Basic bio Flashcards
Neutrophil extravasation. Leukocyte extravasation is a multistep process orchestrated by both hemostatic and cell–cell interactions. Margination and rolling of leukocytes along the vascular endothelium are mediated through interactions between endothelial selectins with their corresponding leukocyte ligands. Chemokines stimulate increased expression and enhanced binding affinity of leukocyte integrins, leading to firm adherence to endothelial cell integrins (e.g., intracellular adhesion molecule [ICAM]-1). Leukocyte diapedesis is facilitated by the adhesion molecule, platelet–endothelial cell adhesion molecule (PECAM)-1, and leukocytes follow chemokine gradients to the site of injury. IL-1, Interleukin-1; TNF, tumor necrosis factor
Proinflammatory response to alarm signals. In response to pathogen-associated molecular patterns (PAMPS) or danger-associated molecular patterns (DAMPS), toll-like receptors (TLRs) on the surface of resident macrophages induce various molecular signaling pathways. Many of these pathways lead to the translocation of nuclear factor kappa B (NFκB) into the cell nucleus, where it acts as a transcription factor, regulating the production of proinflammatory cytokines. The cytokines act directly and indirectly on a number of cell types. Interleukin (IL)-6 induces hepatic production of acute phase proteins, which in turn influence a number of inflammatory systems. Chemokines induce recruitment of inflammatory cells, which produce additional mediators. If the process is not properly balanced by antiinflammatory responses, tissue damage and systemic inflammation may result in serious consequences. CRP, C-reactive protein; NO, nitric oxide; ROS, reactive oxygen species.
The arachidonic acid pathway. Arachidonic acid is metabolized by the cyclooxygenase or lipoxygenase pathway to produce prostaglandins or leukotrienes and proresolution lipoxins, respectively. The inhibitory effects of several drugs on specific enzymes are denoted by a red X. COX, Cyclooxygenase; HETE, hydroxyeicosatetraenoic acid; HPETE, hydroperoxyeicosatetraenoic acid.
Cellular Origins and Functions of Prostaglandins
Functions of nitric oxide. Endothelial-derived nitric oxide synthase (eNOS) functions to maintain normal vascular tone via the vasodilatory effects of nitric oxide on vascular smooth muscle. In addition, nitric oxide modulates the interactions of platelets and leukocytes with the vascular endothelium. At increased levels, inducible nitric oxide synthase (iNOS) facilitates nitric oxide–derived free radical production and removal of target pathogens by macrophages. NO, Nitric oxide.
Complement pathway activation and effector functions. The complement cascade is activated via three different pathways, all of which culminate in cleavage of C3 into C3b and C3a. Complement proteins and breakdown products facilitate several aspects of inflammatory responses as well as pathogen removal via phagocytosis and membrane attack complex (MAC) production
The central dogma of molecular biology. Genomic DNA (gDNA) is transcribed to mRNA, starting at the first exon (E1), after the initiation of transcription. The whole gene sequence, not including the promoter region (P), is transcribed before splicing removes the introns (I). Translation of the mature mRNA sequence produces the protein.
The polymerase chain reaction (PCR). RNA or DNA (gDNA, genomic DNA) can be evaluated, but RNA is usually reverse transcribed into complementary DNA (cDNA) before the PCR occurs. First, the sample is heated to separate the DNA into single strands (denatured). The sample is then cooled to allow the primers to bind to their target sequence (annealing). Finally, the mixture temperature is increased to the optimum for DNA polymerase use. The DNA polymerase then synthesizes a new DNA template (extension or elongation). After each PCR cycle, the number of templates is doubled
The polymerase chain reaction (PCR). RNA or DNA (gDNA, genomic DNA) can be evaluated, but RNA is usually reverse transcribed into complementary DNA (cDNA) before the PCR occurs. First, the sample is heated to separate the DNA into single strands (denatured). The sample is then cooled to allow the primers to bind to their target sequence (annealing). Finally, the mixture temperature is increased to the optimum for DNA polymerase use. The DNA polymerase then synthesizes a new DNA template (extension or elongation). After each PCR cycle, the number of templates is doubled
Figure 5-1 Total body water (TBW) fluid compartments.
Intracelluar and extracellular compartment % of total body water?
Intracellular = 66% total body water and 40% total body weight
Extrecellular 33%, 20% total body weight = plasma 25%, interstital 75%
What is the osmolarity of body fluid compartments?
290-310mOsm/L
What precursors are used in fluids as buffer?
Lactate - liver to bicarb
Acetate - muscle
Gluconate - cells
What isotonic fluid is “unbalanced” and what happens when this is given as a bolus?
0.9% NaCL
mild increase Na, Marked increase Cl, moderated decrease bicarb and K (acidfying effect)
What percent of isotonic fluids (extracellular expanding fluids) are redistributed to the intersitial space?
