Renal/Urinary Flashcards
Vascular organization of the kidneys
Renal artery, segmental artery, interlobar artery, arcuate artery, radial artery, afferent artery, efferent artery, peritubular capillaries/vasa-recta, arcuate veins, interlobar veins, segmental veins, renal vein
Does the medulla contain glomeruli?
No the deepest glomeruli are at the junction bet
What are the three main cell types in the glomerulus?
- endothelial cells
- podocytes
- mesangial cells
Kidneys receive ____ % of the CO, but only ____ % reaches the inner medulla
- 20%
- 5%
This is why the medulla is more prone to develop ischemic injuries
Are there glomeruli in the medulla?
No, the deepest glomeruli are found at the junction between cortex and medulla –> juxtaglomerular nephrones
Describe the two different capillary systems present in the kidneys
- high pressure system –> glomerular capillaries
- low pressure system –> peritubular capilaries
The efferent arteriole can progress into ____ if in cortical nephrones or into ____ if in juxaglomerular nephrones
a. peritubular capillaries
b. vasa recta
What is the renal threshold for glucose in dogs and cats?
Dog: 10-12 mmol/L
Cat: 15-18 mmol/L
Name glucose transporters in PT
- luminal side
SGLT-2 (proxymal - 1 glucose with 1 sodium)
SGLT-1(distal - 1 glucose with 2 sodium) - basolateral
GLUT transporter
What are the two main causes of hypocalcemia in dogs/cats with CKD?
1) hyperphosphatemia
2) Calcitriol deficiency
Where is renin release?
Juxtaglomerular cells
Granular cells?
Draw and label the juxtaglomerular apparatus. What are the three major components of juxtaglomerular apparatus?
1) Macula densa
2) Juxtaglomerular cells
3) Extra-glomerular mesangial cells
In the kidney, where does ammoniagenesis mainly happen? Which amino acid is the source?
Proximal renal tubule
Glutamine (NH4+ + HCO3-)
at physiological pH NH4 will never release H+ (excellent way to trap H+
Where is NH4+ reabsorbed? by which transporter?
Reabsorbed by the thick acending loop of Henle by NCCK transporter (using the K+ site).
Contributes to hyperosmolarity of medulla
True or False: Proteinuria is a negative prognostic indicator in both canine and feline CKD.
True
What is the flow in the hemodialysis filter that can optimize the dialysis efficiency?
Countercurrent flow
What are the four mechanisms of extracorporeal therapy?
Diffusion
Convection
Absorption
Ultrafiltration
Separation
What is the diffusion based on to make the particles move?
Concentration gradient
Membrane charististics
What is the mechanism behind convection in extracorporeal therapy?
Solvent drag
* Hydrostatic pressure gradient
What are the four factors to consider when you determine the modality of the extracorporeal therapy?
Protein-binding
Molecular weight
Volume of distribution
Patient’s volume status
What are the follow extracorporeal therapies based on?
Intermittent hemodialysis (IHD)
Hemoperfusion (HP)
Continuous venovenous hemofiltration (CVVH)
Continuous venovenous hemodialysis (CVVHD)
Continuous venovenous hemodiafiltration (CVVHDF)
Slow continuous ultrafiltration (SCUF)
Intermittent hemodialysis (IHD) - diffusion (+ultrafiltration but limited by short time)
Hemoperfusion (HP) - absorption
Continuous venovenous hemofiltration (CVVH) - convection
Continuous venovenous hemodialysis (CVVHD) - diffusion
Continuous venovenous hemodiafiltration (CVVHDF) - convection + diffusion
Slow continuous ultrafiltration (SCUF) - ultrafiltration
Therapeutic plasma exchange (TPE) - separation
True or False: Smaller molecules are better removed by diffusion, and larger molecules are better removed by convection.
True
* diffusion <500Da
* convection 500-60K Da
What is a safe rate of fluid removal via ultrafiltration
10ml/kg/h
Monitor CV stability (drop of SvO2)
Where should the tip of the dialysis cather lie? what flow rates should it allow for?
