SAM midterm Flashcards
Hypoglycemia
Endocrine vs Exocrine pancreas
Endocrine: islets of langerhans secrete glucagon & insulin to regulate/maintain BG levels
Exocrine: acinar & ductal cells secrete digestive enzymes & bicarb to aid w/ digestion of CHOs, fats, proteins
Hypoglycemia
What 3 things does insulin initiate?
Insulin is present in high levels in a “fed state”:
- Glucose storage (glycogen/glycogenesis in liver + skeletal mm.)
- Protein storage (AAs/proteogenesis in skeletal mm.)
- Lipid storage (FFAs, glycerol/lipogenesis in adipose tissue)
promotes glucose uptake into cells -> “BG-lowering”
Hypoglycemia
Which hormone does insulin prohibit?
In a “fed state”, insulin PROHIBITS glucagon
Hypoglycemia
What does glucagon do?
Glucagon is present in a FASTED state:
- glycogenolysis (release from liver & skeletal mm.) + gluconeogenesis (liver)
- lipolysis (adipose tissue)
Promotes release of glucose out of cells = “BG-elevating”
Hypoglycemia
Role of liver in carbohydrate physiology
Hepatocytes (60% liver mass) possess metabolic activity:
- glucose storage (glycogenesis) and release (glycogenolysis + gluconeogenesis)
injury to hepatocytes can cause hypoBG
Hypoglycemia
How much hepatic mass needed intact to maintain euglycemia?
> 30%
Hepatocytes make up 60% of mass
Hypoglycemia
Which hormones stimulate gluconeogenesis?
Glucagon & cortisol (in liver)
Hypoglycemia
Hypoglycemia
BG < 60mg/dL
Hypoglycemia
Which hormones (4) are released in response to hypoglycemia/why?
1. Glucagon
2. Cortisol
3. Epinephrine
4. Growth Hormone
WHY: glycogenolysis + gluconeogenesis; insulin antagonism/inhibit glucose uptake in peripheral tissues
Hypoglycemia
Causes of hypoglycemia (8)
1. Liver failure (hepatocytes)
2. Insulinoma
3. Iatrogenic insulin excess (diabetes medication)
4. Hypoadrenocorticism (cortisol critical for gluconeogenesis + insulin antagonism)
5. Sepsis (incr. glucose consumption + impaired gluconeogenesis)
6. Juveniles; hunting dogs; toy breeds
7. Xylitol toxicity
8. Spurious (red top sits out too long)
Liver failure usually acute hepatic injury; high xylitol dose -> acute liver injury, low xylitol dose -> hypoglycemia
Hypoglycemia
Work-up for the newly dx hypoglycemic patient
- AUS (adrenals, pancreas, liver; r/o other diseases)
- Bile acids
- Basal cortisol
- Paired BG/insulin
Hypoglycemia
How to treat a stable, hypoglycemic toy breed/neonatal patient
Diet: small, multiple meals high in fat, protein, and complex carbs
Hypoglycemia
How to treat stable insulinoma dog
- Dietary (same as toy breeds)
- Glucocorticoids (pred)
- Diazoxide
- Sx
Diazoxide blocks insulin release by pancreas
Hypoglycemia
Acute hypoglycemic crisis treatment:
50% dextrose IV diluted 1:4 @ 1ml/kg dose
Hypoglycemia
Prognosis of insulinoma
- Short-term: good (sx 1-2yr, medical 6mo)
- Long-term: guarded-poor, almost 100% mets
Tick-Transmitted Disease
Differentials for petechiae (3)
- Thrombocytopenia
- Vasculitis
- Thrombocytopathia
Thrombocytopenia: SPUD
S: Sequestration
P: decreased Production
U: Utilization/consumption
D: immune-mediated Destruction
Tick-Transmitted Disease
Morula in monocyte vs. neutrophil
MONOCYTE = Canine Monocytic Ehrliciosis (E. canis)
- Ehrlichia canis - target cell = monocytes
NEUTROPHIL = Canine Granulocytic Anaplasmosis (A. phagocytophilum) / Ehrlichiosis (E. ewingii)
- Morulae CANNOT be distinguished b/w the two!
