Richard Dean ABSITE Review Manual 2008

Metabolism & Nutrition

Carbohydrate Metabolism and Krebs Cycle (Lange Review of Medical Physiology, 22nd Ed, Ch 17):

- Entry of glc into most tissues (including hrt, mm, and adipose) is dependent upon presence of hormone insulin. Insulin controls uptake/metabolism of glc in these cells and plays major role in regulating blood glc [ ]. Rxns of carbohydrate metabolism can’t take place w/o presence of B vitamins, which fxn as coenzymes. Phosphorous, Mg, Fe, Cu, Manganese, Zn, and chromium also necessary as cofactors

- CHO metabolism begin w/glycolysis, which releases E from glc to form 2 molecules of pyruvate, which enter Krebs cycle (or citric acid cycle), an O2-req’g process, thru which they are completely oxidized. B4 Krebs cycle can begin, pyruvate loses CO2 group to form acetyl CoA – this rxn is irreversible and has important metabolic consequences. Conversion of pyruvate to acetyl-CoA req’s B vitamins

Fuel Substrates during GI Stress (Brunicardi, Schwartz’s Principles of Surgery, 8th Ed, Ch1; Shils, Modern Nutrition in Health & Dz, 8th Ed, pp 18-20, 1424-6)

- Glutamine (amide of acidic AA glutamate) is most abundant AA in body- Glutamine considered nonessential b/c synthesized w/I lungs and skeletal mm when dietary

intake is inadequate – it’s absorbed in gut, where it maybe broken down to alanine and used in process of gluconeogenesis in liver. Glutamine is also used by kidney as source of nitrogen in making ammonia

- Enterocytes use glutamine as primary source of fuel and has been increasingly recognized as important for maintenance of healthy intestinal mucosa and may even protect mucosa from injury induced by chemo, radiation, and other agents

- When given to rats w/shrt bowel syndrome, diet containing glutamine as 25% total AAs promoted mucosal growth in remaining small bowel w/increased villous hght and grtr degree of hyperplasia. Has been hypothesized that glutamine may preserve immune cell and enterocyte fxn and enhance N balance during injury/sepsis clinical evidence in humans remains inconclusive

Ion Assoc’d Active Intestinal Glc Transport (Schwartz – 8E Ch1)

- Hydrophobic cell membr’s relatively impermeable to hydrophilic glc molecules – 2 distinct classes of membr glc transporters in human systems…facilitated diffusion glc transporters (GLUT) that permit transport of glc down [ ] gradient and Na+/glc transport system, which transports glc molecules against [ ] gradients by active transport

- GLUT2 predominantly xpressed in sinusoidal membr of liver, renal tubules, enterocytes, and insulin-secreting beta cells of pancreas…important for rapid xport of glc resulting from gluconeogenesis

- E-dependent Na/glc transport system relatively prevalent on brush borders of SI enterocytes and epithelium of proximal renal tubules. Na/glc transport system are distinct glc transport systems found in intestinal epithelium and in proximal renal tubules…this system transports both Na and glc IC’ly. Glc affinity for this transporter incr’s when Na ions attached

- Na/glc transport system w/I intestinal lumen also enhances gut retention of H2O thru osmotic absorption

Obstructive Jaundice and Malnutrition (Schwartz 8E Ch32)

- Many pt w/pancreatic ca malnourished preop and suffer from gastroparesis in immediate postop period. Some surgeons routinely place feeding jejunostomy tube and gastrostomy tube in all pancreaticoduodenectomies, while others make decision on case-by-case basis. Gastrostomy tubes may decr length of stay in pt w/gastroparesis. Jejunostomy tubes certainly not benign and can result in leaks and intestinal obstruct’n. parenteral nutrition also assoc’d w/serious complications (line sepsis, loss of gut mucosal integrity, and hepatic dysfxn)

Depletion Substrate Starvation (Braunawald, harrison’s principles of Internal Medicine, 16th Ed, pp411-412)

- When nutritional intake (parenteral or enteral) falls below min req’s, body responds by recruiting alt fuel sources. Free fatty acids (FFAs) from adipose and AAs from protein become primary metabolic fuels

- During 1st wk, 4-5kg of body wght can be lost. Composition of wght loss include: adipose – 25%; pr – 40%; ECF – 35%

- As starvation proceeds, metabolic rate decr’s; ketones begin providing E to brain, and pr loss decr’s

- Depletion of minerals occurs as body mass shrinks. K and Mg maybe lost out of proportion to body mass

- Therapeutic Intervention – pr, glc, and fat should be provided early in hospital stay when starvation could occur. Should starvation manifest self, pr, glc, and fat (+ necessary minerals and mvi’s) should be replaced gradually to prevent refeeding syndrome; life-threatening mineral deficits (hypokalemia, hypomagnesemia, and hypophosphatemia) must be judiciously addressed; trace minerals must be provided until PO intake of balanced diet resumed. In severe starvation states, recovery may take as long as 3-4 mos

Dx of thiamine deficiency (Townsend, Sabiston Textbook of Surgery, 17th Ed p156)

- In pt w/severe thiamine deficiency, pt may xhibit beri-beri (characterized by refractory lactic acidosis d/t thiamine facilitating glc’s entry into TCA (tricyclic acid) cycle) Clinical manifestations: disturbed mentation, diabetes insipidus, thrombocytopenia, hyperbilirubinemia, and lactic acidosis; there are higher levels of proline and hydroxyproline

- In pt w/acute thiamine (-)y, Wernicke’s encephalopathy can develop – syndrome characterized by ataxia, opthalmoplegia, confusion, and impairment of shrt-term memory

- Chronic thiamine (-)y can result in Korsakoff’s syndrome – 6 major sx’s:

o Anterograde amnesiao Retrograde amnesiao Confabulation (invented memories which then taken as true d/t gaps in memory

sometimes assoc’d w/blackouts)o Meager content in conversationo Lack of insighto Apathy (pt lose interest in things quickly and generally appear indifferent to change)

- Tx of thiamine (-)y in acute setting is 100mg thiamine per day

Formation of Uric Acid (Harper, Review of Physiological Chemistry, 15th Ed, pp 381-393)

- Nucleic acids (NAs) are primary components of DNA. Purines and pyrimidines represent end pnts of NA synthesis. These products are predominantly products of endogenous synthesis. Catabolism of b/d products of purines/pyrimidines result in form’n of uric acid (UA) and beta-amino-isobutyric acid predominantly xcreted in urine, little metabolic recycling of these products

- Gout characterized by elevated levels of urate in blood and UA in urine. Elevated urate levels lead to deposition of urate crystals in joints, initiate infl’y arthritis. Elevated levels of urate may occur when there’s abnl hi turnover of NAs – polycythemia vera, myeloid metaplasia, chronic leukemia, and other hematopoietic dz’s

- Gouty arthritis resulting from above dz is referred to as 2ndary metabolic gout- In primary gout – no evidence of incr’d destruction of NA and hyperuricemia is d/t lrgly inherited

metabolic defect of purine metabolism – results in xcessive rates of conversion of glycine to UA- Mech’n of elimination of UA nl…in some cases maybe defect in kidney where there’s faulty

enzymatic transport of urates by renal tubules result in lower rates of xcretion of urate as UA

Hepatic glc production (Sabiston 17E pp78, 140)

- Liver stores up to 75g of glc in form of glycogen…in healthy pt, this can last upto 15h in starvation. In stressed/injured pt, this source of glc lasts significant shrtr period of time. Following starvation/injury, blood glc levels fall stimulate release glucagon, GH, catecholamines, AVP, and ANG II w/decr in serum insulin…these all act to incr hepatic gluconeogenesis w/net incr in glc production

- Sustained glc production depend on presentation of AA, glycerol, and FAs to liver. Primary gluconeogenic precursors used by liver are lactate, glycerol and AAs (alanine/glutamine)

- Skeletal mm, erythrocytes, and WBCs release lactate which is reconverted to glc by Cori cycle in liver

- Lactate produced by skeletal mm insufficient to maintain blood glc levels, so pr’s are degraded to provide add’l AAs to liver for gluconeogenesis. Even though skeletal mm provides majority of AAs other tissues lose proportionally more pr than mm

Mech’n of Absorption of vit D Small Intestine (SI) – Schwartz 8E pp1023-1024

- Vit D (A, E, and K) are fat-soluble vitamins (Vits) and dependent on bile salt micelles for absorption, primarily in jejunum

- Vit D, A, and E absorb thru passive diffusion mech’n; vit K appears be absorb’d thru both passive diffus’n and carrier-mediated uptake

- Esters of dietary vit D and E hydrolyzed by cholesterol ester b4 being solubilized w/I micelles. Vit D delivered to liver in Chylomicron remnants where undergos 25-hydroxylation – subsequently, metabolism involves renal synthesis of 1,25-dihydroxy derivative (potent regulator of Ca++ metabolism)

Fuel for Gut (Shils, Modern Nutrition in Health & Dz, 8E pp18-20, 1424-1426)

- Glutamine (amide of acidic AA glutamate) is key component in our biochem- Absorbed in gut where maybe broken down to alanine and used in process of gluconeogenesis

in liver…also used by kdiey as source of N in making ammonia- Glutamine is most abundant AA in body . When no in abundance in diet, synthesized in most prt

in mm and is used as primary source of fuel in intestines. Has been increasingly recognized as important for maintenance of healthy intestinal mucosa and may even protect mucosa from injury induced by chemo, radiation, other agents

- when given to rats w/shrt bowel syndrome, diet contain glutamine as 25% total AAs promoted mucosal growth in remaining small bowel w/incr’d villous height and grtr degree of hyperplasia. Been recognized that in catabolic states, glutamine is released from mm and used by GI mucosa – proposed that this incr in glutamine use may result in signific’t mm wasting

Pr Req’s in Mutisystem trauma (Fischer, Mastery of surgery, 5E, pp36-37)

- in stressed pt, accepted pr regimen is 1.5g/kg/24h. been most xtensively studied in burn pt and been shown improve N balance…incr’g pr ratio above 1.5g/kg/24h no shown to be effective.