In the right atrium
Flow rates up to 150ml/min in cats and 500 ml/min in dogs
The port to the circuit should be proximal vs the port to the patient should be distal
True
Type of dialysis catheters
- temporary
- permanent
surgically placed and tunnelled with cuff
If BUN>200mg/dL a larger and more efficient dialyser is preferred
False: higher risk of dysequilibrium syndrome - a smaller dialyser is preferred (also less chance of clotting)
Ideally the hemodialyser + tubing volume should equate to ____ of the patient’s blood volume
<10%
URR
URR = Serum [urea] before tratment - serum [urea] after treatment / serum [urea] before treatment
TAC
Integrated exposure to uremic toxins overtime
Dialysis dose
Kt = Kd x Td
Kd = clearance of the dialyser for urea (volume of blood cleared of urea in 1 min)
Td = dialysis time
Physics principles behind peritoneal dialysis
- diffusion
- ultrafiltration (very little convection with ultrafiltration possibly responsible of albumin loss)
Three pores model
Three types of pores in the capillary walls, each with a different size and function:
* ultrasmall (<0.8nm) = AQP
* small (4-6nm) = responsible for the majority of the solute transport in PD
* large (20-40nm) = occasional endothelial clefts (albumin)
Expression of AQP enhanced with exposure to hyperosmolar solutions
PD catheter
- percutaneous
- surgical with tunnelling and dacron cuffs
Best type is T-flute
TPE cathegories
According to evidence of efficacy
* I: myastenia gravis and hypergammaglobulinemia
* II: IMHA
* III: IMTP, Sepsis (cytokines)
* IV: no evidence/detrimental
Processing 1.5x plasma volume with TPE removes up to____ % of toxic substance
80%
Dialysis treatment intensity
If no pre-calculated graphs are available an empiric approach must be adopted
When initial BUN > 300mg/dL (110 mmol/L) the Qb should be limited to 1-1.5mL/Kg/min
If BUN 150-300mg/dL the Qb should be limited to 1.5-2mL/Kg/min
Once BUN<150 mg/dL the Qb can be increased up to 5mL/Kg/min
For small animals the machine might not be able to provide safely slow Qb so can introduce ‘bypass intervals’ in which the blood flow continues but the dialysate flow ceases
Na profiling
[Na] in the dialysate adjusted systematically during dialysis session to counteract solute disequilibrium and promote vascular filling (prevent hypovolaemia/hypotension)
Initially dialysate is hypernatraemic to promote shift of sodium into the blood and vascular filling to counteract loss of volume due to circuit priming, ultrafiltration and compensate for the greatest initial urea shift (maintain osmolarity)
In IHD the ____ flow predicts clearance vs in CRRT the ____ predicts clearance
blood flow
dialysate flow
In CVVHF pre-filter fluid replacement reduces risk of clotting but…
decreases efficiancy as blood is diluted when passing through the filter
True or False: During hemodialysis for ethylene glycol intoxication, only ethylene glycol is removed and the metabolites remains in the system.
False
Both ethylene glycol and its metabolites are removed
Which extracorporeal system needs a water treatment system for the dialysate proportioning?
IHD
What are two types of water loss?
Obligatory water loss: water needed to excrete the daily renal solute load
Free water loss: water excreted unaccompanied by solute under the control of antidiuretic hormone [ADH]
In dogs, how many percentage increase of osmolality will induce thirst?
1 - 3%
Which molecule can be filtered through the glomerulus more easily, the positively charged or negatively charged one?
Positively charged one
Because glomerulus is negatively charged
What is the size selectivity limit of glomerulus?
7-9 nm in diameter (nephrin forming slit diaphragm in podocyte layer)
Which layer contributes to the glomerulus charge selectivity?
1) Capillary endothelium
2) Glomerular basement membrane
3) Visceral epithelial cells (podocytes)
2) glomerular basement membrane
The lamina rara interna and lamina rara externa contain polar non-collagenous proteins that contribute to the negative charge of the filtration barrier.
The lamina densa contains nonpolar collagenous proteins that contribute primarily to the size selectivity of the filtration barrier.
The glomerulus has similar net filtration pressure than systemic capillary, but why glomerulus has such high filtration rate than capillary?
1) The glomerulus has much bigger surface area for filtration
2) The permeability for electrolytes are much greater (100x) than systemic capillaries
Both contribute to higher ultrafiltration coefficient Kf
What are the changes in renal blood flow and GFR in each situation?
What are the effects of norepinephrine, angiotensin II and dopamine and ADH on the renal blood flow and GFR?
True or False: norepinephrine, angiotensin II and ADH cause renal arterioles vasoconstriction, and stimulate the production of (PGE2 and PGI2), which counterbalances by their vasodilation effect.
True
True of False: ADH causes vasoconstriction on both afferent and efferent arterioles, and prostaglandin E2 cause vasodilation on both afferent and efferent arterioles.
False
ADH only cause vasoconstriction on efferent arterioles; prostaglandin E2 only cause vasodilation on afferent arterioles.
What is the equation for GFR?
What is normal GFR for dogs and cats? What about renal plasma flow (RPF) and filtration fraction (FF)?
