Pathology Flashcards Preview

Year 2 Semester 2 > Pathology > Flashcards

Flashcards in Pathology Deck (311)
Loading flashcards...

What is the average value for platelet count?

150-500 x 109/L


Platelet clumps are most common in which species?

Feline and bovine


Give 4 causes of thrombocytopenia

Increased destruction
Increased consumption (intravascular coagulation)
Decreased production (destruction of megakaryocytes in bone marrow)
Redistribution/sequestration (splenomegaly-abnormal enlargement of the spleen-platelets are temporarily entrapped within the spleen but are still able to bind Thrombopoietin, so bone marrow is not stimulated)


What is immunomodulation?
Why would we want to use it?

Modification of the immune response

Reduce inflammatory response
Reduce allergic response
Treat neoplasia of the immune system
Enhance immune response to infection
Suppress inappropriate immune response (immune mediated diseases)


How does an immune mediated disease occur?

Something happens to prevent recognition of self-antigens
Immune response is directed towards own tissues
If no detected underlying cause, can be referred to as 'autoimmune'


Which immune system does immunosuppressive drugs act on?
What do they do?

Reduce lymphocyte proliferation or limit their effect


What are the 3 main groups of immunosuppressive drugs?

Drugs which inhibit DNA synthesis
Drugs which inhibit IL-2 production/action
Drugs which inhibit cytokine gene expression


What is IL-2 produced by?
What does it do?

Th cells (CD4+)
Clonal proliferation of T cells, humoral immunity (B cell activity) and innate immune cells (macrophages, NK cells)


What is cyclosporin used for?
What is it metabolised by? Excretion?

Immunosuppressive drug. Inhibits IL-2 and therefore causes decreased proliferation of cytotoxic cells, decreased B cell responses and decreased T cell function in hypersensitivity reactions.
Metabolised by liver (cytochrome P450). Metabolites excreted in bile.


Glucocorticoids are synthetic versions of what?
What do they do?

Stimulate neogenesis
Suppress inflammation. Immunosuppressive.
Reduce clonal proliferation of CD4+ cells (T helper cells)

Binds intracellular receptor which migrates to nucleus and modifies transcription-reduces transcription of IL-2 gene and other cytokine genes


Why must glucocorticoid treatment be withdrawn very slowly?

Glucocorticoids suppress the HPA (hypothalamus-pituitary-adrenal gland) axis; recovery of adrenal function can take months


What is the function of drugs which inhibit DNA synthesis?
Give 3 examples

Inhibit synthesis of purines and/or pyrimidines
Suppress B and T cells
Azathioprine (inhibits DNA and RNA synthesis-disrupts mitosis and cell metabolism)
MMF (mycophenolate mofetil) (selective suppression of B and T cell proliferation)
Leflunomide (inhibits T and B cell proliferation)


What is carprofen?



What is histamine produced by?
What is its release caused by?

Basophils and mast cells
Release is caused by IgE binding to Fc receptors on mast cells


What is the function of COX-1 and COX-2?

Enzyme involved in prostaglandin biosynthesis. Converts free arachidonic acid to prostaglandin
Present at sites of inflammation. Promotes production of mucus in stomach and reduces acid secretion.
Inhibited by NSAIDs eg aspirin


What is the difference between COX-1 and COX-2?

COX-1 is produced under any conditions. It has protective uses like production of stomach mucus, secretion of bicarbonate and reducing gastric acid secretion. Found in the stomach, kidney, platelets.
COX-2 is only produced under certain conditions like inflammation. It causes production of prostaglandins which cause pain and inflammation, and pyrexia. Located in monocytes, macrophages, leukocytes.


Why would we want to inhibit COX enzymes?

