Principles of science Flashcards

Question

How does necrosis present histologically

Answer 1

* Where agent has maximal effect theres a sphere of necrosis. * Next to this is a area where the tissue is damaged but not yet dead, zone of degeneration * Next to this is a dark zone where the body is reacting to the dead tissue, inflammatory zone

Answer 2

1. Coagulstive - Firm and drier appearance. Cell architecture preserved but cells appear larger. caused by bacteria (clostridium) virus (herpesvirus). 2. Liquefactive - tissue transformed into liquid mass. 2 types. Malacia - Affects the CNS. e.g Thiamine deficiency causing cerebrocortical necrosis. Abscess - Pus producing organisms. Cause necrosis and attract neutrophils which they also kill. These release proteolytic enzymes, which digest necrotic tissue, & kill tissue cells 3. Caseous necrosis - Cheese like necrosis. mixture of coagulative and liquefactive necrosis. Large proportion of necrotic tissue is macrophages. caused by specific organisms e.h mycobacterium which invade macrohphages.

Answer 3

* If basement membrane intact then erosion * If basement membrance breached, and host immune system reacts causing ulceration * Internal necros causes the formation of fibrous tissue

Answer 4

Fat necrosis * Adipocytes broken down to fatty acids to form soaps. * Caused by release of pancreatic enzymes, damaging mesenteric fats by trauma or Vit E deficiency Gangrene * Wet - Degredation of dead tissue. Life threatening. New or excisting bacteria putrefy dead tissue * Dry- Air moving over the extremeties removes all the fluid content, mumyfying it

Answer 5

* Vessel is severed **exposing collagen** in the **subendothelin** * **Adhesion** of platelets requires **van wilebrand factor**. platelets activate and undergo conformational changes * Platelets release granules containing **ADP & thrombaxane A2** * Thrombaxane A2 causes expression of **GPIIb**, allows adhesion of platelets. * **Thrombin** activated and causes the conversion of fibrinogen into **fibrin**, acts as a mesh and forms definitive haemostatic plug ## Footnote * Antithrombin III is a endogenous inactivator of coagulation factors* * Endothilin secretes NO (increase cGMP) and prostacyclin (increase cAMP) to stop the formation of thrombi* * Also platelet activation & adhesion blocked by raising cAMP or cGMP levels*

Answer 6

* **Heparin** - **Bins to Antithrombin III & thrombin.** Has a short half life * **Heparin** like low molecular molecules - Enhance inhibitory action of antithrombin III but **does not** bind to thrombin, meaning theres less Anti platelet activity. **Longer half life** than heparin * **Hirudin** - Binds directly to thrombin and inhibits

Answer 7

Warfarin - Structurally similiar to Vitamin K. Prevents reduction of Vitamin K needed as a co factor for the clotting cascade.

Answer 8

* Tissue plasminogen activator (tPA) - Acts specifically on plasminogen inside the thrombus. Plasminogen =\> Plasmin. Plasmin dissolves fibrin into fibrinogen.

Answer 9

Melanocytes in epidermis produce melanin, a endogenous brown pigment that protects against UV damage * Hyperpigmentation - Due to increased number of melanocytes or increased production (can be caused by hyperadrenocorticism). * Hypopigmentation - Can be congenital or aquired (Cu deficiency). Damage to basement membrane can cause melanin to leak into dermis. * Melanoma - Tumour of melanocytes, common in grey horses

Answer 10

Bilirubin is a yellow pigment found in macrophages at the site of macrophage breakdown 1. _Pre-hepatic jaundice_ - **Excessive production** of bilirubin due to **haemolysis**. Increase in **unconjugated bilirubin in blood** caused by large **haemorrhage** or infection e.g **babesiosis** 2. _Hepatic jaundice_ - **Hepatocyte damage** meaning a decrease in conjugation =\> **increased unconjugated** bilirubin in blood. Caused by liver damage due to **toxins/chemicals** or a **hepatocellular tumour** 3. _post hepatic jaundice_ - **Obstruction** of bile **excretion**. Causes an increased amount of **conjugated bilirubin** in the **blood** & is caused by **tumours, inflammation** or **gall stones**

Answer 11

* Dystrophic calcification - Local depostition in necrotic tissue. No regulation of cellular Ca+2 metabolism leads to increase in blood Ca. irreversible change * Metastic calcification - Depostion of Calcium in normal tissue. Disturbed Ca+2 metabolism leads to increase in blood. Can be caused by increased PTH, Chronic renal failure.

Answer 12

1. increased Intravascular hydrostatic pressure - increased blood volume in microvasculature. RHS heart failure can lead to Ascitis ( oedema of peritoneum) & LHS heart failure causes pulmonary oedema 2. Decreased osmotic pressure - decrease in plasma proteins (albumin) causes a decrease in absorption at venous end of capillary beds and builds up in the intersitium. Caused by severe liver disease (cirrhosis) causing a decrease in production or malnutrition/malabsorption. Also protein losin enteropathy (haemorrhage associated with parasites) 3. Increase in capillary permeability - Infamation causes vasodilation. increase permeability =\> increasin in protein escaping into intersitium raising osmotic pressure and causing oedema. 4. Decrease in lymphatic drainage - caused by * lymph vessel constriction * internal blockage * lymphitis * surgical removal of LN * Congenital malformation (aplasia/hypoplasia)

Answer 13

1. **_Rhexis_** - Usually a big hole in the blood vessel. Can be inherited or aquired by vascular erosion by microorganisms, Inflammatory reaction of abscess 2. **_Diapedesis_** - Various small holes. can be caused by: * Endothelial injury due to endotoxins * Decrease in platelet numbers or function * decrease in coagulation factors * Vit k deficiency **Consequences** - \>20% loss = hypovaleamia. Decrease in tissue perfusion & haemorrhagic shock. *Intracranial haemorrhage will cause increased intracranial pressure, comprimising blood supply & possibly causing hernation of brain stem through foramen magnum.*

Answer 14

* **Hyperaemia** - Active process that **increases arterial dilation** and **blood flow** ( inflammatory ) * **Congestion** - Passive process that **decreases outflow of blood**. can be **local** (obstruction of flow e.g **torsion**) or **general** ( decrease passage of blood through heart/lungs. **RHS heart failure** causes **hepatic congestion (nutmeg liver)** and **LHS pulmonary congestion**

Answer 15

Area of peracute ischemia that undergoes coagulative necrosis of tissu, often leading to a wedge shaped areas of necrosis. Causes * Thromboembolic arterial occlusion * Vasospasm * Exetrinsic compression of vessel * Torsion or traumatic rupture

Answer 16

DIC - Widespread activation of clotting factors can cause many thrombi in microvasculature

Answer 17

over production of thrombi, blocking vessels. caused by an increase in coagulation factors or decrease in coagulation inhibitors**.** ***Glomeruli amyloidosis** causes a loss of protein in urine, one being antithrombin III*

Answer 18

* Arterial - Occur at site of endothelial damage with increased turbulance. Dull, pale red apearance due to reduced time for RBC to encorporate into thrombate. grow downstream * Cardiac - Caused by arrythmias and dilated cardiomyopathy. Damaged heart valves can be targeted by bacteria * vonous - Sites of stasis. Slow blod flow allows RBC's to incorporate.

Answer 19

Characterised by **systemic hypertension**. Impaired tissue perfusion and cellular hypoxia 1. _Non-progressive_ - **Decrease in BP** detected by **baroreceptors** causes **Adr** release. **increase** in **CO & arterial vasoconstriction**, also increase in **RAAS**. causes **tachycardua, peripheral vasoconstriction** and **renal retention of water** 2. _Progressive_ - **Widespread hypoxia** causing **anaerobic** respiration and **lactic acid** formation. Leads to **metabolic acidosis** and **arterioles dilate** and **blood pools** in microcirculation. **decreases CO** and risk of **DIC**. 3. _Irreversible_ - Energy stores depleted and **impairs membrane transport. Lysosomal release** and cell integrity lost leading to **necrosis**. **Organs** begin to **fail** and *ishemic bowls can cause intestinal flora to leak into circulation.*

Answer 20

1. **Cardiogenic** - Failure of the heart to pump blood adequately. Caused by *intrinsice mycardial damage, ventricular arrythmias, extrinsic compression and outflow tract obstruction* 2. Hypovalaemic - Decrease blood volume. Haemorrhage or fluid loss e.g vomitting. blood loss of \>35% means CO & BP decrease, also adequate tissue perfusion cant be maintained 3. Blood maldistribution - Peripheral vascular resistance decrease. Due to neural/cytokine induced vasodilation. Normal blood volume but decreased effective circulating BV.