75%
only 25% remain in intravascular space
What are hypotonic fluids?
- 45% saline
- 5% dextrose with 0.45% saline
2.5% dextrose with half strength LRS
Normosol M
Plasmalyte 56
D5W
large volumes can rapidly decrease osmolarity and cause cerebral edema
What are the side effects related to synthetic colloids?
decrese factor VIII and vW factor
impairment platelet function
interference in stability of fibrin clots
dose hypoproteinemia = 0.5-2ml/kg/day
shock dose 5-10ml/kg
What are the standard doses for blood products?
pRBC and FFP = 10-15ml/kg
whole blood = 20-25ml/kg
What is the formula for blood adminstration based on target PCV?
V rbc = blood V x (target PCV- current PCV/ donor PCV)
blood V = 90ml/kg dog and 50ml/kg cat
what is the PCV of packed rbc?
80%
lifespan 20-35 d at 4 C
How do you calculate fluid replacement?
What is the formula for daily water requirement?
FOR CATS: BW(KG)^75 × 80 = ML/DAY
FOR DOGS: BW(KG)^75 × 132 = ML/DAY
Isotonic Crystalloid Compositions?
Albumin accounts for what percent % of plasma oncotic pressure?
80%
Causes of Hyponatremia
Causes of Hypokalemia
Causes of Hyperkalemia
Causes of Hypocalcemia
Box • 5-7 Causes of Hypomagnesemia
What is Wipple’s triad?
A low blood glucose concentration with concurrent clinical signs of hypoglycemia, as well as resolution of clinical signs when the blood glucose level is normalized, constitutes a clinical definition of hypoglycemia known as Whipple’s triad
Box • 5-8 Causes of Hypermagnesemia
A serum concentration of magnesium greater than 2.51 mg/dL in dogs and greater than 2.99 mg/dL in cats is consistent with hypermagnesemia, but clinical signs are generally seen at levels exceeding 4 mg/dL. Electrocardiographic changes that may occur in patients with hypermagnesemia include prolongation of the PR interval, widening of the QRS complex, and, at higher concentrations, heart block and asystole. Hypermagnesemia may cause hypotension and can interfere with normal clotting and coagulation. Hypermagnesemia also has muscular effects similar to hypercalcemia, including weakness and decreased tendon reflexes.77,78 Treatment of hypermagnesemia includes fluid therapy and administration of loop diuretics (furosemide). Severe cases can be treated with calcium gluconate, as calcium is an antagonist of magnesium at the neuromuscular junction. Anticholinesterases such as physostigmine may also help reduce the actions of magnesium at the neuromuscular junction
Causes of Hypophosphatemia
Causes of Hyperphosphatemia
Causes of Corrected Hypochloremia
Causes of Corrected Hyperchloremia
Causes of Hypoglycemia
Causes of Hyperglycemia
Reabsorption of filtered [HCO3−] by H+ secretion in the proximal tubule.
Where does the majority of bicarb resorbtion occur?
Ninety to 95% of filtered HCO3− is reabsorbed in the proximal tubule, and the rest is reabsorbed in the loop of Henle, distal tubule, and collecting duct.
Table • 5-8 Normal Blood Gas Values in the Dog and Cat (mean ± SD)
Serum Anion and Cation Concentrations (mEq/L) in the Dog and Cat
Compensatory Responses to Simple Acid-Base Disturbances in Dogs
Septic chapter equations
Box • 6-3 Defects in Oxygen Uptake
Diffusional shunting: This is caused by slow blood velocity (prolonged transit time), which favors diffusional oxygen transport over convective oxygen transport (i.e., the movement of oxygen following a concentration gradient prevails over transport of oxygen within the bloodstream). It may occur in the intestine during shock states. The intestine relies on countercurrent blood flow to deliver blood to the villi. If the rate of flow is so slow that oxygen from the arterial blood can diffuse to the venous blood before it is delivered to the tip of the villus, the intestine will be hypoxic, but venous saturation will actually be increased.
Diffusional resistance: For cells to utilize oxygen, O2 must diffuse from the vascular space through the tissues, into the cell, and finally to the mitochondria. Oxygen is poorly soluble in aqueous solutions; therefore tissue edema will increase diffusional distance and limit oxygen availability to the tissues. Hypoxia may increase edema by increasing vascular permeability, thus leading to a “feed-forward” cycle of hypoxia and edema and more hypoxia. Impaired diffusion will result in a smaller gradient, less driving pressure for the oxygen to leave the hemoglobin, and thus higher venous saturation, despite tissue hypoxia. •
Arteriovenous shunting: One of the most obvious reasons for failure of oxygen uptake by the cells is the loss of normal capillary flow. In sepsis, trauma, and diseases associated with systemic activation of the inflammatory response, capillary obstruction can result from neutrophil-endothelial interaction, platelet aggregation, thrombi, or loss of normal vasodilatory function. As a result, arterial blood bypasses the hypoxic bed, leading to an increase in venous oxygen saturation.
