ANZCVS 2015

Question 1

a) Using the cell-based model, briefly describe, in the order in which they occur, the major events involved in hemostasis. Include in your answer the important tissues, and the cellular and non-cellular components involved. Your answer should briefly describe the differences between the classical cascade model and the cell-based model and include mechanisms which prevent widespread initiation of coagulation. (22 marks)

Answer 1

Cell-based model of fibrin formation Occurs in distinct overlapping phases and require the participation of two cell types: cell-bearing TF and platelets.

Initiation: TF bearing cells are localized outside the vascular space under normal conditions. Some cells carry TF (monocytes, tumor cells), but in inactive form. Injury leads to exposure of flowing blood to TF bearing cells, allowing FVIIa to bind to TF (FVIIa is the only coag protein that routinely circulate in active form). TF-FVIIA complex activate further FVIIa as well as small amounts of FIX and FX. FXa binds to it’s cofactor FVa to form prothrombinase that cleaves prothrombin into small amounts of thrombin. Any FXa that dissociates from the membrane surface is rapidly inactivated by TFPI or AT, restricting the process to TF-bearing cells.

Amplification: Thrombin diffuses and becomes available to activate platelets that have leaked to the extravascular space. Thrombin caused significant changes in platelet morphology, resulting if membrane phospholipid shuffling. This leads to the formation of a pro-coagulant membrane and release of platelet granule content. Calcium contributes to PS clustering, further contributing to the procoagulable nature of the membrane. In addition to activating platelets, thrombin cleaves FXI to FXIa, activates FV to FVa and cleaves vWF factor off FVIII (they circulate together), releasing them to mediate platelet adhesion and aggregation.

Propagation: Activated platelets express ligands on their surface, leading to aggregation. FIXa can bind to FVIIIa, forming Intrinsic Tenase Complex (FVIIIa -FIXa) which generates FXa on platelets. FXa rapidly binds to FVa (generated by thrombin during the amplification phase) and cleave prothrombinase to thrombin. Thrombin cleaves fibrinogen into fibrinopeptide A. When enough thrombin is generated, soluble fibrin molecules will spontaneously polymerize into fibrin strands, resulting in insoluble fibrin matrix.

Question 2

Describe the importance of thrombin in the coagulation process and at what phase it is produced.

Answer 2

Over 95% of thrombin is produced after fibrin mesh polymerization. This thrombin is important for the following reasons:

• Activation of cross-linker FXIII, which modifies the polymerized fibrin and forms cross-links between strands, thereby drastically impacting the strength and elasticity of the clot.
• Binding to thrombomodulin (TM), activating Thrombin Fibrinolysis Inhibitor (TFI). Fibrin activated by TFI is significantly more resistant to fibrinolysis.
• Binding to TM to activate Protein C (aPC). aPC forms complex with its cofactor ProS (aPC/ProS) which cleaves FVa and FVIIa on the endothelial cells. This shuts down the generation of further thrombin molecules.

Question 3

Briefly describe the differences between the classical cascade model and the cell-based model of coagulation. Include mechanisms that prevent widespread initiation of coagulation. (22 marks)

Answer 3

The Cascade Model suggests that the extrinsic and intrinsic pathways operate independently and redundantly. This concept is contradicted by the fact that individual factor deficiencies such as FII (Intrinsic), sufficient to cause prolongation of aPTT, does not lead to a tendency to bleed. By contract, deficiencies in other factors like FVIII or FIX (hemophilia A and B) ca result in serious bleeding even though these patients can have normal extrinsic pathways function. This suggests that local mechanisms (injury site) must exist to control and regulate hemostasis (i.e. cell contribution).

The cell contribution is, at a most basic level, a function of membrane surfaces. The inactive membrane has neutral phospholipids expressed on the external leaflet, and phosphatyldserine (PS) and phosphatidylethanolamine (PE) located on the inner surface of the membrane. Injury leads to activation of ATP-dependent flippase/floppase/scramblase which transports PS and PE to the external leaflets. This “scrambling” happens in response to increased Ca concentration in the cytosol. The expression of PS/PE on the outer membrane makes it procoagulable, supporting activation, amplification and propagation. The ability of cells to control the nature of their membrane surface is one of the most powerful methods of regulating coagulation.

