preserve heat deep inside the body.

 

(When the body temperature is high)

The process of negative feedback operates is what the homeostasis does in the body.

When the sensor (shell- nerve endings../ core- hypothalamus) detects the stimulus, it sends the afferent signal to the intergrating center (hypothalamus). The center then send the efferent signal to the effector organ (sweat glands, smooth muscles in the blood vessels, muscles) to react ( secreting sweat, shrinking muscles, dilate the blood vessels to the surface)to that stimulus. It gives the negative feed back to the stimulus by lowering the body temperature. And the stimulus is suppressed. 

 

-Be able to briefly describe the thermoregulatory role of the following structures observed in the epidermis: erector pili muscles, sweat glands, hypodermal adipose tissue, superficial blood vessels, naked nerve endings.

Erector pili muscles are constricted when the body temperature is low, making the air layer between those erected hairs for insulation. Sweat glands are responsible for lowering the body temperature. They release heat from our body by evaporating sweat from our body. Hypodermal adipose tissue is a great insulator, trapping heat inside to prevent our body temperature from getting lower. Smooth muscle in superficial blood vessels are relaxed and blood vessels are dilated to increase the blood flow in order to release heat when our body temperature is too high. Free nerve endings detect the shell body temperature and send the signal to hypothalamus to adjust it.

 

-Be able to clearly differentiate between homeostatic responses observed during heat stress and heat stroke, explaining which is the more dangerous and why.

 

Both heat stress and heat stroke are occoured by exposure to high temperature. When we are exposed to high temperature and if it is sepcially combined with physical activities, our body tries to lower down the temperature by excreting more sweat and sending more blood toward the surface of our body. In this process, lots of Na+ and water can be lost. It can result in both heat stress and heat stroke.

 

The main difference between heat stress and heat stroke is the presence of CNS control. 

Heat stress still has control of CNS where the thermoregulation is operated. When the body tries to lower down the temperature, hypothalamus the control center sends the signal to the body section (sweat glands, muscles, smooth muscle in the blood vessels) to function (secrete sweat, relax the muscle, dilate the smooth muscle of the blood vessels). Heat stress can cause dizziniess, thirst, fainting, and increased heart beat. However, the body can control the temperature by drinking enough water, taking shower, looking for shade and so on.

 

Heat stroke is a condition when the body lose the control of CNS. 

When the core body temperature exceeds its normal functioning level, it depresses the  thermoregulation center (hypothalamus) activity. Homeostasis to lower down the body temperature doesn't operate so it results in even more temperature increase. Convulsion, tremor, unconsciousness and coma can be the symptoms. The body temperature can surge up above 41.5 c and the fatality rate of the heat stroke is about 30%.

Heat stress can be correct by homeostasis but the heat stroke cannot. Heat stroke is more dangerous than the heat stress.

 

 

-Describe the role of the proximal convoluted tubule in reabsorption of water and other solutes, detailing the uptake of NaCl and glucose. 

PCT- water and Na+ reabsorption 

Na+/K+ ATPase pump, which is located in the basolateral side of the membrane of the PCT cells towarding to the ISF, transports 3Na+ outside of the cell. It increases the osmolarity in the (ISF), and the water diffuses outside of the cell by osmosis. (Na+ moves toward the ISF from the nephron lining cells and water follows Na+ from the lumen of the nephron.)

 

Also, when we have a salty meal, Na+ moves from the lumen of the nephron to the ECF by the chemical concentration gradient and water follows the Na+ by the osmosis. 

 

-Understand the process of secondary active transport of glucose, as describe earlier in the course in the GI tract, but now in relation to kidney function and diabetes. 

PCT- glucose reabsorption 

Glucose is reabsorbed to the body in PCT by secondary active transport. It uses the energy stored in Na+ concentration gradient, which is made by Na+/K+ ATPase pump(active transport). In the secondary active transport, Na+ flows into the cell by the concentration gradient via Na+ glucose symporter (facilitated diffusion) and glucose is carried by Na+ so it doesn't directly uses energy to move out the cell. 