- Pr turnover is incr’d in traum – incr’d pr synthesis fueled by incr’d mm b/d- Increasing nutritional pr levels to 1.5g/kg/24h shown to decr mm turnover while provide adeq

substrate for new pr synthesis- Formulas containing incr’d branched-chain AAs (BCAAs) shown be as effective but no more

effective in provid’g nutrition support as nl formulas

Coagulation & Hematology

Conditions assoc’d w/nl INR and abnl aPTT (Sabiston 17E pp117-118)

- aPTT (activated partial thrombin time) detects levels of intrinsic coagul’n pathway (high-MW kininogen, prekallikrein, factors XII, XI, IX, and VIII) and common path factors of fibrinogen, prothrombin, factors V/X.

- factor levels of 30% or less needed to affect aPTT levels. Heparin Rx causes prolongation of aPTT w/o affecting PT or INR (international normalized ratio)

- nl INR or PT w/abnl aPTT suggest (-)y in proximal intrinsic pathway or presence of inhibitor (lupus anticoagulant, heparin, or another sp factor (-)r)

- while prolonged PT or incr’d INR suggest abnl’s in vit K dependent factors

If one does not drain pus from wound leads to liquefactive necrosis of fascia and dehiscence

Tx of Chronic Anemia/renal insufficiency (Katzung, Basic and Clinical Pharm, 9E, pp536-538; Harrison’s Ch58)

- chronic renal insufficiency (CRI) can lead to chronic anemia d/t decr’d erythropoietin (EPO) production in kidneys hypoproliferative anemia (marrow no able to adequately compensate for anemia w/incr’d RBC production) – in general, RBCs that are produced are normochromic and normocytic

- Recombinant EPO can be admin’d to HD pts as epoetin alfa – has half life of 4-13h and no cleared by dialysis – stimulates erythroid prolifer’n and differentiation and causes incr in both Hb and Hct

Tx of Methemoglobinemia (Harrison’s Internal Medicine – Fauci – 17E Ch99)

- Methemoglobinemia occur when ferrous moiety of Hb becomes oxidized to ferric (Fe3+) moiety which generates molecule w/much higher affinity for O2 than Hb O2 no unloaded into tissues as efficiently – can be result of genetic mutation in affecting either Hb formation or in enzymes that reduce methemoglobin to Hb (methemoglobin reductase, NADP diaphorase) or can be result of various drug toxicities (dapson, lidocaine, and nitrate-containing cmpds)

- Pt may have sx of hypoxia and cyanosis but still maintatin hi PaO2. Blood characteristically ‘muddy brown’ when freshly drawn and methemoglobinemia is sx’c at concentrations of >15%, and can be fatal at [ ]’s of >60%

- For emergency tx, IV injection of 1mg/kg of 1% methylene blue indicated. In milder cases, methylene blue can be given orally at 60mg TID-QID or w/oral ascorpic acid at 300-600mg/day

Transplant & Immunology

Activation of T-cell Mediated Immune Response (O’Leary Physio Basis of Surgery 4E pp181-182)

- T-lymphocytes (T cells) named for its site of origin, the thymus. Maturing T cells ‘taught’ to recognize ‘self’ MHC Ags and become tolerant of them…process called clonal deletion b4 its release from thymus eliminates T cells that fail xhibit tolerance to self

- T cells carry MHC class I Ag on surface…as specialized immune cell, also carries class II Ags – it xpresses variety of cell-sp and fxnal cell surface mrkrs

- 3 broad classes of T cells:o Helper T cells (Th) – amplify cellular IR – xpress CD 3, 4o Cytotoxic T cells (Tc) – effect target cell killing, xpress CD3, 8o Suppressor T cells (Ts) – buffer IR, xpress CD3, 8

- Most important structure on its surface is T cell receptor (TCR) – its ‘ag recognition platform’ is critical interface for peptide binding w/M0 MHC class II molecules – this precise alignment is signal event in ag presentation

- When appropriately stimulated thru TCR, signal transduced to T cell nucleus…mRNA elaborated, coding for cytokines and cytokine Rs which grtly amplify IR

Components of Adaptive IS

- Adaptive immune system (IS) is comprised of B and T cells- B cells, named for site of origin in chicken (bursa of Fabricus) play important intermediary role in

immune defense; reside in LNs and spleen and xpress various cell-surface mrkrs that include: MHC class I and II Ags, B-cell-sp markers, and Ig’s. when stimulated, B cells differentiate into plasma cells. Plasma cells, w/cytoplasm containing abundant ribosomes on endoplasmic reticulum (ER) are ‘factories’ w/mission to produce sp Ab

- T cells originate in thymus – one of most sophisticated elements in IRo Mature T cells ‘taught’ to recognize ‘self’ MHC Ags and become tolerant of themo Any T cells that fail xhibit tolerance to self eliminated in process called clonal deletiono On its surface, T cells xpress MHC class I&II Ag and variety of cell-sp surface mrkrs

(CD114, CD18, and CD28)o 3 broad classes of T cells include Th cells (amplify cellular IR); Tc cells effect target cell

killing and Ts cells which buffer IRo All T cells xpress CD3 on surface…Tc and Ts xpress CD8 and Thx press CD4o TCR recognize MHC class II Ag of M0’s and represent signal event in Ag presentation.o When appropriately stimul’d thru TCR, messenger RNA (mRNA) elaborated (code for

cytokines and cytokine Rs) which grtly amplify IR

Etiology of Lymphoproliferation after Txp (Schwartz 8E p297)

- Allorecognition = recognition of foreign HLA Ag by recipient T cells – happens by either direct or indirect pathway

o Recipient’s T cells directly interact w/donor HLA molecules, lead to production of activated Tc cells in direct pathway

o In indirect pathway, donor’s Ag (which maybe shed from parenchymal cells of graft into recipient’s circulation or alternatively maybe encountered by recipient’s APCs in graft self) are processed by recipient’s own APCs

o Recipient’s APCs then present donor’s Ag to recipient T cells lead to their activation- In either direct/indirect path, subsequent steps similar

o TCR-CD3 cmplx on surface of lymphocyte is where binding of T cell to foreign molecule occurs – leads to signal transduction to cell (signal 1) – not enough to result in T cell activation

o Full activation req’s 2nd signal that’s not dependent on Ag – signal 2 is from binding of accessory molecules on T cell to corresponding Ags on APC – CD25 on T cell bind w/ligand B7 on surface of APC

o Transmission of signal 1 and 2 to cell nucleus leads to IL2 gene xpression and to production of IL2 – IL2 then permits entire cascade of T cell activation to proceed, lead

to prolifer’n and differentiation of these cells into cells capable of causing damage to graft

o Tcell activation important start rejection process – also B cell activation and Ab production important

o Ig R’s on surface of B cells acquire foreign Ags – then process similar to way APCs process donor Ag – B cell then interact w/activated Th cells – lead to B cell proliferation, differentiation into plasma cells, and to Ab produc’n

Etiology of Renal Allograft Rejection (Schwartz 6E pp445-447)

- Acute rejection occur most common follow 1st wk post txp. Rejection characterized by oliguria, rising serum Cr, or failure of Cr to improve; enlrgmnt and tenderness of renal allograft assoc’d w/malaise, fever, leukocytosis, HTN, and peripheral edema assoc’d w/acute rejection. Lab studies will freq’ly reveal lymphocytemia, red cell casts, proteinuria, decr’d UOP, Na xcretion, and renal tubular acidosis (RTA). Acute renal failure mediated by T cells

- Dx of acute rejection suggested w/renogram demo’g poor perfusion of kidney, swollen kidney by U/S, and confirmed w/renal bx – acute renal failure mediated by T cells

- Tx of acute rejection includes hi doses of CS’s. solumedrol 500mg-1g IV is standard tx. Prednisone (2mg/kg) for 3d maybe used. Failure respond calls for use of antilymphocytic preps (ATGAM or OKT-3)…in event that these drugs fail resolve acute rejection FK506 admin’d

Immune Suppression Medicine which (-) purine synthesis (AHFS Drug Info 2008; 10:00 antineoplastic agents: methotrexate and mercaptopurine)

