I. Glomerular Filtration

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1 The following are review questions that can be used to review the basic concepts of urinary physiology. Please do not limit your knowledge to these questions use your text and your laboratory studies as well as the interactive physiology in BA209 (this is required). Here are my lecture notes. I hope this helps those of you who are still struggling to understand this system. I. Glomerular Filtration 1. Filtration of the blood occurs through the glomerulus w/in Bowman s capsule. Remember, the structure of this filtration membrane is specifically structured for filtration (see page 1005). What makes the glomerulus (glomerular capillaries) specially structured for filtration? (1) large surface area (2) filtration membrane = thin & porous/leaky w/fenestrations (3)high glomerular capillary blood hydrostatic pressure 2. Describe the principles behind glomerular filtration. Blood in the glomerulus is under pressure (blood hydrostatic pressure) which forces blood through the capillary membrane (filtration pressure). 3. Compare the relative diameters of the afferent and efferent arterioles and explain the significance in this size differential. The afferent arteriole is wider than the efferent arteriole which means that blood enters the glomerulus through a wider opening than the blood exiting the glomerulus, thus creating an increased back pressure (=hydrostatic filtration pressure). They hydrostatic pressure is higher in the glomerulus than in other capillaries. By varying the size of the afferent and/or arterioles, the glomerular filtration rate (GFR) may be increased or decreased. 4. What percentage of water and solutes of the blood becomes filtrate (primitive urine)? 20% of the water in the blood is filtered out to become part of the filtrate. This produces 180 liters of water (potential urine) a day. All solutes present in the blood (excluding proteins, especially larger proteins such as albumin) including ions (such as Na+, Cl-, HCO3-, etc.), glucose, amion acids, creatine, and uric acid are also filtered out of the blood to become part of the filtrate (primitive urine). Remember that most of these solutes will be completely or at least partially reabsorbed later on in through the renal tubules. Most of the water will be reabsorbed too all but about 1-2 liters, which will be excreted as urine. (Study normal and abnormal constituents of urine-table 26.6). 5. What is NOT filtered out through glomerular filtration due to their large size? Proteins, especially larger proteins such as albumin, fibrinogen and globulins. RBC s and other large molecules are not filtered out either. Thinking about proteins: Glomerularnephritis (inflammation of the glomerulus) increases the permeability of the glomerular filtration membrane. Now proteins leak through the membrane and are filtered out into the filtrate (primitive urine) with no way to be returned to the blood later on. This then increases the capsular osmotic pressure (see Fig. 26.9) as well as the osmotic pressure within the renal Revised Spring

2 tubules while decreasing the osmotic pressure within the capillaries and within the entire vascular system. Why would this condition cause edema in other areas of the body refer back to cardiovascular system, Edema, where did I go wrong? 6. Where are the juxtaglomerular cells located? The juxtaglomerular cells (modified smooth muscle fibers) are located within the walls of the afferent arteriole and are closely situated next to the macula densa cells in the end of the ascending limb of the loop of Henle just before it enters the DCT. (see Fig. 26.6) The juxtaglomerlular cells w/ the macula densa make up the justaglomerular apparatus (JGA). 7. What is the function of the juxtaglomerular cells? (See Renal Autoregulation of GFR, Table 26.2) The juxtaglomerular apparatus (JGA) helps regulate the arterial blood flow w/in the kidney which then determines the rate of blood filtration by the glomerulus (GFR). These mechanisms work to maintain a constant GFR at a localized level (= renal autoregulation) A. Juxtaglomerular cells: As blood flow increases through the afferent arteriole (a.a), the juxtaglomerular cells detect stretching due to increased blood pressure; they contract in response, which narrows the lumen of the a.a., which results in decreased blood flow to the glomerulus (= GFR). If there is less blood flow through the a.a. there is less stretching, the a.a. relaxes and dilates, allowing more blood flow into the glomerulus (= GFR). B. Macula densa cells are sensitive to increased levels of Na +, Cl - and H 2 0 in the renal tubule as a result of GFR (due to high systemic blood pressure). Their response is to inhibit the release of NO. NO normally causes vasodilation of arterioles as a localized response. Inhibiting NO therefore causes vasoconstriction of the a.a., which decreases blood flow through the glomerulus. This brings the GFR back down to normal (= GFR). If blood pressure drops in the nephron, then more NO will be produced, resulting in vasodilation of the a.a.; which then increases the GFR back to normal. Remember, these are localized responses to maintain a steady glomerular filtration rate (GFR). See Table 26.2 p for regulation of GFR. 8. What is the function of renin? (See Hormonal Regulation of GFR, Table 26.2 p and review Fig , p. 643) Renin is produced by the JGC in response to lowered arterial blood pressure (perhaps due to hemorrhaging). Renin initiates the Renin-Angiotensin-Aldosterone Pathway. Eventually, Angiotensin II causes constriction of the afferent arteriole (and also efferent arteriole) resulting in decreased blood flow to the glomerulus decreased glomerular filtration rate (= GFR). This means decreased urine output (UO) so you conserve fluid and increase your blood pressure. Note: This response is a systemic response to lowered blood pressure. This response may also be stimulated by lowered levels of Na + in the blood and therefore, in the filtrate. Revised Spring

