Renal- Glomerular Filtration

Front 1

1. What exactly is ultrafiltrate?

Back 1

Glomerular filtration is the first step in urine formation. As blood enters the glomerular capillaries (Afferent) a small portion of that blood is filtered into Bowman's space. The fluid that is filtered is similar to interstitial fluid and is referred to as ultrafiltrate.

Front 2

2. What does ultrafiltrate contain?

Back 2

It contains water, plus small solutes of blood. It should not contain proteins and blood cells.

Front 3

3. Are filtration rates in Bowman's capsule the same as in systemic capillaries?

Back 3

Not exactly. The forces responsible for GF are similar, but not equal to systemic capillary mechanisms. All of these are Starling forces. There are differences in the characteristics and surface area of the glomerular capillary barrier. This makes glomerular filtration rates much higher.

Front 4

4. beginning with the capillary lumen and moving closer to Bowman's space, what are the three histological layers?

Back 4

1. Endothelium

2. Basement membrane

3. Epithelium

Front 5

5. Briefly describe the endothelial cell layer.

Back 5

This layer has pores 70-100 nanometers in diameters. Because of this size,dissolved solutes and plasma proteins all are filtered across this layer of the glomerular capillary barrier. Blood cells however, cannot be filtered.

Front 6

6. Briefly describe the basement membrane.

Back 6

Histologically, the basement membrane has three layers. Lamina interna, lamina densa and the lamina externa.

This multilayered basement membrane does not allow filtrstion of plasma proteins, and is considered the significant barrier of the glomerular capillary.

Front 7

7. Briefly describe the epithelium of the glomerular filtration barrier.

Back 7

This layer has specialized cells called Podocytes, which attach to the basement membrane by foot processes. Between the foot processes and filtration slits , 25-60nm in diamter, which are bridged by thin diaphragms.

Due too the size of these slits, the epithelial layer, with the basement membrane is also conidered a significant barrier.

Front 8

8. In addition to size barriers that moderate filtration, what other factor is key in determining what is filtered?

Back 8

The presence of negatively charged proteins. These are present on the endothelium, lamina interna and externa of the basement membrane, on the podocytes and foot processes, as well as on the filtration slits oif the epithelium.

Front 9

9. How do these negative glycoproteins affect filtration?

Back 9

They tend to add an electrostatic component to filtration. Positively charged solutes will be attracted to the negative charges on the barrier and will be more readily filtered.

Negatively charged solutes are repelled from the negative charges on the barrier and will be less readily filtered.

Front 10

10. How are small solutes such as Na+, K+, Cl- or HCO3- affected by the presence of these negatively charged proteins?

Back 10

These small solutes tend to have less import on filtration. Many of these are freely filtered across the glomerular barrier. Larger solutes such as plasma proteins will however be unable to cross the barrier.

It should be noted that in certain glomerular diseases, the negative charges of the barrier are removed, resulting in an increased filtration causing proteinuria.

Front 11

11. What are Starling forces?

Back 11

These are the pressures that drive fluid movement across the glomerular capillary wall.

There are 4 recognized Starling forces:

2 hydrostatic pressures (one in capillary blood and one in interstitial fluid

2 Oncotic pressures- one in capillary blood and one in interstitial

Front 12

12. Technically, the oncotic pressure of Bowman's space is considerded to be zero. True/False

Back 12

True. The oncotic pressure here is analogous to interstitial fluid. Here, the filtration of protein is negligible.

Front 13

13. What is the Starling equation?

Back 13

GFR= K(f){P(gc)-P(bs)- π (gc}

*GFR= glomerular filtration rate (mL/min)

*K(f) -hydraulic conductance (mL/min.. mL Hg

*P(gc)= filtration coefficient (mL/min) mm Hg -Hydrostatic pressure in glomerular capillary mm Hg

*P(bs)= hydrostatic pressure in Bowman's space (mm Hg)

*π(gc)= Oncotic pressure in glomerular capillary (mm Hg)

Front 14

14. Briefly describe K(f) filtration coefficient.

Back 14

This is the water permeabilty or hydrostatic conductance of the glomerular capillary wall.