- granulocytes = neuts, eosins, basos
Blood smear dx sensitivity decreases w/ chronicity
Rickettsial diseases: Ehrlichia cani/ewingii/chafeensis & Rickettsia rickettsii; purebred dogs like German Shepherds more susceptible
Tick-Transmitted Disease
Canine monocytic ehrliciosis is transmitted by which tick?
E. canis = Brown dog tick
- Rhipicephalus sanguineus
Tick-Transmitted Disease
Clinical features of Acute vs. Chronic phases of E. canis infection
Acute (8-20d post inoculation): fever, lethargy, inapp., thrombocytopenia + thrombycytopathia (petechiae)
Chronic: acute plus bone marrow hypoplasia (pancytopenia), marked lymphocytosis, and bone marrow plasmacytosis–>hyperglobulinemia
3rd poss. stage = subclinical
Tick-Transmitted Disease
What is the gold standard for diagnosing E. canis?
Indirect Immunofluorescent Antibody (IFA) test
relies on IgG antibodies
Tick-Transmitted Disease
E. canis: Whole blood PCR is more sensitive for __?__ infections, while serology is more sensitive for __?__ infections.
E. canis: Whole blood PCR is more sensitive for __ACUTE__ infections, while serology is more sensitive for __CHRONIC__ infections.
- PCR can detect DNA as early as 4-10d post inoculation
Serology: Ab testing, IFA, ELISA (snap 4Dx)
Tick-Transmitted Disease
Common clinical findings of E. ewingii and A. phagocytophillum
- Fever & lymphadenomegaly
- Lameness/joint effusion from non-erosive polyarthritis
Tick-Transmitted Disease
Canine granulocytic ehrliciosis is transmitted by which tick?
E. ewingii = Lone Star tick
Amblyomma americanum
Tick-Transmitted Disease
How do clinical features of E. ewingii differ from E. canis?
E. ewingii presents with milder clinical disease/only causes acute disease; clinical signs develop later / 3-4 weeks post inoculation
Tick-Transmitted Disease
Canine granulocytic anaplasmosis is primarily transmitted by which tick on east coast?
A. phagocytophillum = Deer tick/black-legged tick
Ixodes scapularis
Tick-Transmitted Disease
How does A. phagocytophillum clinically appear in most dogs?
No signs; potential ones are non-specific & include polyarthritis
Tick-Transmitted Disease
Rickettsia rickettsii targets what cells? What tick transmitts it?
- Target cell = endothelial cells of smaller a/v–> vasculitis
- RMSF = Dermacentor ticks
Tick-Transmitted Disease
Pathophys of RMSF
R. rickettsii replicates in endothelial cells -> vasculitis -> PLT/coag system activated + thrombytopenia (destruction) -> DIC or thrombosis occur
Tick-Transmitted Disease
Which organs are most adversely affected by RMSF?
skin, brain, heart, kidneys
Tick-Transmitted Disease
Incubation period + clinical findings of RMSF
- 2-14 days
- joint stiffness/pain (arthralgia) + spinal hyperesthesia
- thrombocytopenia
- cutaneous edema + hyperemia
- Neuro signs (meningitis -> encephalomyelitis)
Tick-Transmitted Disease
How is RMSF primarily diagnosed?
Serologic testing (IFA)
Tick-Transmitted Disease
American Canine Hepatozoonosis
- Protozoal name
- how is it spread
- common clinpath findings (3)
- Protozoa: Hepatozooan americanum
- spread via ingestion of Amblyomma maculatum (Gulf Coast tick)
- Leukocytosis (20,000-200,000 cell/uL), increased ALKP, hypoglycemia
Tick-Transmitted Disease
American Canine Hepatozoonosis
- clinical findings
- diagnosis
- treatment
Clinical findings:
- often a CHRONIC infection!!
