Renal Flashcards

1
Q

Function of the proximal tubule?

A

Isosmotic reabsorption of 70 % filtered water and NaCl, 90 % bicarb, NH3 production, reabsorption of almost all glucose and amino acids, reabsorption of potassium, phosphate, calcium, magnesium, urea and urate, secretion of organic anions and cations

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2
Q

Function of loop of henle?

A

Countercurrent multiplier, reabsorption 15-25 % filtered NaCl, active regulation of magnesium excretion

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3
Q

Function of distal tubule?

A

Small amount of NaCl absorption, active regulation of calcium excretion

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4
Q

Function of connecting segment/cortical collecting duct?

A

Aldosterone-mediated potassium secretion by principal cells, H+ secretion and potassium reabsorption by alpha intercalated cells, ADH mediated water reabsorption

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5
Q

Function of medullary collecting duct?

A

Potassium reabsorption or secretion, final NaCl reabsorption, ADH mediated water and urea reabsorption, H+ and NH3 secretion

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6
Q

Why is there more filtration in the glomerular capillaries than systemic?

A

More surface area, but not constant and can change eg with mesangial cell contraction under ATII influence

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7
Q

What substances constrict/relax the glomerular vessels?

A

Constrict afferent and efferent - norepinephrine, ATII, endothelin, thromboxane
Constrict just efferent - vasopressin
Relax both - acetylcholine, NO, dopamine, bradykinin, prostacyclin, PGI2
Relax afferent - PGE2

NE, ATII and ADH promote production of prostaglandins

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8
Q

What is tubuloglomerular feedback?

A

Local intrarenal negative feedback mechanism for individual nephrons:
Increased NaCl in the distal tubule sensed by extraglomerular mesangial cells of the juxtaglomerular apparatus, sensed by tubular cells of macular densa (transport of NaCl across them - requires Na K 2Cl transporter and ROMK potassium channel luminal, and NaKATPase basolateral)
Transcellular NaCl transport + ATII causes afferent constriction and decrease GFR to minimise NaCl loss

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9
Q

What transporter does furosemide inhibit?

A

NaK2Cl in loop of Henle, compete with Cl

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10
Q

What transporter do thiazides inhibit?

A

NaCl in distal convoluted tubule

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11
Q

What is sodium absorbed with in the PCT?

A

Glucose, amino acids, phosphate, bicarbonate

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12
Q

What is sodium absorbed with in the DCT/LoH?

A

Chloride

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13
Q

What transporters mediate luminal uptake of glucose in the PCT?

A

SGLT2 - high capacity low affinity, first and second portion
SGLT1 - low capacity high affinity, third portion

Saturatable

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14
Q

What mediates PCT phosphate absorption?

A

NaPi-IIa and IIc transporters

Low Tmax so ready excretion of phosphate at high conc cf glucose
PTH decreases Tmax and causes excretion

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15
Q

How is urea reabsorbed?

A

Passive (decreased with high tubular flow rates)
Facilitated transporters - UTA1/A3 in inner medulla collecting duct, ADH dependent, urea concentrates in interstitium

Can reenter thin descending LoH via UTA2, and reabsorbed to enter vasa recta (venous) and then arterial (have UTB) - countercurrent exchange

Impermeable to urea - DCT, cortical collecting duct, outer medullary collecting duct

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16
Q

What are the urinary concentrating mechanisms?

A

NaCl transport without water in ascending LoH causes hyper osmotic medullary interstitium
ADH increases water permeability of the collecting duct, tubular fluid equilibrates with hyper osmotic interstitium

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17
Q

What controls inner medullary collecting duct urea absorption?

A

ADH

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18
Q

What effect does aldosterone have in cortical collecting duct?

A

Sodium and chloride absorption and therefore water absorption

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19
Q

How is urine concentrated without ADH?

A

GFR decreased by dehydration, PCT reabsorbs more sodium and water

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20
Q

What is the vasa recta for?

A

Gains solute as moves distally, gains water as moves proximally. Interstitial osmolality increases as move distally (ascending LoH solute absorption) and decreases as move proximally

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21
Q

Where is renin from and what stimulates its release?

A

Juxtaglomerular apparatus, vascular endothelium, adrenal gland, brain.

Decreased renal perfusion sensed by afferent arterioles of granular cells of JGA, hypotension stimulation cardiac/arterial baroreceptors with SNS activity and catecholamines (beta 1 adrenergic receptors), decreased distal tubular flow or NaCl depletion (macula densa)

Inhibited by ATII

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22
Q

What are the effects of ATII?

A

Arteriolar vasoconstriction (most sensitive renal splanchnic cutaneous)
Facilitates NE release from adrenal medulla and sympathetic nerves
Increases PCT sodium absorption d/t NaH antiporter luminal membrane
Increases aldosterone secretion
TXA2 mediated glomerular vasoconstriction (efferent > afferent)
Increased sodium and water reabsorption
Mesangial contraction, decrease surface area
Release of vasodilatory PGE2 and I2

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23
Q

What inhibits 1alphahydroxylase?

A

Calcium, vitamin D, decreased PTH, increased phosphate

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24
Q

Definition of CKD?

