Renal Flashcards
(133 cards)
1
Q
Osmotic diuretics (mannitol)
- mechanism of action
- site of action
A
Inhibit water and solute reabsorption by
increasing osmolarity of tubular fluid
Mainly proximal tubules
2
Q
Loop diuretics (furosemide, bumetanide)
- mechanism of action
- site of action
A
Inhibit Na+/K+/Cl− co-transport in luminal
membrane
Thick ascending loop of Henle
3
Q
Thiazide diuretics (hydrochlorothiazide, chlorthalidone)
- mechanism of action
- site of action
A
Inhibit Na+/Cl- co-transport in luminal membrane
Early distal tubule
4
Q
Carbonic anhydrase inhibitor (acetazolamide)
- mechanism of action
- site of action
A
Inhibits H+ secretion and HCO3- reabsorption, which reduced Na+ reabsorption
Mainly proximal tubules
5
Q
Aldosterone antagonists (spironolactone)
- mechanism of action
- site of action
A
Inhibit action of aldosterone on tubular receptor, decrease Na+ reabsorption, decrease K+ secretion
Potassium sparing
Collecting tubules
6
Q
Sodium channel blockers (triamterene, amiloride)
- mechanism of action
- site of action
A
Block entry of Na+ into Na+ channels of luminal membrane, decrease Na+ reabsorption, decreased K+ secretion
Collecting tubules
7
Q
What determines GFR (equation)
A
GFR = Kf x Net filtration pressure
Net filtration pressure = (Pg-Pb-COPg-COPb)
8
Q
What percentage of cardiac output is supplied to the kidneys
A
22%
9
Q
What are the determinants of renal blood flow (Ohm’s law)
A
Renal blood flow (RBF) = (renal artery pressure-renal vein pressure)/total vascular resistance
10
Q
What do the macula densa cells sense and what is their action?
A
Macula densa cells in the distal tubule
When GFR is reduced they sense a decrease in NaCL
This causes a release of renin
Stimulates RAAS – Angiotensin II
Increase in efferent arteriolar constriction
GFR increased
11
Q
Where are the macula densa cells?
A
Juxtaglomerular complex - consists of macula densa cells around distal tubule and near afferent/efferent arteriole.
12
Q
What is the overall effect of extreme sympathetic nervous system activation on GFR?
A
increased vascular resistance - Decreases GFR
13
Q
What is the action of Angiotensin II and its effect on GFR?
A
Angiotensin increases efferent arteriolar constriction -> increases GFR
Also stimulates aldosterone secretion (increasing sodium and water reabsorption)
Also directly stimulates sodium reabsorption in most segments of nephron
14
Q
What is the effect of nitric oxide on GFR?
A
NO decreases renal vascular resistance and increases GFR
15
Q
What layers make up the glomerular capillary membrane
A
Fenestrated endothelium of capillary
Basement membrane
Podocyte cells - separated by ‘slit pores’
16
Q
Glomerular filtration rate is approximately what percentage of renal blood flow?
What equation demonstrates this?
A
20%
Filtration fraction = GFR/Renal plasma flow
17
Q
What is the effect of prostaglandins and bradykinins on GFR
A
decrease vascular resistance -> increase GFR
18
Q
What is the carbonic acid equilibrium equation?
What enzyme catalyses this?
A
CO2 + H2O <–> H2CO3 <–> H+ + HCO3-
Carbonic anhydrase
19
Q
What percentage of sodium and water are reabsorbed in the proximal convoluted tubule
A
65%
20
Q
What percentage of Lactate, glucose and amino acids are absorbed in the proximal convoluted tubule?
A
100%
21
Q
What percentage of bicarbonate is absorbed in the proximal convoluted tubule?
A
90%
22
Q
What percentage of potassium and chloride are absorbed in the proximal convoluted tubule?
A
60%
23
Q
What percentage of phosphate is absorbed in the proximal convoluted tubule?
A
85% - depending on the influence of PTH
24
Q
How do lipid substances get re-absorbed in the renal tubules (e.g. urea)
A
diffuse through the lipid bilayer
25
How are small proteins reabsorbed in the renal tubule?
receptor mediated endocytosis
they are then combined with lysozymes --> hydrolysis and amino acids released into blood --> proteins recycled
26
What ions are reabsorbed by paracellular transport in the proximal convoluted tubule?
