Homeostasis 14.1

• Organisms require control systems to maintain relatively constant internal conditions for efficient function; this is known as homeostasis
• Homeostasis is critical to maintain optimal conditions for enzyme function and cell function
• Sensory cells detect conditions inside and outside the body
• Physiological factors controlled by homeostasis in mammals include:
  • Core body temperature and blood pH levels
  • Concentrations of glucose, respiratory gases, and water potential in blood
  • Metabolic waste concentration

Principles of Homeostasis

• Most homeostatic mechanisms use negative feedback to maintain balance for physiological factors like blood glucose
• Negative feedback loops include a receptor to detect a stimulus
• A coordination system (nervous and endocrine) transfers information
• Effectors like muscles or glands carry out a response
• These loops continuously monitor the stimulus
• The body decreases a factor if it increases, and vice versa

Coordination Via the Nervous and Endocrine Systems

• Mammals use nervous and endocrine systems to transfer information
• The nervous system transmits electrical impulses via neurons
• The endocrine system transmits chemical messengers called hormones in the blood

Production of Urea

• Metabolic reactions create waste products that are removed through excretion
• Humans form much greater quantities of carbon dioxide and urea than other excretory products
• Urea is produced in the liver from excess amino acids
• Amino acids provide energy when proteins exceed storage capacity
• Deamination removes the amino acid's amino group
• This process creates ammonia (NH3)
  • This is a harmful, soluble byproduct that dissolves in the blood to form alkaline ammonium hydroxide altering pH
  • Impacting reactions needed for cell metabolism and interfering with cell signalling processes
  • Ammonia is converted to urea, which is less soluble and toxic, by combining ammonia and carbon dioxide
• The remaining keto acid then enters the Krebs cycle to be respired, converted to glucose, or converted to glycogen/fat for storage

Structure of the Human Kidney

• Humans have two kidneys which regulate blood water content, which is vital for maintaining blood pressure; this is osmoregulation
• The kidneys also excrete toxic waste and excess substances; this is excretion

Kidney Components and Functions:

• Renal artery carries oxygenated blood containing urea and salts to the kidneys
• Renal vein carries deoxygenated blood with urea and excess salts removed away from the kidneys
• The kidney regulates water content of blood and filters it
• Ureter carries urine from the kidneys to the bladder
• Bladder stores urine temporarily
• Urethra releases urine

Kidney Structure

• The kidney is covered by the fibrous capsule
• Beneath the fibrous capsule, there are three main areas
  • Cortex: contains glomerulus, Bowman’s capsule, proximal/distal convoluted tubules of nephrons
  • Medulla: contains loop of Henle and collecting duct of nephrons
  • Renal pelvis: where the ureter joins the kidney

Nephron Structure

• The kidney contains thousands of tiny tubes called nephrons, responsible for the formation of urine

Blood Vessels of the Nephron

• The Bowman's capsule of each nephron contains the glomerulus
• Blood is supplied to each glomerulus by an afferent arteriole from the renal artery
• Efferent arterioles carry blood away, rejoining into capillaries alongside the nephron
• Blood then flows into the renal vein

Formation of Urine

• The nephron is the functional unit responsible for the formation of urine
• Urine formation occurs in two stages: ultrafiltration and selective reabsorption

Two Stages of Urine Production in the Kidneys

• Ultrafiltration occurs in the Bowman's capsule to filter small molecules from the blood into the capsule to form glomerular filtrate
  • These molecules include amino acids, water, glucose, urea, and inorganic ions
• Selective reabsorption in the proximal convoluted tubule reclaims useful molecules from the filtrate and returns them to the blood