A

> 2-3 m permanent irreversible loss of functioning nephrons

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25
What does carbamylated haemoglobin measure?
Chronic measure of increases in circulating urea
26
Ideal GFR marker
Sole renal filtration, no metabolism, no protein binding, no tubular secretion, non toxic, don't affect GFR NB male dog active creatinine tubular secretion
27
Urinary clearance?
Urine flow rate x conc solute in urine | conc solute in plasma
28
What cats have increased creatinine?
Birman
29
What is SDMA?
Dimethylated derivative of arginine, produced from intranuclear L-arginine residues by protein arginine methyltransferase
30
What is cystitin C?
LMW protein, proteinase inhibitor, intracellular housekeeping gene production Not protein bound and freely filtered, resorbed by megalin endocytosis in proximal tubules and catabolised No secretion Might be increased in tubular dysfunction?
31
What does the sulfosalicylic acid test check for?
Globulin/bence jones protein
32
Why would you measure microalbuminuria?
If suspect hereditary glomerular disease - more sensitive cf UPCR or dipstick Needs to be persistent > 2 w to be of value
33
What impacts UPCR?
Active sediment, marked haematuria, hospitalisation, daily variability Cysto does not change If > 4 pool samples Has to change 35 % if > 12 or 80 % if < 0.5 to be clin relevant change
34
When should a renal biopsy be pursued?
UPCR persistently > 3.5, no response anti proteinurics, progressive proteinuria or azotaemia despite adequate management, if considering immunosuppressive management
35
Important things to do before renal biopsy?
Control BP, discontinue anticoagulants, check haemostasis
36
Contraindications for renal biopsy?
Stage 4 renal disease, tubulointerstitial rather than glomerular, hydronephrosis, pyelonephritis, haemostic disorder, suspect amyloidosis, suspect hereditary, renal abscess
37
What media do renal biopsies go into?
Formalin (standard) Michel's medium (IF) Glutaraldehyde (TEM)
38
How to calculate fractional excretion of electrolytes?
urine conc x (plasma/urine creat) x plasma conc x 100 Increases as GFR decreases - electrolytes used as hypertrophy/compensatory
39
What casts are not necessarily abnormal?
Rare hyaline/granular
40
What are hyaline casts?
Mucoprotein, TammHorsfall protein, uromodulin, albumin Colourless/cylindrical Increase with marked proteinuria and dissolve in urine
41
Epithelial casts?
Direct tubular damage eg gentamicin
42
Granular casts?
Ischaemic/nephrotoxic insult - partially degraded cellular casts
43
Waxy casts?
Due to tubular stasis
44
What causes renal hyperechogenicity?
Non specific - glomerulonephritis, acute tubular necrosis, lepto, FIP end stage CKD Dramatic in ethylene glycol tox Renal dysplasia - corr with histopath
45
Hypoechoic subcapsular thickening?
Lymphoma
46
Medullary rim sign?
Ethylene glycol NB outer medulla may be hyper normally
47
Medullary band sign?
Inner medulla hyper echoic - lepto
48
AKI classification?
1: Non azotaemic AKI - increase creatinine by 27 over 48h, clinical findings eg documented history or volume response, oliguria < 1 2: Mild, 150 - 221 3: Moderate/severe 230 - 442 4: 451 - 884 5: > 884
49
Mortality association with azotaemia?
Increased mortality in ICU even if increased creatinine without azotaemia Hypothermia px indicator
50
Causes of AKI?
Hypoperfusion (haemodynamic), intrinsic, post
51
What factors make the kidney susceptible to injury?
High cardiac output, high metabolic demand, toxicity potential
52
What determines renal blood flow?
Perfusion pressure, cardiac output, intravascular volume
53
What defines volume response in AKI?
If increase UOP to > 1ml/kg/hr with fluid challenge or decrease creatinine to baseline over 48h
54
What happens if you don't address haemodynamic/volume responsive AKI?
Progresss to intrinsic
55
What is required to progress from haemodynamic to intrinsic AKI?
Other factors eg local or systemic inflamm, infrarenal blood flow distribution change, microcirculatory dysfunction/glomerular haemodynamics
56
Phases of AKI?
Initiation - injury Extension - cellular damage - hypoxia/inflamm Maintenance - static 1-3 w Recovery - increased UOP increased Na in urine due to decreased sodium transporters, Na loss can cause vol depletion
57
What is fenoldopam?
Dopamine 1 receptor agonist - causes renal vasodilation, inhibits ADH AT II and NaKATPase Increases UOP
58
What are the cellular mechanisms underlying AKI?
Hypoperfusion, tubular dysfunction, ischaemic injury
59
Explain intrarenal vasoconstriction AKI
Vasoconstriction (decrease NO injured cells increased ET) - decrease GFR, cause ischaemic damage to cells Decreased O2 Decreased cell energy metab Mitochondrial dysfunction (calcium)
60
Explain ischaemic damage AKI
Reperfusion/oxidant injury, intracellular acidosis, phospholipase/protease activation
61
Explain tubule dysfunction AKI
Cell swelling Loss of fence, transporters on wrong side Tubular obstruction detached cells Leaking junctions back leak fluid Energy depletion disrupts cell cytoskeleton
62
What potentiates contrast mediated injury?
Hyponatraemia Ionic contrast Decreased BP and vasoconstriction renal circulation
63
What part of the glomerulus does vasopressin constrict most?
Efferent - maintains GFR
64
Why are aminoglycosides nephrotoxic?
Not metabolised, low molecular weight and water soluble. Ionised to cationic complexes and bind anionic sites on PCT cells, internalised and concentrate there. Potentiation/risk factors = multiple daily dosing, increased concentration, electrolytes low, acidosis, furosemide,antiprostaglandin, dehydration 30S ribosomal binding
65
Why are tetracyclines nephrotoxic?
If expired - metabolites in mitochondria, interfere with PCT oxidative enzymes
66
Penicillin and sulphonamide nephrotox?
Hapten/hypersensitivity/crystallisation
67
Role of prostaglandins in the glomerulus?
Prostaglandin maintains afferent arteriole dilation to maintain GFR when systemic vasoconstriction is present
68
Neutrophil gelatinase associated lipocalin?
