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Unit 8 - Kidney
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Kidney Functions
homeostasis--maintains constancy of the aqueous internal environment by:
- regulation of fluid volume (water)
- regulation of inorganic ions (i.e. Ca++, Na+, K+) and organic compounds such as glucose
- elimination of metabolic waste materials (i.e. urea, lactate) produced elsewhere in the body and of foreign materials, through formation of urine
- regulation of pH (acid-base) balance
- activation of vitamin D which regulates Ca++
- production of renin which regulates blood pressure
- What the kidney KEEPS IN is as important as what it excretes!
- About 20% of the blood pumped by the heart goes directly to the kidneys and then back to the heart through the veinous circulation. This insures that the blood is continuously exposed to the functions carried out in the kidney.
- The entire blood volume is filtered through the kidneys about 65 times per day--about once every 20 minutes!
The Nephron - The Basic Unit of the Kidney
- Each kidney has about one-million nephrons
- Parts of the nephron are specialized for different functions
- In humans, 20% of nephrons are these "deep" type, called juxtamedullary nephhrons, and the rest are the shallower cortical nephrons.
- Animals that need more concentrated urine due to their environment have a higher proportion of juxtamedullary nephrons.
- The desert rat does not drink water and has remarkably concentrated urine that immediately crystallizes on contact with air.
Initial Filtration in the Glomerulus
The glomerulous is the first site of filtration in the nephron.
- Water, ions and small molecules leave the blood and enter the proximal tubule of the nephron via Bowman's capsule--eventually to be reabsorbed or excreted.
- 20% of the fluid that enters the glomerulus is filtered out of the blood and into Bowman's capsule. Proteins and other large molecules are unable to leave the capillary, even though nephron capillaries are more 'leaky' than those elsewhere in the body.
- The rest is dealt with by other parts of the nephron.
- Important componants that leave the blood and enter Bowman's capsule are water, ions, amino acids and glucose.
The nephron tries to maintain constant flow in the face of changing blood pressure.
- This is important because it is simply blood pressure that forces molecules out of the arteriole. There is no active process going on here that transports anything.
Blood pressure can also be sensed by stretch receptors on the afferent arterioles.
An important point is that the nephron self-regulates the flow rate through the glomerulus (the GFR) by feedback mechanisms that can change the rate of flow into the glomerulus.
- The macula densa cells are one part of the justaglomerular apparatus responsible for tuboulo-glomerular feedback - sensing the flow (by NaCl concentration), and then signalling to the glomerulus (possibly via angiotensin ll) to reduce GFR (glomerular filtration rate) by causing contraction of the smooth muscle around the afferent arteriole.
- Note that the output end of the Loop of Henle is being sensed as it passes back over the juxtaglomerular apparatus.
The granular cells secrete renin, which controls blood pressure, as described further later in this presentation.
- This secretion is increased by a fall in [Na+], prostaglandins, sympathetic nerve activity, circulating catecholamines and a fall in blood pressure.
- Renin secretion is decreased by a rise in [Cl-], angiotensin ll, ADH (antidiurectic hormone) and increased blood pressure.
The mesangial cells are phagocytic and remove macromolecules that escape from the capillaries. They can contract and help modify the surface area of the capillaries available for filtration.
The proximal tubule is the first site where molecules are actively reabsorbed--reclaimed--from the tublue so that they do not get excreted. Various mechanism control these processes.
The medulla has a constantly maintained, vertical osmotic gradient that is fundamental in concentrating urine in the collecting ducts. First, the mechanism that sets up this gradient will be discussed. Then, how it concentrates urine will be discussed.
The gradient is set up by a process called countercurrent multiplication, that occurs in the long Loop of Henle. Filtrate enters the loop at 300 milliosmols/liter, the isotonic concentration in the body, and exits at 100 mosm/liter, but along the way, a process sets up the 300-to-1200 gradient in the medulla of the kidney, which is the point of the whole thing.
Differential properties of the descending and ascending limbs are key to the process.
- Key points are that the actual flow is not directly from ascending to descending limb (or vice-versa) but moves from limb-to-limb via the interstitial space of the medulla, which equilibrates its osmolarity with that inside the loop at each point.
- The descending loop is permeable to water, but not NaCl, the ascending loop is permeable to NaCl but not to water.
- NaCl is actively pumped from the ascending limb. The pump is only strong enough to set up a gradient of 200 mosm/liter.
A Web site at NYU Medical School presents a very clear and simplified model of how this works. (Be sure to go to it at this point.)
So, how is the concentration of the urine in the collecting tubule controlled?
A 9-amino acid hormone called antidiuretic hormone (ADH, also known as vasopressin) controls the number of aquaporin channels (side view and end view above) in the collecting tubule. These channels let water cross the collecting tubule wall. Their turnover is rapid. In some situations almost none are present and when concentrated urine is called for many are present.
The distal tubule is also important as another site where active transport of Na+ and K+ readsorbtion, and of H+ transport and thus pH regulation.
An interesting way to see the integration of homeostatic functions that involve the kidney is to examine what happens when blood pressure drops and a variety of related processes work to restore it.
download a PDF version of this figure