a) w/c 6-Jan-14 Tumours/Repro Flashcards
p53 is an example of what type of gene?
Both p53 and Rb protein are examples of TUMOUR SUPRESSOR GENES (BRAKE ANAOLOGY).
For suppresion to be stopped, need both copies to be mutated/deleted
White haired cats are suspectible to which type of UV radiation induced cancer?
Squamous cell carcinoma (ear tips, nose)
The opposite of tumour supppressor genes are known as_____
mitogens Stimulate cell proliferation.
Aka proto-oncogenes e.g. Ras/Raf
5 hallmarks of cancer
- Resisting cell death
- Sustaining proliferative signalling
- Inducing angiogenesis
- Enabliing replicative immortaility
- Evading growth suppressors
- Activating invasion and metastasis
Two types of cancer boxers are predisposed to
Lymphoma and mast cell tumours = boxers are a walking neoplasm.
German shepherd dogs: haemangiosarcoma
3 ways cancer cells can undergon uncontrolled proliferation
- Secretion of endogenous growth receptors
- Mutation of growth factor receptors. Constitutively activate in absence of growth factor. e.g. canine mast cell tumour KIT mutation
- Mutation of intraceullar signalling molecules. Activating proto-oncogenes e.g. Ras/Raf
Rb protein transduces growth-inhibitory signals that originate largely _____
Rb protein OUTSIDE the cell. Determines whether or not the cell cycle progresses
p53, another tumour suppresor gene recieves input from ___ mechanisms
Intracellular mechanisms, if cell viability is suboptimal it calls a halt to cell cycle progression
Can Rb and p53 trigger apoptosis via the caspace cascade? If so, which pathway is involved?
ONLY P53 can trigger APOPTOSIS via the INTRINSIC PATHWAY leading to CASPASE cascade (i.e. intracellular)
What is the significance of the Bcl-2 family in oncogenesis?
Cancer cells need to resist cell death. Regulated cell death has two mechanisms. Intrinsic and Extrinsic pathway.
Cancer cells can downregulate death receptors or UPREGULATE Bcl-2 family which blocks the INTRINSIC pathway
How can tumour cells avoid the EXTRINSIC pathway of cell death?
Cancers can downregulate the death receptors on the cell surface (i.e. extrinsic pathway)
c.f. with intrinsic pathway –> p53 intracellularly. Cancer cells can UPREGULATE Bcl-2 family
Which specialised DNA polymerase is upregulated in cancer cells to enable replicative immortality?
Normal cells undergo cellular senescence due to shorted telomeres (protect end of chromosomes)
Cancer cells contained DNA polymerase Telomerase which adds telomere repeat segments = immortality
Why do tumour cells need to induce angiogenesis? How do they do this?
Once a tumour reaches a critical size, is at risk of hypoxia-induced cellular necrosis therefore requires a blood supply.
SECRETE ANGIOGENIC FACTORS such as Vascular Endothelial Growth Factor (VEGF).
Faciliates metastasis/ Haematogenious spread
What do CARCINOMA cells use to metastasise?
Loss of E-cadherin by carcinoma cells allows them to detach from primary tumour and spread.
- Local drainage LN
- Liver
- Lungs
- Bone Marrow
Significance of tumour-promoting inflammation?
Some tumours demonstrate a significant infiltration of inflammatory cells. Although its an attempt to eradicate it can be COUNTERPRODUCTIVE.
Inflammatatory cells can supply bioactive molecules e.g. growth factors, immunosuppressive mediators
DDx for cancer tumour?
Abscess (systemically ill? pyrexia?), grauloma, haematoma, seroma, cyst
How could a haematoma be differentiated from a tumour?
Painful? Hot? Fluid-filled? Well-defined or ill-define? Fixed to under lying tissue?
What steps should be undertaken when a tumour is identifed?
Cytotoly (fine needle aspirate), no negative pressure to start with, evaculate syreinge using air.
Why is Histopathology preferred to cytology?
Histopathology: Tissue- Gives information on cell type and morphology/ tissue architecqture
Cytology: Cells
Both cytology and histopathology can both examines cell morphology for signs of malignancy (mitotic index, megakaroyocyte)
A fast growing tumour is more likely to be ____
malignant than a slow growing tumour.
