Renal Physiology

 

1.) Slide 1 (Figure 19-1 a,b,c,d,e)

Kidney function is divided into six major areas:

I.)             Regulation of extracellular fluid volume. à When ECF decreases, blood pressure drops. The kidneys work with the Cardiovascular System to maintain an acceptable blood pressure range.

II.)           Regulation of osmolarity. à Kidney function helps to maintain a blood osmolarity that approximates around 290 mOsm.

III.)         Maintenance of ion balance. à Kidneys maintain the bodies ion concentrations by balancing ion dietary intake with excretion.

IV.)        Homeostatic regulation of pH. à Kidneys help to buffer the bloodıs pH with H+ and HCO3-.

V.)          Excretion of wastes and foreign substances. à The Kidneys remove toxins that are a byproduct of metabolism and foreign substances (e.g. Penicillin). Urobilinogen is a metabolite of hemoglobin; this gives urine itıs distinctive yellow color.

VI.)        Production of hormones. à While not true endocrine glands, the kidneys synthesize and release important hormones. (e.g. Erythropoietin).

Urine Production is characterized by plasma moving into hollow tubules. The hollow tubules are referred to as the nephrons. The modified fluid passes to the ureter, which is connected to the urinary bladder. The bladder expands and through reflex action, the urine is passed through the urethra. Process is called micturition.

Between peritoneum and the muscles of the back. Lie on either side of the spine at the level of the 11th and 12th ribs. Renal arteries branch off of the abdominal aorta, while the renal veins carry blood to the inferior vena cava.

 

2.) Slide 2 (Figure 19-1 f,g,h,i,j)

The kidney is divided into two sections: the outer cortex and the inner medulla. The functional unit of the kidney is a nephron. Each kidney contains approximately 1 million nephrons. 80% of the nephrons are found in the cortex (cortical nephrons), while the remaining 20% are found in the medulla (juxtamedullary nephrons). The kidney has both vascular and tubular elements.

Vascular Elements: Portal system in the kidney is found when blood flows from the afferent arteriole into the capillaries of the glomerulus. Blood leaving the glomerulus flows into the efferent arteriole. The efferent arteriole turns into the Peritubular Capillaries, which is also known as the Vasa Recta when found in the medulla. The capillaries finally join with the renal vein.

Tubular Elements: The tubular portion of the nephron begins at a ball-like structure called Bowmanıs Capsule. Bowmanıs Capsule surrounds the glomerulus, where the endothelium of the glomerulus fuses with the epithelium of Bowmanıs Capsule. This whole structure is known as the Renal Corpuscle. Bowmanıs Capsule flows into the proximal tubule, which dips into the Loop of Henle. The Loop of Henle is divided into the descending limb and the ascending limb. The ascending limb joins with the distal tubule, which twists so that it is directed between the afferent and efferent arterioles. This site is called the juxtaglomerular apparatus and is important for paracrine signaling (kidney autoregulation). The distal tubule (and up to eight distal tubules) drain into the collecting duct. The collecting ducts drain into the renal pelvis, which goes to the ureter.

 

3.) Slide 3 (Figure 19-2)

The kidney processes are: filtration, reabsorption, and secretion. Filtration only takes place in the renal corpuscle. 180 liters of fluid is filtered by the nephrons in one day!! Reabsorption occurs when filtered material is moved back into the blood, while secretion removes selected material from the blood and places it in the filtrate.

 

4.) Slide 4 (Figure 19-3)

The filtrate is almost identical in composition to the plasma and is nearly isosmotic, at about 300 mOsM. The primary function of the proximal tubule is bulk reabsorption of isosmotic fluid. The proximal tubule cells transport solute out of the lumen into the capillaries. Water follows by osmosis. Therefore, the filtrate still has the same osmolarity and the overall volume is decreased to 54 liters/day.

   In the Loop of Henle, more solute is reabsorbed that water. Therefore, the osmolarity decreases to 100 mOsM and the overall volume decreases to 18 liters/day.

  Once the fluid reaches the collecting duct (reabsorption and secretion), the volume of urine has decreased to 1.5 liters/day. The concentration varies from 50-1200 mOsM. The osmolarity of the urine is controlled by hormone regulation. The volume and concentration of solute are determined by the bodyıs need to conserve or excrete water and solute. Once the urine reaches the collecting duct, it is ready for excretion. After this point, it cannot be altered further. {Note: Excretion and Secretion are different terms.}

Amount excreted = amount filtered – amount reabsorbed + amount secreted

 

5.) Slide 5 and 6 (Figure 19-4  a,b,c,d)

Substances that leave the plasma must cross three filtration barriers: the glomerular capillary endothelium, the basal lamina(basement membrane), and the epithelium of Bowmanıs Capsule. Glomerular capillaries are fenestrated capillaries. These fenestrated capillaries allow most components to pass, except for blood cells and proteins (negative charged surfaces repel negative charged plasma proteins). Mesangial cells lie between the glomerular capillaries and help to alter blood flow.

