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249 Cards in this Set
- Front
- Back
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What organ is primarily involved in glucose metabolism> |
the liver |
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Where and in what form is glucose stored? |
Glycogen in the liver and muscle |
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What are the steps of glycogenesis? |
Glucose-->G6P (by enzyme Glucose 6 phosphatase)-->G1Phosphate-->Glycogen |
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What are the steps of glycogenolysis? |
-requires ATP for the removal of glucose molecule and dephosphorylation from G6P to glucose |
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What cells have Glucose-6-Phosphatase and which ones do not? |
Have: Liver, kidney, intestine Do not have: brain and muscle (use glucose as primary fuel source, ensures ready supply of energy needs for these cells) |
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What is the net gain of ATP in glycolysis? |
2 |
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What is glucose converted to in aerobic glycolysis? |
Pyruvate is converted to Acetyl CoA |
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Where does glycolysis take place |
cytoplasm |
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Where does citric acid cycle take place? |
mitochondira |
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What happens to pyruvate in aerobic metabolism? |
becomes lactate |
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What is the preferred hepatic energy source in the fed state? |
Hepatic glycolysis can generate energy in the form of ATP but the preferred is oxidation of ketoacids |
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What happens when glucose is scarce and where does this process occur? |
Glycogenolysis (liver and muscle) |
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What happens when glycogen stores are depleted in a fasting state?/ |
Low blood sugar-->glucagon-->gluconeogensis |
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What cells are capable of gluconeogensis? |
Liver and kidney |
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What substrates are usable in gluconeogenesis? |
pyruvate, amino acids, lactate, glycerol |
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What amino acid is most easily converted to glucose? |
Alanine |
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What processes enhanve gluconeogenesis? |
Fasting, critical illness, and anaerobic metabolism |
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What is the the Cori Cycle and it's ultimate purpose? |
The cori cycle is used to convert lactate to glucose as a means of preventing lactic acidosis. lactate in liver-->pyruvate in liver-->glucose in liver-->transported in blood to muscle-->glucose in muscle-->pyruvate (in muscle)-->lactate (in muscle)-->lactate transport ed to liver |
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What is the glycogen storage limit of the liver and what happens to excess glucose? |
100g, govnerted to fat by phosphogluconate pathway |
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What is the breakdown product of fat metabolism? |
Acetyl CoA..this is why free fatty acid and lipid cannot be used for gluconeogensis because Acetyl CoA can't be converted back to pyruvate |
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What are the goals of nutrition? |
minimze protein loss and provide key nutrienst |
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What is the percentage of total body water and how is this divided between cellular component? |
2/3 of total body mass, 2/3 intracellular and 1/3 extracellular |
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What are the body fuels and how many kcal do you get per gram |
Fat-->can be stored-->9 Protein-->can't be stored and in the underfed state proteolysis takes place to provide AA for gluconeogensis Glucose-->stored as glycogen gets rapidly depleted but there is still a demand for carbs in stress metabolism-->4 carbs and protein metabolism are linked |
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How many kcal/kg/day are needed? |
25 (50% from carbs, 20% protein,30% fats) |
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How much does each of the following affect the calorie requirement? Trauma, prnegnancy, lactation, burns |
20-60%, 300kcal/day, 500 kcal/day Burn patients: 25 + (30kcal/dayx % burn) protein intake for burn is 1 + (3g x % burn) |
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What source of fuel needs to be replenished in burn patients? |
Protein |
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How long is the supply of glucose available from stored glycogen? |
24-36 hours |
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What happens when fasting extends beyong the glycogen supply? |
Gluconeogensis from amino acids (proteolysis), ketone body production from fat |
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How does inflammation impact glucose metabolism |
Increased rate of glucose production from proteolysis, decreased glucose recycling and limits ketone production |
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What is the significance of short chain fatty acids? |
Primarlily produced from fermented fiber in the colon, primary source of fuel for colonocytes |
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What is the significance of medium chain fatty acids? |
Diffuse directly into portal circulation |
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Long Chain fatty acids are significant for what? |
Require micelle formation, lipase, chylomicron formation, transport through lacteals, lipoprotein lipase for transport into adipose tisse, and chylomicron remnants go back to the liver for storage, transport as VLDL/LDL, or as energy production, main source of energy for the body |
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What are the essenitial fatty acid? |
Linoleic and linolenic (both long chain) |
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What are the precursors for inflammatory mediators (PG, leukotrienes, thromboxanes) |
Long chain fatty acids |
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How does protein metabolism differ from carbs and lipds |
produces nitrogen |
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What is the route for amino acids |
Protein ingested-->pepsin and pancreatic peptase (trypsinogen,chymotryp)-->AA, di,tri-peptides-->secondary active transport to intestinal cells (primarily jejunum)--> pass through the liver extracted for synthesis of proteins |
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what happens to branched chain AA |
leu, isoleu, val cannot be extracted by liver and are taken up by muscle these are the only AA metabolized outside the liver |
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What happens to excess AA |
degraded, used for glycogenesis or FFA |
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Trypsinogen |
duodenum-->enterokinase-->makes trypsinogen into trypsin-->trypsin activates other pancreatic proteases |
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What organ is the prime regulator for AA production or breakdown |
Liver |
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What does metabolism of protein generate and what are the subsequent processes? |
Ammonia-->converted to urea primarily by liver-->glutamine or alanine trasports ammonia to other orgnans-->then excreted by the kidney |
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Following injury what are the major alterations in glucose metabolism? |
-glucose levels are elevated with low insulin intiially, then insulin levels increase but high glucose levels persist, suggesting insulin resistance. Glucose production is primarily done by the liver from 3 carbon chains from peripheral tissues. Rising insulin concentration fails to regulate glucose mobilization into the cells |
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What are the alterations in protein metabolism following injury? What major amino acids are used? |
Skeletal muscle breakdown to provide AA. The main amino acids are glutamine and alanine.
