7.4.1 Insulin and blood glucose control

Blood glucose rises after carbohydrate

1. Blood glucose concentration is the amount of glucose dissolved in a given volume of blood.
2. Carbohydrate digestion produces glucose, which is absorbed through the small intestine into the blood.
3. After a meal the absorbed glucose makes blood glucose concentration rise.
4. Between meals and during exercise cells remove glucose from the blood for respiration, so the concentration falls.
5. Control keeps the concentration within a narrow range so cells receive glucose without large changes to the water balance of the blood.

Insulin lowers high blood glucose

1. Detection occurs when the pancreas senses that blood glucose concentration is above the normal range.
2. Release follows as the pancreas secretes insulin into the blood plasma.
3. Transport occurs in the plasma, which carries insulin to target cells and organs including the liver.
4. Cell uptake increases because insulin causes body cells to take more glucose from the blood.
5. Storage increases because insulin causes liver and muscle cells to convert glucose into glycogen.
6. Correction occurs as glucose leaves the blood, returning blood glucose concentration towards the normal range.
7. The control pathway can be written as $high\; blood\; glucose\to insulin\; release\to glucose\; uptake\; and\; glycogen\; formation\to blood\; glucose\; falls$.

Glycogen stores excess glucose

1. Glycogen is an insoluble carbohydrate made from many glucose units and stored mainly in liver and muscle cells.
2. Insolubility allows a large amount of glucose to be stored without the glycogen dissolving and strongly affecting water movement into the cell.
3. Liver glycogen provides a store that can later supply glucose to the blood when the concentration becomes too low.
4. Muscle glycogen provides glucose for respiration in muscle cells during activity.

Insulin release falls after correction

1. Negative feedback means that a change away from the normal level causes responses that reverse the change.
2. As blood glucose falls the stimulus for insulin release becomes weaker, so less insulin is released.
3. When the normal range is restored the corrective response is reduced rather than continuing to drive the concentration lower.

7.4.2 Glucagon and blood glucose regulation

Glucagon raises low blood glucose

1. Glucagon is a hormone released by the pancreas when blood glucose concentration is below the normal range.
2. Low blood glucose can occur between meals, during prolonged exercise or when cells have used glucose in respiration.
3. The pancreas responds by releasing glucagon into the blood plasma.
4. The liver is the main target because glucagon causes liver cells to convert stored glycogen into glucose.
5. Glucose enters the blood from the liver, so blood glucose concentration rises towards the normal range.
6. The control pathway can be written as $low\; blood\; glucose\to glucagon\; release\to glycogen\; converted\; to\; glucose\to blood\; glucose\; rises$.

The liver supplies stored glucose

1. Glycogen stores glucose in an insoluble form inside liver and muscle cells.
2. Glucagon acts mainly on liver cells because liver glycogen can be converted to glucose that is released into the bloodstream.
3. Muscle cells use their glycogen locally for respiration rather than releasing the stored glucose to control the concentration in the blood.
4. Conversion changes the stored carbohydrate into soluble glucose that can leave the liver and enter the plasma.

Two hormones correct opposite changes

1. Negative feedback reverses a change away from the normal level.
2. When glucose is too high insulin increases glucose uptake and glycogen formation, so the concentration falls.
3. When glucose is too low glucagon increases the conversion of liver glycogen to glucose, so the concentration rises.
4. The responses oppose each other and keep blood glucose within a narrow range rather than at one perfectly fixed value.
5. Hormone release changes continuously because the pancreas responds to the current blood glucose concentration.

7.4.3 Type 1 and type 2 diabetes

Type 1 diabetes produces too little insulin

1. Type 1 diabetes occurs when the pancreas produces little or no insulin.
2. Without enough insulin body cells take in less glucose and the liver converts less glucose into glycogen.
3. Blood glucose remains too high especially after carbohydrate is digested and glucose enters the blood.
4. Control requires insulin delivered by injection or a pump because swallowing insulin would expose this protein hormone to digestive enzymes.
5. Dose and timing must be matched to food intake, activity and the measured blood glucose concentration.
6. Regular monitoring helps prevent blood glucose becoming dangerously high or falling too low after too much insulin.