- Methotrexate (MTX) used in trophoblastic neoplasms, leukemias, breast ca, psoriasis, rheumatoid arthritis, and infl’y bowel dz – this drug and its metabolites able to be immunosuppressive by reversibly (-) dihydrofolate reductase (DHFR) which is vital step in purine synthesis pathway. (-)’s purine synthesis pathway and Also (-) conversion of deoxyuridylate to thymidylate which used synthesize DNA during cell reproduction

- Reason MTX works well is that MTX has strngr affinity for DHFR than folate – MTX can be reversed w/substantial quantities of folate MTX kills rapidly dividing cells which include malignant cells, mucosal cells in GIT, fetal cells, BM cells, and epidermal cells – destruction of said cell lines seen in adverse effect profile of MTX

o MTX causes oral ulcers, stomatitis, gingivitis, ulcers, pharyngitis, leucopenia, anemia, thrombocytopenia, and Steven-Johnson/toxic epidermic necrolysis syndromes

o Other severe SEs: hepatotoxicity lead to liver failure, nephrotoxicity causing renal failure, and pulm toxicity leading to pulm fibrosis – these toxicities can occur at any dose or duration of MTX and thus LFTs, CBCs, and BMPs must be monitored regularly

o Been shown to have immunosuppressive effects + (-) lymphocyte production – MoA unk, Resistance occur usually d/t decr’d cell uptake of drug and incr DHFR enz synthesis

- Mercaptopurine – purine antagonist used as antineoplastic and immunosuppressive agento Used in conjunction w/MTX for leukemias, Crohn’s dz

o Converted to ribo-nt by body’s own enz’s which act as purine antagonist (-)g RNA synthesis (-) DNA synthesis

Infections assoc’d w/defective cell-mediated immunity (CMI) – Fauci, Harrison’s principles of internal medicine 17E ch182

- T cells created by thymus where each cell learns which is self vs foreign pr’s – once TCR recognize foreign pr the CD4 Th cells activated which release cytokines – 2 types of Th cells – Th1 cells release IL-2, IFN-g, and turns to activate killer T cells (CD8) which effectively kill IC, fungal, and viral pathogens

- Th2 cells turn on humoral/B cell immunity system which kill bacterial infections – T cells responsible for chronic and subacute rejection in txp pt if there’s defect or decr # of T cells body open to many types of infections

- HIV infection/organ txp pt classically show how as CD4 cnt drops body more prone to infection- Classic infections that infect depressed cell-mediated system are:

o Bacteria: Listeria monocytogenes Mycobacterium tuberculosis Mycobacterium avium complex Salmonella typhii – septicemia Streptococcus pneumoniae Haemophilus influenzae Clostridium difficile

o Viral: CMV – colitis, retinitis HSV: >1 ulcer, pneumonitis VZV: zoster >1 dermatome, disseminated HSV-8: Kaposi/?Karpi sarcoma

o Protozoan: Toxoplasmosis gondii Giardia lamblia Leishmaniasis Entamoeba histolutica

o Fungal: Candidiasis: esophageal, thrush, disseminated Pneomocystis jiroveci PNA Mucor rhizoids Aspergillus Histoplamosis capsulatum Cryptococcus neoformans Coccidiomycosis immitis

Initial tx of acute rejection of liver txp (Sabiston 17E p731)

- 30-50% of liver txp have Tcell mediated acute rejection w/I 6mos of txp…most of these are w/I 1st 10d. variable presentations may include fever, abd pain, and elevated brn and hepatic enzymes

o Dx made by liver bx that shows presence of periportal lymphocytic infiltrate that xtends into liver parenchyma + infl’y cell invasion into vascular endothelium

- Hi dose CS’s effective against most episodes of acute rejection. CS-resistant rejections responsive to more potent monoclonal/polyclonal anti-T cell Abs leads to acute rejection being reversed in 90% cases

- Rejection more responsive to tx closer occurs to time of txp

Malignancy Assoc’d w/Txp Immunosuppression (Schwartz 8E p328)

- Txp recipients have disproportionately hi incidence of lymphoma (350x nl individual)- Lymphomas constitute 20% all tumors in pt w/txp- Xtra nodal involvement unusually common (69%) and txp’d kidney often involved (23%)….22%

of these tumors are in CNS an otherwise unsual site for lymphoma- Lymphomas may begin as lymphoproliferative lesions induced by virus

o Epstein-barr virus (EBV) is commonly incorporated into genome of lymphoma cells – these pt often have syndrome resembling mononucleosis w/fever, pharyngitis, and diffuse lymphadenopathy

o Polyclonal B cell proliferation rather than true malignancies are findings in these early lesions.

o Tumors that are initially polyclonal may eventually undergo cytogenic alteration, lead to malignant transformation w/monoclonal tumor that’s characteristically B cell lymphoma

MCC of failure of pancreatic txp (Schwartz 2005 pp313-314)

- Complications common after pancreatic txp- MCC of failure of pancreatic txp is thrombosis – incidence 6%- Low dose heparin, dextran, or anti-plt agents admin’d routinely to prevent such complication- Aa or vv thrombosis is heralded by incr’g blood glc levels or insulin req’s or by decr in urine

amylase levels- Hematuria, tenderness/swelling of graft, and ipsilateral LE edema also accompany vv thrombosis- Tx for thrombosis is graft removal- Thrombosis is much more significant cause of graft loss than bleeding or hemorrhage (<1%)

Tissue typing renal txp (Schwartz 8E pp297, 306)

- Main ag in triggering rejection coded for by major histocompatibility cmplx (MHC) genes in humans known as human leukocyte ag (HLA) ag’s on chromosome 6. b/c of xtreme polymorphism, only rarely do 2 unrelated individuals share all Ag’s xpressed

- Relatives often share some ag’s b/c each person inherits 1 set of HLA ag’s from each parent and all ag’s are xpressed

- 2 classes of HLA ag’so Class I ag xpressed on portions of MHC supergene called HLA-A, B, and C loci and

xpressed on membr of all nucleated cellso Class II ag xpressions of HLA-D, D, DQ, and DW/DR sub-loci generally xpressed by Ag-

presenting cells (APCs) – B cells, monocytes, dendritic cells (Macrophages – M0)- Immunologic eval involves determining blood type, tissue type (HLA-A, -B, or –DR) and any

cytotoxic Ab’s against HLA ag’s (d/t prior txp, transfusions, preg’y). in living donor, cross-match should be performed early on during eval’n

- Tissue Typing Techniques (*done routinely for live txp; +done for cadavers) o 1+* Pretxp Crossmatch: lymphocyte crossmatch using donor lymphocytes and

recipient serum – tests for B&T cellso 2+* microlymphocytotoxicity test:T cell screen. B cell if requested (by 30’

incubation). To screen for anti-HLA cytotoxic Ab’s. (Pt serum incubated w/B&T cells)o 3*. DNA Typing: for class II ag’s. for particular sp’s, mainly DR Ag’so 4 mixed lymphocyte cx: replaced by molecular typing. No freq’ly used,

superseded by other testso 5 flow cytometry crossmatch: detect lo level of cytotoxic ab. Indicated for 2nd

txp’so 6 antiglobulin crossmatch: T cells. Incr’s Sn of standard crossmatch

Apoptosis in Cell Death (Schwartz 8E p409)

- Apoptosis or programmed cell death – way cell use genetically programmed mech’n to kill cells and essential for maintenance of tissue homeostasis

- Apoptosis remove unwanted cells, those that have completed their jobs or have been damaged – can be initiated by stimuli (death R signals (Fas or cytokine TNF), growth factor deprivation, DNA damage, and stress signals)

- 2 major pathways control biochem’l mech’n governing apoptosiso Death R and mitochondrial

- Recent research suggest interweaving of 2 mech’n. important is activation of caspases (cascade of proteinases)

- Pos and neg regulators control activities/xpression of caspases- Cmplx machinery of apoptosis must be tightly controlled- Dysfxn can cause neoplastic transformation

Infection & Abx

Tx of Clostridium difficle (Schwartz 8E p1100)

- C diff is leading cause of nosocomial diarrhea, range from watery diarrhea to life threatening colitis – colitis d/t overgrowth of C difficile and depletion of nl commensal flora of gut w/use of Abx…almost any abx may cause this dz. Immunosuppression, co-morbidities, prolonged hospital stay, and bowel surgery incr the risk. Dx made by presesence of toxins in stool (toxin A – enterotoxin and toxin B – cytotoxin)

- Dx can also be made endoscopically by detection of characteristic ulcers, plaques, and pseudomembr’s

- Mgmt: immediate cessation of offending abxo Mild dz (diarrhea w/no fever or abd pain) treat w/PO metronidazole or PO vanco.o Diarrhea w/fever, abd pain and dehydration treat w/bowel rest, IVF, and oral

metronidazole or vancoo Proctosigmoiditis may respond to vanco enemaso Recurrent colitis occur in up to 20% pt and may need lngr courses of PO metrodizole or

vanco (1 mos)o Reintroduction of nl flora by probiotics suggested for recurrent/refractory dz

