Glomerular Filtration and Renal Blood Flow

Question 1

What is the normal GFR?

Answer 1

~ 180 L/day

GFR= Kf x NFP

Question 2

GFR depends on what two factors

Answer 2

1. Balance of hydrostatic and colloid osmotic forces across the capillary membrane.
2. Capillary filtration coefficient (Kf)- Permeability of capillaries and surface area of capillaries.

Question 3

Filtration fraction

Answer 3

The amount of the plasma that becomes filtrate

~ 20%

Question 4

What are the three layers of the glomerular filtration membrane?

Answer 4

1. Capillary endothelium (with fenestrations)
2. Basal lamina/ basement membrane
3. Epithelium of the outer surface (podocytes)

Each layer contains negative charges that make it difficult/ impossible to pass through the membrane.

Question 5

What are two factors that influence the filterability of solutes?

Answer 5

1. Size (smaller the solute the greater the ability to filter it)
2. Charge (Positively charged more easily filtered)

Question 6

What are two ways that capillary filtration coefficient (Kf) can be decreased?

Answer 6

1. Decreasing the number of functional glomerular capillaries
2. Thickening the basement membrane

These changes could eventually change the GFR

Question 7

Net filtration pressure in the glomerulus: Forces favoring movement out of the capillary

Answer 7

Glomerular hydrostatic pressure= 60

Bowman’s capsule colloid osmotic pressure (zero in normal physiology)

Question 8

Net filtration pressure in the glomerulus: forces opposing filtration (into the capillary)

Answer 8

Bowman’s capsule hydrostatic pressure = 15

Glomerular capillary colloid osmotic pressure = 29

Question 9

Capillary colloid osmotic pressure is influenced by:

Answer 9

1. Arterial plasma colloid osmotic pressure

2. Filtration fraction = GFR/ renal blood flow

Question 10

What are some ways to modify hydrostatic pressure: Bowman’s capsure

Answer 10

We do not usually alter this in normal physiology. But it can be elevated if there is an obstruction of the urinary tract.

Question 11

Ways to modify hydrostatic pressure: Glomerular capillary

Answer 11

This is the primary means of altering GFR for normal physiology. Can be done by constriction and dilation of the afferent and efferent arterioles.

Constrict AA and dilate EA for decreased GFR

Constrict EA and dilate AA for increased GFR

Question 12

Renal blood flow effects on GFR

Answer 12

Increase leads to increased GFR

Decrease leads to decreased GFR

Question 13

Ohm’s law for renal blood flow

Answer 13

RBF= (RAP-RVP)/ Total renal resistance. This is maintained intrinsically by autoregulation for arterial pressures of 80-170 mm Hg.

Question 14

Sympathetic nervous system control of GFR

Answer 14

Moderate to mild sympathetic stimulation has no significant effect of renal blood flow.

Strong sympathetic nervous system activation decreased GFR through strong constriction of the renal arterioles. This can only be useful for minutes and in extreme cases of blood loss.

Question 15

Hormone signaling on GFR: Norepi and Epi

Answer 15

Constrict renal blood vessels and decrease GFR

Question 16

Hormone signaling of GFR: Endothelin

Answer 16

Constricts renal blood vessels and decrease GFR

Question 17

Hormone signaling of GFR: Angiotensin II

Answer 17

Prevents a decrease in GFR by constricting EE

Question 18

Hormone signaling of GFR: Endothelial-derived nitric oxide

Answer 18

Dilate renal blood vessels and cause increased GFR

Question 19

Hormone signaling of GFR: Prostaglandins

Answer 19

Dilate renal blood vessels and cause increased GFR

Question 20

Autoregulation of GFR

Answer 20

Renal blood flow and GFR are relatively constant (to allow for precise control of renal excretion of salt and water).

This is a unique example of autoregulation – not to receive proper nutrients, but for proper excretion of water and solutes. If the kidneys did not have this mechanism then even small increases in BP could cause us to lose larges amounts of fluid in the urine.

Question 21

Tubuloglomerular feedback and autoregulation of the GFR

Answer 21

Links changes in the NaCl concentration in the distal tubule at the macula densa with control of renal arteriolar resistance.

Question 22

What structures comprise the juxtaglomerular complex?

Answer 22

1. Macula densa

2. Granular cells

Question 23

What is the function of the macula densa?

Answer 23

Located in the distal tubule in close contact with the afferent and efferent arterioles that detects the concentration of NaCl in the tubular filtrate. (this is related to GFR, low GFR= low NaCl)

Question 24

Tubuloglomerular feedback: decreased GFR

Answer 24

If decreased GFR, this will be sensed in the macula densa as decreased NaCl.

This will cause a decreased resistance in the afferent arterioles and increase in release of renin from granular cells –> constricts EE.

