Test 5 - renal Flashcards
What are the 3 barriers of glomerular filtration?
Glomerular capillary endothelium
Glomerular basement membrane
Visceral epithelium (podocytes)
How large are the fenestrations in the glomerular capillary endothelium?
~100nm
Is the glomerular basemement membrane positively or negatively charged?
negatively
How large are the filtration slits in the visceral epithelium (podocytes)?
~40nm
What is renal blood flow? What is percentage of renal blood flow?
Renal blood flow is the fraction of blood the kidneys recieve from total cardiac output
20%
What is renal plasma flow?
Renal plasma flow (RPF)
RPF = RBF x (1 - hematocrit)
What is normal glomerular filtration rate?
~125 mL/min
What are the 4 starling forces that govern movement of fluids across the glomerulus? Which force is negligible?
Glomerular Hydrostatic Pressure
Glomerular Oncotic pressure
Bowman’s Capsular Hydrostatic Pressure
Bowman’s Capsular Oncotic Pressure (negligible)
What is the filtration coefficient?
the product of hydraulic permeability (permeability of the capillary) and surface area (of the capillary)
Where is the macula densa? What does it interact with?
The junction between the loop of Henle and the DCT that courses between the afferent and efferent arterioles
Smooth muscle in the afferent arteriole: Granular cells
What do granular cells and the macula densa form? What are its functions?
the juxtaglomerular apparatus
regulation of GFR and systemic blood volume and pressure
What in the juxtaglomerular apparatus secretes renin?
granular cells (smooth muscle in the afferent arteriole)
How does the JGA work? (two functions based on Cl- concentation in the nephron)
tubuloglomerular feedback:
Macula densa senses the amount of Cl- via the NKCC transporter on the macula densa. If Cl- levels are high, the macula densa signals smooth muscle in the afferent arteriole via adenosine to contract, decreasing GHP and thus GFR
Renin response:
Macula densa senses the amount of Cl- via the NKCC transporter on the macula densa. If Cl- levels are low (volume loss), the macula densa signals granular cells in the afferent arteriole via PGE2 to vasodilate and secrete renin
What are the 3 factors that mediate renal autoregulation (RBF and GFR)
Myogenic reflex
tubuloglomerular feedback
neurohormonal factors
Describe tubuloglomerular feedback
Macula densa senses the amount of Cl- via the NKCC transporter on the macula densa. Increased GHP leads to an increase in Cl- levels. The macula densa senses this increase and signals smooth muscle in the afferent arteriole via adenosine to contract, decreasing GHP and thus GFR
Describe myogenic reflex
An autoregulatory range allows for flow to remain constant through afferent arterioles. As pressure increases within the autoregulatory range, smooth muscle contracts in an attempt to maintain steady flow. As pressure decrease within the autoregulatory range, smooth muscle relaxes in an attempt to maintain steady flow.
Describe neurohormonal factors (RAAS components) in regulating RBF and GFR
Renin converts angiotensinogin (liver) to angiotensin I. ACE (lungs and kidney) convert angiotensin I to angiotensin II. Angiotensin II does a lot of stuff
Secretion of renin is regulated by 3 things. What are they?
Intrarenal baroreceptors
macula densa
renal sympathetic nerves
How do intrarenal baroreceptors regulate renin secretion? What would happen if the baroreceptors sensed a fall in pressure?
the granular cells in the JGA are baroreceptors that monitor afferent arteriole pressure.
A fall in pressure would result in the secretion of renin
How does the macula densa regulate renin secretion? What would happen if the macula densa sensed a fall in tubular Cl-?
Macula densa senses the amount of Cl- via the NKCC transporter on the macula densa.
If Cl- levels are low (volume loss), the macula densa signals granular cells in the afferent arteriole via PGE2 to secrete renin
How do renal sympathetic nerves regulate renin release?
vascular baroreceptors sense low BP —> increased sympathetic tone to kidney —> renin release by granular cells
What are the 4 major actions of angiotensin II?
- Vasoconstriction
- contsticts arterioles throughout the body
- Na+ balance
- Na+ reabsorption in PCT
- stimulates aldosterone release –> Na+ reabsorption in the distal nephron
- Water balance
- stimulates ADH release –> H2O reabsorption distal nephron
- stimulates thirst
- Effects on GFR
- low dose, no effect little effect on GFR as it mostly works on efferent arteriole
- High dose, decrease in GFR as it constricts afferent and efferent arterioles
Describe the SNS control over the kidney during hypotension
During hypotension, SNS causes vasoconstriction, which diverts blood from the kidney to other vital organs. This minimizes the loss of water and salt
At rest, is the sympathetic tone to the kidney low?
you betcha
Which prostaglandins are secreted in response to sympathetic stimulation and angiotensin II? What do they dampen?
PGE2 and PGI2
They are powerful vasodilators that dampen vasoconstriciton of the afferent arterioles
What does Kidney Function refer to?
GFR
How does GFR change with age?
GFR decreases
Is urinary excretion the same as GFR?
NO! GFR is the amount of plasma filtered. As filtrate moves along the nephron, reabsorption and secretion alters the volume that is acutally excreted (urinary excretion)
What is fractional excretion?
The amount of filtration that is acutally excreted
What does a clearance fraction of 100% indicate? What does a clearance fraction less than 100% indicate? How is it possible to have a fractional excretion above 100%?
A CF of 100% indicates no reabsorption or secretion occured
A CF less than 100% indicates reabsorption occured
A CF >100% indicates no absortion occured and some secretion occured
What is clearance?
Clearance is the volume of plasma from which a substance is completely cleared per unit time
What is the equation for clearance?
