McNeil's notes - Wound healing, fluids, heme (-coag), endo Flashcards

Question

Which of the following is CORRECT regarding keloids? a) They are best treated with radiation b) They are best treated with steroids c) They are more common in Caucasians d) They are hisotlogically distinct from hypertrophic scars e) They exceed the margins of the original wound

Answer 1

e) They exceed the margins of the original wound

Answer 2

a. Decreased total collagenase * Histologically similar to keloid except they respect the boundaries of the original injury * More frequent in Asians and Blacks * Upper torso and flexor surfaces * Develop within the first month then subside gradually * Improvement: pressure garments, topical silicone sheeting applications, or excision and reclosure (only useful if the wound was not closed primarily or was complicated by infection. Both MMP-1 (collagenase) and MMP-9 (gelatinase involved in early tissue repair) are decreased in hypertrophic scars and keloids. - Townsend: Sabiston Textbook of Surgery, 18th ed. There are histologic differences between hypertrophic scars and keloids. Large collagen bundles occur in keloidal scars but not in hypertrophic scars. - Habif: Clinical Dermatology, 5th ed. During the formation of HS (hypertrophic scar), the increase of type I and decrease of type III are important, and the thick type I collagen is the fibrosis pathology background of scar tissue. The results of the experiment show that type I increased and type III decreased more obviously in the HS group than in the NS (normal scar) group. - Qiu et al. A STUDY ON COLLAGEN CONSTITUTE AND AFFECTED FACTORS IN HYPERTROPHIC SCAR AT DIFFERENT AGE PERIODS. Annals of Burns and Fire Disasters - vol. XVI - n. 2 - June 2003

Answer 3

Interferon-γ (IFN-γ), another proinflammatory cytokine, is secreted by T lymphocytes and macrophages. Its major effects are macrophage and PMN activation and increased cytotoxicity. It has also been shown to reduce local wound contraction and aid in tissue remodeling. IFN-γ has been used in the treatment of hypertrophic and keloid scars, possibly by its effect in slowing collagen production and cross-linking while collagenase (MMP-1) production increases.[7] Experimentally, however, it has been shown to impair re-epithelialization and wound strength in a dose-dependent manner when applied either locally or systemically. These findings suggest that administration of IFN-γ may improve scar hypertrophy by decreasing the strength of the wound. - Townsend: Sabiston Textbook of Surgery, 18th ed.

Answer 4

Answer: epithelialization Within 24 hours, neutrophils appear at the margins of the incision, moving toward the fibrin clot. The epidermis at its cut edges thickens as a result of mitotic activity of basal cells, and within 24 to 48 hours, spurs of epithelial cells from the edges both migrate and grow along the cut margins of the dermis, depositing BM components as they move. They fuse in the midline beneath the surface scab, thus producing a continuous but thin epithelial layer. - Coltran: Robbins Pathologic Basis of Disease, 6th ed

Answer 5

Answer: sutures

Answer 6

Answer: collagen

Answer 7

Answer: Facial skin vs. Intestine

Answer 8

Answer: Tensile strength increases due to collagen synthesis a. Tensile strength increases due to collagen synthesis (yes change from Type III to Type I; net result is less collagen but better collagen) b. Tensile strength increases due to cross-linking of collagen (yes) c. Tensile strength plateaus at 3 months (does plateau at 6 weeks but then continues to remodel upto years) d. Tensile strength achieves 80% of normal e. Tensile strength declines during time (increases) Tensile strength correlates with total collagen content for approximately the first 3 weeks of wound healing. At 3 weeks the tensile strength of skin is 30% of normal. After this time, there is a much slower increase in the content of collagen until it plateaus at about 6 weeks. Nevertheless, tensile strength continues to increase as a result of intermolecular bonding of collagen and changes in the physical arrangement of collagen fibers. Although the most rapid increase in tensile strength is early during the first 6 weeks of healing, there is a slow gain for at least 2 years. The ultimate strength, however, never equals that of unwounded tissue, reaching a level only 80% of original skin strength. - Rush Review of Surgery 3rd edition When sutures are removed from an incisional surgical wound, usually at the end of the first week, wound strength is approximately 10% that of unwounded skin. Wound strength increases rapidly over the next 4 weeks, slows down at approximately the third month after the original incision, and reaches a plateau at about 70% to 80% of the tensile strength of unwounded skin. Lower tensile strength in the healed wound area may persist for life. The recovery of tensile strength results from the excess of collagen synthesis over collagen degradation during the first 2 months of healing, and, at later times, from structural modifications of collagen fibers (cross-linking, increased fiber size) after collagen synthesis ceases. - Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed.

Answer 9

Answer: 8 vs 12 weeks Wound strength gradually increases during the healing process. After 2 weeks, a wound has less than 10% of its final healed strength. By this time, most superficial or percutaneous closure materials are removed, and the resulting wound has little to rely on for strength unless additional support is available. Wound strength increases to 20% by 3 weeks and to 50% by 4 weeks. At 3-6 months, a wound achieves its maximum strength, which is 70-80% that of normal skin. - http://emedicine.medscape.com/article/1127693-overview As we all know, collagen once healed will never be as strong as it was originally (about 80%). Dermis, intestinal submucosa, muscular fascia, tendon, ligament, Scarpa fascia and blood vessel wall represent a partial list of tissues with high collagen content. After 6 weeks, wounded tissue has gained about 50% of its eventual strength. To prevent hernia formation, heavy lifting is avoided after major abdominal surgery for six weeks. Tendon repairs are splinted and activity restricted to avoid full tension for a similar period of time. - Greenfield CD, Ch. 3.

Answer 10

Answer: ? upregulate MHC I Steroids downregulates MHC II … likely the right answer GLUCOCORTICOIDS EFFECTS (14) 1. Suppress IL-2 production 2. Inhibit lymphocyte activation 3. Inhibit neutrophil migration to areas of inflammation 4. Inhibit monocyte migration to areas of inflammation 5. Inhibit histamine release and histamine-induced lysosomal degranulation by mast cells 6. Inhibit B cell activation and proliferation at high doses 7. Retards entry of free water into cells 8. Decreases capillary permeability to water 9. Weak mineralocorticoid effect 10. Stimulation of angiotensin release (maintains BP) 11. Inhibits PGI2 (potent vasodilator) → maintenance of BP 12. Impaired collagen mRNA transcription and fibroblast activity 13. Inhibit osteoblast activity 14. Promotes early closure of epiphyseal plates in kids Long term effects (5): 1. Catabolic state with negative N balance 2. Redistribution of body fat → truncal obesity 3. Emotional and psychological disturbances 4. Cataracts 5. Corneal ulcers - Morell Notes

Answer 11

Answers provided: 1) increase alpha 2 macroglobulin 2) inhibition of collagenase GCSs down-regulate type I collagen gene expression by transcriptional and posttranscriptional mechanisms and up-regulate collagenase 3 expression by posttranscriptional mechanisms. Collagenase 3 from osteoclasts and chondrocytes breaks down type I and II collagen, the major components of bone and cartilage matrix. Matrix proteins are decreased, and proteases for matrix destruction are increased. These effects on bone and cartilage may be mediated partially by GCS inhibition of insulin-like growth factor I.[19] - Update on systemic glucocorticosteroids in dermatology. Dermatologic Clinics. Volume 19 • Number 1 • January 2001 Glucocorticosteroid impairs fibroblast proliferation and collagen synthesis. The amount of granulation tissue formed is also decreased. Steroids stabilize the lysosomal membranes. This particular effect can be reversed by the administration of vitamin A. The decrease in breaking strength caused by the administration of exogenous steroids appears to be both time and dose related. - Townsend: Sabiston Textbook of Surgery, 16th ed., Copyright © 2001 W. B. Saunders Company [B]lunting of angiogenesis by steroids may be related to the inhibition of growth factor production. - Middleton: Allergy: Principles and Practice, 5th ed., Glococorticoid effects: 1. Suppress IL-2 production 2. Inhibit lymphocyte activation 3. Inhibit neutrophil migration to areas of inflammation 4. Inhibit monocyte migration to areas of inflammation 5. Inhibit histamine release and histamine-induced lysosomal degranulation by mast cells 6. Inhibit B cell activation and proliferation at high doses 7. Retards entry of free water into cells 8. Decreases capillary permeability to water 9. Weak mineralocorticoid effect 10. Stimulation of angiotensin release (maintains BP) 11. Inhibits PGI2 (potent vasodilator) → maintenance of BP 12. Impaired collagen mRNA transcription and fibroblast activity 13. Inhibit osteoblast activity 14. Promotes early closure of epiphyseal plates in kids - Morell Notes

Answer 12

Answer: Vitamin A ``` Corticosteroids inhibit inflamm. phase of wound healing (angiogenesis, neutrophil and macrophage migration and fibroblast proliferation) and therefore reduce collagen synthesis and wound strength. Steriods also inhibit epithelization and contraction and increased risk of wound infection (immunosupressive effect). Attempt should be made to avoid for 3-4 days post-op ot alternatively use steriod with less anti-inflammatory action. Vit A (topical) can help by stimulating collagen synthesis and promote epithelization. - Schwartz 2005 ``` Levenson and Demetrio recommend vitamin A supplementation of 25,000 IU daily before and after elective surgery. (14) Research supports perioperative vitamin A supplementation in patients known to be immune depleted or steroid treated. Surgical patients with sepsis and those with fractures, tendon damage, or vitamin A deficiency may also benefit from perioperative vitamin A supplementation. Additional research is necessary to establish the effectiveness of universal perioperative vitamin A supplementation in healthy individuals - http://findarticles.com/p/articles/mi_m0FDN/is_4_8/ai_111303980/pg_3 Corticosteroids blunt the processes of the entire inflammatory phase. Vitamin A (topically or 25,000 IU/d orally) mitigates the detrimental healing effects of corticosteroids, but hepatotoxicity may result from prolonged use (ie, >1 mo). Nonsteroidal antiinflammatory medications (NSAIDs) also interfere with arachidonic acid metabolism and, therefore, wound healing. Additionally, NSAIDs inhibit platelet function, one of the earliest processes in the inflammatory phase. - http://emedicine.medscape.com/article/1298452-overview

Answer 13

Answer: Intravascular protein ``` Oncotic = protein Osmotic = Na ``` Because the capillary barrier is readily permeable to ions, the osmotic pressure within the capillary is principally determined by plasma proteins that are relatively impermeable. Therefore, instead of speaking of "osmotic" pressure, this pressure is referred to as the "oncotic" pressure or "colloid osmotic" pressure because it is generated by colloids. Albumin generates about 70% of the oncotic pressure. This pressure is typically 25-30 mmHg. The oncotic pressure increases along the length of the capillary, particularly in capillaries having high net filtration (e.g., in renal glomerular capillaries), because the filtering fluid leaves behind proteins leading to an increase in protein concentration. - http://www.cvphysiology.com/Microcirculation/M012.htm

Answer 14

In cases of clinical dehydration, children with pyloric stenosis require rehydration with IV fluid therapy before surgery. Administer D5W with 0.45% NaCl IV at 1.5 times the maintenance rate. Severely dehydrated children should receive initial deficit fluid therapy with 0.9% NaCl.When urine output is demonstrated, KCl 10-20 mEq/L can be added to the fluids. Answer: D51/2NS at 16cc/hr or with 20kcl at 25cc/hr The preoperative treatment is directed toward correcting the fluid, acid-base, and electrolyte losses. Intravenous fluid therapy is begun with 0.45-0.9% saline, in 5-10% dextrose, with the addition of potassium chloride in concentrations of 30-50 mEq/L. Fluid therapy should be continued until the infant is rehydrated and the serum bicarbonate concentration is less than 30 mEq/dL, which implies that the alkalosis has been corrected Appropriate fluid therapy in this situation requires maintenance in addition to replacement for estimated deficit and for ongoing losses. Estimated initial volume replacement for the first 24 hours includes maintenance of 100 cc/kg (4 cc/kg/hr) = 400cc/24hrs or 16cc/hr and replacement of approximately half of the estimated deficit (from chart above = approx 90cc/kg = 360 cc/2 = 180/24hrs = 7.5cc/hr) → 16cc/hr + 7.5cc/hr = approx 25cc/hr As far as electrolytes are concerned, sodium, potassium, chloride must be supplied for both maintenance and replacement of gastric losses. They can be supplied by a solution of 5% dextrose with 0.5% NS and KCl ( 20-30 mEq/L)

Answer 15

Answer: Low K, Low Cl, metabolic alkalosis Paradoxically urine is acid because K is so depleted that kidney shifts to H+ excretion. Pyloric Stenosis: marked hypertrophy and hyperplasia of the 2 muscular layers of the pylorus occur….leads to narrowing of gastric antrum . The pyloric canal becomes lengthened, and the whole pylorus becomes thickened. The mucosa usually is edematous and thickened. Mutifactoral etiology but theorized that deficiency of nitric oxide synthase containing neurons, abnormal mysenteric plexus innervation, infantile hypergastrinemia, and exposure to macrolide antibiotics. History will reveal nonbilious vomiting or regurg. Which may become projectile (up to 70%). Emesis can be brown or coffee colour due to gastritis or MW tear at gastroesophageal junction. P/E 60-80% infants will have firm nontender and mobile hard pylorus 1-2 cm in diameter (“olive”) in RUQ at the lateral edge of rectus abdominus. Can become significantly dehydrated. Labs: hypochloremic, hypokalemic metabolic alkalosis. Persistent emesis causes progressive loss of fluids rich in hydrochloric acid, which causes the kidneys to retain H+ ions in favor of potassium. May also have elevated unconjugated bilirubin. Paradoxic acid urea.