The basal lamina acts as a course sieve with negatively charged glycoproteins and a collagen-like material. This helps to further exclude filtration of plasma protein.

The epithelium of Bowmanıs Capsule contains podocytes (podos means foot in Latin). The podocytes have adjacent fingerlike extensions called foot processes. These processes wrap around and leave narrow filtration slits.

Overall, one-fifth of the plasma that flows through the kidneys is filtered. The percentage of plasma volume that filters is called the filtration fraction.

 

6.) Slide 7 (Figure 19-6)

Hydrostatic Pressure – Colloid Osmotic Pressure – Hydrostatic Fluid Pressure = Net Filtration Pressure

Hydrostatic Pressure is the pressure of the blood flowing through the glomerular capillaries. Approximately 55 mm Hg.

Colloid osmotic pressure is the pressure that is created with the presence of proteins within the plasma and the absence of proteins from the filtrate. This opposes the hydrostatic pressure. Approximately 30 mm Hg.

Fluid Pressure is the pressure that the is needed to displace the filtrate that is already present in Bowmanıs Capsule.

 

7.) Slide 8 (Figure 19-7)

Glomerular filtration rate (GFR) is 180 liters/day or 125 mL/minute. That is like filling up a 100 milliliter beaker in less than a minute!!

Since the GFR is controlled by blood pressure, one would assume that if blood pressure increases, GFR would increase. That is not the case!! Notice the constant GFR when blood pressure ranges from 80-180 mm Hg. Also, if bp decreases, then the GFR will decrease to conserve fluid levels in the body.

 

8.) Slide 9 (Figure 19-8 a,b,c,d)

 Autoregulation of GFR is the local control process that maintains a relatively normal GFR in light of blood pressure fluctuations. Autoregulation is determined by two mechanisms: the myogenic response and tubuloglomerular feedback. The myogenic response is characterized as the ability of vascular smooth muscle responding to pressure changes. Tubuloglomerular feedback is the paracrine signaling mechanism through which changes in the distal tubule fluid flow influence GFR.

Increased resistance in the afferent arteriole results in decreased GFR, renal blood flow, and capillary blood pressure.

Increased resistance in the efferent arteriole results in increased GFR and capillary blood pressure. There is a decrease in renal blood flow.

Situation ³d² would result in increases in all three parameters.

 

9.) Slide 10 (Figure 19-9 a,b)

Tubuloglomerular feedback is characterized by two cell types: macula densa and juxtaglomerular (jg) cells. The macula densa is a modified portion of the distal tubule epithelium that sends paracrine signals to the jg cells. These signals can alter afferent arteriole resistance, as seen in the next slide.

 

10.) Slide 11 (Figure 19-10)

If the GFR increases, then there would be an increased flow of filtrate through the tubular elements. Flow past the macula densa would increase and a paracrine signaling mechanism would be sent to the jg cells. This signal would initiate constriction in the afferent arterioles, which would increase resistance. This would help to decrease the GFR.

 

11.) Slide 12 (Figure 19-12)

More than 99% of the original filtrate is reabsorbed in the kidney. Why would you filter 180 liters/day, but then recover most of the fluid? To clear foreign substances and it simplifies filtration at the renal corpuscle.  Most of this is completed in the proximal tubule, but finely tuned reabsorption takes place in the distal tubule.

Sodium transport in the proximal tubule is an easy mechanism to understand. There is a greater Na+ concentration in the filtrate when compared to the tubule epithelial cells. Therefore, sodium moves down itıs concentration gradient into the cells through open leak channels. Na+ is exchanged for K+ at the basolateral membrane by Na+-K+-ATPase. This is at the expense of ATP and moves against itıs concentration gradient.

 

12.) Slide 13 (Figure 19-13)

Na+-glucose transporter moves Na+ down itıs concentration gradient. Glucose harnesses the energy of sodium moving down itıs electrochemical gradient and glucose is transported at the expense of sodium. Again, the Na+ is exchanged for K+ at the basolateral membrane by Na+-K+-ATPase. Glucose diffuses out of the epithelial cell by a facilitated diffusion carrier.