- Fulminant colitis needs emergency laporotomy

Role of H.pylori in MALT Lymphoma (SAbiston 17E pp1279-1281)

- H pylori infection strongly assoc’d w/lo grade B cell mucosa associated lymphoid tissue (MALT) lymphoma which is Ag driven

- Evidence to show MALT lymphoma can regress when H pylori infections eradicated w/antimicrobial agents

- H pylori eradication should be attempted b4 chemo- Standard Rx: Bismuth subsalicylate 2 tab/qid. Tetracycline 500mg/qid and metrodiazole

250mg/tid for 2 wks- Alt Rx: omeprazole 20mg/bid, clarithromycin 250mg/bid, and metrodizaole 500mg/bid or

amoxicillin 1gm/bid for 1 wk

Bacteriology of Perforated Appendicitis (Schwartz 8E p1121)

- Nl appendix bacteriology is that of nl colon. Porphyromonas gingivalis is bacterium seen only in adults; otherwise, bact in appendix no change thru one’s life cx similar to those as in other colonic infections (diverticulitis)

- Primary organisms seen in both acute/perfor’d appendicitis – Escherichia coli and Bacteroides fragilis. May also be variety of facultative, anaerobic, and mycobacterium present. Appendicitis is polymicrobial infection broad-spectrum abx indicated

- Peritoneal cx indicated only in immunocompromised pt or development of abscess after tx of appendicitis

- Common organisms seen in acute appendicitiso Aerobic/facultative

Gram neg bacilli E coli

Pseudomonas aeruginosa Klebsiella sp

Gram pos cocci Streptococcus anginosus Streptococcus sp Enterococcus sp

o Anaerobic Gram neg bacilli

Bacteroides fragilis Bacteroides sp Fusobacterium sp

Gram pos cocci Peptostreptococcus sp

Gram pos bacilli Clostridium sp

Characteristics of Aminoglycosides (AG) – Harrison’s Principles of Int’l Med 15E pp878

- AG Abx have narrow therapeutic index- 2 most common adv rxns: nephrotoxicity and ototoxicity- Incidence of nephrotoxicity is approx 5-10% among adult pt’s who receive Rx for 10-14d – many

cofactors influence freq of toxicity – xtremes of age, concomitant drug Rx, hydration status- Serum cr levels should be monitored every 3-5d or more often if changes seen- Some data suggest once-daily admin’n may cause less nephrotoxicity- Ototoxicity from AG Rx present as either auditory or vestibular damage- Since AG destroy hair cells in inner ear, ototoxicity maybe permanent. Risk of ototoxicity incr

w/prolonged therapy, higher serum [ ]’s, hypovolemia. Clinically apparent ototoxicity is uncommon (<1% when duration kept at minimnum…with more sensitive monitoring (Audiograms) as/x’c hi –tone hearing loss more commonly noted

- Neuromuscular depression from AG caused by reduced Ach activity at postsynaptic membr’s and can result in rare/severe resp depression – this complication lrgly avoided if AG admin’d IV over 30min or by IM injection – if resp depression occurs, revers’d by admin of Ca++

- Value of measur’g serum [ ] controversial…these measures usually unnecessary when pt receive once-daily Rx

Characteristics of Multi-drug microbial resistance (O’Leary 4E pp225-226)

- R to Abx is d/t phenotypic changes that are genetically mediated- Intrinsic resistance : Bact that are inherently different from other organisms and have therefore

always been resistant to certain drugs- Acquired Resistance :

o Spontaneous mutation – may cause structural/biochem changes (cell wall/plasma membr permeability, receptor site affinity)

o Plasmids – MC mech’n, are xtrachromosomal material acquired in 3 ways: Transduction: infection of bact cell by bacteriophage bringing entrapped

plasmids Transformation: acquisition of plasmids from environment surrounding cell Conjugation: direct cell-cell xfer of plasmids via sex pili

Characteristics of Overwhelming Post-splenectomy infection (OPSI) – Sabiston 18E pp513, 1627, 1649-1650

- Spleen is responsible for maintenance of nl immune fx so people lack spleen at increased risk for OPSI – OPSI can be in form of bacteremia, PNA, or meningitis – mainly caused by encapsulated organisms – pneumococci (#1), H.flu, meningococci are MC organisms. These organisms have polysaccharide capsule req’g both Ab and complement as body’s defense. Asplenic pt have lo levels IgM and suppressed Ig response

- Asplenic pt have defective activation of complement d/t decreased production of opsonins. Properdin initiates alternative complement pathway. Spleen also manufactures another opsonin tuftsin, which enhances phagocytic activity of polymorphonuclear leukocytes (PMNs) and mononuclear phagocytes…also neutrophil fxn decreased in asplenic pt

- OPSI is characterized by sudden onset of sx and rapid course that usually only lasts 12-18h. pt c/o fever, nausea, vomiting, HA. AMS can occur…pt’s will go into shock, electrolyte imbalance, and disseminated intravascular coagulation (DIC) – mortality rate is 50-80%. Kids at incr’d risk of mortality. Pt who had splenectomy 2ndary to hematologic d/o vs trauma at higher risk of development of OPSI

- After splenectomy for trauma, pt should be given pneumococcal, meningococcus, and H flu vaccines prior to d/c (w/I 2 wks of splenectomy). For elective splenectomy, vaccines should be given beforehand

Characteristics of hep B virus (Schwartz 8E p124; CDC. STD tx guidelines 2006: hep B)

- Hep b virus is hepadnavirus, dsDNA virus that lead to hepatic infl’n – non-retroviral virus that uses reverse transcript’n as prt of replication cycle. Primary infection w/HBV generally self-limited, can progress to chronic carrier state 5% of time when assoc’d w/cirrhosis, liver failure, and HCC. Death occurs roughly 30% of chronic persons

- Transmitted parenterally, usually either in perinatal period (MC) or via IV drug use/sexual contact

- HBV-infected infants have much higher rate of chonicity. Natural hx of HBV influenced by EtOH consumption, IS competence, obesity, and concurrent viral infections (HCV, HDV, and HIV)

- In primary infection, HBsAg and HBeAg become detectable in blood usually 6 wk after xposure; rate of transmission during acute infection very high. Shrtly after infection, anti-HBc Ab develop (mainly IgM class in early stage). ALT levels start to incr after viral infection well-established. Viral CL phase characterized by disappearance of HBsAg and HBeAg and appearance of anti-HBs and anti-HBe Ab’s

- In chronic cases, HBsAg remains for >6 mos, serum HBV DNA titers remain hi and continued/intermittent elevation of ALT levels. HBeAg usually disappears, and pt seroconverts to anti-HBe pos, assoc’d w/significant reduction in viral load. Timining for HBe seroconversion varies (yrs to decades) HBeAg seroconversion important sign of reduced dz activity and improved prognosis – used as therapeutic endpnt

- Surgeons/other hlth care workers at hi risk for this blood-borne infection and should receive HBV vaccine – kids routinely vaccinated in US. In postxposure setting, hep B immune globulin (HBIG) confers approx 75% protection from HBV infection

Dose/Interval Gentamicin Rx (Marino ICU Book 3E pp801-806; Epocrates Rx Pro, Version 8.10, Gentamicin)

- MoA: gentamicin is AG whose antimicrobial effect works by (-)g pr synthesis by directly binding to 30S ribosomal subunit; it is bactericidal abx whose effectiveness dependent on [ ]

- Clinical uses: gentamicin indicated against G- bacilli including Pseudomonas aeruginosa. Also indicated against infections caused by Serratia, Enterobacter, Citrobacter, and Staph

- Dosage: pt actual body wght should be recorded and pt’s ideal body wght should be calculated. Dosage should be determined by utilizing smaller of 2 #’s

- Adults w/nl renal fxn:o Trad’l interval dosage: 1-1.7mg/kg daily in divided doses q8hr via IM or IV infusiono Once daily dosing: pt may receive up to 5-7 mg/kg q24hr to achieve peak bactericidal

effecto Dosing should be monitored and modified thru peak and trough serum levels +

monitoring of renal fxn Peak levels: 6-8mcg/mL (Life threatening 8-10mcg/mL) Trough levels: 0.5-2 mcg/mL (Life threatening 1-2 mcg/mL) Toxic peak levels: >12 mcg/mL Toxic trough levels: >2 mcg/mL

- Gentamicin and other AGs should be avoided whenever possible 2ndary to their potential for renal impairment. Other options available for treating serious G- infections which possess less potential for harm

Most Likely Organisms in Biliary Sepsis (Schwartz 2005, p1203)

- Biliary sepsis usually occurs w/ascending bacterial infection in assoc’n w/partial or complete obstruction of bile ducts (acute cholangitis). MC organisms cx’d include E.coli, Klebsiella pneumonia, Streptococcus faecalis, and Bacteroides fragilis

Most Likely Organism in Post-splenectomy infection (Sabiston 17E p1704)

- OPSI (overwhelming post-splenectomy infection) is devastating sequelae of asplenia. Being MC fatal late complication, risk of OPSI is grtr after certain indications for splenectomy. OPSI is more common after splenectomy for malignancy or hematologic dz than for trauma. Risk also grtr in kids <4yoa.