Answer 21

1. Septic - Overwhelming bacterial infection which comprimises the mucosal integrity, allowing bacteria toxins into blood. Bacterial endotoxins induce systemic release of excessive amount of vascular and inflammatory mediators. Results in DIC, peripheral blood poolin & leukocyte induced damage. 2. Anaphylactic - Exposure to insect or plant antigen. Interaction with igE and mast cell causing widespread degranulation. systemic vasodilation = hypofusion/tension 3. Neurological

Answer 22

Penicillin can potentially kill commensual organisms, leading to super infection of clostridial bacterial leading to fatal enterotoxaemia

Answer 23

T cells that are important in ruminants and pigs. They recognise stress proteins not MHC. These cells induce apoptosis

Answer 24

* Peyers patches recognise antigen * They are lined with Mcells which sample luminal contents, presenting them to the DC's and lymphocytes on their basolateral side * Plasma cells are stimulated by Th2 to produce IgA or IgE * IgA secreted in submucosa & transported across mucosal epithelium and into lumen. Uses polymeric immunoglobin receptors to do this (plgR)

Answer 25

* Exposure to ANY antigen stimulates an immune response * If antigen doesnt stimulate inflammatory response, Tregs secret IL-10, which down regulate immune system... **mucosal tolerance** * Harmful antigen will cause inflammatory response via recognition of PAMP via TLR. inflammatory cytokines inhibit Tregs. * Occasionally IgE responds to food antigen. known as dietary hypersensitivity. mass dedgranulation of mast cells

Answer 26

* Migration of Bcells to mammary glands * Small amount of Ig transfer via placenta in dogs/cats but no ruminants. * IgG from colostrum absorbed by FcRn receptors in intestinal epithelia. but these receptors last 24 hours * Provides systemic IgG for 8-12 weeks. ## Footnote *Failure of passive transfer can be due to poor colostrum quality (early birth or nutritional defiecieny) or indequate intake or absoprtion*

Answer 27

* Mare can make antibodies that are reactive to RBC's of the foal. * doesnt usually occur on first foal because mare hasnt been expose to 'foreign' antibodies as of yet so hasnt developed the antibodies (unless mare has had a blood transfusion) * Exposure to foals RBC's can occur at birth. * Causes anaemia and jaundice

Answer 28

* Have small lungs and 9 air sacs * Trachea is **2.7x longer** and **1.29x wider** = **4.5x increase in tracheal deadspace**. this is compensated by **larger tidal volumes & lower respiratory rate** (ore time for gaseous exchange) * **Trachea =\> Mesobronchi =\> Ventrobronchi =\> Parabronchi =\> dorsobronchi =\> mesobronchi** * Parabronchi has hundres of tiny **anastomising air capillaries** surrounded by blood capillaries * During expiration air moves out of air sacs (specically abdominal) and pass through parabronchi, undergoing gaseous exchange... meaning gaseous exchange occurs during inspiration and expiration * Air and blood travel at 90 degress of eachother creating efficient C02/02 gradients along parabronchi

Answer 29

* **Etamiphylinne camsylate** - acts on central chemoreceptors, chaging sensitivity to C02 * **Doxapram** - acts on central/peripheral cheorecptors (carotid body), increase tidal volume and respiratory rate ## Footnote *Used for apnoeic newborns or to reverse respiratory depression from overdose*

Answer 30

**Antitussives** are used for the comfort of the animal. Cough recpetors in medulla express opoid receptors that have a negative effect. therefore **opoid receptor agonists** used. **Codein** and **butorphanol**

Answer 31

* **Mucolytics** - **Bromohexine** - alters viscosity * **Nasal decongestants** - Pseudoephedrine - can release endogenous **noradrenaline from presynaptic terminals**. Act on **adrenoreceptors** to **increase calcium** and cause **constriction**. decreasing blood flow to secretory glands

Answer 32

* Muscarinic receptor agonist - atropine. Inhibits vagal input, inhibiting vasoconstriction. also inhibits mucociliary clearance/GIT function. Ipratropium - Adverse effects reduced becuase it is inhaled * B2 agonist (selective) - Clenbuterol. decrease in Calcium causes relaxation. improves ciliary clearance. but can cause tachycardia, hypotension and hypokalemia. Can be inhaled * Methylxanithines - Theophyllin - inhib phosphodiesterase =\> increase camp and decrease calcium. antiinflammatory properties. can cause vomitting (gastric intolerance) tachycardia and restlessness.

Answer 33

Variability of pathogen * Strains/serotype that need to be in vaccine * What antigens stimulate response * Does pathogen demonstrate immune evasion strategies Variability of host * Antibody enough or do u need cell mediated immunity?

Answer 34

* Cheap production * Consistent production * Long shelf life * Easy to administer * No adverse effects * Long lasting immunity with single dose

Answer 35

* _Maternally derived antibodies_ - **Rotavec** vaccines which cover **rotavirus, coronavirus and E.coli K99**. Administered to pregnant cow **3-12** weeks pre-partum. stimulate antibodys in colostrum * _Anti-serum_ - Tetanus antitoxin purified from the blood of horses which are hyperimmunised with tetanos toxoid. provides immediated protection.

Answer 36

1. _Toxoid_ - Some bacteria (clostridial spp) produce endotoxins. **Toxin is inactivated** but **antigenic structure remains** to stimulate immune response 2. _Inactivated_ - Pathogen **chemically treated** to kill it, contains **adjuvant & requires 2 doses 2-4 weeks** apart 3. _Attenuated_ - Grow virus under **abnormal conditions** ( e.g 37 degress instead of 35). Drives **natural selection** towards **lower virulence**. (e.g grown in snow leoprad kidney until strain evolves)**. Non adjuvinated & only 1 dose required** 4. _Recombinant_ - Genes encoding antigen **cloned into viral vector** (**canarypox**) 5. _DNA vaccine_ - Antigen genes closed & **inserted into vector & recombinant plasmid DNA**. **recombinant protein** stimulates immune response

Answer 37

Chemicals added to vaccines to boost immunogenecity. Increase Ig levels and influence specific Ig isotope formation & th1 or th2 balance

Answer 38

(Differentiating Infected from Vaccinated Animals)

Answer 39

Immune system isnt fully developed until 6 weeks of age. MDA's can interfere with any vaccines up until 12 weeks of age.

Answer 40

* **Virus** - Designed to stimulate **neutralising** antibodys. therefore surface antigens very important * **Bacteria** - Stimulate antibody for **opsinisation, compliment & neutralisation**. **sometimes cell mediated immunity required**, can be achieved by addition of **adjuvant** (*leishmania*) * **Parasite** - Irradicate the **L3** stage

Answer 41

Myxomatosis - 0.1ml intra dermally injected, rest of the does given sub cutaneous. This produces better cell mediated immunity

Answer 42

* Vaccine doesnt contain appropriate antigens for serotype/strain * Vaccine expire or not stored properly * Not administered correctly * Animal too young or old * MDA's * Immunosupressed

Answer 43

Dissociation constant for an acid. high value = strong acid. PH = Pka + log([A-][HA])

Answer 44

A buffer is a solution of weak acid and its conjugate salt. Accept H+ to minimise changes in PH _Intracellular :_ H2O + CO2 \<=\> H2CO3 \<=\> H+ +**HCO3**- open system because H2CO3 can never run out _Extracellular_: **Haemoglobin** * CO2 from metabolism diffuses into RBC * Carbonic anhydrase in RBC allows formation of H2CO3, which dissociates in HCO3- and H+ * HCO3- secreted into plasma and CL- replaces it (chloride shift). this acts as a buffer for CO2 * H+ reacts with HbO2 froming HbH & releasing 02 * RBC's reach lungs where 02 tension is high, so favours backwards reaction re forming HbO2 and releasing H+. thus CO2 and H+ removed in lungs.

Answer 45

* PH decrease * Respiration stimulated * PCO2 decreases * H2CO3 decrease * Increase PH * Respiration depressed * PCO2 increase * H2CO3 increase * PH decrease continous cycle trying to keep ph within limits.

Answer 46

1. **_Re-absorption of HCO3_**- - CO₂ from blood moves into tubular cell froming H2CO3 =\> HCO^3-. H⁺passes into the lumen in exchange for Na+. the **HCO^3-moves into the blood**. 2. **_Excreting acid urine_** - H⁺ moves into the lumen in exchange for Na+. **H+ combines with HPO₄-²=\> H₂PO^4- which is excreted.** 3. **_Excretion of NH³_**- NH³ produced from metabolism in **tubular cell & diffuses into lumen to form NH**^4+.can not pass back into cell as its charged and is **excreted**. important in prolonged periods of acidosis.

Answer 47

* **Decreased PH** and **increased CO²** * Caused by **hypoventilation**, no elimination of CO₂ * **HCO**^3- normal in acute conditions and **positive** in chronic * Caused by *Airway obstruction, depression of respiratory centre, neuroloical disease and any disease prevent lung expansion*

Answer 48

* **Increase in PH** & **decrease in CO2** * Due to **hyperventilation** * **HCO³ negative** in chronic conditions * Caused by *Fear/anxiety, PAin, Hyperthermia, Corticosteroids, Decrease in arterial 02 ( causing anemia/hypofusion/hypoxaemia*)

Answer 49

* **Decrease in PH** and **decrease in HCO^3-** * **PCO² decreased** in chronic conditions * Causes include **increased acid** ( *lactate, diabetic ketacidosis, uraemic acids*) or **lose of base** (*diarrhoea*)

Answer 50

* **Increased PH** and **increased HCO^3-** * **Increased PCO2** in chronic conditions * Causes include **decrease in acid** *(vomitting or increased renal loss*) And **addition of base** (*sodium carbonate*)

Answer 51

* **_Initial_** - First arteriole constriction which last seconds. Followed by **hyperaemia** for minute/days. Capillaries Dilate due to chemical mediators. **Opening of pre-capillary sphincters**, large engorgement of blood. * **_Exudative_** - **Increase vascular permeability** due to endothelial contraction. Contraction caused by **histamine** released from mast cells. Opening of tight junctions due to contraction. Allows escape of exudate * **_Migration of leukocytes_** - **margination** of neutrophils allowed by **slowing blood flow**. roll along the endothelium towards site of damage. this is allowed by the **expression of selectins** which **bind to glycoproteins** on the surface of the leukocytes. Undergo changes in morphology as they under go **emigration** through the **leaky blood vessels.** Move along **chemotactic gradient** (chemotaxis) produced by chemokines (IL-8) & C5a.