Non-activated endothelial cells also express several anticoagulant surface factors. These include Heparin sulfated proteoglycans (HSPGs), Thrombomodulin (TM) and Tissue Factor Pathway Inhibitor (TFPI)

Question 4

A six-month-old Doberman pinscher is re-presented the day following ovario- hysterectomy for extensive ventral abdominal petechiation, dripping of sanguineous fluid from the surgical wound, depression and weakness. You are confident that your ligatures were appropriately applied during surgery.

State the most likely diagnosis for this haemostatic abnormality. (1 mark)

Answer 4

Von Willebrand’s disease

Question 5

A six-month-old Doberman pinscher is re-presented the day following ovario- hysterectomy for extensive ventral abdominal petechiation, dripping of sanguineous fluid from the surgical wound, depression and weakness. You are confident that your ligatures were appropriately applied during surgery.

1. For Von Willebrand;s disease which component of haemostasis is abnormal? (1 mark)

Answer 5

Platelet activation

Question 6

A six-month-old Doberman pinscher is re-presented the day following ovario- hysterectomy for extensive ventral abdominal petechiation, dripping of sanguineous fluid from the surgical wound, depression and weakness. You are confident that your ligatures were appropriately applied during surgery.

1. Briefly describe the underlying pathophysiologic mechanism for Von Willebrand’s disease

Answer 6

According to the cell-based model of fibrin clot formation, tissue trauma (i.e surgery) leads to breaching of the endothelial membrane and exposes subendothelial factors to blood components. Von Willebrand’s factor is a large multimeric glycoprotein, largely present in the endothelial membrane but also circulating in the plasma attached to factor VIII. It is produced by platelets and sub-endothelial tissue (Weibel-Palade bodies) and stored in these two sites. vWF plays a major role in platelet adhesion to subendothelium and a minor role in platelet aggregation. When exposed to blood components / activated by cleaving from factor VIII it acts as a “sticky tether”, capturing platelets and slowing their velocity in high flow vessels (like arterioles), allowing slower-acting integrins to form a firmer adhesion to subendothelial collagen.

Question 7

A six-month-old Doberman pinscher is re-presented the day following ovario- hysterectomy for extensive ventral abdominal petechiation, dripping of sanguineous fluid from the surgical wound, depression and weakness. You are confident that your ligatures were appropriately applied during surgery.

e) Name and briefly describe how to perform and interpret the pre-operative screening test that may have identified Von Willebrand’s disease

Answer 7

The most commonly used test for vWF deficiency is the vWF:Ag titer. The test is performed on a citrated plasma sample (whole blood collected with hypodermic needle ad immediately placed into potassium citrate tune). Patients with vWF:Ag for 70-180% are considered normal; 50-69% borderline; 0-49% vWD and < 35% “at risk for hemorrhage”.

Buccal Mucosal Bleeding time is often used as a “in-clinic” test or patients suspected of having vWD (i.e. Doberman Pintcher), but is not sensitive or specific for the disease and therefore does not replace vWF:Ag testing.

Question 8

a) Describe the blood supply to a normal mature canine long bone. You may use diagrams to illustrate your answer.

Answer 8

The blood supply to a long bone derives from nutrient arteries, epiphyseal arteries, _metaphyseal arteries_and periosteal arteries.

The nutrient artery: A branch of major systemic arteries. Esters the bone through the nutrient foramen and divides into ascending and descending branches. These branches give small parallel arteries called radial branches. These branches supply the bone marrow and inner third of the cortex. They divide into smaller spiral branches which anastomose with the metaphyseal and epiphyseal arteries.

The metaphyseal artery: derive from anastomosing arteries around the joint and enter the metaphysis near the edge of the joint capsule. The anastomose with spiral arteries derived from nutrient arteries, making the metaphysis the most vascular area of a long bone.

The epiphyseal artery: Derived from periarticular vascular arcades. Initially divided from the metaphyseal blood supply by the epiphyseal plate (growing individual), later anastomosing with metaphyseal and nutrient arteries.

