Before Final Flashcards
What is an annular sinus?
What is a trabecula?
Annular sinus- blood filled sinus around the hair follicle of a tactile hair
Trabecula sinus- traversed by fibroelasticl trabeculae containing many nerve endings
** merkel’s cells associated with tactile stimulation in the external root sheath (desmosomes)
What dietery deficiencies would result in poor wool growth?
Cysteine and methionine (two sulfur containing proteinogenic aas)
AND
Copper and zinc
Sarcoptic mange. Odor and it is crusty (not just alopecia- which would be more likely allergic disease like Flea Allergy Dermatitis). Diffuse hyperkeratosis and crusting.
The parasite is in the str. corneum (NOT the hair follicle like Demodex).
Acanthosis (epidermal hyperplasia). Either due to metabolic disease or self trauma for example. Chronic disease. Callus, sarcoptic mange, Actinic keratosis.
Hyperkeratosis (str. corneum)
Acanthosis (str. spinosum?)
Actinic keratosis. From UV light exposure. Can progress to squamous cell carcinoma. Erythematous (which means redness of the skin due to congestion of capillaries) lesions with comedones and crusts often. Plaques (epidermal hyperplasia).
Actinic keratosis with a comedone.
What usually causes apoptosis with skin disease? What about necrosis?
Apoptosis- normally from immune mediated disorders.
Necrosis from some type of mechanical injury or vasculitis, thromboembolism.
What are the degrees of burns?
When do vesicles occur in burns (where do they occur?) And when does erosion, ulceration, and crusts occur?
Malassezia dermatitis from lipophylic yeast- Malassezia pachydermatis. Opportunistic secondary pathogen causing canine pruritic skin diseases. Excessive sebum, moisturn accumulation, disruption of the normal barrier function therefore yeast proliferation, inflammation. (common otitis as well)
Acantholysis- loss of cohesiveness of epithelial cells in the epidermis. (disruption of desomosomes). Typically occurs in immune mediated diseases.
Pemphigus foliaceus. Target desmosomal protein in the epidermal layer. (autoimmune). Acantholysis–> vesicles–> crusts
Photosensitisation. Long wavelength UV rays absorbed by photodynamic molecule and biological substrate, therefore releasing energy that produces oxygen free radicals. Ingestion of plant, genetic inability to metabolize heme pigments, or hepatogenous photosensitization occurs with an abnormal build up of phylloerythrin (degradation product of chlorophyl) due to damaged or immature liver.
Hyperadrenocorticism.
Localized demodicosis. Demodex mange.
Flea bite hypersensitivity. Type I or IV.
Feline leprosy. Extending from the dermis through the panniculus adiposus, dense areas of pyogranulamatous inflammation with scattered areas of lytic necrosis (arrow).
epithelial cell tumours from keratinocytes of the epidermis and follicular epithelium, sebocytes and sweat gland eptihelial cells.
* adhere tightly to each other and exfoliate in clusters or sheets
Mesenchymal cells in the dermis include fibroblasts, adipocytes, endothelial cells in vessels. “spindle cell tumours”
Tend to appear “whispy” due to indistinct cytoplasm boundaries
Round cells. Monocyte-macrophages (histiocytes), lymphocytes, mast cells and melanocytes. Interspersed within the dermis and epidermis. Little or no adherence in the body= no intercellular junctonas. Exfoliate in large numbers and lie on the smear without clumping.
Benign Cutaneous Histiocytoma. Very common benign neoplasm in dogs. Usually undergo spontaneous regression within 3 months.
Mast cell tumour. The most common cutaneous malignancy in dogs. Associated with mast cells in the dermis. Graded, the higher the grade, the poorer the prognosis. High grade MCT commonly metastasizes to the LNs.
Cutaneous Lymphoma. Can be infiltrated secondarily in multicentric lymphomas.
Melanocytic tumour. Benign or malignant. Both are common in dogs, grey horses, and some breeds of pigs.
Transmissible Venereal Tumour. Contagious neoplasm of dogs and wild carnivores. Uncommon. Histiocyte origin. Spontaneous regression occurs after 6 months usually.
Lipoma. Commonly in older, obese dogs. Thorax, neck, or proximal limbs. Do not undergo malignant transformation and never metastasize.
Haemangioma- benign tumour of the vascular endothelium. common in dogs but rare in cats. Chronic UV radiation is implicated.
Haemangiosarcoma. Infiltrative, less common than Haemangiomas. Can ulcerate and bleed. Rarely metastasise. Much less malignant then the splenic form.
Soft tissue sarcomas. Fibrosarcoma, myxosarcoma (of the heart), liposarcoma, perivascular wall tumours, peripheral nerve sheath tumours. Similar biologic behaviour though from different cells. Dermis or subcutis- they are infiltrative, not circumscribed and anchored to underlying soft tissues.
Squamous cell carcinoma (nose in a cat, eye in a cow, eye in horses or genitalia). Most common malignant neoplasm of the skin in cats and second most common in dogs. Chronic UV radiation is the most important carcinogenic trigger.
Sebaceous gland tumour and adenomas are very common benign tumours in senile dogs. Commonly arise in the eyelids (from Meibomian glands).
Where do the Pancreaticoduodenal, Hepatic, and Gastric LNs drain to? Where does the Jejunal drain to?
Coeliac for the Pancreaticoduodenal, Hepatic, Gastric
Jejunal LNs are the largest LNs in the abdomen- they are located within the jejunal mesentery and they drain the jejunum, ileum, and pancreas
Why would you give a 12 yo dog with DJD NSAID meloxicam?
To decrease sensitization of nociceptors
What glands secrete via holocrine? What glands secrete via cytocrine?
Holocrine- sebaceous
Cytocrine- melanocytes
What is acantholysis?
Disruption of the intercellular junction between keratinocytes of teh epidermis
Does hypocalcaemia warrant a bone marrow eval?
No
What does hyperalbuminaemia often mean?
Dehydration
What is the production time for mature neutrophils from a myeloblast?
4-6 days
What does mature neutrophilia mean?
Release from storage pool
What would chronic GC exposure do to neutrophils?
Hypersegmented
What is aspirin? How does the first pass effect impact aspirin?
An IRREVERSIBLE cyclo-oxygenase inhibitor (COX with a few day life span)
* reduced thromboxane synthesis
* decreased platelet aggregation
* decreased vasoconstriction
** Aspirin has a low bioavailability- almost 90% of aspirin is absorbed/ destroyed in the first pass of the liver- so very little gets out into the systemic circulation. Excellent thing though because it is present in the portal vein where the platelets are exposed- cyclo-oxygenase inactivated– so vasodilatory and platelet inhibitory activity of PGI2 produced in the endothelium in the systemic circulation are not EXPOSED TO THE ASPIRIN.
