SAM midterm Flashcards
1
Q
Hypoglycemia
Endocrine vs Exocrine pancreas
A
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
2
Q
Hypoglycemia
What 3 things does insulin initiate?
A
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”
3
Q
Hypoglycemia
Which hormone does insulin prohibit?
A
In a “fed state”, insulin PROHIBITS glucagon
4
Q
Hypoglycemia
What does glucagon do?
A
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”
5
Q
Hypoglycemia
Role of liver in carbohydrate physiology
A
Hepatocytes (60% liver mass) possess metabolic activity:
- glucose storage (glycogenesis) and release (glycogenolysis + gluconeogenesis)
injury to hepatocytes can cause hypoBG
6
Q
Hypoglycemia
How much hepatic mass needed intact to maintain euglycemia?
A
> 30%
Hepatocytes make up 60% of mass
7
Q
Hypoglycemia
Which hormones stimulate gluconeogenesis?
A
Glucagon & cortisol (in liver)
8
Q
Hypoglycemia
Hypoglycemia
A
BG < 60mg/dL
9
Q
Hypoglycemia
Which hormones (4) are released in response to hypoglycemia/why?
A
1. Glucagon
2. Cortisol
3. Epinephrine
4. Growth Hormone
WHY: glycogenolysis + gluconeogenesis; insulin antagonism/inhibit glucose uptake in peripheral tissues
10
Q
Hypoglycemia
Causes of hypoglycemia (8)
A
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
11
Q
Hypoglycemia
Work-up for the newly dx hypoglycemic patient
A
- AUS (adrenals, pancreas, liver; r/o other diseases)
- Bile acids
- Basal cortisol
- Paired BG/insulin
12
Q
Hypoglycemia
How to treat a stable, hypoglycemic toy breed/neonatal patient
A
Diet: small, multiple meals high in fat, protein, and complex carbs
13
Q
Hypoglycemia
How to treat stable insulinoma dog
A
- Dietary (same as toy breeds)
- Glucocorticoids (pred)
- Diazoxide
- Sx
Diazoxide blocks insulin release by pancreas
14
Q
Hypoglycemia
Acute hypoglycemic crisis treatment:
A
50% dextrose IV diluted 1:4 @ 1ml/kg dose
15
Q
Hypoglycemia
Prognosis of insulinoma
A
- Short-term: good (sx 1-2yr, medical 6mo)
- Long-term: guarded-poor, almost 100% mets
16
Q
Tick-Transmitted Disease
Differentials for petechiae (3)
A
- Thrombocytopenia
- Vasculitis
- Thrombocytopathia
Thrombocytopenia: SPUD
S: Sequestration
P: decreased Production
U: Utilization/consumption
D: immune-mediated Destruction
17
Q
Tick-Transmitted Disease
Morula in monocyte vs. neutrophil
A
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
18
Q
Tick-Transmitted Disease
Canine monocytic ehrliciosis is transmitted by which tick?
A
E. canis = Brown dog tick
- Rhipicephalus sanguineus
19
Q
Tick-Transmitted Disease
Clinical features of Acute vs. Chronic phases of E. canis infection
A
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
20
Q
Tick-Transmitted Disease
What is the gold standard for diagnosing E. canis?
A
Indirect Immunofluorescent Antibody (IFA) test
relies on IgG antibodies
21
Q
Tick-Transmitted Disease
E. canis: Whole blood PCR is more sensitive for __?__ infections, while serology is more sensitive for __?__ infections.
A
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)
22
Q
Tick-Transmitted Disease
Common clinical findings of E. ewingii and A. phagocytophillum
A
- Fever & lymphadenomegaly
- Lameness/joint effusion from non-erosive polyarthritis
23
Q
Tick-Transmitted Disease
Canine granulocytic ehrliciosis is transmitted by which tick?
A
E. ewingii = Lone Star tick
Amblyomma americanum
24
Q
Tick-Transmitted Disease
How do clinical features of E. ewingii differ from E. canis?
A
E. ewingii presents with milder clinical disease/only causes acute disease; clinical signs develop later / 3-4 weeks post inoculation
25
# **Tick-Transmitted Disease**
Canine granulocytic anaplasmosis is primarily transmitted by which tick on east coast?