Answer 16

Answer: c. 130 2.5 88 28 Eventually the infant will develop a nearly complete obstruction by the second to fourth week of life, and will not be able to hold down even clear liquids. This invariably proceeds to severe dehydration if not treated. These infants develop a metabolic alkalosis with severe depletion of potassium and chloride ions. The serum pH level is high, whereas the urine pH level is high initially but eventually drops as the severe potassium deficit leaves only hydrogen ions to exchange with sodium ions in the distal tubule of the kidney. - Schwartz chp37 In gastric losses, loss of Na, Cl, K, but not bicarb

Answer 17

Answer: increase intravascular volume (?) - NS will stay extracellular, approx ¾ interstitial and ¼ intravascular. - NS does not go into the ICF - Dextrose is distributed evenly among all compartments - Plasma protein solutions stay intravascular

Answer 18

25% of RL or NS will go intravascular

Answer 19

``` 4x8 = 32 cc/h x24h= 768 cc ``` 800c (based on 100/50/20) Weight (kg) Fluid requirement (ml/d) 0 – 10 150/kg 10 – 20 1000 + 50/kg over 10 > 20 1500 + 20/kg over 20 - Kliegman: Nelson Textbook of Pediatrics, 18th ed. - Bope: Conn's Current Therapy 2010, 1st ed. - Townsend: Sabiston Textbook of Surgery, 18th ed. Daily maintenance fluids can be calculated by the formula: 100 mL/kg up to 10 kg, add 50 mL/kg for 11 to 20 kg, and add 25 mL/kg for each kilogram of weight thereafter. Because I.V. fluid orders are written as milliliters per hour, this can be conveniently converted to 4 mL/kg/h up to 10 kg, add 2 mL/kg/h for 11 to 20 kg, and add 1 mL/kg/h for each additional kilogram. - Schwartz Calculation of Maintenance Fluid Requirements for Pediatric Patients Weight (kg) Hourly Fluid Requirements (mL) 20 60 mL + 1 mL/kg for each kilogram above 20 Miller: Miller's Anesthesia, 7th ed.

Answer 20

Restore cardiovascular stability with a rapid bolus of 20mL/kg over 10 to 30minutes - Bope: Conn's Current Therapy 2010, 1st ed. The child is given a fluid bolus, usually 20 mL/kg of the isotonic fluid, over approximately 20 min. - Kliegman: Nelson Textbook of Pediatrics, 18th ed.

Answer 21

C. Decreased urinary output Strange question … at 25% dehydration all signs would be present. The first sign in mild is decreased urine output. Point of this question is that children have large reserve. Minimal HD instability until they are really sick. Of the findings on physical examination, the least accurate are mental status, heart rate, and fontanelle appearance. Clinical Evaluation of Dehydration Mild dehydration (1.5 sec); cool and pale Severe dehydration (>10% in an infant; >6% in an older child or adult): rapid and weak or absent peripheral pulses; decreased blood pressure; no urine output; very sunken eyes and fontanel; no tears; parched mucous membranes; delayed elasticity (poor skin turgor); very delayed capillary refill (>3 sec); cold and mottled; limp, depressed consciousness - Kliegman: Nelson Textbook of Pediatrics, 18th ed.

Answer 22

1) Ca 9 ``` Na 130 K 4 Ca 2.7 Cl 109 HCO3 28 Osm 273 ```

Answer 23

B - Extra cellular fluid NS & D5NS > ECF > RL > D5½NS > 2/3 1/3

Answer 24

b. K + Mg Intracellular Cations: K+ 150, Mg+ 40, Na+ 10 Intracellular Anions: Protein 40, HPO4/SO4 150, HCO3 10 Extracellular Cations: Na+ 144, K+ 4, Mg++ 2, Ca++ 3 Extracellular Anions: Cl- 114, HCO3 30, SO4/PO4 3, Organic Acids 5, Protein 1

Answer 25

About 55% of whole blood is blood plasma, a fluid that is the blood's liquid medium, which by itself is straw-yellow in color. The blood plasma volume totals of 2.7–3.0 litres (2.8–3.2 quarts) in an average human. - http://en.wikipedia.org/wiki/Blood#Plasma ``` TBW = 0.60 x male weight, = 0.50 x young female weight ECF = 1/3 of TBW, plasma is ¼ of this, ¾ is interstitial/lymphatic. Plasma represents 8% of TBW and 5% of body weight. ICF = 2/3 of TBW ``` (Based on standard calculations, plasma for a 70kg male would be 3.5L)

Answer 26

Answer: Vitamin C | Requried for both hydroxylation of proline and lysine

Answer 27

Answer: hydroxyserine Each collagen is composed of three chains that form a trimer in the shape of a triple helix. The polypeptide is characterized by a repeating sequence in which glycine is in every third position (Gly-X-Y, in which X and Y can be any amino acid other than cysteine or tryptophan), and it contains the specialized amino acids 4-hydroxyproline and hydroxylysine. - Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed. Lysyl oxidase is an extracellular copper enzyme that catalyzes formation of aldehydes from lysine residues in collagen and elastin precursors.[3][4] These aldehydes are highly reactive, and undergo spontaneous chemical reactions with other lysyl oxidase-derived aldehyde residues, or with unmodified lysine residues. This results in cross-linking collagen and elastin, which is essential for stabilization of collagen fibrils and for the integrity and elasticity of mature elastin. - http://en.wikipedia.org/wiki/Lysyl_oxidase

Answer 28

a. 4:1 I: 80-85% III: 10-15%

Answer 29

b. Cartilage COMMON TYPES OF COLLAGEN Type Tissue Distribution I Skin, bone, tendon, organ capsules, arteries (not cartilage) II Cartilage, vitreous humor III Skin, vessels, uterus. Usually found with type I (type III collagen is the initial one in scars) IV Basement membranes V Widespread VII Fibrils that anchor epidermis to dermis VIII Cornea, vessels IX, XI Hyaline cartillage - Goldman: Cecil Medicine, 23rd ed. Types 2, 9, 10, and 11 collagens are important structural components of hyaline cartilage. - Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed

Answer 30

e. zinc - not required for collagen hydroxylation but is required for collagen synthesis a. ferrous iron (yes) b. alpha-ketoglutarate (yes) c. ascorbic acid (yes) d. oxygen (yes) TGF-beta is a potent inducer of extracellular matrix production, stimulating the synthesis of collagen types I, II, and V, fibronectin, and glycosaminoglycans. The collagen molecule has abundant quantities of two unique amino acids, hydroxyproline and hydroxylysine. The hydroxylation process that forms these amino acids requires ascorbic acid (vitamin C) and is necessary for the subsequent stabilization and cross-linkage of collagen. Collagen synthesis: - stimulated by ascorbic acid, TGF-beta, IGF-1, and IGF-2. - Required cofactors/coenzymes (4): ferrous Fe, -ketoglutarate, ascorbic acid (vitamin c), and oxygen cofactors. (Morell Notes) Vitamin C, zinc, iron, and copper are all enzyme co-factors in collagen synthesis. - Duthie: Practice of Geriatrics, 4th ed.

Answer 31

Answer: hydroxyproline Proline and hydroxyproline are found in high concentrations in collagen. Neither of these amino acids is normally found in urine in the free form except in early infancy. Excretion of “bound” hydroxyproline (dipeptides and tripeptides containing hydroxyproline) reflects collagen turnover and is increased in disorders of accelerated collagen turnover, such as rickets or hyperparathyroidism. - Kliegman: Nelson Textbook of Pediatrics, 18th ed.

Answer 32

Proline hydroxylation is a rate-limiting step in collagen synthesis by dermal cells; - Townsend: Sabiston Textbook of Surgery, 18th ed.

Answer 33

Answer: hydroxylation of proline to hydroxyproline Ascorbic acid functions in a variety of biosynthetic pathways by accelerating hydroxylation and amidation reactions. The best-established function of vitamin C is the activation of prolyl and lysyl hydroxylases from inactive precursors, providing for hydroxylation of procollagen. - Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed. If you don't have vit C the chains are defective = scurvy The biochemical function of vitamin C is well known, and secondary functions relating to collagen gene expression have also been described. As mentioned in the discussion of collagen metabolism, ascorbate is a cofactor in the hydroxylation of proline to form the amino acid hydroxyproline during the synthesis of collagen. Ascorbate is essential for the addition of molecular oxygen to form the hydroxyl group of hydroxyproline. In human beings, thermally unstable collagen is produced if dietary ascorbate is insufficient. Old healed wounds thus tend to disrupt preferentially compared with the normal surrounding skin for two reasons. First, the scar is never as strong as surrounding skin. Second, there is more collagenase activity in normal scar tissue than in normal skin. - Schwartz 2000

Answer 34

Answer: target cytotoxic T cells cytotoxic t-cells CD8 (MHC1) helper T-cells CD4 (MHC2) ``` Cytotoxic T cells (TC cells, or CTLs) destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. These cells are also known as CD8+ T cells since they express the CD8 glycoprotein at their surface. These cells recognize their targets by binding to antigen associated with MHC class I, which is present on the surface of nearly every cell of the body. Helper T cells become activated when they are presented with peptide antigens by MHC class II molecules that are expressed on the surface of Antigen Presenting Cells (APCs). - http://en.wikipedia.org/wiki/T_cell ``` ``` The function of MHC class II gene products appears to be to regulate the specificity of helper T cells, which, in turn, regulate delayed-type hypersensitivity and antibody response to foreign antigens. - Bradley: Neurology in Clinical Practice, 5th ed. ``` ``` MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules (the other one being simply MHC class II) and are found on every nucleated cell of the body (and thus not on red blood cells though paradoxically are found on platelets). Their function is to display fragments of proteins from within the cell to T cells; healthy cells will be ignored while cells containing foreign proteins will be attacked by the immune system. - http://en.wikipedia.org/wiki/MHC_class_I ``` MHC I – Tc (CD8+) MHC II – Th (CD4+)

Answer 35

Based on below, T cells are involved in: - hyperacute transplant rejection (but mostly IgG antibodies) - acute cellular rejection - contact delayed hypersensitivity ``` Hyperacute rejection is a rare and preventable cause of primary graft nonfunction. It is caused by unrecognized ABO incompatibility or a positive T cell crossmatch (mediated by anti-HLA class I antibodies), both of which are contraindications to kidney transplantation. The diagnosis of hyperacute rejection is usually made by the surgeon in the operating room, as the pink kidney becomes mottled and cyanotic. There is little or no urine output and no renal blood flow by renal scan or duplex Doppler. There is no effective therapy, although plasmapheresis has been tried in uncontrolled reports. Transplant nephrectomy is the usual outcome. - Brenner & Rector's The Kidney, 6th ed. ``` Immune complexes may form locally within solid tissue at sites of high antigen concentration. Autoimmune thyroiditis and Goodpasture's syndrome are examples of such localized immune complex formation called the Arthus reaction. It is generally agreed that the local Arthus lesion is one model of immune complex vasculitis in humans that is also due to the interactions of neutrophils with immune complexes and complement.. - Goldman: Cecil Textbook of Medicine, 21st ed. Acute cellular rejection is most commonly seen within the initial months after transplantation and is heralded by clinical and biochemical signs of renal failure. Histologically, there may be extensive interstitial mononuclear cell infiltration and edema as well as mild interstitial hemorrhage ( Fig. 6-40B ). As might be expected, immunohistochemical staining reveals both CD4+ and CD8+ T lymphocytes, which express markers of activated T cells, such as the α chain of the IL-2 receptor - Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed. Contact dermatitis is a common example of tissue injury resulting from delayed hypersensitivity. It is evoked by coming in contact with urshiol, the antigenic component of poison ivy or poison oak, and manifests in the form of a vesicular dermatitis (Fig. 7-18) . The basic mechanism is similar to that described for tuberculin sensitivity. On re-exposure to the plants, the sensitized CD4+ cells of the TH 1 type first accumulate in the dermis, then migrate toward the antigen within the epidermis. Here they release cytokines that damage keratinocytes, causing separation of these cells and formation of an intraepidermal vesicle (Fig. 7-18) . In this form of delayed hypersensitivity, there is evidence that, in addition to CD4+ cells, some CD8+ cells may also be involved. In certain other forms of delayed hypersensitivity reactions, especially those that follow viral infections, cytokine-producing CD8+ cells may be the dominant effector cells. - Robbins Hyperacute rejection is a complement-mediated response in recipients with pre-existing antibodies to the donor (for example, ABO blood type antibodies) Acute rejection [...] is caused by mismatched HLA, which are present on all cells of the body. [Chronic] rejection is [...] where the rejection is due to a poorly understood chronic inflammatory and immune response against the transplanted tissue. - http://en.wikipedia.org/wiki/Transplant_rejection

Answer 36

?? Adaptations are reversible functional and structural responses to more severe physiologic stresses and some pathologic stimuli, during which new but altered steady states are achieved, allowing the cell to survive and continue to function. The adaptive response may consist of an increase in the size of cells (hypertrophy) and functional activity, an increase in their number (hyperplasia), a decrease in the size and metabolic activity of cells (atrophy), or a change in the phenotype of cells (metaplasia). When the stress is eliminated the cell can recover to its original state without having suffered any harmful consequences. Dysplasia – a loss in the uniformity of individual cells as well as a loss in their architechtural orientation. This is usually referred to as a premalignant lesion, however not all dysplasias progress to cancer. Metaplasia- reversible change in which one adult cell type is replaced by another. May be in response to stress. Examples – smokers, columnar to squamous metaplasia in respiratory tract. Here the most frequent cancer is squamous cell carcinoma. Barrett’s oesophagitis – squamous oesophageal lining is replaced by hardier intestinal cells often giving rise to dysplasia and adenocarcinoma. - Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed

Answer 37

Apoptosis is the process of programmed cell death or cell suicide.

Answer 38

Answer: Initiated by Golgi bodie Golgi body protects from apoptosis Apoptosis is controlled, necrosis isn't The Golgi has a putative (assumed) role in apoptosis, with several Bcl-2 family members localised there, as well as to the mitochondria. A newly characterised protein, GAAP (Golgi anti-apoptotic protein), almost exclusively resides in the Golgi and ***protects**** cells from apoptosis by an as-yet undefined mechanism In adult tissues the size of cell populations is determined by the rates of cell proliferation, differentiation, and death by apoptosis and increased cell numbers may result from either increased proliferation or decreased cell death.[5] Apoptosis is a physiologic process required for tissue homeostasis, but it can also be induced by a variety of pathologic stimuli. - Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed. In many clinical situations (e.g., hypovolemic shock, suprarenal aortic-cross clamping) the kidney is subject to a classic ischemia-reperfusion injury that involves several distinct phases.[80] Acute injury to the tubular epithelium and vascular endothelium initiates a rapid decline in GFR. The injury is extended by epithelial and endothelial cell apoptosis and necrosis. - Miller: Miller's Anesthesia, 7th ed

Answer 39