Benign tumours grow by expansion
Malignant tumours grow more rapidly and disrupt surrounding tissues
Difference between tumour GRADE and STAGE?
Grade: Assigned by the PATHOLOGIST. low, intermediate or high grade
Stage: Assigned by the clinician. EXTENT of the disease in the patient. Use the TNM system
What is the TNM system?
T: Primary tumour: Size, mobility, relationship to surrounding tissue
N: Node: Assess the drainage LN (can be internal)
M: Distant metastasis. Imaging inc CT.
Most common site for metastasis in small animals?
Lungs. Can present with dyspnoea/ cough
X-ray, inflated radiograph, ideally 3
A tumour 3-5cm in diameter would have which TNM grade/
T2
WHO system for staging canine lymphoma. Stage III is when….
Generalised lymph node involvement (both sides of diaphram)
If the liver is involved in canine lymphoma, the WHO classifcation is stage
IV
V: bone marrow/ blood/ other organ systems
(substage a= systemic signs, b= no ss)
Which canine tumour is TNM most commonly used>
Canine mammary tumours
When treating an anal sac carcinoma, what is it important to check for?
Paraneoplastic effect of tumour. DUE TO TUMOUR PRODUCTION OF PTH. Present with hypercalcemia, if untreated = Renal damage
Which other tumours have paraneoplastic effects?
Hypercalcemia? lymphoma, myeloma, lymphoid leukaemia, other carcinomas, thymoma
Hypoglycaemia: Insulinoma
Hyperglobulinema: Myeloma (gamma globulin)
Why can mast cell tumours present with gastric ulceration/ vomiting?
Canine mast cell tumours = histamine release, can also have gastrin secreting tumours
Define Eutocia?
Normal parturition
What happens is Stage 1 of parturition?
Positioning of the foetus for birth, dilation of cervix, exposure of foetus membranes through the vulva
How long should stage 2 last in the COW vs the MARE?
Cow: 0.5-4 hours for stage 2 (expulsion of calf)
Mare: 20 minutes- 30 minutes (expulsion of foal)
MUCH SHORTER.
Also Stage 3 (fetal membranes) much shorted in mare 1-2 hours. 6 hours for COW
Which breed of horse are most likely to have dystocia?
10% of draught breeds have dystocia incidence vs 1-2% of ponies.
Higher in beef than dairy
Why should the water bag not be popped?
The allantochorion provides tension/ pressure to help feedback mechanisms that result in stage 2 of parturition (expulsion of fetus)
The bursting of the bag removes this tension
How can the time at which cows CALVE (time of day) be manipulated?
Cows calve when QUIET
If feed during day–> calve at night
If feed during night –> calve during day
Which presentation is most likely to result in dystocia due to undilated cervic?
Backward presentation, no tapered pressure that the head normally provides.
Manually dilate the vulva, check umbilical cord.
Relative traction forces
- that cow provides=
- that 1 person provides=
- that calving jack provides=
Cow: 70 kg
1 Person: 75kg
Calving jack: 400kg
How do you determine if there is sufficient space in the pelvis for calving?
Hand fits on top of head in pelvis. STRAIGHT LEGS (make sure they don't cross)
A calf should fit if carpal joint is __cm outside cow.
Once head is out, what needs to be done?
carpal joints 10cm outside cow.
Once head is born, ROTATE 90 degrees for hips
When does HIP BLOCK occur?
If following birth of head, calf is not rotated 90 degrees.
to ensure the hips line up in OVAL pelvis . After rotation pull dorsally rather than downwards (as before)
Traction for a caudal presentation should be directed
Dorsally (same as following rotation in normal birth)
When a cow is calving in a longitudinal posterior presentation, what is the critical point?
i.e. backwards
10cm of hock outside vulva. Once get to this point have to deliver quickly by pulling dorsally; umbilical cord will break when head still inside
Difference between early embryonic loss and late embryonic loss?
Early: before maternal regognition (i.e. will cycle normally)
Late: After meteral recognition.
When does pregnancy loss be termed as foetal loss rather than embro loss?