1) GFR: Dog 3-5 ml/kg/min Cat 2.5-3.5 ml/kg/min
2) RPF: Dog 7-20 ml/kg/min Cat 8-22 ml/kg/min
3)FF: Dog 0.32-0.36 Cat 0.33-0.41( approx 30%)
Name two substances that can used to evaluate GFR.
Creatinine
Inulin (a polymer of fructose)
Fill out the blank: In the kidneys, between perfusion pressures (MAP) of __________, GFR and RBF vary less than 10%. The ________ is the site to regulate the pressure.
80 - 180 mmHg
Afferent arterioles
What are the two autoregulation of nephrons? Which one is faster?
Myogenic mechanism
Tubuloglomerular feedback
Myogenic mechanism is faster
What is the RBF when compared to total cardiac output?
20% of cardiac output
How do you assess RBF based on RPF?
Which route does water mainly pass through in the renal tubule, paracellular route or transcellular route?
Transcellular route
Name four renal transport processes and an example for each one of them.
Passive diffusion -
Facilitated diffusion - glucose, amino acid
* it is a saturated process
Primary active transport - H+-ATPase at the luminal side, Na,K-ATPase at the basolateral side
Secondary active transport - (e.g. glucose-Na, Na-H)
True or False: Na is reabsorbed with glucose, amino acids, phosphate, and bicarbonate in the proximal renal tubule.
True
Which tubular transport maximum (Tmax) is the lowest, glucose, phosphate or amino acid?
Phosphate
Explain why during dehydration, patient’s BUN may increase but not creatinine?
50% or urea is passively reabsorbed in the proximal renal tubule. When patient is dehydrated, tubular flow decreases, there is increased water reabsorption and subsequent urea reabsorption via the solvent drag.
On the other hand creatinine is not reabsorbed and only increases after a significant drop in GFR.
True or False: The ascending limb of Henle’s loop is impermeable to water.
True
So NKCC2 can transport the electrolytes without carrying water → important step for urinary concentrating mechanism
There are three segments of collecting ducts, what are they? Which segment is permeable to urea?
Cortical, outer medullary, inner medullary
Inner medullar collecting duct is permeable to urea
* its urea permeability is increased by ADH
Why under normal condition, the medullary interstitium can maintain its hyperosmotic gradient?
The countercurrent exchange of vasa recta → can remove water while keep the solutes in the interstitium
Explain countercurrent mechanism
Where is erythropoietin EPO produced in the fetus and adults?
Fetus: liver
Adults: peritubular cells in kidneys
Name three conditions that will increase renin release.
1) Decreased renal perfusion pressure (release of PGI2 from endothelium and stimulation of granular cells)
2) SNS stimulation & increased circulating catecholamines level (𝛽1 receptors on granular cells)
3) Decreased Cl concentration at the distal tubular flow (release PGE2 by macula densa cells and stimulation granular cells)
In the RAAS system, which step is the rate limiting step?
Renin converts 𝜶2-globulin angiotensinogen to angiotensin I
True or False: The release of renin is inhibited by a direct effect of angiotensin II on the granular cells.
True
How does angiotensin II cause increase proximal renal tubular sodium absorption?
Stimulating the Na-H antiporter in luminal membranes of proximal tubular cells.
Name 5 functions of angiotensin II
1) arterial vasoconstriction
2) inhibit renin
3) stimulate aldosterone production
4) stimulate ADH release
5) stimulate mesangial cells to produce PGE2, PGI2
6) Increase proximal renal tubular Na reabsorption
7) Cause afferent and efferent renal arterioles constriction
Where in the kidney is calcidiol converted to calcitriol?
Proximal tubular cells
Name 5 different types of diuretics, which part of the renal tubules do they work on and their MOA.
1) Carbonic anhydrase inhibitor - acetazolamide
2) Osmotic diuretic - mannitol
3) NKCC2 inhibitor - furosamide, torsamide
4) Thiazide - thiazide
5) Aldosterone receptor antagonist - spironolactone
Mechanism of action of Vaptans
ADH receptor antagonists
Also called aquaretics
Mechanism of action of venagliflozin (Senvelgo)
SLG-2 inhibitor –> osmotic diuresis due to impaired glucose reabsorbtion
in dogs increased urine volume by 3.7x and natriuresis by 1.5x
Consider in cases of diuretic resistance
Why do thiazide diuretic cause hypercalcaemia?
By blocking Na/Cl they induce a lower intracellular [Na+] which causes hyperactivity of the Na/Ca exchanger on the basolateral membrane –> increased gradient for Ca++ reabsorbtion
Mechanism of action of xanthines
- increased CO = increased GFR
- A1 receptor antagonists = reduced NH3 activity in PT
What is MOA of Acetazolamide?
