16 - Homeostasis

• What is homeostasis?

  The regulation of the body's internal conditions in return to changing internal & external conditions
• Why is homeostasis important?

  Keeping your internal environment stable is vital for cells to function normally and to stop them being damaged
• Why is it important to maintain body temperature?

  • If body temperature is too high (e.g. 40C) enzymes become denatured. The molecules vibrate too much, breaks hydrogen bonds of tertiary structure
  • Active site changes, metabolic reactions are less efficient
  • If body temperature is too low enzyme activity, slowing rate of metabolic reactions
  • The highest rate of enzyme activity happens at optimum temperature (37C)
• Why is it important to maintain pH?

  • If blood pH is too high or low, enzymes denature
  • Breaks the hydrogen bonds of the tertiary structure, changes the active site thus making metabolic reactions less efficient
  • The highest rate of enzyme activity is the optimum pH, usually around 7.
  • However, some work at other pH's (stomach enzymes work at acidic pH's)
• Why is it important to maintain glucose levels?

  • If blood glucose concentration is too high the water potential of blood is reduced to a point where water molecules diffuse out of cells by osmosis. It causes cells to shrivel up & die
  • If blood glucose is too low, cells are unable to carry out normal activities because there isn't enough glucose for respiration to provide energy.
• How do Homeostatic Systems respond by Negative Feedback?

  1. Receptors detect when a level is too high or low, and this information is communicated via the nervous/hormonal system to effectors
  2. Effectors restore to normal (negative feedback mechanism)
  3. Negative feedback keeps things about the normal level (i.e. 0.5C range around 37C body temperature)
  4. However it only works within certain parameters. For example, a large drop in body temperature caused by prolonged exposure to cold weather may be too large to counteract.

  
• Why is it advantageous that we have multiple negative feedback systems?

  It means we can actively increase or decrease a level (i.e. we have mechanisms to actively increase & actively decrease body temperature). Having only one mechanism would equal a slower response and less control
• How do Homeostatic Systems respond by Positive Feedback?

  1. Positive feedback systems amplify the change, leading to further increase away from the normal level
  2. Positive feedback is useful to rapidly activate something e.g. a blood clot after an injury
  3. It also occurs when a homeostatic system breaks down e.g. if you're too cold for too long
  4. Positive feedback isn't involved in homeostasis because it doesn't keep your internal environment stable.
• Positive Feedback rapidly activating - Blood Clots:

  1. Platelets become activated and release a chemical which triggers more platelets to be activated
  2. Platelets very quickly form blood clots at the injury site
  3. The process ends with negative feedback when the body detects the blood clot has been formed
• Positive feedback when a system breaks down - Hypothermia:

  1. Hypothermia is body temperature below 35C, occurring when heat's lost quicker than it is produced
  2. As body temperature falls the brain doesn't work properly & shivering stops - this makes body temperature fall even more!
  3. Positive feedback takes body temperature further away from the normal level, and it continues to decrease unless action is taken

  
• Glucose Concentration in the body:

  • Typical concentration is normally around 90 mg per 100cm3 of blood, & its monitored by cells in the pancreas
  • Blood glucose concentration rises after eating food containing carbohydrates
  • Blood glucose concentration falls after exercise, as more glucose is used in respiration to release energy
• What hormones control blood glucose concentration?

  • Insulin & Glucagon are both secreted by clusters of cells in the pancreas called the islets of Langerhans
  • Beta (β) cells secrete insulin
  • Alpha cells (α) secrete glucagon
  • They travel in the bloodstream to act on their target cells (effectors)
• How does Insulin lower blood glucose concentration:

  1. Insulin binds to specific receptors on the cell membranes of liver & muscle cells
  2. It increases the permeability of muscle-cell membranes to glucose, so the cells take up more glucose
  3. This involves increasing the amount of channel proteins
  4. Insulin also activates enzymes in liver & muscle cells that convert glucose into glycogen
  5. The cells store glycogen in their cytoplasm, as an energy source
  6. The process of forming glycogen from glucose is called glycogenesis
  7. Insulin also increases rate of respiration

  
• How does Glucagon increase blood glucose concentration:

  1. Glucagon binds to specific receptors on the cell membranes of liver cells
  2. Glucagon activates enzymes in liver cells that break down glycogen to glucose
  3. The process of breaking down glycogen is called glycogenolysis
  4. Glucagon also activate enzymes that are involved in the formation of glucose from glycerol (a component of lipids) and amino acids
  5. The process of forming glucose from non-carbohydrates is called gluconeogenesis
  6. Glucagon decreases the rate of respiration

  
• Negative Feedback Mechanism of High Blood Pressure:

  1. Pancreas detects blood glucose concentration is too high
  2. β cells secrete insulin and α cells stop secreting glucagon
  3. Insulin binds to receptors on liver & muscle cells
  4. Cells take up more glucose, glycogenesis activated & cells respire more glucose
  5. Less glucose in the blood

  
• Negative Feedback Mechanism of Low Blood Pressure:

  1. Pancreas detects blood glucose concentration is too low
  2. α cells secrete glucagon and β cells stop secreting insulin
  3. Glucagon binds to receptors on liver cells
  4. Glyconeolysis & Gluconeogenesis activated & cells respire less glucose
  5. Cells release glucose into the blood

  
• How does Insulin increase the amount of glucose entering cells?