c) necrosis had minimal effect on surrounding tissues Necrosis is caused by either physical or chemical damage. The cell loses its ability to regulate osmotic pressure and the cell explodes. Apoptosis the cell shrinks and there is Nuclear and cytoplasmic condensation. The main morphological characteristics of apoptosis are nuclear fragmentation and cellular breakdown into apoptotic vesicles. In contrast to necrosis, there is no release of cellular contents in the interstitium, and therefore no inflammation surrounding the cell death. Internucleosomal DNA fragmentation (without any sequence specificity but probably more intense in chromatin in the "open configuration") is another important biochemical feature that is the result of an endonuclease activity that has not yet been isolated (Gerschenson & Rotello, 1992). Apoptosis differs from necrosis because necrosis is a degenerative phenomenon of a group of cells that follows irreversible injury. Necrosis is a progressive dissolution of cell structure always accompanied by random DNA degradation.

Answer 40

c. No nerves or blood vessels. Articular cartilage has a very limited capacity for self repair. Small damage does not repair itself and can often get worse over time. As cartilage is aneural and avascular (does not have nerve supply), shallow damage often does not trigger pain. - http://en.wikipedia.org/wiki/Articular_cartilage_damage

Answer 41

Answer: catecholamines According to below, cytokines as well A counterregulatory hormone is a hormone that opposes the action of another. Nutrition and Metabolic Control - Key Points 1. Sepsis, trauma, and surgery activate complex metabolic and inflammatory responses that affect all body systems. 2. The metabolic response to stress response is characterized by catabolism, hypermetabolism, hyperglycemia (diabetes of injury), and enhanced lipolysis. 3. The counterregulatory hormones (cortisol, glucagon, catecholamines) along with the cytokines (e.g., IL-1, TNF) are major mediators of this response. - Miller: Miller's Anesthesia, 7th ed.

Answer 42

Answer: platelet activating factor Immune responses are regulated by soluble mediators called cytokines that produce a multiplicity of immune events through interactions with appropriate cytokine receptors on tissue and inflammatory cells. Cytokines serve an important role as messengers within the immune system and in conjunction with the rest of the body to regulate immune responses. Colony stimulating factor is secreted by macrophages to help undifferentiated hematopoetic cells differentiate (WBC)

Answer 43

b) Variable regions of the short and long chains Basically the antibody is shaped pretty standardly, except the ends of them that are variable to recognize different antigens The fragment antigen-binding (Fab fragment) is a region on an antibody that binds to antigens. It is composed of one constant and one variable domain of each of the heavy and the light chain. These domains shape the paratope — the antigen-binding site — at the amino terminal end of the monomer. - http://en.wikipedia.org/wiki/Fragment_antigen-binding This variable region, composed of 110-130 amino acids, give the antibody its specificity for binding antigen. The variable region includes the ends of the light and heavy chains. - http://www.biology.arizona.edu/immunology/ tutorials/antibody/structure.html

Answer 44

1) 50g Recommended Daily Protein Intake Normal conditions = 0.75g/kg/day = 52.5g (also seen 0.5g/kf/day) Metabolic stress = 1.0-1.6g/kg/day = 75g to 112g [T]he average normal requirement is 0.8 g of protein per kilogram, or between 56 and 60 g of protein per day. Trauma, infection, and other catabolic conditions will increase this requirement. - Townsend: Sabiston Textbook of Surgery, 18th ed.

Answer 45

a. 0.8 gm/kg (56 gm/day) The extensive studies of whole body protein turnover by Graham Hill and Robert Wolfe during the 1980s documented that exogenous protein administration of 1.5 g/kg/day achieves maximal protein sparing and that when amounts exceeding this value are administered, no further incorporation of nitrogen into protein is possible, with the excess protein being converted to urea and excreted, at least in relatively normal patients. Accordingly, it is most common to administer protein during artificial nutrition, whether enteral or parenteral, at a value of 1.5 g/kg/day. It is not clear in patients with severe protein loss, such as after major burns, whether limiting protein intake to this level is efficacious, and many centers have attempted to administer even greater amounts of protein (e.g., 2 g/day) to correct measured deficits. - Townsend: Sabiston Textbook of Surgery, 18th ed.

Answer 46

Answer: 3% A 70-kg man has between 10 and 11 kg of protein, otherwise referred to as lean body mass. In the fed state, daily protein turnover amounts to between 250 and 300 g, or 3%. The average normal requirement is 0.8 g of protein per kilogram, or between 56 and 60 g of protein per day. Trauma, infection, and other catabolic conditions will increase this requirement. Exogenous protein administration of 1.5 g/kg/day achieves maximal protein sparing and that when amounts exceeding this value are administered, no further incorporation of nitrogen into protein is possible - Townsend: Sabiston Textbook of Surgery, 18th ed.

Answer 47

1) 100:1 Increased protein intake, and a therefore a lower calorie:nitrogen ratio 80:1-100:1 may benefit healing in critically ill or hypermetabolic patients - Schwartz Normal = 150:1 Severe stress = 80-120:1

Answer 48

B. Increase the caloric / nitrogen ratio Want less protein, cause they don't pee out excess nitrogen in the form of urea as well

Answer 49

Answer provided: 100-500g/day Glucose administration during fasting or stress appears to decrease urinary urea production, the so-called protein-sparing effect, with a minimum of 100 g of glucose per 24 hours being required for this response based on Gamble's classic lifeboat ration studies of the 1940s. Maximum suppression of gluconeogenesis is achieved at infusion rates of 4 mg/kg/min (∼400 g/day for a 70-kg man) - Townsend: Sabiston Textbook of Surgery, 18th ed.

Answer 50

c) Increased liver albumin production Just think of all your patients and how they all have hypoalbuminemia Decreased albumin is associated with the following conditions: Starvation, malnutrition, malabsorption, anorexia (decreased synthesis) The liver is the principal organ that maintains total carbohydrate stores by synthesizing glycogen and generating glucose from precursors.[85] Glucose is synthesized from nonoxidative metabolic products of glucose (pyruvate and lactate) that are generated predominantly by red blood cells (RBCs) and from amino acid precursors that are derived predominantly from muscle during prolonged starvation or exercise. - Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed.

Answer 51

d. increased urea What happens to urea, during acute and prolonged starvation? Acute – Nitrogen breakdown 8-12 g/day b/c high gluconeogeneis from aa breakdown; excreted in urine as urea Chronic – Ketogenesis inhibts gluconeogenesis, thus nitrogen breakdown 2-3g/day; excreted as ammonia (not urea) b/c ammonia counters the acidosis from ketosis A maximal rate of ketogenesis is reached by 3 days of starvation, and plasma ketone body concentration is increased 75-fold by 7 days. Muscle protein breakdown decreases to less than 30 g/day, causing a marked decrease in urea nitrogen pro-duction and excretion. - Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed Heart size and cardiac output are reduced, the pulse slows, and blood pressure falls. - Auerbach: Wilderness Medicine, 5th ed.

Answer 52

This question is not clear. Do they mean which is different? Anyways: a) increased lipolysis (yes both, except more in trauma) b) increased epinephrine (only in trauma) c) decreased oxygen utilization (yes – reduced RQ in both) d) something about cortisol, but I forget if it said increase or decrease (increased in both) The metabolic responses to surgical and traumatic stress differ greatly from the response to starvation. Unlike the adaptive responses aimed at preserving body mass that occur during starvation, the response to stress has been called “auto-cannibalism.”[59] This categorization is occasioned by loss of fat and lean body mass caused by an obligate catabolic state with proteolysis, gluconeogenesis, lipolysis, hypermetabolism, and insulin resistance. Auto-cannibalism is not reduced to any great extent by exogenous nutrients. - Miller: Miller's Anesthesia, 7th ed. The metabolic effects of both surgical procedures and trauma (Figure 10–4) differ from those of starvation due to neurohormonal activation, accelerating the loss of lean tissue and inhibiting metabolic adaptation of starvation. The adaptive changes in uncomplicated starvation are a decrease in energy expenditure (as much as a 30% reduction), a change in type of fuel consumed to maximize caloric potential, and preservation of protein.

Answer 53

A. ATP The energy required to perform the mechanical work of exercise is derived from the hydrolysis of adenosine triphosphate (ATP). At rest, skeletal muscle possesses only limited quantities of ATP and other high-energy phosphate molecules. If exercise is to be continued for more than a brief period of time, ATP must be continually replenished through the metabolism of fuels (e.g., fats and carbohydrates). The aerobic metabolism of fuels produces large quantities of ATP per molecule of substrate, but requires an adequate supply of oxygen. - Keane: Nadas' Pediatric Cardiology, 2nd ed.

Answer 54

??? I would guess hemoglobin cause pro athletes that dope use EPO, or use high-altitude training to get their Hb up (via increased EPO).

Answer 55

c. 33 Answer: 33 BMI = kg/meter2

Answer 56

d. Body water content I have no idea what this is and can guess this cause you can't really guess/calculate body water content AFAIK. Harris-Benedict equation is used to calculate a person’s basal energy expenditure or basal metabolic rate. Uses the variables of height/weight/age/gender. Does not take into account lean body mass. Therefore, will underestimate caloric needs in extremely muscular and extremely overweight For men, the B.E.E. = 66.5 + (13.75 x kg) + (5.003 x cm) - (6.775 x age) For women, the B.E.E. = 655.1 + (9.563 x kg) + (1.850 x cm) - (4.676 x age)

Answer 57

d. Hypoglycemia Again you can probably guess this... Why would you be hypoglycemic from getting a constant gavage? Hyperosmolar, nonketotic coma can also occur with enteral feedings as with parenteral nutrition. Though generally considered to be relatively innocuous, nasoenteric feeding tubes are associated with multiple adverse consequences, including tube migration, esophageal and gastric mucosal erosions, pulmonary aspiration, sinusitis, pneumothorax, esophageal stricture, esophageal perforation, and fatal arrhythmias. Inappropriately rapid administration of hyperosmolar solutions may result in diarrhea, dehydration, electrolyte imbalance, and hyperglycemia, as well as loss of potassium, magnesium, and other ions through diarrhea. An additional cause of hyponatremia in patients with impaired consciousness is that many are given enteral nutrition with tube feeding formulations low in sodium. - Townsend: Sabiston Textbook of Surgery, 18th ed Complications of enteral feeds include: - diarrhea, nausea, vomitting (due to high osmolarity) - hyperglycemia - hyper/hyponatremia - hyper/hypokalemia - hyper/hypophosphatemia - feeding tube occlusion - reflux of gastric contents, aspiration - hypertonic, non-ketotic coma may occur in the presence of excessive H2O loss Reference: Schwartz, ICU Book, Nutrition in Critical Care

Answer 58

Answer: NG drainage

Answer 59

Answer: Blood urea nitrogen Urea is continuously formed by the metabolism of ammonia in the liver. Hepatic deamination implies the splitting off of amide (-NH2) groups from amino acids, and their conversion to ammonia, which enters the arginine cycle and is converted to urea. Urea nitrogen is a small, uncharged molecule, not protein bound, that is rapidly cleared from the blood by glomerular filtration. It subsequently undergoes reabsorption by the tubules so the blood urea nitrogen (BUN) does not correlate directly with GFR. - Miller: Miller's Anesthesia, 7th ed.

Answer 60

1) Increase protein synthesis by muscle I remember looking at the evidence for this back in the day and basically the evidence for BCAA supplementation/muscle protein synthesis and it's pretty weak (unless you have a deficiency I guess). Seems like this question was asked with a choice being "metabolized by the muscle" and that's probably the more correct answer. [T]he branched-chain amino acids (BCAAs) [are] valine, leucine, and isoleucine. (LIV) Amino acids in the kidney can have several fates, including [...] metabolism of other amino acids, such as the BCAAs. The rate of degradation of BCAAs in muscle is greater than in the liver, and given that muscle accounts for up to 40% of body mass, it is probably the major site for degradation of BCAAs. - Townsend: Sabiston Textbook of Surgery, 18th ed.

Answer 61

b – Valine. Enterocytes are important sites for degradation of BCAA (valine, leucine, isoleucine).

Answer 62

Answer: 3.4

Answer 63

Answer: sepsis vs. cholestasis Hepatic dysfunction is commonly observed in patients receiving TPN, and these disorders occupy a spectrum ranging from simple elevations in liver function test results to cirrhosis. Most often, if hyperbilirubinemia occurs acutely in a patient receiving TPN, the cause is generally sepsis. Factors responsible for liver disease attributable primarily to TPN administration, as opposed to other causes, remain unclear and are a source of controversy. Hepatic steatosis, cholestasis (presumably from lack of enteral stimulation and reduced release of cholecystokinin), and the presence of chronic inflammation have all been implicated as relevant mechanisms. - Townsend: Sabiston Textbook of Surgery, 18th ed. Several complications of TPN are common and relate to the constituents used and duration of therapy. Elevated gamma-glutamyltransferase (GGT), alkaline phosphatase, and hyperbilirubinemia may reflect cholestasis, and less commonly cholelithiasis or cholecystitis. - http://www.pharmainfo.net/reviews/total-parenteral-nutrition-review ?Cholestasis

Answer 64

A. Ketosis Ketone bodies found in starvation state Carboydrates should be administered at a rate no greater than 5 mg/kg/min via TPN, which is the maximum oxidation rate of glucose. Excess glucose can: 1- increase blood glucose levels and induce hyperosmolar nonketotic coma 2- lead to dehydration 3- lead to lipogenesis with subsequent hepatic abnormalities (ie fatty liver) 4- increased CO2 production - Rush Review of Surgery, Chapter 47, pg 46-7

Answer 65

All seem to be complications. Metabolic complications of parenteral nutrition include hyperglycemia from the high glucose concentration of the infusate, which may lead to osmotic diuresis and dehydration. - Kliegman: Nelson Textbook of Pediatrics, 18th ed. Acalculous cholecystitis can also be found in patients on total parenteral nutrition (TPN), typically those on TPN for more than 3 months. - http://emedicine.medscape.com/article/187645-overview Decreasing the feeding flow rate may alleviate diarrhea by allowing time for intestinal mucosal adaptation to occur when the gastrointestinal tract has not been used for extended periods (in cases of starvation and intestinal atrophy induced by total parenteral nutrition). - Goldman: Cecil Medicine, 23rd ed. Subclavian thrombosis occurs in 5 to 10% of patients.

Answer 66