Clearance = UV/P
U is the urine concentration of the substance
V is the urine volume
P is the plasma concentration of the substance
If a substance is freely filtered, neither secreted or absorbed, and not metabolized, then the clearance of this substance can be used as a measure of ______?
GFR
Therefore, GFR = UV/P
What is inulin?
Gold standard to determine GFR
Inulin is used to help measurekidney function by determining the glomerular filtration rate (GFR) because it is freely filtered, neither secreted or absorbed, and not metabolized
How is renal plasma flow measured? (equation) what substance is used?
RPF = UV/P
para-aminohippurate
How is renal function assessed in clinical practice? (3 things)
Serum creatinine (estimate)
creatinine clearance (calculate)
MDRD equation (estimate)
What is BUN? Can it be used to accuratly determine GFR?
Blood urea nitrogen
No. BUN is not accurate because it also depends on diet, muscle breakdown, GI bleeding, and volume depletion
What is the equation for GFR using creatinine clearance?
GFR= UCr x V/PCr
UCr = urine creatinine concentration
V = urine flow rate
PCr = serum creatinine concentration
What is MDRD formula?
Modification of Diet in Renal Disease
GFR = 186 x (PCr)^-1.154 x (age)^-0.203 x (0.742 if female) x (1.210 if black)
When would you use and NOT use the MDRD equation?
Key points:
- Serum creatinine must be in steady state - do not use in acute kidney injury
- Does not work well at high levels of renal function (anything over 60 ml/min should just be reported as >60)
Do not use for people younger than 18 or older than 75, for obese people, for very muscular or wasted people, or pregnant people
What is the cockroft equation?
What are the 4 major functions of the proximal convoluted tubule?
Main site for tubular reabsorption
secretion of substances from the peritubular capillaries
ammoniagenesis (generation of ammonium from glutamine)
1-alpha-hydroxylation (convertion of cholecalciferol to calcitriol)
How much Na+, H2O, K+, and bicarbonate are reabsorbed at the proximal convoluted tubule (percentages)?
Na+ = 65%
K+ = 65%
H2O = 65%
HCO3- = 80-90%
What channel allows for reabsorption of Na+ and ONLY Na+? What type of channel is it (active, passive, secondary active)? Is this considered transcellular movement or paracellular movement?
epithelial Na+ channel (ENaC)
The ENaC channel is powered by active transport on the basal surface of the cell
transcellular movement
What 3 channels allow for Na+ reabsorption along with the movement of another substance? What type of channels are they (active, passive, secondary active)? Is this transcellular or paracellular movement?
Na+/H+ antiporter (NHE3); secondary active transport; transcellular
Na+/Glucose co-transporter; secondary active transport; transcellular
Na+/Cl- paracellular transport
How is bicarbonate reabsorbed via the proximal tubule?
The NHE3 antiporter (Na+/H+) moves H+ into the lumen of the proximal convoluted tubule. This shifts the equation below to the right to form H2CO3. Carbonic anhydrase (C.A.) converts H2CO3 –> H2O + CO2. H2O and CO2 diffuse into the brush border cells where another C.A converts CO2 + H2O –C.A.–> H2CO3 –> H+ + HCO3-. HCO3- is then reabsorbed into the pericapillary tubules aling with Na+ via the NBC-1 co-transporter
H+ + HCO3- –> H2CO3 –C.A.–> H2O + CO2
What are the 2 major functions of the loop of Henle?
reabsorption
countercurrent system
How much Na+, H2O, K+, and HCO3- is reabsorbed by the loop of Henle?
Na+ (25%)
H2O (25%)
HCO3 (10%)
K+ (25%)
Where in the loop of Henle is water absorbed? Na+? (thin descending, thick ascending)
Water is absrobed in the thin descending
Na+ is absorbed in the thick ascending (impermeable to H2O)
How does the countercurrent system work?
Start from the ascending LOH. Na+ removed from the LOH moves into the opposite flowing vasa recta, increasing blood concentration. When the blood reaches the descending LOH, the water hypotonic filtrate moves into the hypertonic blood, which concentrates the filtrate and dilutes the blood. This loop allows for the removal of water from the filtrate so only waste is removed (along with a little bit of left over water)
How is Na+ removed from the thick ascending loop of Henle?
Via the NKCC channels
What portions of the nephron are considered part of the distal nephron?
distal convoluted tubule and the collecting duct
What are the 4 major functions of the distal nephron?
reabsorption
secretion
site of ADH activity
Site of Aldosterone activity
How does ADH work?
ADH stimulate aquaporin 2 insertion in the collecting duct cells via V2 receptors, which allows for the absorption of H2O into the vasa recta
ADH has 2 receptors: V1 and V2. What does what?
V1 = vasoconstriction
V2 = GPCR in collecting duct resulting in H2O reabsorption
How is K+ absorbed in the Proximal convoluted tubule?
paracelular passive reabsorption
What is the major mechanism of K+ reabsorption in the loop of Henle?
Major is paracellular.
NKCC transporters bring K+ into tubule cells, and K+ can diffuse into peritubular capillaries, also.
How does aldosterone work?
Aldosterone stimulates Na+/K+ pumps in the basal membrane and inserts epithelial Na+ channels (ENaC) and renal outermembrane K+ channels (ROMK) in the apical membrane. The highly activated Na+/K+ pumps increase intracellular removal of Na+ and increase intracellular concentrations of K+. intracellular K+ moves into the filtrate via ROMK and filtrate Na+ moves into the cell via ENaCs. Na+ is pumped out of the cell and into the vasa recta and H2O follows
In general, what are the 4 major functions of the nephron?
filtration
absorption
secretion
excretion
What is the normal range for creatinine excretion (in mg) per day in males, and females, respectively?
Males: 20-25 mg/kg/day
Females: 15-20 mg/kg/day