3 9. Specialized cells, principal cells, in the last part of the distal convoluted tubule (= DCT) and throughout the collecting duct (CD) are sensitive to decreased levels of Na + in the filtrate. Decreased Na + levels in the filtrate stimulate the release of renin, which then activates the renin-angiotensin-aldosterone pathway. As a result, Angiotensin II, a powerful vasoconstrictor, constricts the afferent (and to some extent the efferent) arteriole, resulting in (increased, decreased) GFR. 10. What happens to the pressure (glomerular filtration pressure) if the diameter of the afferent arteriole increases? If the a.a. dilates then more blood flows into the glomerulus which results in increased GFP (= GFR) and potentially more urine output (UO). 11. A decrease in the level of renin results in Angiotensin II, vasoconstriction of a.a. (= vasodialtion/diameter of a.a.) and therefore = GFR. 12. How are afferent arteriole diameter, blood flow, and pressure in the glomerulus interrelated? (See Neural Regulation of GFR, Table Note that the afferent arteriole and the efferent arteriole can be regulated independently. What happens if a sympathetic response causes constriction of the afferent arteriole? Think about what happens if the efferent arteriole is dilated/or constricted. diameter of the a.a. = blood flow into glomerulus and glomerular filtration pressure and GFR and UO. 13. What effect does ANP (atrial natriuretic peptide) have on GFR? (See Hormonal Regulation of GFR Table 26.2 p. 1008) What is the stimulus? When the atria of the heart are stretched due to increased blood pressure (increased venous return) the hormone ANP is released. It targets specialized cells in the glomerulus. The response is to increase capillary surface area which then increases the GFR resulting in UO and blood pressure due to decreased blood volume. We have been focusing on the localized, hormonal, and neural effects on GFR. Some of these mechanisms are also involved in tubular reabsorption and secretion. We will discuss this in a bit more detail with Tubular Reabsorption. II. Tubular Reabsorption is the movement of substances from the filtrate (urine) in the renal tubules back into the blood via the peritubular capillaries and the vasa recti. It is a very discriminating process which involves specialized cells in specific regions of the nephron (Table 26.1). Only specific substances and certain amounts of those substances will be reabsorbed in specific regions of the renal tubules. 1. What percent of tubular filtrate is excreted as urine? Only 1%. We make about liters of filtrate/day (= about 45 gallons), but only about 1% of the original filtrate is actually excreted as urine. We produce about 1-2 liters of urine/day (average = 1 liter), depending on fluid intake and other personal conditions. Revised Spring