 

13.) Slide 14 (not in this edition of the book)

Urea is passively reabsorbed in the proximal tubule by a simple mechanism. Since the initial filtrate is similar in composition to the plasma, there would be no reason for urea to undergo passive reabsorption. Since sodium and other solutes are reabsorbed, the extracellular fluid of the epithelial cells become more concentrated. Water then moves into the cells through osmosis. This creates a higher concentration of Urea in the filtrate because there is less water to dilute the fluid. Therefore, urea diffuses out of the lumen and into the cells.

 

14.) Slide 15 (Figure 19-14)

Saturation refers to the maximum rate of transport that occurs when all available carriers are occupied with substrate. When concentration are below the saturation point, then the transport rate is dictated by solute concentration.

The transport rate at saturation is called the transport maximum.

The plasma concentration of substrate at which the transport maximum occurs is called the renal threshold.

 

15.) Slide 16 (Figure 19-15 a,b,c,d)

Slide a – Filtration rate is directly dependant on plasma glucose concentration. As plasma glucose increases, filtration rate increase infinitely.

Slide b – Notice that reabsorption follows the same pattern. As plasma glucose increases, reabsorption increases. Reabsorption stops at glucose saturation (300 mg/ 100 mL). Transport maximum is 375 mg/min.

Slide c – Therefore, glucose will not be secreted in the urine until the renal threshold is reached. Glucose secretion increases infinitely beyond this point.

Slide d – Composite graph showing all processes. Notice that filtration rate equals reabsorption up to 300 mg/100mL. At this point, Excretion = filtration (increasing) – reabsorption (constant).

 

16.) Slide 17

Secretion

€       Selective process of transferring molecules from the extracellular fluid into the lumen.

€       K+ regulation by Aldosterone in the distal tubule.

€       Aldosterone is synthesized in the adrenal cortex and released when there are increased levels of K+.

 

17.) Slide 18

Secretion Cont.

€       Through translation of protein channels and modifier proteins, K+ is secreted into the lumen of the distal tubule.

€       Remember the Na+-K+-ATPase on the basolateral membrane??

€       Well, Na+ reabsorption is necessary for this mechanism.

 

18.) Slide 19 (Figure 19-18)

Urine is stored in the bladder until urination or micturition. The bladder is a hollow sac that can expand to store 500 mL of fluid. The opening between the bladder and urethra is closed by two rings of muscle called sphincters. The internal sphincter is a continuation of the bladder wall (smooth muscle) and normally stays passively contracted. The external sphincter is composed skeletal muscles and is innervated by somatic motor neurons (it is normally contracted). When the stretch receptors are stimulated, they send a message to the CNS. The CNS sends a message to pull open the internal sphincter and relax the external sphincter.

 

19.) Slide 20

Vasopression/ADH

€       Vasopressin is released by the posterior pituitary and aids in water retention.

€       Controls urine concentration in the collecting duct by reabsorbing water.

€       ADH bind to itıs receptor and through a cAMP signal, Aquaporin-2 water pores are moved to the apical membrane.

€       Water is recovered.

 

20.) Slide 21

Effects of Alcohol

€       Alcohol inhibits ADH secretion.

€       Water recovery is significantly diminished and urine volume increases.

 

Acknowledgement, This lecture was first prepared by Katie Richards, 2005 TA

 

Quiz questions from 2005 relating to this outline

 

Short Answer

1.) List four overall functions of the kidney (HintŠthere are six total).

Regulation of ECF Volume; Regulation of Osmolarity; Maintenance of Ion Balance; Homeostatic Regulation of pH; Excretion of Wastes and Foreign Substances; Production of Hormones

 

2.) Name the hormone that is responsible for water reabsorption in the kidney.

ADH or Vasopressin

 

3.) Name the two structures that are found in the renal corpuscle. 

Glomerulus and Bowmanıs Capsule

 

True of False

4.) Pertaining to reabsorption, Na+ freely moves down itıs concentration gradient on the basolateral membrane of the tubule epithelial cell.

True / False

 

5.) Glomerular capillaries are fenestrated capillaries.

True / False

 

6.) Hydrostatic fluid pressure is the pressure that is needed to displace the filtrate that is already in Bowmanıs Capsule.

True / False

 

7.) Tubuloglomerular feedback is the paracrine signaling mechanism through which changes in the proximal tubule influence GFR.

True / False

 

Circle the Correct Answer

8.) If resistance in the afferent arteriole increased, then there would be an increase / decrease in the GFR.

 

9.) An increased / decreased rate of flow in the tubular elements would initiate paracrine signaling in the macula densa to increase resistance in the afferent arterioles.