- severe muscle wasting, generalized hyperesthesia, stiff gait, purulent ocular d/c
- signs wax/wane in severity
- xrays: periosteal bone proliferation (proximal aspect of limbs)
Diagnosis:
- skeletal muscle biopsy
Treatment:
- TCP combo therapy for 2 weeks (TMS + clindamycin + pyrimethamine), followed by 2 years of decoquinate (anticoccidial drug)
- Does NOT respond to doxycycline!
Tick-Transmitted Disease
What protozoa is primarily transmitted by the brown dog tick (Rhipicephalus sanguineus) in the U.S.?
Babesia canis
- strain in U.S. = Babesia canis vogeli
- Large, piriform-shaped protoza living within RBCs
Tick-Transmitted Disease
Clinical features of Canine Babesiosis
- US = uncomplicated (non-specific signs, thrombyctopenia, hemolytic anemia)
- South Africa = complicated (same + acute RF, cerebral signs, hepatic injurt, ARDS, pancreaittis, red biliary syndrome)
Tick-Transmitted Disease
Which dog breeds have high prevalence of sublinical canine babesiosis infection?
- Greyhounds (B. canis vogeli)
- American pit bull terriers (B. gibsoni)
Hypertension
BP = ?
CO x SVR
- CO = HR x SV
- BP regulated by RAAS and SNS
SV = end diastolic volume - end systolic volume
Hypertension
Explain RAAS system in relation to hypotension
The kidneys detect hypotensive state -> renin released -> renin facilitates angiotensin I conversion in the liver -> ACE converts angiontensin I into II in the lungs -> angiotensin II stimulates adrenals to release aldosterone -> vasoconstriction -> increased SVR
Hypertension
Systemic hypertension
Persistent elevation of systemic BP
- Systolic > 160mmHg
- Diastolic > 120mmHg
Hypertension
What is the most common cause of systemic hypertension in dogs/cats?
Secondary (to a condition that increases CO or SVR)
Hypertension
BP cuff width should be ____?____ % of the circumference of the chosen site (limb or tail).
30-40%
Hypertension
Possible areas of TOD
eyes, kidneys, brain, heart & vasculature
Minimal risk: normotensive < 140
Low risk: prehypertensive 140-159
Moderate risk: hypertensive 160-179
High risk: severe ≥ 180
Hypertension
Top causes of hypertension in cats
CKD; hyperthyroidism
Hypertension
Top causes of hypertension in dogs
Kidney disease (acute & chronic), Cushing’s, DM
Hypertension
When should hypertension be treated?
- Severe hypertension (≥ 180mmHg)
- Evidence of TOD w/ moderate (160-179mmHg) or severe
If mod-severe with no evidence of TOD, recheck in 1-2 weeks
Hypertension
First line of tx in cats for hypertension
Amlodipine
- calcium channel blocker (relax vascular smooth muscle -> vasodilation -> decreased SVR)
used in dogs with severe hypertension
Hypertension
First line of tx in dogs for hypertension
ACE-I like enalapril or benazepril
- can be used to also treat associated proteinuria, but can reduce GFR/cause azotemia in some patients
- avoid in dehydrated patients
Are INEFFECTIVE in cats!
Hypertension
When is telmisartan used? What drug class is it?
- Moderate hypertension in cats (< 200 mmHg)
- Alternative tx for reducing proteinuria compared to ACE-I
- Is an angiotensin II receptor blocker
Hypertension
How are pheochromocytomas treated?
With alpha adrenergic antagonists (prazosin, phenooxybenzamine)
tumor of adrenal glands that results in excess catecholamines release
Hypertension
Goals of treatment for hypertension
- Avoid or correct TOD
- Reach systolic BP b/w 110-140 mmHg
start meds on low end to avoid hypotension
Hypertension
When is spironolactone used to treat hypertension?