Same things found cats & dogs NGAL - increased before creatinine in AKI and CKD Corr with AKI grade Poss higher in intrinsic vs volume AKI and inflammatory AKI No diff outcome AKI Predict progression CKD Made in neuts, increased production, decreased absorption and increased secretion during tubular injury
69
What is insensible loss?
22 ml/kg/day
70
What to give to an anuric patient fluid-wise?
Only insensible loss (may need to not give this if over hydrated)
71
What effect would increased chloride in the DCT have?
Afferent glomerular vasoconstriction (higher chloride increase incidence AKI?)
72
What factors to check to ascertain whether an animal is oligoanuric?
Optimise renal perfusion, BP MAP > 60, systolic > 80 and check cath NB relative versus absolute oliguria
73
Mannitol mechanism of action?
Osmotic diuretic, extracellular volume expansion Inhibits renin and renal sodium reabsorption Increases tubular flow, decreases vascular resistance, decreases cell swelling, protects cf vascular congestion/RBC aggregation, scavenges free radicals, increases intrarenal prostaglandin and vasodilation Increases renal blow flow and GFR - increases solute excretion, ANP, decreases the mitochondrial response to the calcium influx and therefore decreases progression from sublethal to lethal cell injury BUT no evidence that it improves AKI Can't use if dehydrated or over hydrated
74
Furosemide mechanism of action?
Loop diuretic - inhibits NaK2Cl pump in LoH - increases tubular flow with no increase in GFR Makes basal NaK pump unnecessary Decreases medullary O2 consumption Renal vasodilatory effects Use for over hydration/hyperkalaemia? CRI gives more sustained diuresis with lower dose
75
Calcium channel antagonists?
Eg diltiazam, which might help with more complete resolution in dogs with lepto Reverse vasoconstriction, dilate mostly afferent, inhibit glomerular feedback-mediated vasoconstriction GFR independent natriuresis
76
Peritoneal dialysis?
Probably more helpful in cats
77
Mechanisms of calcium, magnesium and phosphate changes in AKI?
Increased calcium - usually inc total with N ionised but can be increased if decreased GFR and no excretion Decreased calcium - complex with phosphate Phosphate - decreased excretion Magnesium - decreased excretion/increased loss if PU
78
Problem with ACEi in AKI?
Afferent arteriole vasoconstriction
79
What AKI cause has best outcome?
Obstructive in cats, toxic and other = worst Ischaemia = better px
80
How often does azotaemia persist after AKI?
Around half
81
Distribution of types of CKD dogs and cats?
Dog - 60 % tubuloint, quarter glomerular, rest amyloidosis/other Cat - three quarters tubuloint, 15 % glomerular, rest lymphoma/amyloidosis
82
How does the failing kidney adapt?
Increased load per nephron, increased tubular secretion to maintain electrolyte and water excretion. Maintained better for Na/K/water than phosphate
83
Organic solutes
Mediators of uraemia - accumulate as can't be secreted when GFR starts to fall. Inhibit NaKATPase, alter platelet, red cell and white cell function NB as kidney fails can't catabolise compounds like PTH and cytokines. PTH is a uraemic toxin
84
Uraemic gastric changes in dogs and cats?
Dogs - can get uraemic gastropathy with ulceration Cats - fibrosis, gland atrophy, mineralisation in stage III/IV, no evidence ulceration, Gastric hyperacidity not documented
85
Halliitosis in renal dz?
Bacterial urease converts urea to ammonia
86
Enterocolitis in renal dz?
Ammonia produced in colon is irritant
87
What mediates impaired urine concentrating ability in CKD
Impaired genesis of concentrating gradient due to medullary architecture disruption/countercurrent multiple disruption Impaired response to ADH (uraemia), increased distal tubular flow rate
88
What is the most common cause of secondary hypertension?
CKD Renin, sodium/water retention Aldosterone and SNS imp
89
Factors causing anaemia in renal disease?
EPO - decreased production and decreased efficacy d/t nutrient deficiency and uraemic factors Blood loss (GI, thrombocytopathy) Inflammation Decreased RBC lifespan
90
What does hypoxia inducible factor do?
Increases EPO production and intestinal iron uptake
91
What does FGF23 do?
Causes phosphate excretion Inhibits 1alpha hydroxylase FGF/klotho system
92
Renal secondary hyperparathyroidism?
Phosphate retention, PTH, FGF23, 1alphahydroxylase inhibition Decreased calcitriol, decreased neg feedback, increase PTH. Initially calcitriol production is increased to normal at the expense of persistent increases in PTH CKD progression decreases amount of viable renal cells and more calcitriol deficiency Calcitriol deficiency impairs bone response to PTH and elevates the set point for PTH so continues to be secreted despite normal or increased calcium. Uraemic toxins impact PTH response to calcitriol 50 % cats advanced CKD hypocalcaemic. May get inc PTH prior to azotaemia RSHP majority cats with CKD and corr with creatinine
93
Metabolic acidosis in CKD?
Decreased GFR, can't get rid of daily acid load, no filtration phosphate/sulphate products, impaired tubular proton excretion Nephrons compensate by increasing ammonium secretion. Structural damage impairs renal ammonium production., Retention of organic acids increases the anion gap Stimulates branched AA degradation - catabolism of muscle
94
What does urea correlate with?
Uraemic toxins
95
When does SDMA increase?
Decreased GFR by 25 - 40 % 17/10m earlier than creatinine on cat/dog
96
IRIS staging categories
I - dog < 125 cat < 140 SDMA < 18 both II - dog < 250 cat < 250 SDMA dog < 35 cat < 25 III - dog and cat < 440 SDMA dog < 54 cat < 38 IV > 440 > 54 > 38 Proteinuria - dog 0.2 - 0.5/>0.5, cat 0.2 - 0.4/>0.4 BP: <140. 140 - 159, 160 - 179, > 180 Breed spec - 10/10-20/20-40/>40 inc from RI
97
Sighthound blood pressure?
40 mmHg higher
98
Phosphate restriction CKD?
Stage II onwards dog and cat - slow progression, decrease RSHP, decrease mortality I < 1.45 II < 1.45 III < 1.61 IV < 1.94 Diet 4-6 w then add binder Diet can be effective alone in II and III