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What are all the uses of glutamine during stress? |
-Liver: glutamine converted to alanine for glucoenogensis -Kidney: glutamine-->ammonia-->excretion along with acids -Gut: glutamine converted to alanine and ammonia-->portal venous blood-->ammonia converted to urea and excreted |
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What increased the rate of uptake of glutamine by kindey and gut? |
glucocorticoids |
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How do you calculate nitrogen balance? |
Protein/6.25 - (Total Urea Nitrogen + 4) -between -2 and 2 is normal -sick patients usually <-2 because of protein catabolism |
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What are the early and pro-inflammatory cytokines? |
IL1, TNF, IL6, Prostaglandins, and Leukotrienes (fever, acute phase proteins, insulin resistance) |
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What stimulates release of IL 6 and what does IL 6 do |
IL1 and TNF, releases IGF-1 which increases proteolysis and AA release from the muscle |
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What are that anti-inflammatory cytokines, eicosanoids? |
IL 4, 10, 13, PG3, LT5 |
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How does IL6 regulate protein metabolism during injury? |
It alters hepatic protein synthesis by reducing the amount of albumin and transferrin that are produced and increaseing acute phase protined (fibrinogen and C-reactive protein) -Acute phase proteins limit the destruction done by inflammation |
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What causes bacterial translocation? |
1) gut permeability (injury) 2) decreased host immunity (medications) 3) increased bacterial load in the gut (gut stasis) |
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What prevents translocation? |
glutamine or enteral feeds |
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How is glutamine used in sepsis? |
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How do you calculate Respiratory Quotient and what is the significance? What is the RQ for pure metabolism of fat? protein?carbs? |
-CO2/O2, it all boils down to metabolism of fats, protein, and carbs. Patients with high RQ are overfed and can be difficult to wean from vent. Patients with low RQ are underfed .7, .8, 1.0
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With RQ > 1 what is happening with carbs and lipids? How do you treat? What about RQ <.7? |
-excess carbs are being converted to fat, treat by decreasing carbs, when <.7 treat by increasing carbs |
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What is the caloric need and what percentage comes from each component> |
-25kcal/kg/day, (50% glucose, 20% protein, 30% fat) |
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What is the composition of TPN? |
1000cc bag TPN and 250 fat emulsion bag Glucose-->50% (20%-->200x3.4 =680) LIpids-->30% (1.1kcal/cc 10% soln, 2kcal/cc 20%)-->250x2=500 Protein-->20%-->7% x1000=70 (70x4=280) 500+680+280=1460 |
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What is the timeline of phases of wound healing? what cells show up in what order? |
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What is the initial inflammation response to tissue injury? |
1. Exposed collagen and endothelium release Platelet activating factor and Tissue factor 2. Tissue Factor-->clotting cascade 3. Vasoconstriction from platelets and TXA 3. Platelets release PDGF-->macrophages and neutrophils 4. Fibrin crosslinks platelets to make plug 5. Vasodilate-->leukocyte migration |
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What is the first nucleated cell to arrive for wound healing? Function? |
-PMNs, phagocytize and remove debris |
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When do macrophages arrive and what is the function? |
-after PMN's to replace them, DOMINANT role, releases IL-1 and TNF alpha |
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What releases TNF alpha and what does TNF alpha do? |
One of the first cytokines activated -stimulates proteolysis -increases cell adhesion molecules -promotes clotting -increases HR, CO, and decreases SVR (high concentrations can cause circulatory collapse) |
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What releases IL1, when do you see it during inflammation and wound healing, what does it do? |
-Macrophages -At the beginning with TNF -Synergistic with TNF alpha, causes fever Alveolar macrophages cause fever by releasing IL-1 during atelectasis |
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What releases IL-6? |
-TNF alpha and IL1 -stops production of albumin, prealbumin, and transferrin -increases synthesis of acute phase proteins |
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What is the function of IL8? |
promote chemotaxis and angiogenesis |
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In response to hypoxia, what factors are released by platelets and macrophages? |
Angiogenesis factors: PDGF, FGF, EGF, IL8 |
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What are chemotactic factors for inflammatory cells? |
-PDGF, PAF, complement 3 & 5, IL8 (bring in the platelets and PMNs and get rid of stuff) |
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What are chemotactic factors for fibroblasts |
PDGF, EGF, FGF (growth factors) |
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What are the main producers of growth factors? |
Macrophages |
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What is the only GF that is immunosppresive |
TGF beta-inhibits lymphocytes and leukocytes |
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Which cytokine in innate immunity downregulates the immune response? |
IL 10 |
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What is the function of IL 15 and IL 18? |
15: activates NK cells in response to viral infection 18: increase interferon release from NK and T cells |
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What is the function of interferons? |
-releases by IL 18 -activated macrophages, NK cells, and cytotoxic T cells -inihibit viral replications -MHC upregulation |
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What is the function of dendritic cells? |