Disease Modifying Osteoarthritis Drugs (DMODs)
* supplement glycoproteins in articular cartilage to repair it in order to repair the joint
* retard degradation of articular cartilage and boost chrondrocyte metabolism
* Anticoagulant activity therefore improved joint circulation (microthrombi are common in arthritis)
* Reduced pain
* Stimulates production of hyaluronan in synovial fluid– hyaluronan: limits leukocyte migration, inhibits release of inflammatory mediators, scavenges reactive oxygen radicals
** claim to act this way– no evidence in clinical trials to suggest that these drugs do anything
** increased risk of bleeding– especially if there is an undiagnosed splenic tumour for example
Why is gamma carboxyglutamate so important?
3 proteins bind to Calcium which binds to gamma carboxyglutamate DUE TO A CHANGE IN Glutamate residue PUT A CARBOXYL group on it…. the carboxyl group binds Calcium!!! Production of the gamma carboxyglutamate involves VITAMIN K!!!
Those three proteins are: Xa, Va, and II (which combine and form THROMBIN!)
What is involved in the production of gamma carboxyglutamate?
Vitamin K
What causes Warfarin and Dicoumarol to compete with vitamin K? Why does this stop coagulation??
Similar structures (Dicoumarol- sweet hay– also main component of rat bait)
** This stops coagulation because it means you are not producing the GLA domain which binds the thrombin (or the 3 factors that “make” thrombin). Which means that you cannot bind to CALCIUM. Calcium will still be there (because it is still bound to the PF on platelet surface). BUT IF YOU DON’T GET GLA– THROMBIN CANNOT BIND TO THE SITE OF INJURY. THEREFORE NO COAGULATION CASCADE. You just rely on platelets being there… which is not strong enough
Why is thrombin so important?
Pro-coagulant and anti-coagulant
- Cleaves fibrinogen to fibrin which crosslinks (fibrinogen will not crosslink until thrombin cleaves!!)
- Activates Factor XIII
- Can activate ITSELF– Thrombin can activate prothrombin (cyclic- the more factor IIa (thrombin) produced– the more thrombin is cleaved and the more IIa is produced)– AMPLIFIES THE SYSTEM
- Enhances platelet aggregation
- Induces secretion of platelet factor XIII- the negatively charged phospholipids which is on the platelets.. just having thrombin around there induces the realease of more negatively charged phospholipids
** has some negative effects as well: anti-coagulant activities:
* activates protein C– which inactivates clotting factors VIIIa and Va
The initial soft plug has what kind of bonding? What does fibrin do?
Initial soft plug is hydrogen bonding, covalent cross linking of fibrin adds strength…. Mediated by transglutaminase (factor XIIIa)– mediated by thrombin itself.
** all about strengthening the clot
What are the two big proteins (factors) involved in the balance between clot formation and clot dissolution?
Thrombin and Plasmin….
Too little thrombin– too much plasmin = haemorrhage
What are the keys to limiting clot formation to the site of injury?
We need rapid formation, but confined to the site of injury
* Labile clotting factors
- diluted by blood flow
- actions of the liver can remove clotting factors (when the injury signals stop)
- we have a number of anti-coagulant mechanisms
– anti-thrombin III: inactivates thrombin by forming a complex with it IRREVERSIBLY BOUND– reinforced by HEPARIN
– thrombomodulin and Calcium act as co-factors for thrombin’s activation of protein C–> protein C and protein S inactivates factors Va and VIIIa through proteolytic cleavage
What is thrombomodulin?
BInds thrombin– activates protein C– which inactivates factor Va and factor VIIIa through proteolytic cleavage.
To activate these factors… thrombomodulin binds thrombin and makes it INACTIVE!!!
** this happens in HEALTHY ENDOTHELIAL CELLS ON EITHER SIDE OF THE INJURY– IT IS ON THE ENDOTHELIAL CELL SURFACE.
(another way of not allowing clots to form to healthy endothelium, like ADP)
Role of endothelial cells in anti-clotting
Fibrinolysis
* plasmin degrades fibrin into peptides– dissolving the blood clot
* because plasminogen is activated only when bound to fibrin, fibrin promotes its own breakdown
* Streptokinase and tissue plasminogen activator (cleaves plasminogen–> plasmin) are used clinically to promote fibrinolysis
Why is the coagulation cascade important?
Each step involves activation of an enzyme = AMPLIFICATION (it also allows control)
** Living on a knife edge between adequate coagulation and not having enough
What stimulates extrinsic pathway?
Thromboplastin- also called tissue factor caused by trauma to tissue
What starts the intrinsic pathway?
Will happen with exposed collaged or other negative charges– it is not dependent on tissue trauma– put blood in a test tube and it will clot
Which pathway is faster? The instrinsic or extrinsic?
The extrinsic pathway is faster– the intrinsic pathway has many more steps
What are the two controls of blood coagulation?
Antithrombin III (direct enzyme inhibitor) and plasmin (fibrinolysis- breaks down the clots once it has formed)
What is Virchow’s Triad?
Hypercoagulability, Blood stasis, and vessel damage (exposure of sub endothelial collagen= attraction and binding of platelets and starts the coag. cascade)
** If you put them all together then you are tipping the balance and increasing the risk for inappropriate clot formation
What do drugs affect?
* coagulation, platelets (adhesion and activation), fibrinolysis
What are the steps of coagulation? What is the picture you are going to draw on the exam to show how things bind?
when would you use fibrinolysis?
Saddle thrombus in the heart
Drugs that affect fibrin formation- are?
Procoagulant drugs- vitamin K
* Anti-coagulant drugs: injectible- heparin, warfarin (oral)- drug or rodenticide
Why does heparin have to be given by IV?
* Such a large compound, it would be digested in the gut and would not be absorbed if given orally
* increases activity of antithrombin
* used in acute settings
What are coumarin derivatives- e.g. warfarin? What is their mechanism of action?
Compete with vitamin K– therefore inhibit carboxylation of clotting factors… cannot form thrombin
What is a major difference between warfarin and heparin? And why is this important clinically?
Warfarin only active in vivo. Unlike heparin in a test tube. This is because it doesn’t affect already active factors, only affects the activation of factors. THIS IS IMPORTANT BECAUSE DOSE AND WHEN IT IS ADMINISTERED– DEPENDS ON THE HALFLIFE OF THE CLOTTING FACTORS. Clinically, rodenticide poisoning, you won’t see the signs for up to a week. e.g. holiday house rodenticide and a week later it presents bleeding because it took that length of time for the attrition of the clotting factors not to be replaced. Some clotting factors have SHORTER HALF LIVES THEN OTHERS!
What are some side effects of warfarin? But what is something awesome about warfarin?
Haemorrhage!!! Bleeding form mucosal surfaces
** Reversal– vitamin K (oral)– you can help calcium win the competition and therefore GLA– and therefore THROMBIN!
What is scary about second generation rodenticides?
First gen- you would need multi feeds– lower potency
Second generation- single feed poisons… Higher efficacy and longer half life– effects more catastrophic
How do you monitor the affect of thrombin?