99
Diet in CKD?
Renal diets evidence stage III onwards (maybe II cats?) - increase survival time decrease risk renal death decrease risk uraemic complications. Maintain QoL and decrease clin signs. Decrease phosphate decrease PTH decrease FGF23 in stage II - IV cats. Rec all proteinuric dogs. Protein restriction - decreases glomerular protein loss which is detrimental to tubules Controversial otherwise. Restrict in stage III/IV, decrease urea and uraemia. But renal diets not restricted enough to cause protein malnutrition if consumption adequate. Omega 3 - decrease mortality, improve renal function, decrease renal lesions/proteinuria/cholesterol, favourable lipid metab, suppress inflammation and coagulation, decrease BP, antiox, may be synergistic with antioxidants to reduce the decrease in GFR Phosphate restriction - dog and cat stage II onwards, slow progression decrease mortality Also: B vitamins neutral acid base soluble fibre increased caloric density and potassium supp feline.
100
Benefit of subq fluids CKD?
Decrease dehydration which can cause AKI, imp appetite/activity/decrease constipation
101
Hypokalaemia in CKD?
Around 1/3 of stage II and III cats Might get hyperkalaemic in stage IV
102
Hypertension and renal mortality?
Risk factor in canine CKD
103
What factors should be taken into consideration when using amlodipine in CKD?
Make sure BP not < 120, no signs hypotension, creatine doesn't increase > 45 or SDMA >2
104
Development of EPO ABs?
30 % cats 50 % dogs (not all anaemic) when tx epoietin less darbo
105
When to use rhEPO?
Stage III onwards, PCV < 22 % with clin signs anaemia Half to all cats reach target (bottom end RI), responders live longer Aim 1 - 3 % increase per week
106
Calcitriol use in CKD?
Decreases PTH Decreases mortality in canine stage III and IV by slowing progression - cats maybe not so much (?improve podocyte viability and decrease RAAS?) Use in canine III onward (? II?) with normal phosphate. and iCa Give fasted to minimise. increase in Ca and phosphate Make sure calcium phosphorous product <52
107
Proteinuria and CKD?
Every 1 increase UPCR increases risk of death/uraemic crisis 1.5 x in dogs Benazepril assoc with survival benefit in cats if UPCR > 1 Intervene if stage I > 2 or stage II onwards > 0.4/0.5
108
ACE escape?
Chymase enzymes Bradykinin also degraded by ACE - vasodilation and renoprotection via NO stim
109
ARB mech?
Block type 1 not 2 - latter imp for vasodilation
110
Aldosterone blockers?
Attenuates renal damage independent. of BP Aldosterone might be fibrogenic in kidney (TGFbeta)
111
Prognostic factors feline CKD?
Stage (1000, 700 and 30d for II - IV) Phosphorous, proteinuria, anaemia (?), weight loss NOT nephrolithiasis NOT BP
112
Prognostic factors canine CKD?
``` Stage (2.6/4.7 X risk death stage III and IV) BUN Creatinine if no renal diet fed Diet (stage III 250 d vs 600 d) Proteinuria - clin signs, uraemia, death, every 1 UPCR increases death risk 60 % Increased BCS longer survival BP Cause - hereditary slower ```
113
HMWP in AKI?
Higher ratio of HMWP to albumin could indicate more severe glomerular injury
114
Urinary retinol binding protein?
Marker of tubular damage
115
Why are urinary enzymes more sensitive than protein?
Increased before overt dysfunction Also, easier to measure and amount of leaked enzymes might be predictive of degree of ongoing damage
116
Overhydration and AKI?
Might be prognostic (worse disease) or may worsen outcome
117
Most common glomerular diseases in dogs?
Immune complex glomerulonephritis, glomerulosclerosis, amyloidosis
118
Signalment of dogs with nephrotic syndrome?
Younger
119
What glomerular diseases have what USG?
Normal common in general, amyloidosis more frequent isosthenuria
120
Most common cast in glomerular disease?
Hyaline - Tamm Horsfall mucoprotein secreted due to proteinuria
121
Membranoproliferative glomerulonephritis?
Immune complex glomerulonephritis Most severe clin signs and clin path changes BMD - mesnagiocapillary, familial, auto recessive - asco with lyme dz Immune complex deposition subendothrlial GBM, cytokine complement activation (NB congenital C3 deficiency in Brittany sp) C3 IgG/M/A deposition If can't fix with address underlying dz consider immunosupp
122
Membranous nephropathy?
Most common feline, NB young dobermann Immune complex glomerulonephritis AB deposition sub epithelial GBM, less complement/cytokine activation Primary - immune mediated, ABs interact with podocyte antigens Also secondary - circulating immune complex Progresses through stages - spikes, GBM thickening and projections surround the immune complexes, bearded appearance due to immune complex deposition May not have GBM thickening in later stages Px - later stages poor, C3/IgG better than IgM/A, may be slowly progressive Immune supp if progressive and no dz to manage
123
Proliferative glomerulonephritis?
ICGM Milder Less likely to be caused by infectious. dz Mesangial hyperplasia with mononuclear infiltrate IgG/M GBM or mesangium or cap walls Immunesupp if no dz and prog
124
Immunoglobulin A nephropathy?
Enteric/hepatic dz IgA - polymeric, nonspecific trapping in mesangium increased formation/decreased clearance Can also have less intense IgG/M/C3
125
Amyloidosis?
Familial breeds? Sharpei, beagle, foxhound, Abyssinian, siamese More medulla in cats and shar pei, otherwise glomerular dep Other dogs chronic inflamm - collie, female, walker hounds Beta pleated amyloid Don't need TEM Colchicine may be helpful in deposition face (decreased SAA release from hepatocytes?) DMSO maybe in deposition phase? Decrease SAA conc? Anti-inflamm/decrease interstitial fibrosis?
126
Hereditary nephritis?
ECS/ESS auto rec Bull terrier/Dalm auto dom Samoyed one fam X link dom Type 4 collagen defect causes GBM deterioration (5. in samoyed) Samoyed males v severely affected ECS proteinuria from a few months. Both terminal CKD < 2y BT/Dal more variable Need TEM to dx - splitting and fragmentation of GBM
127
Minimal change glomerular disease?