The two factors that contribute to K(f) are the water permeabilty per unit of surface area and the toatal surface area.

K(f) for glomerular capillaries is more than 100 fold that of systemic capillaries (skeletal muscle capillaries) due to the combination of a higher total surface area and a higher intrinsic water permeability of the barrier. Much more fluid is is filtered from glomerular capillaries than from other capillaries.

GFR= 180L/day.

(About 125 mL is filtered every minute. This totals app. 7,500mL in an hour. In 24 hours that would result in 180L being filtered by normal kidneys.

Front 15

15. Briefly describe P(gc).

Back 15

This is the hydrostatic pressure in glomerular capillaries. This force favors filtration. When compared with systemic capillaries, P(gc) is high (45mm Hg).

In systemic capillaries, hydrostatic pressure tends to fall along the length of the capillary. In glomerular capillaries, it remains constant along the entire length.

Front 16

16. Briefly describe P(bs).

Back 16

This is hydrostatic pressure in Bowman's space. This force opposes filtration. It is about 10mm Hg.(Capsular hydrostatic pressure). This is the fluid present in the lumen of the nephron

Front 17

17. Briefly describe π(gc).

Back 17

This is oncotic pressure in glomerular capillaries. This also opposes filtration. This is determined by the protein concentration of glomerular capillary blood.

This force does not remain constant along the capillary length, it progressively increases as fluid is filtered out of the capillary.

Note: π(gc) eventually will increase to the point where net ultrafiltration pressure becomes zero and the glomerular filtration stops. (filtration equilibrium).

Front 18

18. How are changes in P(GS) produced?

Back 18

These are produced by changes in the resistance of the afferent and efferent arterioles.

In constriction of the afferent arteriole results in increased afferent arteriolar resistance. RPF will decrease. GFR will decrease, due to less blood flowing into the glomerular capillary, P(gc) decreases, reducing net ultrafiltration pressure.

Sympathetic nervous system and high levels of angiotensin 2.

Front 19

19. What are the results of efferent arteriolar constriction?

Back 19

Efferent arteriolar resistance increases. RPF is the same as with constriction of the afferent arteriole, it decreases.

GFR , however,increases.

GFR increases because blood cannot leave the glomerular capillary. Filtration continues to move forward. Caused by low levels of angiotensin 2, and mild shock conditions.

Front 20

20. Angiotensin 2constricts both afferent and efferent arterioles, but has a greater constricting effect on efferent arterioles. True/False

Back 20

True. With both high and low levels of angiotensin 2, because of its preferential effect on efferent arterioles the GFR is protected .

ACE inhibitors block the production of angiotensin 2 and offset or eliminate its protective effect on GFR.

Front 21

21. What factors or conditions result in changes in oncotic pressure (π(gc)?

Back 21

This is affected by changes in plasma protein concentration. Increases in plasma protein will produce increases in oncotic pressures.

Both the net ultrafiltration pressure and GFR are decreased.

In nephrotic syndrome (decreases in plasma protein, hepatic disease etc), larger amounts of protein will be lost in the urine. Ultrafiltration is increased.

Front 22

22. What causes changes in P(BS), hydrostatic pressure in Bowman's space?

Back 22

Obstruction of urine flow (stone, ureter constriction, tumor).

If urine cannot flow through the ureter, urine will bacvk up in the kidney. Hydrostatic pressure in nephrons will increase, all the way back to Bowman's space resulting in P(bs) increase. GFR will decrease.

Front 23

23. What substance is considered an ideal glomerular marker?

Back 23

Inulin. This is a fructose polymer with a MW of 5,000 daltons. It is not bound to plasma proteins.

It is freely filtered across the glomerular capillary wall.