 

For diabetes, they have high glucose level in the blood ,which makes high glucose concentration in the filtrated blood in the PCT. As  Na+/glucose symporters in the PCT membrane are all packed, excess glucose is secreted by urine. 

 

-With regard to the Loop of Henle, understand only that a very high osmotic pressure  is generated in the medulla of the kidney (ignoring how it is generated).

 

The loop of henle is surrounded by the highest osmolarity fluid. With the very high osmotic pressure, water molecules move toward the ISF from the descending loop of the henle. It makes the fluid in the nephron highly concentrated, which makes ions flow out of the loop in the ascending limb. 

 

-Relate the high medullary osmolarity to the role of anti diuretic hormone, which, by stimulating the insertion of aquaporins into the wall of the collecting ducts, causes the production of a concentrated urine

ADH- collecting duct

Vasopressin, Anti diuretic hormone binds to the receptor in the DCT lining cell membrane. It activates g protein and enzyme to convert ATP into cAMP. cAMP stimulates the casacade which increases the number of acuaporins in the lumen side of the collecting ducts. More water is reabsorbed to the body via the aquaporine and urine get more concentrated with less water.

 

-Be able to describe how aldosterone affects the handling of NaCl in the distal tubule, and thus potentially, how this can influence water balance

Aldosterone - PCT and Na+

Aldosterone increases Na+/K+ pump in the membrane of the PCT lining cells, which increase sodium reabsorption. When more Na+ is reabsorbed to the body, water follows Na+ by the osmosis, which in turn increase the water balance in our body.

 

-Understand that kidney tissues release renin in the face of falling blood pressure and what this causes.

 

Renin is an enzyme produced in kidney, converting angiotensinogen into angiotensin1. ACE (Angiotensin converting enzyme) converts angiotensin1 into angiotensin2. It then stimulates adrenal cortex to release aldosterone, which increases Na+ and water reabsorption in the kidney. Also angiontensin2 constricts the arterioles. These results in increase in blood pressure which then send the negative feedback to kidney and the loop stops.

As this process results in increase in blood pressure, low blood pressure can be a stimulus to make this result.

 

 

 

 

 

PPT

Thermoregulation

When the body temperature is high

When the receptors detect the stimulus, which is an increased body temperature (receptors : shell- free nerve endings,epidermal receptors / core- hypothalamus), it activates thermoregulation center, hypothalamus.

It then sends the signals to the effectors. Sweat glands secrete sweat, which release body heat by vaporizing. Skeletal muscle is relaxed. Smooth muscle in the blood vessels are relaxed and dilates the blood vessels to send more heated blood to the skin surface. 

1. Receptors detect the stimulus : increased body temperature; body warmer than hypothalamic set point

(receptors)

-Shell or peripheral : numerous epidermal receptors, usually nerve endings, which send signals to the CNS

-Deep body receptors : most importantly are cells located in hypothalamus itself, these respond to changes in core body temp (eg.blood) by stimulating the hypothalamus to instigate approtriate and widespread responses.

2. It activates heat-loss center in hypothalamus

-Hypothalamus in the brain measures the temperature of the blood flowing through, collects information from the tempsensors around the body

3. -Sweat glands activated : secrete perspiration, which is vaporized by body heat, helping to cool the body

    -Skin blood vessels dilate : capillaries become flushed with warm blood : heat radiates from skin surface 

4. Body temperature decreases : blood temperature declines and hypothalamus heat-loss center "shuts off"

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When the body temperature is low

When the receptors detects that the body temperature is low, everything (sensor, integrating center, signals..) is same as when the body temperature is high. However, it activates effectors differently. It contracts skeletal muscles to generate more heat, and shiverring begins. Smooth muscle in the blood vessels is constricted to send blood deep inside the body to prevent heat loss. Goose bumps are made. Hairs in the goosebumps are erected by the constriction of pilli muscle to make the air layer which act as an insulator.

1. Receptors detect the stimulus : dereased body temperature; blood cooler than hypothalamic set point

(receptors)

-Shell or peripheral : numerous epidermal receptors, usually nerve endings, which send signals to the CNS

-Deep body receptors : most importantly are cells located in hypothalamus itself, these respond to changes in core body temp (eg.blood) by stimulating the hypothalamus to instigate approtriate and widespread responses.

