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C3 - Homeostasis and the Kidney (Kidney Failure and its Treatment (Effects…
C3 - Homeostasis and the Kidney
Homeostasis
Homeostasis
- the mechanisms by which the body maintains a constant internal environment. E.g. body temperature, pH and water potential fluctuate around a set point by negative feedback
Why is it important?
Keeps the concentration of body fluids constant
Protects against changes in the external environment
Ensures reactions continue at a constant rate
Negative feedback
- a change in a system produces a second change, which reverses the first change. E.g. Insulin/glucagon is secreted to keep glucose concentration constant
Homeostasis operates by negative feedback
A
set point
is the norm
A
receptor
detects the level of the factor and its deviation from the set point and sends instructions to a co-ordinator
The
co-ordinator
tells effectors to make changes to return it to the set point and is monitored by the receptors
Positive feedback
- An effector increases a change, moving it further away from the set point. E.g. oxytocin stimulates uterus contractions, which stimulates the production of more oxytocin
Excretion
The removal of body waste e.g. carbon dioxide made in respiration is removed by expiring air from the lungs
Excretion of water
From respiration
Secreted e.g. in tears/saliva
Egested in faeces
Kidney
Functions:
Excretion
Osmoregulation - the control of the water potential of the body's fluids by regulating water content
Producing urea
Excess amino acids from protein digestion are deaminated (removed an amine group) and turned to urea in the liver.
Structure of the kidney
Made up of nephrons - 30mm long for large SA
Receives blood from renal artery
Returns blood to renal vein
Blood is filtered at the Bowman's capsule in the cortex (outer-layer)
The medulla contains loops of Henle and the collecting ducts that carry urine to the pelvis
The pelvis empties urine into the ureter
The ureter carries urine to the bladder
Filtration
An afferent arteriole from the renal artery brings blood to the nephron
Glomerulus - a network of capillaries surrounded by the Bowman's capsule filter the blood
An efferent arteriole take the blood to a capillary network around the proximal and distal convoluted tubules, and the vasa recta - capillary network surrounding the loop of Henle
Ultrafiltration
Filtration under high pressure
Ultrafiltration in the Bowman's Capsule
Blood pressure in the glomerulus capillaries forces solutes and water through the fenestrae, basement membrane and filtration slits, and into the Bowman's space
Blood from the afferent arteriole has a high pressure
because:
Contraction from the heart increases arterial blood pressure
The afferent arteriole has a wider diameter than the efferent arteriole
The blood in the glomerulus is separated from the Bowman's space by three layers:
Capillary wall -
made of a layer of endothelium cells with pores called fenestrae
The
basement membrane
, made of collagen and glycoproteins. It's a filter and a selective barrier between the blood and the nephron
The
wall of the Bowman's capsule
- made of squamous epithelial cells.
Pedicels from each podocyte wrap around a capillary, pulling it closer to the basement membrane, shortening the diffusion distance. The gaps between pedicels are filtration slits
Glomerular filtrate
It contains water, glucose, salts, urea and amino acids.
Larger molecules over 68,000 RMM e.g. blood cells, platelets, antibodies stay in the blood
It's like plasma but without large proteins
It has a low water potential from the glomerulus to the efferent arteriole because most of the water's been lost and there's a high protein concentration
Glomerular filtration rate
It's the rate at which fluid passes from the blood in the glomerular capillaries into the Bowman's capsule
Determined by the difference in water potential between the glomerulus and the Bowman's capsule i.e. the balance of hydrostatic pressures and solute potentials
Adult kidneys get 1.1dm3 min-1 and produce 125cm3 min-1 glomerular filtrate
Blood vol entering kidneys = 1100cm3
Vol of filtrate produced per min = 125cm3
Blood vol leaving glomerulus per min = 1100-125=975cm3
% filtered = 125/1100 x 100 = 11.4%
Selective reabsorption
The uptake of specific molecules and ions from the glomerular filtrate in the nephron back into the bloodstream
Proximal Convoluted Tubule (PCT)
Longest and widest part of the nephron
Carries the filtrate away from the Bowman's capsule
Blood in the capillaries around it reabsorbs all the glucose and amino acids, some of the urea, and most of the water and sodium and chloride ions
PCT Structure
Large SA because it's long
Cuboidal epithelial cells in its walls. SA is increased with microvilli ad basal channels
Contains many mitochondria providing ATP for active transport
Close to capillaries
Tight junctions between the cuboidal epithelial cells - multi-protein complexes that attach a cell to its neighbours (like a stitch). They prevent molecules from diffusing between cells or from the cell back into the glomerular filtrate
Selective reabsorption in the PCT
70% of salts are reabsorbed by active transport
All the glucose and amino acids are reabsorbed to the blood by co-transport with sodium ions.