Useful w/ hyperaldosteronism
- diuretic that acts as an aldosterone antagonist
Hypertension
When to do BP rechecks for hypertension (relative to TOD presence or not)
- Yes TOD = 3 days
- No TOD = 7-10 days
- Once stable, q3 months
Feline HT4
Describe the thyroid pathway
TRh from hypothalmus signals TSH release from pituitary, which signals T4 (and T3) release from thyroid.
Feline HT4
Clinical signs and cause of feline hyperthyroidism
- weight loss despite normal appetitie
- thyroid adenoma
dogs: lymphocytic thyroiditis
HT4 = most common endocrinopathy of cats
Feline HT4
Goals of hyperthyroid therapy in cats
Achieve euthyroidism (T4 = 1.5-3.0 ug/dL)
RR 0.8-4.0 ug/dL
Feline HT4
How to treat HT4 cat with CKD and/or hypertension
Prioritize treating HT4
- CKD: once T4 stabilized, true renal values appear
- Hypertension: T4 stabilization usually resolves high BP
Feline HT4
Treatment options (4) and which are used for management vs. curative
- Methimazole - mgmt.
- Diet (low iodine, Hill’s y/d) - mgmt.
- Sx thyroidectomy - curative
- Radioiodine therapy - curative
both curatives can relapse
Feline HT4
Benefits of Methimazole (3)
- Cheap, effective, reversible
- Oral or transdermal application
- Long-term administration effective
if GI signs develop from PO, can switch to TD
Feline HT4
What is the typical starting dose for methimazole? Dosage options?
- Starting dose = 5mg/day
- Dosages: 2.5mg BID; 5.0mg SID
SID may take longer to control HT4 (up to 8 weeks)
If CKD, start at lower doses & titrate to aid with preventing decompensation of cats presenting with azotemia at time of HT4 diagnosis.
- creatinine/azotemia often rise during methimazole therapy since true GFR revealed.
Feline HT4
Describe potential consequences of treating HT4 w/ Methimazole long-term in cats (3).
- Tumor progresses –> increase dosage
- thyroid hyperplasia (large goiter) –> difficult to manage
- Adenoma transforms into carcinoma –> resistant to antithyroidal drugs
Feline HT4
Describe methimazole monitoring once therapy is initiated.
Re-check CBC/Chem/T4 and BP in 4 weeks
- want to evaluate for hepatotoxicity, blood dyscrasias, azotemia, T4 progress
Blood dyscrasias: include thrombocytopenia, neutropenia, anemia
Feline HT4
The presence of which methimazole side effects should make you stop therapy?
- blood dyscrasias
- hepatotoxicity
- facial pruritus
Feline HT4
Pros/cons of low-iodine diet for HT4 cats
- Good option for cats who don’t tolerate methimazole and can’t undergo radioiodine therapy due to concurrent diseases
- Bad option for cats where difficult to control diet (these cats must be exclusively eating y/d)
Feline HT4
Pros and cons of radioiodine therapy
Pros
- 95% efficacy w/ one treatment
- treatment of choice (destroys abnormal thyroid tissue)
Cons
- requires isolation b/c radioactive ( cats w/ severe, life-threatening diseases not good candidates)
- can cause permanent iatrogenic hypothyroidism (and cat will need to be pilled)
Lower doses of I131 work best
Feline HT4
When would surgical thyroidectomy be a good treatment option for cat w/ HT4?
- less common due to increasing availability of radioiodine therapy, but good for cats with carcinoma progression
- risks of hypothyroidism, hypoparathyroidism, recurrence even w/ bilat. thyroidectomy
Feline HT4
How to diagnose and treat iatrogenic hypothyroidism
Common post HT4 treatment
Diagnosis
- Overt: LT4, HTSH
- Subclinical: L-normalT4, HTSH
Treatment
- treat when persistent signs + new/worsening azotemia
- Rx = Levothyroxine
benefits of tx: increase GFR -> increase survival
Testing Thyroid Function
Free T4 vs. TT4
Thyroxine (T4) - 80% of thyroid hormone produced by thyroid gland.