The periosteal artery: Derived from local systemic arteries, periosteal arteries penetrate the bone at the site of attachment of fascial sheath or aponeurosis. The constitute a low-pressure system forming numerous anastomoses underneath the periosteum. Periosteal arteries penetrate the Volkmann canal of osteons, providing blood supply to the outer one third of the diaphysis.

Venous drainage: Long bones drain into the central venous sinus. The sinus drains into the nutrient vein which drains into periosteal vein and to the emissary vein successively.

Question 9

b) Following fracture, the blood supply to a bone is often extensively damaged. Briefly discuss how the blood supply is re-established to enable fracture healing.

Answer 9

Immediately following fracture, platelets and local cells secrete pro-inflammatory cytokines including TNF-Alpha, BMP’s and Interleukins (IL-1; IL-6, IL-11; IL-23). These cytokines stimulate local cellular biology, attracting macrophages, monocytes and lymphocytes. These cells secrete Vascular Endothelial Growth Factor (VEGF) which stimulates local angiogenesis. The concomitant production of fibrin-rich granulation tissue allows migration of mesenchymal stem cells which differentiate into multiple cells, particularly fibroblasts. Vascular buds from periosteal and endosteal origin proliferate towards the center of the fibrovascular callus following the low O2 gradient. The external callus remains heavily dependent on periosteal and extraosseous blood supply (muscle) in the early stages of healing. During the late osteochondral and early remodeling phase the reorganization of the Harversian systems will allow reestablishment of the original intra-osseous, periosteal and endosteal blood supply.

Question 10

c) Define the terms ‘malunion’ and ‘delayed union’ in the context of fracture healing. (2 marks)

Answer 10

Malunion: a healed fracture with improper limb alignment as a result of failure of mechanical reestablishment of form and function of the fracture. Typically, a result of poor surgical reduction or failure of fixation.

Delayed Union: Defined as the prolongation in the expected time for fracture healing.

Question 11

d) List the factors that may contribute to delayed fracture healing in dogs. For each factor state why it may contribute to delayed fracture healing. (8 marks)

Answer 11

• Mechanical causes: include the presence of fracture gaps and motion at the fracture site. The larger the gap, the more time it will take to bridge it with new bone. Motion induces fracture strain, which may elicit a robust cellular response with the formation of a large callus. This is only true to a certain point, however, since strain great enough to exceed the tolerability of certain tissues will prevent further callus formation and lead to a viable nonunion.
• Biological causes: may include intrinsic, extrinsic or both, leading to inadequate cellular activity. Most delayed unions are caused intrinsic patient and fracture factors. The biologic environment of a fracture, particularly its soft tissue envelope, is fundamental for adequate vascular supply. The energy imparted to the bone during trauma frequently traumatizes these tissues, impairing oxygenation, nutrient delivery and cell migration despite the presence of growth factors.

Question 12

Draw and label a diagram of the gross anatomy of the female canine reproductive tract. Include all major ligaments and organs. You do not need to label neurovascular structures. (10 marks)

Answer 12

Question 13

i. the artery supplying the ovaries and the vessel(s) from which it arises

Answer 13

Paired ovarian arteries. Arise from the Aorta, caudal to the renal arteries and cranial to the deep circumflex iliac arteries.

Question 14

ii. the vessel draining the ovaries and the vessel(s) they lead into 16-weeks of age. (12 marks) The right ovarian vein drains directly into the caudal vena cava. The left ovarian vein drains into the left renal vein.

Answer 14

The right ovarian vein drains directly into the caudal vena cava. The left ovarian vein drains into the left renal vein.

Question 15

iii. the lymphocenter the lymphatics from the female urogenital tract drain into. (1 mark)

Answer 15

Lumbar lymph nodes

Question 16

c) List six (6) complications specific to ovariohysterectomy in the dog. (3 marks)

Answer 16

Ovarian remnant syndrome; ureteral ligation; urethral obstruction; hemorrhage; infection; herniation;

Question 17

d) List the advantages and disadvantages of desexing dogs and cats aged less than 16-weeks of age.