Prothrombin time monitoring. Effectively the EXTRINSIC PATHWAY. It is the time for clot formation of plasma after addition of Calcium and tissue factor (because in this case tissue factor is given in the drug… not from trauma)
** Warfarin is LABILE
- needs to be constantly monitored
- because of fluctuations in diet of vitamin K for example
- *****99% of the drug is plasma bound– the active part is the UNBOUND… change in liver function, for example, if there is a 30% drop in plasma protein levels–> hypoproteinaemia– then you’d have a lot more UNBOUND WARFARIN….. So warfarin availabilty FLUCTUATES DRASTICALLY.
Drug interactions with Warfarin
* Alcohol
* aspirin
* NSAIDs (competition for plasma protein binding)
How do new anti-coagulants work? What is a problem with the new anti-coagulants?
They are direct factor inhibitors, which is good because they are not metabolism dependent. The problem is there is no anti-dote.
How does Clopidogrel work?
ADP receptor antagonist– prevents platelets from activating each other.
How does aspirin work?
Irreversible Cyclo-oxygenase inhibitors– therefore preventing production and release of thromboxane
** Platelets exposed to aspirin in the portal vein… but systemic endothelial cells will not be. So it acts on the platelets but does not cause systemic effects on endothelial cells who need ADP to prevent clot formation on healthy endothelium near sites of endothelial injury! PRESERVES endothelial production of PGI2 as well which is necessary for VASODILATION
** 90% is cleared by first pass effect by the liver…
Fibrinolysis as a drug- what are the two? How do they work?
Induce fibrinolysis especially with a saddle thrombus.
Used Streptokinase or Alteplase.
* Streptokinase- activates plasminogen to plasmin– which digests the fibrin– problem with it microbial in origin and large molecule– highly antigenic– if you use a second time– the animal would have produced antibodies and you can expect an ANAPHYLACTIC REACTION
* Alteplase- clot selective but VERY EXPENSIVE!!!
What is haemorrhage diapedesis?
Microscopic form of haemorrhage
Haematuria
Coughing blood
Vomiting fresh blood
Stool with digested blood
Diarrhoea with blood
Stool with frank blood (polyp, for example)
Bleeding into anterior chamber of the eye
Haemoptysis
Haematemesis
Melena
Dysentry
Haematochezia
Hyphaema
Petechiae- tiny, pinpoint foci of haemorrhage 1-2 mm in diameter– typically found in skin and on mucosal and serosal membranes
NON- PALPABLE
2 terms, what’s the difference?
> 3 mm purpura
Ecchymoses- larger foci of haemorrhage- 2-3 cm in diameter; usually blotchy and of irregular shape
NON- PALPABLE
Paintbrush haemorrhages (suffuse haemorrhage)
NON-PALPABLE
Haematoma PALPABLE haemorrhage
Haematoma PALPABLE haemorrhage
* epidural haematoma could cause death
How do you age haemorrhage? What do you look for? Why is this important?
The gross colour of haemorrhage depends on whether the blood was arterial or venous, the volume of extravasated blood and the time elapsed since haemorrhage occurred.
* erythrophagocytosis by macrophages commences within a few hours of onset of haemorrhage
* ACUTE PHASE: ** few hours** red-blue due to poorly oxygenated haemoglobin
* Subacute phase: ** day 1 ish** blue-green: due to the formation within macrophages of BILIVERDIN AND BILIRUBIN (derived from the porphyrin component of haemoglobin)
* Chronic phase: **2-3 days…** gold-brown– due to the formation of HAEMOSIDERIN (iron component of haemoglobin) and haematoidin +/- lipofuscin pigments
* USE THIS KNOWLEDGE TO AGE HOW LONG HAEMORRHAGE HAS BEEN PRESENT– look for pigments in macrophages CYTOLOGICALLY AND HISTOLOGICALLY
(bruise is only a haematoma if it is palpable)
If you have a big haematoma, what can happen?
Haematoma if sufficiently big–> macrophages come in and gobble up extravasated RBCs, platelets, Fibrin, etc.–> GRANULATION TISSUE will fill the gap where the blood was and lays down COLLAGEN that can remain persistently
Where are tiny bleeds a massive problem?
* Cerebrovascular accidents- bleeding inside the skull–> raising intracranial pressure
* bleeding into the cardiac sac–> cardiac tamponade– right ventricle can’t fill–> right sided CHF and death
* haemorrhage into the retina can dissect the retina off and cause blindness
Why is internal bleeding better than external? What are some examples of external bleeding that are internal?
Recycle iron, plasma proteins, RBCs– gradually brings PCV back up… Especially if persistent or repetitive bleeds
** external bleeding– bleeding from GI tract is external, respiratory tract, bleeding from the bladder
How much blood can we safely remove from nearly any animal for blood testing?
What happens if you take more than 20%
10% of BLOOD VOLUME- 1% of BODY WEIGHT
(in a healthy animal, you could take 20% of blood volume, but you never know if they are truly healthy)…
Beyond 20%– hypovolaemic– shock.
Beyond 50%– fatal unless rapid transfusion
Causes of haemorrhage
Almost always trauma (even if the owner doesn’t know)
* Aspergillosis (necrotising, ulcerative process)
* Anything intesively acute inflammation will have haemorrhage
* Systemic infections
* Ulcers
* Bleeding tumours– haemangiosarcoma, very vascular tumour- commonly bleeds
* Spontaneous ruptures of spleen (well vascularized organ)
* Parasites (hookworm, fleas, etc.)
* Bleeding into GI tract
** IF YOU RULE THESE OUT then…. perhaps a bleeding disorder??
Disorders of Haemostasis
Primary Haemostasis- formation of platelet plug
Secondary Haemostasis- defects in the generation of fibrin or (rarely) the stability of fibrin formed via coagulation cascade
** DIC HAMMERS BOTH
Congenital- Haemophilia A- Factor VIII activity
Secondary haemostasis because you are competing with vitamin K– which when the rat bait wins (coumadin)– no GLA– therefore no binding of 3 factors that produce thrombin– therefore no clot.
How does our body keep from exsanguinating?
What happens if you have a primary haemostasis disorder?
Cannot build primary platelet plug but your body will still undergo the clotting cascade. Only bleed for a very short amount of time. SMALL VOLUME BLEED.
** petechiae, purpura, paintbrush, bruises (all over), epistaxis, haematochezia (poo), haematuria, haemoptysis (BUT ALL SMALL)
** platelets are too low to do all the normal little tiny holes that are happening normally
haematomas UNCOMMON– but can be occasionally seen– most of the time these are big volume bleeds and typical of secondary haemostasis
What would happen if you have a secondary haemostasis disorder? Sequelae?
* delayed bleeding- platelet plug would form- but it’s not strong enough/ unstable–> not generating fibrin for longer lasting seal–> UNPREDICTABLE for when you stop bleeding could lose 20% of circulating blood volume–> HYPOVOLAEMIC SHOCK
** you may be able to clot but it is how QUICKLY it will occur…
Sequelae:
* deep bleeds into cavities or muscles or joints- haematomas, (excessive haemorrhage for the amount of trauma received), VOLUME helps localize bleed
Haematoma more likely to be secondary haemostasis if it is a bleeding disorder
Can be either primary or secondary haemostasis disorder (if not from trauma or another cause like aspergillosis, ulceration, etc.)