- 99.9% of circulating T4 = protein-bound
- 0.01% of circulating T4 = free/unbound (free T4) = active form that can enter cells
Free T4 = fT4
- highly sensitive & specific
Total T4 =TT4 measures protein-bound + free T4
- very sensitive (90%) but not specific (prone to false positives)
TT4 inaccurate as stand-alone marker for evaluating thyroid function
Testing Thyroid Function
Euthyroid Sick Syndrome
suppression of TT4 +/- fT4 in response to clinical illness (e.g., megaE/asp. pneumonia)
Testing Thyroid Function
Does presence of thyroid slip indicate hyperthyroid?
NO- have to correlate slip with clinical signs.
if the mass will cause HT4, clinical signs arise within 14 months
Testing Thyroid Function
Cats and non-thyroidal illness
Often, cats with a non-thyroidal illness will have increased TT4
if high-normal TT4, can be early HT4 or NTI
Testing Thyroid Function
Clinical signs of hypothyroidism
- decreased activity; exercise intolerance
- truncal alopecia/hair easily epilated
- mild obesity
Testing Thyroid Function
Which drugs can increase TT4/fT4?
phenobarb, clomipramine (TCA), sulfonamides, glucocorticoids, NSAIDs
Testing Thyroid Function
50% of hypothyroid cases in dogs are caused by what?
Autoimmune thyroiditis
- autoantibodies to T4 or T3
- can falsely elevate values even if truely LT4
- fT4 measured by equilibrium dialysis in unaffected
all other assays for TT4 or fT4 are inaccurate w/ autoantibodies
Testing Thyroid Function
How often is levothyroxine dosed?
0.022mg/kg once per day
- 4hr post administration should result in high-normal T4
Testing Thyroid Function
70% of LT4 dogs have this finding on serum chemistries
hypocholesterolemia
Testing Thyroid Function
Low++ TT4, low-normal fT4, high++ TSH
Most likely hypothyroid
- pituitary releasing TSH to thyroid gland but thyroid not responding
Testing Thyroid Function
90% of HT4 cats have this enzyme elevation
liver
ALKP (inducible)
Testing Thyroid Function
Cat with high-normal TT4, increased fT4, detectable TSH
possibly HT4, but assess for non-thyroidal illness
e.g., CKD, DM, neoplasia, heart disease, IBD, hepatic disease
Fluid Therapy
Maintenance fluid rate
Maintenance = 30-60 ml/kg/day
large breed -> small breed
Fluid Therapy
How to calculate hydration deficit
BWkg * dehydration decimal = hydration deficit in LITERS
rehydration corrected over 12-24h, faster azotemic, slower heart dz
Approach to Anemic Pt
Causes of Loss
Hemorrhage
- Induced - trauma v. parasites
- Spontaneous - thrombocytopenia (SPUD) v. coagulopathy v. DIC
- See decreased plasma protein!