Perfusion/metabolism mismatch: A cause of inadequate tissue oxygenation is perfusion/metabolism mismatch. Despite the normal excess (approximately four-fold) of oxygen delivery in relation to tissue demand, in some tissues and in some disease states the increased metabolic demand combined with reduced blood flow can lead to tissue hypoxia. A classic example is sustained tachycardia, when c_oronary perfusion is reduced because of shortened diastole, yet the metabolic demand of the myocytes is increased_.
Cytopathic hypoxia (mitochondrial dysfunction): Cytopathic hypoxia is classically associated with sepsis. Experimental studies of sepsis have demonstrated that despite direct measurement of adequate cellular oxygen, mitochondrial respiration is impaired. Proposed mechanisms to explain this “cytopathic hypoxia” include the following: •Inhibition of pyruvate dehydrogenase and subsequent lactate accumulation •Nitric oxide–mediated inhibition of mitochondrial electron transport •Poly-(ADP-ribosyl)-polymerase activation by reactive oxygen species and subsequent depletion of NAD+/NADH for oxidative phosphorylation
What does a CVP <0 and a CVP >10 indicate?
<0 = hypovolemic shock
>10 = cardiogenic shock
What level of deoxygenated hemoglobin is present in the blood before cyanosis occurs?
>5mg/dL
Normally what is PaO2 on room air and on 100% O2?
Room air >90mmHg
should be 5x inspired O2
O2 toxicity occurs if FiO2>60% for greater than 24 hours
Vasoactive and Inotropic Agents—Intravenous Constant Rate Infusion
SIRS Criteria for Dogs, Cats, and People
Diagnostic Criteria for Veterinary Acute Respiratory Distress Syndrome (ARDS)
What is the normal BMBT in the dog and cat?
Dog = 1.7 -4.2 min
Cat = 1.4 -2.4 min
Prolonged with thrombocytopenia, thrombopathia and vasculopathy
Affected by hematocrit and blood viscosity
Upto 2min intraoperator variation
What is activated clotting time, what pathway does it test and what is it influenced by?
Whole blood into 37 C tube with diatomaceous earth (contact activator 12)
Normal clot time dog <100s, normal cat <75s
Less sensative than PTT, influence by thrombocytopenia <15,000, thrombopathia, anemai, blood viscosity, incubation temperature
In order for PT, aPTT and ACT to be prolonged, what level is fibrinogen?
<50-100 mg/dL
Thrombin clotting time prolonged in hypofibrinogenemia
Differential Diagnoses of Prolonged Coagulation Times: Prothrombin Time and Activated Partial Thromboplastin Time
Differentials thrombocytopenia
Diffenertials thrombopathia
Disorders secondary hemostatsis
What is a massive transfusion?
Transfusion >patient blood volume (dog 90ml/kg, cat 66ml/kg) in 24 hours
OR
50% within 3 hours
Fibrinogen critically reduced
No clot is formed <50mg/dL livearly up to 300mg/dL
What clotting factors does hetastarch influence?
fibrinogen, vWF, F8
How does temperature affect platelet function?
33-37 (98.6F) = Decreased vWB mediated platelet adhesion
<33 C (91F) = decrease platelet function and TF-fVIIa complex activity
How does acidemia effect clotting?
Increased fibrinogen degredation
impairs coagulation protein activity
F10-F5a complex activity decreased 50% ph 7.2, 70% at ph 7
Plasma Component Transfusions
What is the MOA aminocaproic acid?
Lysine analogues, block binding and activation of plasminogen
anti-inflammatory via inhibition of interleukin
Other antifibrinolytics: aprotinin (serine protease, inhibits plasmin), Recombinant factor 7a
Platelet Transfusions
Antithrombotic Drugs: Preoperative Discontinuation and Therapeutic Recommendations in Cases of Uncontrolled Bleeding
What are the types of Von Willebrand disease?
Type 1: Reduced conc of all multmers - most common, Dobie, poodle, GSD, Airdale, Shetland sheepdog
Type 2: Disproporiate loss high MW multimers - German SHP and wirehair = severe bleeding
Type 3: almost complete absence vWF (<.01%) - Shetland sheep dogs, scottish terriers, chesapeake bay retrievers, dutch Kooikers
What is Virchow’s triad?
1) endothelial injury
2) vascular stasis
3) hypercoagubility
What is the pathopysiology of thromboembolism?