2. It activates heat-promoting center in hypothalamus

-Hypothalamus in the brain measures the temperature of the blood flowing through, collects information from the tempsensors around the body

3. -Skin blood vessels constrict : blood is diverted from skin capillaries and withdrawn to deeper tissues,              minimizes overall heat loss from skin surface

    -Skeletal muscles activated when more heat must be generated, shivering begins

    -goose bumps : each bump has hair, and the erected hair makes the air layer on the skin which act as an             insulator.

4. Body temperature increases : blood temperature rises and hypothalamus heat-promoting center "shuts off"

 

 

 

Rectal measurement. Taking a rectal measurement is the most reliable way to obtain a core temperature value. Result variation with this type of measurement is low and the precision is particularly high. The normal temperature range is approximately between 36.6 °C and 38.0 °C.

 

 

 

 

 

 

 

 

 

 

 

Fever, Heat stroke and Heat stress

FEVER

The inflammatory cytokines are secreted from Th1 cells, CD4+ cells, macrophages, and dendritic cells. They stimulate hypothalamus to increase the set point of the body temperature so that the high temperature can kill the virus or bacteria which caused the infection. 

Because of the increased body temperature, even the surrounding temperature is high enough/warm enough, body reacts as it is cold. It happens when the peripheral mechanism tries to conserve heat energy to increase our body temperature to reach the set point which is elevated by the hypothalamus.

When the body recovers and normal set point is brought back, blood vessels dilates and the sweat is secreted to lower the body temperature (= The fever is broken).

 

 

Heat stress (heat exhaustion)

-Heat associated collapse/ discomfort after vigorous excercise and/or exposure to high environmental temperature

-Symptoms: elevated core body temperature, mental confusion, and fainting

-dehydration (headache), maybe difficulty maintaining BP

-heat-loss mechanisms are functional - responses are corrective : eg. cease excercise, drink water, sweat profusely, look for shade..

 

 

Heat stroke (hyperpyrexia)

: Hyperpyrexia is a condition where the body temperature goes above 106.7 degrees Fahrenheit (41.5 degrees Celsius) due to changes in the hypothalamus

-When core temp exceeds> 40c brain/hypothalamic activity is depressed, and thermoregulatory control mechanisms work less well

-As control is lost, sweating and blood flow to the periphery are reduced which leads to further increases in temp, therefore even more inhibition of brain and tissues, therefore even less control over responses..and so on

-A positive-feedback becomes established, which unless promptly dealt with can easily spiral into death

 

 

 

 

 

 

 

 

 

 

 

 

Positive feedback

-Negative feedback -> reduce or correct deviation from set point

-Positive feedback (pathological) -> error in signally -> increase deviation from set point 

(a vicious circle)

-Establishment of positive feed back loops usually leads to "an acceleration into catastrophe"

-There are a few examples of positive feedback loops in "normal" physiology, but they are of limited duration, ceasing once the process had been driven to completion

 

What cause positive feedback to stop?

Positive feedback loops do not go on forever; they are ultimately stopped by negative feedback loops once the process they were used for is complete.

 

 

 

 

 

 

 

 

 

 

 

 

The kidney and the nephron

The nephron

-Huge quantities of blood fluid are filtered at the kidneys, via nephrons.

-Almost all of this fluid and everything it contains, is reabsorbed and returned to the body.

-However, some toxic wastes are excreted, and the amount of water and salt retained or lost in the final urine or will depend on the bodies needs

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Reabsorption in the PCT

The proximal convoluted tubules (PCT) are the major site of reabsorption of many electrolytes such as sodium, potassium, chloride, and calcium, but only 10%–25% of magnesium is reabsorbed in this segment 

 

PCT- water and Na+ reabsorption 

Na+/K+ ATPase pump, which is located in the basolateral side of the membrane of the PCT cells toward the ISF, transports 3Na+ outside of the cell. It increases osmolarity in the ECF(ISF), and the water diffuses outside of the cell by osmosis. (Na+ moves toward the ECF(ISF) from the nephron and water follows.)

