Renal Blood Flow. Filtration and CLearnace Week 1

Question 1

Average urnie flow per day

Answer 1

1.5 L

Question 2

Is water filtered, reabsorbed and secreted

Answer 2

Water is NOT secreted

Is is filtered and reabsorbed (almost compeltely reabsorbed)

Question 3

What are the advantageous and disadvantagous of our kidneys filtration?

What are solutes that are good examples of the disadvantage?

Answer 3

Advantage- filtration is that no specific transport system is needed for something to be eliminated from the body - just allow it to be filtered and do not reabsorb it

Disadvantange- nonselective filtration is that the body must expend considerable energy to reabsorb filtered substances that it needs to retain. We almost entirely reabsord Na, CL, Glucose HCO3 and water into the peritublar capillaries.

Question 4

Value of Renal Blood Flow

Relation to CO

Answer 4

1.1 L/min

20-25% of CO

This far exceeds what the kidney needs to iver, so if change in reponse to other physiological needs withou kidney cells paying metaboolic price/death

Question 5

Value of Renal Plasma Flow RPF

Answer 5

625 ml/min

A little less than half of RBF

RBF- (1-hemotacrit)= RPF

Question 6

Average GFR

Answer 6

125ml/min

Question 7

Average Urine Flow rate

Relation to GFR

Answer 7

1ml/min

Less than 1% of GFR

Question 8

Filtration Factor

What does this mean for easily filtered solutes?

Answer 8

Filtraiton factor= GFR/RPF= .2

Remember about 20% of plasma is filered

They are also filtered at about 20% into BC since they are freely filtered.

Question 9

What are the major differences between capillaries in the renal system and those throughout the body?

Answer 9

1. Most capillaries have a net filtration on the capillary end and net reabsorption on the venous end…. the renal capillaries have net filtraiton in BC along the length of the capillary
2. Renal system has a a higher hydrostatic pressure ~55mm Hg, while the rest of the body is about 25mmHg. HIgher pressure because the afferent arteriole diameter is larger than the efferent.
3. Hydrostatic pressure decreases in most of the body because there is high resistance so pressure falls with distance, but in the renal system is constant because there is relatively low resistance.
4. In renal system the colloid oncotic pressure increases with distance (makes sense because we are filtering out a larger volume of water leaving higher concentration of solutes in plasma), but in the capillary else where oncotic is fairly constant.

Question 10

What are the pressures that favor filtration and the values

Oppose filtation and average values

So what’s the equation for net filtration

Answer 10

Favor- Hydrostatic in GC AKA the BP of GC
~55mmHg

Oppose- PLasma Colloid Oncotic pressure ~30mmHg

Oppose- Hydrostatic of Bowman’s Space/Capsule ~15 mmHg

Net filtration= Pressure of GC- (πGC + Pressure of Bowmans Space)

55- (30+15)= 10mmHg net filtrtaion into BC

Question 11

What factors affect GFR

Answer 11

K_f - this is the filtration coefficient and considers the hydraulic permeability of the glomerular capillaries and SA- physical properities

Net Filtration Pressure-

So GFR= K_f x NFP

Question 12

Why is the K_f filtraiton coefficient larger in the renal system?Amoutn filtered per/day?

Do other processes (secretion/reabsorption) happen at the GC?

Answer 12

The glomerular capillaries hydraulic permeability is larger because of the fenestrated endothelial and SA is higher because of the extensive branching and looping of the glomerular capillaries.

So filtration coeffieicnt being high combined with a postive NFP favor filtration– hence the 180 L/day filtered.

Remember that NO reabsorption happens at the Glomerular capillaries- they are solely specialized in filtration.

Question 13

What are factors that can influence GFR…other than K_f and NFP? (6)

Answer 13

1. Urinary tract obstruction (like a kidney stone)- leads to an increase in Pressure_BC (oppose filtraiton) so there is more filtration and lower GFR
2. Changing MAP- increaing MAP leads to an increase in P_GC so more filtration and higher GFR — although this can be limited through autoregulation
3. Renal artery stenosis- would reduce P_GC so less filtraiton and lower GFR in affected kidney
4. Reduction in the amount of nephrons- this would reduce K_f and thus reduce GFR – each kidney has about 1 million nephrons so loss in half would proportionally reduce Kf and GFR to half.
5. Sympathetic NS- through mesangial cells which can 1. Constrict affernet arteriole and reduce P_GC 2. K_f by closing down some of the loops in the glomerular capillary bed. Can happen together or indivdually and reduce GFR
6. Loss in plasma oncotic proteins- (possibly due to starvation or renal disease) this opposes filtration so loss in proteins would lead to an increase in GFR.

Question 14

Interestingly, RBF (and GFR) can remain relatively constant even when arterial blood pressure changes. Why?

Answer 14

Autoregulation! instrinic property of kidneys that can happen even when the kidneys are isolated and denervated without hormonal help. Normal MAP is 80-180mmHg and RBF remains 1.1l/min and GFR 125ml/min.

Autoregulation will fail at extreme MAPs (like under 80mmHG MAP we get a decrease in GFR).

Question 15

Can autoregulation be overrideen?

Answer 15

YES! It doesn’t need innervatin or hormones to work but it can be overridden by exstrinic signals to the kdieny from the sympathetic NS or circulating angiotensin II.