4 2. What happens to the remaining 99% of the water and dissolved substances in the filtrate? It is reabsorbed back into the blood. 3. What are the two basic processes of tubular reabsorption? Contrast the two. (1) Passive transport (2) Active transport 4. List and describe three examples of passive transport. (does not require energy) (1) Osmosis (reabsorption of water) (2) Diffusion (& facilitated diffusion) (3) Electrochemical attraction (where a negatively charged ion (Cl - ) is attracted to and follows a positively charged ion (Na + ) and vice versa. 5. Active transport involves carrier molecules to move the transported molecules through the membrane. Active transport requires the expenditure of energy (ATP) or the use of antiporters (opposite direction) or symporters (same direction). Note: each type of transporter has a limited capacity to transport its product within a given amount of time (= tubular maximum, Tmax, or renal plasma threshold). When the Tubular Maximum is surpassed, we say the product spills over into the urine. An interesting example is when a person with uncontrolled diabetes mellitus has hyperglycemia and exceeds his/her Tmax for glucose (>200mg/ml). The result is glucosuria. Because of the resulting increased osmotic pressure of the filtrate there will be less reabsorption of water, resulting in UO and, therefore, dehydration. Remember the 3 polys associated with diabetes mellitus (polydypsia, polyuria, polyphagia). 6. Give examples of ions and molecules reabsorbed (via passive and/or active processes) from the kidney tubules into the renal intersititial spaces and on into the peritubular capillaries. (Table 26.3) H2O, glucose, amino acids, uric acid, urea, Na +, K +, Ca 2 +, Cl -, HCO 3 -, HPO Note: large proteins such as albumin are not included in this list. Explain. What happens with glomerular nephritis? What is the Tmax for proteins? 7. How much water is reabsorbed due to passive and active transport? Osmosis = 85-90% in the PCT, LH, DCT and Active Transport = 5-10% in the latter portion of the DCT and CD (principle cells) under the influence of ADH. 8. Where does the majority of tubular reabsorption occur? PCT Note: About 70% of the Na + is reabsorbed in the PCT. Angiotensin II stimulates the reabsorption of Na + and Cl - and water follows by osmosis while aldosterone stimulates the reabsorption of Na + and Cl - followed by water in the CD. 9. By the time the filtrate reaches the DCT what major changes have occurred? (1) +/- 80% of the filtered was has been reabsorbed (PCT). More or less water will be reabsorbed at the end of the DCT and in the CD depending on ADH level. (2) glucose has been totally reabsorbed into the blood (PCT) (3) the majority of the electrolytes, minerals and nutrients have been reabsorbed. (4) there is an increased concentration of waste products Revised Spring

5 10. What are some of the waste products found in the filtrate as it approaches the DCT? These would normally be found in the urine. (1) urea (2) creatinine (3) uric acid (4) ammonia 11. Fluid and electrolyte balance of blood and acid base balance of the body is primarily regulated in the DCT and CD. They are regulated by hormones which increase/decrease tubular reabsorption and/or tubular secretion. The body has the ability to secrete a dilute or a concentrated urine, depending on the needs of the body. Explain how this works. While the ph of the blood is maintained within very narrow limits of (average =7.4), the urine is much more flexible with a broader range between 4.6 and 8 (average = 6) depending on the diet and other conditions/needs of the body. The urinary system helps maintain the proper ph of the blood by secreting either H + or HCO 3 - in the urine the urine is much more flexible in its levels and acts as the dumping ground for many excesses. III. Regulation by Hormonal Influence 1. What three hormones regulate the amount of fluid and electrolytes conserved or excreted by the kidneys? a. Antidiuretic Hormone (ADH) b. Renin-Angiotensin-Aldosterone Pathway (Aldosterone) c. Atrial Natriuretic Peptide (ANP) 2. ADH (antidiuretic hormone) is produced by the hypothalamus and is stored in the posterior pituitary gland. 3. What is the stimulus for the release of ADH? Osmoreceptors in the hypothalamus detect decrease in blood volume, increased osmolarity of plasma/extracellular fluid (=dehydration). 4. What is the target of ADH? Principal cells of the last part of the DCT and throughout the CD (especially the CD). 5. What effect does ADH have on DCT and CD? Increases the permeability of the DCT and CD by inserting water channel proteins in the membrane of the principal cells. This then causes increased reabsorption of water into the blood and increases hydration (decreases osmolarity of body fluids). 6. Does increased ADH levels cause you to excrete more or less urine? LESS 7. What is the negative feedback mechanism involved in turning off ADH secretion? As the person increases hydration (osmotic concentration of body fluids (blood) decreases due to increased blood volume), osmoreceptors are no longer stimulated and the level of ADH decreases. Revised Spring