 

10.) Urea is actively / passively absorbed in the proximal tubule.

 

Fill in the Blank

11.) The transport rate at saturation is called the _transport_   _maximum_.

 

12.) Potassium secretion is controlled by _Aldosterone_.

 

13.) The opening between the bladder and the urethra is closed by two rings of muscle called __sphincters.

 

 

Final exam questions from 2005 relating to this outline

 

Kidney Final

 

1.) What are the three forces (pressures) affecting filtration at the glomerulus. In which direction (towards the blood or towards the filtrate) does each of the forces push fluid?

            Hydrostatic pressure toward blood

            Colloid pressure toward filtrate

            Fluid pressure toward filtrate

 

 

2.) If you ingested five beers in a relatively short timeframe (say 30 minutes), you may have to make several trips to the bathroom to relieve yourself. Why would your urine volume increase? What is responsible for this action?

            ADH (vasopressin) is inhibited, water resorption is inhibited

 

 

3.) Glucose is filtered into Bowman's capsule then "recovered." Why, then, do patients with untreated diabetes mellitus have glucosuria (glycosuria)?

            Reuptake is saturated

 

 

4.) What segment of the tubular elements is found in the kidneyıs medulla?

            Loop of Henle

 

5.) Secretion and excretion are terms that are commonly confused when studying renal

physiology. What is the difference between these two terms?

            Excretion is transfer out of the body

            Secretion is transfer from blood to lumen

 

 

6.) In the kidney lab itself, we obtained a variety of measurements. List two of the measurements taken (can be quantitative or qualitative).

            Specific gravity, pH, volume, glucose, blood, protein, ketone

 

 

7.) Increased resistance in the efferent arteriole results in an increased / decreased GFR.

 

8.) Briefly explain how urea is passively reabsorbed.

            There is active transport for Na+, then water follows then urea (passively)

 

 

9.) Approximately how many nephrons are there in each kidney?

            1 million

 

10.) Which is a more selective process: glomerular filtration or reabsorption? Briefly discuss.

            Resorption. Filtration is everything, resorption is for specific substances

 

 

11.) ____aldosterone_______ is synthesized in the adrenal cortex and released when there are increased levels of K+.

 

Quiz questions from 2006:

 

1. The inner portion is the kidney is referred to as the ___________ while the "bark" is

called the ___________.

 

medulla, cortex

 

2. How many nephrons are in each kidney?

 

1 million

 

3. How many liters/day of fluid does the kidney filter?

 

180

 

4. What is the difference between excretion and secretion?

 

out of the body, one place to another (internally)

 

5. What enzyme do JG (juxtraglomerular) cells release that affects salt balance?

 

renin

 

6. When the adrenal glands are taken out of a rat, what substance is significantly lost?

 

salt

 

7. What type of transporter allows sodium to leave the cell and return to the interstitial fluid?

 

Na+K+-ATPase

 

8. Water moves from a hypotonic solution to a hypertonic solution

via what process?

 

osmosis

 

9. What is the name of the pore that allows H2O to be recovered?

 

aquaporin-2

 

 

10. Which disease may allow glucose, in high concentrations, to enter the urine?

 

diabetes mellitis

 

Final questions from 2006

 

14. What is the functional unit of the kidney?

 

nephron

 

15. The glomerulus and Bowman's capsule are collectively referred to as what?

 

renal corpuscle

 

16. What type of capillaries have large pores that aid in the first stages of filtration?

 

fenestrated

 

17. Why is a podocyte so named?

 

has foot processes

 

18. Roughly what percent of plasma is reabsorbed back into systemic circulation?

 

99%

 

19. What is the main driving force, under normal conditions, that affects filtration rate?

 

blood pressure

 

20. The macula densa communicates with what to respond to low blood pressure and release renin?

 

juxtaglomerular cells

 

21. Renin is involved with the activation of what powerful hormone to re-establish blood pressure?

 

angiotensin

 

22. With what ion does glucose enter the proximal tubule cell?

 

Na+

 

23. The function of urea is to eliminate what byproduct of metabolism?

 

nitrogen

 

24. What portion of the kidney does the loop of Henle "dip" into?

 

medulla

 

25. Which, of the two convoluted tubules, is closer to Bowman's corpuscle?

 

proximal

 

26. Normally, do blood cells pass into the filtrate?

 

no

 

27. Vasopressin is a hormone from the posterior pituitary. What is a more common name?

 

ADH

 

28. Name a drug that inhibits Vasopressin.

 

alcohol, caffeine

 

 

 



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