Ultrafiltration

• After reabsorption, the remaining filtrate is now urine and leaves the nephron
• It then flows out of the kidneys into the ureters and into the bladder to be temporarily stored
• Arterioles branch off the renal artery, leading to a knot of capillaries inside the Bowman's capsule (glomerulus)
• Narrowing of capillaries increases blood pressure, forcing smaller molecules out to form filtrate
• Two cell layers and a basement membrane separates glomerular capillaries from the Bowman’s capsule’s lumen:
  • Endothelium of the capillary: perforated by tiny membrane-lined circular holes
  • Basement membrane: made of collagen and glycoproteins
  • Epithelium of the Bowman’s Capsule: epithelial cells have finger-like projections (podocytes)
• Holes and gaps enable dissolved substances in blood plasma to pass into the Bowman's capsule
• The glomerular filtrate includes: amino acids, water, glucose, urea, and inorganic ions
• Red blood cells, white blood cells, and platelets are too large to pass through the holes and remain in the blood
• The basement membrane stops large protein molecules from getting through

How Ultrafiltration Occurs

• Ultrafiltration follows differences in water potential, the afferent arteriole is wider in comparison to the efferent arteriole making the blood pressure higher, along with solute concentrations between plasma and filtrate
• As the afferent arteriole is wider than the efferent arteriole, blood pressure is relatively high
• This raises the water potential in the glomerular capillaries above the water potential of the filtrate in the Bowman's capsule
• This results in water moving into the Bowman's capsule
• Blood plasma’s basement membrane stops plasma protein passage
• Solute concentration is higher, decreasing water potential in the glomerular capillaries
• Overall, the pressure gradient is greater than the solute gradient
• Therefore. overall water moves down the water potential gradient into the blood

Selective Reabsorption

• Substances in the glomerular filtrate are reabsorbed into the blood along the nephron
• Selective reabsorption only reabsorbs the substances needed
• Glucose reabsorption occurs in the proximal convoluted tubule
• Its lining is composed of a single layer of epithelial cells adapted for reabsorption
  • Microvilli
  • Co-transporter proteins
  • High numbers of mitochondria
  • Tightly packed cells
• Water and salts are reabsorbed via the Loop of Henle and collecting duct

Adaptations for Selective Reabsorption

• Many microvilli on the luminal membrane, facilitate surface area for reabsorption
• The many co-transporter proteins in the luminal membrane transport specific solutes
• The many mitochondria in the cells provide energy for sodium-potassium pumps on basal membranes
• Tightly packed cells prevent fluid from passing between the cells

Selective Reabsorption of Solutes

• Blood capillaries run close to the proximal convoluted tubule
• Blood has little plasma and has lost much of its water, inorganic ions, and small solutes
• Sodium-potassium pumps in the basal membranes move sodium into the blood, lowering sodium concentration inside epithelial cells
• Sodium diffuses down the concentration gradient using co-transporter proteins
• These co-transporter proteins transport a sodium ion and another solute, like glucose or an amino acid
• Once inside the epithelial cells, solutes diffuse down their concentration gradients, using transport proteins to pass into capillaries

Molecules Reabsorbed During Selective Reabsorption

• All glucose in the glomerular filtrate is reabsorbed, so no glucose is present in urine
• Amino acids, vitamins, and inorganic ions are reabsorbed
• Movement of all solutes into capillaries increases water potential, decreasing water potential of the blood
• This creates a water potential gradient that causes water to move in by osmosis
• A significant amount of urea is reabsorbed
• The high concentration of urea in the filtrate causes urea to diffuse back into the blood

Reabsorption of Water and Salts

• Necessary salts are reabsorbed back into the blood by diffusion as the filtrate drips through the Loop of Henle
• Water follows the reabsorbed salts by osmosis
• Water is also reabsorbed from the collecting duct based on the body's needs

Osmoregulation

• The control of body fluids’ water potential
• It's an important part of homeostasis
• Specialised sensory neurones (osmoreceptors) monitor blood water potential in the hypothalamus
• If osmoreceptors detect a decreased blood water potential, nerve impulses are sent to the posterior pituitary gland
• The nerve impulses trigger the gland to release antidiuretic hormone (ADH)
• ADH is released in the blood and causes the kidneys to reabsorb more water to reduce water loss