Type 2 diabetes reduces insulin response

1. Type 2 diabetes occurs when body cells respond less effectively to insulin.
2. The pancreas can still make insulin but glucose uptake and glycogen formation do not increase enough.
3. Blood glucose remains high because glucose is removed from the blood more slowly.
4. Control often begins with lifestyle changes including a controlled carbohydrate intake, regular exercise and loss of excess body mass.
5. Medication may be needed when lifestyle changes do not control blood glucose adequately.
6. Risk is influenced by several factors including excess body fat, physical inactivity and inherited variation.

BMI relates mass to height

1. Body mass index is calculated using $\mathrm{BMI}=\frac{\mathrm{mass}(\mathrm{kg})}{[\mathrm{height}(\mathrm{m}){]}^2}$.
2. Mass must be in kilograms and height must be in metres before the values are substituted.
3. BMI estimates weight category but it does not distinguish between muscle mass and body fat.

Waist-to-hip ratio estimates fat distribution

1. Waist-to-hip ratio is calculated using $\mathrm{waist}:\mathrm{hip}\mathrm{ratio}=\frac{\mathrm{waist}\mathrm{circumference}}{\mathrm{hip}\mathrm{circumference}}$.
2. Both circumferences need the same unit so centimetres divided by centimetres gives a ratio with no unit.
3. A larger ratio indicates that more body mass is carried around the abdomen and is associated with a greater risk of type 2 diabetes.

Correlation does not prove cause

1. A positive correlation exists when the incidence of type 2 diabetes tends to increase as body mass or waist-to-hip ratio increases.
2. Correlation is evidence of an association but it does not show by itself that increased body mass directly caused diabetes in every person.
3. Other variables such as diet, physical activity, age and inherited variation may affect both body mass and diabetes risk.
4. Evaluation should consider the trend, the amount of variation, the sample size and whether important variables were controlled.

A glucose test can model urine screening

1. Glucose in urine may indicate that blood glucose has been high enough for glucose to remain in the filtrate instead of all being reabsorbed.
2. A chemical test can compare simulated urine samples for reducing sugar without handling human body fluid.

The result supports a diagnosis, not proves it

1. A positive simulated result shows that reducing sugar is present in that sample.
2. A real screening result would need confirmation with controlled blood glucose measurements and clinical assessment.
3. The strongest comparison links the result to insulin action while recognising that one observation does not identify the diabetes type.

7.4.4 Structure of the urinary system

The urinary system removes urine

1. The urinary system consists of two kidneys, two ureters, the bladder and the urethra.
2. Its route can be written as $kidneys\to ureters\to bladder\to urethra\to outside\; the\; body$.
3. Each structure has a distinct position so a labelled diagram should show the kidneys above the bladder and one ureter joining each kidney to the bladder.

Kidneys receive and filter blood

1. Each kidney is a bean-shaped organ supplied by a renal artery and drained by a renal vein.
2. The renal artery carries blood containing urea, water, ions, glucose and other dissolved substances into the kidney.
3. The renal vein carries blood away after the kidney has removed urea and adjusted water and ion contents.
4. Urine leaves separately through the ureter rather than through a blood vessel.

Ureters carry urine to the bladder

1. A ureter is a tube that carries urine from one kidney to the bladder.
2. There are two ureters because each kidney has its own connection to the bladder.
3. The ureters do not carry blood and they do not carry urine directly out of the body.

The bladder stores urine

1. The bladder is a muscular sac that stores urine until urination.
2. Storage separates continuous urine production by the kidneys from periodic removal from the body.
3. The bladder is not a filter because filtration and urine formation occur in the kidneys.

The urethra leads outside

1. The urethra is the single tube that carries urine from the bladder to the outside of the body.
2. Ureter and urethra have similar names but different connections and functions.

Blood and urine follow different routes

1. Blood enters through the renal artery and leaves through the renal vein.
2. Urine leaves through a ureter and then passes through the bladder and urethra.
3. The two routes meet inside the kidney because substances are removed from blood to form urine without blood itself entering the ureter.

Diagram labels need exact connections

1. Urine is the liquid formed by the kidneys that contains urea, excess water and excess mineral ions.
2. A correct diagram distinguishes the two ureters from the one urethra and keeps the blood vessels separate from the urine pathway.
3. A label line should end on the named structure rather than the space beside it.

