1. Substitute teacher: Omar Murray Teacher: Mrs.Haughton
Excretion
Substitute teacher: Omar Murray
Teacher: Mrs.Haughton

2. Objectives
Outline the function of the nephron in filtering blood. Mention:
Ultra filtration in the glomerulus
Factors affecting glomerulus filtrate
Selective reabsorption in the proximal convoluted tubule
Description of the regions of the Loop of Henle and functions
Selective reabsorption in the distal convoluted tubule.
Urine collection in the collection duct.

3. The human kidney
The basic unit of structure and function of the kidney is the nephron and its associated blood supply. Each kidney, in a human, contains an estimated 1 million nephrons each having an approximate length of 3cm. The total length of tubules in each kidney is about 120km. This offers an enormous surface area for the exchange of materials.

4. Each nephron is composed of six regions, each having its own particular structure and function:
Renal corpuscle, composed of renal capsule ( bowman’s capsule) and glomerulus;
Proximal convoluted tubule;
Descending limb of the loop of Henle;
Ascending limb of the loop of Henle;
Distal convoluted tubule;
Collecting duct.

6. Ultrafiltration
The first step in the formation of urine is ultrafiltration of the blood. This takes place in the bowman’s capsule. Ultrafiltration is filtration under pressure. The pressure comes from the blood pressure and is know as hydrostatic pressure, or pumping pressure. Blood enters the glomerulus at high pressure direct from the heart via the dorsal aorta, renal artery and finally an arteriole.

7. Glomerulus
The glomerulus is a knot of capillaries in the renal capsule. The diameter of the capillaries in the glomerulus is less than that of the arterioles, so as the blood enters the narrow capillaries pressure rises. Water and small solute molecules are squeezed out of the capillaries through the epithelium of the renal capsule and into the interior capsule. Large molecules like proteins, as well as red blood cells and platelets , are left behind in the blood.

9. Filtration takes place through three layer:
Endothelium of the blood capillary- this is very thin and is perforated with thousands of pores of about 10nm in diameter. They occupy up to 30% of the area of the wall. The pores are not a barrier to plasma proteins because they are too large
Basement membrane of the blood capillaries- all epithelial cells rest on a basement membrane. It consist of a meshwork of fibers, including collagen fibers. Water and small solute molecules can pass through spaces between the fibers. Red blood cells and platelets are too large. Protein molecules are repelled by negative charges on the fibers.

10. Epithelium of the renal capsule- this is made of cells which are highly modified for filtration, called podocytes. Each cells has many foot-like extensions projecting from neighboring cells . They fit together loosely, leaving slits called slit pores or filtration slits about 25nm wide. The filtered fluid can pass through these slits.

11. Glomerular filtrate
About 20% of the plasma is filtered into the capsule. Of the 3 layers, the basement membrane is the main filtration barrier. The filtered fluid in the capsule is called glomerular filtrate. It has a chemical composition similar to that of blood plasma. It also contains glucose, amino acids, vitamins, ions, nitrogenous waste, some hormones and water. Blood passing from the glomerulus has a lower water potential due to the increase concentration of proteins and a reduced hydrostatic pressure.

12. Factors affecting glomerular filtrate (GF)
Hydrostatic pressure
Solute potentials
Blood pressure(higher the blood pressure the higher the filtrate rate.)
Vasodilatation(decreasing resistance to the flow of blood to the glomerulus thereby increasing filtrate rate)
Vasoconstriction(increase resistance in the efferent arteriole slows rate blood exit glomerulus thereby more blood is filtered)

13. Hydrostatic pressure
The filtration pressure forcing fluid out of the glomerulus depends not only on the hydrostatic pressure of the blood, but also on the pressure of the glomerular filtrate. If this equaled the hydrostatic pressure of the blood they would cancel each other out(plasma would not enter the nephron). In fact, the hydrostatic pressure of the glomerular filtrate is much less than that of the blood, although not zero.

14. Solute potential
Similar to the hydrostatic pressure, the solute potential on either side of the filtration barrier will affect the fluid flow. As you know water tends to move from a less concentrated solution to a more concentrated solution. As the blood flows from the afferent arteriole to the efferent arteriole through the glomerulus it loses water and other substances, but proteins remain in the blood increasing the concentration by 20% as a result of the water lose. This makes the solute potential, of the blood more negative and tends to decrease (GFR) . The greater the water potential of the blood compared with the GF, the greater the filtration pressure and the GFR.