Acute: trauma, coag., cancer. Chronic: parasites, ulcers, cancer
Approach to Anemic Pt
Causes of Destruction
Hemolysis
Infectious (mycoplasma spp.) v. immune-mediated (IMHA) v. drugs v. DIC (fragmentation)
- See icterus/hyperbilirubinemia! (bilirubin = by-product of Hg breakdown)
Also: oxidative (zine, acetaminophen), fragmentation (iron deficiency)
Intravascular hemolysis: direct lysis from shear stress, toxin, complement autoantibody in the blood vessels
Extravascular hemolysis: macophages destroy damaged/abnormal RBCs in the spleen, liver, bone marrow
Heinz bodies -> oxidative HA
Spherocytes -> IMHA
Hemoparasites -> infectious HA
Approach to Anemic Pt
Causes of Hypoplasia
Decreased production
- Refractory - anemia of chronic disease v. renal failure
- Bone marrow - aplastic anemia v. pancytopenia v. drugs
- Bone marrow - immune-mediated v. neoplasia v. idiopathic
Approach to Anemic Pt
Common PE findings for anemia
pale gums, tachycardic, bounding or weak pulses, dullness/collaspe, icterus, petechiae, effusion
Approach to Anemic Pt
Leukogram pattern for IMHA
profound inflammatory leukogram
Approach to Anemic Pt
1º vs. 2º IMHA
1º - idiopathic
2º - drugs, neoplasms, infection
Rule out 2º via infectious disease testing and imaging (neoplasia)
2º to infection: Babesia (dog), FeLV or Mycoplasma (cat)
Approach to Anemic Pt
IMHA treatment
Prednisone(-olone), Clopidogrel
want to prevent thrombotic complications
Approach to Anemic Pt
Anticoagulant rodenticide toxicity causes what type of anemia? How is it treated?
- Loss
- Anticoag. rodenticide interferes with vitamin K metabolism
- Clotting factors 2, 7, 9, and 10 require Vitamin K to be functional (present in all 3 arms of cascade)
- Tx –> fresh frozen plasma OR fresh whole blood
Need to replace functional clotting factors
Dx: increased PT/PTT
- Fresh frozen plasma = clotting factors, plasma proteins (albumin, immunoglob, fibrinogen)
- Whole blood contains = RBCs, WBCs, PLTs, plasma
Approach to Anemic Pt
Iron deficiency anemia
- characterize type
- common cause
- PE and clinpath findings
- CHRONIC, external blood loss
- Gastrointestinal (parasitism, ulceration, neoplasia)
- Animal has learned to compensate for anemia
- Non-regenerative; microcytic, hypochromic
RBC loss continues -> bone marrow regen weak to absent
Approach to Anemic Pt
Which anemias are regenerative v. non-regenerative?
Regenerative: blood loss, destruction
Non-regenerative: hypoplasia
If you suspect loss or destruction, but non-regen, may be pre-regenerative or long-term chronicity.
1º bone marrow disease: primary failure of erythropoiesis (pure RBC aplasia). Can be immune-mediated (idiopathic), drugs (chemo, methimazole, pheno, sulfonamides, chloramphen, estrogen)
Approach to Bleeding Pt
Ddx for increased PT/PTT
- VitK absence or antagonism
- DIC
- Hepatic failure
liver makes coag factors
Approach to Bleeding Pt
Common findings with IMTP and what to transfuse
- Non-regen. anemia, severe thrombocytopenia (PLT 0-20,000/uL)
- Splenomegaly
- Treat with either fresh whole blood or packed RBCs. Usually the latter due to immediate destruction of PLTs in the whole blood.
Most common cause = immune-mediated
initial therapy includes immunosuppressants
Approach to Bleeding Pt
Clinical evidence of failure of 1º vs 2º hemostasis
1º = PLTs
- Mucosal surface bleeding, multi-focal (epistaxis, petechiae, hematuria, melena or hematochezia)
2º = clotting factors
- Body cavity bleeding, localized (hemothorax/abd; hemarthrosis)
Approach to Bleeding Pt
Why is total protein WNL with acute HGE?