- endothelial damage: decreased ADPase
- Platelet agonists: hypoalbulmenima = increased TxA2
- Disease states: decreased NO
- Drugs: PGi2 inhibition by Cox
- Hyperactivty secondary hemostasis:
- increased exposure TF (damage)
- neoplasia - TF and procogaulant activates F10
- AT deficentcy
- activated protein C deficiency = sepsis, cancer, pancratitis - Hypofibrinolysis - PAI-1 acute phase protein
When is a does a low AT increase risk hypercoagubility?
<60%
What does a PTE look like on rads and what are most common lung lobes?
Most common lung lobes = right and caudal
Oligemia: areas of radiolucency on VD or DV (hypovasular lung)
Enlarged main pulmonary a
Attenutatio lobar a or v
Effusion in cats
27% dogs and 0-7% cats have normal rads
How do you test for PTE?
Supportive:
- Thoracic rads
- Arterial blood gas
- D-dimers - strong neg. predicitve value and supportive if quantive test high (>1000ng/dL)
- Echocardiography - pulmonary hypertension, thrombus, right MPA and heart enlarged.
- TEG
Definative:
- Selective pulmonary angiography - not clincially useful, gold standard
- non-selective pulmonary andgiography - less sensitve
- Pulmonary scintigraphy
- Helical CT pylmonary andiography (CTPA)
What are thrombolytic agents?
Streptokinase
Urokinase
t-PA (tissue plasminogen activator)
What conditions are associatd with feline DIC?
40% neoplasia (LSA, carcinoma)
26% pancreatitis
19% sepsis
13% infectious
What are causes of DIC?
Cytokines = endothelial damage
Leukocyte secreated platelet activiting factor
Decrease AT levels - consumption, impaired hepatic syn, degradation neutrophil elastase
Decreased activated protein C - consumption, cytokine downregulated thrombomodulin on endothelial cell, decrase protein S, impaired hepatic syn
Stimylate PAI-1 = suppress fibrinolysis
Underlying condition plus 3 or more of the following factors have been associated with diagnosis of DIC
thrombocytopenia
Increased PT, aPTT
Elevated fibrin-split
D-dimers
hypofibrinogenemia
reduced AT activity
red blood cell fragmenation
What is refeeding syndrome?
Sudden increase insulin = severe hypophosphatemia, hypokalemia and hyperglycemia
What is the temperture and timing of a steam sterilizer?
emperature and time requirements are interdependent, although typical temperature may be 121° C (250° F) for 30 minutes in a gravity-displacement sterilizer, or 132° C (270° F) for 4 minutes in a prevacuum unit. At higher temperatures, less exposure time is required, and vice versa.
Recommended Safe Storage Times for Sterile Packs Using Various Wrapping Materials
The “anatomy” of an articulating instrument (a needle holder)
The four blades that fit a #3 scalpel handle (i.e., 10, 11, 12, and 15) and four blades that fit a #4 scalpel handle (i.e., 20, 21, 22, and 23)
A Beaver surgical knife handle and selected beaver blades (#64 and #67
Three commonly used scissors: A, Curved Mayo; B, curved Metzenbaum; and C, operating (utility) scissors
A pair of Westcott scissors
Wire-cutting scissors, including A, the “notch” and B, serrated cutting edges
Four different rongeurs: two (A, Stille-Luer and B, Ruskin) double-action type and two (C, Lempert and D, Kerrison) single-action type.
Four periosteal elevators: A, Freer, B, Sayre, C, ASIF (Synthes/AO), and D, Langenbeck
This figure shows each of the following: A, Bone chisel. B, Osteotome. C, Gouge. D, Gigli saw. E, Bone-cutting forceps, and F, a trephine
Mayo-Hegar and B, Olsen-Hegar needle holders.
Castroviejo needle holder.
Right-angle; B, Babcock; C, Allis; and D, Ochsner-Kocher forceps.
Noncrushing forceps: A, Doyen intestinal; B, DeBakey; and C, Satinsky forceps
Patterns for thoracic and vascular DeBakey (A) and Cooley (B) forceps
Three commonly used hemostatic forceps: A, Halsted mosquito; B, Kelly; and C, Crile forceps
Brown-Adson; B, DeBakey, C, dressing; and D, Adson forceps
Backhaus (penetrating) clamps; and B, Lorna (nonpenetrating) clamps.
Figure shows five bone-holding forceps: A, Kern; B, Lane; C, Vebrugge; D, reduction forceps with a speed lock; and E, reduction forceps with points and a ratchet
malleable; B, Hohmann retractors; and C, spay (Snook) hooks.
Lister bandage scissors; and B, Spencer stitch scissors.
Jewelers’ forceps; B, vessel dilators; C, dissecting forceps; and D, tying forceps.
Nonlocking microsurgical needle holders with three different types of tips (straight, curved, and extra fine).
A microsurgical vessel clamp
An Alm microsurgical retractor
Comparison of the breaking strength of different tissues across time
Composition of collagen in GI submucosa?
type 1 = 68%
type 2 = 20%
type 5 = 12%