Answer 17

Advantages:

• Guarantees population control
• Smaller incision; “potentially” lower chance of complications

Disadvantages:

• Increased risk of anesthesia-related complications, including hypoglycemia and hypothermia.
• Immature hepatic function (microsomal cytochrome p-450 enzyme activity)
• Lower plasma protein concentration = higher unbound fraction of anesthetics
• Immature renal function = higher chance of NSAID-induced renal injury
• Immature renin-angiotensin-aldosterone system = prone to hypotension

Question 18

a) Draw and label a diagram of the microscopic anatomy of the cartilaginous component of the physis of a long bone in a skeletally immature animal. Provide a brief description of the differences in cellular morphology in eachregion.

Answer 18

5 zones of the physis

• Resting (reserve) Zone (R)
• Proliferative Zone (P)
• Hyperthophic zone (H)
• Zone of Calcification (C)
• Zone of Ossification (O)
• Resting (reserve) zone: composed of hyaline matrix with small, oval-shaped chondrocytes. Nearly identical to the hyaline cartilage at the joint surface.
• Proliferative zone: Chondrocytes actively undergo mitosis. Classic “stacked coin” appearance. Less matrix, but still composed of collagen Type II. Contains multiple growth factors line MPS’s.
• Hypertrophic zone: Newly former chondrocytes begin to hypertrophy and undergo apoptosis. Hypertrophic chondrocytes produce Collagen Type X and decrease expression of Collagen II. Collagen type X is not a triple-helical collagen like Type II. It contains fibers that provide stiffness but prevent nutrient diffusion. This leads to tissue hypoxia, which stimulates hypertrophic chondrocytes to produce VEGF. VEGF will lead to vascular invasion via angiogenesis. This zone contains little matrix, making is weak and prone to fractures (typical site of SH fractures in juvenile patients – Type II is the most common).
• Zone of Calcification: chondrocytes undergo apoptosis due to persistent hypoxia, all the while secreting APL which scavenge Ca and P from adjacent tissues. This process leads to the formation of calcium-phosphate aggregates and matrix calcification.
• Zone of Ossification: Osteoblasts derived from perivascular mesenchymal stem cells follow the vascular network in vascular access channels and produce woven bone on the surface of calcified tissue. Osteoclasts remodel woven bone into lamellar bone over time.

Once the activity in the Zone of Ossification exceeds the Reserve Zone’s ability to repopulate chondrocytes the physis is obliterated, leaving behind a small mineralized line known as the epiphyseal line.

Question 19

c) Explain why distal ulna physeal trauma is a clinically significant injury in the dog. Include in your answer potential sequelae to premature closure of the distal ulna physis. (14 marks)

Answer 19

Distal Ulna physeal trauma (typically SH-V Fx) frequently results on premature closure of the physis, resulting in growth deformities. The degree of deformity will depend on the patient’s residual growth potential. The radius receives 40% of its axial growth from the proximal physis and 60 % from the distal physis. The ulna receives only 15% from the proximal and 85% from its distal physis. Premature closure of the distal ulnar physis interferes with radial growth by acting as a “restraint”, often leading to radial shortening, rotation and angulation deformity (cranial bowing, external rotation and shortening, with carpus valgus). This results in elbow and carpal incongruity, leading to DJD.

Question 20

A 10-year-old male Labrador presents to your clinic with signs consistent with an upper airway obstruction. On physical examination, rectal temperature is 39.8°C; he is panting and has a heart and pulse rate of 120 beats per minute. Upper airway auscultation reveals high pitched noise over the larynx.

a) Describe your stabilization of this patient. Include your rationale for each treatment given.

Answer 20

Patients with UAO are initially treated in a similar fashion regardless of the cause of obstruction.

• Oxygen therapy is immediately provided via face mask or oxygen cage. This is done with the intention of providing a higher O2 concentration in the inspired air, minimizing hypoxemia and the patient’s urge to forcefully breathe. Excessive respiratory effort leads to a cycle of edema and inflammation with progressively worse obstruction.
• Anxiety control: Anxiety and discomfort are controlled with the administration of anxiolytic agents like acepromazine (0.005 to 0.02mg/kg IV or IM) in cardiovascularly stable patients. Butorphanol (0.1 to 0.5 mg/kg IV or IM) also provides sedation, cough suppression and minimal analgesia.
• Glucocorticoids (Dexamethasone sodium phosphate 0.05 to 0.2 mg/mg IV, IM or SQ) can be considered to reduce airway inflammation secondary to obstruction. This must be dose with consideration to the risk of GI ulceration in hypovolemic/hypoperfused patients, as well as any recent use of NSAID’s.