Embryo loss: before day 42
Foetal loss: After day 42 (most mortality before this day)
The majority of early embryo loss is due to…
STRESS/ Environmental/ Genetic factors
NOT DUE TO INFECTIOUS AGENTS
What Iatrogenic factors can lead to embryo loss?
Corticosteroids (>255days)- used to induce
prostaglandins (remove CL)
Oestrogens
Oxytocin
Definition of abortion in cows?
Birth between day 152 and 270 days
Neospora caninum is most commonly associated with…
still births (born dead, or survive less than 24 hours)
What types of Hydrops is there? If a cow if going to be induced with this condition, what do you need to be aware of?
Hydrops: Oedema of the placenta RARE Last three months, normally cull. ALWAYS RETAINED FETAL MEMBRANES -Hydropsamni (hydraamnios) Hydropsallantois (hydrallantois)
Torsion of the uterus in the cow is normally is what direction?
Counterclockwise,
palpate vaginally and note twist angle or par rectally and feel which ligament is tensed.
Can reposition internally or externally. GYN STICK
DIfference in timing between vaginal and uterine prolapse?
Vaginal: Before parturition (associated with High AND low BCS, high roughage diet, oestrogens)
Uterine: After parturition
TREAT UTERINE PROLAPSE WITH CALCIUM DUE TO UNDERLYING HYPOCALCEMIA
Frog position to treat. Can use osmotically active sugar to remove oedema
What is a sarcoma?
A malignant tumour of mesenchymal origin.
Feline infection site sarcoma
What type of biopsy must be done when investigating feline injection site sarcomas? Which must NEVER be done?
Always DO INCISIONAL BIOPSY.
NEVER DO EXCISIONAL= dirty margins
Example of a tyrosine kinase inhibitor
Masitinib. Used to balance over production of tyrosine kinase receptors by tumour cells which can lead to constititive activation in very low levels.
When should a suspected injection site sarcoma be biopsied?
If lump persists >3 months
or >2 cm in diameter
Can’t assess grade using cytology, only from pathologists examining histeopathology
During the puerpreium, involution occurs; this is the ____
Involution is the reduction in size of uterus and cervix after calving. Hypertrophy to Atrophy (loss of collagen and smooth muscle- reduction in size of myofibrils)
How many days post partum should the whole uterus be palpable per rectum?
8-10 days postpartum.
Complete involution is said to occur within ____ days,
26-50 days.
By day 25 the diameter of the cervix should EXCEED that of the previous gravid horn
Describe normal lochial discharge (and timings)
Occurs at 2-9 days post partum, yellowish or reddish brown. Does NOT have a fetid odor
Main method of elimination of uterine bacterial contamination
Phagocytosis by migrating leucocytes plus physical expulsion by uterine contractions and SECRETIONS (don’t let bacteria adhere to surface)
After replacing a uterine prolapse, what drug MUST be given?
Calcium (as uterine prolapse normally caused by hypocalcaemia)
How does normal seperation/expulsion of the placenta occur?
-Changes in p4 and E2 concentration
-Changes in collagenase/proteases
-Reduction in number of binucleate cells
-Distortion of placentomes
- Contaction of uterus
(if hypocalcaemic, inadequate uterine contractions= RFM)
Lack of which anti-oxidant is thought to predispose to retained fetal membranes (RFM)?
Selenium/ Vit-E (OVERDOSE= DEATH)
Does RFM have an effect on fertility?
No effect on its own. if leads to metritis then increases services per conception (i.e. decreased fertility).
rfm: reduces milk yield due to decreased appetite
Treatment for RFM
Hormones (prostaglandins, oxytocin), collagenase infusion into stumps of umbilical arteries of retained membranes
Difference between endometritis and metritis
Endometritis: No systemic signs (does affect fertility) mucopurulent discharge. Poorly involved uterus on rectal. LOCAL ANTIBIOTICS
METRITIS: Systemic illness, fetud purulent fluid. Distended fluid flilled abdo, sore, swollen or inflamed vagina
Dytocia in a cow with a ‘dirty’ calf should be delivered via….
Fetotomy, Caesarian will lead to peritonitis as it passes through the open wound
What is contraindicated in the treatment of Metritis?