90% of water is reabsorbed by osmosis, as reabsorbed ions lower the water potential in the blood
50% of the urea and small proteins are reabsorbed by diffusion, resulting in a high protein concentration and a steep concentration gradient
Co-transport of glucose and sodium ions
They attach to a carrier protein in the cuboidal epithelium cell membrane and are released into the cell. They then diffuse through the cell to the opposite membrane and diffuses into the capillary. This provides the energy for secondary active transport of glucose into the blood
Secondary active transport
The coupling of diffusion, e.g. of sodium ions, down an electrochemical gradient providing energy for active transport, e.g. of glucose up its concentration gradient
Glucose threshold
If glucose in the filtrate is too high, it will pass through into the loop of Henle and be lost in the urine. This may happen if:
The pancreas secretes too little insulin (type 1 diabetes)
Damaged insulin receptors slowing the response of liver cells to insulin (type 2 diabetes)
Water reabsorption
PCT and the Loop of Henle always reabsorb the same volume of water but the distal convoluted tubule (DCT) and collecting duct vary
Process of water reabsorption
Glomerular filtrate passes through the PCT and enters the descending limb of the loop of Henle under high pressure.
It moves down a hairpin bend and up into the ascending limb and through the DCT into the collecting duct
Descending limb
Walls are permeable to water and slightly permeable to sodium and chloride ions
Water diffuses out by osmosis into the tissue fluid of the medulla and into the vasa recta around the loop of Henle
Some sodium and chloride ions diffuses into the descending limb
The filtrate has a lower WP and more ions at the apex so it's hypertonic
Ascending limb
Walls are impermeable to water
Actively transport sodium and chloride ions out of the filtrate in the tubule into the tissue fluid in the medulla
Longer loop = more ions exported
Less salts so higher WP and therefore hypotonic at the top
Collecting duct
High WP and hypotonic at the top
Water leaves the collecting duct by osmosis into the vasa recta
At the bottom, the filtrate has a lower WP so it's hypertonic to the blood, and is urine.
Counter-current multiplier
Filtrate flows in opposite directions in the descending and ascending limb of the Loop of Henle, enabling maximum solute concentration at the apex of the loop, which is higher than in the medulla. This means that more water is in the medulla and the urine at the end of the collecting duct is more concentrated
Osmoregulation
Osmoregulation
Keeps blood isotonic so the water potential is the same in cells
Maintains concentrations of enzymes and metabolites so that reactions within cells occur at a constant and appropriate rate.
How does osmoregulation operate by negative feedback?
Receptor: Osmoreceptors of hypothalamus monitor blood solute potential
Co-ordinator: Hypothalamus signals the effector
Effector: Posterior pituitary gland releases ADH
ADH increases the permeability of the cells lining the walls of the distal convoluted tubule and collecting duct, increasing water reabsorption and produces a small volume of concentrated urine.
Increasing/limiting the release of ADH returns the system to normal
Dehydration
Caused by reduced water intake, sweating and having too much salt
Too little water in blood = Hypertonic = lower water potential
Less water for reactions such as hydrolysis of glycogen
Less moisture at exchange surfaces e.g. alveoli
Need water for thermoregulation - higher body temperature = enzymes can denature
Less water acting as a solvent - can't dissolve glucose, amino acids, Na+, K+, etc.
Overhydration
Caused by drinking too much water
Blood becomes hypotonic = higher water potential than cells so water moves into cells and they burst
Aquaporins
Intrinsic membrane proteins with a pore through which water molecules move. Found in the walls of the distal convoluted tubule and collecting duct
Aquaporins allow water to enter the cell
ADH binds to membrane receptors
Adenyl cyclase catalyses the production of cyclic AMP, the second messenger
Vesicles with aquaporins in the cytoplasm move and fuse with the cell membrane
Aquaporins are incorporated into the membrane
Water molecules move through their pores into the cell, down a water potential gradient
When intracellular cyclic AMP levels fall, the aquaporins are removed from the cell membranes and accumulate again in vesicles
Kidney Failure and its Treatment
Effects of kidney failure
Urea isn't removed so its concentration increases to toxic levels
Excess water isn't removed so body fluid volume increases and are diluted, compromising metabolic reactions
Causes of kidney failure
Diabetes: High glucose concentration in the plasma makes glomeruli lose protein, especially albumin in the filtrate. The proteins link together, causing glomerulosclerosis and scarring
High blood pressure: damage to glomerulus capillaries prevents ultrafiltration
Auto-immune disease: the body makes antibodies against its own tissues
Infection
Crushing injuries e.g. car accident
Treatments to regulate solute concentration
Reduce protein intake to reduce urea formation and ions e.g. calcium and potassium
Drugs to reduce blood pressure e.g. ACE inhibitors, ARBs, calcium channel blockers, and beta blockers
Treat potassium concentration with glucose and insulin and intravenous calcium to stabilise heart muscle membranes. If left untreated, heart arrhythmias can develop
Treat calcium concentration with bisphosphonates, which decreases the activity of osteoclasts (cells that break down bones), and calcium accumulates in bone and less in the blood.