The vasculature has not yet responded quickly enough to fluid loss from v+/d+
Immunosuppressive Therapy
Glucocorticoids
- MoA
- Side effects
- Contraindications
- First-line therapy
- Prednis(ol)one, dexamethasone
- MoA: inhibits before arachidonic acid (gets inflammatory mediators and prostaglandins)
- Side effects: PU/PD, panting, polyphagia, muscle atrophy/weakeness, vaculoar hepatopathy, GI ulceration, can facilitate DM development in cats, steroid hepatopathy
- Contraindications: DM, infections, Cushing’s, NSAIDs
- MUST BE TAPERED OFF! (decrease dose by 25% of original dose every 2-4 weeks once 1-2 weeks beyond resolution)
Immunosuppressive Therapy
Azathioprine
- MoA
- Side effects
- Contraindications
- Second line therapy
- MoA: inhibits purine synthesis//lymphocyte proliferation
- Side effects: cytopenias, hepatotoxicity, chronic subclinical anemia
- Contraindications: CATS (myelosuppression), already on glucocorticoid
Immunosuppressive Therapy
Cyclosporine
- MoA
- Side effects
- Contraindications
- Second line therapy
- MoA: Impairs T-cell function//lymphocytes
- Side effects: Primarily GI
- Contraindications: long list of drug interactions
Atopica®
Immunosuppressive Therapy
Chlorambucil
- MoA
- Side effects
- Second line drug in cats; chronic PLE in dogs
- MoA: Antineoplastic (lymphoma!)
- Side effects: GI, myelosuppression, neuro signs, alopecia
Immunosuppressive Therapy
Leflunomide
- MoA
- Side effects
- Contraindications
- Add-on (w/ pred) or stand-alone
- MoA: reduces lymphocyte proliferation
- Side effects: well-tolerated; GI, myelosupp.
- Contraindications: liver disease, pregnant/nursing, kidney disease
Immunosuppressive Therapy
Mycophenolate mofetil
- MoA
- Side effects
- Contraindications
- Lone agent in “stable” disease, or combo w/ pred
- MoA: Reduces lymphocyte proliferation
- Side effects: GI
- Contraindications: current infections, liver or kidney disease
Immunosuppressive Therapy
What is human intravenous immunoglobulin (IVIG) used for?
Adjuncrtive treatment
- Rapidly stops RBC destruction
- Used for short-term stabilization of IMHA or IMTP patients
Immunosuppressive Therapy
What is vincristine used for?
Adjunctive tx for ITP
- increases megakarycytopoiesis (PLT precursor)
- increases thrombopoiesis
- reduces PLT destruction
Immunosuppressive Therapy
Anti-PLT vs. anti-coagulent therapy
Anti-PLT: clopidogrel (1-3 mg/kg/day)
Anti-coagulent: heparin
Immunosuppressive Therapy
Treatment plan for dog w/ IMTP
- Primary tx. = prednisone or dexamethasone
- Adjunctive (to improve PLT recovery time) = vincristine or IVIG
- Add on second-line drug if inappropriate response to therapy
Overall tx likely 3-6 months (includes taper)
Melena = poor prognostic indicator b/c suggests significant upper gastrointestinal bleeding
Icterus
Describe bilirubin physiology
When RBC dies, its hemoglobin is also broken down. Produces waste product = indirect bilirubin. Converted into direct bilirubin in the liver prior to excretion in the gallbladder (and stored as bile). Later used to aid with digestion of fatty foods in duodenum.