Front 24

24. What happens once inulin is freely filtered?

Back 24

Inulin is inert, within the tubule. It is neither reabsorbed or secreted by the tubule cells. In fact, The amount of inulin filtered across the glomerular capillaries is equal to the amount of inulin that is excreted in the urine.

Front 25

25. The clearance of inulin equals the GFR. What is the formula expressing this sum?

Back 25

GFR = [U](inulin) X V

____________________________ = C(inulin)

[P] (inulin)

GFR= Glomerular filtration rate mL/min

[U] = inulin- urine concentration of inulinmg/mL

[P] = inulin Plasma conc. of inulinmg/mL

V= urine flow rate

C(inulin)- clearance of inulin mL/min

Front 26

26. Other than inulin, which is considered a near perfect marker, what other substance is almost equal to inulin as a marker?

Back 26

Creatinine. This is freely filtered across the glomerular capillaries, but is also secreted to a very small extent. The clearance of creatinine overestimates the GFR.

Creatinine is endogenous. Inulin is an exogenous substance.

Front 27

27. When there is a decrease in GFR (renal failure), BUN and serum creatinine decrease. True/False

Back 27

False. They tend to increase because they are inadequately filtered.

Front 28

28. What happens to GFR in volume contraction?

Back 28

In hypovolemia, there is decreased renal perfusion and there is decreased GFR. This is a form of prerenal azotemia. BUN and creatinine will be increased.

Front 29

29. IN prerenal azotemia, why does BUN increase more than creatinine?

Back 29

Urea is reabsorbed and creatinine is not. BUN increases more than serum creatinine in volume contraction.

Front 30

30. One indicator of volume contraction (prerenal azotemia) is an increased ration of BUN/creatinine to more than 20. True/False

Back 30

True. True renal failure due to renal causes (chronic renal failure)produces an increases in both BUN and serum creatinine, but does not produce an increase in the ratio of BUN/creatinine.

Front 31

31. What is filtration fraction?

Back 31

This ratio expresses the relationship between the GFR and renal plasma flow (RPF).

Filtration fraction =GFR

_________

RPF

The filtration fraction is the fraction of the RPF that is filtered across the glomerular capillaries. The value for the filtration fraction is about 20%. 20% of the RPF is filtered and 80% is not.The non-filtered portion leaves the glomerular capillaries via the efferent arterioles and becomes the peritubular capillary blood flow.

Front 32

32. Regarding tubule reabsorption, list some substances reabsorbed from the glomerular filtrate into the peritubular capillary blood.

Back 32

Na+ Cl-, HCO3, glucose, amino acids, urea, calcium, magnesium, phosphate, lactate and citrate.

Mechanisms for reabsorption involve transporters in the membranes of the renal epithelial cells.

if reabsorption did not occur, most ECF constitiuents would be rapidly lost in the urine.

Front 33

33. Organic acids, organic bases, and K+ are secreted from peritubular capillary blood into tubular fluid. True/False

Back 33

True. Secretion provides a mechanism for excreting substances in the urine. This process also involves transporters in the membranes of the epithelial cells lining the nephron.

Front 34

34. What is the excretion rate?

Back 34

This refers to the quantity of substance excreted per unit time. Excretion is the net result, or sum, of the processes of filtration, reabsorption and secretion.

The excretion rate can be compared to the filtered load in order to determine whether a substance has been reabsorbed or secreted.

Front 35

35. Glucose is filtered across glomerular capillaries and reabsorbed by the epithelial cells of the PCT. True/False

Back 35

True. It is a 2 step process involving Na+-glucose cotransport(SGLT) across the luminal membrane and facilitated glucose transport across the peritubular membrane.

Front 36

36. It is known that glucose transport has a transport maximum. What does this mean?

Back 36

Because there are a limited number of glucose transporters, the mechanism is saturable, it has a transport maximum.

Front 37

37. Glucose moves from tubular fluid into the cell on the Na+ glucose cotransporter. True/False

Back 37

True. Two sodium ions and one glucose bind to the cotransport protein, the protein rotates in the membrane and sodium and glucose are released into the ICF.