7.4.5 Structure and function of the nephron

Nephrons form urine

1. A nephron is a microscopic kidney tubule that filters the blood and then reabsorbs useful substances.
2. The nephron begins with a glomerulus enclosed by Bowman's capsule.
3. The filtrate then travels along a tubule before entering a collecting duct.
4. Capillaries surround the tubule so substances can move from the filtrate back into the blood.
5. Urine formation has two linked stages: ultrafiltration followed by selective reabsorption.

High pressure filters small molecules

1. Ultrafiltration is high-pressure filtration of the blood at the glomerulus.
2. Blood pressure forces water and small dissolved molecules through the filtration barrier into Bowman's capsule.
3. The filtrate contains water, glucose, urea and mineral ions because these molecules are small enough to pass.
4. Blood cells remain in the capillaries because they are too large to cross the filtration barrier.
5. Large plasma proteins remain in the blood because their molecules are too large to pass through the barrier.

The glomerulus produces filtrate

1. The glomerulus is a knot of capillaries inside Bowman's capsule.
2. Its capillary network provides a large surface area for filtration.
3. Bowman's capsule collects the liquid and small solutes that leave the glomerular blood.
4. The first liquid is filtrate rather than urine because it still contains useful glucose, water and ions.

Selective reabsorption returns glucose

1. Selective reabsorption returns useful substances from the nephron filtrate to the blood.
2. All glucose is normally reabsorbed from the first part of the tubule into the surrounding capillaries.
3. Active transport moves glucose against its concentration gradient when necessary and requires energy released by respiration.
4. Tubule cells contain many mitochondria to supply energy for active transport.
5. Microvilli increase surface area so glucose can be reabsorbed rapidly.

Water returns to the blood

1. Water is reabsorbed from the filtrate into the blood by osmosis.
2. The amount reabsorbed varies according to the water content of the blood and the permeability of the collecting duct.
3. Useful quantities of ions are reabsorbed while excess ions remain in the tubule.
4. Urea remains in the filtrate together with excess water and ions, forming urine.

Structure explains each movement

1. Bowman's capsule surrounds the glomerulus and receives the filtrate directly.
2. A long tubule provides time and surface area for selective reabsorption.
3. A close capillary supply carries reabsorbed glucose and water away and helps maintain concentration gradients.
4. The collecting duct provides a final route in which water reabsorption can be adjusted before urine leaves the kidney.

7.4.6 ADH and water regulation

ADH changes collecting duct permeability

1. Antidiuretic hormone is released from the pituitary gland into the blood.
2. Its target is the kidney where it increases the permeability of the collecting duct to water.
3. A more permeable collecting duct allows more water to move by osmosis from the filtrate into the blood.
4. More water reabsorption produces a smaller volume of more concentrated urine.
5. Less water reabsorption produces a larger volume of more dilute urine.

The brain detects low water content

1. Osmoregulation keeps the water and ion content of the body within narrow limits.
2. The hypothalamus detects when the blood contains too little water and is therefore too concentrated.
3. The pituitary gland responds by releasing more ADH into the blood.
4. More ADH makes the collecting duct more permeable to water.
5. More water returns to the blood by osmosis, so less water remains in the urine.
6. The result is a small volume of concentrated urine and restoration of the blood water content.

High water content lowers ADH

1. When the blood contains too much water the hypothalamus detects that it is too dilute.
2. The pituitary releases less ADH so the collecting duct becomes less permeable to water.
3. Less water returns to the blood and more water remains in the filtrate.
4. The result is a large volume of dilute urine and a fall in the water content of the blood towards normal.

Negative feedback reverses each change

1. Too little water causes more ADH and more water reabsorption, which reverses the original decrease.
2. Too much water causes less ADH and less water reabsorption, which reverses the original increase.
3. As normal water content returns the corrective change in ADH release becomes smaller.

Urine volume and concentration move oppositely

1. A small urine volume is usually more concentrated because more water has returned to the blood.
2. A large urine volume is usually more dilute because less water has returned to the blood.
3. Concentrated urine contains less water per quantity of dissolved waste, not more urea produced by the liver.