Cl-, K+, Mg2+, some Ca2+
27
How is bicarbonate absorbed in the proximal convoluted tubule?
What percentage is re-absorbed here?
Using the carbonic acid equilibrium
- Carbon Dioxide (CO2) - moves into the cell + react with water to form carbonic acid (H2CO3)
- Carbonic acid is unstable - dissociates into a proton (H+) and bicarbonate (HCO3-)
- The proton (H+) is moved out of the cell using a Sodium-Hydrogen Antiporter (secondary active transport)
- H+ combines with HCO3-outside of the cell (in tubule) to form carbonic acid
- This is again converted by carbonic anhydrase to CO2 and H2O
- Most bicarbonate (HCO3–) gets pushed back into the blood
90%
28
What is the vasa recta and what is its purpose
The vasa recta is a peritubular capillary network present in the deep part of the medulla
It is a counter current exchanger and maintains the medullary interstitial gradient
29
Aldosterone
- site of action in the nephron
- effects
DCT + CD
Increased reabsorption of: Na CL and H2O
Increase secretion of K+ and H+
30
Angiotensin II
- site of action in the nephron
- effects
PCT, thick ascending loop of Henle, DCT, CD
Increased reabsorption of: Na CL and H2O
Increase secretion of H+
31
Antidiuretic hormone (ADH)
- site of action in the nephron
- effects
DCT, CD
Increased water reabsorption
32
Atrial natriuretic peptide
DCT/CD
Reduced Na Cl reabsorption
33
Parathyroid hormone (PTH)
PCT, thick ascending loop Henle, DT
Increased calcium reabsorption
Decreased phosphate reabsorption
34
What are the stimuli for aldosterone release
- AT II
- Hyponatremia
- Hyperkalaemia
35
What are the stimuli for ADH release
- High plasma osmolarity
- AT II
36
Which ion transporter on the basolateral membrane of the tubular cells creates a concentration gradient for passive diffusion on the luminal membrane
Na+/K+ ATPase - 3Na+ out and 2K+ into cell
37
How does ADH facilitate water reabsorption in the collecting duct?
Stimulates Aquaporin II to be added to the membrane
38
What substance leaves in the thin descending loop of Henle
Water
39
Which part of the nephron is impermeable to water
Thin and thick ascending limb of the loop of Henle
40
How much water is reabsorbed in the thin descending loop of Henle
15-20%
41
What substances are reabsorbed in the thick ascending loop of Henle
by which transporter
and what percentage
Na+/K+/Cl-
by NKCC2 transporter
25%
As well as other ions by paracellular transport: Ca2+ Mg2+ , (also Na+ and K+)
42
What are the two cell types in the late distal tubule and collecting duct
Describe their action
Principle cells
- reabsorb sodium and secrete potassium under the influence of aldosterone
- water reabsorption under the influence of ADH
Intercalated cells (A and B)
- A cells secrete H+
- B cells secrete HCO3-
43
Which portion of the nephron contains urea transporters for facilitating urea re-absorption
What is the purpose of this?
Late collecting duct
Allows urea recycling to contribute to the medullary concentration gradient
44
Clearance of which substances can be used to assess GFR
Creatinine and inulin
45
What nervous system pathways control the micturition reflex?
Autonomic
- SNS and PSNS
Somatic
- Pudendal nerve
46
What nervous pathway controls the internal urethral sphincter?
Autonomic - sympathetic
activates alpha 1 receptors and causes contraction
47
What nervous pathway controls the external urethral sphincter?
Somatic - pudendal nerve
contraction of external sphincter
48
Activation of which nervous pathway causes detrusor contraction?
parasympathetic
49
Which nervous pathway causes detrusor relaxation?
sympathetic
Beta 3 receptrs are inhibited and causes relaxation
50
What is the area of the pons called that helps control the micturition reflex
pontine micturition and pontine storage centres
51
What triggers the voiding phase of the micturition cycle
- Bladder volume strongly activates stretch receptors.