According to IRIS CKD staging, what is the UPC cutoff for proteinuria in dogs and cats? What about the cutoff for pre-hypertensive and hypertensive?
UPC
Dog: > 0.5
Cat: > 0.4
Blood pressure
Pre-hypertensive 140-159
Hypertensive 160-179
What is the creatinine range for grade II AKI?
140-220 umol/L
According to IRIS AKI grading system, what is the definition of fluid responsive?
UOP > 1 ml/kg/hr over 6 hours, or creatinine decrease to baseline over 48 hours
What are the two subgrading for AKI in IRIS guidelines?
1) Non-oliguric or Oligo-anuric
2) Requiring RRT
According to IRIS AKI grading system, how many days does it normally take for grade I and II AKI to regain adequate renal function?
2-5 days
What are the three mechanisms of pathological causes of diuresis?
1) Failure of ADH to function
2) Pressure diuresis (e.g. hypertensive hypervolemic state)
3) Osmotic diuresis (e.g. glucosuria)
Among all classes of diuretics, which one reach its site of action from the blood instead of urinary space?
Spironolactone
How does furosemide reach its site of action?
Not freely filtered as highly protein bound, so via blood to the baso-lateral membrane where picked up by OAT (competition with NSAIDs and uremic anions) transporter and then excreted to lumen by MRP4
What is the MOA of amiloride?
Amiloride is not an aldosterone receptor antagonist like spironolactone, but a direct inhibitor of ENaC → excrete water, retain K and H+
What is the MOA of acetazolamide?
Inhibits type II (cytoplasmic) and type IV (membrane) carbonic anhydrase at the proximal renal tubule → decrease reabsorption of sodium bicarbonate
How many percentage of Na is reabsorbed at the proximal renal tubule, loop of Henle, distal convoluted tubule and collecting duct, respectively?
Proximal renal tubule: 67% (2/3)
Loop of Henle: 25%
Distal convoluted tubule: 5%
Collecting duct: 3%
What are 4 types of renal tubular acidosis?
Type I (classic distal RTA): inability of distal renal tubule to excrete H+
- Hyperchloremic metabolic acidosis + increased urine pH (pH > 6.0)
- Ammonium chloride challenge test
Type II (proximal RTA): inability of proximal renal tubule to prevent loss of bicarbonate
- Mild metabolic acidosis + acidic urine or alkalotic urine (bicarbonate can be reabsorbed in the distal tubule as long as the concentration is <20mEq, if more bicarbonate is lost in urine)
- HCO3- fraction excretion > 15% after normalizing the plasma bicarbonate (normally is < 5%)
Type IV (hyperkalemic distal RTA): distal RTA and hyperkalemia secondary to hypoaldosteronism or aldosterone deficiency
Type III: a rare combination of proximal and distal RTA caused by carbonic anhydrase II deficiency and carbonic anhydrase inhibitors blocking the metabolism of bicarbonate and carbonic acid
List 5 lab abnormalities of Fanconi syndrome. Which segment is affected?
1) Proximal renal tubular acidosis (normal AG hyperchloremic acidosis)
2) Glucosuria, proteinuria, aminoaciduria, phosphaturia, hypophosphatemia.
Nephrotoxic mechanisms of aminoglycosides
- membrane accumulation in tubular epithelium due to positive chages attracted by negative phospholipid layer (neomycin most toxic due to most positively charged)
- lisosomal accumulation when internalised
How many percentage of calcium is reabsorbed at the proximal renal tubule, loop of Henle, distal convoluted tubule and collecting duct, respectively?
Proximal renal tubule: 60-70% (paracellular)
Loop of Henle: 20% (paracellular)
Distal convoluted tubule: 10% (transcellular)
Collecting duct: almost none
The release of vasopressin is more sensitive to change in osmolarity or effective circulating volume?
osmolarity
An increase of only 1% in plasma osmolality will stimulate vasopressin release, whereas a drop in blood volume of approximately 10% is needed to stimulate vasopressin release
List 8 causes of Nephrogenic diabetic Insipidus (NDI).
Hypercalcemia
Hypokalemia
Pyelonephritis
Pyometra or gram (-) sepsis
Hyperthyroidism
Hypoadrenorcorticism (decreased Na → unable to maintain the interstitial concentration gradient)
Hepatic insufficiency (decreased urea production → unable to maintain the interstitial concentration gradient)
PSS (decreased urea production → unable to maintain the interstitial concentration gradient)