DIC– so if you have both small volume bleeds, and big volume bleeds
Four major mechanisms when an animal presents with petechiae, purpura, etc.?
* Thrombocytopenia (most common)
* Thrombocytopathies (rare congenital disorders, but acquired platelet dysfunction systemic lupus erythematosus, deficiency or decreased functional activity of vWF)
* von Willebrand’s disease
* blood vessel disorders
Reasons for thrombocytopaenia
* decreased platelet production (bone marrow problem?)
* increased platelet destruction (immune mediated, bacteria and viruses can also destroy platelets like Anaplasma platys)
*consumption of platelets (DIC, heart worm)
*sequestration of platelets (in the spleen, splenomegaly or hepatomegaly- more platelets in capillaries- sinusoids then out circulating)
*haemorrhage (losing leukocytes and platelets, RBCs as well– is it caused by haemorrhage or contributing to haemorrhage?
2 possible reasons for decreased platelet production
neoplasia (FeLV- retroviral infection), parvo virus target stem cells, toxins (affect bone marrow)
** MARROW SAMPLE
Systemic Lupus Erythematosus
* Autoimmune disease immune response to self- Antigens
* Dogs, cats, horses
* target- DNA, histones, nucleolar antigens
** Ab develop against MULTIPLE antigens in the body**
EVERY CELL IN THE BODY AFFECTED but skin, kidney, and joints are where the immune complexes are deposited
TYPE III HS REACTION** immune complex circulating in blood causing damage
What are the three tissues mostly affected with autoimmune diseases?
Kidney, skin, and joints
because antibodies usually have a preference for these sites
Why do we need vWF?
Where is it?
Adhere platelets to collagen in high velocity, high pressure vessels to build primary haemostatic plug
In capillaries with no significant shear forces and velocity of blood flow– platelets can hang on in other ways– not just vWF… but anything bigger with higher pressure flow– you NEED vWF
** some circulating in blood, fibroblasts naturally express it, endothelial cells store vWF, in some species (humans, cats)– when platelets get activated they release vWF– there are large, medium size, and small repeating units– the large ones are the most active…. type 1 have all and all have reduced acitivity
Type I vWF disease (autosomal recessive- all 3 types are- dobermans 60% are carriers)
**if activity gets below 20% then they become at risk of spontaneous bleeding or in response to minor trauma
Type 3 vWF disease
* Almost negligible vWF
* trauma in homozygotes–> severe haemorrhage
** can have haematomas!! (even though it is a primary haemostatic disorder)
How old would vWF disease become apparent?
Type 2 or Type 3– potentially very young– can cause abortions, litters of puppies bleeding out from umbilical cord cut first day
But if type 1– can manifest during rough and tumbles or when their first teeth are erupting
How would vWF present?
* Epistaxis, bleeding from any mucosal surface, GI haemorrhage, blood in urine, paint brush haemorrhages or Ecchymosis over oral mucosa- common presentation
** haematomas– type 2 and 3 easy to explain- bleed longer and bigger volume– but also vWF goes with factor VIII AS A COMPLEX– so vWF helps to stabilize and protect factor VIII… so if you’re low, you may not be protecting VIII as much!!
What do you consider in order in primary haemostasis?
- Thrombocytopaenia- bone marrow, IMHA, etc.
- vWF disease
- Thrombocytopathies
- Blood vessel dissorders- diseases where something is hammering multiple small vessels around the body- Rocky Mountain Spotted Fever– nothing wrong with platelet function but you’re using them up– lots of small little bleeds
Why does scurvy make you bleed?
Vitamin C deficiency because it is has to do with strengthening and cross linking of collagen- so you are weakening blood vessel walls and so they are leaking.
Mostly guinea pigs
How does Cushing’s potentially cause a primary bleeding disorder?
Hyperadrenocorticism or poorly controlled diabetes mellitus– skin fragility and blood vessel fragility – collagen disorder— small bleeds
What happens with the coagulation cascade after you cut yourself?
The short route (extrinsic) gets activated first with tissue factor 3 release and it is not until you have enough thrombin– then extrinsic pathway gets shut down (via inhibitors)– then thrombin acts as an AMPLIFIER– activating other pro-enzymes and if you have to maintain fibrin production because it is a big wound you do it via the INTRINSIC PATHWAY
** they are both being switch on simultaneously– but the extrinsic is switched off– so key is INTRINSIC KEEPS GOING AND MAINTAINS FIBRIN PRODUCTION
What are the disorders of secondary haemostasis?
* inherited coagulation factor deficiencies
* vitamin K antagonism (most common)
* vitamin K deficiency
* severe acute or chronic liver
* excessive fibrinolysis or fibrinogenolysis
Haemophilia A
Most common- genes coding are very prone to spontaneous mutation
** german shepherds and vislas
* Severe bleeding potential
* often do not survive to puberty in order to transmit gene
Haemophilia B
Sex linked- X linked recessive haemophilia– Queen Victoria– transmitted gene
Why is it possible to be deficient in certain clotting factors and okay?
Factor 10 deficiency for example with cocker spaniel.
A lot of amplification loops and redundcies.
Factor 7 in Australia in these breeds– never bleed or just some bruising– not really a clinical problem.
Haemophilia C
Inherited deficiency of factor XI. Most minor traumas do not result in major bleeds because of REDUNDANCIES– once you’ve activated enough thrombin– thrombin can then activate steps upstairs.
** but if hit by a car with multiple fractures, used up all factor XI reserves– now in surgery to fix liver– it now can no longer maintain via redundancies and can now get a major bleed
Haemophilia B (factor IX deficiency)
* Devon Rex
* Test results make you think rat bait poisoning
* Deficiency in enzyme from the liver in the last step of the vitamin K dependent clotting factors II, VII, IX, and X
* Autosomal recessive inheritence of this enzyme…
SEVERE BLEEDING PROBLEM
How do you become deficient in vitamin K?
Why is this uncommon?
What is normally the vitamin K problem?
Because it is a fat soluble vitamin, you need to be able to break down fat to absorb it.
* Pancreatic insufficiency, cholestasis but has to be complete extra-hepatic bile duct obstruction, severe small intestinal villous atrophy (lost absorptive surface)- you’d have other clinical signs
* uncommon because GI bugs can make vitamin K
* ANTAGONISM is much more common– RAT BAIT OR
If you are deficient in factors II, VII, IX, and X, what happens OR if one or both reductase enzymes (gamma glutamyl carboxylase and hydroguinone), what happens?
Vitamin K dependent factors and enzymes key in the coagulation cascade.
Vitamin K is required by gamma glutamyl carboxylase to add the carboxyl group of factors II, VII, IX, and X in order to render them functional. In order for vitamin K to be activated it has 2 reductase enzymes that aid.
** if one or both reductase enzymes are antagonised OR if there is a vitamin K deficiency, the liver produces proteins that are antigenically similar to factors II, VII, IX, and X but they are NOT FUNCTIONAL in the COAGULATION CASCADE– these non-functional proteins are called “proteins induced by vitamin K antagonism or absence” PIVKA
What are PIVKA?