Answer 52

* Neutrophils - 6 hour half life & replaced twice daily, most are lost through mucous membranes. Release granules into exudate that enhance inflammatory response. * Eosinophil - Large numbers in parasitic infection. cause greenish gross appearance

Answer 53

* Pyrogens act on control centres in the hypothalamus of the brain to increase body temperature * Released from neutrophils ( phagocytosis), Gram - bacteria (when broken down), Damaged tissue cells & tumour cells, especially when they mastasised

Answer 54

* Dilutes toxic agent * Contain IgG which acts as a opsin * Can contain fibrin which immobilises irritant * Wash away irrittant and bring them to LN

Answer 55

* **_Serous_** - **mild vascular injury**. Vesicles on skin. resolves when irritant is overcome * **_Catarrhal_** - occurs on **goblet cells and mucous glands**. Can be watery or gelatinous * Fibrinous - Severe endothelial injury, escape of fibrinigoen. Common on serous surfaces. Will peel away from underlying tissue * **_Diphtheritic_ - Severe fibrinous exudate.** Considerable **necrosis of underlying tissue**. Attempts to **remove will tear tissue**. Internal surface of **fungal** infection. common in nose and gutural pouch * **_Haemorrhagic_** - Severe acute/peracute inflammation whe haemorrhage is main compoent. If widespread, associate with death but if localised = bruise * **_Purulent_** - **Pus** due to **dead neutrophil**s releasing **proteolytic enzymes.** Can be detrimental if ruptures in body cavity. End result is fibrous scar

Answer 56

* Lymphocytes * Plasma cells - Deposited at damaged tissue * Macrophages - derived from circulatory monocytes. phagocytose, present antigen and stimulate fibroplasia & fibrosis

Answer 57

Caused by organisms of **low virul**ence and **great persistance.** histology - **Central core** of irritant surrounded by chronic inflammatory cells encapsulated in a fibrous capsule

Answer 58

Granulation tissue froms at the **site of skin injury.** Formation of **connective tissue and new microscopic blood vessel**s. When skin doesnt grow over and granulation tissue continue to grow forms **proud flesh.**

Answer 59

* **_Ability of species to cope_** - E.g Ox's can wall off peritonitis whereas in horse can be fatal * **_Age_** - Old animal has less scope of healing ability, also very young animals have immature immune system * **_Nature of damage_** - highly specialised tissue (e.g neurones) wont heal * **_Amount of tissue damaged_** - If its still functional * **_Subsequent fibrosis_** - Progressive destruction of tissue causes furthur injury to adjacent normal tissue (e.g liver cirrhosis)

Answer 60

* Repair - Replacement of damaged tissue by fibrous scar tissue, does not retain function * Regeneration - Replacing damaged tissue with normal tissue of the same type. Functional status is repaired

Answer 61

1. **_Liable_** - **Constantly replineshses** tissue in life E.g skin & bone marrow 2. **_Stable_** - **Limited** ability to replace E.g Renal tubules and liver 3. **_Perminant_** - **Poor or no regenration**. Highly specialised cells e.g Cardiac or neurones

Answer 62

1. Haemostasis - Blood escapes damaged vessels. Fibrin clot formed 2. Inflammation - develops within 24 hours. Adds exudate. Macrophages release enzymes digesting scab and promoting repair 3. Epithelial regeneration - Within 48 hours. small amount of granulation tissue. blood vessels grow 4. Consolidation - Final scar is small. Sutures can be removed 7-10d

Answer 63

In livestock mostly caused by infectous agents that entered circulation via naval. in small animals usually immune mediated. Infection can also come from adjacent tissue, deep lacerations or poor aseptic techniques

Answer 64

**_Pneumonia_** * **_Airborne agent_** - **Bronchopheumonia** (*mannheimia haemolytica),* infectous droplets cranio ventral portion of lungs. Forms **large lymphoid follicles that obstruc airways** * **_Haematogenous_** - **Interstital pneumonia**. Distribution throughout lung, viral (**viral** infection e.g *canine distemper*) **thickens alveolar wall** * **_Traumatic implantation -_** Rare, tends to cause pleural inflammation

Answer 65

Usually inflammation of **_mucous membranes_** (*Catarrhal*), can cause damage to villi. Resulting in **Malabsorption** & **progressive loss of fluid** with protein. (*granulomatous enteritis - Johnes disease*)

Answer 66

**Acute pancreatic necrosis** is the main cause in dogs. **Release of pancreatic enzymes** into surrounding fatty tissues. Can cause **death** soon after painful episode or continue normally **asymptomatically** until little pancreatic tissue remains. Can lead to *diabetes mellitus*

Answer 67

* At service (livestock), often mild * At parturition & is usually life threatenting

Answer 68

In episodes of severe acute inflammation, Neutrophil need be so excessive that immature forms are released from bone marrow

Answer 69

* **Urticaria (hives) -** characterised by **red itchy skin rash** * _Angioedema_ - Severe **swelling** of tissues, especially eyelids & lips * **Anaphylaxis** - **Widespread** mast cell degranulation, life threatening because Histamine causes **vasodilation**, Cause **hypotension** & reduced blood flow to the brain

Answer 70

e.g's Feline asthma & canine allergic bronchitis. Clinical signs - Coughing, weezing & excercise intolerance Mast cells cause bronchospasms & systemic eosinophilia may been seen Corticosteroid & allergen avoidance are treament options

Answer 71

Irritabal bowl disease (IBD) - classified by type of cellular infulatrate. Loss of mucosal tolerance and inappropriate immune reactivity to dietary or enteric microbes. Cause : * Increased intestinal permeability to antigen * IgA deficieny * Innapropriate IgE response * Defective Tregs Treatment includes antibiotics to reduce the bacterial load, hypoallergenic diet & corticosteroid or ciclosporin

Answer 72

Innapropriate immune response to self antigen Factors: * Genetic - predominately MHC genes * Hormonal * Environmental - diet, stress, infection

Answer 73

The production of **IgE** instead of IgM or IgE in response to an allergen. IgE becomes **sensitised** and subsequent reexposure leads to **degranulation** of **mast cells**, causing *vasodilation, oedema, smooth muscle contraction and increased mucous secretions*.

Answer 74

IgG or IgM response to **fixed self antigen**. one form is ***_immune mediated haemolytic anaemia_***. Rbc's are brocken down causing *jaundice, pale mucous membranes, tachycardia*. Can be diagnosed by **positive saline augoagglutination**

Answer 75

Caused by **accumulation of Antibody-antigen** *complexes*. gives rise to inflammatory **response that causes destruction of blood vessels - Vasculitis**. E.gs include *_Feline infectous peritonites or Glomerulonephritis._*

Answer 76

Mediated by CD4 th1 cells and CD8 cells. **Reactive CD4 th1 cells** release **interferon gamma** which **activates macrophages** to secrete **pro-inflammatory mediators**. **CD8** cells kill **healthy cells**. Can be due to *_Hypothyroidism, Hypoadrenocorticism, exocrine pancreatic insufficiency_*

Answer 77

An aquired form of immune deficiency * Retrovirus induced immunosuppression - FeLV * Toxin induced immunosuppresion - poisons * Malnutrition, stress, chronic disease - drugs

Answer 78

_Tolerance_ - Deliberate state of unresponsivness to antigen by the immune system * **_Central_** - Clonal deletion of self reactive T-cells in Thymus (negative selection) * **_Peripheral_** - 1. **_Active suppression_** - T regulatory (Tregs) cells function to strategically supress the immune system 2. **_Clonal anergy_** - T cells unresponsive in absense of danger signals (inflammatory response)

Answer 79

PGE₂ * Gastric cytoprotection * vasodilation of renal blood flow PGI₂ * Gastric cytoprotection * vasodilation of renal blood flow * Prevents platlet aggregation and is a vasodilator

Answer 80

the majority of NSAID's act as **Non selective COX inhibitor**s. **COX-1** is involved in **normal physiological processes** producing prostaglandins. whereas **COX-2** is induced by **bacterial toxins** and **cytokines**. Thus inhibits the inflammatory mediators (PGE₂). **_Clinical uses:_** * Control pain in acute and chronic inflammatory conditions * Decrease swelling * Reduce fever **_Side effects:_** * **Damage to GIT** (increase acid & decrease bicarbonate) * **Nephrotoxicity** when **dehydrated** (*suppression* of protective *afferent artery vasodilation*) * **Hepatotoxicity**