Oestrogens increase absorption of endotoxins.
Uterine lavage followed by antibiotics
What antibiotic in CONTRAINDICATED in farm animals?
Metrinidazole
Treatment of bovine pyometra?
PGF2a and intrauterine cephaprin
Anaesthesia is required by LAW at which age?
a) Bull, goat=
b) Ram =
Bull/Goat: >2 momths
Ram: >3 months
Elastrator ring for animals <1 week
Technique when using Burdizzo castrator
-Position, Halter, Sedation.
Draw right testie into bottom of scrotal sac
-Hold spermatic cord against lateral edge of scrotum
-Clamp cord about 4cm above testis, second clamp 1cm distal to first.
Repeat for left testis LEAVING A GAP to PREVENT NECROSIS
Why should open castration incisions involve the bottom of the scrotum?
Dependent drainage due to gravity, prevents oedema.
ONLY TOUCH TISSUES WHICH ARE BEING REMOVED
How should anesthetic be infiltrated before doing castrations? How much procaine for a calf?
3-5ml of procaine each side calf.
Can infiltrate directly into teste (PAINFUL)
Better to infiltrate around cord, will deliver into testicle .
Give NSAID’s post op
How does the motion of removing the testicle differ between a) calfs and b) boars
a) calfs: Pull and twist (following J-shaped incision)
b) boars: Cut and pull
It is important to check the _____ vaccination status before castration to prevent infection
Clostridial
What external examination can tell you the liklihood of a dam needing a C-section?
Body condition - >3.5 = fat
or very thin beef dam = big calf taken all the nutrients
Function of Clenbuterol in C-section?
Which other drugs are commonly used?
Uterine Spasmolytic (illegal in NL, BE)
Xylazine (sedation)
Epidural
Anasethesia options
Paravertebral: T13, L1, L2, L3
Local block: Line or inverted L
Epidural if excessive straining
TRY NOT TO USE XYALAZINE i.e. sedation due to effects on foetus (depression of respiration)
Function of Doxapram in C-section
Respiratory stimulant for new born. Useful if Xyalazine was necessary for sedation. Can check urgency by testing in-utero calf reflexes–> slow = quicker!!)
Size of uterus sutures required and pattern necessary
5 TO 8 M catgut. Continuous inverting pattern. Test by squeezing for water-tightness.
What age is a gilt first mated?
8 months (second oestrous, i.e. 3 weeks after maturity) should be 120kg
Weaning weight should be
7kg at around 4/5 weeks (weaning age)
What is the average weaning-oestrous interval
<7 days (therefore weaning to farrowing interval= 115+7 days)
Pigs are normally culled after parity ___
SIX.
A parity 2 drop in litter size is normally and is a management problem (poor nutrition)
What is disease matching?
If already have a disease on the farm, don’t bother buying in stock which is free from disease (paying a premium). Buy in animals with same disease
Do you want replacements from a small or large litter?
Genetic element: want a large little
Environmental: Only species (pigs) where oocytes still developing therefore want good nutrition therefore smaller little. Wean off boars so gilts get better nutrition
How does maternal regognition of pregnancy vary between cows/sheep and pigs?
Cows/Sheep: Trophoblast-interferon tow
Pigs: Oestradiol secretion preventing pg production
When would inducing parturition in sows be useful?
If lots of sows are dying, need to adopt piglets onto other sow, induce using prostaglandins.
If weekend with no staff; use prostaglandin *check dates**
Why do you not want pigs to be too fat at time of insemination? q
Common misconception that feeding= good
fat sows don’t eat in farrowing house therefore no flushing= less productive
Potential explation as to why the UK dairy herd fertility has falen over the past 20 years?
In pigs, presence of boars is essential
Dairy farms have less bulls on the farm, potentially explaining why there has been a decrease in fertility over past decade.
Which is the only way to increase pig productivity
Can’t change gestation length, of lactation (legally 4 weeks), CAN CHANGE Weaning to oestrous interval.
Culling percentages on average UK pig farm
35-40%! Parity 6
How can sunburn lead to abortion?