-Antigen presenting cells that bridge innate and adaptive immunity |
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What is the function of Natural Killer Cells? What activates Natural killer cells? |
-activated by IL 15 - phagocytizes cells that have low MHC expression -Does not eat pathogen itself, but eats the cell infected with the pathogen |
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What is the classical complement pathway? |
-C1, C2, C4 -C1 binds to antigen or binds to antibody bound to antigen -these form eventual C3/5 convertase whch is the common convergence point of complement pathways for destruction of the pathogen |
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What is the alternative complement pathway? |
activated by endotoxin, the intial step is C3 activation, with the production of factors B D and P |
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What electrolyte is required for the activation of both the alternative and classic complement pathways |
Magnesium |
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Where are the complement proteins synthesized? |
the liver |
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What are the products of complement? |
-anaphylotoxins: C3a, C4a, C5a - membran attack complex: C5b-C9b, inserts into the cell membrane of the pathogen for destruction -can also attack normal cells infected with bacteria |
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Which complement proteins are responsible for opsonization? |
-C3b and C4b |
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what are the oxidants generated in inflammation by what enzymes and what are the defenses against these oxidants? |
NAPH Oxidase-->Superoxide radical-->Dismutase Xanthine Ox-->Peroxide-->Peroxidase Myloperox-->Hydrochlorous-->taurine scavenger
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What is the deficiency in CGD? |
-NAPH oxidase is missing and there is no formation of the superoxide radical |
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What is the main substrate for inflammation regulation by the cyclooxegenase/lipoxygensase pathway> |
-phopholipids from essetial fatty acids (linoleic, linolinic) |
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What catalyzes the reaction of phospholipid to arachadonic acid and what inhibits this reaction? |
-Phospholipase -GLucocorticoids: this is how they stop inflammation |
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What are the mediators for the cycloxygenase pathway? |
Prostoglanding, PGI, PGE -cause vasodilation, decreased SVR Postoglanding PGG and TXA -causes vasoconstricition, and platelet aggregation |
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What are the mediators for the lipoxygendase pathway? |
leukotrienes and lipoxins -Leukotrienese LTC,D,E-cause vasoconstriction -LTB is for chemotaxis of PMN's and eosinophils -Lipoxins are antiinflammatory
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What are COX1, COX2, and reversible and irreversible binders? |
-COX1 constitutively expressed on all cells -COX 2 selective to inflammation -NSAIDS reversibly bind -ASA irreversibly binds -if these bind, decrease prostaglandin, decreased mucosal barrier in stomach, increase risk for ulceration |
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What are the different components of the proliferation phase of wound healing? |
-Granulation, Epithelialization, Wound contraction, Collagen deposition |
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How does granulation tissue form? |
-Fibroblasts-->firbronectin and hyaluronic acid (5-7 days after injury) -used to build Provisional Extracellular matrix -PDGF, EGF, FGF, and fibronetctin stimulate myofibroblasts to migrate Over this matrix -Neovascularization from these factors -MMPs (need Zn) digest ECM and allow for enothelial proliferation |
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What happens during epithelialization? What is the major source of cells? |
-1-2mm/day and requires granulation tissue -Keratinocytes from hair follicles(#1) migrate (also from sweat glands and wound edge) -migration of cells stimulated by growth factor -as cells migrate, MMPs and tpa destroy scap to allow for proliferation -Epithelial cells form new basement membrane |
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When does wound contraction peak |
10 days |
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What is the maximum peak of collagen deposition, what is the percentage of strength of the wound at 6 weeks? 12 weeks? |
-3 weeks, breakdown ECM, put down chondroiton sulfate, stop GF stimulation -60% and 80% |
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What is the predominant collage present? |
Type 1 |
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What is the rate of perinpheral nerve regeneration |
1 mm/day |
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What is weakest time point for small bowel anastamosis? What is the strength layer of the bowel? |
-3-5 days -submucosa |
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What are the types of collage in the body and where are they found? |
Type 1: bone, teeth, most common Type 2: Cartilage Type 3: Granulation tissue Type 4: basement membrane, eye |
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How does collagen undergo crosslinking? |
Every 3rd residue on collagen is proline with abundant lysine, these residues must undergo hydoxylation (hydorxylase) to cross link. In order for hydroxylation to occur you need: Vitamin C, alpha ketoglutarate, Oxygen, Fe |
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What inhibits crosslinking of collagen |
d-penicillamine |
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What are impediments to wound healing? What is a treatment for issues with wound healing due to steroid administration? |
-Bacteria, necrotic tissue, edema, diabetes, steroids, ischemia -Vitamin A (25,000 IU per day) |
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What Defects are associated with the following diseases? Osteogenesis imperfecta, Ehlers-danlos? Epidermolysis bullosa? Scurvey? Pyoderma gangrenosum? Marfans? |
-Type I collagen, Collagen defect, Excessive fibroblasts (tx phenytoin), Vit C, immune dysfuntion, fibrillin |