Every direction must stay consistent

1. For low blood water write more ADH, greater permeability, more reabsorption, smaller urine volume and more concentrated urine.
2. For high blood water write less ADH, lower permeability, less reabsorption, larger urine volume and more dilute urine.

7.4.7 Treatments for kidney failure

Kidney failure disrupts blood composition

1. Kidney failure occurs when the kidneys cannot filter the blood adequately or regulate its water and ion content.
2. Urea accumulates because it is not removed from the blood quickly enough.
3. Water and ion balance changes because selective reabsorption and urine formation no longer work effectively.
4. Untreated failure is dangerous because toxic waste and abnormal fluid balance disrupt cell and organ function.
5. The two main treatments are dialysis and a kidney transplant from an organ donor.

Dialysis removes wastes by diffusion

1. During dialysis blood is taken from the patient and passed through a machine before being returned.
2. A partially permeable membrane separates the blood from dialysis fluid.
3. The dialysis fluid contains no urea so urea diffuses from a higher concentration in the blood to a lower concentration in the fluid.
4. The dialysis fluid contains a normal glucose concentration so there is no net loss of glucose from healthy blood.
5. Its ion concentrations are controlled so excess ions can diffuse out while useful concentrations are maintained.
6. Fresh dialysis fluid flows continuously to maintain steep concentration gradients for diffusion.
7. The cleaned blood returns to the patient with less urea and a safer balance of dissolved substances.

Dialysis has repeated costs

1. Advantages include avoiding donor shortage and providing treatment without placing a donor organ in the patient.
2. Regular sessions are required because dialysis works only while the blood is connected to the machine.
3. Time and travel can restrict work, school, diet, fluid intake and daily life.
4. Risks include infection, blood clotting and sudden changes in blood pressure.
5. Dialysis can bridge the wait by keeping a patient alive until a suitable donor kidney becomes available.

A transplant replaces kidney function

1. A kidney transplant places a healthy kidney from a living or deceased donor into the patient.
2. A successful kidney filters the blood continuously, so regular dialysis is no longer needed.
3. Benefits can include fewer dietary restrictions, more freedom and lower long-term treatment costs.
4. Limits include donor shortage, a major operation and the possibility that the transplanted kidney will fail.

Tissue matching reduces rejection

1. Tissue rejection occurs when the immune system recognises antigens on the donor kidney as foreign and attacks the organ.
2. Tissue matching selects a donor whose antigens are as similar as possible to those of the recipient.
3. Immunosuppressant drugs reduce the immune response and lower the chance of rejection.
4. Reduced immunity increases susceptibility to infectious disease and makes long-term monitoring necessary.

Treatment choice depends on evidence

1. Dialysis may be preferred when no suitable donor is available or transplant surgery would carry a high risk.
2. A transplant may be preferred when a suitable kidney is available and the patient can tolerate surgery and immunosuppressant treatment.
3. A justified decision weighs effectiveness, availability, risks, lifestyle effects and long-term consequences for that patient.

7.4.8 Production of urea in the liver

The liver makes urea

1. Urea is a nitrogen-containing waste substance produced in the liver from the breakdown of excess amino acids.
2. The liver is the production organ while the kidneys remove urea from the blood.
3. Urea enters the blood after it is produced and travels dissolved in the plasma.
4. The kidneys filter urea into the nephron so it can leave the body in urine.
5. The route can be written as $excess\; amino\; acids\underrightarrow{liver}urea\underrightarrow{blood}kidneys\to urine$.

Excess amino acids cannot be stored

1. An amino acid is a small molecule used to build proteins.
2. Dietary proteins are digested into amino acids that are absorbed into the blood.
3. Cells use amino acids to make the proteins required for growth, repair, enzymes and other cell structures.
4. Excess amino acids cannot be stored as amino acids, so the liver breaks them down.
5. Nitrogen-containing waste from this breakdown is converted into urea for transport to the kidneys.

The liver and kidneys have different roles

1. The liver produces urea from excess amino acids.
2. The blood transports urea dissolved in plasma from the liver to the kidneys.
3. The kidneys remove urea from the blood and include it in urine.
4. The urinary system then carries, stores and releases the urine.