** if one or both reductase enzymes are antagonised OR if there is a vitamin K deficiency, the liver produces proteins that are antigenically similar to factors II, VII, IX, and X but they are NOT FUNCTIONAL in the COAGULATION CASCADE– these non-functional proteins are called “proteins induced by vitamin K antagonism or absence” PIVKA
Giving vitamin K can do what?
Overrides the antagonism of warfarin or rat bait
Why is there a delay in bleeding?
The animal needs to use up factors II, VII, IX, and X before you see any bleeds- but when they bleed- they will be big volume bleeds
Problem with second generation rodenticide poisonings?
Secondary poisoning of cats eating mice
Cows eating mouldy hay
What are other differentials for big volume bleeds when you suspect a secondary haemostatic disorder?
Liver disease- because livers are the major source of clotting factors (endothelial cells and macrophages can make factor VIII)
* if you have severe liver disease– severe necrotising acute liver damage (dog got into poison mushrooms), advanced cirrhotic liver
** you have to remove 70% of a liver in order to see loss of clotting factors produced
** most animals do not spontaneously bleed– but surgery YES they will– So even a LIVER BIOPSY!!! So always run a clotting test– and have transfusion blood available in case the test was not sensitive enough
** PARADOXICALLY THEY COULD ALSO BE AT RISK OF THROMBOSIS
What is a granulocytic hypoplasia leukogram?
Caused by a bone marrow production problem
* persistent neutropenia with no left shift (> 5 days)
- cyclic neutropenia of Grey collies
- immune mediated neutropenia
- drug toxicity
- myelodysplastic syndrome
What is the main characteristic of a stress leukogram?
* Lymphopenia (NO LEFT SHIFT AND NO TOXIC CHANGE)
What are the main components of a severe acute inflammation leukogram?
* Neutropenic– slightly overwhelmed– no degenerative left shift necessarily, but the marrow is not coping very well
* Can see neutrophilia as well- marked
Causes: Pneumonia, Pyelonephritis
What are the keys to a mild acute inflammation leukogram?
* Band count is not that far out of the reference range, mild neutrophil count (thinking about the species too)
e.g. mild infection- wound
What are the keys to a chronic active inflammation leukogram?
* no left shifting
* monocytosis– has to be chronic– but neutrophil count can be high and therefore active
Chronic inflammation can basically balance out– but all high
Possible causes: severe pyoderma, necrotic neoplasm, chronic hepatitis
What are the cells of myelopoeisis?
* Granulocytes: neutrophils, eosinophils, basophils
AND
* Monocytes
When you say “Leukopoeisis” you are including LYMPHOPOIESIS INTO THAT!!!
What regulates Myelopoiesis?
G-CSF, GM- CSF– increase in cell proliferation, differentation, and function
** Also cell line specific cytokines: IL-6 (neutrophils), IL-5 (eosinophils), IL-3 (basophils)
How long total does it take for a neutrophil to mature?
What percentage of neutrophils are in the mitotic pool? Maturation pool?
4-6 days.
20% of neutrophils are in the mitotic pool
80% of neutrophils are in the maturation pool
What stimulates release from the marrow of neutrophils?
G-CSF, GM-CSF, C5a, TNF alpha, TNF bravo (inflammatory demand)
How big is the supply of neutrophils in the maturation and storage pool?
What are the functions of neutrophils?
How long do neutrophils stay in each pool? Including circulation and tissues?
5 days supply
Function of neutrophils: phagocytic and microbicidal in tissue, primarily respond to bacterial infections, role in tissue necrosis, fungal infections, chemotaxis to PGs etc.
BM: 2-3 days
Maturation: 2-3 days (mature segmented ready for release)– can be shortened in a powerful cytokine storm
Circulation: 10 hours
Tissue (marginal pool): 24- 48 (then they die)
What are the main four stages of neutrophil maturation?
How soon can the marrow increase neutrophil production in response to an infection? How long do you wait until you expect a bone marrow problem (
If a cow shows hyperfibrinogenaemia, what might you think?
Possibly acute inflammation
Species relative differences with neutrophil count in inflammation
What might you see with a physiologic leukogram?
* neutrophilia, lymphocytosis, NO LEFT SHIFT OR TOXIC CHANGE +/- monocytosis
* young animal or a pig
How soon should we repeat the CBC to monitor response to antibiotic therapy for this patient?
12 hours!
Is the marrow responding at all? Kicking out bands. The concern is sepsis.
Where do leukocytes go when they die?
Phagocytosis by macrophages
spleen, liver, bone marrow, tissue
What is the platelet lifespan in the blood? Where do many platelets live? Who regulates platelets? How many days does it take for them to mature?
5-9 days
30-40% sequestered in the spleen
Thrombopoeitin from the liver, kidney, and marrow stromal cells regulateds platelets
Maturation: 2-10 days
What is the maturation time of a neutrophil? Monocyte? Erythrocyte? Platelet?
How long do neutrophils circulate? How long do monocytes circulate? How long do erythrocytes circulate? Platelets?
If an animal develops neutropenia due to transient chemotherapy marrow toxicity, how long before we hope to see neutrophil numbers rise in the blood?
4-6 days
What is the delay before we see a regenerative response in the blood in dogs after RBC loss?
3-5 days
What are some mechanisms of physiologic leukocytosis?
* Neutrophilia- shift marginating to circulating pool (increased blood pressure and heart rate)
* Lymphocytosis and monocytosis- same as neutrophils
What would you see with acute myeloid leukaemia?
Acute= immature/ blastic cells
Lymphocytosis
What severe illness is similar to a chronic myeloid leukogram, why?
Chronic myeloid leukaemia
Chronic= mature cells- CML is difficult to distinguish from “leukaemoid” or severe inflammatory leukogram
What does this leukogram reflect?
Recovery from severe acute inflammation
What does this leukogram reflect?
Bone marrow disease and severe acute inflammation
Excessive lysis of fibrin, which means excessive plasminogen/ plasmin- when is this seen?
DIC, venomous snakes, heat stroke (excessive production of plasminogen activators from endothelium)
(as fast as fibrin is being generated, it is being dissolved)
DIC
Thrombotic disease– MICROSCOPIC– damaging because there are many of them– in lung capillaries and renal glomeruli for example
** Always a secondary disease
DIC
What puts you at risk for DIC?
FIP, heat stroke, bacteraemia, Infectious Canine Hepatitis, heart worm, Babesia, tumours, acute toxic or necrotizing aphlotoxin, IMHA, GDV, necrotizing pneumonia, big areas of ischaemic necrosis, pyometra, snake envenomation
** GENERALLY they all have in common– LOTS OF TISSUE NECROSIS, VASCULAR ENDOTHELIAL DAMAGE
** minority will go into DIC, but you have to have you “antennae” up in order to monitor patients at risk closely so you can intervene early enough
Mechanisms of DIC
Tissue factor III (protease) normally in a cell in the tissues–> release into circulation–> procoagulant–> therefore blood is hypercoagulable
* at risk for DIC
** Some tumours– white cell series– if they are releasing their granules, they act as proteases–> adding procoagulants to the blood stream= DIC risk
* some carcinomas releasing blebs of mucus (short cut to coagulation cascade) = DIC risk
* snake venoms- proteases (pro-coagulant)= DIC risk
* Haemangiosarcomas (vascular endothelial cell tumours)– express excess tissue factor on their surface= DIC risk
* Pancreatic necrosis- activation of trypsin and other enzymes- naturally proteases in circulation meant to mop that up– if you then had trypsin activated in circulation–> could kick start clotting cascade– Factor X for example
At risk of DIC
How are endothelial cells like Dr. Jekkyl and Mr. Hyde?
