ANZCVS 2012 Flashcards
- a) Name the end products of primary and secondary hemostasis and briefly describe how they are formed. (8 marks)
Primary hemostasis – end product: platelet clot; Endothelial disruption exposes subendothelial collagen to which platelets adhere via platelet glycoprotein VI receptor and to collagen-bound Von Willebrand’s factor via glycoprotein Ib receptor. Adherence stimulates the release of platelet cytosolic granular contents (ADP) which stimulate arachidonic acid metabolism and production of prostanoids like Thromboxin A2, recruiting and activate further platelets.
Secondary Hemostasis – end product: fibrin mesh; Simultaneously with platelet aggregation, blood cells are exposed to Tissue Factor (TF) immediately after tissue injury. TF is a cofactor to Factor VII, which then activated factors IX and X leading to the activation of prothrombin to generate thrombin. Thrombin is the central protein in the coagulation cascade, cleaving fibrinogen into fibrin and activating further platelets.
- b) Describe the clinical signs expected in animals with significant defects in primary and secondary haemostasis. (8 marks)
Primary Hemostasis: Petechia, mucosal damage, prolonged bleeding at injury sites.
Secondary Hemostasis: hematomas, hemarthrosis, intramuscular hemorrhage, effusions.
c) State the beneficial properties of transfusions of fresh frozen plasma, fresh whole blood and packed red blood cells and give an example of a surgical clinical situation in which each of these products could be used. (9 marks)
Fresh Frozen Plasma (FFP): contains all constituents of plasma, including coagulation proteins, vWF, natural anticoagulants, albumin and globulins. Indicated for inherited or acquired coagulation disorder, vWD and hypoproteinemia. Example: Doberman Pincher with vWD, presented with GDV.
Fresh Whole Blood: Same as FFP but including RBC’s. Low platelet concentration, requiring large volume to affect platelet levels. Example: Hemoabdomen (replaces volume, RBC’s and “some” platelets and clotting factors. Supplementation with FFP or Cryoprecipitate likely necessary depending on the level of platelet/clotting factor consumption).
Packed Red Blood Cells (pRBC’s): Does not contain clotting factors, vWF, natural anticoagulants, albumin or globulins. Exposes recipient to large amounts of RBC antigens. Example: Anemic but normovolemic patient who requires a surgical procedure (avoids fluid-overload); anemic patient with cardiac disease who needs surgery (volume -sensitive
- b) Describe, at a cellular level, the stages of wound healing in a small intestinal anastomosis from scalpel incision to wound maturity. (9 marks)
Mention the approximate time period for each stage. (3 marks)
Inflammatory phase – 48 hours – hemostasis and vasoconstriction, followed by diapedesis of inflammatory cells like neutrophils (first 24 hours) and macrophages (48 hours). Macrophages are fundamental for production of growth factors and cytokines, stimulating the migration and function of fibroblasts. Fibroblasts produce fibrin to seal the serosal layer.
Proliferative phase – 3 to 5 days- granulation tissue is formed (collagen + blood vessels) and collagen undergoes synthesis and lysis. Different from skin, where collagen is exclusively produced by fibroblasts, in the GI tract fibroblasts and smooth muscle produce collagen and elastin. Smooth muscle present in the muscularis mucosa and muscularis propria is primarily responsible for collagen production in the small intestines. Skin has collagens type I and III. GI tract has I, III and V.
Maturation phase – 5 to 21 days – Collagen is remodeled and reorganized to improve strength. Intestinal wall becomes thinner (less edema, better collagen fiber orientation).
- c) Describe how the integrity and strength of the sutured anastomosis changes over the timeline from incision to wound maturity. (7 marks)
Immediately following surgical incision, the strength of the wound is reliant upon the holding power of the sutures upon the collagen-rich layer (submucosa), as well as on a relatively fragile fibrin seal. Significant collagen breakdown occurs in the first 4 days due to upregulation of MMP’s, leading to relevant decrease in the strength of anastomosis (up to 70% for small intestines and colon). This is when dehiscence is most likely to occur. Risk factors include hypotension, poor O2 saturation, infection, excessive tissue trauma and tissue tension. Around 1 week post-surgery the intestines will have regained nearly 100% of the original bursting strength, but the strength of the scar will continue to increase for several months.