Answer 81

Glucocorticosteroids are anti inflammatory drugs that **inhibit the formation** & **action of pro-inflammatory mediators** but also induce the formation of **anti-inflammatory mediators** (*mimicing cortisol*) **_Mechanism_**: * **Decrease** in **inflammatory mediators,** inhibiting the induction of COX-2 * Induce **lipocortin**, reducing lipid mediators * **Decrease** in stored mediator release * **Decrease** in **inflammatory cell production** in BM * **Decrease** in **circulating compliment** components

Answer 82

Clinical uses: * Allergic disease ( anaphlaxis ) * Inflammatory conditions of skin/eye * Immunosuppression with prolonged use (making it useful for autoimmune/chronic inflammatory conditions) * Induce parturition of cattle/sheep Contra indications: * Renal disease * Diabetes mellitus Side effects: * Suppression of wound healing * inhibition of osteoblasts & increased osteoclast activity * Induction of iatrogenic cushing syndrome * Can cause adrenal atrophy due to endogenous cortisol * Rapid withdrawel can cause addisonian crisis ( acute sudden death due to decrease in cortisol)

Answer 83

* Inflammatory stimuli not effectiively removed * Stiumulus overwhelms system * Stimulus by passes immune response (parasite) * Lack of effective resolution & repair * Immunosuppressed

Answer 84

first generation H1 antagonist had side effects such as **antipruritic, antiemetic, anti nausua** and **sedative**. Second generation drugs **do not cross the blood brain barrier** to access the H1 receptors in the CNS. Meaning **these side effects are negated.**

Answer 85

**_Malformations_** - Disorders of growth which occurs during gestitation **_Congenital defect_** - Disorder of growth detected at birth **_Hereditary defects_** - Genetically transmitted disease

Answer 86

1. _Chromosome_ - results in early **abortion/resorption** 2. _Viral disease_ - Can cross placenta E.g **bovine virus diarrhoea** can cause **cerebellor hyperplasia** 3. _Toxins_ - '**Corn lilly**' can produce **cyclopia** when ingested in 12-14 days into pregnancy 4. _Drugs_ - **Griseofulvin** (ring worm treatment) given to pregnant queen results in kittens with **cleft palate** (*aspiration pneumonia*) 5. _Ionising radiation_ 6. _Nutritional deficiency_ - **Copper deficiency** in pregnant ewe = **Degredation of white matter.** Can be ***'sway back***' which is seen at **birth** or ***Enzootic atoxia*** which is a **delayed onset** of upto **6 months** 7. _Physical factors_ - umbilical cord can wrap around limbs causing **amputations** 8. _Anoxia_ - can be caused by **aneamic mother** Various types of defects include : * *Cyclops* * *Bulldog calg in dextor calfs* * *Cleft palate (failure of palatine bones to close)* * *Cystic kidneys* * *Cardiac defects*

Answer 87

**Decrease** in **size** of cells & organ **After** organ has reached it **normal size**. *Occurs in normal physiology with the thymus and uterus post partum* **_Cause:_** * Decrease in blood supply * Compression * Work load * Denervation ( temporal muscle in cats when trigeminal damaged

Answer 88

Hypertrophy is an **increase** in **size** of **individual cells** 1. **_Funtional hypertrophy_** - In response to **increase in physiological need** e.g *heart diseases* 2. **_Compensatory hypertrophy_** - when one of a **paired** organ is **impaired** e.g *kidney* 3. **_Obstructional hypertrophy_** - **Hollow organs thicken around an obstruction** e.g *bladder/intestines* 4. _Hormone mediated hypertrophy_ - Induced by **anabolic steroid**. **Thyroid hormone** has general **hypertrophic effect** on cells. E.g *hyperthyroidism cause cardiac hypertrophy*

Answer 89

**Reduction** in **size** of **cells** due to **failure to grow to normal size** ## Footnote *E.g pituitary dwarfism*

Answer 90

Failure of an organ or tissue to develop

Answer 91

Hyperplasia is an **increase** in **size** of an organ to due **increased number of cells** Cause: * **Hormonal** E.g *parathyroid hyperplasia in chronic renal failure.* * In response to cell loss/damage. **Regeneration**

Answer 92

Transformation of **one type of tissue into another**. occurs in connective tissue and epithelium. ## Footnote *E.g in prostate of dogs, Transitional epithelium to stratified squamous epithelium.*

Answer 93

Abnormal growth within tissue. Loss of normal arrangement

Answer 94

A congenital discontinuinity of squamous epithelium. Autosomal recessive disorder in cattle.leaves animal prone to bacterial infection

Answer 95

Papillomavirus is a double stranded DNA virus which is NON enveloped. Pathogenesis: * Entry via lesion in the epithelium * Infection of dividing basal cells of the skin * Expression of early proteins in basal epithelium causes proliferation * Virus particles only produced in upper layer of epithelium, where cells are differentiated * Transmission via exfoliated cells

Answer 96

**_Bovine_** * **10** different strains * Clinically presents as skin tumour on head, neck & shoulders * Most frequent in **calves and yearlings**. spontaneously **regress** after **6 months** * Viral protein **E5** binds to **receptor** for **platelet derived growth factor (PDGF**), causing cell **proliferation**. Also stops communication with neighbouring cells. E5 **downregulates MHC I,** meaning it **avoids immunosurveilance** * Malignant tumours from **BPV-4** requires co factor... **Bracken fern** contains **mutagens** **_Canine_** * Presents as **oral papillomatosis**, benign tumours on lips, tongue, palate which **spontaneously regress** **_Equine_** * Causes benign skin tumours * **BPV-1/2** Can cause equine sarcoids. Frequently reoccur after surgical removal. * Commonly mistaken for ringworm or granulation tissue

Answer 97

Retroviruses are **enveloped RNA viruses**. They posses **Reverse transcriptase** which transcribes RNA into DNA. This viral DNA is then incorporated into the host genome by **Integrase**. Transforms the Cell in 3 different ways: 1. **Carry Oncogenes** within viral genome. This can often lead to defects in the viral genome. 2. **Activate** cellular **pro-oncogenes** Via **insertional mutagenesis** 3. **Inactivate Anti-oncogenes**

Answer 98

FeLV causes lymphomas and transmitted oronasally **_Pathogenesis_**: * Initial viral replication in **lymphocytes** of **tonsils** = **Primary viraemia** which presents as **pyrexia** * Causes uncontrolled **expression** of **MYC**, causing **uncontrolled cell proliferation** * *immunosuppression = secondary infection* Outcome * **20-30%** - **seroconvert** without detectable viraemia * **30-40%** - **transient virameia**, remain **latently infected** in BM, may reactivate if animal immunosuppressed * **30%**- **persistenly viraemic**. Infects dividing stem cell of BM. Larger amounts released, infects epithelia in salivary glands and intestines. Animal becomes immunosuppressed, anaemic and has lymphoma. FeLV detected by *immunochromatography*

Answer 99

Uncontrolled purposeless cell proliferation. Continous without cause & forms from single mutation Rate of growth exceeds normal for the tissue

Answer 100

**_Carcinoma_** - Malignancy of **epithelial** origin E.g *squamous cell carcinoma* **_Sarcoma_** - Malignancy of **mesenchymal** origin. E.g Osteosarcoma **_Sarcoid_** - Low grade fibrosarcoma, skin of horses & cats. viral involvement **_Granuloma_** - NOT neoplastic. Chronic inflammatory reaction

Answer 101

1. **_Clonal expansion_** - Genetic & epigenetic changes overtime. **Traits** with **selective advantage** outcompete others 2. **_Cancer stem cell theory_** - States that cancer is driven by small number of cancer stem cells that can reporduce & sustain cancer. ## Footnote *Importance in treatment. Because treatments that shrink cancer cells will have no effect if the stem cell theory is correct because stemm cells stil proliferating*

Answer 102

A **normal** gene that becomes an oncogene following **mutation** or **over expression** * RAS - involved in kidney signalling pathway, controlling transcription of genes * MYC - Transcription factor

Answer 103

1. **_Initiation_** - Introduction of **irreversible** genetic change by **mutagenic initiator** (e.g chemical carcinogens that damage DNA). Cells can remain **morphologically quiescent** for **years**. Have mutations which give growth advantage. e.g resistant to apoptosis. 2. **_Promotion_** - initiated cells exposed to certain stimuli, driving **proliferation**. Begins to grow **more rapidly** and **less controlled** than normal cell. May lead to benign tumour, this is ***reversible*** step. 3. **_Progression_** - Conversion of benign tumour into **malignant & metastatic**. This conversion is ***Irreversable***. Increase in cell heterogeneity.

Answer 104

* Accumulation of genetic changes over time * Immune function decreases * Lag between transformation & clinically detectable tumour

Answer 105

* Spayed bitches reduce incidence of malignant tumours on mammary glands. * Castration of dogs causes regression of perianal tumours

Answer 106

Tumours larger than **2mm** must become vascularised. Production of _tumour angiogenesis factor_ causes host vessels to branch into tumour. Tumour vessels are **tortous, irregular, leaky and less efficient.** *Density of vessels can be used for prognosis.* Malignant tumours can also outgrow blood supply and cause **necrosis**.