Anti-coagulant activites in health
But if you upset them- they can go to pro-coagulant state
* any damaged endothelial cell become more pro-coagulant state– SUB ENDOTHELIAL COLLAGEN EXPOSED, Releasing TISSUE FACTOR 3
** e.g. Rocky Mountain Spotted Fever
What is a general rule about the time frame of DIC if it does occur?
Unpredictable how long it will take- weeks to months OR minute or hours. Fulminant form.
What is Phase 2 of DIC? Where does this occur?
Clinical DIC now
NOW there are no more checks and balances (consumption of antithrombin, Protein C, Protein S)– you are now OVER GENERATING FIBRIN. More than enough to plug the holes– you are making PATHOLOGICAL THROMBI
** it is superimposed on the PRIMARY DISEASE PROCESS
* may be compounded by the inhibition of fibrinolysis– if you are generating lots of thrombin- forming the microthrombi- thrombin causes endothelial cells to produce plasminogen converter inhibitors THEREFORE FIBRIN STICKS AROUND LONGER THAN IT SHOULD. (just a contributor)
**Where does this occur?? Where is the primary disease process?? Haemangiosarcoma– maybe just in the spleen
What phase of DIC?
Phase 2
Why does this happen? What is it called?
Schistocytes in DIC- fragmented RBCs
* RBCs are still trying to move through blood vessels even though they are blocked
* Spleen or liver gobbles them up
* Some can lyse if they are really badly damaged
** Could have an intravascular and extravascular haemolytic component
“fragmentation anaemia” or “haemolytic anaemia”
Why shock in DIC?
thousands of microthrombi therefore less venous return therefore less cardiac output… especially if it is happening in the myocardium
What is true of clotting factors that makes DIC worse?
When you activate clotting factors they are usually pro-inflammatory– even PLASMIN is PRO-INFLAMMATORY.Blood is bringing in neutrophils– which are releasing proteases. So we are switching on inflammatory cascades which makes things worse.
What else are switching on in DIC?
Kinins–> making everywhere in the body hypoxic
This happens during Stage 2
** start to see why many animals die in this stage
Phase 3
Some will survive long enough–> in making all the clots you have dropped platelets and coagulation factors so low- they are all consumed
** if you do enter this phase, you will have little bleeds, but you are also running out of clotting factors, so you will have big volume bleeds as well– so if you ever see those 2 together– DEATH IS COMING
** and fibrinolysis is enhanced (activation of factor XII, XI, kalikrein, kininogens– they can cleave plasminogen to plasmin giving you breakdown of fibrin– you made controlled amounts in phase 1, phase 2 out of control fibrin, at this point you have so many of these precursor molecules activated– you’ve switched on plasmin– now munching fibrin BUT the PRIMARY DISEASE is still there so you still need to plug holes
** At this point everything is favoring haemorrhage
What are the three parts called?
What is important in the third?
What does it mean if the cells look hazy?
What are you looking for with leukocytes?
What are you looking for with erythrocytes?
What would a blue background suggest?
Feathered edge- check for platelet clumping- if not clumping, you can count within the smear
Hazy cells- lipaemia
Leukocytes- toxic change or left shifting or atypical cells
Erythrocytes- rouleaux, agglutination, density, polychromasia, anisocytosis, abnormal erythrocyte shapes, haemotropic Mycoplasma etc.
Blue background= HYPERPROTEINAEMIA
Why can’t you store open system blood?
What can you make from whole blood?
Where is plasma stored? Whole blood?
Good place for bacteria to grow- you have to give immediately but this is usually not done anyway
Plasma is frozen
Whole blood- refridgerator (otherwise they would die in the freezer)
** never heat it, even if you’re in a hurry
When to transfuse?
* Depends on all factors that affect oxygen delivery (Hb, SaO2, CO)
* Euvolaemia vs. hypovolaemia
* Acute vs. chronic anaemia (sooner with acute)
* not just an isolated PCV
* If Haematocrit (PCV- same thing? used these terms interchangeably) is below 30, you always have to transfuse
Macule- circumscribed flat areas of colour change vs. papule which is raised, red solid mass < 1 cm +/- crusting
What is a rash?
Collection of erythematous macules, papules, and pustules
What is a comedone?
Dilated hair follicle with sebaceous material but no hair shaft
Wound strength at week 1, 3, and 3 months?
Is the resultant scar weaker or stronger?
1 week- 3%
3 weeks- 30%
3 months- 80%
Process is ongoing months or years
** resultant scar is weaker: typically not more than 80% strength of the native tissues…
** cats only 50% as strong as dog wounds at day 7
What are some examples of skin pattern diagnosis for the epidermis? Follicle? And panniculus?
Acanthosis (epidermal hyperplasia)
* always present in chronic skin diseases of all causes
* epidermis (epithelium) and follicular infundibular keratinocytes
Comedone
What is this? What is the other kind of oedema?
Ballooning degeneration (intracellular oedema)
Spongiosis (intercellular oedema)
Acantholysis- Loss of cohesiveness of epithelial cells in the epidermis
Vesicles- fluid filled blisters in the superficial epidermis
How do vesicles form?
Spongiosis, ballooning degeneration, or acantholysis
e.g. FMD: cytopathic viral effect–> ballooning degeneration of epithelial cells–> rupture of epithelial cells and loss of cohesiveness–> vesicle
How do crusts evolve?
Dermatophylosis- hair is matted by a crust of dried exudate, str corneum, and bacteria.
How does the adnexa respond to injury? What is adnexa again?
Atrophy (endocrine dermatoses), dysplasia, inflammation
Adnexa- glands and hair follicles
Dermatophytosis- folliculitis- e.g. Microsporum sp.
Recall: how shallow does the dermis run? Where is the epidermis?
What are the major layers of the epidermis?
Str corneum
str granulosum
str spinosum- polygonal cells become squamous toward the surface, DESMOSOME JUNCTIONS (tonofilaments are anchored to the inner surfaces of the desmosomes, contributes to this layers cohesion and the resistance to abrasion)
str basale- cuboidal to columnar cells
What’s going on as you go deeper into the skin?
Where do melanocytes live? how do they secrete?
Str basale- they secrete in a cytokrine manner (unlike sebaceous glands- holocrine)
What are langerhans cells? Where do they live?
What are merkel cells?
DCs of the skin- most prominent in the str spinosum
Merkel cells- sensory, associated with tactile stimulation and nerve cells
Name the layers and what are they?