Outdoor pigs very susceptible to sunlight. Sunburnt skin releases prostaglandins which lead to abortion
Specific pathogens that can lead to swine abortion
- Swine influenze
- PPRS (NOT YET NOTIFIABLE)
- Leptospirosis
- Erysipelas
- (CSF,CSF, Aujeskys)
Clinical signs of ‘blue-eared’ pig diease
Blue-eared pigs = Porcine Reproductive and Respiratory Syndrome (PPRS)
-Reproductive losses.
-Increase pre weaning mortality
-Severe respiratory efforts in neonates
-Flu in older pigs
-Blue extremities (<1%)
Susceptible to secondary pathogens as immunosupresed
When to suspect PPRS?
> 20% born dead
25% die before 7dayys
8% abortions
SEROLOGY
Treatment of PPRS
NOT NOTIFIABLE (SHOULD BE)
- Vaccination avaliable
- Treatment involves support against secondary pathogens
Risk factors and TREATMENT of leptospirosis in pigs
Arterivirus. Risks factors: Rodent reservoirs, outdoor herds, WATER BORNE. L.bratislava.
Treatment: Antibiotics for secondary.
Streptomycin. Treat BOARS as well.
Use cattle lepto vaccination
Notifiable diseases in pigs
Leptospiroris, African Swine Fever (never in UK), Classical swine fever, vesciular stomatitis, FMD, Aujeskys
which samples should be taken if leptospirosis is suspected?
Three fetuses (+placenta), stomach contents, liver
How can variations in litters tell you the likely cause of intra-uterine death?
Small number born: embroys loss pre-ossification therefore re-absorbed (= infectious causes commonly VIRAL
What day does ossification of the piglet begin? What is the significance of this?
Day 35-40. Cannot be reabsorbed after ossification.
What are some non-infectious causes of intra-uterine death?
Nutrition: Micronutrient deficiency: VitE/A
Toxic: Misuse of hormonal drugs
Chemicals- HEMLOCK?
Mycotoxins (wet harvest, poor fertility in 2012 due to wet harvest)
Result in dead fetuses of same gestational age.
c.f. infectious: different gestational ages
What is SMEDI? Cause=
NOT ABORTION!!!
Stillbirth, Mummification, Embryonic Death, Infertility
Causes by porcine PARVOVIRUS
less implicated: Porcine enterovirus
Transmission of smedi?
i.e. parvovirus. Oronasal/venereal.
Non-preg= immune
pregnancy: smedi
VACCINATION AVALIABLE
How can pre/intra/ post partum fetus be differentiated?
Pre/intra partum: Non-inflated lungs
Prepartum: Sunken blue cornea
Intrapartum: Bulging eyes
LOOK AT FEET: SLIPPERS???
How to estimate approximate gestational age of pigelets?
Approx age (days): 21+ (3x crown/rump length in cm) CAN ONLY BE USED 25 DAYS +++
How do uterine prolapses present differently in sows c.f. cows?
Sows often in shock, can try to correct if not. Poor prognosis advice euthanase
What is the significance of Zearelenone?
Abortions, is a mycotoxin. Can present as swollen vulva
Causes of downer sow
Lactational osteoporosis Muscle weakness Apophysiolysis Rupture of lesser trochanter Normally cull/ move to deeper bedding
What is the first thing to check when there are several pigs with agalactia?
Water supply.
Treatment: inject Oxytocin.
Ergot poisoning (no response to oxytocin)
Dilate ergot from ration by adding grain.
Mastitis? Klebsiella, E.coli.
Sudden death, 3 weeks post mating with concurrent haematouria and pyrexia/ pus when urinating. What is the likely diagnosis?
Bacterium Actinobaculum suis is found in prepuce of most boars >10 weeks old
Causes Pyelonephritis/Cystitis
Ineffect treatment once signs are seen–> euthanase
very early causes: potentiated sulphonamides
In a indoor pig farm that uses old heat lamps and has poor ventilation the farmer has reported high piglet mortality rates. He also has a headache when working in the farrowing house. What is the probably cause?
Carbon Monoxide poisoning.
Very common other cause of post-partum death = Starvation. Sow factors (mastitis, agalactiae) and Piglet factors (Splayleg, weak piglets- umbilicus/chilling/CO))