Masitinib Rare in dog and cat Human - lymphokine dysfunctional T cell increase GBM, perm, dx TEM, response steroid
128
Glomerulosclerosis?
20 % dogs end stage lesion DM? Hypertensive damage? Non spec Ig/C3 trapping Focal segmental glomerulosclerosis = primary dz
129
How many dogs with glomerular disease have a secondary cause?
Just over half
130
Target protein in glomerular dz?
< 0.5 or 50 % decrease Decrease dose or stop if creat increases > 30 % or to stage 4, K > 6.5 or BP < 120
131
Other tx?
Thromboxane synthase inhibitor may decrease proteinuria, decrease glomerular inflammation Omega 3 - renoprotective, decrease BP, decrease trig/chol
132
How many immune mediated glomerular disease in dogs?
Half
133
When to use immunosuppression in glomerular disease?
Biopsy evidence immune mediated - subepi/endothelial, intramembranous or mesangial electron dense deposits, immunofluorescent staining for immunoglobulin or complement with anti-GBM pattern No response standard tx
134
Steroids and glomerular disease?
Use short term, as steroid excess induces glomerular lesions Myco/ciclosporin considered Ciclosporin only one prospective (wasn't found to be of benefit...) Use immune supp 8-12w before change If response, use 3-4 m then taper
135
When to recheck glomerular disease dogs?
Stable stage I/II 3 - 14 d Unstable or III 3-5d No need to rebx, changes don't necessarily resolve
136
Albumin and hypercoag?
Albumin binds arachidonic acid - if free may get increased platelet aggregation
137
Hypercoagulability in glomerular dz?
Less alb and AT | More fibrinogen, cholesterol, procoag cytokines, alpha2macroglobulins, alpha 2 antiplasmin
138
Hyperlipidaemia and glomerular dz?
LDL/oxLDL alter mesangial cell function, increase matrix synthesis and cause glomerulosclerosiss Lipoprotein deposition is cytotoxic
139
Prognostic factors glomerular disease?
Azotaemia Type - GN and amyloidosis worst Nephrotic syndrome
140
Cystinuria breeds and causes?
Newfie and lab type 1 - SLc3a1 (rBAT protein) autosomal recessive Aussie cattle dog - SLc3a1 auto dom incomplete pen (non-type 1) Min Pin - SLc7a9 - bo+ AT protein Eng bulldog, rottie, SBT, JRT, welsh corgi, chih, dachs Form calculus 5 y, newfie/lab younger Type III = androgen dependent Cats described Cysteine, carnitine fail to resorb NB cardiac
141
Management cysteineuria?
Alkalinising diet Low protein Diuresis 2 - mercaptopropionylglycine
142
Breeds and cause hyperuricosuria?
Dalmatian - can't move uric acid into hepatic cells, impaired PCT uric acid absorption, active urate excretion DCT. Slc2a9 - auto recessive, all dals have mutation English bulldog, Black Russian terrier Slc2a9, auto rec Primary hepatic dz Cats PSS and idiopathic NB neoplasia HAC CKD
143
Management of hyperuricosuria?
Allopurinol, xanthine oxidase inhibitor Purine restricted diet, alkalinising to decrease tubular ammonia Medical dissolution in PSS if fix
144
Breeds and cause of hyperxanthinuria?
Allopurinol tx CCKS wire-haired dachs Cats Decreased xanthine oxidase activity
145
Breeds for primary renal glucosuria?
Basenji, scottie, Norwegian elkhound
146
How many Basenjis get Fanconi?
10 - 30 %
147
Causes of acquired Fanconi?
Gentamicin, hypoparathyroidism, tubular necrosis Chlorambucil cats Jerky treats
148
Common amino acid in urine of Fanconi?
Cysteine
149
What is lost from tubules in Fanconi?
AAs glucose bicarb sodium potassium urate uric acid phosphate
150
What acid base disturbance do Fanconi dogs get?
Hyperchloraemic (nonAG) metabolic acidosis (bicarb loss)
151
How to manage Fanconi?
Potassium citrate, aim bicarb 18 - 24 K 4 - 6
152
Prognosis Fanconi?
Good - MST 5 y (and some don't present until 4-8y). most good/excellent qol. 50 % die reasons unrelated
153
Type I renal tubular acidosis?
Distal tubular acidosis Failure excrete H+ Hyperchloraemic metabolic acidosis, severe acidosis, urine pH > 6 Hypercalciuria, hyperphosphaturia More severe bone dz and nephrocalcinosis poss, urolithiasis poss Can have severe hypoK No PCT defects Good response to alkali tx and don't need as much Low bicarb excretion Urine pH > 6 in acidaemia and if give ammonium chloride Citrate in urine decreased NB: pyelonephritis cats and lepto dogs
154
Type II renal tubular acidosis?
Proximal tubular acidosis Failure to prevent bicarb loss (DCT compensates) Basolateral Na-bicarb cotransporter defect, bicarb leaks to tubular lumen Hyperchloraemic MA (less severe) Other tubular defects poss Need large amount of alkali tx and less good response - marked bicarbonaturia with increased pH and increased fractional excretion of bicarb Urine pH acidic and decreased with ammonium chloride challenge Less clin consequences eg bone, no nephrocalcinosis and urolithiasis unusual Still have calcium and phosphate in urine
155
Type IV renal tubular acidosis?
Hypoaldosteronism/aldosterone antagonism Loss HATPase stim, decreased distal sodium absorb Hyperchlor MA and increased K
156
High and intermediate molecular weight protein used for acute tubular injury?
Systemic circulation Albumin - glomerular/prox tubule - non specific Immunoglobulin IgA/G - glomerular, no advantage over UPCR
157
Low molecular weight protein used for acute tubular injury?
From PCT or systemic circ and decreased resorption Retinol binding protein - from prox tubule, stable in acidic urine and frozen, increases progressively in CKD, wide interindividual variation Alpha 1 microglobulin - stable in acidic urine, decreased in hepatic disease Beta 2 microglobulin - UNSTABLE acidic urine - predictor GFR in dogs but not sensitive enough to monitor progression
158
Tubular enzymes used in acute tubular injury dx?
Large molecules expressed in urine from damaged tubular cells and increased before overt dysfunction. May predict degree/severity of injury? Neutrophil gelatinise associated lipocalin - PROX tubule only, haematuria/pyuria interfere and infection or inflammation decreases specificity. Is freeze/thaw stable. Lactate dehydrogenase - PROX tubule Gamma glutamyl transferase - PROX tubule, UNSTABLE in acidic urine. Haemorrhage and pyuria interfere N acetyl D glucosaminidase - prox and distal affected by HT4/DM, pyuria and storage Intestinal ALP - prox and distal