  1. Skeletal & Cardiac muscle cells contain a channel protein called GLUT4. GLUT4 is a glucose transporter
  2. When insulin levels are low, GLUT4 is stored in vesicles in the cytoplasm of cells
  3. Insulin binds to receptors on the cell-surface membrane, it triggers the movement of GLUT4 to the membrane
  4. Glucose can than enter these muscle cells via facilitated diffusion
• How does Adrenaline increase Blood Glucose Concentration?

  1. Adrenaline is a hormone that's secreted from your adrenal glands when there's a low concentration of glucose in your blood
  2. Adrenaline binds to receptors in the cell membrane of liver cells

  • It activates glycogenolysis (the breakdown of glycogen to glucose)
  • It inhibits glycogenesis (the synthesis of glycogen from glucose)

  3. It activates glucagon secretion & inhibits insulin secretion

  4. Adrenaline makes glucose more available for muscles to respire

  
• How do Adrenaline & Glucagon activate Glycogenolysis by acting via second messengers?

  • Receptors for adrenaline/glucagon have specific tertiary structures, making them complementary.
  • When the hormones bind, they activate an enzyme called adenylate cyclase
  • Adenylate Cyclase converts ATP into a chemical messenger, a 'second messenger' called cyclic AMP (cAMP)
  • cAMP activates an enzyme called protein kinase A. Protein kinase A activates a cascade (a chain of reactions) that breaks down glycogen into glucose (glycogenolysis)

  
• How does Type 1 Diabetes work?

  1. Immune system attacks β (beta) cells so they can't produce any insulin.
  2. Scientists believe this is either due to a genetic predisposition or by viral infection
  3. After eating, blood glucose level rises & stays high. This is called hyperglycaemia. As not all glucose can be reabsorbed by the kidneys, some is excreted in urine
  4. It's treated with insulin therapy - but this has to be controlled carefully as too much insulin can cause a drop (hypoglycaemia)
  5. It can also be controlled via a simple carbohydrate diet
• How does Type 2 Diabetes work?

  1. Type 2 diabetes is usually linked with obesity, diet, family history
  2. It occurs when β (beta) cells don't produce enough insulin or body cells respond to insulin.
  3. This causes blood glucose concentration to be higher
  4. It can be treated by eating a healthy balanced diet & regular exercise. Extreme cases may require insulin injections.
• Type 2 Diabetes:

  • It's becoming increasingly common due to levels of obesity + unhealthy diets
  • Can cause additional health problems (visual impairment & kidney failure) so it's important to educate
• How to reduce risk of developing Type 2 Diabetes?

  • Diet low in fat, sugar & salt, instead with plenty grain, fruit & veg
  • Regular exercise
  • Lose weight
• How to reduce risk of developing Type 2 Diabetes?

  • Diet low in fat, sugar & salt, instead with plenty grain, fruit & veg
  • Regular exercise
  • Lose weight

  NHS campaign 'Change4Life' aim to educate and implement these strategies. The food industry must reduce their advertising of junk food to allow consumers to make healthier choices.
• How are food companies making products healthier?

  Using sugar alternatives to sweeten food/drink & reducing sugar, fat, salt content of products. There is pressure on companies to increase profits to alter public perception.
• How do you use Colorimetry to determine Glucose Concentration of Urine?

  1. Line 5 test tubes in a dilution series with concentrations of 4mM, 2mM, 1mM, 0.5mM, 0.25mM
  2. Add 10cm3 of the initial 4mM glucose solution to the first test tube and 5cm3 of distilled water in the other 4 tubes
  3. Use a pipette, draw 5cm3 of solution of first (4mM) test tube, add to second (2mM) test tube & mix thoroughly
  4. You now have 10cm3 of solution that's half as concentrated as the solution in the first tube
  5. Repeat 3x more times for the other solutions

  
• Making a calibration curve from your glucose solutions:

  1. Add quantitative Benedict's reagent to each sample (+ a negative control of water)
  2. Heat in a water bath that's brought to the boil
  3. Use a colorimeter (with a red filter) to measure the absorbance of Benedict's Solution
  4. Plot calibration curve on a graph based on results
  5. Then you can test the urine in the same way & then compare to graph

  
• What are the Kidneys' purpose?