Answer: severe pancreatitis a) Parenteral — Parenteral nutrition should be initiated only in patients who do not tolerate enteral feeding as the use of parenteral nutrition as an adjunct to enteral feeding may be harmful b) I guess a PEG would be more appropriate c) ?? no d) if unable to use enteral feeds e) no Indications for Parenteral Nutrition Efficacy shown * Gastrointestinal cutaneous fistulas Renal failure (acute tubular necrosis) Short bowel syndrome Acute burns – if unable to use enteral feeds Hepatic failure (acute decompensation superimposed on cirrhosis) Efficacy not shown Crohn's disease Anorexia nervosa - Townsend: Sabiston Textbook of Surgery, 16th ed. Common Indications for Long-Term Parenteral Nutrition The most appropriate patients receiving home parenteral nutrition suffer from short-gut syndrome after having lost a large portion of the GI tract either by repeated resections for Crohn's disease or by massive small bowel resection after midgut volvulus or mesenteric thrombosis, or both. Additional indications may include GI motility disorders (chronic pseudo-obstruction, sprue, scleroderma), management of a high-output enterocutaneous fistula, intractable chylous ascites, active Crohn's disease, cystic fibrosis, and chronic pancreatitis. - Townsend: Sabiston Textbook of Surgery, 16th ed.

Answer 67

c) Hypoglycemia When oral nutrient intake is low, discontinuation of TPN may cause rebound hypoglycemia unless the infusion is decreased gradually. - Current surgical Dx and Tx p.166

Answer 68

B. Catecholamines Marked and sustained increases in circulatory catecholamines lead to hypermetabolism, and treatment with β-blockers may be protective. Sustained increases in glucagon and glucocorticoids result in excessive gluconeogenesis and an insulin-resistant state. Increased glucocorticoids also lead to a severe catabolic state, especially because anabolic hormones (growth hormone and testosterone) are decreased after a burn injury. - Goldman: Cecil Medicine, 23rd ed. Hypermetabolism, characterized by tachycardia, increased cardiac output, elevated energy expenditure, increased oxygen consumption, proteolysis and lipolysis, and severe nitrogen loss, develops after severe burns and resuscitation. Even though this response is seen in all major injuries, it is present in its most dramatic form in a severe burn, in which it may be sustained for months and lead to weight loss and decreased strength (particularly when strength is needed to recover from the complications associated with the injury). These alterations in metabolism are due in part to the release of catabolic hormones, which include catecholamines, glucocorticoids, and glucagon. - Townsend: Sabiston Textbook of Surgery, 18th ed.

Answer 69

d) Epidural Neuraxial anesthesia for lower abdominal and lower extremity surgery reduces or abolishes the hyperglycemic response to surgery, likely because of the lack of stimulation of hepatic glycogenolysis due to a reduced epinephrine response or blockade of hepatic sympathetic pathways or both. Reduced sympathetic and adrenal activity with epidural blockade also prevents normal intraoperative increases in free fatty acids and glycerol (lipolysis) during lower abdominal surgery. - Miller: Miller's Anesthesia, 7th ed. Delay surgery to feed if malnourished, possibly add glutamin to TPN??? Watters et al 1992 Can J Anaes says epidural and pain control have no effect on hypermetabolic state post abdo surgery.

Answer 70

Answer: Pre-op and post-op enteral and parental support The hypermetabolic response to burns is the greatest of any other trauma or infection. A major burn injury provokes a complex disruption of hormonal homeostasis that induces an increased resting metabolic rate and oxygen consumption, increased nitrogen loss, increased lipolysis, increased glucose flow and loss of body mass. Normal metabolic rates of 35-40 kcal/mBSA/hr are increased by 50% in a 25% BSA burn and doubled in burns greater than 40% BSA. The normal central core temperature is elevated by 1-2 C° due to a reset of the thermostatic control center in the hypothalamus. This post-burn stress response is associated with severe fat and muscle wasting, growth delays in children, immunologic compromise, cardiomegaly, hepatic lipodystrophy, poor wound healing and prolonged recovery times. The main principles for successful management of the post-burn hypermetabolic response are : 1) Providing adequate nutritional support 2) Controlling the external environment by warming 3) Preventing burn sepsis 4) Achieving early wound closure

Answer 71

4) decreased release of branch chain amino acids from skeletal muscles

Answer 72

d-Clinical history of bleeding

Answer 73

- e. It is a carrier of carbohydrates - proteins Other "except" answers for similar question: The (non-infused) half life is 24 hours - it's 21 days Increase hepatic synthesis in severe stress - actually decreased Albumin is normally present in the blood and constitutes 50—60% of the plasma proteins and 80—85% of the oncotic pressure. Exogenously administered albumin increases the oncotic pressure of the intravascular system, pulling fluids from the interstitial space, thereby decreasing edema and increasing the circulating blood volume. The duration of volume expansion usually lasts for approximately 24 hours if there is no protein loss. - MDConsult Drugs Albumin seems most active in maintaining the serum oncotic pressure, where it normally has about 4 times as much importance as globulin, accounting for about 80% of the plasma oncotic pressure. Albumin also acts as a transport protein for some drugs and a few other substances. Most serum albumin is produced by the liver. Half-life of albumin is relatively long, approximately 3 weeks. A third function ascribed to albumin is that of a general transport or carrier protein. Many organic and inorganic ligands (e.g., thyroxine, bilirubin, penicillin, cortisol, estrogen, free fatty acids, warfarin [Coumadin], calcium, magnesium, and heme) complex with different regions of the albumin molecule. - McPherson & Pincus: Henry's Clinical Diagnosis and Management by Laboratory Methods, 21st ed.

Answer 74

e. Low serum Fe and increased TIBC Examination of a bone marrow aspirate stained with Prussian blue to determine the presence or absence of iron is regarded generally as the "gold standard" for the assessment of storage iron, especially in hospitalized patients. - http://www.medscape.com/viewarticle/420923 The serum ferritin level is the most reliable, noninvasive, and cost-effective indicator that is routinely available in most clinical laboratories ( Table 163-1). Although some recent studies have questioned the accuracy of routine determination of stainable marrow iron, this test is still generally considered to be the gold standard of available tests for iron deficiency. However, determination of total bone marrow iron stores is rarely necessary to make a diagnosis of iron deficiency anemia except when there is some other complicating process. - Goldman: Cecil Medicine, 23rd ed.

Answer 75

c. DDAVP The goals of therapy for vWD consist of correcting the deficiencies in vWF protein activity to above 50% of normal and Factor VIII activity to levels appropriate for the clinical situation. Although cryoprecipitate is licensed by the FDA for prophylaxis or treatment of vWD-related bleeding complications, the lack of viral safety relegates its use exclusively to emergency circumstances when no other options are readily available. Replacement therapy with viral-attenuated, intermediate- or high-purity Factor VIII concentrates containing high-molecular-weight multimers of vWF, e.g., Humate-P or Alphanate, is preferred and should be reserved for patients with type 1 and 2A variants who are unresponsive to DDAVP and for patients with type 2B and type 3 disease. These products are also indicated for the 2N variant and provide a source of normal vWF to complex with the normal intrinsic Factor VIII. Otherwise, DDAVP is the recommended treatment and eliminates potential exposure to blood-borne pathogens. - Goldman: Cecil Textbook of Medicine, 21st ed., pg 1009

Answer 76

(Uptodate) Major bleeding and trauma We suggest the use of VWF concentrate over DDAVP in order to reach a target level of approximately 100 IU/dL of VWF ristocetin cofactor activity. Levels sustained for 7-14 days after trauma. von Willebrand Disease: Treatment & Medication For prophylaxis in major surgery or for treatment of serious bleeding episodes, vWF-containing FVIII concentrates are the treatment of choice. Platelet transfusions * These may be helpful in some patients with vWD whose disease is refractory to other therapies. * Cryoprecipitate and fresh frozen plasma contain functional vWF but should be avoided whenever possible because of the potential transmission of viral disease. An additional drawback of fresh frozen plasma is the large infusion volume required. - http://emedicine.medscape.com/article/206996-treatment Fresh-frozen plasma is too dilute for the specific treatment of VWD in most cases. Cryoprecipitate is prepared from frozen plasma by thawing at 4°C (39.2°F). The precipitate that forms is collected by centrifugation and refrozen. When thawed, cryoprecipitate from 1 unit of blood donation can be dissolved in 10 mL of saline for intravenous administration. One unit of cryoprecipitate contains approximately 100 U of factor VIII and VWF, and 200 to 250 mg of fibrinogen, representing a 10-fold concentration relative to plasma. Cryoprecipitate is not generally subjected to virus inactivation treatments and, therefore, may transmit certain infections. For this reason, virucidally treated factor VIII-VWF concentrates are preferred for therapy of VWD in countries where they are available (Table 129-5). - Hoffman: Hematology: Basic Principles and Practice, 5th ed.

Answer 77

Water retention, a slight increase in total body water, hyponatremia, and a decrease in plasma osmolality are potential side effects of desmopressin, which are more likely to occur when excessive amounts of the drug are used. Because of this, desmopressin should be started at the lowest dosage and titrated up to the dosage that controls polyuria and is sufficient to normalize urinary osmolarity completely. - Rakel: Textbook of Family Medicine, 7th ed.

Answer 78

Vasoconstriction is the initial vascular response to injury, even at the capillary level. It is dependent upon local contraction of smooth muscle that has a reflex response to various stimuli. The initial vascular constriction occurs before any platelet adherence at the site of injury. Adherence of endothelial cells to adjacent endothelial cells may be sufficient to cause cessation of blood loss from the intravascular space.

Answer 79

a. dilutional thrombocytopenia Complications of massive transfusion include hypothermia, hypocalcemia, and acid–base disorders. Hypothermia can be avoided by use of high-flow warming devices. When the transfusion rate exceeds about 100 mL/min there may be a clinically significant drop in ionized calcium due to accumulation of citrate, and calcium supplementation may be indicated. Liver disease, hypotension, and hypothermia may exacerbate hypocalcemia. Monitoring the corrected QT interval is useful. Measurement of total calcium will not accurately indicate the level of ionized calcium. During rapid transfusion of RBC, a modest decrease in arterial pH may be seen while metabolic alkalosis is common after massive transfusion because of metabolism of citrate. - McPherson & Pincus: Henry's Clinical Diagnosis and Management by Laboratory Methods, 21st ed. The citrate load associated with massive blood transfusion (>6 U) causes hypocalcemia in up to 94% of patients. - Marx: Rosen's Emergency Medicine, 7th ed. Serum potassium levels may be as high as 19 to 30 mEq/L in blood stored for 21 days. Although hyperkalemia is occasionally reported, [60] [61] large amounts of blood must be given. For significant hyperkalemia to occur clinically, bank blood must be given at a rate of 120 mL/min or more. - Miller: Miller's Anesthesia, 7th ed. Causes of Metabolic alkalosis: Chloride-responsive: Massive blood transfusion - Ferri: Practical Guide to the Care of the Medical Patient, 7th ed. Most commonly metabolic alkalosis, hypokalemia, hyperkalemia hypocalcemia, hypothermia

Answer 80

?? hypothermia or hyperkalemia However, anaphylactic or anaphylactoid reactions, which can occur after the transfusion of only a few milliliters of blood or plasma, include skin flushing, nausea, abdominal cramps, vomiting, diarrhea, laryngeal edema, hypotension, shock, cardiac arrhythmia, cardiac arrest, and loss of consciousness. - Goldman: Cecil Medicine, 23rd ed. Individuals who receive a unit of contaminated blood may develop fever, rigors, skin flushing, abdominal cramps, myalgias, DIC, renal failure, cardiovascular collapse, and cardiac arrest. - Hoffman: Hematology: Basic Principles and Practice, 5th ed.

Answer 81

Answer given: hypocalcemia (?)

Answer 82

c) or d) TRICC trial transfuse for Hb

Answer 83

b) platelets 1/432 Others are

Answer 84

Answer: Anaphylaxis / acute transfusion reaction a. Bacterial sepsis Rare b. Anaphylaxis (1/20,000) c. HBV (1/200,000) d. HCV (1/500,000 – 2,000,000) e. HIV (1/900,000 – 2,000,000) Posttransfusion viral hepatitis remains the most common fatal complication of blood transfusion. It is estimated that for every case of icteric posttransfusion viral hepatitis there are four anicteric cases, many of which are asymptomatic. Hepatitis is caused either by hepatitis B virus, or the non-A, non-B viruses, including C. The incubation period of the former is up to 6 months, the latter's may be as short as 2 weeks. The risk of hepatitis transmission per unit of blood is 0.035 percent. - Schwartz.

Answer 85

2) Anti-thrombin III For clinical purposes, cryoprecipitate should be considered the blood product most rich in factor VIII, vWF, XIII, fibrinogen, and fibronectin—the plasma proteins with the highest molecular weights. Cryoprecipitate is used predominately to treat bleeding associated with fibrinogen and factor XIII deficiency states.[33] It is rarely used to treat vWF and factor VIII deficiencies. - Hoffman: Hematology: Basic Principles and Practice, 5th ed. Cryoprecipitate is a concentrated source of von Willebrand factor, fibrinogen, factor VIII and fibronectin. It is produced by slow-thawing (at 4 C) fresh frozen plasma, followed by centrifugation at 4 C. Cryoprecipitable proteins (those mentioned above) precipitate at this temperature and are maintained in a very small amount of remaining plasma (approximately 1/10 of the starting volume of FFP, or about 20 to 30 ml). One unit of cryoprecipitate is defined as that obtained from a single FFP bag (approximately 250 mL plasma).

Answer 86

Answer: - Pooled 1/10000 - RBC single donor 1/300 Acute hemolytic reactions are estimated to occur in 1 of 30,000 transfusions, usually because of clerical errors. [NOTE: Doesn’t specify post type and screen] - Critical Care Handbook of Mass General pg 201 Generally, antibodies that are not detected in the type and screen are weakly reactive antibodies that do not result in serious hemolytic transfusion reactions. In a study of 13,950 patients, Oberman and associates discovered only eight “clinically significant” antibodies after complete crossmatch that were not detected during the antibody screening. The antibodies were all in lower titer and were believed by Oberman and coworkers to be unlikely to cause serious hemolytic reactions.

Answer 87

- WBC alloantibodies Febrile Nonhemolytic Transfusion Reactions (FNHTRS) are attributed to white blood cells (WBCs) in blood products that synthesize and release proinflammatory cytokines during storage. Preformed recipient antibodies that target donor WBCs can also lead to cytokine release after transfusion. - Bope: Conn's Current Therapy 2010, 1st ed. Nonhemolytic reactions occur with the frequency of 1% to 2% of all transfusions and consist primarily of chills and fever during the transfusion or during the first 2 or 3 hours after the transfusion is complete. The severity of this condition is variable, and management is symptomatic, including antipyretics. The mechanism of these reactions includes the presence of antibodies to white-cell antigens in the transfused blood, especially in the multitransfused or multiparous patient. These reactions can be prevented by the use of acetaminophen pretreatment, steroids, and leukocyte-free blood or by the use of filters that remove leukocytes from the transfused blood. Allergic reactions are also commonly associated with transfusions, with urticaria and pruritus seen in as many as 1% to 3% of all transfused patients. Acute anaphylaxis occurs infrequently at a rate of about 1 per 150,000 components given. - Greenfield