- a) Describe the process of direct bone healing of fractures. Include in your answer reference to inter-fragmentary strain theory. (20 marks)
Direct bone healing: Occurs under conditions of “absolute stability”, when strain at the fracture site has been functionally eliminated via anatomical reduction, compression of bone fragments and rigid fixation of the bone column. Healing occurs through intramembranous ossification, in which surviving osteoblasts and osteoblast precursors directly deposit new bone at the fracture gap. Since complete and perfect congruence of the entire bone surface is nearly impossible, primary bone healing occurs via a combination of Contact Healing and Gap Healing.
• Contact Healing – Only possible is fracture gap < 0.01mm (10 microns) and interfragmentary strain has been eliminated (less than 2%). Osteoclasts immediately ahead of injured osteons for a “spearhead” and advance across the fracture gap (cutting cones), removing devitalized one. Osteons elongate and directly bridge the fracture gap. Osteoblasts follow closely behind and deposit new bone. This results in a process of concomitant resorption and deposition of bone. Osteoblast orientation and multiple cutting cone elongation result on the formation of lamellar bone across the fracture gap (oriented parallel to the long axis of the bone).
• Gap Healing – Occurs when small gaps exist between zones of contact healing. Absolute stability is provided by the contact zones. Interfragmentary strain must have been eliminated (<2%) and the gap must not exceed 1mm. The gap is initially filled with fibrin matrix and vascular sprouts, which are quickly remodeled with collagen Type I and III. Within days lamellar bone fills the gap in a process similar to intramembranous ossification. This lamellar bone is initially oriented perpendicular to the long axis of the bone (in contrast to contact healing), making it mechanically weak. Within 3 to 4 weeks cutting cones cross the fracture gap and unite perpendicularly-oriented lamellar bone with each end of the fracture. Over time, remodeling transforms the perpendicular lamellar structure into longitudinally oriented lamellae.
- a) Describe the process of indirect bone healing of fractures. Include in your answer reference to inter-fragmentary strain theory. (20 marks)
Indirect Bone Healing: Occurs when fractures are not anatomically reconstructed or stabilized by rigid internal fixation. Implants are used to bridge zones of comminution and provide “relative stability”. (this is also how fractures not treated with internal fixation will heal). The process is organized in five overlapping stages:
- Inflammation: Loss of vascular integrity leads to hemorrhage and reduction of local oxygen tension. Primary hemostasis occurs and platelets release cytokines and growth factors, recruiting macrophages, neutrophils and other inflammatory cells. Fibroblast and platelet growth factors activate progenitor mesenchymal cells within periosteum, muscle and soft tissues. These progenitor cells will differentiate into osteoprogenitor cells, modulate inflammation and provide anabolic factors to encourage bone healing. Secondary hemostasis produces a hematoma composed of fibrin matrix, which provide further degranulating platelets and serves as a scaffold for mesenchymal cell infiltration as well as macrophages, endothelial cells and fibroblasts. The end result of this phase is the production of a provisional cell, growth factor and matrix-rich scaffold along the cortex, medullary cavity and periosteum into adjacent soft tissues. This scaffold is eventually remodeled into granulation tissue to form a reparative granuloma, termed external callus.
- Intramembranous ossification: Mimics the process of skeletal development. Progenitor cells from the overlaying periosteum proliferate and differentiate into osteoblasts to start new bone production adjacent to the fracture gap, between the periosteum and cortex (no cartilaginous intermediate). This leads to the formation of an early hard callus, but is insufficient to bridge and stabilize the fracture.
- Soft Callus Formation (chondrogenesis): Starts as soon as a robust bed of granulation tissue is formed across the fracture gap (external callus). Granulation tissue transitions to fibrovascular tissue and finally to fibrocartilage containing collagens type I and III over several weeks. The matrix is initially avascular as resembles the proliferative zone of the physis. The persistent tissue hypoxia, presence of growth factors and cell-matrix interaction cause stem cell population to differentiate into chondrocytes. These chondrocytes produce extracellular matrix rich in collagen Type II, aggrecan and other cartilage-specific proteins. The resulting callus is termed “soft callus” and bridges the fracture gap. This callus is fragile, however, and remains insufficient to decrease strain to a level that permits osteoblast survival.