Overall this will lead to increased GHP and increased GFR

Question 25

Tubuloglomerular feedback: Increased GFR

Answer 25

If increased GFR, this will be sensed in the macula densa as increased NaCl. This will cause an increased resistance at the afferent arteriole and decrease in renin release from granular cells to dilate EE. Overall this leads to decreased GHP and GFR

Question 26

Emergency kidney protection : Myogenic mechanism

Answer 26

Individual blood vessels resist stretching during sudden increased arterial pressure by smooth muscle contraction. This helps to maintain relatively constant renal blood flow and GFR.

Question 27

High protein intake and GFR

Answer 27

Partly due to growth of the kidneys long term. After a high protein meal, GFR, and RBF increased 20-30% due to increased AA reabsorption at the proximal tubule which occurs concurrently with sodium reabsorption (decreased NaCl sensed at the macula densa)

Question 28

Increased blood glucose and GFR

Answer 28

Glucose is reabsorbed with sodium in the proximal tubule so increasing it will cause decreased NaCl concentration.

Question 29

Urinary excretion rate

Answer 29

Rate at which substances are excreted in the urine is affected by: 1. Glomerular filtration (GFR) 2. Tubular reabsorption (RR) 3. Tubular secretion (SR) = GFR- RR + SR

Question 30

Tubular reabsorption

Answer 30

The substances coming back into the blood after being filtered. It is very large as most substances are almost entirely reabsorbed.

Question 31

What are the two mechanisms by which reabsorption from kidney tubules into the blood can occur?

Answer 31

1. Paracellular pathway | 2. Transcellular

Question 32

Paracellular pathway of reabsorption

Answer 32

Movement of substances through tight junctions and intercellular spaces.

Question 33

Transcellular pathway of reabsorption

Answer 33

Through the cells themselves. Movement from lumen --> apical membrane of tubule cell --> basement membrane --> interstitial fluid --> Through peritubular capillary wall by ultrafiltration which is a net absorption force that moves solutes into the blood.

Question 34

What is an example of some primary active transporters in the kidney?

Answer 34

1. Na/K ATPase pump 2. Hydrogen ATPase 3. Hydrogen-potassium ATPase 4. Calcium ATPase

Question 35

Movement of solutes across the proximal tubule

Answer 35

Most everything moves from the lumen to the basolateral membrane and into IF. Na, anions, and water move down concentration gradient through lumen. Na/K pumps gets sodium across the basolateral membrane.

Question 36

Secondary active reabsorption

Answer 36

Glucose and amino acids are move against their concentration gradient across the lumen. This requires co-transport with Na (SGLT2, SGLT1) Glucose and amino acids exit through the basolateral membranes by facilitate diffusion (GLUT2, GLUT1)

Question 37

Secondary active secretion

Answer 37

Na/H counter-transport moves Na does its electrochemical gradient into the cell while H is move against its gradient back into the lumen. Vital in maintaining pH in the body!

Question 38

Pinocytosis of proteins

Answer 38

A form of active transport to remove any proteins that do make it into the filtrate.

Question 39

Transport maximum

Answer 39

Most substances that are actively reabsorbed have a maximum rate of transport due to saturation of carrier proteins, limited ATP, etc. once this transport speed is reached for all nephrons, further increases in tubular load are not reabsorbed and are excreted. Ex: Glucose ~ 2 mmol/min

Question 40

Threshold

Answer 40

The tubular load at which the transport maximum is exceeded in some nephrons. At this point the substance begins to appear in the urin. This is lower than the transport maximum.

Question 41

Gradient-time determined absorption

Answer 41

Many passively absorbed substances do not exhibit transport max but do absorb differently based on: 1. Electrochemical gradient 2. Permeability of the membrane to the substance 3 Time that the fluid containing substance remains in the tubule.

Question 42

Tansport maximun: Na+

Answer 42

Some actively tansported substances do not exhibit transport maximums at all times. Transport capacity of Na+/K+ pump on basolateral membrane far exceeds actual rate of net sodium absorption in proximal tubule so it is mainly guided by gradient-time characteristics. In later parts of tubule, sodium does exhibit transport maximum because cells have tighter junctions and much smaller amounts of sodium are transported there

Question 43

Passive water reabsorption

Answer 43

As solutes are transported from lumen to IF, water follows by osmosis. water permeability: Proximal tubule – high Ascending Loop of Henle and early distal tuble – zero Late distal tubules, collecting tubules, collecting ducts – variable depending on ADH

Question 44

Passive diffusion: Cl

Answer 44

Electrical attraction to the interstitial across paracellular pathway due to remove of Na of tubule leaving it negative. Osmosis to interstitium causes increased in Cl- in lumen which causes it to go down concentration gradient to intersitium.

Question 45

Passive diffusion: Urea

Answer 45

Osmosis to interstitial causes increase in urea in lumen which then passively diffuses (~50%) to the IF.

Question 46

Solute that is NOT reabsorbed

Answer 46

Creatinine | A waste product of metabolism that is too larger to be reabsorbed. ALL that is filtered is excreted in the urine.