- sends signals to the pontine micturition centre
- initiates parasympathetic activation (causing detrusor contraction)
- inhibits sympathetic and somatic pathways (causing sphincter relaxation).
52
What urine crystal is this?
Struvite
53
What urine crystal is this?
Calcium oxalate dihydrate
54
What urine crystal is this?
Calcium oxalate monohydrate
55
What urine crystal is this
Uric acid crystals
56
What urine crystal is this?
Bilirubin
57
What urine crystal is this?
Ammonium biurate
58
What crystal is this?
Cystine crystal
59
Which area of the nephron is solute impermeable
descending limb of the loop of Henle
60
What type of aqauporin are present in the descending loop of Henle
Aquaporin 1
61
What transporter helps to create the medullary concentration gradient
Na/K/Cl transporter in the thich ascending loop of Henle
62
What helps to maintain the counter current multipier mechanism
* Vasa recta - the counter current exchanger
- prevents rapid removal od Na and Cl
63
What is the effect of the medullary concentration gradient?
* Water flows out due to medullary tonicity
* filtrate becomes hypotonic to the blood plasma
64
Which factors stimulate potassium shift into cells (decrease extracellular K+)
- insulin
- aldosterone
- beta adrenergic stimuation
- alkalosis
65
Which factors stimulate potassium shift out of cells (increase extracellular K+)
- insulin deficiency (DM)
- Aldosterone deficiency (Addisons)
- B adrenergic blockade
- Acidosis, cell lysis or increased ECF osmolarity
66
What percentage of water is reabsorbed where in the nephron
* 65% reabsorbed in the PCT
* 15% reabsorbed in the descending limb of Loop of Henle
* 20% reabsorbed in DCT (dependent on aquaporin-II, which is dependent on ADH)
67
What percentage of sodium is reabsorbed where in the nephron
* 65% reabsorbed in the PCT
* 25% reabsorbed in the ascending limb of Loop of Henle
* 5-6% reabsorbed in early DCT
* Remaining 4-5% is reabsorbed depending on the presence of aldosterone
68
Micturition - parasympathetic
- receptor
- location
- Nerve
- Function when stimuated
- Function when blocked
- M3 muscarininc
- Bladder body (detrusor)
- Pelvic nerve S1-S3
- stimulated = contraction + bladder emptying
- blocked = relaxation and filling
69
Micturition - parasympathetic
- Function when inappropriately stimulated
- Function when inappropriately blocked
- inappropriate stimuation = overactive bladder
- inappropriate block = bladder atony and urine retention
70
Micturition - Sympathetic B3 adrenergic
- location
- Nerve
- Function when stimuated
- Function when blocked
- bladder body (detrusor)
- Hypogastric (L1-L4)
- stimulation = Detrusor relaxation and bladder filling
- block = detrucor contraction and urination
71
Micturition - Sympathetic B3 adrenergic
- Function when inappropriately stimulated
- Function when inappropriately blocked
- inappropriate stimulation = urine retention
- inappropriate block = decreased bladder compliance and increased filling pressure
72
Micturition - Sympathetic A1 adrenergic
- location
- Nerve
- Function when stimuated
- Function when blocked
- Internal urethral sphincter
- hypogastric nerve (L1-L4)
- stimulated = contraction + continence
- blocked = urination
73
Micturition - Sympathetic A1 adrenergic
- Function when inappropriately stimulated
- Function when inappropriately blocked
- inappropriate stimulation = urine retention
- inappropriate block = open urethra and incontinence
74
Micturition - somatic
- receptor
- location
- Nerve
- Function when stimuated
- Function when blocked
- external urethal sphincter
- Pudendal nerve (S1-S2)
- Stimuation = conscious+reflex contraction + continence
- Block = urination
75
Micturition - Somatic
- Function when inappropriately stimulated
- Function when inappropriately blocked
- inappropriate stimulation = urine retention
- inappropriate block = open urethra and incontinence