Question 16

Two mechanism of intrinsic autoregulation

Answer 16

• *1. myogenic**- less important but used throughout body- when arterioles are stretch due to increase BP, they contract increasing resistance so in this cause the afferent arteriole constracts. Believe that stretching depolarizes the smooth muscle cells in the wall, activating Ca2+ channels and leading to contraction.– reduced stretch would lead t hyperrolzarizationand relaxation
• *2. tubuloglomerular feedback** - at the Juxtaglomerular apparatus. The distal tube (and its macula dense) and the arterioles that control blood supply are juxtapositioned. Increase in MAP–> INcrease in P_GC—> incrase GFR–> increase tubular flow so increase NaCL to macula densa

The macula dense sense this increas and release ATP? (uncertain) wihch diffuses LOCALLY causing and constricts the afferent arteriole decreasing P_GC and thus decreasing filtration and flow into the distal tube

Note the renin on the distal tube is not involved in augoreulgation

Question 17

Define renal clearance

Answer 17

Renal clearnace of any substance is defined as the volume of plasma cleared of that substance by the kidneys per minute.

Think about the plasma leaving through the veisn that has left behind it’s solutes for excretion in the kidneys.

Clearnace can be calculated and tells us how well the kidneys are working. REMEMBER IT”S THE VOLUME OF PLASMA that has been cleared of a solute of ML/MIN

Question 18

Equation for clearnace.

Answer 18

C_{x =} (U_x x V)/P_x

The amount of X from cleared plasma (P x C)= amouinf of X excreted (U_x x V)

Question 19

What are the 3 substances often considered when probing for diagnsotic tools of renal function

Answer 19

Inulin ~ GFR (gold standard, but not natural in body)

PAH ~ RPF

Creatinin rough approx of GFR

Question 20

Explain the clearance of INulin

Answer 20

This is the gold standard of calculatigGFR. Freely fitlered but not absorbed or secreted. So everything that enters the nephrons through filtrtion witll be excreted, so plasma cleared of inulin/time = GFR.

1. Inulin is freely filtered.
2. Inulin is neither reabsorbed nor secreted. The nephron tubules have no inulin transporters and inulin can not diffuse out of the tubules so all that is filtered will be excreted.
3. There are no enzymes in the tubules that break down or synthesize inulin.

Downfall is that inulin isn’t natural occurring so must be infused in body

Question 21

Explain clearnace of PAH

Compare it to Inulin- higher or lower?

Answer 21

1. Freely filtered (like inulin)
2. Also rebostly secreted in proximal tubule but there is a max secretion limited by T_M
3. This filtration and robust secretion means almost all of the PAH from plasma is secreted (~90%)
4. Since filtration is only about 20% such a high value needs secretion as well.
5. So PAH is a good estimate (although a little under) RPF

Question 22

When is PAH a good indicator of RPF

Answer 22

The point is that PAH clearance predictions of RPF are best when the PAH secretion mechanism
is not saturated (i.e. when its working below its TM).

If only a little is filtered, then more needs to be secreted and if at a trasnport max than this can’t happen.

Question 23

Why isn’t all PAH excreted?

Answer 23

Some come outs in fitleration (20%) and about (70%) is secreted

The PAH secretory mechanism is in the proximal tubule and PAH in the peritubular capillaries surrounding the proximal tubule is secreted. However, some PAH containing plamsa goes to capillaries that perfuse other regions of the nephron (e.g. vasa recta). PAH in this plasma is not secreted and will
escape back into the systemic circulation. Typically, this amounts to 10% of the PAH explaining the “nearly all 90%” value given above. This is why CPAH underestimates true RPF

Question 24

What two things can PAH estimate? Explain

Answer 24

RPF- 90% is excreted (10 through filtrationa nd 70 through secretion)

RBF X (1 - hemotocrit)= RPF

PAH isn’t usally used– creatinine is used in clinical settings normally

Question 25

Eplain the clearnace of creatitine.

Answer 25

1. CINULULI is the “gold standard” for clinical GFR determinations. Unfortunately, inulin is not a naturally occurring substance in the body. A CINULULI measurement requires administration
   of inulin into the blood at a rate that will keep its concentration in the plasma constant throughout the measurement period.

Creatinine is the the end product of creatine metabolism and is continously dumped inot blood by skeletal muscle at a fairly cosntant rate proportotional to person’s muscle mass.

1. Creatinine is freely filtr
2. Not reabsorbed and a little bit is secreted in proximal tubule (10-20%) – thus a little higher than GFR but still most common indictoar of GFR

Question 26

Normal values of Plasma Creatine and GFR

What happens if GFR is cut in half one day to the plasma creatinine? Why doesn’t it just contiune to rise

Answer 26

Plasema Creatine= 1mg/dl

GFR= 125ml/min

If GFR cut in half the plasma creatinine will double. It won’t rise past double because our body still makes 1 mg/dl regardless of kidney function.

Question 27

Problems with creatinine cliinically.

Answer 27

1. this method is not completely accurate because some creatinine is secreted.
2. Another issue is that a person’s normal PCREATININE may be unknown before a renal crisis arises
   so a sudden change may not be obvious.

However, an abnormally high PCREATININE is always a
red flag and suggests that there may be a renal problem

Question 28

What is the third (less accurate) estimator of GFR?

Answer 28

BUN

Used after creatinine and iulin usually