6 Note: ADH is an ANTI diuretic anti diuresis = decreased urine output. A diuretic on the other hand, would increase urine output. A person with high ABP might take a diuretic such as Lasix to decrease blood volume via increased urine output. Diuretics work in several ways: Inhibitors of ADH Water = the best diuretic as water increases ADH decreases Alcohol inhibits ADH causing increased urine output and corresponding headaches and dry mouth (thirst). Diabetes insipidus ( watery urine ) = lack of ADH resulting in increased urine output. See chapter 18 for more detail. Inhibitors of Na + reabsorption (if Na + is not reabsorbed then H 2 O does not follow by osmosis) Caffeine decreases Na + and H 2 O reabsorption resulting in increased urine output, dehydration and thirst, so drink water to quench your thirst, not coffee or coke. Lasix (a common diuretic) for lowering blood pressure Remember: Increasing diuresis increases urine output which decreases blood volume. Decreasing diuresis decreases urine output which increases blood volume. 8. Aldosterone is produced by the _zona glomerulosa in the adrenal cortex of the adrenal gland. (See Endocrine LAB) 9. Renin via the renin-angiotensin-aldosterone pathway), in addition to decreasing the diameter of afferent arterioles, triggers the release of aldosterone. 10. What effects does aldosterone have upon kidney function? (1) increases Na + and Cl - reabsorption (2) increases H 2 O reabsorption (3) increases K + secretion (blood to urine = increases loss of K + ) As a result of increased aldosterone, the body conserves Na + and H 2 0, increases hydration, and increases ABP by decreasing urine output. 11. Describe the affect ANP has on fluid and electrolyte balance. Review from Chapter 18: ADH, ANP, Renin-Angiotensin Pathway, Aldosterone stimulus, mechanism of action (negative feedback mechanism), and how they influence fluid and electrolyte balance. These are very important concepts that you must know very well for exam 5. They will help you pull systems and concepts together. Revised Spring

7 IV. Tubular Secretion A. Tubular secretion moves products from the blood and tubule cells into the tubular fluid (urine). B. 3 main functions of tubular secretion 1. Remove wastes such as creatinine, urea, uric acid, etc. 2. Maintain electrolyte balance (Na +, K +, Cl -, etc.) 3. Maintain Acid-Base balance of blood (maintain proper ph) a. Normal plasma (blood) ph = b. Through tubular secretion the ph of the blood _usually increases_ (becomes less acidic) while the urine becomes more acidic (4.5-8, average = 6) c. This is accomplished by secreting (into urine) 1) H + (or HCO 3 - ) as needed 2) ammonia (NH 3 )/ammonium ion (NH 4 + ) C. Mechanisms of tubular secretion 1. Secretion of Potassium (K + ) a. Most K + in the glomerular filtrate is passively reabsorbed by diffusion in the PCT (urine blood) and also actively reabsorbed in other areas of the nephron. b. Some K + may be passively secreted by principal cells in the late DCT and CD through leakage channels in the DCT and CD. This amount is variable and adjusts for dietary intake. c. The Na+/K+ pump mechanism in the DCT and the CD actively reabsorbs Na+ while actively secreting K+ ions. d. Active reabsorption of Na+ out of the tubule into the blood peritubular capillaries creates a temporary negative charge within the tubule. d. K + in the peritubular capillary is displaced by Na+ and therefore K + is secreted into the urine. e. The hormone aldosterone allows for variable secretion of K + and simultaneous reabsorption of Na + by principle cells in the DCT and CD. Aldosterone increases the activity of the Na + /K + pumps and K + leakage channels and makes new pumps and channels. Study Renin/Angiotensin/Aldosterone Pathway (chapter 18, page 643). Note that K + in blood can stimulate the zona glomerulosa of the adrenal cortex. aldosterone = K + (hyperkalemia) which can cause cardiac arrest. Just as a review: Remember reabsorption of Na + and Cl - causes H 2 O reabsorption and UO. Remember, the stimulus could have been dehydration, Na + deficiency, ABP, hemorrhage or even K +. Revised Spring