Dialysis: unclean blood and dialysis fluid are separated by a partially permeable membrane. Dialysis fluid has the same water potential as blood but has a low ion concentration and no urea. So, inorganic ions, water and urea diffuse out of the blood. Dialysis fluid has glucose at a normal concentration so none diffuses out of the blood.
A kidney transplant can be offered to patients with end-stage renal disease
How do drugs reduce blood pressure?
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) reduce the effect of angiotensin, a hormone that constricts blood vessels, increasing the pressure of the blood within
Calcium channel blockers dilute blood vessels and reduce blood pressure
Beta blockers reduce the effect of adrenaline e.g. blood pressure increases as the heart rate increases
Haemodialysis
Uses a dialysis machine
Blood is taken from an artery and run through thousands of selectively permeable dialysis tubing made of long, narrow fibres
Dialysis fluid surrounds the fibres
Pores on the tubing let molecules in solution out into the dialysis fluid but not large proteins, blood cells and platelets
Blood and dialysis fluid run in opposite directions to each other (counter-current multiplier), which enhances diffusion out of the blood
Blood is returned to a vein
Heparin thins blood and prevents clotting
A sensor in the dialysis fluid detects haemoglobin that would diffuse through if red blood cells were damaged
Patients use it for several hours every day
Continuous ambulatory peritoneal dialysis (CAPD)
Can carry out normal activities
The patient drains 1-3dm3 of dialysis fluid trough a catheter in the abdomen into the body cavity
Peritoneum is the membrane lining of the body cavity. It has many capillaries and acts as a dialysis membrane
Materials are removed from the blood into the dialysis fluid
After 40 minutes, the fluid is drained from the abdomen by gravity, result8ing in an empty back
Must be repeated 4 times a day
Liquid stays in the blood and potassium ions accumulate
Patients must drink very little and avoid potassium rich foods e.g. bananas and tomatoes
Requirements for kidney donation
Donors may be living or have suffered a brain stem or circulatory death
A kidney from a live donor works immediately and lasts longer
Dialysis is used while waiting for deceased donor kidneys to work
The donor and recipient must be compatible in their ABO blood group and in most of their Human Leucocyte antigens (HLA)
Higher risk donors are aged over 50 and those with high blood pressure and diabetes
Process of kidney transplant
Transplanted kidney is placed in the lower abdomen, in the groin
The renal artery and vein emerging from the kidney are attached to the iliac artery and vein
Circulation to the new kidney is then restored
When it turns pink, urine is coming from the, which takes it to the bladder
Negatives of kidney transplants
The recipient has to take immunosuppressive drugs for the rest of their lives to stop the body rejecting the kidney
Rejection may still occur, especially on patients that are susceptible to infection. This damages the kidney so long-term low-due antibiotics are used
The donor kidney may infect the recipient. Anti-virals are needed
Immunosuppressants can increase the risk of cancers e.g. skin and lymphoma
Excretion and osmoregulation in different environments
How does the environment affect the type of molecules excreted by animals?
Aquatic organisms
excrete ammonia, which is toxic but soluble in water so it's diluted
Birds, reptiles and insects
have no excess water. Amino acids are converted to uric acid for excretion. Uric acid is insoluble and non-toxic and little water is needed for its excretion, conserving water and allows the organism to live in dry areas and makes them light enough to fly
Mammals
excrete urea. It needs energy but it's less toxic than ammonia because it's diluted by tissues and body fluids so the body can briefly tolerate it
Adaptations of the Loop of Henle for water reabsorption
The longer it is, the more chance it has of pumping ions into the medulla
Ion pumps in the ascending limb increase concentration in the medulla
Low water potential in the medulla enhances water reabsorption from the descending limb and collecting duct making more concentrated urine
Types of nephron
Cortical nephrons - glomerulus in outer cortex and a short loop of Henle for dilute urine
Juxtamedullary nephron - the Bowman's capsule is close to the cortex-medulla boundary. It has a long loop of Henle deep in the medulla, making more concentrated urine, which is better for water conservation