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What is the only immunoglobulin the crosses the placenta? breast milk? |
IgG, IgA |
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What is the function of IL2? |
-activated cytotoxic T cells and NK cells |
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What is the classification of B cells? |
-Cell mediated Immunity - Memory Cells - Effector Cells (humoral)
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What is the classification of T cells |
Helper T cells Cytotoxic T Cells Natural Killer Cells |
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What are the subclassifications for helper T cells and what cytokines are involved? |
-Effector and Memory -Effector is divided in to TH1 and TH2 -TH1 cells produce IFN gamma-->targets macrophages-->cell mediated immunity -TH2 cells-->produce IL4-->targets B cells-->secretes more Ab (Ab mediated immunity) |
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What activated cytotoxic T cells? What is the result? |
-IL2 -attacks cells that are infected -CD8 stabilizes the reaction -Attacks cells with antigens attached to MHC 1 receptors |
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What activates natural killer cells? How is this different from cytotoxix T cells? |
-IL2 -attacks cells with low MHC expression and attacks cells with bound Ab |
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What is IL 4 associated with |
relaeased from TH2 cells to increase antibody production |
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B cell secretion of Ab is impacted by? |
-needs Th2 activation |
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What class cells do cytotoxic T cells attack? |
-Attack cells with MHC I receptors that are presenting non self antigens |
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What does MHC class II receptor interact with? |
-CD4 cells -on antigen presenting cells (dendritic, ab) -present exogenous antigen -The MHC II-antigen complex present on B cells or dendritic cells activates Tcells |
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What happens in bacterial infection? |
-APC recognizes, engulfs and presents on MHC II receptor -this antigen-receptor complex is recognized by T cells and activated effector T cells -There are 2 types of effector cells (TH1-->IGN gamma--> activates macrophages for cell mediated immunity and TH2-->IL4-->activates B cells for antibody mediated immunity) |
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What happens in viral infection? |
-Cell engulfs virus and presents on MHC 1 receptor -this is recognized and attacked by cytotoxic t cell |
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What antibodies are opsonins? |
IgM and IgG |
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What ab has role in mucosal immunity? |
IgA |
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What are the hypersensitvity reactions> |
Type I: immediate-allergies Type 2: ab mediated- hyperacute rejection Type 3: Deposition- serum sickness Type 4: delayed, chronic rejection |
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What are the primary lymphoid organs |
liver, bone, thymus |
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What happens during activation of platelets during coagulation after injury? |
Endothelium releases PAF -GP1b on platelets is linked to collagen on vessel wall by vwf -This activates GpIIb, which allows for platelet aggregation, requires Calcium -released thromboxane from platelets causes vasoconstriction |
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How does ASA work? |
binds COX receptors -Prostaglandins: made in the epithelium and can be resynthsized so these can continue to inhibit platelet aggregation -Thromboxane: inhibited and platelets cannot resynthesize COX, so platelet aggregation is inhibited |
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Where is vwf made and what is it;s function? |
Endothelium, links GpIb on platelets to collagen on endothelium |
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In the coagulation cascade, what is the convergence factor for both pathways? |
Factor 10 |
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What is the prothrombin complex and what is it's function? |
-Factor X, V, Ca, Prothrombin -Forms on platelets and catalyzes formation of thrombin -aka Xase complex |
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What is the function of thrombin? |
-Converts fibrinogen to fibrin -activates factor V and VII -activates platelets |
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Which factor has the shortest half life? |
Factor VII |
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What factors are not present in FFP? Where are factors sythesized? Which are not synthesized in the liver and where are they synthesized? |
-Factor V and VIII -Liver -Factor VIII -Endothelium |
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What are the Vitamin K dependent factors? |
2, 7, 9, 10 |
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What is the half life of RBC, platelet, PMN? |
-120 days, 7 days, 2 days |
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Which factor crosslinks fibrin> |
XIII |
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Which coagulation test measures extrinsic pathway? intrinsic pathway? which is the best for measuring liver synthetic function> |
-Extrinsic: PT -Intrinsic: PTT (measures 8,9 ,11) does not measure 7 or 13 -PT is the best for liver b/c it measures 2, 7, 5, 10 |
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What is the PTT goal for heparin anticoagualtion? What are ACT goals? |
-60-90 -150-200 |
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What does bleeding time measure> |
-platelet function |
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What is the normal mechanism of anticaogulation in the body? |
-Antithrombin 3, Protein C, TpA |
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What does antithrombin III do? |
-binds and inhibits Thrombin, Factor 9, 10, 11 -heparing binds this and makes it more active |
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What does Protein C do? |
-inhibits Factor V and VIII -degrades fibrinogen |
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What does TPA do> |