• Interfragmentary strain: The formation of various tissue types during bone healing is directly dependent on the degree of interfragmentary strain. Strain is defined as the effect of loading on a fracture gap. Practically it is calculated by dividing the resulting length of the gap after loading by the original length. Smaller fracture gaps experience greater strain (concentrate strain) than large gaps. Granulation tissue can withstand almost 100% deformation, and is therefore the tissue found it to be formed within fracture gaps undergoing significant strain. As strain is reduced, tissues region collagen can develop and form a soft callus. Specifically, fibrocartilage is capable of accommodating 10 to 15% deformation. Osteoblasts and osteocytes can only survive in a very low strange environment, and bone can only tolerate 2% deformation.
- Hard Callus formation (endochondral ossification): Chondrocytes within the soft callus undergo hypertrophy and begin to mineralize the adjacent extracellular matrix next to the zone of intramembranous ossification. This occurs due to down-regulation of cartilage-specific genes, leading to decreased production of collagen type II and aggrecan and increased production of collagen type X. Collagen type X is unique to hypertrophic chondrocytes and a marker of endochondral ossification. MMP’s are expressed and degrade the matrix in preparation for calcification. Hypertrophic chondrocytes also secrete Vascular Endothelial Growth Factor (VEGF) which stimulates vascular invasion of peripheral parent bone. Mineralized cartilage has the necessary stiffness and strength to limit strain to levels that will support the survival of osteoclasts and osteoblasts. These cells can now advance from the periphery to the center of the callus. Osteoclasts remove mineralized cartilage and osteoblasts lay new woven bone. Radiographically this woven bone appears larger than normal and is often misshapen.
- Bone remodeling: This final phase of bone healing lasts months to years. The abnormally large and misshapen woven bone produced during ostechondral ossification is weaker than primary bone, and therefore gradually replaced by lamellar bone. Resorption occurs withing each of the four bone envelopes (periosteal, endocortical, trabecular and intracortical). Osteoclasts and osteoblasts work together as Bone Multicellular Units (BMU) is a continuous process of activation, resorption, reversal, formation and quiescence. The result is the formation of Osteon, a structure composed of concentric layers of bone enclosed by a cement line with a central Harversian canal. Bone remodeling is strongly influenced by Wolff’s Law, which states that bone in a healthy animal will adapt to the loads under which it is placed. This occurs through the process of mechanotransduction. Bone generates a small electrical potential when it deforms, with an electropositive environment on the concave surface (compression) and electronegative environment on the convex side (tension). Electropositivity is associated with an increase in osteoclastic activity, whereas electronegativity induces osteoblastic activity. This justifies the fact the cortical bone under compression (concave surface) typically appears osteopenic on radiographs, while bone under tension (convex side) appears sclerotic.
- b) With respect to direct and indirect bone healing explain your choice of repair method for a fracture of the lateral aspect of the humeral condyle in an adult dog. (5 marks)
The lateral humeral condyle is responsible for a significant amount of weight bearing, increasing the chance of complications which mostly stem from inadequate stability. This is particularly a problem in adult dogs. The approach is usually craniolateral. The goal with this fracture is to achieve anatomical reduction, interfragmentary compression and rigid stability. This is typically achieved via the use of a transcondylar screw placed in lag fashion across the condyles (intercondylar compression), followed by a caudolateral plate extending from the lateral epicondyle to a few centimeters proximal to the fracture line (enough to ideally allow the application of 3 screws per segment). Screws are directed craniomedially. Care must first be taken to carefully align the articular surface, followed by the lateral epicondylar crest. Meticulous anatomical reconstruction and interfragmentary compression will eliminate fracture gaps. This, coupled with adequately sized and positioned implants will effectively eliminate strain (below 2%), allowing primary bone healing to take place.