Icterus
3 categories of hyperbilirubinemia
Pre-hepatic (hemolysis)
Hepatic (liver failure)
Post-hepatic (biliary obstruction)
Icterus
Examples of pre-hepatic hyperbilirubinema (3)
AKA Hemolysis
- IMHA
- Toxic (zinc, onions, garlic)
- Post-transfusion (alloautoantibodies)
Icterus
Examples of hepatic hyperbilirubinema (5)
AKA liver failure
- Toxin (xylitol, blue-green algae, sago palm)
- Hepatitis (viral)
- End-stage PSS
- Microvascular dysplasia
- Hepatic lipidosis
Icterus
Examples of post-hepatic hyperbilirubinema (4)
AKA biliary obstruction
- Gall bladder mucocele
- Pancreatitis
- Cholelithiasis
- Tumors
Icterus
Clinpath findings with hepatobiliary diease
1. Elevated liver enzymes
- Hepatocellular: ALT > ALKP
- Cholestatic: ALKP > ALT
2. Decreased Alb, Chol, Gluc, BUN
Pancreatitis
What is pancreatitis
Inappropriate or early activation of the digestive enzymes released by exocrine pancreas –> INFLAMMATION due to “auto-digestion” of pancreas
Presence of AAs & fat in duodenum stimulate acinar cells of exocrine pancreas
Pancreatitis
Clinical signs of pancreatitis
- Dogs: vomiting, painful abdomen
- Cats: lethargy, anorexia
Pancreatitis
Clinpath findings that help support pancreatitis dx
- Elevated hepatic enzymes
- Inflammation
- Hyperbilirubinemia (esp. cats)
Pancreatitis
Serological test to aid in dx pancreatitis
Pancreatic Lipase Immunoreactivity snap test
Pancreatic Lipase Immunoreactivity (PLI)
Source: Pancreas
Clearance: Kidneys
Measures: Pancreatic lipase (specific for lipase originating from the pancreas)
Available for both dogs (Spec cPL) & cats (Spec fPL)
Increased fPLI—Diagnostic utility in cats: improved sensitivity and specificity over TLI in cases of pancreatitis. (NOTE: chronic pancreatitis and mild pancreatitis may still be missed!!)
Increased cPLI—Diagnostic utility in dogs: Most sensitive and specific test for canine pancreatitis but likely some overlap with other diseases
Decreased PLI—Exocrine pancreatic insufficiency, but lower sensitivity than TLI
Pancreatitis
Why is low-fat diet paramount for treating pancreatitis?
B/c pancreas is responsible for releasing digestive enzymes in response to presence of FAT in the duodenum -> want to MINIMIZE pancreatic enzyme release so it can heal
Increased Liver Enzymes
Hepatocellular vs cholestasis induction enzymes
Hepatocellular: ALT, AST
Cholestatic: ALKP, GGT
Persistent ALT elevation indicates continued hepatocyte injury
Increased Liver Enzymes
Decreases in which values on chemistry indicate impaired liver function?
- Cholesterol
- Albumin
- Glucose
- BUN
All above DECREASE; Bilirubin increases
Protein breakdown -> ammonia produced -> transformed into urea in liver
Increased Liver Enzymes
On chemistry, ALKP (ALP) is the combined measurement of…
3 isoenzymes
1. Liver
2. Corticosteroid (dogs)
3. Bone (young growing dogs)
half life: 70h (D), 6h (C)
Increased Liver Enzymes
Half life of ALT
2.5 days in dogs, shorter in cats
Increased Liver Enzymes
Most common cause of abnormal liver enzymes = ?
2º to non-hepatic disease
PU/PD, hyperthyroid signs, cushing’s signs, GI upset, cough/dyspnea
- A moderate-to-marked increase din ALKP w/out concurrent hyperbilirubinemia is most compatible with drug induction (glucocorticoids) or adrenal function
Increased Liver Enzymes
When should you further investigate elevated liver enzymes?
- Showing clinical signs
- ALT > 2x RI over several months
- Non-hepatic causes have been r/o
Increased Liver Enzymes
What are the 2 breed-associated hepatitis conditions?
1. Idiopathic (Chonic Hepatitis)
- labs, cocker spaniels, dobermans, westies
2. Copper-Associated Hepatitis
- labs, dalmations, dobermans, Westies, skye & bedlington terriers
Increased Liver Enzymes
Obvious indicators of 1º liver disease
- icterus
- ascites
- hepatic encephalopathy
- liver mass
- abnormal bile acids
next steps: imaging, FNA/cytology, biopsy, copper staining or quant.
Increased Liver Enzymes
What does an abnormal bile acids test indicate? When is this test contraindicated?
- indicates decreased bile flow in biliary tract -> accumulated in liver & causing damage (> 25umol/L)
- contraindicated in icteric patients due to cholestasis, or in patients with evidence of cholestasis (hyperbilirubinemia)
bile acids cannot give info on liver function or PSS with cholestasis