- OPSI begins w/prodromal phase of nonSp sx (fever, chills, sore throat, myalgias, diarrhea, and vomiting)

- Progression is rapid and progress to hypotension, DIC, resp distress, coma, and death. Occurs all w/I hrs of presentation. Mortality rate = 50-70%

- Most freq’ly involved organisms is S.pneumoniae and seen in 50-90% of cases. Other organisms involved w/OPSI include H flu, Neisseria meningitiditis, Streptococcuss sp, and Salmonella sp

Most Common Infection Organisms in non-aneurysmal aorta (Fischer, mastery of surgery 5E vol 2 pp2100-2101)

- Salmonella has been ID’d as MC organism causing primary aortic infection. Staph follows close 2nd. Term non-aneurysmic aortic infection xclude any pt undergone aortic prosthetic graft procedure. Over 90% of pt who develop aortic infection have pre-existing atherosclerotic or aneurismal aortas. Infection maybe seeded during period of bacteremia or thru direct invasion of vaso vasorium. While salmonella can infect nl aortic tissue, has distinct predilection to diseased aorta

- Clinical presentation typically that of overt sepsis – pt may c/o abd or back pain. CT scan most reliable radiologic test to obtain. Gas found in aortic wall is pathognomonic for aortic infection. Ligation of involved aorta and either bypass w/vein or xtraanatomical bypass are tx options w/Abx

Toxicity of bacterial endotoxin (sabiston 17E p58; Schwartz 7E pp100, 125, 137; Sherris Medical Microbio 2E p20)

- Endotoxin (agent responsible for septic shock) ID’d as lipopolysaccharide (LPS) outer membr common to Gr neg bact. Outer membr consist of inner leaflet of ordinary Phospholipids (PLs) and outer leaflet consist of lipopolysaccharide molecules

- LPS consist of:o Toxic lipid A portion: PL containing glycocyamine rather than glycerolo Core polysaccharide: contain some unusual CHO molecule and fairly constant in

structure among related sp of bacteriao O-Ag polysacc side chains: major surface Ag of Gram neg cells. Highly variable among sp

and subsp and major determinant of Ag specificity- All endotoxins produce same S/S regardless of sp organism, but not to same degree. Responses

include fever, weakness, generalized aches, miscarriage, and shock- Fever is result of direct stimul’n of hypothalamus by endotoxin + M0 produced IL-1 which

stimulates prostaglandin synthesis in hypothalamus. ASA and APAP block this PG synthesis- Shock caused by release of cytokine TNF or cachectin from M0 stimulated by endotoxin. TNF

causes neutrophil activation, uncontrolled intravascular coagulation, compliment activation, and generalized incr in vascular permeability which can lead to drop in BP. Other cytokines IL-6, IL-8, G-CSF have been ID’d as contributors of the events

Organisms in acute wound infection (Schwartz 8E pp238-239)

- MC organisms seen in wound infections: Staph sp, coag neg Strept sp, and E.coli sp- Wound pathogens typically endogenous to pt’s skin, mucosa, and hollow organs. Likelihood of

infection predicted by degree of contamination in operation and by admin’n of prophylactic Abx peri-operatively.

- Wound infections most typically become apparent 7-10d postop. About ¾ of wounds superficial and involve only skin and SC tissues – can present w/erythema and edema around wound, mild fever, leukocytosis, and disproportionate incisional pain

- If infection suspected, remove several staples/sutures and allow wound to drain – remember send cx

- Deep wound infection located adj to fascia and present w/fever and leukocytosiso Most dangerous of deep infections = necrotizing fasciitis which is mixed infection and

fascial involvement typically lrgr than skin involvemento Surgical tx is to remove all infected skin + fascia and start on broad spectrum abxo MC organisms involved: clostridium, strept, and staph. Pt should be monitored in ICU

w/fluids and vasopressors prn

Risk-Adjusted infection rates (Sabiston 17E pp257-260)

- Surgical site infections (SSIs) = infections found anywhere in surgical tract following procedure. They are most common nosocomial infection, dependent on 3 risk factors: (1) bacterial/microorganism factors (virulence/bact load), local wound factors (surgical site, contamination, sterile procedure, surgical technique) and pt factors (age, morbidity, immunosuppression, obesity, DM, malnutrition, malignancy, etc.) These RFs been stratified into infection rates based on wnd class

- Accepted range of infection:o Clean 1-5%o Clean-contaminated: 3-11%o Contaminated: 10-17%o Dirty: >27%

- NNIS System (national Nosocomial infection surveillance system) also predicts risk of SSI, incorporate wound class, American society of Anesthesiologists score, and duration of procedure compared w/national avg of same operation

Risk factors # of pos risk factors Risk of SSI (%)Procedure time >75%ile 0 1.5Contaminated or dirty wound 1 2.9ASA III, IV, V 2 6.8

Wound

Action of thromboxane A2 (TXA) on wound healing (Schwartz 8E pp62-63)

- TXA plays key role in hemostasis. Derived from arachadonic acid that released from plt membr. Arachidonic acid 1st converted to prostaglandin G2 (PGG2) by cyclooxygenase (COX) then to prostaglandin H2 (PGH2), which in turn converted to TXA2

- Primary hemostasis achieved when plt bind to vWF on endothelium of disrupted vessel walls – in 2nd wave of plt aggregation, release rxn occur in which several substances (TXA2 w/ADP, Ca, 5HT, and alpha-granule pr’s) released result in compaction of plt into ‘amorphous’ plug in process no longer reversible

Difference in adult vs fetal wound healing (Schwartz 8E p234)

- Humans and other mammalian sp undergo fetal skin healing w/little or no scar if injury occur early enough during gestation. Several factors lend to this difference in wound healing – include:

o Wound environment – wounds submersed in warm, sterile, temp controlled mediumo Inflammation – reduced infl’n secondary to relatively immature fetal IS appears play role

in fetal wound healingo Growth factors – fetal wound lack TGF-b and this cascade appears play integral role in

scar formationo Wound matrix – studies shown fetal wounds heal w/little or no infl’n and no xcess

collagen formation – fetal wound matrix also higher in hyaluronic acid than adult wound – this substance is seen only early in adult wound healing. Amniotic fluid rich in hyaluronic acid and may provide hyaluronic acid found in fetal wound

- ‘transitional wounds’ – wounds inflicted into 3rd trimester when more mature, ‘adult’, method of wound healing begins. Wound at this pnt still heal releatively scar free but fetus lacks ability to regenerate appendage

Cell type key to wound healing (Sabiston 17E p187)

- M0 is cell central to wound healing – orchestrate release of cytokines. Assist in angiogenesis, cell recruitment, and activation. Regulate synthesis of wound matrix. Responsible for wound debridements and antimicrobial fxn – attract fibroblasts which responsible for laying collagen, elastin, and adhesive glycopr’s

Characteristics of Healing by 2ndary intention (Schwartz 8E p230)

- All wounds undergo some degree of contraction. For wounds that no have surgically approximated edges, area of wound will be decreased by this action (healing by 2ndary intention) – shortening of scar self results in contracture. Myofibroblast has been postulated as being major cell responsible for contraction, and differs from nl fibroblast in that it contains actin. Typically this cell contains alpha-sm mm actin in thick bundles called stress fibers, giving myofibroblasts contractile capability. Alpha-sm mm actin undetectable until d6 and then increasingly xpressed for nxt 15d of wound healing

Differences in Healing process of bone vs skin (Chapman, Chapman’s Orthopedic surgery 3E p221; Sabiston 18E p191)

- Bone: o Infl’y process (immed to 1wk) – hematoma formationo Reparative/proliferative phase (~2d – mos)

Development of primary/soft callus in and around fx site which forms into boneo Remodeling phase (2-24 mos)

Xternal hard callus contributes most to bony strength following fx until bone is healed. After simple bone healing there’s no scar and heals to 100% of its original strength

- Skin: o Infl’y phase (immed-1wk)o Proliferative phase (~3d-3wks)o Maturational/remodeling phase (~3wks-1yr)

Skin heals to 70-80% its original strength

Anesthesia/Drugs/Operative Assessment

Nitroprusside Toxicity (Katzung, Basic/Clinical Pharm pp172-175)

- Na nitroprusside is vasodilator agent given to tx hypertensive emergencies and hrt failure – dilates both aa and vv, causing decr’d PVR and decr’d venous return

- Complex of Fe, Cyanide, and nitros units and cyanide rleased when nitroprusside taken up by RBCs. CN metabolized to thiocyanate by mitochondria which then distributed in ECF. Xcess use of nitroprusside leads to CN poisoning w/metab acidosis, arrhythmias, and hypotension – reversed w/Na thiosulfate (donates sulfur to convert CN to thiocyanate)

- Hydroxocobalamin can also be given – combines w/CN to form cyanocobalamin- Thiocyanate may accumulate in pt w/renal failure who have been given nitroprusside over

prolonged period of time cause weakness, disorientation, psychosis, mm spasms, and convulsions