Similar fractures involving any degree of comminution cannot be anatomically reconstructed nor compressed. Care must be taken to align the articular surfaces (critical step). Intercondylar compression may be possible, but the remaining epicondylar fracture will have to be bridged using an adequately sized plate. Healing will be indirect, involving the production of a bone callus.
- Discuss the use of perioperative antibiotics in routine, elective orthopedic surgery in dogs. Include in your answer a discussion of the relevant indications for use, the likely micro-organisms to be targeted, the level of contamination required for sepsis to occur and your choice, dose and scheduling of antibiotic agent. (25 marks)
Perioperative antibiotics are generally indicated in elective orthopedic surgeries where implant infection can lead to catastrophic results. These are typically clean procedures when contamination and infection are not suspected at the time of the procedure. The use of antibiotics should NEVER replace the need to meticulous surgical technique and adherence to surgical asepsis. The most-likely microorganism to be encountered include Staphylococcus pseudointermedius, but S. aureus, Enterobacteriaceae, Enterococcus spp and Pseudomonas spp are also possible. A bactericidal antibiotic predominantly effective against gram positive bacteria should be administered at least 30 minutes before the beginning of surgery and repeated every 90 minutes. Good options include beta-lactam antibiotics like first-generation cephalosporins (Cefazolin 22mg/kg IV). Clean surgical wounds without breakage of sterile technique or known contamination do not require post-operative antibiotics. Contaminated wounds should be swabbed for culture at the end of the procedure. Antibiotics should be prescribed for 48 hours, and extended for 7 days based on culture results (if positive).
One exception to this rule may be the TPLO procedure. Recent data appears to indicate that the use of post-operative antibiotics may have a protective effect against surgery-site infections.
Theoretically any level of contamination may cause infection. In practical terms, however, only contaminated or dirty wounds require post-operative antibiotics (guided by culture). Minor breaks in sterile technique can be managed with thorough lavage and perioperative antibiotics alone. A swab should still be obtained for culture prior to surgery site closure.
A five-year-old male Dalmatian is presented to your clinic in a near comatose state. He has a very large bladder on palpation and you quickly discover this is due to a blockage in the urethra as you are unable to pass a catheter beyond the base of his penis due to the presence of a urethrolith.
- a) What is the most likely underlying primary composition of this urethrolith?
a) Ammonium Urate
A five-year-old male Dalmatian is presented to your clinic in a near comatose state. He has a very large bladder on palpation and you quickly discover this is due to a blockage in the urethra as you are unable to pass a catheter beyond the base of his penis due to the presence of a urethrolith.
b) Provide a pathophysiological explanation for this dog’s presentation. Include expected biochemical, electrolyte and ECG abnormalities. (6 marks)
b) Dalmatians do not convert most of their metabolic urate into allantoin like other breeds, and excrete urate in bulk (30-40% urate conversion versus 90% for other breeds).
Prolonged urethral blockage leads to severe hyperkalemia, metabolic acidosis and post-renal azotemia. Hypocalcemia (ionized) may also be present. Hyperkalemia may lead to life-threatening cardiac arrhythmias due to its effect on cardiac electrical conductivity. These may begin as bradycardia and spiked T-waves, progressing to depressed R-waves, prolonged QRS and PR intervals and ST segment depression.
A five-year-old male Dalmatian is presented to your clinic in a near comatose state. He has a very large bladder on palpation and you quickly discover this is due to a blockage in the urethra as you are unable to pass a catheter beyond the base of his penis due to the presence of a urethrolith.