 

Also, when we have a salty meal, Na+ moves from the lumen of the nephron to the ECF by the chemical concentration gradient and water follows the Na+ by the osmosis. 

 

PCT- glucose reabsorption 

Glucose is reabsorbed to the body in PCT by secondary active transport. It uses the energy stored in Na+ concentration gradient, which is made by Na+/K+ ATPase pump(active transport). In the secondary active transport, Na+ flows into the cell by the concentration gradient via Na+ glucose symporter (facilitated diffusion) and glucose is carried by Na+ so it doesn't directly uses energy to move out the cell. 

 

The function of the proximal tubule is essentially reabsorption of filtrate in accordance with the needs of homeostasis (equilibrium), whereas the distal part of the nephron and collecting duct are mainly concerned with the detailed regulation of water, electrolyte, and hydrogen-ion balance.

 

 

 

 

 

 

 

 

 

 

 

ADH

ADH stands for Anti diruretic Hormone.

ATP convert into cAMP

 

ADH and water retention by aquaporins. Blood pressure increases

When ADH binds to the receptor in the membrane of collecting duct/DCT, the enzyme converts ATP into cAMP. cAMP increases the permiability of H2O by generating aquaporins in the membrane towards the lumen. Then the water flows into the ECF from the lumen of nephron. This inturns increases blood pressure and decreases diurination.

 

ADH Aldosterone difference

ADH increases the blood pressure by reuptaking water via the aquaporins from the distal tubule and collecting duct. 

Aldosterone changes the activity of Na+ pump to increase reuptaking of the Na+, which in turns increases the water retention by the osmosis. (Water follows Na+ flow by the osmosis)

 

 

 

 

 

 

 

 

 

 

 

Action of renin

Where is juxtaglomerular apparatus in kidneys located?

The juxtaglomerular apparatus is a specialized structure formed by the distal convoluted tubule and the glomerular afferent arteriole. It is located near the vascular pole of the glomerulus and its main function is to regulate blood pressure and the filtration rate of the glomerulus.

 

Is renin an enzyme?

Renin is an enzyme made by special cells in your kidneys. 

ACE stands for angiotensin converting enzyme

 

How might Aldosterone increase salt and water retention?

Aldosterone is a mineralocorticoid hormone produced in the zona glomerulosa of the adrenal cortex that influences water and salt regulation in the body. Aldosterone's primary function is to act on the late distal tubule and collecting duct of nephrons in the kidney, favoring sodium and water reabsorption and potassium excretion while also contributing to acid-base balance. To execute these tasks, it influences epithelial sodium channels, sodium-potassium exchange pumps, hydrogen ion ATPases, and bicarbonate-chloride antiporters.Aldosterone affects blood pressure by regulating the sodium gradient in the nephron to either increase or decrease the water reabsorped to contribute to the volume of the extracellular fluid (ECF). This, however, is not to be confused with the effect of anti-diuretic hormone (ADH), also referred to as vasopressin. ADH is often released simultaneously with aldosterone in order to support water reabsorption to the ECF by mobilizing aquaporin channels to the apical (lumen-facing) membrane of principal cells in the collecting tubule. Overall, aldosterone is a key player in the multi-factorial regulation of salt, potassium, blood pressure, and acid-base balance.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Self-paced quiz

During the inflammation, The inflammatory cytokines are secreted from Th1 cells, CD4+ cells, macrophages, and dendritic cells. They stimulate hypothalamus to increase the set point of the body temperature. Because of the increased body temperature, even if the surrounding temperature is high enough/warm enough, body reacts as it is cold. Skeletal muscle constricts/shivers to generate heat energy and blood vessels constrict to preserve heat. This mechanism conserves heat energy to increase our body temperature to reach the set point which is elevated by the hypothalamus.

When the body recovers and normal set point is brought back, blood vessels dilates and the sweat is secreted to lower the body temperature (= The fever is broken).

Baby birth

-Stimulus : cervix stretches

-Receptors : sensory receptors in the cervix send signals to the hypothalamus

-Integration/control center: hypothalamus secretes oxyotcin through the posterior pituitary gland (via hypothalamic hypophyseal tract)

-Effector : myometrium in the uterus contracts

-Result : cervix stretches more and the baby pushes down from the birth canal.