Answer 107

1. Cells must **detatch** and **migrate** from primary malignant tumour 2. **Adhere** to vesel wall 3. **Invasion** of vessel 4. Transport of **micrometastasis** 5. Evasion of host defences 6. Exit vessel & **migrate** to form second tumour ## Footnote *Some tumors preferentially migrate. E.g Mammary gland tumours commonly metastasises to the lung*

Answer 108

* Local invasion * Intraorgan spread * Intra-vascular/lymphatic - A few tumour cells within blood vessel suggests intra-vascular metastatic potential * Serosal spread (pancreatic carcinoma) Spread via lymphatics Easier as they have thinner walls & lower pressures

Answer 109

* **Replaces** functional tissue = **malfunction** * Can cause compression on tissues * Can grow into blood vessels causing **haemorrhage** or **infarction** * **_Cachexia_** - Weakness/wasting of the muscle due to systemic cytokines * **_Paraneoplastic effects_** - **Innapropriate production** of **hormones**. E.g *_parathyroid hormone related peptide_* released promotes **osteoclasts**, therefore resorption occurs causing **release** of **Ca⁺²** = **Hypercalcaemia**. excess Calcium can be **deposited** e.g in alveoli, can also cause * . Another E.g is hypertrophic osteopathy. symmetrical lameness & extensive periosteal new bone in distal limb

Answer 110

1. Failing to show **antigenic molecules** or mask them 2. May express antigens of **normal** tissue 3. Express **immunosuppresives** ## Footnote *Tumours have immune cells surrounding them sugesting that immunosurveilance detects them*

Answer 111

**Catalase** test. Bacteria inoculated with **hydrogen peroxide.** Presence of catalase enzyme will produce **bubbles**. ## Footnote ***Positive result = Staphylococcus*** ***Negative result = Streptococcus***

Answer 112

**Coagulase** test. Bacteria suspended with **saline & plasma**. If coagulase present it causes conversion of pro-thrombin =\> **thrombin** which converts fibrinogen =\> **fibrin**. Can visibly see bacteria clumping from **insoluble fibrin**. **Pathogenic Staphylococcus include S.aureus, S.intermedius & S.hyic**us **Negative** result could be **S.epidermis or S.xylosus.** These are of low virulence and are oppertunistic. adhere to plastics.

Answer 113

* **_Haemolysins_** - 2 types. 1) **alpha** - Produced by *S.aureus & S.intermedia*. Produces zone of **B-Haemolysis** on blood agar. causes **necrosis**. B)**Beta toxin** - A **sphingomyeinase** converting sphingomyelin into **ceramide**. Causes **sensitisation** of **RBC's** to **weaker haemolysins**, Also damages cell membrane causing cell leakage. * **_TSST - 1_**: Toxin shock syndrome toxin is a **superantigen**. Cross links **invariable** region of **MHC class II** & **T-cell receptors**. Without antigen processing. Then reacts with variable region causing **T-cell proliferation & over production** of TNFalpha (cause cardiovascular shock) *

Answer 114

* **_Fibronectin binding protein_** - On surface of *S.auereus*, Allowing them to **adhere** & **colonise** on **damaged** tissues. * **_Protein A_** - **Anti-opsin**. binds to **Fc** receptor on IgG, leaving **Fab** region free to bind to antigen **BUT** can no longer bind to WBC via Fc. S.auereus * **_Capsule_** - Produced **in vivo** & **inhibits phagocytosi**s, C3 cant stabilise on surface

Answer 115

* Catalase negative * Aerotolerant * survival outside body is poor 4broad groups: 1. Pyrogenic 2. Viridians 3. Lactic 4. Faecal Pathogenecity: Hyaluronic acid capsule - Anti phagocytic M protein - Anti phagocytic

Answer 116

* **_Group A_** - **S.pyogens**. Infections of the tonsils, human throat infection & scarlet fever * **_Group B_** - S.agalactiae. is B-haemolytic & causes chronice bovine mastitis * **_Group C_** - 4 species 1. **S.equisimillis**- arthritic joints in pigs aged 1-2 weeks 2. **S.zooepidemicus** - Wound infections, abortion in cattle 3. **S.dysgalaticae** - Acute bovine mastitis & joint ill 4. **S.Equi** - Strangle in horse,stongly B-haemolytic * **_Group D_** - Faecal streptococci, opppertunistic, wounds, UTI, antimicrobial resistance * **_Group G_** -S.canis - Severe acute kennel cough

Answer 117

Slender gram positive rods that are catalase negative.Non motile. Normaly inhabit lymphoid tissue of pig. has 23 serotypes. Causes diamond shaped skin lesions & poly arthritis

Answer 118

**Catalase postive**, **motile** gram positive rod. Present in faeces, soil and silage. Growth at 4 to 45 degrees. Can cause **septicaemia, abortion and CNS disease.** Can survive in cells by producing **listeriolysin** which **lyses phagosome**. Cellmediated response required to eradicate.

Answer 119

**Catalase negative**,non motile gram positive rods that are surrounder by B-haemolysin. A.pyogens commonly **inhabit upper respiratory tract** & causes *liver abscesses and summer mastitis*. produces several extracellular toxins such as **haemolysin, proteases and neuraminidase**

Answer 120

Filamentous & branching gram positive rods that are catalase positive. Part of normal mouth baterium but are inoculated upon trauma

Answer 121

Cause thorasic lesions in canine & A.bovis causes lumpy jaw

Answer 122

Gram positive, aerobic ,partially acid fast. Branching rods containing **mycolic acid**. Making them **resistant** to a number of **antimicrobials**, making them harder to treat. Cause *granulamatous lesions & survive in macrophages*

Answer 123

**Strict aerobes** that are **slow growing**. Repell aquoes stains becuase of **mycolic acid** therefore must use **zeihl neelsen** stain. this is where smear heated & decolourise with 3% HCL in ethanol, giving a red stain. Pathogenecity - Inhalation/ingestion. Uptake into macrophages. Migration to LN where they form granulomas. Type IV hypersensitivity. shed via respiratory tract and udders.

Answer 124

Comparative intradermal tuberculosis test ## Footnote Pure protein derivitive of avian tuberculosis injected intradermally. And so is Bovine tuberculosis. Cell mediated responce measured by the size of the swelling 72 hours after injection. Allows for differentiation between exposure to tuberculin and exposure to bovine tuberculin.

Answer 125

* **_Pathogenicity_** - Ability of infectous agents to cause disease * **_Virulence_** - Measure of ability to cause disease * **_Pathogenesis_** - Process of disease progression

Answer 126

* **_Adhesion_** - Must adhere to surfaces to avoid being flushed out. Have fimbrae. The **K88 fimbrae** bind to receptor mannose * **_Aquiring nutrients_** - Initial survival dependant on **ability** to **aquire iron**. Bacteria produces **siderophores**, take iron of **chelators**, e.g haemoglobin. Siderophores bind to bacteria on outer membrane

Answer 127

* LPS plays a role in **preventing phagocytosis**. The **M protein** destroys C3 convertase, preventing C3a formation = **decreased opsinisation.** release **antichemotoxins** which are ant-opsinins. * Can hide intracellularly to **avoid humoral/cellular** defences. 3 mechanisms to survive in cell: 1. Inhibit **phagosome-lysosome fusion** (*salmonella*) 2. **Lyse** phagosomal membrane & escape into cytoplasm 3. Resist inactivation by lysosomal factors

Answer 128

* **_Exotoxins_** - produced by **G+ve** bacteria. Heat liable proteins e.g anthrax * **_Endotoxins_** - **Lipid A** portion of **LPS**. Outer membrane of **G-ve**. interacts with **macrophages** membrane receptors. Cause release of **tumour necrosis factor (TNF)** then **IL-1**, acts on hypothalamus to cause **fever**.

Answer 129

**Anaerobic** gram **positive spore** forming bacterium. inhabit soil and faeces. **Motile** and produce many toxins. Types: * **_A_** - **Alpha toxin**. causes *enteritis* in pigs & chickens. * **_B_** - Has **alpha, beta & epsilon** toxins. Causes lamb *dysentry* * **_C_** - Has alpha and beta toxins. Causes *enterotoxaemia* in sheep. death without premonitory signs. also *nectrotic enteritis* is lambs & pigs * **_D_** - Has **alpha** and **epsilon** toxins. causing *enterotoxaemia* in sheep and causes in lambs. * **_E_** - Less important. necrotic enteritis in australia

Answer 130

**_C.botulinum_** * Ingestion of toxins, usually from **inadequetely heat treated canned food** or hay silage with contaminated rotting carcase * Enters circulation & **peripheral NS**. **blocks Ach** release at **NMJ**, causing a **flaccid paralysis** and death **_C.tetani_** * Found in soil and faeces * Grows superficially on deep **anaerobic** wounds * Releases **tetanospasmin**, **blocking** release of **neurotransmitter** for inhibitory synapses (*glycine*) * Causes uncontrolled excitory synaptic activity, **paralysis** by constant contraction.