Definition of Drug Volume of Distribution (O’Leary 4E pp275-276)

- Total volume into which drug appears distribute known as apparent volume of distribution (Vd) – calculation of Vd based on assumption drug [ ] in blood inversely proportional to how xtensively drug distributed thru-out body, e.g. if drug xfer to rest of body restricted will be retained in plasma and higher [ ] will be found in blood…if drug distributes thru-out body then lower drug [ ] found in blood

- Vd calculated as follows: Vd = X / [A]t=0, where X represents total amnt of drug injected and [A]t=0 is [drug] in body xtrapolated to time zero

- Drug that tends stay in plasma has Vd of 5L; drug xfer to interstitial fluid and plasma has Vd of approx 15L; drug uniformally distributes thru-out bod has Vd approx 40L

- Some drugs have very lrg Vd; lrgr than total fluid volumes of body…reasons for xtremely lrg volumes is binding of drugs to tissue components. If drug binds tightly to tissue components, will tend accumulate in that tissue leading to lower drug [ ] in blood

Drugs Affecting Warfarin Metabolism (ACS Surgery Principles and Practice 2005, p816)

- Interactions most dangerous when warffarin and any of following drugs taken in parallel, but sporadically

- Several drugs/food/body factors incr CL of warfarin. Accomplished by activ’n of hepatic enzymes…drugs/body states include: barbiturates, etoh, diuretics, phenytoin, rifampin, vit K, bulky green vegetables, pregnancy, uremia

- Several drugs/body factors incr response to warfarin…hemorrhage can be induced by both displacement of pr-binding site by drugs or simply by slowing warfarin metabolism – manifested by acute rises in INR. Some interactions w/plt-inhibiting drugs can result in incr’d risk of hemorrhage w/o change in INR – these drugs/body states include: allopurinol, amiodarone, ASA, cephalosporins, disulfiram, etoh, heparin, metronidazole, TMP-SMX, liver dz

Etiology of Hypotension caused by isosulfan blue (Smith, atlas of gyne oncology, 2E, pp79-80; Mulholland and Doherty complications in surgery p623)

- Isosulfan blue dye mostly lymphotrophic and very weakly bnd to serum pr’s – side effects can occur d/t small distribution in serum…most usual SE is skin discoloration and blue-colored urine

- Type I hypersensitivity allergic rxn range from hives/erythema to anaphylaxis – pt usually become s/x’c w/I 10min of IV injections or w/I 30 min of intradermal injections – can present w/CV collapse (rapidly decr BP), angioedema, bronchospasm, GI sx, and pulm edema – incidence is 0.6-1%

- Immediate tx for anaphylaxis is epinephrine, followed by antihistamine and steroids

Initial tx of epidural hypotension (Barash, Clinic Anesthesia, pp782-783)

- MC CV complication of epidural anesthesia, hypotension result from widespread symphathetic blockade. Normovolemic pt will usually no have xcessive fall in arterial BP. Epidural blockade to T10 level seldom cause any decr in P, but blocks extend into upper thoracic segments can decrease MAP, usually no >10-20mmHg

- Drop of 20mmHg in healthy pt usually well tolerated and maybe of benefit to decr blood loss. If drop in BP is xcessive, or if there’s need to maintain BP, positioning pt in head-down position and admin’n of fluids usually adequate to reverse hypotensive state. Pharmacological intervention maybe req’d

SEs of Neostigmine (Schwartz 8E p1646)

- Neostigmine is reversible cholinesterase (-)r – parasympathomimetic. Prevents b/d of Ach by binding to active site of AchE, thus allow further stim’n of nicotinic and muscarinic R’s – by

lowering threshold, new impulse can be triggered more easily in next neuron…crosses BBB poorly

- Used in tx of myasthenia gravis where there are too few R’s. by preventing b/d, Ach can bind few R’s present and cause mm contraction…also used postop to reverse effects of non-depolarizing agents and used for urinary retention d/t anesthesia. Another use is in Ogilvie syndrome

- SEs include bradycardia so it’s given w/parasympatholytic medication (atropine)

Malignant hyperthermia (sabiston 15E p343; Scientific American surgery, 1998 CDROM; Mackowiak, Fever Basic mechanism & Mgmt, 2E)

- Malignant hyperthermia is rare complication following admin of mm relaxants – Succinylcholine and inhalation general anesthetics and amide local anesthetics

- d/t genetically determined defect in Ca release from sarcoplasmic reticulum – sarcoplasm of skeletal mm and manifest in approx 1/50000 adults but more common in kids

- blood cr, phosphokinase is elevated in 70% pt but mm bx is req’d to establish dx. Usually presents w/hi fever, tachycardia, rigidity, skin modeling, and cyanosis w/I 30min after induction anesthesia but occasionally w/delay of several hrs – assoc’d w/metab acidosis and hyperkalemia

- tx: dantrolene – blocks Ca release from SR. admin of Na bicarb and dextrose and insulin to combat potentially lethal hyperkalemia maybe necessary.

- Efforts to cool pt should be immed implemented. Early recognition + prompt tx essential to survive. Mortality is in xcess of 30%

Characteristic Anesthetic Agents (Sabiston 17E p405)

- Propofol (lipid soluble substituted isopropyl phenol) – cmpd w/rapid acting properties of total anesthesia – effects of which include amnesia, analgesia, and some degree of mm relax’n - SE include hypotension on induction and also painful on IV admin’n

- Ketamine (phencyclidine derivative) also used as anesthetic agento Causes dissoc’n b/w thalamus and limbic systemso Produces intense amnesia and analgesiao SE: auditory/visual hallucinationso Direct and indirect stimulatory effects on symp nervous systemo Ketamine useful in hypovolemic pt – CI in pt w/hx of ischemic hrt dz since causes incr’d

myocardial O2 consumption. Also CI in pt w/elevated ICP as its use will exacerbate this condition

- Benzos are anxiolytics w/some amnesia production – no have any analgesic properties- MC used hypnotics used in anesthesia: thiopental, midazolam, etomidate, propofol, and

ketamineo Xcept for ketamine, none of above drugs produce analgesia so must be given

w/analgesic drugs to produce satisfactory anesthesia

Preop Plavix (Goodman, Limberd, et al. Goodman and Gilman: Pharm basis of therapeutics 9E pp1353-1358; Williams et al Hematology 3E pp1480; Katzung Basic/clinical pharm, p554)

- Plavix (clopidogrel) reduce plt aggregation by irreversibly (-)g ADP R on plt prevent ADP-mediated activation of GPIIb/IIIa – no effect on PG metab – shown to reduce vascular events in pt w/ h/o TIAs, completed strokes, and stable angina

- This class of drugs has wide spectrum of use include prevention MI, unstable angina, occlusion of saphenous v bypass grafts, and prevention of ischemic stroke, PV, and aa thromboembolism

- Should be stopped 1 wk prior to major operation as it incr’s risk of bleeding and hematoma format’n

Tx of Postop Cardiac Dysfxn (Cameron, Current Surgical Therapy, 8E, pp1105-1108)

- Operative cardiac risk is fxn of pt age, sx’c cardiac status, EKG findings, and magnitude of surgery- Typical intra-op monitoring isn’t Sn for ST or T wave changes that would suggest MI. pt who are

hi-risk for cardiac complications, or are undergoing surgeries w/hi risk for cardiac dysfxn should receive serial Tn levels and EKG immediately post-op and daily for 2d post-op. BP monitoring, UOP monitoring and EKG usually sufficient to monitor volume status; pt may req aa lines if need for constant BP monitoring post-op, ventilator support, or ionotropic support. Pts benefit from CVCs (central venous catheters) to measure central venous P (CVP) to indirectly measure vascular volume status and possibly a pulm artery (PA) catheter placement to measure CO (cardiac output).