--> This positive feedback ends when the labour ends

 

Milk ejection

-Stimulus : baby suckles the nipple

-Receptors : sensory receptors in the nipple send the signal to the hypothalamus

-Integration/control center: hypothalamus secretes oxyotcin via the posterior pituitary gland 

-Effector : myoepithelial tissue in the mammary gland contracts 

-Result : milk is ejected

--> This positive feedback ends when the baby stop suckling the nipple.

 

Blood clotting

When the blood vessels are destroyed, the damaged tissue releases factors that bring platelets to the site of the wound. As the plateletes are gathered, the chemicals released by platelets attract more plateletes to the site. This positive feedback ends when the damaged tissue is healed

 

-Bowmans capsule/ Glomerular capsule

: Filtration occurs. (180L/day), It filtrates glucose, NaCl, aminoacids and water. Plasma proteins and blood cells are not filtered and remain in the blood vessel.

 

-The proximal convoluted tubule (reabsorption of glucose secondary active tp, Na+ pump)

: Most of the reabsorption occurs. Most of the glucose, salt and aminoacids which are filtered in the bowman's capsule are reuptaken. When these solutes are reabsorbed to the ECF, water follows them by the osmosis, and these fluid and solutes enter to the blood stream. While glucose is reuptaken, it uses secondary active transport generated by Na+ gradient.

 

-The loop of Henle

: Located in the medulla of the kidney, where it has high osmolarity (1200mOsm). 

 

-The distal tubule (and Aldosterone)

: Na+ and Ca2+ reabsorption is the most important thing in the distal tubule. Aldosterone secreted in the adrenal cortex stimulates the Na+/K+ ATPase pump to increase reuptake of Na+.

 

-The collecting duct (and ADH)

: ADH acts prominently in the collecting duct. They bind to the receptors in the lining cell of the collecting duct, which then convert ATP into cAMP. cAMP increases aquaporins in the membrane toward the lumen of the collecting duct. It increases H2O reabsorption.

PCT- water and Na+ reabsorption 

Na+/K+ ATPase pump moves 3Na+ outside of the cell(lining cell of the PCT). This increases osmolarity in the ECF(ISF). Water diffuses outside of the cell by osmosis.(Na+ moves toward the ECF(ISF) from the nephron and water follows.) Na+/K+ ATPase pump is located in the basolateral side of the membrane. 

Also, when we have a salty meal, Na+ moves from the lumen of the PCT to the ECF by the chemical concentration gradient and water follows the Na+ by the osmosis. 

This is how the Na+ and water reabsorption occurs in the PCT.

 

ADH is produced by the hypothalamus and released via posterior pituitary gland. It is secreted when the blood pressure is low and the plasma volume is low. It stimulates the aquaporins in the collecting duct to increase water reuptake. By combining with the receptors in the lining cell of the collecting duct, it activates Gprotein and enzyme to convert ATP to cAMP which activates aquaporins towards the lumen of the collecting duct. It consequently increases the blood pressure by reuptaking more water in the body.

When the blood pressure is low, juxtaglomerular apparatus in kidney releases renin and it converts angiotensinogen to angiotensin1. ACE then converts angiotensin1 to angiotensin 2.

Angiotensin2 directly constricts the blood vessels and increases the blood pressure.

Angiotensin2 also increases ADH and aldosterone secretion. Aldosterone activates Na+ pump in the PCT, increasing Na+ reuptake. When Na+ flows to the body, water follows Na+ by the osmosis, which increases the blood pressure. ADH increases aquaporin in the collecting duct membrane, which increases water reuptake . Both ADH and aldosterone increases the blood pressure.

 

PCT- glucose reabsorption 

By using the energy stored in Na+ concentration gradient made by Na+/K+ ATPase pump(active transport), glucose is reabsorbed to the body in PCT. This process is called secondary active transport. It doesn't directly uses energy to move out the cell. 

Na+/K+ ATPase pump moves Na+ outside of the lumen 

 

Secondary active transport is

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Summary

Kidney overview

 

 

 

 

 

 

 

 

Nephron