8 2. Secretion of Hydrogn ions (H + ) a. Na + /H + antiporters of PCT (reabsorb Na + and secrete H + ) while also passively reabsorbing HCO3 - (an important buffer for the blood). b. Proton pump mechanism of intercalated cells of DCT and CD secretes H + against their concentration gradient and urine can become much more acidic than blood (dumps acid into urine). Note: the intercalated cells also have a proton pump mechanism that pumps H+ into the cells and into the blood and antiporters that move HCO 3 - into the URINE if the ph of the blood is too high (alkaline). c. How does secretion of H + work? 1) Formula: CO 2 + H 2 O (CA) H 2 CO 3 H + + HCO 3 - Source for CO 2 = cellular respiration 2) Stimulus: CO 2, H, acid internal environment 3) H + are secreted into the urine and displace a Na +. 4) Na + enters the peritubular capillaries where it joins with HCO 3 - to form NaHCO 3 (an important buffer for the blood) d. So what s the point (conclusions): 1) H + (acid) is removed from blood 2) Na 2 conserved and HCO 3 - reabsorbed 3) NaHCO 3 formed which acts as a buffer for other H + in the blood. A buffer makes a strong acid weaker. NOTE: Blood leaving the kidney via the renal vein has a (higher/lower) level than blood entering the kidney via the renal artery. Blood = ph (less acidic) 3. Secretion of Ammonia to raise ph of blood a. Back up system Used if acidic for long periods (eg: emphysema/ COPD, retaining CO 2 ) b. Normally, the liver converts ammonia to urea (which is filtered out and is in the urine), which is not as toxic as ammonia. (Note: Ammonia is a waste product from the deamination of amino acids. c. During prolonged increases in H + concentrations 1) NH 3 (ammonia) is produced by epithelial cells of the DCT and CD of the renal tubule. 2) NH 3 diffuses readily through the cell membrane into the urine. Revised Spring

9 3) NH 3 accepts a H + and becomes NH 4 +, the ammonium ion in urine. 4) The cell membrane is impermeable to NH4-, so they are trapped in the urine. 5) Na + is displaced by NH 4 +, and it goes back into the cells where it joins with HCO 3 - to form NaHCO 3 which diffuses into the blood. d. So.what s the point? (conclusions): 1) You get rid of a H+ = H+ are removed from the body via urine. 2) You trap H+ in the urine so they can t diffuse back into the blood. 3) NH 3 + H + NH 4 + buffers the URINE (makes a strong acid =H a weaker acid) 4) Conserves Na+ and HCO 3 - NaHCO 3 to buffer BLOOD. Note: HPO H + H 2 PO 4 - is another similar buffering mechanism. The tubule membrane is also impermeable to H 2 PO 4 - so again the H + is trapped inside the urine and the urine is buffered. 4. Due to secretion of H + and NH 4 +, the urine is usually acidic with a normal ph ranging between (average = 6). 5. What s the reason for secreting K +? There is no acid/base balance connection here. K + is secreted to rid the body of excess K + ions and to maintain the proper fluid and electrolyte balance via aldosterone. V. Regulation of Acid-Base Balance this is very basic, but it works as a review. 1. An increase in H + ions decreases the ph (or increases the acidity). 2. CO 2 joins with H 2 O to form H 2 CO 3 (carbonic acid) under the influence of carbonic anhydrase (an enzyme). 3. H 2 CO 3 H + + HCO 3 - then 4. HCO Na + NaHCO 3 + H + 5. The purpose here is to get rid of excess H+ ions while sending a base (HCO 3 - ) (i.e., NaHCO 3 ) to the blood. Go to the next handout on Acid/Base Balance, which has been basically completed for you and study it. It should help you pull several systems together. Review what you know about acid-base balance from the respiratory system and digestive system and use the Acid Base Balance handout to your best advantage this means STUDY it well. Revised Spring

10 VI. Micturition (Don t forget to do this It won t be covered in lecture, but will be on the exam.) 1. Study the anatomy of the bladder 2. After urine formation where does it go? Trace the path through the kidney and on to the bladder then out of the body. 3. What is micturition? 4. Describe the micturition reflex (in detail). Revised Spring