Answer 88

FFP is the only currently available therapeutic product that contains factor V. Factor V is lost rapidly from stored FFP. - Kliegman: Nelson Textbook of Pediatrics, 18th ed.

Answer 89

Most of the factors are stable in stored blood, with two exceptions: factors V and VIII.[48] These factors gradually decrease to 15% and 50% of normal, respectively, in whole blood after 21 days of storage. - Miller: Miller's Anesthesia, 7th ed. Levels of factors V and VIII decrease significantly at 1°C to 6°C (T1/2 = 10-14 days and 7 days, respectively), although levels of other factors remain essentially unchanged (T1/2 > 21 days). - Townsend: Sabiston Textbook of Surgery, 18th ed. Factor VIII degrades the fastest, then V.

Answer 90

Anticoagulants are added to the blood during apheresis to prevent clotting of the extracorporeal circuit and clumping of cells in the component. Citrate anticoagulants have a proven record of safety in the apheresis of healthy platelet donors and are used extensively for collection of PBSC. The major drawback is the risk of a symptomatic decrease in the level of ionized calcium (“citrate toxicity”), especially during processing of large volumes of blood.[233,234] Citrate ions chelate calcium ions (and other divalent cations such as magnesium), making them unavailable for Ca2+-dependent metabolic reactions. - Hoffman: Hematology: Basic Principles and Practice, 5th ed.

Answer 91

1) Decreased cost

Answer 92

Estimation of blood to be withdrawn is EASILY achieved Acute Normovolemic Hemodilution ANH involves the removal of 1 to 3 units of the patient’s blood and replaces it with crystalloid and/or colloid to restore the intravascular volume. Done after induction of anesthesia but before commencement of the operative procedure, ANH is tolerated well in most patient populations. The withdrawn blood is anticoagulated and maintained at room temperature for up to 4 hours. It is reinfused into the patient as needed during the surgical procedure. If ANH is combined with autologous predonation, 6 or more units of blood can be available for a procedure in which significant blood loss is expected. Studies comparing ANH with preoperative autologous blood donation show equal rates of allogeneic blood transfusion, but ANH costs are lower. There is no role for this technique in acute hemorrhage. - Townsend: Sabiston Textbook of Surgery, 18th ed. A clinical analysis of patients who had undergone “minimal” ANH (representing 15% or less of patients’ blood volume) estimated that only 100 mL of RBCs (the equivalent of 1/2 unit of blood) was “saved” under these conditions.[35] With moderate hemodilution (target hematocrit levels of 28%), the “savings” becomes more substantial. The removal of 3 blood units in a patient who subsequently underwent a blood loss of 2600 mL resulted in surgical RBC losses “saved” by hemodilution of 215 mL, or the equivalent of 1 allogeneic blood unit ( Fig. 57-1 ).[36] This RBC volume approaches the RBC volume expansion generated by autologous bqlood predonation under standard phlebotomy conditions. - Miller: Miller's Anesthesia, 7th ed.

Answer 93

c. better would be rl/mannitol [A]dministration of lactated Ringer's solution to maintain the central venous pressure between 10 and 15 cm H2O while initially administering 12.5 to 50 g of mannitol. If this is ineffective, the dose of mannitol may be increased or the use of more potent diuretics, such as furosemide, which increases blood flow to the renal cortex, may be required to maintain adequate urinary output. Alkalinization of the urine to prevent precipitation of acid hematin in the distal tubules is of questionable value but is easy and therefore recommended. - Miller: Miller's Anesthesia, 7th ed.

Answer 94

A by elimination (B & C are treated by transfusions) could be something else depending on what the other choices are

Answer 95

Prothrombin complex concentrates are the treatment of choice although fresh frozen plasma can serve as an alternative source of prothrombin. - McPherson & Pincus: Henry's Clinical Diagnosis and Management by Laboratory Methods, 21st ed.

Answer 96

Answer: oxygen delivery declines significantly below Hb 100 RBC last about 35 days in citrate phosphate dextrose adenine solution In the absence of increased red cell destruction or sequestration, 1 unit of red cells can be expected to increase the Hb level by 1 g/dl or the hematocrit by approximately 3%. - Hoffman: Hematology: Basic Principles and Practice, 3rd ed.,

Answer 97

Answer: e. 3,4,5,1,2 Acute hemolytic reactions are estimated to occur in 1 of 30,000 transfusions, usually because of clerical errors. Symptoms include anxiety, agitation, chest pain, flank pain, headache, dyspnea and chills. Nonspecific signs include fever, hypotension, unexplained bleeding (DIC) and hemoglobinuria. If a transfusion reaction is uspected the following steps should be taken: a. stop transfusion b. send unused donor blood and a fresh patient smaple to the blood bank to be re-crossmatched c. send blood samples for free hemoglobin, haptoglobin, coomb’s, and DIC screening d. treat hypotension with fluids and vasopressors as indicated e. consider corticosteroids f. preserve renal function by increasing renal blood flow and maintaining brisk urine output (IV fluid, furosemide, mannitol) g. be alert for DIC - Critical Care Handbook of Mass General pg 201

Answer 98

Stimulators of Platelets - ADP = most important - collagen = attracts platelets to the subendothelium - vWF - thrombin Inhibitors - NO - PGI2 (“platelet gathering inhibitor”) - ADPase ?fibrin is neither? IL-6 may?? The relatively small amount of thrombin formed serves to further enhance platelet activation and accelerate the coagulation response. Platelets, already primed by exposure to collagen, are synergistically primed by the addition of thrombin. - Townsend: Sabiston Textbook of Surgery, 18th ed. Exposure of subendothelial collagen with injury to intimal layer of vessel wall…platlet bind with assistance of vWF which binds glycoprotein I/IX/V on plt membrane. This adhesion stimulates plts to expand and develop pseudopodal processes and intiates the release reaction that recruits other plts. Primary mediators at this step (primary hemostasis) are ADP and serotonin. IL-6 stimulates growth and diff. of more plts. Interleukin-6 (IL-6): It increases platelet count in a dose-responsive manner. - Hoffman: Hematology: Basic Principles and Practice, 5th ed. The release of ADP and TXA2 induces further platelet activation and aggregation. - Davì,Patrono. Platelet Activation and Atherothrombosis. NEJM Volume 357:2482-2494, December 13, 2007, Number 2

Answer 99

Answer: b. Von Willebrands Factor Many of the biologic actions of NO·, including vasodilation, induction of vascular hyperpermeability, and inhibition of platelet aggregation .... - Townsend: Sabiston Textbook of Surgery, 18th ed. Prostacyclin (PGI2) chiefly prevents formation of the platelet plug involved in primary hemostasis (a part of blood clot formation). It does this by inhibiting platelet activation[4]. It is also an effective vasodilator. Prostacyclin's interactions in contrast to thromboxane (TXA2), another eicosanoid, strongly suggest a mechanism of cardiovascular homeostasis between the two hormones in relation to vascular damage. - http://en.wikipedia.org/wiki/Prostacyclin Von Willebrand factor is not an enzyme and therefore has no catalytic activity. Its primary function is binding to other proteins, particularly Factor VIII and it is important in platelet adhesion to wound sites - http://en.wikipedia.org/wiki/Von_Willebrand_factor

Answer 100

Answer: 1-3 days NSAIDS – 1-3 days Aspirin – 7-10 days The remaining COX-1 NSAIDs such as naproxyn, ketorolac, diclofenac, piroxicam, ibuprofen, and others also act as prostaglandin synthesis inhibitors. All of them cause reversible competitive platelet inhibition, and platelet function usually returns to normal within 1 to 3 days after stopping the drug - Fleisher: Evidence Based Practice of Anesthesiology, 2nd ed. Platelet function normalizes within 24 hours of the last dose of ibuprofen in healthy volunteers. - Goldenber et al. Duration of Platelet Dysfunction after a 7-Day Course of Ibuprofen. Ann Intern Med April 5, 2005 142:506-509 There is controversy in the literature as to whether or not preoperative aspirin use increases postoperative bleeding risk. It is generally recommended that aspirin be discontinued 7-10 days before an elective surgical procedure if possible. It is recommended that NSAIDs be discontinued 2 days before surgery.

Answer 101

Answer: b. Papaverin This is probably an old question, only asked one year ASA inhibits COX decreases Thromboxane A2 which stimulates platelet aggregation Papaverin smooth muscle relaxant. “PVD, CVD” Dipyrimadole (persantine)-impairs platelet function by inhibiting activity of ADP. Used in pulomonary HT. Phenylbutasone-NSAID COX inhibition. [A]fter infusion of more than 20 mL/kg in 24 hours, dextran 70 may interfere with normal blood clotting, causing a deficiency with crossmatching procedures and possibly a bleeding diathesis. These clotting defects reflect reduced platelet adhesiveness resulting from an antithrombin effect. - Miller: Miller's Anesthesia, 7th ed. The mechanism of antiplatelet action of dipyridamole is unclear. Although this drug has been previously demonstrated to stimulate PGI2 synthesis, potentiate the platelet inhibitory effects of PGI2 , raise platelet cyclic AMP levels by inhibiting phosphodiesterase, and block uptake of adenosine into vascular and blood cells, these potential antiplatelet actions generally do not occur at therapeutically achievable drug concentrations. - Braunwald: Heart Disease: A Textbook of Cardiovascular Medicine, 6th ed., Copyright © 2001

Answer 102

b. Qualitative platelet defect Urea makes platelets not stick well An association between renal failure and bleeding tendency has long been recognized. A qualitative defect in platelet function produced by uremia itself seems to be central. The defect results from accumulation of the compound guanidinosuccinic acid in uremic blood, which inhibits adenosine diphosphate–induced platelet aggregation. - Miller: Miller's Anesthesia, 7th ed.

Answer 103

Answer: C Heparin acts on ATIII so in AT III deficiency, it is insensitive to heparin The most common thrombotic manifestations in patients with antithrombin deficiency (AT deficiency) include lower extremity VTE, with recurrent VTE being common. Other sites of thrombosis include the inferior vena cava, hepatic and portal veins, and renal, axillary, brachial, mesenteric, pelvic, cerebral, and retinal veins. Arterial thrombosis is strikingly less common. In a patient with a known inherited antithrombin deficiency (AT deficiency), management of the acute thrombotic event depends on the type of antithrombin deficiency, because a variable response to large doses of heparin occurs in some of these patients. When a therapeutic response to intravenous heparin is not achievable, additional support with an antithrombin concentrate may be necessary. Antithrombin concentrates are used to raise the plasma antithrombin level from a reduced value to approximately 120%. - http://emedicine.medscape.com/article/198573-treatment In antithrombin III deficiency, the activity of LMWH is not as reliable as in an otherwise healthy person. Careful monitoring of the anti-Xa activity in the patient should be performed. Consider alternative anticoagulation medications (eg, warfarin) because the effectiveness of LMWH is likely reduced. - http://emedicine.medscape.com/article/954688-treatment

Answer 104

a) bernard soulier. This is probably low yield von Willebrand disease is due to an abnormality, either quantitative or qualitative, of the von Willebrand factor, which is a large multimeric glycoprotein that functions as the carrier protein for factor VIII (FVIII). von Willebrand factor is also required for normal platelet adhesion. As such, von Willebrand factor functions in both primary (involving platelet adhesion) and secondary (involving FVIII) hemostasis. - http://emedicine.medscape.com/article/959825-overview Bernard-Soulier syndrome (BSS) was first described in 1948 as a congenital bleeding disorder characterized by thrombocytopenia and large platelets. - http://emedicine.medscape.com/article/954877-overview Bleeding time is generally very prolonged in patients with uremia, signifying a major defect in platelet function, which improves after dialysis - http://emedicine.medscape.com/article/201722-overview The life span of platelets in circulation is 7 to 10 days. Under normal conditions, the spleen stores about one third of circulating platelets. Circumstances that increase splenic volume, such as hepatic cirrhosis or portal hypertension, cause a reduction in the circulating platelet count by a sequestration within the splenic sinusoids. - Firestein: Kelley's Textbook of Rheumatology, 8th ed.

Answer 105

Like heparin, low-molecular-weight heparin exerts its anticoagulant activity by activating antithrombin. With a mean molecular weight of 5000, which corresponds to approximately 17 saccharide units, at least half of the pentasaccharide-containing chains of low-molecular-weight heparin are too short to bridge thrombin to antithrombin (Fig. 137-4). However, these chains retain the capacity to accelerate factor Xa inhibition by antithrombin because this activity is largely the result of the conformational changes in antithrombin evoked by pentasaccharide binding. Consequently, low-molecular-weight heparin catalyzes factor Xa inhibition by antithrombin more than thrombin inhibition.[125] Depending on their unique molecular weight distributions, low-molecular-weight heparin preparations have anti–factor Xa to anti–factor IIa ratios ranging from 2 : 1 to 4 : 1. - Hoffman: Hematology: Basic Principles and Practice, 5th ed. Antithrombin is also termed Antithrombin III (AT III). - http://en.wikipedia.org/wiki/Antithrombin

Answer 106

LMWH is more anti-Xa than heparin Compared with UFH, LMWHs have higher anti-Xa/anti-IIa ratios Like heparin, low-molecular-weight heparin exerts its anticoagulant activity by activating antithrombin. With a mean molecular weight of 5000, which corresponds to approximately 17 saccharide units, at least half of the pentasaccharide-containing chains of low-molecular-weight heparin are too short to bridge thrombin to antithrombin (Fig. 137-4). However, these chains retain the capacity to accelerate factor Xa inhibition by antithrombin because this activity is largely the result of the conformational changes in antithrombin evoked by pentasaccharide binding. Consequently, low-molecular-weight heparin catalyzes factor Xa inhibition by antithrombin more than thrombin inhibition. Depending on their unique molecular weight distributions, low-molecular-weight heparin preparations have anti–factor Xa to anti–factor IIa ratios ranging from 2 : 1 to 4 : 1. - Hoffman: Hematology: Basic Principles and Practice, 5th ed.

Answer 107

2) There is a decreased incidence of heparin-induced thrombocytopenia and thrombisis associated with LMWH therapy Low-molecular-weight heparins (LMWHs) derived from UFH have more selective anti-Xa activity than UFH does. LMWH has been associated with less bleeding complications and has become the first-line therapy for prophylaxis and treatment of deep venous thrombosis (DVT) and acute coronary syndromes. LMWH can also cause HIT (

Answer 108