c) Discuss how you would go about emergency medical stabilization of this patient given the derangements noted in part 1b) above, prior to attempting urethrolith removal. (6 marks)
c) Management of this patient should include evaluation of hemodynamic status, correction of metabolic derangements (particularly hyperkalemia, and metabolic acidosis) and urinary diversion. The passage of a retrograde urinary catheter for urohydropulsion can be attempted in such moribund status. The use of lubrication, local anesthetics and sacro-coccigeal epidural block with local anesthetic may facilitate the process. If urinary catheter passage is not possible, intermittent cystocentesis can be performed to relieve and prevent recurrence of bladder distension. In the case the bladder should be completely emptied with each drainage to decrease the risk of urine leakage within the abdomen. A cystostomy tube can also be placed using sedation and local block or simply local block in such moribund patient. Intravenous fluids should be provided for at least 15 minutes prior to the induction of anesthesia. LRS is currently considered the fluid of choice (over 0.9 % NaCl) for these cases. Its potassium concentration is too low to create further hyperkalemia (about 4 mEq/L) and the lactate is converted into NaHCO3 by the liver, exerting a much needed alkalinizing effect. If this patient’s hyperkalemia exceeds 8 mEq/L, 10% Ca Gluconate should be administered which the EKG is closely monitored. Ca Gluconate does not affect potassium levels, but raises the threshold for cardiac myocyte depolarization, thereby acting as a cardioprotective agent. Intravenous dextrose can be administered to drive potassium intracellularly by cotransportation. Sodium Bicarbonate can be administered if severe metabolic acidosis is present, particularly is concurrent ionized hypocalcemia.
A five-year-old male Dalmatian is presented to your clinic in a near comatose state. He has a very large bladder on palpation and you quickly discover this is due to a blockage in the urethra as you are unable to pass a catheter beyond the base of his penis due to the presence of a urethrolith.
d) You are successful in your attempts at emergency medical stabilization. Describe the technique to non-surgically relieve the urethrolith obstruction. (6 marks)
d) An adequately-sized urethral catheter should be lubricated and sterily introduced into the urethra. Once the obstruction is met a syringe containing sterile fluid (LRS or 0.9% NaCl) can be attached and the plunger “pulsed” with mild to moderate pressure to cause intermittent urethral distension. This is done concomitantly with progressive advancement of the catheter with the intention of driving the calculus back into the bladder.
A five-year-old male Dalmatian is presented to your clinic in a near comatose state. He has a very large bladder on palpation and you quickly discover this is due to a blockage in the urethra as you are unable to pass a catheter beyond the base of his penis due to the presence of a urethrolith.
e) If your method to relieve the obstruction non-surgically is unsuccessful, describe the technique for surgical removal of a urethrolith at the base of the os penis, including the relevant anatomical features. (6 marks)
e)The technique of choice would be a pre-scrotal urethrotomy. The patient is positioned in dorsal recumbency and the area extending from the scrotum to the prepuce is clipped and aseptically prepared. The scrotum is included in the surgical field in case conversion to scrotal urethrotomy/urethrostomy becomes necessary. The prepuce is flushed with dilute antiseptic solution to decrease contamination prior to skin prep with chlorhexidine and alcohol swabs. The urethra is catheterized in retrograde fashion to facilitate identification during the surgical approach. A 1 to 2 cm long incision is performed on the midline immediately cranial to the scrotum. Dissection is continued through the subcutaneous until the paired retractor muscles are identified and laterally retracted. The urethra and surrounding corpus spongiosum are identified as a purple, 3 to 4 mm wide longitudinal structure bordered on either side by the white tunica albuginea. A longitudinal incision is made on the urethral midline, over the catheter, the calculus or just proximal to the calculus using #15 blade. Hemorrhage is expected due to the highly vascular carpus spongiosum and should be controlled using only pressure (avoid electrocautery). The calculi are removed, and the catheter is advanced into the bladder. A cystotomy can be performed to retrieve cystic calculi. The urethrotomy can be either closed primarily or allowed to heal by second intention. The latter option will be associated with much more hemorrhage, but the wound will heal within 14 to 21 days. The skin surrounding the stoma must be kept lubricated to prevent urine scalding. If primary closure is elected, both the urethral mucosa, submucosa and muscularis, as well as the surrounding corpus spongiosum should be closed using 5-0 monofilament absorbable sutures on a taper needle. Suture pattern can be simple-interrupted or continuous. Subcutaneous and skin are closed in routine fashion.
- A six-year-old Labrador is presented to your clinic with progressive dyspnea. On thoracic auscultation the heart and lung sounds are muffled. Thoracic radiography confirms a bilateral pleural effusion.
Answer all subparts of this question: - a) List the different types of pleural effusions. (5 marks)
Pure transudate, modified transudate, exudate, hemorrhagic, chylous, “other” (i.e. pseudochylous, biliary effusion across the diaphragm)