PHYSIOLOGY 03028 WEEK 8: OVERVIEW OF RENAL PHYSIOLOGY 3/6/00
Cormack, Ch. 7; Guyton and Hall, Chs. 25-31; Michael and Rovick, Units 7, 10, 11;
van Wysberghe and Cooley, Cases 22-24
W. Crone (303 FTZ, 629-7439, cronewil@hvcc.edu, http://www.hvcc.edu/academ/faculty/crone/index.html)
possible web sites: http://www.med.virginia.edu/medicine/clinical/anesth/education/blood.htm
(issues in blood, fluid, and electrolyte replacement)
http://courses.physiology.uiowa.edu/slideshows/072-150/pessin/JP-Renal%20lec%204/sld001.htm
(power point lecture on renal physiology)
INTRODUCTION TO RENAL PHYSIOLOGY:
The primary function of the kidney is to regulate the ECF by forming urine, a modified filtrate of plasma. The urine is formed by the functional unit of the kidney, the nephron.
Three main processes in forming urine:
excretion: elimination of a substance in urine
Therefore, amount of a substance excreted = filtered - reabsorbed + secreted
renal and urinary structures:
renal blood supply:
Arterial blood enters into the kidney via a renal artery, eventually, in the cortex, branching off to afferent arterioles, which deliver blood to the glomeruli, or capillary networks where blood filtration takes place. The blood that's left in the glomerulus leaves via efferent arterioles, and from them to peritubular capillaries that surround tubules (and eventually back to the renal vein).
So, this is a unique situation with sequential capillary systems:
a) the glomerulus for filtration
b) the peritubular capillaries for reabsorption (and setup of countercurrent exchange)
renal tubules:
The tubular part of a nephron consists of the following:
A collecting duct then receives fluid from several nephrons. The collecting duct passes through a medullary pyramid to a calyx.
FILTRATION:
Glomerular capillaries are fenestrated, so are quite permeable to plasma water and solutes (but do not allow cells and platelets in). This fluid is called ultrafiltrate, since it was derived from hydrostatic pressure. There is a net filtration pressure of only 10 mm Hg, but with the permeable, fenestrated glomerular capillaries and massive surface area, there is a large amount of filtrate.
REABSORPTION (especially in the PCT):
Most of the water and salt of the filtrate is reabsorbed in the PCT. The water reabsorption is osmotic, following the active extrusion of sodium chloride from the tubule into the peritubular capillaries. Otherwise, most of the other water reabsorption occurs across the wall of the collecting duct in the renal medulla, as a result of the osmotic draw of the surrounding tissue fluid, which is set up by transport processes in the loop of Henle. We produce 1-2 L/day of urine, with an obligatory water loss of 400 ml/day to excrete metabolic wastes.
The driving force of reabsorption is the active transport of Na+ from the filtrate to the peritubular blood. The simple cuboidal epithelial cells that make up the PCT walls have lots of active sodium pumps on their basal and lateral sides, setting up a gradient in the cell that favors the passage of Na+ from the lumen of the PCT to the epithelial cells and then out. This also sets up an electrical gradient, which encourages Cl- to accompany the Na+ out into the interstitial fluid.
With all of these osmotic particles leaving (and with the apical surface of the PCT epithelial cells permeable to water), water then also leaves the PCT lumen to interstitial fluids, and is eventually reabsorbed by the peritubular capillaries. This takes care of about 2/3 of the salt and water in the glomerular ultrafiltrate.
ACTIONS IN THE LOOP OF HENLE:
Ascending limb of the loop of Henle described first (since more active processes occurring here in the cells of the thick segment of the ascending loop): Na+, K+, Cl- diffuse from the filtrate in the lumen into the ascending limb cells (ratio of 1:1:2) via an electrocally neutral Na-K-2Cl cotransporter. The ascending limb cells then use their sodium pumps to get Na+ across their basolateral membranes. Cl- follows because of electrical attraction, and some K+ diffuses back into the filtrate in the lumen of the ascending limb.
The walls of the ascending limb of the loop of Henle are impermeable to water. With the salt being pumped out of it, the fluid in the tubule is hypoosmotic (100 mOsm) as it reaches the distal convoluted tubule (DCT). Deep down in the medulla, though, it can reach 1,200-1,400 mOsm, or quite hyperosmotic, so somehow that the salt being pumped out of the ascending limb of the loop of Henle is accumulating in the tissue fluid of the medulla.
In contrast to the ascending limb, the descending limb of the loop of Henle does not actively transport salt, but is permeable to water. With the surrounding interstitial fluid hyperosmotic, the water of the filtrate is drawn out of the descending limb and enters peritubular capillaries. The ascending/descending limbs of the loop of Henle are close to each other, allowing for a countercurrent mechanism, with a positive feedback mechanism. As the ascending limb extrudes more salt, the more concentrated the fluid heading down the descending limb becomes, because of the countercurrent multiplier system. For this to work:
1) the majority of the salt from the ascending limb needs to remain in the medulla
2) the water that is exiting the descending limb must be taken up by blood vessels leaving the area
These goals are accomplished by the vasa recta, or peritubular capillaries that form capillary loops around the long loops of Henle of the (juxtamedullary) nephrons. Briefly, salts and solutes like urea diffuse into blood as the blood descends to the medulla in the vasa recta, but then diffuse out of the ascending capillaries into the descending capillaries, a countercurrent exchange. With plasma proteins helping to set up an osmotic attraction, the vasa recta ultimately trap salt and urea in the interstital fluid but carry out water of the medulla.
THE DCT: MAJOR SITE OF ALDOSTERONE FUNCTION:
Aldosterone, a mineralcorticoid secreted by adrenal cortex, regulates renal absorption of Na+ and secretion of K+. Under the influence of aldosterone, K+ is secreted from peritubular blood to the later part of the DCT and cortical collecting duct. The two main stimulations of aldosterone are:
1) renin-angiotensin system
2) potassium ion concentrations
The mechanism of aldosterone function is not fully known, but seems to require transcription/translation to form new sodium pumps and a luminal channel to enhance sodium influx from the lumen of the tubule.1
THE COLLECTING DUCT: MAJOR SITE OF ADH FUNCTION:
After the DCT, the tubular fluid goes to the collecting ducts. As the collecting ducts head down through this hypertonic medullary territory, the walls of the collecting duct are permeable to water. Water osmoses out and is taken away by capillaries to the general circulation (so that there's little diluting of the medullary interstitial fluid). The rate at which the water osmoses out of the collecting duct is dependent on how permeable to water the walls of the collecting duct are, and that permeability is dependent on anti-diuretic hormone, ADH. ADH is secreted by the posterior pituitary in response to increased blood osmolality sensed in the hypothalamus.
ADH method of action: water channels are proteins in the cells membranes of the epithelial collecting duct cells. ADH stimulates the exocytosis of these proteins from the Golgi apparatus so they are fused with the cell membrane. When ADH is absent, these water channels are reabsorbed by an endocytotic process. So more ADH, more water channels, more water reabsorption, more concentrated urine.1
MICTURATION:
Micturation is controlled by an involuntary internal urethral sphincter and a voluntary external urethral sphincter. As the bladder fills, stretch receptors stimulate a parasympathetic message to contract the detrusor muscle of the bladder and to relax internal urethral sphincter, but we have control over the external sphincter.
1 AC Guyton, JE Hall, Textbook of Medical Physiology, 9th ed. (WB Saunders, Philadelphia, 1996), pp. 943, 960-961.
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