If the combination of O2 supplementation and anxiolytic agents do not relieve respiratory distress and the patient is believed to be at imminent risk of respiratory arrest, rapid anesthetic induction for endotracheal intubation should be considered. This can be accomplished with propofol + diazepam or midazolam, ketamine + diazepam and/or etomidate.

Question 21

A 10-year-old male Labrador presents to your clinic with signs consistent with an upper airway obstruction. On physical examination, rectal temperature is 39.8°C; he is panting and has a heart and pulse rate of 120 beats per minute. Upper airway auscultation reveals high pitched noise over the larynx.

b) List four (4) differential diagnoses for this dog’s clinical signs.

Answer 21

• Laryngeal paralysis
• Upper Airway foreign bodies
• Pharyngeal/Laryngeal tumors
• Inflammatory laryngeal disease

Question 22

A 10-year-old male Labrador presents to your clinic with signs consistent with an upper airway obstruction. On physical examination, rectal temperature is 39.8°C; he is panting and has a heart and pulse rate of 120 beats per minute. Upper airway auscultation reveals high pitched noise over the larynx.

c) Describe your initial diagnostic plan for this patient.

Answer 22

Blood gas analysis: Arterial sample preferred, but often difficult to obtain. Venous sample may have to be used instead. Allows measurement of PvCO2 to determine the degree of respiratory acidosis.

Thoracic and cervical radiography: Only obtained once the patient is stable enough to withstand the stress. O2 supplementation is continued throughout. Three orthogonal projections are obtained (Lat R, Lat L and VD) to rule out non-cardiogenic pulmonary edema, bronchopneumonia, lung-lobe torsion, intra-thoracic tracheal collapse, mainstem bronchial collapse and neoplasia. Cervical radiographs can rule out extra-thoracic tracheal collapse, tracheal foreign bodies and possible laryngeal/pharyngeal masses. Dynamic disease may or may not be appreciated and may require fluoroscopy.

Laryngoscopy: Performed under injectable light plane of general anesthesia using a short-acting agent like propofol or alfaxalone. Used to rule out tumors, foreign bodies, laryngeal collapse, epiglottic retroversion, caudal displacement of the epiglottis into the rima glottis and laryngeal paralysis. Doxapram (CNS stimulant, increases electrical activity in inspiratory/expiratory centers of medulla. Also stimulates carotid and aortic receptors) can be used if inspiratory rate or anesthetic depth are concerning. Doxapran may also increase the likelihood that a normal laryngeal function could be verified. Flow-by O2 can be administered using a cannula attached to a laryngoscope or videoendoscope. Laryngeal paralysis is diagnosed when one of both arytenoid cartilages and vocal folds are immobile or draw towards the midline during inspiration. If available, flexible endoscopy can be performed in the trachea to grade tracheal collapse. Ridgid endoscopy can be used to rule out nasopharyngeal collapse.

Question 23

A 10-year-old male Labrador presents to your clinic with signs consistent with an upper airway obstruction. On physical examination, rectal temperature is 39.8°C; he is panting and has a heart and pulse rate of 120 beats per minute. Upper airway auscultation reveals high pitched noise over the larynx.

d) Temporary tracheostomy can be used to bypass upper airway obstructions. Briefly describe the technique for surgical placement of a temporary tracheostomy tube.

Answer 23

A 2 to 5 cm ventral cervical skin incision is made extending from the cricoid cartilage towards the sternum. The sternohyoid muscles are separated along the midline by blunt dissection and retracted laterally. The peritracheal connective tissue is dissected with care to avoid damaging the left recurrent laryngeal nerve and tracheal blood supply (stay close to the midline). A transverse or longitudinal incision is made into the trachea. For the transverse method the incision is performed into the annular ligament between the third and fifth tracheal rings. No more than 50% of the tracheal circumference is incised, and extreme care is taken to avoid the left recurrent laryngeal nerve. Long loops of suture are applied around the tracheal rings cranial and caudal to the incision to facilitate retraction during tracheostomy tube placement. During the vertical technique the incision is made through 2 to 4 tracheal rings and the stay sutures are placed around the cartilage rings lateral to the incision. Segmental lateral tracheal collapse may be a long-term complication with this method. After tube placement the skin is routinely closed, but space must be left around the tube to allow air to escape and avoid SQ emphysema. The tube can be secured using sutures or umbilical tape around the neck.