COX enzymes convert arachidonic acid to prostaglandins
Prostaglandins play a key role in development of pain and inflammation
Therefore by inhibiting COX, we get relief from pain and inflammation


Give some examples of NSAIDs

Oxicans (eg meloxicam)
Coxibs (eg celecoxib)
Propionates (eg carprofen)
Pyrazolones (eg phenylbutazone)
Salicylates (eg aspirin)
P-aminophenols (paracetamol)


What are the adverse effects of NSAIDs?

Stomach ulcers
GI bleeding


What is metastasis?

Movement of cancerous cells to other parts of the body


Why are smaller tumours more sensitive to chemotherapy?

Cells are dividing more quickly so are more sensitive
Larger tumours have more G0 cells (not dividing) so are less sensitive


Explain the 2 theories as to why some tumours are resistant to chemotherapy?

1. Goldie-Coldman theory:
Detectable tumours are heterogenous. High likelihood that some of the cells will be resistant. Chemo can't kill the resistant cells, which then multiply and quickly make up the majority of the population

2. Stem cell theory:
Chemo kills daughter cells. Stem cells naturally resistant. Tumour proliferation rate greater than chemo kill rate due to required inter-treatment recovery interval


How do you measure drug dose intensity?

Drug dose per unit time


What are the 2 broad categories of chemotherapy?

1. Damages DNA (cell cycle non-specific)
2. Inhibits DNA replication (cell cycle specific)


What are the general side effects of chemotherapy?

Bone marrow-lowest WBC count typically after 7-10 days
Alopecia- uncommon except in a few breeds
Gastrointestinal-usually lasts longer than the first 4 days


What is the function of alkylators (chemotherapy drugs)?
How are they metabolised?
Give some examples
Give some possible side effects

Bind DNA and insert an alkyl group, leading to a change in structure. Inhibits transcription and replication, leading to apoptosis if the lesion is not repaired.
Metabolised by liver, excreted by kidneys
Melphalan, Cyclophosphamide, Lomustine
Side effects: Low WBC count -> GI problems, cystitis (Cyclophosphamide), hepatic toxicity (Lomustine)


What is the function of vinca-alkaloids (chemotherapy drugs)?
How are they metabolised?
Give some examples
Give some possible side effects

Either bind to or inhibit formation of microtubules thus preventing the formation of the mitotic spindle. Cell cycle specific-cells die in M phase by are most sensitive in S phase.
Metabolised to active forms in liver, excreted in bile.
Vincristine, Vinblastine.
Side effects: GI effects, low WBC counts, perivascular irritation of drug goes outside the vein


What is the function of anti-tumour antibiotics (chemotherapy drugs)?
How are they metabolised?
Give some examples
Give some possible side effects

3 mechanisms of action:
1. Topoisomerase inhibition -> DNA strand breaks
2. Intercalation with DNA -> Prevents transcription
3. Free radical formation -> DNA damage
Cycle non-specific
Metabolised to active forms in the liver (via hydrolysis), excreted in bile
Doxorubicin, Epirubicin
Side effects: Anaphylaxis, GI problems, low WBC count, severe perivascular irritation if drug goes outside the vein, kidney damage (cats), cumulative cardiotoxicity (dogs)


What is the function of platinating agents (chemotherapy drugs)?
How are they metabolised?
Give some examples
Give some possible side effects

Insert a platinum group into DNA. Transcription and replication are inhibited, cells die if lesion is not repaired
Mainly excreted unchanged by kidneys
Myelosuppression, occasional GI toxicity, rare kidney toxicity


What is the function of anti-metabolites (chemotherapy drugs)?
How are they metabolised?
Give some examples
Give some possible side effects

Interact with DNA production pathways. Cell cycle specific to S phase.
Cytosine arabinoside, Methotrexate.
Cytosine arabinoside is metabolised by liver, plasma and peripheral tissues. Excreted by kidneys.
Methotrexate is metabolised by normal and malignant tissues, peripheral tissues. Excreted by kidneys.
Side effects: myelosuppression, GI side effects, hepatic dysfunction (cytosine)