Where is the pinky layer located?
Epidermal papilla
Dermal pegs
Finger prints
Str Lucidum is only located in some non-haired structures such as digital pads, teats, and planum nasale
What are the two layers of the dermis?
What’s going on in the dermis?
* cells, intercellular substances, appendages, VASCULAR PLEXUSES- shunting of blood through different levels of the dermis, response to changes in env. temp, fluctuations in circulating blood volume
What could this be on a horse?
- Tubular horn
- Intertubular horn
** chestnut or ergot (epidermal thickenings)– tubular horns and intertubular horns
- Tubular horn
- Intertubular horn
- str. corneum
- str granulosum
What are horns made up of?
** horns consist of a hard keratinized epidermis, a dermis, and a hypodermis
* epidermis has a thick hard stratum corneum: tubular horns and intertubular horns
- horn tubules
- dermal papilla
* cornual process on the inside– horn sheath on the outside
* keratinized epidermis–> papillated dermis–> thin hypodermis–> periosteum of the bone
* epikeras: at the root of the horn, similar to the epidermis of the periople of the hoof
What are claws made up of?
What is number 17? 13? 9? 11?
Hard keratin produced by the epidermis covering the ungual process of the third phalanx
- wall
- sole
- limiting furrow
- middle phalanx
What is the cuticle made up of? And the cortex?
Cuticle- overlapping flat keratinised cells- free edges upwards
cortex- contain melanin acquired from melanocytes, fibrillar keratin in an amorphous matrix
Medulla- a solid column of cuboidal cells to a system of air filled spaces
What is a protofibril made up of? And what are the two main amino acids dealing with hair health?
Two alpha helical proteins
Cysteine & glycine/ tyrosine
What are keratin associated proteins? What do intermediate filaments make up?
Constitute the matrix of the keratin composite of wool- up to 100 different proteins… The dense aggregates within bundles of intermediate filaments are KAP proteins (intermediate filaments make up macrofibrils)
Also, what is the dermal papilla?
The region of connective tissue
What are hair matrix cells?
The dark part of the picture shows the germinal matrix.
Comparable to the str basale cells of the regular epidermis, give rise to the cells that keratinize to FORM THE HAIR, differ from keratinocytes of the surface epidermis, produce a HARD KERATIN with low lipid and high sulfur.
What is a? s? and f?
a = arrector pili muscles
s= sebaceous glands
f= hair follicles
Dermal papilla
Sebaceous glands- sebum- waterproofing (arrector pili assist in emptying near the hair shaft)
Tubular gland
Usually in primary hair follicles- merocrine or aprocrine- location and species dependent
Cytology vs. histology
How do you process histology samples?
Fixation
Trimming, Histocassettes (hold and protect tissue while it undergoes processing, used for tissue ID), then tissue processing: dehydration (via ethanol solutions of increasing concentrations until 100% water free- the series avoids excessive distortion of the tissue), clearing (xylene replaces ethanol because ethanol and wax do not mix– then xylene will be replaced by molten paraffin wax), infiltration
*microtome sectioning, put the section on the slide, and then stain
What is this?
What is this?
What are the two main lymphatic drainage pathways in the dog?
Tracheal Duct and the Thoracic duct
What sits above the Mesenteric lymph nodes?
Cysterna chyli
Primary vs. Secondary hair follicles
Primary hair follicle- deep set and possess sebaceous and tubular glands and an arrector pili
Secondary hair follicle- smaller and more superificial, may have a sebaceous gland but lack tubular gland and arrector pili muscle. Produce secondary or under hairs which lack a medulla.
* Simple- is a single hair follicular canal vs. compound- several follicles grouped together- each with its own root but not necessarily its own glands. They fuse at the level of the sebaceous gland duct and hairs emerge onto surface via single opening. Usually have one primary hair and several secondary hairs.
What is this? what is 1? What is 18?
Sinus (tactile) hair follicle
- annular sinus
- trabeculated sinus traversed by fibroelastic trabeculae containing many nerve endings
* merkel’s cells, associated with tactile stimulation in the external root sheath
** in carnivores, the upper region is nontrabeculated forming an annular sinus
* in horses, pigs and ruminants the sinus is trabeculated throughout its length
What are the three stages of the hair cycle? What controls them?
What is a pilosebaceous unit?
Hair follicle and associated sebaceous glands
what causes lymph node hypoplasia?
Cachexia, aging, SCID
What causes lymphoid necrosis? What else will be affected?
Herpes, Parvo
Spleen
Anthracosis of the lungs affects the lymph nodes as well
What are the 3 types of inflammation in the lymph nodes?
What else is affected?
Caseous Lymphadenitis from traumatic injury to the skin- Corynebacterium pseudotuberculosis
* Spleen can also be affected
Chronic suppurative lymphadenitis- Streptococcus porcinus
Equine strangles- Streptococcus equi- subacute suppurative lymphadenitis
Postweaning Multisystemic Wasting Syndrome (PMWS)
Porcine Circovirus 2
Die within 6-12 weeks of age
Granulomatous lymphadenitis and lymphoid depletion
Bovine Tuberculosis- Secondary lymph node infections (indirect)
Wooden Tongue, Bovine, Actinobacillus
Rhodococcus equi- Secondary lymph node infection
Lymphoma- medium high power will show starry sky appearance.
** this will vary from hyperplasia in a reactive lymph node– the architecture will have germinal centers, no cortex, no medulla, it is probably enlarged but no more normal tissue left
* with lymphoma all the cells look the same (this is TOTALLY UNIQUE TO LYMPHOMA– all other tumours are pleomorphic)
Lymphoma (FNA)
Multicentric lymphoma
Enlarged peripheral lymph nodes
Most common
* how do you differentiate tumour or infection? Presence of enlargement on both sides. BILATERAL= likely LYMPHOMA. Monolateral= likely to be infection. CONFIRM WITH HISTO
Lymphoma- no differentiation between cortex and medulla. Tissue is white because proliferation of white cells.
Bovine sporadic lymphoma- thymic/juvenile form
Siderofibrosis- siderotic plaques. Haemosiderin, fibrous tissue– micro traumatic injuries therefore haemorrhage and fibrosis. Not a lesion, no problem. Common in older animals.
What would cause this?
Aging, SCID
Splenic contraction due to a haemorrhage for example. Can be uneven. In disease conditions- extramedullary haematopoeisis. Always a haemopoietic organ early in life.
Barbituate euthanasia (most common), any condition that impairs circulation or drainage of blood from the spleen (GDV great example!!)– passive congestion.
** GDV- spleen will be C shaped because of the torsion
Splenic infarcts (not common) but any virus or bacteria can cause this. e.g. Cholera caused by Pestivirus
** cannot tell the difference grossly. Peritonitis at the level of the infarct.
Splenic haematomas. Can become really big. Most likely consequence of a big haematoma is rupture- major haemorrhage- therefore hypovolaemic shock.