- Clinical predictors of increased periop CV Risk:o Major:

Unstable coronary syndrome Decompensated HF Significant arrhythmias Severe valvular dz

o Intmd: Mild angina Previous MI or pathologic Q waves Compensated/prior HF DM Renal insufficiency

o Minor: Advanced age Abnl EKG Rhythm other than sinus (i.e. afib) Low fxnal capacity Hx of stroke Uncontrolled systemic HTN

- Cardiac risk stratification of noncardiac surgical procedures

o High (>5%) Emergent operations (esp in elderly) Aortic/major vascular surgery Peripheral vascular surgery Anticipated prolonged surgical procedures w/hi fluid shifts or blood loss

o Intmd (usually < 5%) Carotid endarterectomy Head and neck surgery Orthopedic surgery Prostate surgery

o Low (usually <1%) Endoscopic procedures Superficial procedures Cataract surgery Breast surgery

Complications of Furosemide (Ford, Clinical Toxicity, 1st Ed)

- Furosemide = loop diuretic, (-) Na/K/2Cl symporter in thick ascending limb of nephron, block reuptake of Na and Cl as well as calcium and magnesium

- Onset: 20-60min; Peak effect 1-2hr; duration of action: 6-8hr; elimination – 88% renal, 12% biliary/fecal

- Loop diuretics alter electrolyte composition in endolymph of inner ear, which can lead to ototoxicity. Hearing loss known to occur at doses as low as 40mg. Usually reversible, few cases of permanent hearing loss described. Pt w/renal insufficiency who receive rapid IV infusion of lrg dose are at increased risk. Other less common complications: cardiac dysrhythmias, dehydration, and electrolyte abnl’s (esp hypokalemia)

Adrenergic Effects of NE (Katzung, Basic/Clinica Pharm 9E)

Adrenoreceptor Stimulation

Tissue ActionAlpha1 “contraction” Vascular smooth mm Contraction

Increase vascular tone Increase afterloadincrease DBP

Increase venous return Increase preloadincrease SBPPupilary dilator mm Contraction – dilates pupilPilomotor sm mm Contraction – erects hairprostate Contraction – seminal fluid

emissionheart Increases F of contraction

Alpha2 “inhibition” Plts Aggregation – (-) flowNn terminals (-) of NT releaseFat cells (-) lipolysis

Beta1 “heart” myocardium Increase chrono (HR), increase dromo (conductivity), increase ino (contractility), increase O2 consumption

Beta2 “relaxation” Resp, uterine, and vasc sm mm Sm mm relaxationSkeletal mm K uptakeliver Activates glycogenolysis

D1 “kidney” Sm mm Dilates renal bv’sCatecholaminesEpinephrine Beta1>alpha>beta2 Vasoconstriction/cardiac

stimulant; increase sys, decrease dias, increase blood Q to skeletal mm

NE Beta1 = alpha Increase peripheral R, incr sys incr dias increase ino > chrono

isoproterenol Beta only Potent vasodilator, incr ino and chrono incr CO, decr sys decr dias

Dopamine D1 VasodilationLow dose Decr peripheral RHi dose beta1 > alpha > beta2 Vasoconstriction/cardiac

stimulant

Fluids & Electrolytes

Calcium Absorption (Sabiston 16E pp876-877; Murray, Harper’s Illustrated Biochem 27E Ch42)

- Small bowel plays vital role in digestion/absorption of nutrients, H2O, electrolytes, and minerals; digestive process initiated in stomach, which breaks down solids to particles 1mm or smaller in size

- Fat soluble vitamins ADEK absorbed in jejunum. H2O soluble vit B, C, folate absorbed in jejunum w/exception of vit B12 which is absorbed in ileum

- Ca is divalent cation that regulates cellular movement, hormone release, enzyme activity, and coagulation. Ca also palys role in cell injury/death. 99% of total body Ca is located in bone/teeth. Normally, cytosolic Ca is very low w/ratio of EC to IC ionized Ca of 10,000:1

- 30-80% of ingested Ca is absorbed. Thru this vit D derivative, Ca absorption adjusted to body needs; absorption incr’d in presence of Ca (-)y and decr’d in presence of Ca xcess. Ca absorption also facilitated by protein – (-)’d by phosphates and oxalates b/c these anions form insoluble salts w/Ca++ in intestine. Mg absorption facilitated by protein

- In addition to role in regulating Ca homeostasis, vit D req’d for intestinal absorption of Ca. synthesis of IC Ca binding pr, calbindin, req’d for Ca absorption, is induced by vitD (which also affects permeability of mucosal cells to Ca++ effect that’s rapid and independent of pr synthesis)

Characteristics of Renin (Sabiston 17E pp1038-1039)

- Renin= enzyme secreted by juxtaglomerular cells of kidney in response to decr’d P in renal afferent arterioles. Following are stimulants to rennin secretion:

o Decr plasma Na sensed by osmoR’s in macula densao Decr BP in renal afferent arterioleso Hyperkalemia

- Renin secretion stimulated by factors that decr renal aa blood flow – e.g. hemorrhage, dehydration, upright posture, or renal aa stenosis. Renin secretion inhibited by K depletion

- Renin hydrolyzes angiotensinogen in liver to form angiotensin I (ANGI). ANG I converted to ANG II via angiotensin-converting enzyme (ACE) in lungs. ANG-II acts directly on vasc sm mm as potent vasoconstrictor and facilitates formation of aldosterone in zona glomerulosa of adrenal cortex, aldosterone stimulates conservation of salt and water by kidney

Acute renal failure/prerenal azotemia (Sabiston 17E pp314-316)

- Acute tubular necrosis (ATN) – manifested by rapid deterioration of renal fxn and azotemia not d/t xtrarenal factors (e.g. prerenal decr in blood Q or postrenal obstruction)

o Ultimately histological dx and common denominator of most acute intrinsic renal failure o May present in oliguric, polyuric, and nonoliguric forms

- Maybe distinguished from prerenal azotemia w/following urine indices (note that may present similar to outlet obstruction):

Prerenal azotemia Tubular injury (ATN) Postrenal obstructionUrine osmolality >500 <350 VariableU/P osmolality >1.25 <1.1 VariableU/P urea >8 <3 VariableU/P creatinine >40 <20 <20Urine Na <20 >40 >40FE Na <1 >3 >3U/P = urea/plasma ratioFE (Na fractional xcretion) = (Urine Na/Plasma Na) x (Plasma Creatinine/Urine Creatinine)

- Polyuric pt w/urine osm near 300mOsm/L likely to have ATN, while pt w/prerenal azotemia more likely have osm > 500mOsm/L…in actuality, many pt in either group have values b/w 300 and 500 mOsm/L Osm values no provide precise, discriminatory info

- Urine to plasma urea and urine to plasma Cr ratios more useful than Osm ratio – grey zone b/w prerenal and tubular injury is common and thus these tests also non-discriminating. Urinary Na values b/w 20 and 40 mEq/L nondiscriminatory

- B/c so many pt appear be in this non-dx’c zone, FENa has been hailed as more precise index of renal Na handling and generally believed be more effective in discriminating acute tubular injury from prerenal azotemia. FENa req’s simultaneous measure of serum Na and Cr and spot urine for Na and Cr levels. Urine volume not pertinent

- Although FENa become widely used and credible dx’c guide for ARF, 2 xceptions are radiocontrast induced ATN and admin’n of diuretics w/I 12h prior to test

Fluid Req’s in SBO (Sabiston 17E p1339)

- Intestinal obstruction usually associated w/dehydration and lo levels of Na, Cl, and K. this necessitates aggressive IV replacement w/an isotonic saline solution (e.g. LR) Foley catheter should be placed to monitor UOP. KCl should be added to soln once adequate urine being produced. To adequately judge fluid repletion, serial electrolytes + WBC and Hct measurements should be obtained. CVP and Swan-Ganz catheters maybe necessary in pt’s such as elderly who may req lrg amnts of fluids

- Based on some findings of bacterial translocation occurring even in simple mechanical obstruction, some surgeons give broad spectrum Abx prophylactically

Hypophosphatemia of Re-Feeding (Braunwald, Harrison Principles of Internal Med, 14E, pp2259-2261)

- Cachectic pt represents catabolism of mm mass and fat. b/d of mm and contraction of ICF volume leads to loss of H2O and minerals including phosphorus. Phosphorus may remain nl, total body phosphorus is low. Resp alkalosis adds to loss of serum phosphorus, which further amplifies total body phosphorus (-)y. w/refeeding of nutrients via GI tract or IV, phosphorylation of glc intmd causes cell uptake of phosphorus and resulting hypophosphatemia. Hi levels of glc initiate insulin release, which adds further to hypophosphatemia

- Resp insufficiency occurs as result of malnourished pt’s receiving hi levels of nutrients w/inadequate phosphorus. Profound weakness assoc’d w/hypophosphatemia leads to failure of diaphragm fxn, hypoxia, and resp acidosis

- Failure to xtubate pt often 1st clue leading to dx – admin of phosphorus rapidly corrects mm weakness and resp insufficiency

Mg Replacement in Crohn’s Dz (Sabiston 17E, pp90, 1348)

- (-)y of Mg causes weakness, mm cramps, cardiac arrhythmias, incr’d irritability of nervous system w/tremors, athetosis, jerking, nystagmus, and extensor plantar reflex + maybe confusion, disorientation, hallucinations, depression, epileptic fits, HTN, tachycardia, and tetany

- Mg can become quite depleted in pt who have chronic diarrhea or who take diuretics over prolonged period of time. Alcoholic also commonly have Mg (-)y. IV infusion of Mg sulfate (MgSO4) will usually correct hypomagnesemia. Severe hypomagnesemia (<1.0mEq/L) may need sustained tx 2ndary to slow equilibration of EC and IC Mg stores

- In pt w/Crohn’s, severe diarrhea may necessitate Mg replacement Rx. Will allow for wound healing, intestinal pr synthesis, and prep for surgery if necessary

Hypercalcemia (Schwartz 6E pp1648-1650)

- Primary hyperparathyroidism – MCC of hypercalcemia in nonhospitalized pt; in hosp’l setting, pt w/carcinoma metastatic to bone most often assoc’d w/elevated serum Ca level