Glucose is transported against an electrochemical gradient. The energy for this uphill transportof glucose comes from the downhill movement of sodium.

Front 38

38. In glucose transport, how is the sodium gradient maintained?

Back 38

It is maintained by the sodium -potassium ATPase in the pertubular membrane. ATP is used to energize this reaction. This is secondary active transport.

Front 39

39. Glucose is transported from the cell into peritubular capillary blood by facilitated diffusion. True/False

Back 39

True. Glucose is moving down its electrochemical gradient and no energy is required.

Front 40

40. What are Glut-1 and GLUT-2 proteins?

Back 40

These proteins are involved in facilitated diffusion of glucose. These belong to a larger family of carriers.

Front 41

41. What is the glucose titration curve?

Back 41

This shows the relationship between plasma glucose concentration and glucose reabsorption. this is obtained by infusing glucose and measuring its rate of reabsorption as the plasma concentration is increased.

Front 42

42. Regarding glucose, what is meant by filtered load?

Back 42

Glucose is freely filtered across glomerular capillaries and the filtered load is the product of GFR and plasma glucose concentration.

(Filtered load= GFR X [P]x.

As the plasma glucose concentration is increased, the filtered load increases linearly.

Front 43

43. At what level (numerical) can all filtered glucose be absorbed?

Back 43

At 200mg/dL. This is so because Na+ glucose cotransporters are plentiful. Reabsorption = Filtration.

Front 44

44. In reference to question 43, at plasma glucose concentrations above 200mg/dL?

Back 44

The reabsorption curve bends because some of the filtered glucose is not reabsorbed.

At plasma concentrations above 350mg/dL, the carriers are completely saturated and reabsorption levels off at its maximal value, T(m).

At concentrations above 200 mg, carriers are nearing the saturation point. Glucose that is not reabsorbed is excreted in urine.

Front 45

45. In reference to glucose, define threshold, and compare it to T(m).

Back 45

The plasma concentration at which glucose is first excreted in the urine is called threshold. This occurs at a lower plasma concentration than does T(m). Above 350mg/dL, T9m) is reached and the carriers are fully saturated.

Front 46

46. Define "splay" regarding glucose absorption.

Back 46

Splay is that portion of the titration curve where reabsorption is approaching saturation, but it is not fully saturated. Due to splay, glucose is excreted in the urine (threshold) , before reabsorption levels off at the T(m) value.

Front 47

47. What are the two explanations for Spaly?

Back 47

1. Low affinity

2. Heterogeniety

Front 48

48. Explain briefly the low affinity theory for splay.

Back 48

This is based on a low affinity of the Na+ glucose cotransporter. Near T(m) if glucose detaches from its carrier, it will be excreted into the urine (before it can be reabsorbed) because there are few remaining binding sites where it may reattach.

Front 49

49. Explain briefly the heterogeniety theory for splay.

Back 49

This is based on the heterogeniety of nephrons. T(m) for the whole kidney reflects the average T(m) of all nephrons, yet not all nephrons have exactly the same T(m). Some nephrons reach T9m) at lower plasma levels than others and glucose will be excreted in the urine before the average T(m) is reached.

Front 50

50. What occurs in Diabetes mellitus regarding glucose reabsorption and excretion?

Back 50

In uncontrolled Diabetes mellitus, lack of insulin causes the plasma concentration of glucose to increase to very high levels. The filtered load of glucose exceeds the reabsorption capacity (above the T(m). Glucose is excreted in the urine.

Front 51

51. How does pregnancy affect reabsorption and excretion of urine?

Back 51

During pregnancy, GFR is increased, which increases the filtered load of glucose to the extent that it may exceed the reabsorptive capacity.

Some congenital abnormalities of the Na+ glucose cotransporter are associated with decreases in T9m), resulting in the excretion of glucose at lower than normal plasma levels.