``` Enoxaparin Half-life = 4.5 hours Duration = 12 hours Dalteparin Half-life = 3-5 hours - Medscape ```

Answer 109

1) Stop the coumadin 5 days prior to surgery and administer LMWH 3 days prior to surgery Not sure why she is anticoagulated with CHADS2 but whatever 9.2.5. Bridging Therapy in Patients With Mechanical Valves Who Require Interruption of Warfarin Therapy for Noncardiac Surgery, Invasive Procedures, or Dental Care Class I 1. In patients at low risk of thrombosis, deﬁned as those with a bileaﬂet mechanical AVR with no risk factors,* it is recommended that warfarin be stopped 48 to 72 h before the procedure (so the INR falls to less than 1.5) and restarted within 24 h after the procedure. Heparin is usually unnecessary. (Level of Evidence: B) 2. In patients at high risk of thrombosis, deﬁned as those with any mechanical MV replacement or a mechanical AVR with any risk factor, therapeutic doses of intravenous UFH should be started when the INR falls below 2.0 (typically 48 h before surgery), stopped 4 to 6 h before the procedure, restarted as early after surgery as bleeding stability allows, and continued until the INR is again therapeutic with warfarin therapy. (Level of Evidence: B) - ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guideline

Answer 110

2) 7 days pre-op stop coumadin, start on full dose LMWH holding 12 hrs before surgery

Answer 111

3) Stop warfarin and start heparin infusion I think in 2016 we would do LMWH (depending on GFR)

Answer 112

C. VIII II, VII, IX, X, proteins C+S

Answer 113

I think the answer is actually D. HIT is from non-immune mediated platelet aggregation. From this article it actually causes aggregation: "Effect of Heparin and Heparin Fractions on Platelet Aggregation" Previous answer: Answer: Decreases thromboxane A2 production Unfractionated heparin effects anticoagulation by enhancing antithrombin activity, increasing factor Xa inhibitor activity, and inhibiting platelet aggregation. - Gabbe: Obstetrics: Normal and Problem Pregnancies, 5th ed.

Answer 114

a. Transfuse plasma Probably a pre-octaplex question On warfarin In terms of how fast in acts: Octaplex > FFP > vitamin K

Answer 115

Answer: b. Stop LMWH 12 hrs before the epidural Another risk factor for the development of spinal hematoma is a high-risk parturient who is receiving low-molecular-weight heparin (LMWH). Recent guidelines by the American Society of Regional Anesthesia suggest that neuraxial techniques should be deferred for 10 to 12 hours in a parturient who has received preoperative LMWH or 24 hours for parturients receiving higher doses of LMWH (e.g., enoxaparin, 1 mg/kg twice daily). - Miller: Miller's Anesthesia, 7th ed. 6 hours for regular heparin

Answer 116

d. 30 year old male going for hernia repair

Answer 117

a) DIC Hypotension is the major side effect weak basic anticoagulant (alone) due to interactions with plts and many proteins including fibrinogen. In the presence of heparin (strongly acidic) a stable salt is formed and anticoag activity of both drugs is lost For every 100 units of Heparin given, reverse with 1mg Protamine (reduce protamine dose by half for every 60 minutes from last injection) IV Protamine: hypotension and bradycardia Analphylaxis….especially those exposed to protamine through use of protamine-containing insulin (eg NPH) Complement activation by heparin-protamine complexes and lysosomal release from neutrophils High-protein, non-cardiogenic pulmonary edema (cardioplumonary bypass patients) Commonly, what is seen is either (1) isolated hypotension, with normal to low filling pressure and normal airway pressure, or (2) hypotension accompanied by elevated PA pressure, evidence of bronchoconstriction with elevated airway pressure, evidence of acute RV failure on visual inspection or intraoperative echocardiography, or any combination of these findings. A study by Kimmel and associates[150] found that neutral protamine Hagedorn (NPH) insulin use, documented fish allergy, and a history of nonprotamine medical allergies were independent risk factors for protamine hypersensitivity reactions. - Miller: Miller's Anesthesia, 7th ed. [Regarding] protamine paracoagulation test: If properly done, a strongly positive test is less sensitive for DIC than measuring FDP levels but is more specific and, in a patient in whom DIC is suspected, constitutes strong supportive evidence. - http://labtests.wetpaint.com/page/Protamine+Paracoagulation+Test Differential Diagnosis of Thrombocytopenia in Children and Adolescents Drug-induced via direct platelet effects (ristocetin, protamine) - Kliegman: Nelson Textbook of Pediatrics, 18th ed. The neutralization of heparin by intravenous injection of protamine sulfate takes about 30 to 60 seconds. Protamine sulfate is used in severe overdosage or bleeding caused by heparin. Hypersensitivity (anaphylaxis, anaphylactoid) reactions may occur. When protamine is given in a dose of 50 mg (10 mg/mL) over 10 minutes, acute hypotension, bradycardia, dyspnea, transient flushing, and a feeling of warmth can be avoided. - Ellenhorn's Medical Toxicology, 2nd ed., Copyright © 1997 Protamine may cause anaphylaxis or serious hypotensive episodes in approximately 2 percent of patients. - Braunwald: Heart Disease: A Textbook of Cardiovascular Medicine, 6th ed., Copyright © 2001

Answer 118

Answer: transformation of plasminogen into plasmin Thrombolytic agents available today are serine proteases that work by converting plasminogen to the natural fibrinolytic agent plasmin. Plasmin lyses clot by breaking down the fibrinogen and fibrin contained in a clot. - http://emedicine.medscape.com/article/811234-overview

Answer 119

(no TPA within 10 days of major surgery?) TISSUE PLASMINOGEN ACTIVATOR THERAPY FOR ACUTE ISCHEMIC STROKE Contraindications - Evidence of intracranial hemorrhage on pretreatment evaluation - Suspicion of subarachnoid hemorrhage - Recent intracranial surgery, serious head trauma, or previous stroke - History of intracranial hemorrhage - Uncontrolled hypertension at the time of treatment—>185 mm - Hg systolic or >110 diastolic—that cannot be reduced with acute antihypertensive therapy - Seizure at stroke onset - Active internal bleeding - Intracranial neoplasm, AVM, or aneurysm Goldman: Cecil Medicine, 23rd ed ``` Contraindications to Thrombolytic Therapy - Absolute o Recent major bleeding o Recent stroke o Recent major surgery or trauma o Irreversible ischemia of end organ o Intracranial pathology o Recent ophthalmologic procedure - Relative o History of gastrointestinal bleeding or active peptic ulcer disease o Underlying coagulation abnormalities o Uncontrolled hypertension o Pregnancy o Hemorrhagic retinopathy Townsend: Sabiston Textbook of Surgery, 18th ed. ```

Answer 120

A. Warfarin (acutely) was the previous answer, but I think Vit K is a better answer cause there's never a reason to use it as far as I know Warfarin should not be started until thrombocytopenia resolves, in order to avoid the transient increase in hypercoagulability induced by warfarin and the associated potential risk of limb gangrene Patients who have heparin-induced thrombocytopenia should not be treated with low-molecular-weight heparins, since these have high cross-reactivity with circulating PF4–heparin antibodies. Warfarin monotherapy in active heparin-induced thrombocytopenia is also contraindicated, on the basis of reports of warfarin-induced skin necrosis and venous gangrene in the limbs. Aspirin, the placement of an inferior venacaval filter, or both are not considered adequate therapies. - Arepally GM, Ortel TL. Clinical practice. Heparin-induced thrombocytopenia. N Engl J Med. 2006 Aug 24;355(8):809-17.