-Degrades factor 5,8 -degrades fibrinogen and fibrin so you get fibrin degradation products -converts plasminogen to plasmin |
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Why is there increased risk of bleeding in prostate surgery? What is the treatement? |
-Urokinase is released, induces fibrinolysis and plasmin production, treatment is aminocaproic acid |
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What is the factor V leiden mutation> |
-Factor 5 is resistant to protein C and prevents natural anticoagulation mechanisms, makes the patient more susceptible to clotting |
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What is the treatment for patients with hypercoagulable syndromes? What are the exceptions? |
-Heparin then coumadin -Will not work in patients with AT III deficiency must give these patients FFP then heparin then coumadin -Hyperhomcystenemia: B12 and folate |
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How do you know when to check for lupus anticoagulant ab? |
-PTT that does not correct with FFP but does with the administration of platelets. |
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What is the etiology of warfarin induced skin necrosis? |
-Warfarin inhibits Protein C and all vitK dependent factors -Protein C has short half life, so balance between procoagulation and anticoagulation tips toward procoagulation -patients with protein C deficiency are very susceptibleTx: heparin |
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Which leg is more susceptible to DVT and why> |
-Left because left iliac vein is compressed by right iliac artery in the pelvis |
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What are the most likely sites of thrombus if patient develops pulmonary embolism with filter in place |
ovarian veins, IVC superior to filter, SVC route |
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What happens in HITT? |
-antiplatelet antibodies form and cause platelet destruction and at times thrombosis -dx: ELISA -tx: d/c heparin, put on direct thrombin inhibitor (lepivirudin,etc), convert to coumadin |
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What are the different variants of von willebrand disease and the treatments? |
-Type I: reduced amount, tx with DDAVP, cryo -Type 2: there but doesnt work well, try DDAVP if not then cryo -Type 3: no vwf present, cryo |
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What is the etiology of uremic coagulopathy and how do you treat> |
-uremia inhibits release of vwf -treat with DDAVP |
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What are the lab findings for patiens with vwd? |
-normal PT and pTT, increased bleeding time |
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What are the lab findings for DIC |
-decreased platelets, increased FDP, decreased fibrin, prolonged PT and pTT -treat underlying cause , FFP, cryo, platelets |
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What are the recommendations? Elective Surgery-Bare metal stent, drug eluting stent |
In all cases stop plavix 5-7 days before surgery and continue ASA throughout perioperative, period, restart plavix postop -6 weeks -1 year |
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If the patient has recent stents and they need semi urgent surgery within window of plavix treatment? |
-if surgeru is not contraindication, continue plavix -if surgery is contraindication, trasnition to ASA and start plavix postop |
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What do you do with a patient on coumadin for mechanical valve that presents with GI bleed? |
-reverse with FFP, treat underlying problem, start heparin after 48 hrs, then coumadin |
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MOA Plavix |
-inhibits ADP receptors, decreases GPIIb/IIIa activation |
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MOA Dipyridamole |
-Adenosine reuptake inhibitor |
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MOA Pentoxifylline |
cAMP phosphodiesterase inhibitor, increases CAMP |
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MOA Argatroban |
-Direct thrombin inhibitor -metabolized by liver -use when patient has HITT -follow Factor X levles, falsely elevates PT and INR |
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MOA Lepivirudin |
kidney metabolism. most commonly used during PTCA |
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What are the thrombolytics? What lab do you follow? How do you treat overdose? |
-tpa, streptokinase, urokinase -follow firbrinogen levels -treat overdose with aminocaproic acid |
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Heparin. Goal PTT? half life? how is it cleared? |
-60-90 -60-90 minutes -macrophages |
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What is a protamine reaction? |
-cross reaction with NPH insulin or previous protamine reaction -anaphylactic reaction: hypotension and bradycardia |
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What are the low molecular weight heparin, MOA? |
-fondapirunx, dalteparin, lovenox -selectively inhibits Xa |
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What does amiocaproic acid do? |
-used to treat overdose of thrombolytics -plasmin inhibitor |
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How long do stored PRBC's last? |
-3 weeks
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Why is citrate important? |
Blood store in citrate, Ca binds citrate, can make patient coagulopathic because Ca needed to bind platelets |
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What is present in cryoprecipitate? |
vwf, Factor 8, fibrinogen, factor 13 |
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What is the most common blood product with bacterial contamination? |
-platelets becasue they are stored at room temp -GNR most frewuent contaminant |
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What is the benefit of irradiated blood prdocuts |
-kills t cells -used in patients for risk of graft versus host disease |
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What is the benefitof leukoreduced blood cells? |
-WBCs can cause alloimmunization, fever -used for chronically transfused patients, potential transplant recipients |
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How is angiotensin II produced? |
