Renal Blood Flow. Filtration and CLearnace Week 1 Flashcards
Average urnie flow per day
1.5 L
Is water filtered, reabsorbed and secreted
Water is NOT secreted
Is is filtered and reabsorbed (almost compeltely reabsorbed)
What are the advantageous and disadvantagous of our kidneys filtration?
What are solutes that are good examples of the disadvantage?
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.
Value of Renal Blood Flow
Relation to CO
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
Value of Renal Plasma Flow RPF
625 ml/min
A little less than half of RBF
RBF- (1-hemotacrit)= RPF
Average GFR
125ml/min
Average Urine Flow rate
Relation to GFR
1ml/min
Less than 1% of GFR
Filtration Factor
What does this mean for easily filtered solutes?
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.
What are the major differences between capillaries in the renal system and those throughout the body?
- 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
- 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.
- 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.
- 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.
What are the pressures that favor filtration and the values
Oppose filtation and average values
So what’s the equation for net filtration
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
What factors affect GFR
Kf - this is the filtration coefficient and considers the hydraulic permeability of the glomerular capillaries and SA- physical properities
Net Filtration Pressure-
So GFR= Kf x NFP
Why is the Kf filtraiton coefficient larger in the renal system?Amoutn filtered per/day?
Do other processes (secretion/reabsorption) happen at the GC?
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.
What are factors that can influence GFR…other than Kf and NFP? (6)
- Urinary tract obstruction (like a kidney stone)- leads to an increase in PressureBC (oppose filtraiton) so there is more filtration and lower GFR
- Changing MAP- increaing MAP leads to an increase in PGC so more filtration and higher GFR — although this can be limited through autoregulation
- Renal artery stenosis- would reduce PGC so less filtraiton and lower GFR in affected kidney
- Reduction in the amount of nephrons- this would reduce Kf and thus reduce GFR – each kidney has about 1 million nephrons so loss in half would proportionally reduce Kf and GFR to half.
- Sympathetic NS- through mesangial cells which can 1. Constrict affernet arteriole and reduce PGC 2. Kf by closing down some of the loops in the glomerular capillary bed. Can happen together or indivdually and reduce GFR
- 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.
Interestingly, RBF (and GFR) can remain relatively constant even when arterial blood pressure changes. Why?
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).
Can autoregulation be overrideen?
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.
Two mechanism of intrinsic autoregulation
- *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 PGC—> 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 PGC and thus decreasing filtration and flow into the distal tube
Note the renin on the distal tube is not involved in augoreulgation
Define renal clearance
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
Equation for clearnace.
Cx = (Ux x V)/Px
The amount of X from cleared plasma (P x C)= amouinf of X excreted (Ux x V)
What are the 3 substances often considered when probing for diagnsotic tools of renal function
Inulin ~ GFR (gold standard, but not natural in body)
PAH ~ RPF
Creatinin rough approx of GFR
Explain the clearance of INulin
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.
- Inulin is freely filtered.
- 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.
- 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
Explain clearnace of PAH
Compare it to Inulin- higher or lower?
- Freely filtered (like inulin)
- Also rebostly secreted in proximal tubule but there is a max secretion limited by TM
- This filtration and robust secretion means almost all of the PAH from plasma is secreted (~90%)
- Since filtration is only about 20% such a high value needs secretion as well.
- So PAH is a good estimate (although a little under) RPF
When is PAH a good indicator of RPF
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.
Why isn’t all PAH excreted?
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
What two things can PAH estimate? Explain
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
Eplain the clearnace of creatitine.
- 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.
- Creatinine is freely filtr
- 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
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
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.
Problems with creatinine cliinically.
- this method is not completely accurate because some creatinine is secreted.
- 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
What is the third (less accurate) estimator of GFR?
BUN
Used after creatinine and iulin usually