Answer 121

Answer: e. none of the above HEPARIN-INDUCED thrombocytopenia (HIT) type II is a potentially life-threatening complication. In contrast to HIT type I, the underlying mechanism of which has not been clearly identified and which is not associated with clinically relevant sequelae, immune-mediated HIT II is frequently associated with thromboembolic complications. [1] [2] [3] [4] In patients with HIT II, antibodies against complexes of heparin and platelet proteins, in particular platelet factor 4, are generated. The antigen-antibody complexes bind to platelet receptors and induce platelet aggregation. This leads to a decrease of the platelet count and is often associated with thrombosis and embolism of the venous or the arterial system, or both, with a ratio of venous-to-arterial thrombotic events of 3-4:1. In patients diagnosed with HIT II, an alternative anticoagulation must be used. In cardiac surgery, this poses a problem because anticoagulation of the cardiopulmonary bypass (CPB) system with unfractionated heparins (UFH) is the only well-established protocol. The heparinoid danaparoid sodium and the thrombin inhibitor recombinant hirudin (r-hirudin) have been successfully used in a large number of patients with HIT II during CPB. [5] [9] [10] [11] However, when impaired renal function is present, no antidote is available. Severe hemorrhaging in patients with renal failure where these agents have been used during CPB have been described, [10] [12] because these drugs are normally excreted and no antidote is available. - Koster A - Anesthesiology - 01-Feb-2001; 94(2): 245-51

Answer 122

The heparin-induced thrombocytopenia antigen is a complex between platelet factor 4 (PF4) and heparin; heparin-induced thrombocytopenia antibodies bind to regions of the PF4 molecule that have been conformationally modified by its interaction with heparin. A minimum of 12 to 14 saccharides are required to form the antigenic complex with PF4, so heparin molecules with a molecular weight of more than 4000 have the potential to cause heparin-induced thrombocytopenia, and heparin-induced thrombocytopenia occurs less commonly with LMWH than with unfractionated heparin. Documentation of the heparin-induced thrombocytopenia antibody confirms the diagnosis. - Goldman: Cecil Medicine, 23rd ed.

Answer 123

HIT is relatively common, occurring in approximately 1% to 5% of postoperative patients, and 0.5% to 1% of medical patients who receive unfractionated heparin derived from porcine intestine for 7 to 14 days. HIT is highly prothrombotic: In at least 50% of patients, a thrombosis develops in association with HIT.[1,22–26,45] Both venous (deep vein thrombosis, pulmonary embolism) and arterial (especially aortic and iliofemoral arterial thrombosis, cerebrovascular accidents, myocardial infarctions) thrombi occur. - Hoffman: Hematology: Basic Principles and Practice, 5th ed.

Answer 124

2016: I think Warfarin is a better answer since it's contraindicated until platelets >150 due to risk of hypercoagulability/limb necrosis. Warfarin can be started once the patient has been stably anticoagulated with a non-heparin anticoagulant and the platelet count has recovered to ≥150,000/microL. -uptodate Currently, a NOAC would be the best answer to start after HIT Previous answer c. platelet transfusion Bleeding is rare in patients with heparin-induced thrombocytopenia (HIT) because platelet counts are usually >20,000/microL. However, if bleeding occurs, platelet transfusion is appropriate. -uptodate

Answer 125

1) fetal Hb fetal Hb protective cause it's not sickly

Answer 126

d) no sons, and all daughters will be carriers X-linked recessive

Answer 127

Answer: Activated protein C resistance (factor V Leiden mutation) Basically factor V leiden is a hyperactive factor V that doesn't get inhibited by protein C, so you become pro-coagulant. Most common congenital bleeding diasthesis is vWd 1% ``` The frequency of asymptomatic heterozygous antithrombin deficiency in the general population may be 1 in 350. Most of these individuals have clinically silent mutations and never have thrombotic manifestations. The frequency of symptomatic antithrombin deficiency in the general population has been estimated to be between 1 in 2000 and 1 in 5000.' The prevalence of heterozygous protein C deficiency in the general population is about 1 per 200 to 500. Protein C deficiency is found in 3 to 4% of all patients with venous thromboembolism. The prevalence of protein S deficiency in the general population is unknown. Its frequency in all patients evaluated for venous thromboembolism (2 to 3%) is comparable, however, to that of protein C deficiency. The factor V Leiden mutation is remarkably frequent (3 to 7%) in healthy white populations but is far less prevalent in certain black and Asian populations. In various studies, APC resistance was found in a wide range of frequencies (10 to 64%) in patients with venous thromboembolism. In homozygous (hyperhomocysteinemia) individuals with the autosomal recessive C677T mutation of the MTHFR gene, which occurs in 15% of certain populations, moderate hyperhomocysteinemia may occur and is correctable with folic acid, but its relationship to venous thrombosis is controversial. - Goldman: Cecil Medicine, 23rd ed. ``` Although heterozygous cystathionine-β-synthase deficiency (hyperhomocysteinemia) is found in only approximately 0.3% of the general population, a MTHFR variant with an alanine to valine substitution at amino acid 677 is common[198] and can be present in 1.4 to 15% of the population, depending on their origin. - Hoffman: Hematology: Basic Principles and Practice, 5th ed. Unfortunately the last reference gives a range between the factor V Leiden prevalence. Answer likely Factor V Leiden.

Answer 128

Answer key says C. Maybe E? Increased GH ie acromegaly causes epiphyseal closure in adults. Glucocorticoids inhibit osteoblast function, which is thought to account for the osteopenia and osteoporosis that characterize glucocorticoid excess. In addition to centripetal obesity, patients develop fat depots over the thoracocervical spine (“buffalo” hump), in the supraclavicular region, and over the cheeks and temporal regions, giving rise to the rounded “moon-like” facies. Glucocorticoid excess impairs skeletal growth, interferes with normal bone metabolism by inhibiting osteoblastic activity, and enhances bone resorption, [871] [872] [873] effects related to the duration of steroid excess,[874] regardless of whether Cushing's syndrome is due to ACTH hypersecretion, adrenal tumor, or glucocorticoid administration. The effects of glucocorticoids are probably at the level of the epiphysis, [747] [749] [750] [875] because GH secretion and serum concentrations of IGF peptides and IGFBPs are usually normal. Long-term but not acute administration of glucocorticoids increases the risk of developing peptic ulcer disease. Osteonecrosis of the femoral and humeral heads is a recognized feature of endogenous Cushing's syndrome - Kronenberg: Williams Textbook of Endocrinology, 11th ed.

Answer 129

serum metabolites of catecholamines (READ BELOW) High-risk patients, including those who have a genetic syndrome that predisposes them to pheochromocytoma (eg, MEN 2A or 2B, VHL disease or neurofibromatosis, a prior history of a pheochromocytoma, a family history of a pheochromocytoma), should be screened with plasma metanephrine testing. In these scenarios, a higher-sensitivity test that lacks specificity is justified.[13] Patients at lower risk for a pheochromocytoma, including those with flushing spells, poorly controlled hypertension, or adrenal incidentalomas with an adrenocortical appearance, should be screened with a 24-hour urine collection for catecholamines and metanephrines. This test has a high specificity and acceptable sensitivity.

Answer 130

d) Pancreatic cancer VON HIPPEL-LINDAU DISEASE (CNS ANGIOMATOSIS). von Hippel-Lindau disease is an autosomal dominant disorder caused by a defective tumor suppressor gene at chromosome 3p25-p26 and characterized by retinal angiomas, brain and spinal cord hemangioblastomas, renal cell carcinomas, endolymphatic sac tumors, pheochromocytomas, papillary cystadenomas of the epididymis, angiomas of the liver and kidney, and cysts of the pancreas, kidney, liver, and epididymis. Both sexes are affected equally. The diagnosis is established if patients have more than one CNS hemangioblastoma, one hemangioblastoma with a visceral manifestation of the disease, or one manifestation of the disease and a known family history.

Answer 131

Answer: b. uremia Diabetic ketoacidosis is an emergent condition that often manifests in a diabetic patient with leukocytosis and an acute surgical abdominal emergency or with nausea, vomiting, lethargy, and signs of hypovolemia. - Miller: Miller's Anesthesia, 7th ed.

Answer 132

c) ketoemia Non-ketotic hyperosmolar syndrome is characterized by severe hyperosmolarity (greater than 320 mOsm/L), hyperglycemia (>600 mg/dL), and dehydration. Unlike diabetic ketoacidosis, severe acidosis and ketosis are absent.

Answer 133

a. diabetes mellitus dissolving sugar in pee makes it more dense

Answer 134

b) Diabetic ketoacidosis A. Clinical features include nausea, vomiting, and vaguely localized abdominal pain. Prominent GI symptoms may give rise to suspicion for intra-abdominal pathology. Dehydration is invariable, and respiratory distress, shock, and coma can occur. B. Laboratory evaluation shows an increased ion gap metabolic acidosis and positive serum ketones. Plasma glucose usually is elevated, but the degree of hyperglycemia may be moderate (300 mg/dl or lower) in 10-15% of patients in DKA. Pregnancy and alcohol ingestion are associated with "euglycemic DKA." The urine ketone reaction correlates poorly with ketonemia but is usually positive in DKA. Hyponatremia, hyperkalemia, azotemia, and hyperosmolality are other findings. Serum amylase and transaminases may be elevated, again raising suspicion for intra-abdominal pathology. A focused search for a precipitating infection is always prudent. - Washington Manual of Medical Therapeutics, 30th ed., Copyright © 2001

Answer 135

Answer: immune suppression (?) Weird question Diabetes is a risk factor for pancreatic cancer and is associated with an increased mortality rate. Diabetes of new onset may also be an early sign of pancreatic cancer. - Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed. Diabetes mellitus is a well-established risk factor for ischemic stroke. Diabetes associated with arterial hypertension or hyperlipidemia adds significantly to stroke risk. A variety of platelet, rheological, coagulation, and fibrinolytic abnormalities may play a role in the pathogenesis of stroke in diabetic patients. - Bradley: Neurology in Clinical Practice, 5th ed. Immunosuppressive Drugs Used in Solid Organ Transplantation and Their Side Effects Prednisolone results in osteoporosis, diabetes mellitus, glaucoma, infections - Miller: Miller's Anesthesia, 7th ed. The earliest studies of therapies to prevent beta cell destruction used immunosuppressive agents. - Kronenberg: Williams Textbook of Endocrinology, 11th ed. Recent studies have shown that 1% of patients diagnosed with diabetes after the age of 50 years will be diagnosed with pancreatic cancer within 3 years of their diagnosis of diabetes (Link here to PubMed- Probability of pancreatic cancer following diabetes: a population-based study.Gastroenterology. 2005 Aug;129(2):504-11. PMID: 16083707 ).

Answer 136

a. PTH Parathyroid hormone is therefore the primary regulator of rapid changes of extracellular calcium levels. The action of vitamin D affects delayed changes in calcium balance as opposed to the more immediate direct action of PTH. Calcitonin plays a much smaller role in calcium homeostasis. - Cummings: Otolaryngology: Head & Neck Surgery, 4th ed.

Answer 137

d) Increased urinary calcium Tip: PTH = phosphate trashing hormone Ca goes up (I hope you knew this) PO4 goes down (now you know this forever) [PTH] acts on proximal tubular cells to inhibit the reabsorption of phosphate. Dehydration develops because an increase in the filtered load of calcium leads to variable degrees of hypercalciuria. Alkaline phosphatase levels may be elevated in patients with overt bone disease. - Goldman: Cecil Medicine, 23rd ed. PTH converts 25-hydroxyvitamin D to its most active metabolite, 1,25-dihydroxyvitamin D-3 [1,25-(OH)2 D3], by activation of the enzyme 1-hydroxylase in the proximal tubules of the kidney. Also promotes calcium reabsorption in the ascending loop of Henle, distal tubule, and collecting tubule, as well as blocking reabsorption of phosphate in the proximal tubule. The hypercalciuria observed in patients with primary hyperparathyroidism appears secondary to the increased filtered load of calcium and to the hypercalcemia activating the calcium-sensing receptor on the basolateral membrane of the thick ascending loop leading to a suppression of potassium secretion in the lumen, a decrease in the lumen positive charge, and thus a decrease in calcium reabsorption in this segment. - Brenner: Brenner and Rector's The Kidney, 8th ed. ``` HYPERPARATHYROIDISM ↑ PTH ↑ Serum Ca2 ↓ Serum phos Normal/↑ alkaline phosphatase ``` ``` HYPOPARATHYROIDISM ↓ PTH ↓ Serum Ca2 ↑ Serum phos Normal/↓ alkaline phosphatase ↓ 1,25-OH- vitamin D3 ``` - Johns Hopkins: The Harriet Lane Handbook, 18th ed.