-angiotensinogen (made in liver)-->cleaved by renin-->angiotensin I-->ACE in lung-->Angiotenstin II |
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What are the effects of angiotensin II? |
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What are the Na electrolyte concentrations of fluids given to patients? .9% NS? .45% NS? LR? 3% NS? |
154, 77, 130, 513 |
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What is the algortihm for treatment of hyponatremia? |
get from internet |
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Diagnosis of patient with hyponatremia? |
-Measure Serum osmolarity (2Na+Glucose/18+BUN/2.8)-->if elevated then eval for increased concentration of other osmoles (glucose, lipids) -if serum osmolality is low, assess volume status (dehydrated vs elevated JVD and edema) -measure urinary sodium ->20 hypovolemic (diuretics, etc) -<20 hypovolemic (dehydration) -euvolemic always >20 (SIADH) ->20 hypervolemic: renal disease -<20 hypovolemic: heart failure, cirrhosis |
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Treatment of patient with hyponatremia? |
1) slow infusion (rapid leads to central pontine myelinolysis)-->.5mEq/L/hrx24hr=12mEq/L/day 2) water restriction 3) calculate Na required=(Desired-Actual)xTBW
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How do you treat hypernatremia? |
-Calculate the free water deficit -D5 should be use to correct, Na should be corrected at .7mEq/L/hr, in 24hr this is 16mEq -FWD = (16 x TBW)/(Acutal Na-16) |
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What are EKG changes seen in hyperkalemia? What is treatment? |
-Peaked t waves, (if severe: flat P waves, prolonged QRS, deep S waves) -Ca, insulin/glucose, Na bicarb (alkalosis trades H, for K, albuterol nebs, diuretic |
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How is calcium regulated? |
get from GF |
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what are the symptoms and treatment of hypercalcemia? |
-N/V, kidney stones, shortened QT interval, weakness, lethargy, ulcers, decreased DTR -for hypercalcemic crisis, fluids at 200-300 cc/hr, then lasix 20-80 every 1-2 hours -if caused by malignancy: bisphosphanates, calcitonin, glucocorticoids, mithramycin |
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Hypocalcemia symptoms, diagnosis, and treatment? |
-increased deep tendon reflexes, perioral tingling, parasthesias, prolonged QT interval -Chvostek's sign: tap facial nerve and observe for spasm, Trousseau's: occlude brachial artery for 3 min and observe for carpal spasm -Ca gluconate, ca chloride, Vit D |
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What does alkalosis do to Ca concentration> |
increases calcium excretion |
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What increases Magnesium excretion by the kidneys acidosis or alkalosis? |
-hypermagnesemia, hypercalcemia, hypophosphatemia, acidosis (opposite of calcium) |
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What are the sypmtoms and treatment for hypermagnesemia? |
-decreased DTR, N/V, lethargy, arrythmias -Caclium (competetively binds) |
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What are the symptoms of hypomagnesemia? |
-confusion, prolonged QT, torsdaes de pointe -tx: magnesium |
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What is the cause and treatment for hyperphosphatemia? |
-renal failure, usually seen with hypocalcemia -tx phosphate binders |
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What is the cause, symptoms and treatement for hypophosphatemia? |
-refeeding syndrome, glucose gets phosphorylated -difficulty to wean from vent, muscle weakness, mental status changes, increased infection risk -KPhos |
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What electrolyte is important to avoid in patients with renal failure on laxatives? |
Magnesium |
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What are the indications for dialysis> |
A-Acidosis E-Electrolyte abnormalities I-poIsoning O-Overload U-uremia |
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What are the etiologies for metabolic alkalosis? |
-Gastric Losses -Overdiuresis -HYpertensive -Primary hypoaldoseronism -Secondary Hypoaldosteronism -Cushing's
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What is the abnormality seen with gastric reasons for metabolic alkalosis? How do you treat |
Hypochloremic, hypokalemic, paradoxical aciduria -HCL: chloride losses -decreases in volume, reuptake of Na in kidney in exchange for K (hypokalemia) -Hypokalemia at distal tubule, causes reuptake of K for exchange and excretion of H (paradoxical aciduria) -NS bolus followed by maintenance fluids |
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What is the mechanism of metabolic alkalosis in overdiuresis? treatment? |
Contraction alkalosis: decrease in fluid volume, increases HCO3 present with diuretics there is hypokalemia and reuptake of K in exchange for H occurs in kidney (excretion of H causes alkalosis) tx: bolus and if still overloaded treat with acetazolamide |
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How do the hypertensive types of metabolic alkalosis cause metabolic alkalosis? treatment? |
-Primary hyperaldosteronism: Increase uptake of Na, excrete K, exchange K for H, also Na/H exchanger excretes H for Na -Secondary Hyperaldosteronism: same as above (due to reninoma or renal arterial stenosis) -Cushing's: same as above tx with spironolactone |
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How do you calculate anion gap? |
NA - (HCO3 + Cl) |
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What is the major factor leading to acute and chronic rejection? |
HLA |
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What is HLA class I, class II? |
Type I: A, B, C Type II: DP, DQ, DR |
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What HLA's are using in kidney allocation and which is most important? |
-A, B, DR -DR |
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What causes hyperacute rejection? |
ABO incompatibility |
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How do you work around transplanting non ABO compatible individuals? |
-plasmapharesis or IVIG |
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What is a positive cross match? |
