Elimination & Detox 2: Nephrotoxins Flashcards
2 UNIQUE functions of the kidneys?
- VITAMIN D SYNTHESIS
- BP REGULATION
TOXICANTS are more likely to cause RENAL INJURY because… (2)
- KIDNEY TAKES 25% OF ALL CO, so EXPOSED to a HIGH AMOUNT OF BLOOD FLOW
- some toxicants can CONCENTRATE in URINE or TUBULE EPITHELIUM than the rest of the body
give 3 drugs that can ALTER RENAL BLOOD FLOW/GFR
- NSAIDs
- ACE-INHIBITORS
- DIURETICS
if AKI develops, what 3 interventions should we administer?
what should we BE WARY OF? how should we handle it? (2)
- IV fluids
- anti-emetics
- early NUTRITIONAL support
BEWARE OVERHYDRATION;
- patients with AKI can have VARIABLE URINE OUTPUT, so if they become OLIGURIC or ANURIC then MULTIORGAN DAMAGE IS LIKELY
- if URINE OUTPUT DECREASES = DECREASE or STOP IV FLUIDS
what is the MOST COMMON TOXICANT in SMALL ANIMAL MEDICINE?
NSAIDs!
how do NSAIDs STOP PAIN?
what are the 3 ORGANIS that they can IMPACT? how?
what 2 OTHER THINGS can occur with NSAID OVERDOSE?
they INHIBIT COX-1 & COX-2, which then INHIBITS PRODUCTION OF PROSTAGLANDINS, PROSTACYCLIN & THROMBOXANE A2
4 organs?
1. GI TRACT = PROSTAGLANDINS are INHIBITED by NSAIDs, and they help REGULATE PRODUCTION OF GASTRIC ACID, BICARB & MUCOUS
–> NSAIDs can lead to GI ULCERS!
- KIDNEYS = PROSTAGLANDINS usually help cause GLOMERULAR VASODILATION, so NSAIDs can cause TUBULAR NECROSIS & AKI
- PLATELETS = THROMBOXANE A2 helps PLATELET AGGREGATION, so WITHOUT IT w/ NSAIDs CAN CAUSE GI BLEED/THROMBOPATHIA
ACUTE LIVER INJURY & CNS SIGNS can also occur with NSAID OVERDOSE
DECONTAMINATION in NSAID TOXICITY
we should start with ___ INDUCTION or ___ ___ if appropriate (quickly enough)
what 2 other things should we start with?
if an animal has ingested a LIFE-THREATENING OVERDOSE, consider WHAT intervention? why?
we should start with EMESIS INDUCTION or GASTRIC LAVAGE if appropriate (quickly enough)
2 other things?
1. ACTIVATED CHARCOAL to ABSORB WHATEVER IS STILL IN GI TRACT
2. IV LIPID EMULSION = NSAIDs are often LIPID-SOLUBLE, so we can EMULSIFY/BREAK IT DOWN
if LIFE-THREATENING OVERDOSE, consider EXTRACORPOREAL BLOOD PURIFICATION via HEMOPERFUSION or THERAPEUTIC PLASMA EXCHANGE
–> THROWING OUT NSAID & replacing with DONOR PLASMA
NSAID toxicity…
we should monitor WHAT 2 kinds of organ values?
4 other options for MEDICAL TREATMENT? 2 are +/-
MONITOR HEPATIC & RENAL VALUES
MEDICAL tx?
1. GASTROPROTECTANTS
–> MISOPROSTOL (PGE analog)
–> ANTACIDS like FAMOTIDINE
–> SUCRALFATE to BIND & PROTECT ulcers
- IV FLUIDS to MAINTAIN EUHYDRATION & RENAL PERFUSION, but caution with OVERHYDRATION
- +/- HEPATOPROTECTANTS
- +/- DIURETICS if OLIGURIA develops
ETHYLENE GLYCOL…
what is the MOST COMMON kind of EXPOSURE?
this substance is ALSO found in what other 4 things?
