Glomerular Filtration and Renal Blood Flow Flashcards
What is the normal GFR?
~ 180 L/day
GFR= Kf x NFP
GFR depends on what two factors
- Balance of hydrostatic and colloid osmotic forces across the capillary membrane.
- Capillary filtration coefficient (Kf)- Permeability of capillaries and surface area of capillaries.
Filtration fraction
The amount of the plasma that becomes filtrate
~ 20%
What are the three layers of the glomerular filtration membrane?
- Capillary endothelium (with fenestrations)
- Basal lamina/ basement membrane
- Epithelium of the outer surface (podocytes)
Each layer contains negative charges that make it difficult/ impossible to pass through the membrane.
What are two factors that influence the filterability of solutes?
- Size (smaller the solute the greater the ability to filter it)
- Charge (Positively charged more easily filtered)
What are two ways that capillary filtration coefficient (Kf) can be decreased?
- Decreasing the number of functional glomerular capillaries
- Thickening the basement membrane
These changes could eventually change the GFR
Net filtration pressure in the glomerulus: Forces favoring movement out of the capillary
Glomerular hydrostatic pressure= 60
Bowman’s capsule colloid osmotic pressure (zero in normal physiology)
Net filtration pressure in the glomerulus: forces opposing filtration (into the capillary)
Bowman’s capsule hydrostatic pressure = 15
Glomerular capillary colloid osmotic pressure = 29
Capillary colloid osmotic pressure is influenced by:
- Arterial plasma colloid osmotic pressure
2. Filtration fraction = GFR/ renal blood flow
What are some ways to modify hydrostatic pressure: Bowman’s capsure
We do not usually alter this in normal physiology. But it can be elevated if there is an obstruction of the urinary tract.
Ways to modify hydrostatic pressure: Glomerular capillary
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
Renal blood flow effects on GFR
Increase leads to increased GFR
Decrease leads to decreased GFR
Ohm’s law for renal blood flow
RBF= (RAP-RVP)/ Total renal resistance. This is maintained intrinsically by autoregulation for arterial pressures of 80-170 mm Hg.
Sympathetic nervous system control of GFR
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.
Hormone signaling on GFR: Norepi and Epi
Constrict renal blood vessels and decrease GFR
Hormone signaling of GFR: Endothelin
Constricts renal blood vessels and decrease GFR
Hormone signaling of GFR: Angiotensin II
Prevents a decrease in GFR by constricting EE
Hormone signaling of GFR: Endothelial-derived nitric oxide
Dilate renal blood vessels and cause increased GFR
Hormone signaling of GFR: Prostaglandins
Dilate renal blood vessels and cause increased GFR
Autoregulation of GFR
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.
Tubuloglomerular feedback and autoregulation of the GFR
Links changes in the NaCl concentration in the distal tubule at the macula densa with control of renal arteriolar resistance.
What structures comprise the juxtaglomerular complex?
- Macula densa
2. Granular cells
What is the function of the macula densa?
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)
Tubuloglomerular feedback: decreased GFR
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
Tubuloglomerular feedback: Increased GFR
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
Emergency kidney protection : Myogenic mechanism
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.
High protein intake and GFR
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)
Increased blood glucose and GFR
Glucose is reabsorbed with sodium in the proximal tubule so increasing it will cause decreased NaCl concentration.
Urinary excretion rate
Rate at which substances are excreted in the urine is affected by:
- Glomerular filtration (GFR)
- Tubular reabsorption (RR)
- Tubular secretion (SR)
= GFR- RR + SR
Tubular reabsorption
The substances coming back into the blood after being filtered. It is very large as most substances are almost entirely reabsorbed.
What are the two mechanisms by which reabsorption from kidney tubules into the blood can occur?
- Paracellular pathway
2. Transcellular
Paracellular pathway of reabsorption
Movement of substances through tight junctions and intercellular spaces.
Transcellular pathway of reabsorption
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.
What is an example of some primary active transporters in the kidney?
- Na/K ATPase pump
- Hydrogen ATPase
- Hydrogen-potassium ATPase
- Calcium ATPase
Movement of solutes across the proximal tubule
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.
Secondary active reabsorption
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)
Secondary active secretion
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!
Pinocytosis of proteins
A form of active transport to remove any proteins that do make it into the filtrate.
Transport maximum
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
Threshold
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.
Gradient-time determined absorption
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.
Tansport maximun: Na+
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
Passive water reabsorption
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
Passive diffusion: Cl
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.
Passive diffusion: Urea
Osmosis to interstitial causes increase in urea in lumen which then passively diffuses (~50%) to the IF.
Solute that is NOT reabsorbed
Creatinine
A waste product of metabolism that is too larger to be reabsorbed. ALL that is filtered is excreted in the urine.