Question 24

A 10-year-old male Labrador presents to your clinic with signs consistent with an upper airway obstruction. On physical examination, rectal temperature is 39.8°C; he is panting and has a heart and pulse rate of 120 beats per minute. Upper airway auscultation reveals high pitched noise over the larynx.

e) Outline the routine care of a tracheostomy tube in the first 24-hours after placement.

Answer 24

Goals: Prevent obstruction with respiratory secretions and minimize the risk of airway trauma or nosocomial infection.

Precautions: tracheostomy tubes require intense monitoring. The staff members in charge must be able to quickly respond to tube obstruction by removal of the inner cannula or tube replacement.

Tube cleaning: The patient is positioned in sternal or dorsal recumbency with the neck extended. The tracheostomy tube inner cannula is removed and thoroughly cleaned every 4 hours using the stay sutures to facilitate tracheostomy opening. This is typically tolerated without sedation. Tubes without inner cannula should be replaced every 24 hours even if unobstructed.

Tube suctioning: The inner cannula is removed for cleaning and temporarily replaced with a temporary cannula. The patient is pre-oxygenated with humidified 100% O2 for 5 min. A sterile suction tube is inserted to the level of the carina and suction is applied as the tube is retracted over 10 seconds using a circular motion. Repeat suction 2 to 3 times, administering humidified 100% O2 for 3 to 5 min between cycles. Replace clean inner cannula, clean incision around the tube and make sure well secured.

Question 25

A five-year-old Irish wolfhound presents with right forelimb lameness. There is unilateral metaphyseal bone pain and swelling in the distal radius. An osteolytic bone lesion in the distal radius is identified on radiographs. You suspect appendicular osteosarcoma.

a) List four (4) alternative differential diagnoses.

Answer 25

• Fungal infection (Histoplasmosis, Blastomycosis, coccidiomycosis)
• Bone cyst
• Bone infarct
• Bacterial osteomyelitis

Question 26

A five-year-old Irish wolfhound presents with right forelimb lameness. There is unilateral metaphyseal bone pain and swelling in the distal radius. An osteolytic bone lesion in the distal radius is identified on radiographs. You suspect appendicular osteosarcoma.

b) Describe your initial diagnostic plan for this patient prior to treatment. Include in your answer the reason for performing each suggested diagnostic test.

Answer 26

• Routine CBC/Chem/UA: Typically normal but recommended to rule out comorbidity. ALKP elevation may be of prognostic value.
• Thoracic radiographs: Less that 10% of OSA cases will have radiographically evident pulmonary metastasis. If present, however, the prognosis is poor.
• Advanced imaging (CT): If available, CT can reveal occult local bone disease (more sensitive for cortical erosion, fractures, and internal bone characteristics). It is also more sensitive that radiographs for the detection of pulmonary metastasis. CT can also be used to rule out metastasis to less common sites such as kidneys, spleen, myocardium, lymph nodes, diaphragm, mediastinum, spinal cord, small intestines, gingiva and SQ tissue.
• Bone biopsy:
• Jamshidi 8-11G (92% specific and 82% sensitive)
• Michelle Trephine (94% specific, higher risk of fracture)
• Fine Needle Aspirate (97% sensitive, 100% specific). When a diagnosis of sarcoma is made on cytology, ALKP staining is 100% sensitive for OSA (Britt et al, 2007). Can be performed with sedation, quick results, tissue-core Bx can be performed if FNA is unsuccessful. Possibly affected by excessive blood contamination. Limited to tumor group – unable to differentiate between embers of sarcoma family.
• Bone Scintigraphy: Not often performed and likely not necessary as part of every workup. Recommended whenever the “primary” lesion is located at an unusual site for OSA. Improves the likelihood of detecting bone metastasis.