159
Breeds predisposed to renal agenesis?
Beagle, doberman, sheltie
160
Breeds for renal dysplasia?
Lhasa/shih tzu, SCWT, Gret, Boxer
161
AUS renal dysplasia?
Loss corticomedullary definition, hyper echoic speckles
162
Histopath renal dysplasia?
Inappropriate differentiation of nephron components - immature alongside mature Functional nephrons hypertrophied
163
Podocytopathy?
SCWT NPH1/KIRREL2 genes (split diaphragm proteins nephrin neph5 filtrin)
164
Polycystic kidney dz breeds and cause?
Persian and crosses, auto dominant PKD1 (polycystin) gene mutation - also Himalayan and British blue. Probably other mutations too as described in absence of this mutation. Bull terrier - auto dominant PKD1 gene mutation Cairn/WHWT auto recessive PKD1- get liver cysts too
165
Cystadenocarcinoma?
GSD, auto dom mutation, BHD gene
166
False neg protein dipstick?
Bence Jones acid dilute, quite sensitive overall though for albumin Also poor specificity
167
What does the sulfosalicylic acid test check for?
Bence jones proteins and globulins Poor sens and spec for albumin
168
Physiological proteinuria?
Stress, exercise, seizures, hyperthermia
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Pre-renal proteinuria?
Bence jones
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Postrenal?
Cysto help but prostatic secretion can reflux
171
How is persistent proteinuria defined?
Three or more tests more than 2w apart. NB proteinuria may decrease as renal dz progresses (less nephrons)
172
When is protein change significant?
35 % at UPCR 12, 80 % at 0.5 Need to pool 3 if > 4
173
When should proteinuria be treated?
No renal dz - > 1 | Renal dz stage 1 onwards - > 0.4/0.5
174
What effect does enalapril have on glomerular disease?
Sig decrease proteinuria, delay onset and progression of azotaemia
175
Why might potassium be high in glomerular disease?
ACEi/ARB | Pseudohyperkalaemia d/t thrombocytosis
176
Why less cell response in membranous glomerulonephropathy?
immune complex dep not endothelial, is sub epithelial GBM
177
Difference between familial and reactive amyloidosis?
Familial Abyssinian shar pei medullary mostly some glomerular, reactive all glomerular
178
What colloid to use in nephrotic syndrome?
Not colloids - HMW molecules lost quickly and leave high sodium fluid behind, increasing hydrostatic pressure Use plasma or human albumin
179
When to give aspirin in glomerular disease?
< 20 g/l albumin
180
When to use bicarb/citrate in CKD?
Cat bicarb < 16 dog < 18
181
Most common NSAID nephrotoxicity?
Acute cortical nephrotoxicity, chronic medullary cytotoxicity less common Doesn't differ selective/non-selective
182
General risk factors for renal NSAID tox?
``` Dehydration Hypotension Admin of anti-hypertensives which are not renal vasodilators Higher NSAID dose Hypoalbuminaemia Genetic? GSD? ```
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Only risk factor for acute cortical NSAID nephrotox?
Dietary salt restriction, diuretic, GA
184
Pathophys of the NSAID nephrotox's?
Acute cortical nephrotox: Loss renoprotective effects vasodilatory prostaglandins. Decreased renal blood flow/GFR Cox 1 > cox 2 Chronic medullary cytotoxic: Loss cytoprotective prostanoids. Medullar interstitial/tubular cell papillary necrosis Cox 2 > Cox 1
185
Clin findings NSAID nephrotox?
Acute cortical nephrotox: Early: Renal cells/casts in urine, renal enzymuria, proteinuria, microalbuminuria Intermediate - electrolytes abnormal, decreased conc Late - creatinine Chronic medullary cytotoxic: No early Intermediate - renal enzymuria, decreased conc ability Late - electrolytes, acid base, creatinine
186
What factors may be problematic when using NSAIDs in CKD?
Hypoalbuminaemia (protein bound) Metabolites might be renally excreted Low reserve so damage may be disastrous NB cat CKD NSAID slowed progression... low dose 0.01-0.03 Use sub therapeutic dose at first, titrate up, and use in bursts rather than continuously
187
When does risk of UTI increase with indwelling ucath?
3d onwards
188
Furosemide and diuresis?
CRI more effective cf intermittent bolus
189
Dopamine agonists for diuresis?
Dopamine itself not recommended Fenaldopam D1 receptor antagonist, renoprotective in people - might be effective? Monitor for hypotension
190
How to give amlodipine if you can't give it orally?
Rectally
191
Negative prognostic indicators AKI?
Ethylene glycol and azotaemia Severe azotaemia No imp/worsening despite tx Concurrent dz eg pancreatitis, sepsis
192
What marker of renal function has least within individual variability in azotaemic cats?
Creatinine, better than GFR
193
What does high phosphate diet do to healthy cats?
Glucosuria and microalbuminuria and decreased creatinine clearance in the short term
194
What happens to magnesium in CKD cats administered gastroprotectants?
Decrease over time with combined PPI H2 blocker Also increased sodium PPI No increase in CKD progression though
195
What is subclinical bacteriuria associated with in cats?
``` Uncommon - 6% Most single organism (E coli) More likely female Assoc with bacteriuria and pyuria Assoc with low USG and CKD Hepatic disease ```
196
NAG in feline idiopathic cystitis?
N-acetyl beta D glucosaminidase: NAG/creatinine higher in FIC - > degrade GAG? Is in tubules (PCT) and can degrade glycoprotein and mucopolysaccharide UPCR higher too UPCR corr with NAG
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CKD risk factors cat?
Feeding commercial dry food PROTECTIVE Periodontal dz increased risk
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Feline familial amyloidosis?
Oriental/siamese - mainly liver - Abyssinian/somali - renal, die young Difference between - ? different kind of amyloid?
199
Glomerular proteinuria in cats?
Young male with higher proteinuria Immune mediated dz common ICGN: live longer if get immunosuppressive, effusion neg prog 75 % immune complex mediated Membranous glomerulonephritis most common Poor px overall
