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
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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.
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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.
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Cellular Origins and Functions of Prostaglandins
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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.
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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
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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.
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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
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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
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Figure 5-1 Total body water (TBW) fluid compartments.
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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?
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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?
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Albumin accounts for what percent % of plasma oncotic pressure?
80%
Causes of Hyponatremia
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Causes of Hypokalemia
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Causes of Hyperkalemia
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Causes of Hypocalcemia
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Box • 5-7 Causes of Hypomagnesemia
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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
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Causes of Hypophosphatemia
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Causes of Hyperphosphatemia
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Causes of Corrected Hypochloremia
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Causes of Corrected Hyperchloremia
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Causes of Hypoglycemia
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Causes of Hyperglycemia
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Reabsorption of filtered [HCO3−] by H+ secretion in the proximal tubule.
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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.