76
What are the cause and features of LMN bladder
- S1-2 spinal cord lesions
- affect muscular sphincter
- Easily expressible bladder
- Decreased anal tone and poor perineal reflex
- Cannot voluntarily void
- Requires manual expression
77
What are the features of Detrusor Hyperreflexia
- what can be used to treat it
* parasympathetic overstimulation
* Sudden urgency and involuntary evacuation
* Detrusor contractions at low bladder volumes
* Loss of bladder compliance and capacity
* Anti-muscarinincs (oxybutynin)
78
What are the features of detrusor atony
- what can be used to treat it
- neurogenic (sacral SC/pelvic nerve injury)
- non-neurogenic due to overdistension
- bladder atony and urine retention
- consider muscarininc agents - bethanecol
79
What are the features of functional urethral outflow obstruction
- what can be used to treat it
- failure of urethral sphincter to relax during voiding
- large breed male dogs
- interruypete urine stream, large residual urine volume and overflow incontinenence
- alpha blockers - prazosin, skeletal muscle relaxants (diazepam, methocarbamol)
80
What are the features of upper motor neuron bladder
- what can be used to treat it
- spinal cord lesions cranial to sacral segment
- unable to urinate normally, difficult to express
- common in dogs with IVDD
- alpha blockers (prazosin) and manula expression
81
What is the Henderson hasselbalch equation
pH = 6.1 + log([HCO₃⁻]/(0.03 × PCO₂))
82
What are the main buffer systems in blood/cells
- bicarbonate buffer
- phosphate buffer
- protein buffer
83
What is the respiratory response to metabolic acidosis
Increased ventilation --> Reduces PCO₂ --> reduces H⁺
84
What is the respiratory response to metabolic alkalosis
Decreased ventilation --> Increases PCO₂ --> increases H⁺
85
What are the three main mechanisms the kidneys use to control H+
- secretion of H+
- Reabsorbtion of filtered HCO3-
- Production of new HCO3
86
What are the two renal buffer systems that allow excretion of H+ in urine
- Phosphate buffer: NaHPO4 + H+ - HCO3- reabsorption in process
- Ammonia buffer: AA glutamine used for ammonium synthesis, NH3 + H+ or NH4 excretion , reabsorption of HCO3-
87
If acidaemia is present alongside low blood K+ then it should be noted that the true potassium value is (HIGHER/LOWER)
lower
88
Respiratory acidosis causes
- Decreased ventilation and increased pCO2
- airway obstruction, pneumonia, pleural effusion and pneumothorax
89
Respiratory alkalosis causes
- Increased ventrilation and decreased pCO2
- rare due to pathology - parenchymal disease, pain, hypoxemia
90
Metabolic acidosis causes (broad mechanisms)
* Decreased ECF HCO3- concentration
* Failure of kidney to secrete acids - renal tubular acidosis
* Formation of excess acid in body - renal failure and uremia
* Addition of acid to body - diabetes
* Loss of base - diarrhoea
91
Metabolic alkalosis causes
* Increased retention of HCO3- or loss of H+ from body
* Vomiting - loss of acid
* Cushings and Conns (aldosterone = H+ secretion)
* diuretics (Na secretion coupled with H+ absorption)
92
What is the anion gap
- whuy is it useful
- considers unmeasured anions
- - useful to determine whether metabolic acidosis is due to loss of bicarbonate or gain of acid
AG = [Na+] + [K+] - [HCO3-] - [Cl-]
93
How do you calculate serum osmolality
- what is normal
Osmolality = 2(Na + K) + (glucose/18) + (BUN/2.8)
- 18 and 2.8 being factors, which convert mg/dL (conventional units) to mmol/L (SI units)
- 290-310 mOsm/kg
94
What are causes of high anion gap metabolic acidosis
L - lactic acidosis
U - uremia
K - ketosis
E - ethylene glycole
95
What are causes of normal anion gap metabolic acidosis
- hyperchloremia
- bicarbonate gain
- Hypernatremia
96
What are three broad categories of intra renal AKI and an example of each
- Glomerular capillary injury (vasculitis, glomerulonephritis)