A. phagocytophillum = Deer tick/black-legged tick
| *Ixodes scapularis*
26
# **Tick-Transmitted Disease**
How does A. phagocytophillum clinically appear in most dogs?
No signs; potential ones are non-specific & include polyarthritis
27
# **Tick-Transmitted Disease**
*Rickettsia rickettsii* targets what cells? What tick transmitts it?
- Target cell = endothelial cells of smaller a/v--> vasculitis
- RMSF = Dermacentor ticks
28
# **Tick-Transmitted Disease**
Pathophys of RMSF
R. rickettsii replicates in endothelial cells -> vasculitis -> PLT/coag system activated + thrombytopenia (destruction) -> DIC or thrombosis occur
29
# **Tick-Transmitted Disease**
Which organs are most adversely affected by RMSF?
skin, brain, heart, kidneys
30
# **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)
31
# **Tick-Transmitted Disease**
How is RMSF primarily diagnosed?
Serologic testing (IFA)
32
# **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**
33
# **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!
34
# **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
35
# **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)
36
# **Tick-Transmitted Disease**
Which dog breeds have high prevalence of ***sublinical*** canine babesiosis infection?
1. Greyhounds (B. canis vogeli)
2. American pit bull terriers (B. gibsoni)
37
# **Hypertension**
BP = ?
**CO x SVR**
- CO = HR x SV
- BP regulated by RAAS and SNS
| SV = end diastolic volume - end systolic volume
38
# **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***
39
# **Hypertension**
Systemic hypertension
Persistent elevation of systemic BP
- Systolic > 160mmHg
- Diastolic > 120mmHg
40
# **Hypertension**
What is the most common cause of systemic hypertension in dogs/cats?
Secondary (to a condition that increases CO or SVR)
41
# **Hypertension**
BP cuff width should be ____?____ % of the circumference of the chosen site (limb or tail).
30-40%
42
# **Hypertension**
Possible areas of TOD
eyes, kidneys, brain, heart & vasculature
## Footnote
Minimal risk: normotensive < 140
Low risk: prehypertensive 140-159
Moderate risk: hypertensive 160-179
High risk: severe ≥ 180
43
# **Hypertension**
Top causes of hypertension in cats
CKD; hyperthyroidism
44
# **Hypertension**
Top causes of hypertension in dogs
Kidney disease (acute & chronic), Cushing's, DM
45
# **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
46
# **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**
47
# **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!
48
# **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**
49
# **Hypertension**
How are **pheochromocytomas** treated?
With **alpha adrenergic antagonists** (prazosin, phenooxybenzamine)
| tumor of adrenal glands that results in excess catecholamines release
50
# **Hypertension**
Goals of treatment for hypertension
1. Avoid or correct TOD
2. Reach systolic BP b/w 110-140 mmHg
| start meds on low end to avoid hypotension
51
# **Hypertension**
When is **spironolactone** used to treat hypertension?
Useful w/ hyperaldosteronism
- diuretic that acts as an aldosterone antagonist
52
# **Hypertension**
When to do BP rechecks for hypertension (relative to TOD presence or not)
1. Yes TOD = 3 days
2. No TOD = 7-10 days
3. Once stable, q3 months
53
# **Feline HT4**
Describe the thyroid pathway
**TRh** from hypothalmus signals **TSH** release from pituitary, which signals **T4** (and T3) release from thyroid.
54
# **Feline HT4**
Clinical signs and cause of feline hyperthyroidism
- weight loss despite normal appetitie
- thyroid adenoma
| dogs: lymphocytic thyroiditis
## Footnote
HT4 = most common endocrinopathy of cats
55
# **Feline HT4**
Goals of hyperthyroid therapy in cats
Achieve euthyroidism (T4 = **1.5-3.0** ug/dL)
| RR 0.8-4.0 ug/dL
56
# **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
57
# **Feline HT4**
Treatment options (4) and which are used for management vs. curative
1. Methimazole - mgmt.
2. Diet (low iodine, Hill's y/d) - mgmt.
3. Sx thyroidectomy - curative
4. Radioiodine therapy - curative
| both curatives can relapse
58
# **Feline HT4**
Benefits of Methimazole (3)
1. Cheap, effective, reversible
2. Oral or transdermal application
3. Long-term administration effective
| if GI signs develop from PO, can switch to TD
59
# **Feline HT4**
What is the typical starting dose for methimazole? Dosage options?
