Renal Flashcards
What are the parts of the nephron in order of flow of filtrate?
Glomerulus
Proximal convoluted tubule
Loop of Henle (descending, thin ascending, thick ascending)
Distal convoluted tubule
Collecting duct
What are the 2 mechanisms that create glomerular selectivity?
Size (pore slit of the diaphragm is 25-60kDa; >65kDa structures can’t make their way through the glomerulus)
Charge (negatively charged substances can’t pass through the glomerulus because all three layers carry a negative charge)
What type of collagen is found in the basement membrane of the glomerulus?
Type IV (negatively charged)
4 = floor (basement membrane)
What is normal GFR for dogs and cats?
Dogs: 3.5-4.5mL/min/kg
Cats: 2.5-3.5mL/min/kg
Amlodipine causes __ which increases glomerular filtration pressure
selective dilation of the afferent arteriole
ACE inhibitors like enalapril cause __ which decreases GFR
selective dilation of the efferent arteriole
What is the Donnan effect?
Effect where an increase in colloid osmotic pressure secondary to severe efferent arteriolar constriction causes decreased GFR
How much functional nephron mass must be lost before an azotemia develops?
75%
How is renal clearance calculated for a substance (formula)
Clearance = (Urine clearance * Urine flow rate) / (plasma concentration of substance)
What properties of a substance would make it a good estimator of GFR?
Substance that is neither reabsorbed or secreted by the tubules
Should be freely filtered
What is the gold standard for measurement of GFR?
Inulin
For an inulin clearance test, how is inulin administered?
IV
Why is inulin not used clinically?
Assay is not readily available
What are other ways to measure GFR via renal clearance besides inulin?
Creatinine clearance
What is the difference between endogenous creatinine clearance and exogenous creatinine clearance test?
Endogenous - use body’s natural creatinine as marker and measure changes over time
Exogenous - give creatinine bolus and measure urine and plasma concentrations over time
How is plasma clearance calculated for a substance (formula)?
Clearance = Dose / Area under the curve
What substances are commonly used for plasma clearance tests?
Iohexol
Radioisotopes
What is the most frequently used clinical test for measurement of GFR?
Iohexol clearance
What is a risk of iohexol clearance (more common in people)
AKI
If clearance rate of substance X is equal to clearance rate of inulin, the substance in being FILTERED/ABSORBED/SECRETED.
Filtered only
If clearance rate of substance X is less than clearance rate of inulin, the substance in being FILTERED/ABSORBED/SECRETED.
Reabsorbed
If clearance rate of substance X is greater than clearance rate of inulin, the substance in being FILTERED/ABSORBED/SECRETED.
Secreted
How much of cardiac output do kidneys receive?
25%
Through what mechanisms do the kidneys regulate arterial pressure?
Changes in extracellular fluid volume
Renin-antiogensin-aldosterone system
What makes up the juxtaglomerular apparatus?
Mesangial cells
Macula densa
Vascular baroreceptors detect what?
Changes in stretch
(Send signals to the renal sympathetic nerves)
What things can trigger RAAS?
- Vascular baroreceptors - detect decreased stretch of the afferent arteriole
- Intrarenal baroreceptors (granular JG cells) - detect decreased blood flow in the afferent arterioles
- Intrarenal NaCl detection by macula densa cells - detect drops in reabsorption to trigger RAAS
Where is the macula densa located?
Distal convoluted tubule
What is the first substance secreted by RAAS activation?
Renin
What does renin do?
Acts on angiotensinogen to convert it to angiotensin I
Angiotensinogen is produced where
Liver - it is constitutively released to make sure it’s always in circulation
After angiotensin I is produced, what happens next in RAAS pathway?
Angiotensin I travels to the lungs via the blood where angiotensin converting enzymes on the endothelial cells of the lungs convert it to angiotensin II
What are the major functions of angiotensin II in the RAAS pathway ?
Acts on the brain to drive increased thirst
Acts on arterioles to cause vasoconstriction
Stimulates adrenal gland to produce aldosterone
Aldosterone acts on the __ causing activation of __ which leads to __ of sodium and __ of potassium
Principle cells of the collecting tubule/collecting ducts
Na/K/ATPase pumps
Absorption of sodium
Excretion of potassium
Aldosterone receptor on principle cells is under the control of what drug?
Spironolactone
What is the MOA of spironolactone
Blocks aldosterone receptor of the principle cells of the collecting tubule/collecting ducts
What is the MOA of amiloride?