- Renal tubular epithelial damage (tubular necrosis due to ischemia or toxin)
- Renal interstitial damage (acute pyelonephritis)
97
What are the three broad causes of CKD
- Injury to renal vasculature - atherosclerosis or nephrosclerosis
- Injury to glomeruli - glomerulonephritis
- Injury to renal interstitium - intersitial nephritis
98
What characterises nephrotic syndrome
- proteinuria, hypoalbuminemia, oedema or ascites, hypercholesterolemia
99
Renal tubular acidosis is caused by what mechanism in the nephron
- what are the two types
Tubular inability to secrete H+ or reabsorb HCO3-
- Type 1: impairment of tubular HCO3- reabsorption --> HCO3- lost in urine
- Type 2: inability of H+ secretion to establish normal acidic urine
100
What is nephrogenic diabetes insipidus characterised by
Failure of kidneys to respond to ADH --> excretion of large volumes of dilute urine
101
What is Fanconi syndrome characterised by
* Generalized resorptive defect
* Increased urinary excretion of virtually all amino acids, glucose, and phosphate
102
What is SDMA
symmetric dimethylarginine
- synthesised by all nucleated cell by methylation of arginine
- 90% normally excreted by glomerular filtration
103
What is Cystatin C
- low molecular weight protein
- freely filtered at glomerulus but reabsorbed and catabolised in PCT
104
What are the indications for renal biopsy
- presistent proteinuria >3.5
- proteinuria un-responisive to anti-proteinuric therapy
- progressive proteinuria or decline in renal function despit therapy
105
what are contraindications for renal biopsy
- IRIS CKD stage 4
- primary tubulointerstital disease
- hydronephrosis, pyelonephritis, haemostatic disorders or renal abscess
106
Hereditary nephropathy is a mutation in which gene:
- in cocker spaniels
- in samoyeds
- cocker - COL4A4
- samoyes - COL4A5
107
Which breed are pre-disposed to focal segmental glomerulosclerosis
Wheaten terriers
108
Which breeds are pre-disposed to cystinuria
English bulldog, newfoundland, dachshund, bassett, rottweiler
109
Which breeds are pre-disposed to hyperoxaluria
Coton de Tulear
110
Which breeds are pre-disposed to Hyperuricosuria
Dalmatian, English Bulldog, Black Russian Terrier
111
What are the grades of AKI
- I - Non-azotemic: Creatinine <140umol/l, increase of >26.4umol/L within 48hrs), >6hrs oligoanuria
- II - Mild: Creatinine 140-220umol/l increase of >26.4umol/L within 48hrs), >6hrs oligoanuria
- III - Moderate-severe: 221-439umol/L
- IV - Severe 440-880umol/L
- V- Severe >880umol/L
112
What are some common nephrotoxic agents
- Amphotericin B (direct tubular damage and vasconstriction)
- Aminoglycosides (cellular dysfunction)
- Cyclosporine and tacrolimus (calcineurin inhibitors)
- Grapes/raisins, Lillies (glycoalkaloids)
- Ethylene glycol (tubular necrosis secondary to CaOx crystals)
- Vitamin D rodenticides (hypercalcemia)
113
In a uroabdomen what are the effusion creatinine and potassium compared to serum
effusion creatinine>2x plasma
effusion potassium > plasma
114
How can hypercalemia be managed in AKI
- IV calcium glconate (stabilse cardiac cells)
- insulin with dextrose oralbuterol - shft K into cell s
- Furosemide, fludrocortisone - increase renal excretion
- Dialysis - removal
115
What are the common electrolyte abnormalities with AKI
- Hyperkalemia
- Hypocalcemia
- Hyperphosphatemia
- metabolic acidosis (high anion gap)
116
What is the urine output for:
* relative oliguria
* absolute oliguria
* anuria
* Relative oliguria: UOP <2 mL/kg/hr
* Absolute oliguria: UOP <1 mL/kg/hr
* Anuria: 0-0.5 mL/kg/hr
117
What are negative prognostic indicators for AKI
- non-infectious cause
- oligo/anuric
- Hypocalcemia
118
What are the stages and substages of CKD (canine + feline)
- 1 (no azotemia): D<125 C<140
- 2 (mild): D - 125-250 C - 140-250
- 3 (moderate): D 251-440 C - 251-440
- 4 (severe): D >440 C> 440