* Organizing haematomas- with fibrosis tissue- less likely to rupture
Splenic rupture can cause splenosis- seeding of splenic tissue on the omentum. Red pulp and white pulp are released in the abdominal cavity and seed. Red nodules are little accessory spleens- baby spleens.
Bacillus anthracis- congestive splenitis- more blood in the spleen.
* haemorrhages throughout the body, oozing from the nose, splenomegaly- cutting– oozing blood.
(African Swine Fever also can cause splenomegaly)
Splenic abscess
Hyperplasia due to extramedullary haematopoeisis
* this picture: enlarged lymphoid follicles- white pulp
What does Bacteraemia cause? Septicaemia?
Septicaemia- acute congestive splenitis (whole organ is enlarged and congested)- big dark and oozing blood.
Bacteraemia- white pulp hyperplasia, abscesses/ granulomas
** from the spleen it can tell you what is going on in infectious diseases
Multifocal hyperplasia
What is the double two-thirds rule? Sequelae for rupture?
Haemangiosarcoma
* Multiple blood filled haematomas or blood nodules
* 2/3 tumours are going to be malignant and 2/3 of the malignant are haemangiosarcomas
COMMON AND MALIGNANT (highly metastatic!)- if you are diagnosing- likely metastatic already- liver, right auricle of the heart (can be multicentric)
** vessels with haemangiosarcoma!
** need histo to confirm!
** RUPTURE is another problem- this is the TYPICAL PRESENTATION– haemoperitoneum– release of malignant cells– implants on peritoneum and omentum
Lymphoma. Gross appearance- variable.
Uniform enlargement or nodular
Histiocytic sarcoma- pleomorphic- giant cells. Bernese mountain dogs.
Where can splenic sarcomas arise from?
Capsule, trabeculae, smooth muscle
** since there are mesencymal cells in the spleen- you can have sarcomas
You need to take multiple samples and do histo
What are the two problems in the thymus?
* Thymus is in the MEDIASTINUM!!!!
* Thymic atrophy/ hypoplasia- normal atrophy but in young animals you can have EHV-4 or something else that causes this
* Thymic neoplasia: Lymphoma and Thymoma– LOOK SIMILAR. Thymic lymphoma is common in cats, but not so much in other species.
Thymoma- usually nodular compared to smooth lymphoma- BUT you still need histo!
What is the difference between epithelial, mesenchymal, and round cell tumours?
* Epithelial cell tumour- CLUSTERS
* Mesechymal cell tumour- live in connective tissues- do not have intercellular junctions- on the slide as single cells- NO CLUSTERS
* Round cells- NO CONNECTIONS- Single cells- ROUND
Mast cell tumour
* the more malignant- the less they resemble the cell of origin
Grade 1: most benign form (remove surgically likely not to come back)
Grade 2
Grade 3: high grade (you can do surgery to increase survival times but poor prognosis- 2-3 months survival time)
** histo diagnosis is crucial to understand prognosis and treatment– TREATMENT VARIES ON GRADE!!
The less melanin you have- the more malignant the tumour
Transmissible venereal tumour
What can look like this grossly? But drastically differ histologically?
Haemangioma.
Can look grossly like a melanoma- but histologically look completely different.
In what organ is the prognosis worse than the skin in this tumour?
Haemangiosarcoma. If you catch them early and remove them, the prognosis is pretty good.
** Haemangiosarcoma- bad prognosis in the spleen!!!
Most likely a fibrosarcoma
Could be a fibroma but not as common
** tumour can arise after rabies vaccination
** so invasive and malignant- you can remove them but they keep coming back!
Fibrosarcoma
* any time you have giant cells = bad
What are the two types?
Equine Sarcoid
Viral infection that affects fibroblasts- Bovine Herpes
- Verrucous- Keratin and epithelium
- Proud flesh (excuberant granulation tissue)
Squamous cell carcinoma- can be on a digit in dogs for example.
poor prognosis. UV radiation.
keratinized cytoplasm
Sebaceous gland adenoma
What are the lipid derived autacoids?
Prostaglandins, Leukotrienes, Platelet activing factor (TXA2)
* very similar to a fatty acid because it is a breakdown of a lipid membrane
* not stored pre-formed
* major role in inflammation and other physiological processes
What are the stable prostaglandins? What is the more labile?
Which are the opposite to TXA2?
PGI2 is the opposite to TXA2
What is the difference between the two forms of Cyclo-oxygenase?
Cox 1- constitutive- present all the time producing prostanoids
Cos 2- inducible- induced in inflammatory cells in response to inflammation
** lots of overlap in COX 1 and COX 2– that means you cannot specifically target COX 2
What two genes are inhibitory for the cell cycle at checkpoint 1?
Many cells sit in G0 and then re-enter the cell cycle in G1 and proceed into S phase.
* Checkpoints- where a cell is prevented from going forward in the cell cycle. Prevent mitosis or DNA synthesis
* Positive forces that promote the cell cycle: growth factors, cyclins, cyclin dependent kinases
* Negative forces that inhibit the cell cycle: p53 gene- checkpoint 1, Rb gene- checkpoint 1–> they recognize damaged DNA and stop the cell from entering the cell cycle! (mutation- you don’t want the cell to be replicated)
What are you trying to do with cancer drugs? What is a problem with targeting a part of the cell cycle with cancer drugs?
Toxic to cancer cell but not toxic to the patient.
Most early ones act at some point in the cell cycle to inhibit the cycle.
However, this means that cells in the body will be susceptible like GI, lymphocytes, any of the cells in the bone marrow turn over rapidly.. any high turnover of cells.
** BUT even with cancer cells, not all of them will be in the same part of the cell cycle
What are the major lymph centres and drainage routes?
Coeliac lymph centre lymph drains to coeliac trunk
Cranial mesenteric lymph centre drains to intestinal trunk
What are the main superifical lymph nodes?
* parotid, lateral retropharyngeal, mandibular, superficial cervical, axillary, accessory axillary, superficial inguinal, popliteal
What is the major route of lymphatic drainage?
Right lymph duct (drains the right forelimb, shoulder area, and the right side of the head and neck) and the left lymph duct (AKA thoracic duct)–> drains everything else—> these ducts then drain into the external jugular veins or subclavian veins on each side
What is the blue arrow? (sheep)
Hemal node (secondary lymphoid organ)
What is the black arrow? Tracheal trunk
What is the blue arrow? Thoracic duct
What is this? What does it do?
Cisterna chyli- located dorsal to the aorta caudal to the diaphragm.
Dilation of the thoracic duct- it drains the intestinal trunk. Receives fatty chyle from the intestines and thus acts as a conduit for the lipid products of digestion.
What is the main component of the bursa of fabricius in birds?
Plica (folds) and follicles
What are PALS and where are they found?
Periarterial lymphatic sheaths, dense accumulated lymphocytes around central arteries
What is the function of the red pulp?
What runs between sinusoids?
Removal of deteriorating red cells and platelets, immune function in ID of antigens by macrophages and DCs
* Splenic cords run between sinusoids
Where are peyer’s patches found?
Ileum and ileocaecal junction
Contain M cells- sample antigen directly from the lumen and deliver it to APCs