Answer 138

A. Impaired calcium metabolism Hypocalcemia: stones, bones, abdominal groans, thrones and psychiatric overtones Disorders associated with hypercalcemia, such as hyperparathyroidism, multiple myeloma, vitamin D intoxication, metastatic cancer, or excess calcium intake (milk-alkali syndrome), may induce the formation of calcium stones and deposition of calcium in the kidney (nephrocalcinosis) - Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed. Most patients with primary hyperparathyroidism have mild disease and commonly have no symptoms, the diagnosis being made by the finding of asymptomatic hypercalcaemia. The most common clinical presentations, particularly in younger patients, are related to renal stones and nephrocalcinosis (25–35%), high blood pressure (40–60%), acute arthropathy (pseudogout) caused by calcium pyrophosphate dihydrate deposition (chondrocalcinosis) ( Fig. 49.10A, B ), osteoporosis, peptic ulcer and acute pancreatitis, depression, confusional states, proximal muscle weakness and mild nonspecific symptoms such as lethargy, arthralgia and difficulties with mental concentration. - Adam: Grainger & Allison's Diagnostic Radiology, 5th ed. Argument for C: (this person was clearly overthinking, a big nono for POS) Oxalate gives joint pain? Hypercalcinosis - getting bone pain b/c that's where you're losing your bone from Note nephrocalcinosis mostly caused by oxalate... primary PTH is most common cause note calcium oxalate manage by managing oxalate

Answer 139

A. decreased PTH secretion Vitamin D3 produced in the skin is biologically inert and must be hydroxylated in two successive steps to become active. The first hydroxylation is performed in the liver by the cytochrome P-450 vitamin D 25-hydroxylase and generates 25-hydroxyvitamin D3. This has little biologic activity but is metabolized by cells in the proximal renal tubule to form the active hormone, 1,25(OH)2 vitamin D3. [In the kidney] PTH also inhibits 24-hydroxylase, thus preventing the formation of the inactive metabolite, 24,25(OH)2 vitamin D. - Goldman: Cecil Medicine, 23rd ed.

Answer 140

Increases osteoclastic activity Increases Ca and Phos absorp from gut Causes kidney reabsoption of Ca and Phos Net effect: Bone resorption ↑ Serum Ca ↑ Serum Phos

Answer 141

D. Osteoclast inhibition

Answer 142

A: Thyroid Calcitonin is a 32-amino acid protein produced by the parafollicular C cells of the Thyroid. C cells are derived from neural crest. They are incorporated into the superior and lateral aspects of the thyroid lobes. - Greenfield

Answer 143

c) Elevated PTH Answer: Hyperparathyroidism (elevated PTH) Most cases of hypercalcemia (>90%) are caused either by primary hyperparathyroidism or by malignancy-associated hypercalcemia (MAHC). The most common cause of elevated calcium levels in hospitalized patients is MAHC. - Goldman: Cecil Medicine, 23rd ed. Primary HPT and malignancy-associated hypercalcemia are responsible for the vast majority of cases of hypercalcemia, each contributing roughly an equal number. - Brenner: Brenner and Rector's The Kidney, 8th ed. Primary hyperparathyroidism occurs in 25 per 100,000 persons in the general population and in 75 per 100,000 hospitalized patients. This condition is the most common cause of mild hypercalcemia, which can be treated on an outpatient basis. In the United States, more than 50,000 new cases occur each year. - http://emedicine.medscape.com/article/766373-overview

Answer 144

Answer: loss of Bicarbonate Tip: I just assume everything GI that is past the stomach is higher in bicarb than your blood so you get acidosis if those things come out of you

Answer 145

Answer: metabolic acidosis with normal anion gap (loss of HCO3-) Chronic diarrhea – GI loss of HCO3-, non-AG metabolic acidosis

Answer 146

A. Salicylate poisoning ``` MUDPILES Methanol Uremia Diabetic Ketoacidosis/Alcohol and Starvation Ketoacidosis Paraldehyde Isopropyl alcohol Lactic Acidosis Ethelyene glycol Salicylates ```

Answer 147

a. Alcohol.

Answer 148

a- hypokalemia Another example of increased production of acids occurs in starvation and diabetic acidosis. It is due to the accumulation of ketoacids (ketosis) and reflects a severe shift from glycolysis to lipolysis for energy needs. - http://en.wikipedia.org/wiki/Acidosis Type 4 RTA leads to hypokalemia AG = [Na+]-([Cl-] + [HCO3 -]) = unmeasured anions - unmeasured cations This equation indicates that an increase in the AG can result from either a decrease in unmeasured cations (eg, hypokalemia, hypocalcemia, hypomagnesemia) or an increase in unmeasured anions (eg, hyperphosphatemia, high albumin levels). - http://emedicine.medscape.com/article/242975-overview

Answer 149

C. TPN ``` Causes of NAGMA Renal Tubular Acidosis Type I (Distal, Classic), Hypokalemic Type II (Proximal), Hypokalemic Type III (Type I and II) Type IV, Hyperkalemic Nonrenal Hyperchloremic Acidosis Diarrhea Pancreatic drainage Ureterosigmoidostomy Cholestyramine (diarrhea), NH4Cl and hyperalimentation with amino acid infusions, CaCl2 Toluene exposure (hippurate production) Loss of ketones that could have been converted to bicarbonate - Mason: Murray & Nadel's Textbook of Respiratory Medicine, 4th ed. ```

Answer 150

Metabolic acidosis?

Answer 151

D. 20 year old with an acute asthma exacerbation acidosis with increased CO2, and HCO3 is normal Urinary excretion of NH4+ accounts for approximately two thirds of net acid excretion usually, but can represent an even larger proportion of net acid excretion with acid loads. - Brenner & Rector's The Kidney, 7th ed

Answer 152

Answer: c. Partialy compensated metabolic Acidosis B might be a better answer …. Metabolic acidosis doesn’t “partially compensate” like a respiratory acidosis or alkalosis (doesn't take long to change your CO2)

Answer 153

Answer: intracellular acidosis Tip: Vomiting is analogous to bicarb infusion If have a lot of bicarb in the blood, then cell will compensate by booting out H+ thereby causing alkalosis in the cell- therefore causes alkalosis. It is associated with muscular twitchings, irritability, and tetany) and hypernatremia. Also get hypokalemia (b/c switching H+ for K+) Increased ECF osmolarity secondary to all the Na being infused along with the bicarbonate Also get cardiac abnormalities Get too much Na intravascularly therefore the cells themselves shrink

Answer 154

Answer: ammonia

Answer 155

??? Answer: Don’t see hypokalemia Metabolic acidosis Acidemia may exert a negative inotropic effect on the heart. The stress of either an underlying illness or an increase in adrenergic and corticosteroid activity associated with acidemia may elevate the peripheral white blood cell count and cause hyperglycemia. Other laboratory findings include variable degrees of hyperkalemia, hyperphosphatemia, and hyperuricemia (in lactic acidosis), as well as hypocalcemia as a result of decreased renal 1,25-dihydroxyvitamin D synthesis. - Goldman: Cecil Medicine, 23rd ed. Serum potassium is increased in: Metabolic Acidosis. The level in the serum goes up while the level inside the cell goes down as the potassium is pumped out of the cell in exchange for the excess hydrogen ion (acid). - http://www.drkaslow.com/html/potassium.html

Answer 156

e – metabolic alkalosis ?think pyloric stenosis Patients with gastric outlet obstruction represent the classic clinical scenario for metabolic alkalosis in which a deficiency of chloride and potassium in ECF is also present. Parietal cells in the stomach mucosa produce gastric fluid that has a high hydrochloric acid concentration. For each proton pumped into gastric fluid, bicarbonate is added to ECF by the parietal cell. Patients who lose large amounts of gastric fluid deplete their ECF of protons and chloride, as well as potassium. Renal function plays a key role in hypochloremic, hypokalemic metabolic alkalosis. In these alkalemic patients urine pH can be lower than 7. Such patients paradoxically produce an acid urine despite having alkalemia because of three phenomena. - Townsend: Sabiston Textbook of Surgery, 18th ed.

Answer 157

I would pick DVT... Never heard of a chronic leg ulcer from a DVT, but I've seen plenty of the other ones Probably the most common cause of healing delays is wound infection. If the bacterial count in the wound exceeds 105 organisms per gram of tissue, or if any β-hemolytic streptococci are present, the wound will not heal by any means including flap closure, skin graft placement, or primary sutures. Molecular oxygen is essential for collagen formation. Ischemia can be caused by atherosclerosis, cardiac failure, or simple wound tension preventing localized perfusion. Under hypoxic conditions, energy derived from glycolysis may be sufficient to initiate collagen synthesis, but the presence of molecular oxygen is critical for the post-translational hydroxylation of prolyl and lysyl residues required for triple-helix formation and cross-linking of collagen fibrils. Varicose dilation of veins renders the valves incompetent and leads to venous stasis, congestion, edema, pain, and thrombosis. The most disabling sequelae include persistent edema in the extremity and trophic changes in the skin that lead to stasis dermatitis, ulcerations, vulnerability to injury, and poorly healing wounds and infections that may become chronic varicose ulcers DVT→chronic edema→chronic ulcer

Answer 158

Characteristics of arterial ulcers include: * Usually found on the feet, heels or toes. * Frequently painful, particularly at night in bed or when the legs are at rest and elevated. This pain is relieved when the legs are lowered with feet on the floor as gravity causes more blood to flow into the legs. * The borders of the ulcer appear as though they have been ‘punched out’. * Associated with cold white or bluish, shiny feet. * There may be cramp-like pains in the legs when walking, known as intermittent claudication, as the leg muscles do not receive enough oxygenated blood to function properly. Rest will relieve this pain. Characteristics of venous ulcers include: * Located below the knee, most often on the inner part of the ankles. * Relatively painless unless infected. * Associated with aching, swollen lower legs that feel more comfortable when elevated. * Surrounded by mottled brown or black staining and/or dry, itchy and reddened skin (gravitational or venous eczema). * May be associated with varicose veins due to incompetence of the superficial venous system (50%). * May be associated with lipodermatosclerosis, in which the lower part of the leg is hardened * Often associated with swelling, which may be caused by local inflammation. Chronic inflammation destroys underlying lymphatic vessels, causing lymphoedema. This increases the pressure in the lower leg. * Thickened skin, hyperkeratosis (scaliness), papillomatosis (tiny rough bumps on the lower legs and feet), fissuring, oozing. Neurogenic (like diabetic ulcers): From not being able to feel that your foot/heel is getting ischemic so you don't move it so it gets ulcerated (+ for diabetics they have microvascular disease). In weight-bearing areas (ball of foot at MTP classically)

Answer 159

c: III Easy way: 1: no skin break 2: partial thickness dermis affected 3: full dermis affected +/- fat but not past fascia 4: past fascia European Pressure Ulcer Advisory Panel grading system: - Grade 1: non-blanchable erythema of intact skin. Discolouration of the skin, warmth, oedema, induration or hardness may also be used as indicators, particularly on individuals with darker skin - in whom it may appear blue or purple. - Grade 2: partial thickness skin loss involving epidermis, dermis, or both. The ulcer is superficial and presents clinically as an abrasion or blister. Surrounding skin may be red or purple. - Grade 3: full thickness skin loss involving damage to or necrosis of subcutaneous tissue that may extend down to, but not through underlying fascia. - Grade 4: extensive destruction, tissue necrosis, or damage to muscle, bone, or supporting structures with or without full thickness skin loss. Extremely difficult to heal and predispose to fatal infection.

Answer 160

a. epidermis Cells of the stratum corneum contain keratin, a protein that helps keep the skin hydrated by preventing water evaporation. - http://en.wikipedia.org/wiki/Stratum_corneum Cells of the stratum corneum are the largest and most abundant of the epidermis. This layer ranges in thickness from 15-100 or more cells depending on anatomic location and is the primary protective barrier from the external environment. - http://emedicine.medscape.com/article/1294744-overview

Answer 161

A central component of the epithelial immune system are a specific subset of dendritic cells (DC) known as Langerhans cells (LC) - Adkinson: Middleton's Allergy: Principles and Practice, 7th ed.

Answer 162

Answer: Neuropathy Chronic foot infections in patients with diabetes mellitus are common and difficult problems. They usually begin after minor trauma in patients with peripheral neuropathy, neuropathic ulcers, and arterial vascular insufficiency and take the form of cellulitis, soft tissue necrosis, or osteomyelitis with a draining sinus

Answer 163

??? If green = pseudomonas, pick something that covers it if MRSA or risk for it, pick something that covers it

Answer 164

c. Contact dermatitis Latex allergy occurs in up to 10% of operating room nurses. Delayed-type hypersensitivity (type IV) T-cell–mediated sensitization to rubber accelerators (e.g., thiurams, carbamates, mercapto compounds) and antioxidants (not latex proteins) in latex gloves causes an allergic contact dermatitis usually limited to the sites of direct contact (e.g., dorsum of the hand). - Habif: Clinical Dermatology, 5th ed. Irritant Contact Dermatitis. The most common reaction to latex products is the development of dry, irritated areas on the skin, especially on the hands of glove wearers. These reactions are not immunologic but are due to the irritant effects of repeated hand-washing, use of detergents and sanitizers, or powders added to the gloves. - Allergy: Principles and Practice, 5th ed

Answer 165

Hidradenitis suppurativa is an annoying chronic condition characterized by swollen, painful, inflamed lesions in the axillae, groin, and other parts of the body that contain apocrine glands. The disease is a chronic acneiform infection of the cutaneous apocrine glands that also can involve adjacent subcutaneous tissue and fascia. The hallmark of the disease is sinus tracts (which can become draining fistulas) in the apocrine gland body areas. Velpeau first described the condition in 1839. It's a really stinky/unfortunate disease

Answer 166

b) Normal saline