Question 27

A five-year-old Irish wolfhound presents with right forelimb lameness. There is unilateral metaphyseal bone pain and swelling in the distal radius. An osteolytic bone lesion in the distal radius is identified on radiographs. You suspect appendicular osteosarcoma.

c) Discuss the surgical and medical treatment options for distal radial appendicular osteosarcoma in a giant breed dog. Include in your answer the prognosis and median survival times for the treatments discussed.

Answer 27

Surgical options include Limb Amputation, Limb-sparing procedures. Medical options include Radiotherapy, Chemotherapy and Bisphosphonates therapy.

• Amputation: Considered the most effective pain-relief procedure. Palliative, but still the standard treatment for appendicular OSA.
• Limb-sparing procedure: The OSA is excised, and the remaining bone defect is filled with another material (bone autograft, allograph or steel prosthesis) or by distraction osteogenesis. Tumor must be clinically and radiographically confined to the limb and involve less than 50% of the bone.
• Radiotherapy: Palliative therapy for primary and metastatic bone pain. Response (improved pain score) is observed in 75 to 92% of cases and may last an average of 130 days.
• Chemotherapy: Typically based on Carboplatin alone or in combination with doxorubicin. Significantly improves life span. Median survival 300-365 days; 20 to 25% of patients survive beyond 2 years.
• Bisphosphonate therapy: shown to decrease pain from primary and metastatic bone neoplasia. Improves life quality and delays progression of bone lesions. Inhibits bone resorption without affecting bone mineralization. Pamidronate + NSAID alleviated pain for more than 4 months in 28% of 43 dogs, MST 231 days (Fan et al, 2007)

Expected prognosis (rounded numbers):

• Analgesics only (NSAID’s, Bisphosphonates, opioids): no effect on survival beyond 3 months
• Amputation alone: MST 4-6 months; 12 months MST 10-20%
• Amputation or Limb-sparing + Chemo: 8-18 months; 12 months MST 30-70%
• Radiation therapy alone: Improvement noticed in 75-92%. Median duration 4 months.

Question 28

You have just performed an ovariohysterectomy on a thin, 10-month-old, female Yorkshire terrier. The dog remains in a near comatose state four hours after the cessation of anesthesia. Your anesthetic protocol consisted of methadone premedication, intravenous propofol induction and maintenance on a pediatric circuit with isoflurane in oxygen. The dog was bright and alert with normal mentation prior to anesthesia. You suspect a deficiency in drug metabolism and elimination.

a) State the most likely diagnosis.

Answer 28

Portosystemic shunt, likely extrahepatic given signalment (Odds ratio of 35.9 times that of other breeds combined)

Question 29

You have just performed an ovariohysterectomy on a thin, 10-month-old, female Yorkshire terrier. The dog remains in a near comatose state four hours after the cessation of anesthesia. Your anesthetic protocol consisted of methadone premedication, intravenous propofol induction and maintenance on a pediatric circuit with isoflurane in oxygen. The dog was bright and alert with normal mentation prior to anesthesia. You suspect a deficiency in drug metabolism and elimination.

b) Briefly explain the pathophysiological events that account for the delayed recovery from anesthesia in a PSS case.

Answer 29

Patients affected by PSS typically have poor hepatic function and hypoalbuminemia. This delays the clearance and increases the available fraction of highly protein-bound anesthetic agents that are metabolized in the liver, such as propofol.

Question 30

You have just performed an ovariohysterectomy on a thin, 10-month-old, female Yorkshire terrier. The dog remains in a near comatose state four hours after the cessation of anesthesia. Your anesthetic protocol consisted of methadone premedication, intravenous propofol induction and maintenance on a pediatric circuit with isoflurane in oxygen. The dog was bright and alert with normal mentation prior to anesthesia. You suspect a deficiency in drug metabolism and elimination.

c) List the clinical pathology tests and the expected abnormalities you would expect to confirm the presumptive diagnosis of PSS

Answer 30

CBC:

• Microcytic, normochromic, mildly non-regenerative anemia
• Target Cells
• Poikilocytosis (abnormally shaped RBC’s composing more that 10% of RBC popul.)