200
FGF 23 in canine CKD?
Increased in stage 2-4 cf 1 and corr with stage Corr with increased phosphate More stage 2 have increased FGF23 cf PTH PTH, creatinine and phosphate predict FGF23 Correlated with survival
201
What is FGF23?
Phosphotonin. Released from osteocytes when phosphate and calcitriol increased, increases urinary phosphate excretion by decreasing sodium phosphate cotranssporter Inhibits calcitriol As CKD progresses, less alpha klotho (cofactor) Binds to FGF receptor
202
Cat CKD and FGF23?
Increased earlier than phosphorous or PTH, neg px indicator Corr with low magnesium, magnesium corr with risk of death Corr SDMA and creat, increased in non-azotaemic but SDMA inc cats
203
Bacteria and disease progression feline CKD?
No effect positive urine culture if treat with ABs PUC around 22 % CKD cat Most no clin signs
204
Telmisartan in proteinuria in dogs?
Probably more effective than enalapril Combo might cause azotaemia
205
Predictor of short term outcome in acute on chronic AKI?
AKI grade
206
Vitamin D in PLN?
Decreased in non-azotaemic - corr with amount of protein loss and with decreased albumin Decreased vitD binding protein as albumin decreased
207
Risk factors for enterococcal bacteriuria in dogs?
Recurrent bacteriuria, anatomical abnormalities, urolithiasis, neoplasia Is this bacteria a marker of concurrent dz?
208
Glucosuria and USG?
Not actually that much change
209
What confers fluoroquinolone resistance?
DNA gyrase/topoisomerase genetic mutations in bacteria
210
Blood in urine and UPCR?
Microscopic might effect UPCR
211
Platelet changes in CKD dogs?
Hypercoag. | Increased alpha IIb beta 3 and P-selectin
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Experimentally, what may accelerate renal regeneration after AKI?
Autologous bone marrow derived mesenchymal stem cells, GCSF (latter decrease fibrosis)
213
Cranberry extract and canine UTI?
Prevented UTI Prevent E coli kidney cell adherence in vitro In another study not better than placebo
214
Recurrence in feline urinary obstructions?
No difference any outcome measure for saline lavage Less if indwelling Meloxicam didn't help Intravesicular pentosan polysulfate didn't help
215
How many SUBS cats survive to discharge?
94 %
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Prevalence bacteriuria CKD dog?
Not assoc stage Around 20 % Sub clin then pyelonephritis then cystitis most common
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How to maximise renal bx yield?
16 g, US guided
218
Stent vs SUBS cat?
Mortality more, survival less, hosp more, complication more in stent Stent lower urinary signs and get infected more
219
Calcium oxalate urolithiasis and weight?
More in fat dogs
220
Amoxicillin and feline kidney disease?
Amoxicillin decreased in urine of azotaemic cats, may be inc in serum ? SEs?
221
Mirtazapine in CKD
Transdermal works to increase appetite and weight
222
Troponin I in renal disease?
Increased in serum same as cardiac Increased in urine more than cardiac Cats
223
Categories for bacteriuria?
Sporadic cystitis (< 3 in a year) Recurrent cystitis (3+ in a year or 2+ in 6m) - relapse/reinfection/persistence/superinfection Pyelonephritis - acute uncomplicated/complication, chronic Subclin bacteriuria - no clin signe Bacteriuria with implant or ucath
224
UTI in FLUTD?
Low prevalence (3 - 19 %) in young but. up to 45 % in > 10y
225
Prevalence pos urine cultures cats diff dz?
CKD up to 30 %, DM/HT4 around 13 % Clin signs more common latter two? Pos in 30 % ureteral obstruction, also SUBS infections reach 30 %
226
Where does KIM1 live?
Kidney injury molecule - prox tubule - increased in sepsis/urethral obstruction
227
Cat breed with higher creatinine?
Birman
228
Homocysteine/CKD?
Uraemic toxin Dogs: Increased if decreased renal excretion or impaired metabolism Corr proteinuria Cats: Increased and corr with stage/UPCR, not hypertension NB may not be assoc with cobalamin deficiency in cat
229
Main difference bacterial cystitis in cats?
Often comorbidity present and far more common older cats
230
How to treat sporadic UTI?
3-4d amoxicillin or TMPS Always culture cats NSAID alone might be enough This also applies to males with no evidence prostatitis, and comorbidities not affecting utract This does not apply to recurrent (additional UTI < 3m) Check culture afterwards not recommended
231
How to treat recurrent UTI?
Determine relapse/persistence/recurrence Evaluate for cause Check AB propriety and compliance 3-5 day for recurrent, longer (7-14) persistent/relapse NB amoxicillin-clav ineffective against E. coli in tissue Can reculture during if using longer course/after, but ? change tx if clin signs gone
232
How to treat pyelonephritis?
Do blood culture if immune supp or fever Interpret susceptibility with serum/tissue breakpoints not urine Check lepto if culture neg Quinolone (efficacious cf e coli) 10 - 14d, recheck culture 1-2w after stop AB but NB ? change tx if clin response
233
AB for prostatitis?
Weakly alkaline, lipid soluble high pKa ABs Quinolone or trimethoprim Chloramphenicol, tetracycline don't penetrate, and macrolide/clindamycin penetrate but no e coli efficacy so poor choice
234
How to treat prostatitis?
Always check for in male dog with bacteria in urine Breakpoints for serum ? aspirate prostate? 100000CFU bacteria might be normal in prostatic wash Drain abscess 4-6w + castrate, longer chronic Rpt wash if clin signs remain + consider other ddx
235
How to manage subclinical bacteriuria?
Not assoc with survival or development of clin signs Poss treat if high risk ascending inf or if think caused inf elsewhere Poss treat if can't show signs (paralysed) with fever or other clin signs - short course 3-5d Poss treat if plaque/urease forming (Corynebacterium urealyticum or Staph), 3-5d
236
Risk factors subclinical bacteriuria dog?
DM, obesity, parvo pup, acute disc, paralysed dogs, steroid/ciclosporin
237
Enteroccous tx?
Need aminoglycoside with ampicillin
238
Bacteria assoc with struvite?