1. Starting dose = 5mg/day
2. Dosages: 2.5mg BID; 5.0mg SID
| SID may take longer to control HT4 (up to 8 weeks)
## Footnote
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.
60
# **Feline HT4**
Describe potential consequences of treating HT4 w/ Methimazole long-term in cats (3).
1. Tumor progresses --> increase dosage
2. thyroid hyperplasia (large goiter) --> difficult to manage
3. Adenoma transforms into carcinoma --> resistant to antithyroidal drugs
61
# **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
62
# **Feline HT4**
The presence of which methimazole side effects should make you stop therapy?
- blood dyscrasias
- hepatotoxicity
- facial pruritus
63
# **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)
64
# **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
65
# **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
66
# **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
67
# **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
68
# **Testing Thyroid Function**
Euthyroid Sick Syndrome
suppression of TT4 +/- fT4 in response to clinical illness (e.g., megaE/asp. pneumonia)
69
# **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
70
# **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
71
# **Testing Thyroid Function**
Clinical signs of hypothyroidism
- decreased activity; exercise intolerance
- truncal alopecia/hair easily epilated
- mild obesity
72
# **Testing Thyroid Function**
Which drugs can increase TT4/fT4?
phenobarb, clomipramine (TCA), sulfonamides, glucocorticoids, NSAIDs
73
# **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
74
# **Testing Thyroid Function**
How often is levothyroxine dosed?
0.022mg/kg **once** per day
- 4hr post administration should result in high-normal T4
75
# **Testing Thyroid Function**
70% of LT4 dogs have this finding on serum chemistries
hypocholesterolemia
76
# **Testing Thyroid Function**
Low++ TT4, low-normal fT4, high++ TSH
Most likely hypothyroid
- pituitary releasing TSH to thyroid gland but thyroid not responding
77
# **Testing Thyroid Function**
90% of HT4 cats have this enzyme elevation
liver
| ALKP (inducible)
78
# **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
79
# **Fluid Therapy**
Maintenance fluid rate
Maintenance = 30-60 ml/kg/day
| large breed -> small breed
80
# **Fluid Therapy**
How to calculate hydration deficit
BWkg * dehydration decimal = hydration deficit in LITERS
| rehydration corrected over 12-24h, faster azotemic, slower heart dz
81
# **Approach to Anemic Pt**
Causes of **Loss**
| Hemorrhage
1. **Induced** - trauma v. parasites
2. **Spontaneous** - thrombocytopenia (SPUD) v. coagulopathy v. DIC
- See decreased plasma protein!
| Acute: trauma, coag., cancer. Chronic: parasites, ulcers, cancer
82
# **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)
## Footnote
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
83
# **Approach to Anemic Pt**
Causes of **Hypoplasia**
| Decreased production
1. **Refractory** - anemia of chronic disease v. renal failure
2. **Bone marrow** - aplastic anemia v. pancytopenia v. drugs
3. **Bone marrow** - immune-mediated v. neoplasia v. idiopathic
84
# **Approach to Anemic Pt**
Common PE findings for anemia
pale gums, tachycardic, bounding or weak pulses, dullness/collaspe, icterus, petechiae, effusion
85
# **Approach to Anemic Pt**
Leukogram pattern for IMHA
profound inflammatory leukogram
86
# **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)
87
# **Approach to Anemic Pt**
IMHA treatment
Prednisone(-olone), Clopidogrel
| want to prevent thrombotic complications
88
# **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**
## Footnote
Dx: increased PT/PTT
- Fresh frozen plasma = clotting factors, plasma proteins (albumin, immunoglob, fibrinogen)
- Whole blood contains = RBCs, WBCs, PLTs, plasma
89
# **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
90
# **Approach to Anemic Pt**
Which anemias are regenerative v. non-regenerative?