15. Selective reabsorption in the proximal convoluted tubule
The proximal convoluted tubule cells are adapted for reabsorption as followed:
Large surface area due to microvilli and basal channels;
Numerous mitochondria;
Closeness of blood capillaries

16. Over 80% of the glomerular filtrate is reabsorbed here, including all the glucose, amino acids, vitamins, hormones and about 80% of the sodium chloride and water. The mechanism of reabsorption is as follows
Glucose, amino acids, and ions diffuse into the cells of the proximal convoluted tubule from the filtrate and are actively transported out of the cells into the spaces between them and the basal channels. This is done by carrier proteins in the cells surface membranes.

17. Once in these spaces and channels they enter the extremely permeable blood capillaries by diffusion and are carried away from the nephron.
The constant removal of these substances from the proximal convoluted tubule cells creates a diffusion gradient between the filtrate in the proximal tubule and the cells, down which further substances pass. Once inside the cells they are actively transported into the spaces and channels and the cycle continues.

18. The loop of Henle
The function of the loop of Henle is to conserve water. The longer the loop of Henle, the more concentrated the urine that can be produced. The urine of a human can be 4 to 5 times as concentrated as the blood. The loop of Henle , together with the capillaries of the vasa recta and collecting duct, creates and maintains an osmotic gradient in the medulla which extends from cortex to the tips of the pyramids.

19. ` The loop of Henle has three distinct regions, each with its own function.
The descending limb which has thin walls
The thin ascending limb this is the lower half of the ascending limb and has thin walls like the descending limb;
The thick ascending limb this is the upper half of the ascending limb and has thick walls.

21. The descending limb is highly permeable to water and permeable to most solutes. Its function is to allow substances to diffuse easily through its walls. Both parts of the ascending limb are almost totally impermeable to water. The cells in the thick part can actively reabsorb sodium, chloride, potassium and other ions from the tubule. Normally water would follow by osmosis the movement of these ions into the cells, but this cannot occur because the cells are permeable to water as stated. The fluid in the ascending limb therefor becomes very dilute by the time it reaches the distal convoluted tubule.

22. The distal convoluted tubule and collecting duct
In the last two regions of the nephron, the distal convoluted tubule and the collecting duct, fine tuning of the body fluid composition is achieved. Fine control of the precise amounts of water and salts reabsorbed is important in osmoregulation. This is one role of the distal convoluted tubule and collecting duct.

23. The cells of the distal convoluted tubule have a similar structure to those of the proximal tubule, with microvilli lining the inner surface to increase the surface area for reabsorption , and numerous mitochondria to supply energy for active transport.

24. The collecting duct carries fluid from the outer region of the medulla, next to the cortex, to the pyramids. As the fluid moves down the collecting duct, the tissue fluid in the medulla surrounding the duct gets more and more concentrated. Water therefore leaves the collecting duct by osmosis. The final concentration of the urine can be as high as the medulla, about 1200 units, although the actual amount of water lost is controlled by ADH.

25. ADH and the formation of urine
The body maintains the solute potential of the blood at an approximately steady state by balancing water uptake from the diet with water lost in evaporation, sweating, egestion and urine. The precise control of solute potential, however, is achieved primarily by the effect of a hormone called antidiuretic hormone (ADH). Diuresis is the production of large amounts of dilute urine. Antidiuresis is therefor the opposite. ADH is antidiuretic in its effects, so has the effect of making urine more concentrated. It is also know as vasopressin.

26. ADH is made in the hypothalamus and passes the short distance to the posterior pituitary gland by a process called neurosecretion. When the blood become more concentrated (solute potential more negative), as in a situation where too little water has been drunk, excessive sweating has occurred or large amounts of salt have been eaten, osmoreceptors in the hypothalamus detect a fall in blood solute potential. Osmoreceptors are special receptors which are extremely sensitive to changes in blood concentration. They set up nerve impulses which pass to the posterior pituitary gland where ADH is released.

27. In the presence of ADH, the increased number of water channels allows water to from the glomerular filtrate into the cortex and the medulla by osmosis, reducing the volume of the urine and making it more concentrated. ADH also increases the permeability of the collecting duct to urea, which diffuses out of the urine to the tissue fluid of the medulla. Here it increases the osmotic concentration, resulting in the removal of an increased volume of water from the thin descending limb.

28. The opposite occurs when there is a high intake of water
The opposite occurs when there is a high intake of water. The solute potential of the blood begins to get less negative. ADH is inhibited, the walls of the distal convoluted tubule and collecting duct becomes impermeable to water, less water is reabsorbed as the filtrate passes through the medulla and a large volume of water of dilute urine is excreted. Failure to release sufficient ADH leads to a condition known as diabetes insipidus in which large quantities of dilute urine are produced (diuresis). The fluid lost in the urine has to be replaced by excessive drinking.