Exam 7 L. 7 Flashcards
Paraneoplastic syndromes
1) CANCER ASSOCIATED ALTERATIONS OCCURRING DISTANT TO TUMOR
2) typically result from tumor production of small molecules
- hormones, cytokines, peptides, enzymes
3) other causes = immune -related
- antibody cross-reactivity, immune complex development, autoimmune component
Clinical importance of Paraneoplastic Syndromes (PNS)
1) PNS often are the 1st sign of cancer!!*
- They may be a hallmark of certain types of tumor
2) PNS frequently parallel underlying malignancy
- treatment of tumor often resolves PNS
3)PNS MAY CAUSE GREATER MORBIDITY THAN PRIMARY TUMOR
Gastrointestinal manifestations of cancer
1) cachexia -wasting syndrome and weight loss
2) inappetence
3) protein losing enteropathy
4) Gastroduodenal ulceration
Cerenia (Maropitant): acts on..
1) Acts on the chemoreceptor trigger zone
- NK1 receptor
2) Emetic Center
- NK1 receptor
Metoclopramide acts on..
1) Chemoreceptor trigger zone
- D2 antagonist
2) Afferent neurons
- 5-HT3 receptors
NOTE: sedation +/-, behavioral changes
Ondansetron
Acts on chemoreceptor trigger zone
- 5-HT3 receptor
Control of food intake is complicated
1) increases feeding: Ghrelin
2) decreases feeding: stretch receptors, cholecystokinin, insulin, leptin
* ***a lot of negative input to the brain saying “not hungry” ===> many of these are upregulated in oncology patients
Capromorelin
1) the 1st FDA approved veterinary product for inappetence!
2) mimics the action of ghrelin*
- effect at appetite center to increase food intake
3) potent and selective growth hormone secretagogue receptor agonist = increases growth hormone secretion!!!!
- NOTE: because negative feedback loop is in place, these animals WON’T have abnormal growth
Gastroduodenal ulceration: mast cell tumors
1) mast cell tumors ==> hyperhistaminemia
- elevated plasma histamine = negative prognostic factor
2) histamine binds gastric H2 receptors ==> increased HCl***
- predisposes dog to gastric and duodenal ulcers
3) treatment: PPI, H2 blocker, misoprostol, sucralfate
NOTE: gastrinoma (gastrin secreting non-islet pancreatic tumor) can also cause G.I. ulceration
Endocrine manifestations of cancer
1) hypercalcemia
2) hypoglycemia
Causes of hypercalcemia
H-hyperparathyroidism A-Addison's disease (hypoadrenocortiscism) R-renal disease D-hypervitaminosis D I-idiopathic (cats) O-osteolysis (not common) N-neoplasia**(very common!) S-Systemic granulomatous disease
NOTE: most significant levels of hypercalcemia are seen with:
- malignancy/neoplasia
- primary hyperparathyroidism
- vitamin D toxicity
What is the number 1 cause of hypercalcemia in dogs?
CANCER!!
1) neoplasia is diagnosed in approximately 2/3 of dogs with hypercalcemia
- lymphoma: 10-35%
- apocrine gland anal sac adenocarcinoma (AGASACA)
- multiple myeloma
- ANY tumor can potentially cause hypercalcemia!
CATS: ~10-30% have hypercalcemia with neoplasia
- lymphoma
- squamous cell carcinoma (usually oral)
How do tumors cause hypercalcemia of malignancy?
-Most common cause of pathologic hypercalcemia in dogs and cats**
1) Ectopic production of parathyroid hormone (PTH) or PTH-related peptide (PTH-rp)
Clinical signs of hypercalcemia
1) PU/PD*
2) listlessness
3) urinary incontinence (secondary to PU/PD)
4) weakness
5) exercise intolerance
6) inappetence
NOTE: if you can’t find cause for hypercalcemia, remember to do a rectal exam! (AGASACA)
Therapy for hypercalcemia
1) IV fluid therapy (0.9% NaCl)
- Saline diuresis (2-3x maintenance): it will increase calcium excretion in kidneys
2) diuretic therapy (furosemide)
- IF and ONLY IF fluid deficits have been replaced
3) glucocorticoid therapy (prednisone)
- IF and ONLY IF diagnosis has been made (prednisone will kill lymphoma cells => makes it hard to get diagnosis!)
4) bisphosphonates: decrease osteoclast resorption
*determine/treat underlying cause of hypercalcemia!
Causes of cancer induced hypoglycemia
1) insulinoma (beta-islet cell tumor)
- produce excessive circulating insulin levels
2) non-islet cell tumors associated with PNS hypoglycemia
- hepatocellular carcinoma**(most common)
- hepatoma
- leiomyoma/leiomyosacoma
* most common = liver and small bowel*
Note: rule out other causes - lab error, liver failure, sepsis, hypoadrenocortiscism
Hypergammaglobulinemia PNS
1) excessive production of immunoglobulin proteins from MONOCLONAL line of plasma cells or lymphocytes
2) most commonly seen plasma cell tumor (i.e. multiple myeloma), lymphoma
3) non-neoplastic differentials:
- Rickettsial diseases
- chronic granulomatous diseases (systemic fungal infections)
Hypergammaglobulinenemia PNS
1) clinical signs:
- hyperviscosity: ataxia, depression, cardiac signs, seizures, coma
- tissue hypoxia
- bleeding (often from mucous areas) due to platelet coating with immunoglobulins
- ocular changes: retinal hemorrhage/detachment
DIC
1) ~10% in dogs with malignant tumors
2) especially associated with hemangiosarcoma
Cutaneous manifestations of cancer
1) alopecia
2) nodular dermatofibrosis
Alopecia as PNS-cats
1) Pancreatic carcinoma*
2) acute, bilaterally symmetric alopecia (ventral, limbs),glistening
Neurologic manifestations of cancer
Myasthenia gravis
peripheral neuropathy
Myasthenia gravis
1) associated with THYMOMA
2) causes: antibody to acetylcholine receptor/calcium channel
Hypertrophic osteopathy
1) associated with primary or metastatic lung tumors**
2) clinical appearance: periosteal proliferation of new bone along the shafts of long bones
- shifting leg lameness, can be quite painful (all 4 limbs affected)