Answer 131

**Gram positive spore forming rod bacteria.** Aerobic and found in soil and faeces. most are not pathogens. **_B.anthrax_** * **Capsule** enables it to **resist phagocytosis** and survive in vivo * spores ingested and germinate in lymphatics * Appear on smear as dark blue chain of square ending rods in capsule * Produce **B toxin in vivo**, 3 protein exotoxin. * Leads to **death of phagocytic cells**, **increased capillary permeability** and **thrombosis**. death by **systemic shock** due to **haemorrhage, hypotension and oedema.**

Answer 132

They disrupt the **cell wall synthesis** by non competitvely inhibiting **Transpeptidases,** **No peptidoglyan cross links**. *As bacteria **grow**, They **burst** under osmotic stress! therefore.. If used with a **bacteriostatic** drug **NOT** effective.* **Cidal** drugs 1. **_Natural_** - **Narrow** spec agains **+Gve**. beta **lactomase sensitive** (produced bby staphylococcal infections) 2. **_Anti-Staphylococcal penicillins_** - Narrow spec & **resistant** to B-lactamase 3. _**Aminopenicillins** (*amoxycillin*)_ - **Broad** spec. **Sensitive** to B-lactamase 4. **Extended spec penicillines** - **Broad** spec *Penicillins are organice acids therefore are ionised at Physiological PH=\> **poor oral availability.** Except aminopenicillins*

Answer 133

Cephalosporins are antimicrobial drugs that non competiitively inhibt Transpeptidases.. no peptidoglycan Cross links. developed from penicillins to **improve** the **spectrum**. Also **B-lactamase sensitive.** * **_1st gen_** - **Broad** spec and **resistant** to Beta lactamase * **_2nd gen_** - Improved effectivenss against **+Gve** * **_3rd gen_** - Improved effictiveness against **-Gve**

Answer 134

Quinolones are **narrow** spec **-Gve** antibiotics that **inhibit the super coiling of bacterial DNA.** **Fluoroquinolones** Have there structere altered and now **Wide spectrum**. **Highly lipophilic**, meaning they can cross INTO cells making them **effective against intracellular pathogens**. **Oral availability good and volume of distribution good.** **Poor against obligate anaerobes**

Answer 135

Antibacterial drug that is **only effective** against obligate anaerobes. **Highly lipophilic** and has **good oral availability and volume of distribution**. Requires **hepatic metablism** before it can be excreted

Answer 136

* **Competitve inhibitor** of **glutamic acid, Blocking production of nucleotides** * **Broad spectrum** * Weak acid with good oral availability * Good volume of distribution * Extent of plasma binding varies in species * **Not good vs obligate anaerobes** * Rate of metabolism & excretion varies within species & with urine PH ( more acidic less excretion)

Answer 137

DHR's are **wide spectrum** antibacterial drugs. **Orally active** and cleared via hepatic metabolism. **Not good vs obligate anaerobes.**

Answer 138

* **Inhibit peptidyl transferase**, inhibiting peptide formation. **Bacteriostatic** * **Broad spec including obligate anaerobes** * Orally active * Requires hepatic metabolism

Answer 139

* Inhibit tRNA joining A site. **bacteriostatic** * **Broad spectrum** * Hydrophilic and lipophilic * Renally excreted

Answer 140

* Binds to ribosome causing wrong amino acids to bind. **Wastes all metabolic energy making pointless proteins** * **Narrow spec -Gve with some anti staphylococcal activity** * Poorly distributed - confined to extracellular * Renally excreted

Answer 141

* Cause peptide chain to dissociate duuring translocation * Narrow spec +Gve * **Good vs olbligate anerobes** * **Good vs special organsims** (mycoplasma and mycobacteria) * orally active distribute widely * Hepatic metabilism prior to metabolism

Answer 142

**_1. Target DNA & cell division_** * Inhibit nuclei acid syntheis (*sulphonamides*) * Interfere with DNA synthesis (*rifampin*) * Prevent cell division (*cisplatin*) **_2. Protein synthesis_** - ribosomes of **prokaryotes** are **70s** and **eukaryotes 80s**. **Bacteriostatic** effect * Bind to 30s subunit - *tetracyclines* * Bind to 50s subunit - *chloraphenicol* **_3. Plasma membrane_** - Alter permeability E.g Ionophore cause formation of pores

Answer 143

Antibacterials put selective pressure of bacteria meaning a change in phenotype can cause survival. Can be transfered by **conjugation** (horizonatal), **transduction** (virus induced) & **Transformation** (uptake from cytoplasm) * **Increased production of metabolite that competes with drug.** * **Loss of cell permeability, increases trasportation of drug out of cell.** * **Over production of drug target**

Answer 144

**_P.aeruginosa_** * **Aerobic gram negative Rod** * Secretes a green pigment called pyocyanin * **oppertunistic** infectous agent, **damaged tissue** * Has an effective **efflux system** pumping out disenfectant quicker than it diffuses in * **Resistant** to some antibiotics, therefore when **antibiotics given kills competing bacteria**

Answer 145

* **Strict aerobic gram negative Rod** * Grows on MacConkey medium * **secondary infection** of ciliated epithelium of trachea **following damage to tissues** by virus or mycoplasm * Filamentous haemogglutinin alows adherence * **Leukotoxins destroys neutrophils**

Answer 146

Gram negative rod bacteria that inhabits the upper respiratory mucosa and GI tract. * **_Primary pathogen_** - Fowl cholera & atrophic rhinoitis * **_Secondary pathogen_** - Bovine pneumonia, wound infections and enzootic pneuomonia

Answer 147

Non fermenting gram negative Rod. Usually **secondary** to **mild viral infection**. **_Bovine respiratory disease_**. Secrete **leukotoxins** & fills alveoli with **serous** fluid .

Answer 148

Gram negative bacteria, oxidase negative that are facultative anaerobes. 1. **_Lactose fermenters_** - **Harmless** commensual of the gut E.g *_E.coli and Enterobacter_* 2. **_Non lactose fermenters_** -pathogens of the gut E.g *_salmonella_* *Neutral red added to detect any acid produced from lactose fermentation*

Answer 149

E.coli normally inhabits LI, & is a indicator of water contamination * Rare strains with special properties e.g *fimbrae, reversable Na+ pumps=\>diarrhoea & metabolite loss =\>acidosis* are **enteropathogens** of gut. an example is **_enterotoxigenic Escherichia coli (ETEC)_** * Many strains are pathogenic outside of the gut and are known as **extraintestinal** pathogens. * Pathogenecity factors include **K antigens, Fe aquisition , haemolysins & compliment resistance**

Answer 150

Is a Non lactose fermenting gram negative rod. Produces **H₂S.** Must use **enrichment** because present in very small numbers and then place on a **strong selective medium** and use **phenal red**. Will remain red as no acid is produced but **colonies appear black** due to H₂S. Can identify using **API test** **Agglutinisation** with specific antisera determines grouping based on **O side chain of LPS and flagellae, _Kaufmann-white scheme_**. However an inverted segment of DNA allows **'switch phasing' of flagellae.** Causes ***cytotoxicity of enterocytes, septicaemia and enteritis.*** Can survive in macrophages, so after recovery can be intermittently released in faeces, **active carriage**.

Answer 151

Camplybacter is a **curve gram negative rod**. Motile and is **microaerophilic** (5-10%) **C.jejuni** is the largest cuse of food poisining in man. When chicken slaughtered **intestinal contents splattered onto abdominal wall**. **Inadequate thawing** causes bacteria to be viable. Causes ***necrosis of the spithelial cells of GIT, erosion of mucosa and cyptic abcsesses***.

Answer 152

Balance between host immune protection & pathogen immune evasion. E.g **vaccinia virus** - multiple modulatory proteins. inhibits inflammatory & immune response

Answer 153

Expresses actin tail. repells viral proteins away from already infected cells. repelled to adjacent non infected cells to ensure rapid spread

Answer 154

**_Direct effects_** *Cytopathic effects (CPE)* - changes visible under light microscopy * host cell shuts off * lysosomal damage * inclusion bodies * syncitia formation (measles) **_Indirects effects -_** immune mediated pathology

Answer 155

Is the specificity of a virus to a cell type, tissue or species. Determined by: 1. Appropriate cell surface receptor 2. requirements of a virus for expression of intracellular gene products to complete infection 3. accessibility 4. overcoming host immune defences

Answer 156

**_Entry_** 1. _Via ingestion_ - Must be bile and stomach acid resistant. Can also gain access via a buffer E.g milk. Also can be activated by proteases *(rotavirus has its outer capsid cleaved*) 2. **_Via oropharynx_** - primary infection of lymphocytes. spread to GI via blood **_Pathogenesis_** * Destruction of spithelial cells, replaced by **transitional cells** which **lack enzyme production** & absorbitive function

Answer 157

* Non enveloped, RNA segmented virus * Group A causes diarrhoea in calves. short inoculation (1-4 days) * Infects vili tips * Less differentiated cells **secrete less disaccharides**, causing a **decrease in glucose coupled transporters**. * **Build up** of **undigested lactose** promotes **bacterial growth**, exerting furthur osmotic effects = **diarrhoea**. *milk scours* ## Footnote *Diagnosis - by antigen detection in faeces by ELISA. antibody detection not useful due to passive immunity*

Answer 158

* Lysis of cells - erosion of mucosa * Loss of ciliated cells=\>decreased ciliary clearance =\> increase in spread of virus * Mucus, accumulation of fluid and inflammatory cells inhibits airflow, increasing sucseptibility to secondary infection **_Equine influenza virus_** * Segmented ss RNA enveloped virus * transmission via aerosol & direct contact * Diagnosis - Antigen detection by ELISA or nasal swabs