ADH Pathway

• Water reabsorption occurs in the nephron by osmosis
• This reabsorption happens as filtrate passes through the collecting ducts ADH causes the luminal membranes of collecting duct cells to become more permeable to water, increasing aquaporins
• These cells contain vesicles with aquaporins
  • ADH molecules bind to receptor proteins and cause phosphorylation of aquaporin
  • This activates aquaporins, which causes vesicles to fuse membranes and increases its water permeability
  • Water moves out of the collecting duct through aquaporins because of this and enters the tissue

In the Absence of ADH

• The filtrate moving through the collecting duct concentrates the water
• This concentrated urine flows from the kidneys, through the ureters, and into the bladder
• Osmoreceptors in the hypothalamus are not stimulated instead
• The individual will not release ADH, making the collecting duct cells permeable. The filtrate will go through the collecting duct, resulting in a very dilute substance that produces a large volume of urine

The Control of Blood Glucose

• If blood glucose concentration decreases cells will lack required glucose for respiration to function normally
• If it increases above a certain level this disrupts cells, potentially causing major problems
• Blood glucose is controlled by two hormones secreted by endocrine tissue in the pancreas
• The islets of Langerhans contain two cell types:
  • α cells secrete glucagon
  • β cells secrete insulin
• These cells act as receptors to initiate responses
  • The principles of cell signaling can be demonstrated via glucagon regulation of blood glucose concentration

Decrease in Blood Glucose Concentration

• A decrease in blood glucose concentration is detected by the alpha and beta cells in the pancreas
  • The alpha cells respond by secreting glucagon
  • The beta cells respond by stopping the secretion of insulin
• Decreasing insulin reduces glucose use by the liver and muscles
• Glucagon binds to receptors on liver cell membranes, causing a conformational change to activate a G protein
• The G protein then activates the enzyme adenylyl cyclase
• Active adenylyl cyclase converts ATP to cyclic AMP (cAMP), the second messenger
• CAMP binds to protein kinase A activating them
  • The active protein kinase A enzymes activate phosphorylase kinase enzymes by adding phosphate groups
  • Active phosphorylase kinase enzymes then activate glycogen phosphorylase enzymes
  • Active glycogen phosphorylase enzymes catalyse the breakdown of glycogen to glucose in glycogenolysis

Increase in Blood Glucose Concentration

• Increase detected by the beta cells that produces a change in the membrane potential when glucose molecules enter through facilitated diffusion
• Potassium channels close causing voltage gated calcium to open
• In response, the cells secrete insulin which stimulates uptake of glucose within muscle and fat cells
• Stimulating the target cells of the glucose transporter
• Insulin is used to increase the rate of facilitated diffusion which has increased Glut proteins

Insulin Causes Activation of Two Enzymes

• Glucokinase phosphorylates glucose, trapping it inside cells
• Glycogen synthase converts glucose into glycogen in glycogenesis

Negative Feedback Control of Blood Glucose

• The blood glucose concentration levels are regulated by feedback control mechanisms
• Receptors detect whether a level is too low or too high, sending messages through hormonal or nervous systems to the effectors
• Effectors bringing level back to normal
• Alpha and beta act as receptors while the hormones(glucagon and insulin) release
• Liver cells along with the effector respond to glucagon

Test Strips & Biosensors

• People with diabetes cannot regulate blood glucose concentration to stay in safe limits
• Elevated glucose levels in urine indicate diabetes
• If concentrations increase higher than the renal threshold cannot all be reabsorbed leading these to be left in the urine
• The presence and concentration can be tested by test strips, while the urine is collected in the bladder
• Two enzymes immobilised on a small pad at one end of the urine strip are the glucose oxidase and peroxidase
• If glucose is present, glucose oxidase will catalyse a reaction where its oxidised to form gluconic acid and hydrogen peroxide
• Peroxidase then catalyses a reaction between hydrogen peroxide and a colourless chemical in the pad to form a brown compound and water
• The colour of the pad when compared to the colour chart illustrates different concentrations (higher the colour of glucose, darker the colour)

Measuring Blood Glucose Concentration

• A biosensor, which uses glucose oxidase immobilised on a recognition layer
• A partially permeable membrane covers the recognition layer and allows small molecules from the blood to reach enzyme