Staph pseudintermedius, proteus mirabilis
239
Urolithiasis and AB?
Always culture as could be struvite component Cats almost all sterile Culture urine, and urolith if urine neg AB 7d if signs, if struvite with urease producing bacteria (duration? 7d ab seemed fine in one study)
240
Urinary heat shock protein 72 in renal dz?
Stress induced cytoprotective protein Predict survival time CKD cat Increased in CKD and AKI cat Sens > spec cat Dog - same, sens and spec better than cat, sens still > spec. AKI only. Predict survival AKI.
241
Parvo and AKI?
Increased urinary IgG, CRP, retinol binding protein and neutrophil gelatinise associated lipocalin Also increased UPCR Urea/creatinine not increased
242
Plasma indoxyl sulfate in CKD?
Protein bound uraemic toxin, metabolic breakdown of tryptophan in intestine > indole > hepatic metabolism. Renal tubule excretion. Accum in tubular cells cause progression? Predicts stage progression in dogs and cats Cats - assoc with FGF23 (assoc with phosphate metabolism?), strong corr with phosphate
243
GGT/ALP in AKI?
Urinary - both prox tubule brush border Poor sens/spec, ALP better than GGT
244
Urinary IgM/IgG?
Increased in AKI and CKD More increased in ICGN - also prognostic
245
Urinary retinol binding protein?
Inefficient tubular absorption Increased AKI Increased CKD and prognostic Higher in proteinuria animals
246
Urinary NGAL?
Decreased tubular absorption and prox tubular cell damage releases Gentamicin - early marker and corr with injury Increased AKI/sepsis Also increased CKD, glomerular dz, lower utract dz Active sediment big problem Increased neoplasia same as CKD
247
Which urine markers glomerular which tubular?
Tubular - UPCR SDSPAGE albumin NAG clusterin cystatin C GGA KIM NGAL RBP THP Glomerular - UPCR SDSPAGE albumin CRP Ig NAG NGAL
248
Urinary N-acetyl beta d glucosaminidase?
Tubular cell lysosomal enzyme - released on damage. Higher intact males. AKI/CKD Corr proteinuria Sensitive Glomerular dz (better glomerular?)
249
Serum cystatin C?
Small protein cf SDMA (which is creatinine sized) More sens GFR cf creatinine? Inferior creatinine SDMA for GFR dogs
250
Urinary active transforming growth factor beta?
Increased 6m pre azotaemia in cats Predict fibrosis, renal inflamm and UPCR Also assoc with fibrosis:
251
Mini schnauz and proteinuria?
Corr trig and UPCR UPC >0.5 60 % hypertrig cf none normal trig No azotaemia/hypoalb/hypertension, no cardiac dz, AT3 normal Lipid induced glomerular injury? Decreased lipoprotein lipase? Segmental glomerular sclerosis
252
Immune supp and glomerular dz?
Mycophenolate +/- chlorambucil - all/6 alive at end of study vs one/7 with no immune supp ICGN less common in UK? 27 % vs 50 %?
253
Risk factors urinary incontinence dog?
Early onset (<8y)= neutering and neutering <6m, no impact age of spay in UI overall Hazard increased with inc bodyweight, Irish setter most hazard breed Decreased oestrogen, LH/FSH, COX2/gonadotropon receptors? Increased GAG/collagen? High risk breeds - Irish setter, doberman, bearded collie, dalmatian
254
Type III cystinuria?
Androgen dependent - mastiff, staffie, Scottish deerhound, Irish terrier. Entire males.
255
Grape/raisin tox?
Neuro signs 75 % in a group of AKI not assoc severity outcome etc
256
Focal segmental glomerulosclerosis?
Non immune complex, podocyte injury, compression of capillary lumen Females 26 % cases Severe hypoalb/ascites/oedema and azotaemia uncommon, hypertension frequent Creatinine and alb assoc with survival NB SCWT, Airdale, mini schnauz
257
USMI bulking outcomes?
70 - 100 % effective
258
Acute on chronic kidney disease cats?
Phosphate assoc short term outcome creatinine long term Short survival after discharge Around 60 % discharged
259
Most common infectious dz exposure proteinuric dogs?
Rickettsia, Ehrlichia, Borrelia More if alb lower/creatinine higher
260
Neuroendocrine alterations in FIC cats?
Increased systemic/localised sympathetic Decreased HPA increased muscarinic stim response
261
Feline CKD microbiome?
Decreased diversity. May increase SCFA Dysbiosis exacerbates colonic derived uraemic toxins eg indoxyl sulfate and p cresol sulfate
262
What is beraprost sodium?
Prostacyclin analogue, might help with renal hypoxia/fibrosis
263
Name urease producing bacteria
Corynebacterium urealyticum, Staph, Klebsiella, Proteus, Mycoplasma
264
What urinary tract infection bacteria are catalase negative?
Enterococcus/strep
265
UTI bacteria in dogs/cats?
E coli most common in both Mostly gram negative dogs, equal gram neg/pos cat Enterococcus second most common cat
266
What UTI bacteria express fimbriae?
E coli Gram neg Klebsiella pneumoniae
267
Most common compound urolith?
CaOx inner struvite outer, then struvite inner calcium phosphate outer
268
Urate stone former mutation?
SLC2A9 Failure reabsorption prox tubule Secretion DCT
269
Breeds for feline urate and cysteine stones?
Urate - Egyptian mau, Birman, siamese Cystine - siamese
270
Additional amino acids which are deficient with cysteine loss in urine?
Carnitine/taurine dogs Cats - COLA
271
What makes up the COLA transporter?
2 heterodimers, RBAT and bo+AT SLC3A1 and SLC7A9 genes
272
Deficiency in what vitamin can predispose to calcium oxalate deficiency?
B6 - decreased oxalate metabolism
273
USMI response for various management options?
Oestrogen: 89 % Phenylpropanolamine: 75 - 90 % female, 43 % male Collagen: 60 %, more if add phenylpropanolamine Artificial sphincter: 90 % medical refractory
274
Risk factors for FIC?
Overweight, multicat household, fearful behaviour, less outdoor access, decreased water intake
275
Ectopic ureter morphology?
Dog - male and female most intramural and bilateral Cat - intramural, equal bilateral/unilateral
276
Characteristics of bacteria causing UTI?
Fimbriae/pili adhesins Toxins eg haemolysin Host immune system evasion eg capsular antigen Utilise host nutrients eg aerobactin Uropathogenic E coli B2/D
277
Risk factors UTI dog/cat?
``` Dog: Steroids/immunosuppressivess DM Parvo Obesity Chemo ``` ``` Cat: DM CKD Female HT4? ```