Answer 159

* Primary replication at lymphoid tissue at site of entry * Viraemia to sites * Destruction of lymphoid cells causing immunosuppression **_Feline pandeukopenia virus_** * **Non enveloped ss DNA virus** * Targets rapidly diving cells * **Entry via oropharynx**, infects **tonsils** and infects **blood** * **Destroys white blood cells without preference** * Also targets crypts, causing diarrhoea * Diagnosis - **Antigen** detection via **ELISA** from faeces

Answer 160

**_Pox virus_** * Encodes all **enzymes required for replication**, therefore **independant** of **nucleus** and can replicate in cytoplasm _Pathogenisis_ * Targets skin **abrasions**, spreading locally * **Replicates** in **epithelial cells** & causes **cytoplasmic swelling/rupture**. Inflammatory cells attracted * Dilation of blood vessels, **increases permeability** and causes **dermal oedema forming papule** * Degeneration and formation of **intradermal vesicle**. Ruptures releasing viral proteins **_ORF_** * Lesions of lips and gums * Spreads direct or via formites * Vaccination can cause clinical signs therefore **shouldnt** be given to **herds free** of ORF **_Myoxoma_** * Generalised infection of **rabbits** * Causes **conjunctivitis**, **swelling of muzzle** and subcutaneous nodules. * Transmitted by **arthropods**

Answer 161

**_Rabies_** ## Footnote Bite containing virus inoculated into muscle. Uses motor nerves to travel to the VNS and furthur replicate Clinical signs include a foamy mouth (**paralysis of pharyngeal muscles inhibits swallowing**, animals can becomes aggressive or paralyses Diagnosed by immunofluorescence of brain smear

Answer 162

* Gains entry via **respiratory trac**t, infecting **lymphocytes** and causing **viraemia** * Causes **vasculitis** and haemorrhaging causing **abortion** in pregnant mares * Blood vessels of **spine** can be affected and cause **ataxia** or **paralysis** * **Diagnosed by PCR from nasal swab**

Answer 163

* Enveloped ss RNA virus * Gains entry via **upper respiratory** tract causing a **viraemia** * Spread to **lymphoid organs** & epithelial cells (widespread) * Clinicals signs include **cough, conjunctivitis, v&d, seizures and hyperkeratosis (hard pad)** * Clinical signs are dependant on **age, strain of virus and environmental stresses** upon hosy * Diagnosed by **serology** (IgM), PCR or CSF

Answer 164

**_Virus isolation_** * Virus need cells to replicate. CPE's can be see on cells * Virus is amplified and easier to detect * *BUT can take several days, requires live virus and can be cultured* **_Directly visualise_** * Electro microscopy. Use negative staining. Heavy metals bind to backround and not substrate. * Can be used for virus that cant be cultured & can identify new agents * *BUT requires specialised machinery and personal. sample often needs to be purified* **_PCR_** * Taq polymerase used to amplify DNA. Short oligoucletide primers specific to virus structure used. If its RNA then must be first coverted into cDNA by reverse transcriptase * Very sensitive and doest require live virus * *High sensitivity means dager of contamination*

Answer 165

**_Antigen ELISA_** * Plates coated with antibody specific to virus, virus then binds. Second virus specific antibody is added which carries enzyme label. enzyme acts on substrate generating colour * Fast, Virus can be dead and test is specific * *No amplification means low sensitivity* **_Immunoassays_** * Virus antigen in cells detected by specific antibody. Antibody carries either fluorescent marker or enzyme which reacts with substrate. * Fast, non living viruses can be used and is specific * *No amplification, relatively low sensitivity*

Answer 166

**_Neutralisation assay_** * Serum mixed with virus. antibodies in serum bind. mixture added to cells. if antibodys are present they do not infect cels **_Haemagglutination inhibition assay_** * Some viruses have the ability to agglutinate red blood cells. E.g influeza. Serum mixed with virus. Red blood cells added to mixture. If theres NO antibodies, RBC's agglutinate **_Antibody ELISA_** * Plate coated in antigen. Antibody in serum binds to antigen. Second antibody whic recognises *

Answer 167

**Type 1 interferons** are secreted by viraly infected cells. IFN's act in a **paracrine** manner making cells resistant to viral replication by: 1. Increasing degradation of viral mRNA 2. Reduced synthesis of virus protein & increased antigen presentation (MHC class I) 3. NK cells destroy cells with reduced MHC class I ***Pestiviruses** (BVDV) produce **NON structural proteins** that interfere with signlling to **prevent IFN production. Pox virus** interferes via **blocking IFN receptors***

Answer 168

1. **Taking up residence in privilidged sites** in the body E.g CNS, eyes and testis. No immune response in these areas to protect against damage from inflammation. E.g's ***Rabies in CNS*** and ***BVDV in testis*** 2. **Avoiding the extracellular matrix** where Ig's are lurking by syncitia formation ***E.g parainfluenza-3 virus.*** 3. **Integrating viral DNA into genome inducing malignant transformation**. cell proliferation propogates virus ( ***Retroviruses, FeLV***). Some also integrate into germline, main concern when considering **xenotransplants** 4. Secrete an **antigen decoy** in large quantities, **saturating** the binding sites of Ig's. Infectous virus particles are therefore **not neutralised** (***E.g Ebola***). Decoy antigen can also be expressed on **surface**, distracting immune system away from antigen of attachment. Impacts on **developing vaccines *(E.g Retroviruses*)** 5. **Antigenic variation:** * **Antigenic _drift_** - Genes subject to **_mutation_**. slight change making antigen not recognisable * **Antigent _shift**_ - Fast process, whole _**genes swapped_** between viruses radically changing proteins expressed. ***E.g mutation in feline panleuokpenia virus allowed spike antigen to bind to transferrin on canine entoerocytes. Also feline calicivirus. Also equine infectous anaemia is a persistent infection occuring in cycles, with each cylce due to new antigenic variant thats mutated.***

Answer 169

1. **_Superantigens_** - Cross link **MHC** to **TCR** non specifically **outside peptide binding groove**. Causes clonal expansion of T-cells, **diluting antigen specific T-cells** (***E.g retroviruses***) 2. **_Resistance to apoptosis_** - Produce **sepsins** which **inhibit caspase cascade**. Also produce **analogues** of **anti-apoptosis proteins** (Bcl2) 3. **_Preventing presentation to CD8 T cells:_** * **Block TAP** transporter, preventing MHC presentation * **Prevent** MHC **transport**, retined in ER * Misdirects newly synthesised MHC into cytosol to be **dissolved by proteosome.** *This however increases susceptibility to NK cells due to lack of MHC. therefore can produce **fake MHC***

Answer 170

* **_Direct immuno suppression_** - **Direct destruction** of **T helper cells** and cells of monocyte lineage (**macrogohages and DC's**). **Increases susceptibility** to **cancers** (reduced tumour surveleince) and **oppertunistic infections**. (e.g ***FIV***) * **_Indirect immunosuppression_** - Produce **cyotokine analogue** that acts to mimic **regulatory Tcells**, **downregulating** the immune system ( ***E.g herpesvirus, ORF and epstein bar virus)***

Answer 171

* **_Acute primary phase_** - Transient **viraemia**, **fever**, **lymphodenopathy** as virus replicates in lymphoid tissue * **_Asymptomatic phase_** - immune response fails to eradicate virus & **persistant infection** develops. **animal remains healthy** * **_Feline AIDS_** - lyphopenia develops. CD4 T cells number reach critical low levels, causing **immunosuppression**

Answer 172

Example **BVDV**. Has 2 stains, **cytopathic** and **non cytopathic**. Infection with **ncp early** in **gestation** causes **abortion/resorption**. If infection occurs **80-125** days into gestation, foetus may survive with **persistant infection**. **T & B cells reactive** to **virus** are **eliminated** as its treated as self. developing calf is **tolerant** but **sheds large amount of virus**. Can **mutate** and become **cytopathic** causing **ulcerations** to **mucosal epithelium**.

Answer 173

**_Latency_** - Initial infection causes clinical signs. Virus then enters **quiescence**. **viral genome maintained** in host cell with **no replication**. **_Recrudescence_** occurs when host immunity lowered: * **Stress** * **Medication (corticosteroids)** * **Pregnancy** Examples: 1. **_Feline herpesvirus -1_** : Transmission to **kittens**, develop **latent infection**. Vaccination useless post infection 2. **_Equine herpesvirus-1/-4_**: Causes **abortion** in pregnanct mares. Causes **depression, fever and nasal discharge**. **-1** strain can also cause **neurolgical clinical signs** in which **euthanasia** is required. Large proportion of healthy horses are latently infected with EHV. Vaccination is licensed but every horse on yard needs to be vaccinated and many boosters required.