Potassium sparing diuretic - inhibits sodium channels on the luminal membrane of principle cells of the collecting tubule/collecting ducts
What is responsible for RAAS inhibition?
Atrial natriuretic peptide (ANP)
Where is ANP produced and what is the stimulus for production?
Secreted by cardiac atrial muscle fibers
Release is stimulated by distention of the atria (plasma volume expansion)
What are the effects of ANP?
- Inhibit release of renin from kidney
- Inhibits actions of angiotensin II (aka decreased aldosterone secretion)
- Inhibits sodium reabsorption (from the decreased in aldosterone; natriuresis and diuresis)
- Vasodilation (to decrease blood pressure)
- Increases GFR (to try and further decrease sodium and excess water levels; increased GFR also leads to decreased renin production)
What percentage of glucose is filtered through the glomerulus?
100%
What part of the nephron reabsorbs all glucose and by what?
Proximal tubule by sodium glucose co-transporters (SGLT)
There is SGLT 1 and SGLT2
Where are sodium glucose co-transporters located on proximal tubular cells?
Brush border
Approximately 90% of the filtered glucose is reabsorbed by __ in the __ part of the proximal tubule.
SGLT2
early (S1) part of the proximal tubule
Glucose is brought into the interstitial fluid from what receptors and in what part of the proximal tubule are they located?
GLUT2 - located in S1
GLUT 1 - located in S3
What is the renal threshold of glucose in a dog?
Dog: 180-220
Higher in cats
Other than glucose, what is reabsorbed in the proximal tubule?
All amino acids
65% of Na and H2O (water is passive, follows sodium)
40-50% of urea
80% of bicarbonate
80-85% calcium
80-95% phosphorus
65-90% of citrate (metabolized to bicarb)
**If you’re asked where something is reabsorbed, the PCT is a good guess!
Where is the majority of calcium reabsorbed? Is it passive or active?
Proximal tubule - 65%
Both passive and active
In what three areas of the nephron is calcium reabsorbed?
Proximal tubule - 65%
Thick ascending limb of loop of Henle (this is passive) - 25-30%
Distal convoluted tubule and collecting tubules - 4-9%
Where does PTH act in the nephron?
Distally - thick ascending limb of loop of Henle and distal convoluted tubule and collecting tubules
Hyperphosphatemia is most often due to
Decreased GFR
Where in the nephron is phosphate reabsorbed?
Proximal tubule - 75-80%
Distal convoluted tubule - 10%
Loop of Henle and Collecting tubules - <1%
How does PTH influence phosphorus balance by the kidneys?
PTH decreases transport maximum for phosphate by renal tubules, leading to more phosphate loss in urine
Where in the nephron is the majority of magnesium reabsorbed?
LOOP OF HENLE - 65% (mostly from thick ascending limb)
Some is reabsorbed by proximal tubule and distal convoluted tubule and collecting ducts, but less than loop of Henle
Definition of osmolarity
Number of osmoles per liter of solution (plasma)
Affected by volume and temperature
Definition of osmolality
Number of osmoles per kilogram of solvent
NOT affected by volume and temperature
What is the equation for calculating plasma osmolality?
Osmolality (calculated) = 2 x (Na + K) + (Glucose / 18) + (BUN / 2.8)
What is the normal urine osmolality in dogs and cats?
Dog: 300mOsm/kg
Cat: 310mOsm/kg
= ISOSTHENURIA
What is needed to concentrate urine?
- Functional nephron - need at least 1/3 nephron mass to concentrate urine
- Medullary gradient
- Antidiuretic hormone (ADH)/Vasopressin
- ADH response at level of the kidney - mediated by V2 receptors
What osmolality does filtrate have when entering nephron?
300mOsm
Why does osmolality of filtrate not change in the proximal convoluted tubule?
Because of absorption of electrolytes but also b/c of absorption of water –> no net change here, happens further down (distally) in nephron
As you progress down the medullary gradient, what happens to water? What structure allows this?
Diffuses out of filtrate
Facilitated by aquaporin 1 channels (AQP-1)
This is PASSIVE process
As you move up the thin ascending loop of Henle in the medulla, is it more permeable to solute or water?
Solute
Why do we require active transport of NaCl in the thick ascending loop of Henle?
It lies in the cortex and there is no concentration gradient to drive diffusion
What diuretic acts in thick ascending loop of Henle?
Loop diuretics
Tubular filtrate entering the distal convoluted tubule is HYPO/ISOS/HYPERsthenuric?
HYPOSTHENURIC