Regenerative: blood loss, destruction
Non-regenerative: hypoplasia
## Footnote
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)
91
# **Approach to Bleeding Pt**
Ddx for increased PT/PTT
1. VitK absence or antagonism
2. DIC
3. Hepatic failure
| liver makes coag factors
92
# **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
## Footnote
initial therapy includes immunosuppressants
93
# **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)
94
# **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+
95
# **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)
96
# **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
97
# **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®
98
# **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
99
# **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
100
# **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
101
# **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
102
# **Immunosuppressive Therapy**
What is vincristine used for?
Adjunctive tx for ITP
- increases megakarycytopoiesis (PLT precursor)
- increases thrombopoiesis
- reduces PLT destruction
103
# **Immunosuppressive Therapy**
Anti-PLT vs. anti-coagulent therapy
**Anti-PLT**: clopidogrel (1-3 mg/kg/day)
**Anti-coagulent**: heparin
104
# **Immunosuppressive Therapy**
Treatment plan for dog w/ IMTP
1. Primary tx. = prednisone or dexamethasone
2. Adjunctive (to improve PLT recovery time) = vincristine or IVIG
3. Add on second-line drug if inappropriate response to therapy
| Overall tx likely 3-6 months (includes taper)
## Footnote
Melena = poor prognostic indicator b/c suggests significant upper gastrointestinal bleeding
105
# **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.
106
# **Icterus**
3 categories of hyperbilirubinemia
Pre-hepatic (hemolysis)
Hepatic (liver failure)
Post-hepatic (biliary obstruction)
107
# **Icterus**
Examples of **pre-hepatic** hyperbilirubinema (3)
| AKA Hemolysis
1. IMHA
2. Toxic (zinc, onions, garlic)
3. Post-transfusion (alloautoantibodies)
108
# **Icterus**
Examples of **hepatic** hyperbilirubinema (5)
| AKA liver failure
1. Toxin (xylitol, blue-green algae, sago palm)
2. Hepatitis (viral)
3. End-stage PSS
4. Microvascular dysplasia
5. Hepatic lipidosis
109
# **Icterus**
Examples of **post-hepatic** hyperbilirubinema (4)
| AKA biliary obstruction
1. Gall bladder mucocele
2. Pancreatitis
3. Cholelithiasis
4. Tumors
110
# **Icterus**
Clinpath findings with hepatobiliary diease
**1. Elevated liver enzymes**
- Hepatocellular: ALT > ALKP
- Cholestatic: ALKP > ALT
**2. Decreased Alb, Chol, Gluc, BUN**
111
# **Pancreatitis**
What is pancreatitis
Inappropriate or early activation of the digestive enzymes released by exocrine pancreas --> INFLAMMATION due to "auto-digestion" of pancreas
## Footnote
Presence of AAs & fat in duodenum stimulate acinar cells of exocrine pancreas
112
# **Pancreatitis**
Clinical signs of pancreatitis
- Dogs: vomiting, painful abdomen
- Cats: lethargy, anorexia
113
# **Pancreatitis**
Clinpath findings that help support pancreatitis dx
- Elevated hepatic enzymes
- Inflammation
- Hyperbilirubinemia (esp. cats)
114
# **Pancreatitis**
Serological test to aid in dx pancreatitis
Pancreatic Lipase Immunoreactivity snap test
## Footnote
**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
115
# **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
116
# **Increased Liver Enzymes**
Hepatocellular vs cholestasis induction enzymes
Hepatocellular: ALT, AST
Cholestatic: ALKP, GGT
| Persistent ALT elevation indicates continued hepatocyte injury
117
# **Increased Liver Enzymes**
Decreases in which values on chemistry indicate impaired liver function?
- Cholesterol
- Albumin
- Glucose
- BUN
| All above DECREASE; Bilirubin increases
## Footnote
Protein breakdown -> ammonia produced -> transformed into urea in liver
118
# **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)
119
# **Increased Liver Enzymes**
Half life of ALT
2.5 days in dogs, shorter in cats
120
# **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
## Footnote
- A moderate-to-marked increase din ALKP w/out concurrent hyperbilirubinemia is most compatible with drug induction (glucocorticoids) or adrenal function
121
# **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
122
# **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
123
# **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.
124
# **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
125