Answer 174

**_Disease:_** * Acute enteric disease in young dogs ( diarrhoea, vomitting, dehydration and shock) * Loss of intestinal barrier allowing bacterial infection * Immunosuppression * Myocarditis in pups **_Pathogenesis:_** * Replicates in pharyngeal lymphoid tissue * Viraemia proceeded by targeting of rapidly dividing stem cells * In pups **\<2weeks** causes **myocarditis** * In older pups invade crypts ***Aminoacid change mutation in FPLV capsid protein (VP2) allowed host change from feline panleukopenia virus to efficiently attach to canine vili.***

Answer 175

Causes **enteric** disease in **birds** and **respiratory** disease in **horses**, swine & humans _Pathogenisis:_ * Replicates in Upper respiratory tract in humans * Replicates in ciliated epithelium and nasal mucosa in horse & bronchioles Influenza is subject to **antigenic shift**. 2 viruses infect same cell, causing **reassortment** of **viral segments**. Recombination causes **new strain**. **Pigs** act as **mixing vessels** causing pandemics.

Answer 176

**_Life cycle_** * _Attachment_ - Attaches to virus receptor via **HA**, **binds to sialic acid** * _Penetration_ - Endocytosis. **Acidic PH** in endosome causes **conformational change** in HA causing **exposure** of **cleavage site**. HA cleaved to **HA1** & **HA2**. * _Uncoating_ - Viral genome released * _Replication_ * _Viral synthesis_ * _Release_ - Virus progeny released. **Neuraminidase cleaves sialic acid** to prevent virus binding to infected cell. Cleavibility of HA determines pathogenicity. Normally linked by **argenine residues** and only cleaved by **limited proteases in few cells**. Whereas **highly pathogenic** strains **easily cleaved** by **proteases** found in the **majority of cells**, allowing viral replication throughout body. In humans the bond between **galactose** and **siliac acid** gives it a **kinked shape**, whereas in **avain** is **linear**. This determines what strain binds to which species. HOWEVER in **lower respiratory tract**, siliac acid is **linear** in **humans**, therefore **close contact** with **avain** can cause **infection**.

Answer 177

_Urban clycle_ - Transmission of virus between **human** and **arthropod** _Dead end host_ - **Infected** but **not sufficie**nt replication in **blood** to infect arthropod when feeding _Sylvatic cycle_ - Transmission between **arthropod** and **other vertebrates**

Answer 178

_Emergence_ * Movement of vector * Climate change * Movement of animals * New vector _Spread_ * R₀ - Ability to infect * Population of vector and host * Movement of animals * Host range _Persistance_ * Ability to evade immune system * Segmented genome alows genomic shift

Answer 179

**_West nile virus_** * Disease in **birds** in the **USA** * *Human and horses are dead end hosts* * Rapid spread due to **migration** of birds * **Mosquito** vector **_Louping ill_** * **Tick** borne virus * Disease in **sheep** causing **encephalomyelitis**, ataxia, leaping gait and **parlysis** * *Cattle, horses and humans are dead end hosts* **_Bluetongue virus_** * Affects domestic **ruminants** * Spread via **midges** * Causes ulceration of upperlip and erosion of tongue * Clinical signs include **oedema**, fever, congestion, **necrosis of skeletal & cardiac muscle** * **Haemorrhage of pulmonary artery** **_African horse sickness virus (AHSV)_** * Affects **ruminants** * **Midge** vector * Pathogenisis - Cell associated **viraemia**, causing **vasculitis** =\> increased permeability of vessels * _Mild_ form presents as **supraorbital oed**ema * _Cardiac_ form presents as **oedema** in the **head**, **neck** and **chest** * _Pulmonary_ form presents as **pulmonary oedema** and has a **mortality** rate up to **95%**

Answer 180

A disease that must be reported to the AHVLA if suspected (Legal requirement) * Endemic diseases (Bovine TB) * Exoctic disease not usually seen in the UK * Zoonotic disease (Rabies)

Answer 181

**Pet Travel Scheme** _Requirements:_ * Microchip * Rabies vaccination * Pet passport * Tapeworm treatment * Travelling via approved route

Answer 182

Highly transmissable virus that has **7 serotypes**. Can be transmissed via **fomites**, vesicular fluid, milk, faeces, salivia & **aerosol**. Can be **diagnosed** from **serum** or **vesicular fluid**. Control based on disease status of control. Basis of control: * *Import control* * *Early detection* * *Tracing to identify source* * *Movement control* * *Intensive surveillance* **Prophylactic vaccination**: Seeks to maintain immunity against 1 or more serotypes. 2billion administered a year.

Answer 183

**P_rP^sc** is a disease associated **isoform** of the **P_rP^c** protein. P_rP^c is alpha helix **recylcing protein** which is continously produced on **neuron**es. P_rP^scHas a beta pleated sheet structure, allows it to **aggregate** and form **plaques**. Can convert P_rP^c into P_rP^sc.Replicate **inside** Follicular **DC's**. Causes **Neuroinflammation**. **Astrocyte proliferate** and **hypertrophy**. Theres an **influx** of **microglia** but not WBC's due to BBB. **No B** or **T cells** because proteins are recognised as **self antigens** & therefore any reactive lymphocytes would have been destroyed. Histologically causes **vacuolisation** (**reversible**) inside **neurones,** **extracellular plaques** of aggregated proteins. **Exceptionally resistant** to conventional sterilisation techniques. Requires **121 degrees for 1 hour**. New methods in **1980's reduced temp** of sterilisation and no solvent used.

Answer 184

_Diagnosis_ - **Western blot** * P_rP^sc is a **surrogate marker** * Proteins seperated into **molecular weight** & bloted onto paper. * **Antibody** specific to prion protein detect protein and bind resulting on **3 lines** on paper * 3 lines represent **same protein** but **differently glycosolated** * To distinguish between P_rP^cand P_rP^scproteases are used as **P_rP^sc** is **protease resistant** Antibodies are produced by: 1. **Immunising PrP knockout mice with PrP** 2. **Immunice with PrP from different species** 3. **Add T-cell epitope to PrP** _Bovine spongiform encephelopathy (BSE)_ - neurological symptoms affects cows of **4-5 years.** was transmitted by **meat and bone meal** _Scrapie_ - Occurs in sheep of **2-5 years**, death within **6-7 months**. **Persistant in environment** for over **16 years.**

Answer 185

ECM is a network of locally secreted macromolecules. Produced by **fibroblasts**. Cells determine ECM turnover and production _Function:_ * Cell shape * Cell migration * Cell proliferation * Cell function the 2 main components are **Glycoaminoglycans** (GAG) and **fibrous protein** (collagen)

Answer 186

_GAG_ * **Polysaccharides** which are covalently linked to **protein core** * **Negatively charged**, **attract** sodium and thus **water** * Strong at with standing **compressive forces** * Example - **_Hyaluronan_**. **Unsulphated** and is **not covaletly linked to protein**. synthesised at PM and not golgi. Functions as a **space filler, lubricant** and facilitates shape change. Can link to Protein of Proteoglycans. _fibrous protein_ * Collagen. 3x alpha helix, forms a triple helix which is covalently cross linked * **High tensile strength** * **Fibril associated collagens (type IX**) influence fibrular collagen structure (type II). Allowing for alternate structure and resistance of **tensile strength in more than one plane**

Answer 187

_ECM synthesis_ * Transforming growth factor beta **(TGF-b)** increases ECM production * **Decorin** (PG) **inhibits** TGF-b. * **TGF-b upregulates decorin synthesis**. this is a built in **negative feedback** system. _Co-receptor_ * **Syndecan** is a **transmembrane** protein. Brings FGF towards its receptors. Intracelullarly domain binds to actin. _Modulate tissue breakdown - By binding to enzymes or their inhibitors_ * Bind to enzyme/inhibitor to **restricts its range of action** * Bind & store enzyme/inhibitor to **directly control** * Bind to enzyme/inhibitor to **modulate activity** * Bind to enzyme/inhibitor to **control effective concentration**

Answer 188

* _Tight_ - Prevent leakage. Transmembrane proteins that dimerise. * _Anchoring_ - Can be cell to cell or cell to matrix. Also can be actin dependant or intermediate filament dependant * _Gap_ - Allow chemical and electrical signals to pass. 2-4nm gap. Flow of ion

Answer 189

Contraction of the throat muscles of birds, pushing air through moist air sacs, releasing heat upon expiration. a form of thermoregulation

Answer 190

Range of temperature in which a homeotherm can regulate its body temperature by adjusting heat loss at negligible energy cost

Answer 191

* **Vasodilation** of **superficial veins** for heat loss or **vasoconstriction** of deep veins for heat conservation * _Sweat glands_ - Controlled by sympathetic innevation & circulating catecholamines * _Adrenals_ - Release **adrenaline**, speeding up metabolism and producing heat * _Piloerection_ - Maximises **boundary layer**, increasing insulation

Answer 192

* Wet surface area from foetal fluids * Limited subcutaneous fat * Large surface area:volume ratio * Poorly developed coat * Poorly developed central control of hypothalamic set points Born with large amount of **brown fats** that are activated at birth by **cold shock and placental seperation**. Increase in adrenaline, cortisol and T3. increased activity of **mitochondrial uncoupling protein**, increasing the amount of **non shivering thermogenesis**

Answer 193

_Hypothermia_ - Depletion of glycogen stores causes * Decrease of CO & BP * Increased Blood viscosity * Decrease oxygen cosumption and GFR _Hyperthermia_ - **Loss** of **water** and **salts** leading to organ dysfunction _Fever_ - Release of **TNF, IL-6 and IL-1.** causes the release of **PGE₂**causing and **increase** in the **hypothalamic set points.**