METABOLISM of ETHYLENE GLYCOL occurs PRIMARILY in the ___ within ___-____ ____ of INGESTION
pathophysiology (4)
the LETHAL DOSE is..
MOST COMMON EXPOSURE = ANTIFREEZE
this substance is ALSO FOUND IN…
1. SOLVENTS
2. DEICERS
3. STAINS
4. PHOTOGRAPHY DEVELOPING SOLUTIONS
METABOLISM of ETHYLENE GLYCOL occurs PRIMARILY in the LIVER within 2-4 HOURS of INGESTION
pathophysiology?
1. ETHYLENE GLYCOL gets converted to GLYCOALDEHYDE by ALCOHOL DEHYDROGENASE
- eventually, forms OXALIC ACID
- OXALIC ACID will COMPLEX WITH CALCIUM to form CALCIUM OXALATE STONES
- CALCIUM OXALATE STONES will cause TUBULAR OBSTRUCTION & NEPHROTOXICITY
the LETHAL DOSE is NOT MUCH
CLINICAL STAGES of ETHYLENE GLYCOL POISONING (3)
give TIMING post-ingestion, clinical signs
which stage DOES NOT ALWAYS OCCUR?
- STAGE 1 = 30 MINS to 12 HOURS POST-INGESTION
–> V+
–> PU/PD
–> CNS depression
–> ataxia - +/- STAGE 2 = 12 to 24 HOURS POST-INGESTION
–> CNS signs MIGHT IMPROVE SLIGHTLY
–> “FALSE RECOVERY” but even though this doesn’t always happen, MORE COMMON IN DOGS - STAGE 3 = 12 to 36 HOURS POST-INGESTION
–> OLIGURIC to ANURIC AKI
–> severe DEPRESSION
–> SWOLLEN & PAINFUL KIDNEYS
–> ANOREXIA
–> SEIZURES
–> COMA/DEATH
what are the BEST 3 DIAGNOSTIC PARAMETERS we can use for ETHYLENE GLYCOL POISONING?
& include WHY we see them
- HIGH ANION GAP METABOLIC ACIDOSIS = from GLYCOLIC ACID, GLYOXYLIC ACID & OXALIC ACID
–> noticed at 3 HOURS, PEAKS at 6 HOURS, can stay UP TO 48 HOURS - ISOSTHENURIA, HYPOCALCEMIA & CALCIUM OXALATE CRYSTALLURIA within 3 HOURS post-ingestion
- AZOTEMIA around 12-24 HOURS POST-INGESTION
in ETHYLENE GLYCOL POISONING, when does HIGH ANION GAP METABOLIC ACIDOSIS…
BECOME noticeable?
PEAK?
how LONG can it stay increased?
NOTICED WITHIN 3 HOURS post-ingestion
PEAKS at 6 HOURS post-ingestion
can REMAIN INCREASED for 48 HOURS
can we use ACTIVATED CHARCOAL for ETHYLENE GLYCOL?
NO!
3 TREATMENTS for ETHYLENE GLYCOL POISONING?
include WHEN they’re effective, what they can do
- FOMEPIZOLE = EFFECTIVE if given WITHIN FIRST 8 HOURS
–> INHIBITS ALCOHOL DEHYDROGENASE from converting ETHYLENE GLYCOL into GLYCOALDEHYDE - ETHANOL (GRAIN ALCOHOL) = EFFECTIVE if given WITHIN FIRST 8 HOURS
–> has HIGHER AFFINITY FOR ALCOHOL DEHYDROGENASE than ETHYLENE GLYCOL
–> EASILY AVAILABLE - HEMODIALYSIS = usually WITHIN HOURS OF EXPOSURE
–> helps REMOVE EG & METABOLITES to try and PREVENT AKI
why might giving FOMEPIZOLE for ETHYLENE GLYCOL POISONING in a CAT be CONTRAINDICATED? (2)
- CATS NEED A MUCH HIGHER DOSE > DOGS
- EXPENSIVE MEDICATION
GRAPES & RAISINS TOXICITY…
what is the PROPOSED method of action of toxicity?
dose-response relationship?
method of action? = TARTARIC ACID causes ACUTE PROXIMAL TUBULAR NECROSIS, CASTS & TUBULAR OBSTRUCTION
NO DEFINITIVE DOSE-RESPONSE RELATIONSHIP
if an animal RECOVERS from an AKI, WHAT is likely to REGENERATE?