Biochemistry:

• Hypoalbuminemia (Most common finding, but occ. normal in congenital PSS)
• Low BUN
• Low cholesterol

Urinalysis:

• May reveal Ammonium Biurate crystals

Hepatic function tests:

• Serum Bile Acids (Traditionally considered the “standard” hepatic function test for dogs but has limitations). Must measure both pre and post-prandial values. Elevations above reference range are compatible with hepatic disfunction, but approximately 20% of dogs have a higher pre-prandial value. The degree of elevation does not correlate with severity of clinical disease. Substantial variation in serum bile acid concentration can occur from day to day, sometimes by over 100%. Bile acids can also be measured in the urine.
• Protein C: sensitive for hepatic insufficiency (decreases with loss of hepatic function). Dogs with congenital PSS usually have lower Protein C levels that dogs without macroscopic shunting. Dogs with hepatic failure have the lowest values of all.
• The Ammonia Tolerance Test is very sensitive (100% in one study) but has drawbacks (animals vomit or defecate the ammonia). Fasting ammonia concentration can be combined with fasting BA (reported specificity 97% and predictive value 97%), Ammonia tests, however, are prone to artifactual errors and require in-house handling

Question 31

You have just performed an ovariohysterectomy on a thin, 10-month-old, female Yorkshire terrier. The dog remains in a near comatose state four hours after the cessation of anesthesia. Your anesthetic protocol consisted of methadone premedication, intravenous propofol induction and maintenance on a pediatric circuit with isoflurane in oxygen. The dog was bright and alert with normal mentation prior to anesthesia. You suspect a deficiency in drug metabolism and elimination.

d) List three (3) diagnostic imaging modalities that would help to confirm the diagnosis of PSS. List the relative advantages and disadvantages of each.

Answer 31

• Ultrasonography: Can identify both intrahepatic and extrahepatic shunts. Non-invasive and does not require sedation or anesthesia. An inconclusive examination does not rule out congenital PSS. Affected by operator experience, bowel location obscuring the shunt, etc… At a minimum may detect micro hepatica and few detectable hepatic and postal veins, supporting the clinical suspicion of CEPSS. Able to locate renal calculi and hepatic AV fistulae. Identification of a retrograde pulsatile flow (hepatofugal) in the abnormal portal vein branch of the main portal vein may allow one to discern the involved liver lobe and reset it.
• CT angiography: Current “gold standard” for diagnosis of hepatic vascular disorders. 3D reconstructions enhance anatomy and surgical planning. Allows calculation of hepatic perfusion. Superior to intra-op mesenteric angiography. Requires sedation or anesthesia.
• Nuclear Scintigraphy: Rapid and non-invasive method to document abnormal hepatic blood flow. Utilizes Technetium-99m administered to the colon, allowing quantitation of time difference between liver and heart activity. Able to differentiate hepatic microvascular dysplasia (HMD) from CPSS (HMD has normal scintigraphy study). Very specific (non false-positives), but false-negative results may occur in very small shunts.

Question 32

You have just performed an ovariohysterectomy on a thin, 10-month-old, female Yorkshire terrier. The dog remains in a near comatose state four hours after the cessation of anesthesia. Your anesthetic protocol consisted of methadone premedication, intravenous propofol induction and maintenance on a pediatric circuit with isoflurane in oxygen. The dog was bright and alert with normal mentation prior to anesthesia. You suspect a deficiency in drug metabolism and elimination.

e) List three (3) surgical techniques that can be used to treat extra-hepatic PSS and the relative advantages and disadvantages of each.

Answer 32

• Ameroid constrictor: composed of hygroscopic material contained within a metal ring. The material swells over time, leading to gradual constriction of the shunt within. Additional shunt occlusion is provided by fibrosis around the vessel. This method offers the advantage of a gradual shunt attenuation, preventing acute portal hypertension. Disadvantages include the unknown rate of occlusion (dependent on plasma protein concentration among other factors) and often incomplete occlusion.
• Cellophane banding: Leads to acute inflammatory response, followed by low-grade foreign body tissue reaction. Vascular attenuation may be slower and less complete than with ameroid constrictors, but reports indicate that clinical signs resolve or are substantially improved in patients that survive the procedure.
• Direct ligation: allows immediate resolution of shunting and is quite reliable (no partial attenuation). May lead to severe portal hypertension and decrease in cardiac preload, precipitating cardiogenic shock. Portal and central venous pressure must be closely monitored and the ligature adjusted according to response.