- substage: proteiuria
- Dogs none < 0.2, boderline 0.2-0.5, protinuric >0.5
- Cats none < 0.2, boderline 0.2-0.4, protinuric >0.4
- substage: hypertensive (normotensive <140mmHg, prehypertensive 140-159, hypertensive 160-179)
119
* What is FGF23
- what triggers it
- what is its effect
- phosphaturic hormone
- FGF23 released when there is high phosphate
- downregulates proximal tubular PO4 transporters
- Decreased GI PO4 absorption (inhibits alpha -1 hydroxylase)
- Inhibits PTH secretion
120
What is the mechanism of renal secondary hyperparathyroidism
- AS CKD progresses FGF23 no longer adequately controls PO4
- PTH stimulated (normally supressed by FGF23) to try and excrete PO4
- calcitriol syntheses decreases and intestinal calcium absorption is impaired
- final result: HyperPO4, HypoCa, Calcitriol deficiency, elevated PTH and FGF23
121
What are the consequences of CKD-MBD
- renal osteodystrophy (maxilla/mandible in dogs)
- Soft tissue mineralisation and nephrolithiasis: CaOx 98%, ST mineralisation with CaP product >70mg2/dL2
122
What are the IRIS phosphate targets for stage 2 and 3 CKD
* Stage 2: <4.5 mg/dL (<1.45 mmol/L)
* Stage 3: <5.0 mg/dL (<1.6 mmol/L)
123
What is cincalcet
- calcimemietic acting on calcium sensing receptors
- reduced PTH secretion and lowers serum calcium
124
Type 1 cystinuria is typically caused by defects in which gene
- which breeds are pre-disposed
SLC3A1 gene
- Labradors, newfoundlands
125
Type 2 cystinuria is typically caused by defects in which genes
- which breeds are pre-disposed
SLC3A1 and SLC7A9
- australian cattle dogs and miniature pinschers
126
Type 3 cystinuria is caused by what
Androgen dependence
127
What drug can be used to treat cystinuria
- Thiol drugs: D penacillamine and 2-MPG
- form disulfide bonds with cystine to create more soluble complex
128
What is the genetic defect in Dalmatians with hyperuricosuria
Missense mutation in Slc2a9 gene
129
Struvite
- Prevalance
- risk factors
- mechanism
- signalment
- diagnostic features
- treatment
- 40% dogs, 50% cats
- UTI (dogs), Alkaline urine
- Urease producing bacteria (SPUK), increase urinary ammonium and pH resulting in struvite precipitation
- more common in females
- Typically radiopaue, smoothly marginated
- medical dissolution (acidifying diet) + antibiotics
130
Calcium oxalate
- Prevalance
- risk factors
- mechanism
- signalment
- diagnostic features
- treatment
- prevention
- 35% dogs, 35% cats
- hypercalciuria, hypercalcemia, primary HPTH, acidic urine
- Increased urnatury calcium excretion
- mini schnauzer, yorkie, Shih Tzu, Bischon
- genetic in english bulldog
- typically radiopaque, rosette shaped
- cannot be medically dissolved
- Diet: low oxalate moderate calcium,
- potassium citrate if persistent aciduria, hydrochlorothiazide to reduce urine Ca reabsorption
131
Cystine
- Prevalance
- risk factors
- mechanism
- signalment
- diagnostic features
- treatment
- prevention
- 6%
- Gentic and androgen dependent
- Mutations in genes encoding subunits of a renal amino acid transporter (SLC3A1 and SLC7A9)
- Most (70-80%) intact males
- Moderately radiopaque (70% visible), crystalluria abnormal
- Medical dissolution (low protein diet), tioporonin (cystine chelation), potassium citrate (alkalinise urine)
- castration
132
Urate
- Prevalance
- risk factors
- mechanism
- signalment
- diagnostic features
- treatment
- prevention
- 5%
- PSS, genetic, acidic urine
- PSS impair hepatic conversion of uric acid to allantoin causing hyperuricosuria
- SLC2A9 mutation
- Dalmatians, english bulldogs, black russian terrier
- Moderately radiopaque (70% visible), crystalluria abnormal, bile acid testing
- Medical dissolution Low-purine alkalinizing diet
- Allopurinol (XDH inhibitor)
133
Xanthine
- Prevalance
- risk factors
- mechanism
- <1%
- 75% iatrogenic, 25% hereditary
- XDH therapy for urate stones or leishmania (allopurinol)