when the recipient Abs react against donor lymphocytes, causing hyperacute rejection |
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What organ does not require a preop crossmatch? |
-the liver, almost never gets hyperacute rejection -and HLA compatibility can actually potentiate reaction to viral infections -also HLA antibodies in primary biliary cirrhosis can cause recurrence of the disease |
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What is the panel reactive antibody? |
-tests recipient ab against a panel of antigens -used in lung and heart transplant - if high need plasmapharesis or IVIG, rituximab -if >10 PRA or HLA, A, AB, DR detected then patient needs a crossmatch |
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Hyperacute rejection, what is the etiology? |
-preformed recipient Ab against donor cells, Ab mediated -usually a problem with crossmatch, but is preventable in 99% of cases -immediately organ turns blue and mottled
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Treatment for hyperacute rejection |
extransplant and emergency retransplantation |
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What mediated vascular rejection? |
-undecteable Ab present in recipient -memory B cells are reactivated -intial graft function with deterioration by POD 3 -tx with plasmapharesis, IVIG, steroids |
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What is the etiology of acute rejection? What is the time frame for occurence? Treatment? |
-1 week-6months -T cells that form, either donor cells make APCs that the host then reacts too or T cells directly attack donor -steroids, thymoglobulin |
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How do you diagnose acute rejection? |
-monitor organ carefully for 6 months postop, any signs of organ dysfunction must be evaluated rapidly and biopsied to evaluate for infiltration of lymphocytes |
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Chronic rejection etiology? treattment? |
-Fibrosis or accelerated atheroscleorsis of blood vessels in transplanted tissue, likely due to chrnoic rejection of blood vessels, lymphocytes are sparse and fibrosis is prominent -difficult to treat by methods of immunosuppression -re-transplantation is the only definitive tx |
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What is AB mediated rejection? dx? tx? |
Can occur at any time point, usually against HLA antigens -dx with HLA ab levels and C4d (complement degradation product) -tx with increased immunosuppression |
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What is the MOA for steroids in transplantation? |
-immunosuppressive -blocks the production of NFkB which is needed to mount an immune response -used mostly |
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What is the MOA for Azathioprine? |
-Antiproliferating agent -Metabolized to 6 Mercaptopurine -Alkylates DNA precursors -prevents conversion of IMP-->GMP or AMP -Inhibits purine synthesis, specifically adensoine -works nonselectively on cells that divide rapidly (bone marrow, Gut) |
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What is the MOA for mycophenolate mofetil? |
-Antiproliferation agent -inhibits IMP dehydrogenase and prevents GMP and GTP production, no guanine means no RNA or DNA synthesis -selective to lymphocytes, has largeley replaced azathioprine -used for maintenance and salvage -must be used with steroids or calcineurin inhibitor |
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What are the classifications for transplant drugs? |
-Calcineurin Inhibitor -Antiproliferative Agents -mTOR inhibitor -Immunoglobulin -Steroids |
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What are the Calineurin inhibitors? |
These drugs block the production of IL2, IFN gamma, and T cells -CyclosporineA: binds cyclophilin which binds calmoldulin and decreased Ca needed for IL2 synthesis, excreted in bile, metabolized by the liver -Tacrolimus(Prograf): binds FK receptor in cell, and inhibits production of IL2, more potent that CycA -both increase TGF beta causing renal HTN, nephrotoxicity, hepatotoxicity, HUS, neurologic SE's |
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What are the antiproliferative Agents |
Blocks DNA synthesis of T cells -Azathioprine: metabolite is 6MP which alkylates DNA and stops T cell synthesis, targets all rapidly dividing cells -Mycophenolate: inhibits iMP dehydrogenase and prevents production of guanine, targets graft cells |
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What are the mTOR inhibitors? |
-Sirolimus: binds the FK protein like tacrolimus but inhibits the mTOR pathway which inhibits the RESPONSE to IL2, not nephrotoxic |
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What are the antibodies? |
-ALA, ATA: globulin used in induction and rescue, directly attacks cells, can cause PTLD and cytokine release syndome (anaphlactic type reaction) -OKT3: targets CD3 on T cells, fallen out of favor -Daclizumab, Basiliximab: attack IL2 receptors, used with induction, since after IL2 has done it's job and T cells are not highly dependent on IL2, not effective in reversing rejection |
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What is the MOA for each of the immunosuppressant drugs? |
BLOCK T CELLS -Block IL2 production (calcineurin) -Block response to IL2 (sirolimus) -Block T cell production (antiproliferatives) -Block Ab response - provide Ab's to kill the T cells - provide Ab to attack IL2 |
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What agents are used in induction? Maintenance? |
- Induction: Antibodies, Prograf, Daclizumab - Maintenance: Mycophenolate, prograf, CycA
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What is the most common malignancy following transplant? 2nd most common? etiologic agent? Treatment> |
-Skin Ca (squamous) -PTLD, decreased T cells with immnosuppression causes increased B cells, when patients get EBV, proliferation of B cells is unchecked and can progress to NonHodgkins lymphoma -tx: decrease immunosuppression, start on CHOP for NHL |
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What is the most common infectious agent in transplant recipients? |
-CMV, bx shows inclusion bodies, treat with gangcylcovir |