  • Excreting waste products such as urea + regulate water potential
  • As the blood passes through capillaries in the cortex (outer layer), substances are filtered out into long tubules surrounding the capillaries.
  • This process is called ultrafiltration
  • Useful substances (glucose + adequate amounts of water) are selectively reabsorbed.
  • Remaining substances are excreted as urine
• Kidneys Part 1:

  1. Blood from renal artery enters smaller arterioles in the kidney cortex
  2. Each arteriole is split into glomerulus - a bunch of capillaries looped inside a hollow ball called a Bowman's capsule
  3. This is where ultrafiltration takes place
  4. The afferent arteriole takes blood into each glomerulus & the efferent arteriole takes the filtered blood away
  5. The efferent arteriole is smaller, so the blood in the glomerulus is under high pressure

  
• Kidneys Part 2 (The Sequel):

  1. The high pressure forces liquid & small molecules in the blood out the capillary & into the Bowman's Capsule
  2. They pass through 3 layers to reach the Bowman's Capsule (the capillary wall, a membrane, the epithelium)
  3. Larger molecules such as protein & blood cells can't pass through. The substances that enter the Bowman's capsule = glomerular filtrate
  4. The glomerular filtrate passes along the rest of nephron & useful substances are reabsorbed along the way
  5. Finally, the filtrate flows through the collecting duct and passes out of the kidney along the ureter

  
• Reabsorption along the Nephron Tubule:

  1. Useful substances leave the tubules of the nephrons & enter the capillary network that's wrapped around them
  2. Proximal Convoluted Tubule absorbs glucose by facilitated diffusion & active transport. Water absorbed by osmosis. Has microvilli to increase surface area for reabsorption
  3. Loop of Henle - At the bottom of ascending limb, Na+ ions diffuse out. This creates a lower water potential so water diffuses out.
  4. Distal Convoluted Tube removes water by osmosis
  5. Collecting Duct reabsorbs water based on body's hydration state
  6. Remaining filtrate is urine

  
• What is urine typically made of?

  Water, dissolved salts, urea, hormones, excess vitamins

  SHOULDN'T CONTAIN

  Proteins + Blood cells (too big to filter out), Glucose (it's actively reabsorbed into the blood)
• Why is it important kidneys regulate water potential?

  • Water is essential for keeping the body functioning, so water levels must be kept constant
  • Mammals excrete urea in solution, meaning water is lost during excretion. It's also lost in sweat
  • The kidneys ensuring the body has the right amount of water is called osmoregulation
  • Water is reabsorbed into the blood along almost the entire nephron, but regulation occurs in the loop of Henle, DCT, & collecting duct.
  • The volume of water reabsorbed by the DCT & collecting duct is controlled by hormones

  
• How does Blood Water Potential affect urine?

  • If the water potential of the blood is too low, more water is reabsorbed by osmosis back into the blood. This makes urine more concentrated, so less water is lost during excretion
  • If the water potential of the blood is too high, less water is reabsorbed by osmosis back into the blood. This makes urine less concentrated , so more water is lost during excretion
• How does the Loop of Henle maintain a Sodium Ion Gradient?

  1. Top of ascending limb, Na+ ions are pumped into medulla by active transport. The ascending limb is impermeable to water, so water stays, low medulla water potential
  2. Water moves out descending limb into medulla, making the filtrate more concentrated. Water in medulla then reabsorbed through capillaries
  3. By bottom of ascending limb, Na+ ions diffuse into medulla, lowering water potential
  4. Water moves out DCT, is reabsorbed into blood
  5. Stage 1-3 massively increase ion concentration in medulla. Water moves from collecting duct -> blood

  
• Water Reabsorption + Hormones:

  1. Osmoreceptors in the hypothalamus monitor water potential of blood
  2. As water potential decreases, water moves out of osmoreceptor cells by osmosis + they decrease in volume.
  3. This sends a signal to other cells in hypothalamus, signal sent to posterior pituitary glands
  4. ADH secreted into blood, makes walls of DCT & Collecting Duct more permeable
  5. More water is reabsorbed, more concentrated urine, less water lost.
• When you're dehydrated:

  1. Water potential drops
  2. Detected by osmoreceptors in the hypothalamus
  3. Posterior pituitary gland is stimulated + releases more ADH into the blood
  4. More ADH means DCT & collecting duct become more permeable, so more water is reabsorbed into the blood by osmosis
  5. A small amount of highly concentrated urine is produced & less water is lost

  
• When you're overhydrated:

  1. Water potential rises
  2. Detected by osmoreceptors in the hypothalamus
  3. Posterior pituitary gland is stimulated + releases less ADH into the blood
  4. Less ADH means DCT & collecting duct become less permeable, so less water is reabsorbed into the blood by osmosis
  5. A large amount of dilute urine is produced & more water is lost