EPITHELIAL CELLS LIKELY TO REGENERATE IF THEY’VE NECROSED
4 steps for TREATMENT of GRAPES & RAISINS?
one is +/-
- EARLY DECONTAMINATION via EMESIS +/- ACTIVATED CHARCOAL (if 8-12 hours post)
- IV FLUID THERAPY for MINIMUM of 48 HOURS
- SERIALLY MONITOR SERUM CHEM VALUES & URINE OUTPUT for 48 HOURS
- +/- DIURETIC if OLIGURIA DEVELOPS, may also need DIALYSIS
LILY TOXICITY…
ALL ___ of ____ genera and ____ genera are considered ____ to ____
EVERY ___ of the ____ are ____, even the ____
what do we see on HISTOPATH?
ALL SPECIES of LILIUM genera and HEMEROCALIS genera are considered NEPHROTOXIC to CATS
EVERY PART of the LILY are TOXIC, even the POLLEN
on HISTOPATH = WIDESPREAD DEGENERATION & NECROSIS of PROXIMAL TUBULE EPITHELIAL CELLS
LILY TOXICITY…
WHEN do clinical signs usually occur?
2 EARLY clinical signs?
what 3 DANGEROUS clinical signs can occur & when?
clinical signs usually seen WITHIN 6-12 HOURS AFTER EXPOSURE
2 EARLY clinical signs?
1. V+
2. LETHARGY
3 DANGEROUS clinical signs?
1. AKI usually within 24-48 HOURS, usually first POLYURIC than OLIGURIC/ANURIC
- SEIZURES
- DEATH can occur 3-7 DAYS POST-INGESTION
4 steps for TREATMENT in LILY TOXICITY?
one is +/-
OVERALL, if the patient is NOT ___/there’s NO SIGNS OF ____ by ___-___ ____, they’ll….
- EARLY DECONTAMINATION via EMESIS +/- ACTIVATED CHARCOAL; BATHE if exposed to POLLEN
- IV FLUID THERAPY for MINIMUM 48 HOURS
- SERIALLY MONITOR SERUM CHEM VALUES (baseline, 24 & 48 hours) and URINE OUTPUT
- +/- DIURETIC if OLIGURIA develops, may need DIALYSIS
OVERALL, if the patient is NOT AZOTEMIC/there’s NO SIGNS OF AKI by 24-48 HOURS, they’ll LIKELY BE OK
what is the MOST IMPORTANT intervention we can do to PREVENT AKI from LILY TOXICITY in CATS?
EARLY DECONTAMINATION (EMESIS +/- ACTIVATED CHARCOAL) & SUPPORTIVE CARE
RED MAPLE LEAF TOXICITY…
aka?
toxicity is reported in what 3 SPECIES?
most commonly occurs WHEN? why?
aka = ACER RUBRUM
3 species?
1. HORSES
2. ALPACAS
3. ZEBRAS
most commonly occurs in FALL when LEAVES FALL or LESS FOOD AVAILABLE
RED MAPLE LEAF TOXICITY…
pathophysiology? (4)
what 4 other CLINICAL SIGNS can be seen?
pathophysiology?
1. LEAVES are METABOLIZED by INTESTINAL BACTERIA & produce TANNINS
- TANNINS broken down into GALLIC ACID & PYROGALLOL
- these products then cause OXIDATIVE INJURY to RBCs & Hb, causing INTRA/EXTRAVASCULAR HEMOLYSIS & METHEMOGLOBINEMIA
- can lead to RENAL HYPOXIA and AKI
what 4 other signs?
1. FEVER
2. GENERALIZED ICTERUS
3. COLIC
4. LAMINITIS