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For kidney transplant: What is the most common cause of postop oliguria? diabetes? diuresis? proteinuria? |
-ATN, s/e CSA or steroids, high glucose and urea preop, renal vein thrombosis |
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How do you manage urine leaks postop? |
-decreased UOP, get ULS, drain urine and stent |
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How do you manage renal artery stenosis postop? |
-duplex shows decreased flow, PTA+stent |
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What are the symptoms and treatment for lymphocele? |
-vein thrombosis, external compression of vein -percdrain and if that fails intraperitoneal marsupiliazation |
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What is the most common mortality after kidney txp? |
MI |
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How do you manage increased Cr and decreased UOP in kidney txp patient? |
- check fluid status with central line, check catheter -diurese if necessary -ULS+biopsy -empirically decrease CSA or prograf (these are nephrotoxic) and start on pulse steroids |
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How is MELD score calculated? |
-Tbili, INR, creatinine -patients with MELD>15 will benefit from txp, patients with MELD <15 will more likely die from txp than liver dz (better to wait in these patients) |
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Contraindications to liver txp? |
-severe cardiopulmonary disase -active sepsis -active extrahepatic malignancy |
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What is the most common indication for liver txp in the US? |
-Hep C, then Alcoholic liver disease and NASH |
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What is the criteria for transplant in HCC patients? |
-1 tumor less than 5cm -<3 tumors each <3cm -Favorable histology |
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HOw long can a donor liver be stored? |
24 hours |
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If given from a living donor what is the most common side of the liver given in adults, and in the donor, how long does it take for the liver to regenerate to 100% |
-right, 6-8 weeks |
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For acute fulminant hepatic failure, what are the criteria for transplant? |
-King's criteria -First determine if its related to acetaminophen or not -Acetominophen related: ph<7.3 or and of the following 3-->encephelopathy, PT>100, Cr>3.4 -Non-Acetominophen: PT>100 or any of the 3-->etiology, age <10 or >40, PT >50, Tbili>17 |
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What is the order of anastamoses? |
-IVC first, bile duct last |
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Where do biliary ducts receive blood supply from? |
-hepatic arteries |
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How is PSC managed? |
-if patient has repeat episodes of cholangitis, better to evaluate with ERCP before patient develops cholangiocarcinoma and perform liver transplant -more oftne patients get transplant and then colectomy for UC -PBC reoccurs less frequently than PSC in the graft after transplant |
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What is the most common complication of transplant? |
-biliary leak: treat with ERCP, sphincterotomy and stent |
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In the first 24 hours what are possible causes for failure? |
-Labs, ULS elevated Tbili, bile output decrease, PT/PTT elevated, encephelopathy Primary Nonfunction: macrosteatosis of the donated liver -only tx if retransplantation |
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How do patients with arterial thrombosis present? |
-elevated LFTs, decreased bile output, possible failure, possible abscess, strictures, if it is late thrombosis usually presents with strictues and abscess no fulminant failure -treat with PTA/stent (esp if late complication) or reoperation |
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How does portal vein thrombosis present? |
-ascites, edema, renal insufficiency -doppler or CT with triple phase - reop and thrombectomy -late manifestation UGI bleed |
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What is the most common cause of liver abscess after transplant? |
-hepatic artery thrombosis |
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How is hepatic vein stenosis/thrombosis treated? |
-PTA and stent |
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How do you manage biliary leak post transplant? |
-drain, ERCP, stent or PTC if hepaticoJ was created -interrogate the vasculature because most likely due to ischemia to donor biliary tree |
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What is the most common arterial anomaly in liver txp? |
-aberrant right hepatic artery off SMA |
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How do you definitively diagnose acute rejection? |
-biopsy: portal vneous lymphocytosis, endothelitis, bile duct injury -tx with pulse steroids and immunosupressants |
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How do you manage a patient s/p liver transplant with elevated LFTS or decreased bile output? |
-ULS to evaluate vasculature, biopsy (detect rejection or primary non function) |
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How are Hep B and Hep C patients treated? |
-Hep B give Ig and lamivudine (protease inhibitor to prevent postop infection) this reduces reinfection rate by 20% there is no way to prevent Hep and virtually all patients get reinfected |
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How long can you store the heart? |
-6 hours |
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What is the MCC of early mortality? late? MI? |
-infection, chronic vasculopathy with accelerated atherosclerosis, vagal nerve dennervation |
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What is the absolute indication for double lung txp? what is the mcc of early mortality? late? acute rejection? chronic rejection? |
-CF, reperfusion injury, bronchilitis obliterans, perivascular lymphocytosis, bronchilitis obliterans |
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In pancreas tranplants what is the donor arterial supply? venous? |
-the celiac and the SMA, iVC |