- Primary hyperparathyroid is 2nd MCC of hypercalcemia in hospitalized pt; Hypercalcemic crisis – usually assoc’d w/Ca levels in range of 15mg/dL or above. Acute hypercalcemic crisis occurs most commonly when there’s rapid rise in serum [Ca], and much more likely occur in presence of severe renal damage. At least 90% of pt have some degree of renal failure. If early sx’s of hypercalcemia ignored (nausea, vomiting, constipation, generalized mm weakness, thirst,

polyuria) sx’s may progress to lethargy, drowsiness, confusion, prostration, and coma. EKG changes consist of short QT interval and nearly absent ST segment

- Tx : Saline and furosemide (Lasiz) most effective in that pt’s are dehydrated; Cortisone effective in some pt w/bone met’s and useful in sarcoidosis; may take up to wk to be effective; mithramycin works rapidly by (-)g bone reabsorption and used commonly for malignant processes; thrombocytopenia and other hematologic problems occur if mithramycin used in xcess

o IV phosphate admin’n no longer used – PO phosphate Rx can be effectiveo Calcitonin work rapidly and effectively in some cases, in which xcessive bone resorption

present- Optimal tx depend on rapid resuscitation w/NS and Lasix – w/confirmed dx of primary

hyperparathyroid (hypercalcemia w/elevated PTH), early operation w/correction of hyperparathyroid state is curative

Tx of Metabolic Acidosis/Hypokalemia (Scientific American I, 5, p11; VI, 1, p9)

- Metab alkalosis is most often caused by loss of hydrogen ions from GIT thru vomiting and NG suctioning…may also occur as result of diuretic Rx. Loss of H ions and Cl provides abundance of bicarb. Hypokalemia further amplified thru IC xchange of H ion for K. loss of intravascular vol, H ion and Cl lead to hypochloremic, hypokalemic metab alkalosis and release of ADH and aldosterone, 2ndary to hypovolemia, lead to resorption of Na and bicarb by kidney producing ‘paradoxical aciduria’

- Tx focused at replacing volume w/Na and Cl and aggressively replacing K as KCl. b/c serum [K] may no reflect full xtent of total body K (-)y, goal of Rx should be to achieve serum level of 4.5-5.5 mEq. Admin of H2 R antagonist may help attenuate further losses of H ion from GI tract (GIT)

Anion Gap in Xcess Organic Acids (Hall, Principles of Critical Care, 3E, Ch77)

- Lactic acid is released from mm and from gut as consequence of hypoxia and often most important cause of metab acidosis in critically ill pt

- Lactic acidosis correlates w/outcomes in hemorrhagic and septic shock and most prominent cause of acidosis in sepsis. Amnt of lactate produced is directly related to amnt of hypoperfusion, O2 debt, and severity of shock. Lung may also be source of lactate during episodes of acute lung injury. Lactate is strong anion and at physiologic pH almost totally dissociates, generating lrg amnts of [H+] contributing to incr’g anion gap. Dx made by measuring serum lactic acid levels

- Ketone bodies include acetone, acetoacetate, and beta-hydroxybutyrate and are also strong anions at physiologic pH. Ketoacidosis also significant cause of anion gap acidosis. Ketones formed by beta-oxidation of fatty acids in process that’s blocked by insulin. w/o insulin, as in DM, ketones can quickly form as osmotic effects of hi blood glc cause relative volume contraction – this process also contributes to incr’d levels of cortisol and catecholamines that in turn lead to further increases in FA secretion. Ketoacidosis occurs most commonly in type I

diabetics (DKA) and in alcoholics (AKA). Measuring serum ketones makes dx. Admin’g glc, fluids, and insulin treats DKA. AKA typically less severe and can be treated w/only glc and fluids – remember administer thiamine b4 giving glc to prevent causing Wernicke’s encephalopathy. While measuring serum ketone level aid in dx, following serum anion gaps more reliable means measuring response to tx as ketones metabolized from one form to another and overall ketone level maybe misleading

- Chronic renal failure may cause sl elevated anion gap acidosis d/t accumul’n of sulfate. Uncomplicated renal failure usually no cause severe acidosis

- Other causes of metab acidosis include poisons. Methanol, ethylene glycol, toluene, and salicylates all known causes of metab acidosis

Shock & Trauma

Transected Pancreas (EL Bradley, 3rd, PR Young Jr, MC Chang, JE Allen, CC Baker, W Meredith, L Reed, and M Thomason Ann Surg. 1998 June; 227(6):861-869; Schwartz, Principles of Surgery 8E Ch6; Principles of Critical Care 3E Ch95)

- Blunt pancreatic transaction usual occur after impact of pancreas against vertebral column…dx of blunt pancreatic injury difficult early in course b/c of its retroperitoneal location prevents early signs of peritoneal irritation. Sx’s may include epigastric and/or back pain, N/V, ileus, and abd tenderness. Initial serum amylase maybe w/I nl limits but does become elevated in 80% of pt’s. this finding alone no indication for xploration

- CT imaging is useful…however if done w/I 1st 6h post injury only results in Sn of 71% for pancreatic injury and 43% for main pancreatic duct injury

- Tx of minor contusions/lacerations w/o ductal injury consist of controlling bleeding and external drainage; deeper lac’s or crush injuries w/ductal injury or devitalization of gland best treated w/distal resection of injured gland (preserving spleen if possible) and extern’l drainage

- Injury to head of gland and dudodenum may occasionally req pancreaticodudodenectomy once pt stable. In unstable pt, hemostasis should be obtained and gland should be extern’lly drained

- Minority of pt’s will develop fistula (usually of pancreaticocutaneous type) – these fistulas should be treated only when pt has been stabilized

- Mortality approx 20% and usually d/t massive bleed from erosion of adjacent vessels

Etiology of hypotensive hypovolemic shock (Sabiston 17E pp96-98)

- Hypovolemic shock caused by any process that contributes to intravascular volume depletion including hemorrhage, fluid sequestration, GI/urinary losses or insensible loss. S/S of each of these causes of shock are same; however w/hemorrhage they come on more quickly and are more easily recognized

- Physical findings are as follows:

Mild (<20% blood vol) Mod (20-40% blood vol) Severe (>40% blood vol)

Pallor Pallor PallorCold extremities Cold extremities Cold ext.Diminished cap refill Diminished cap refill Diminished cap refillDiaphoresis Diaphoresis DiaphoresisCollapsed Sub q vv Collapses Sub q vv Collapsed sub q vv

Tachycardia TachycardiaOliguria OliguriaPostural Hypotension Hypotension

Mental Status Change

- Those in hypovolemic shock typically have decreased central venous and pulmonary capillary venous P’s + decr’d CO and venous O2 saturation. Systemic vasc R is incr’d

- Primary hormonal response to hypovolemia includes:o Catecholamine release (epi and NE)o ADH release from post’r pituitary in response to incr’d osmolarity and hypovolemiao Aldosterone secretion in zona glomerulosa of adrenal gland in response to ACTH and

ANG IIo Renin-angiotensin system activation causing vasoconstriction d/t ANG II, aldosterone

release and activation of catecholamines

Def’n of Full-Thickness Burn (Sabiston 18E p561; Greenfield Surgery Scientific Principles and practice 4E p239)

- 1st degree burns confined to epidemis. Very painful and red, blanch to touch, and don’t scar- 2nd-degree burns – divided into superficial and deep dermal

o Superficial dermal burns are blisters, erythematous and painful, and blanch; retain rete ridges, hair follicles, and sweat glands – after healing there’s usually discoloration

o Deep dermal burns don’t blanch to touch. These heal b/c of hair follicles and sweat glands that are left – but often w/severe scarring

- Third degree burns are full thickness (burn off epidermis and dermis). Usually appear leathery eschar that’s painless. No hair follicles or sweat glands remain, so healing occurs from skin edges of burn. These burns req eschar excision and skin grafting

- 4th degree burns involve deeper tissues (mm, bone, and brain)

Dx of tension PTX (Schwartz 8E p101)

- Tension PTX occurs when injury to lung parenchyma allows air to enter pleural space w/each resp’y effort. A flap valve effect prevents air from reentering bronchial tree for egress thru trachea during xpiration. Shift of mediastinum and compression of vena cava and RA results in decr’d CO that may lead to sudden death. Dx is clinical and becomes evident w/resp distress, hypotension, diminish’d breath sounds, hyperresonance, to percussion, JVD, and shift of mediastinal structures toward unaffected side w/tracheal deviation; confirmed w/portable AP

chest roentgenography, but should be treated empirically w/tube thoracostomy in midaxilla 5-6th intercostals space or needle decompression in midclavicular line 2nd intercostals space

Etiology of Different O2 Content in aa and vv blood (Sabiston 16E p 394; Schwartz 7E p496; Schweiss, Continuous Measure of O2 Saturation in High Risk Pt, Vol I)

- Aa O2 content in ambient/nl conditions primarily dependent upon Hb in RBCs and O2 saturation. O2 content of plasma is minimal and only becomes contributing factor in oxygenation w/hyperbaric tx

- O2 content of blood (C-O2) is calculated:o C-O2 = (1.37 x % SO2 x Hbg) + (0.003 x PaO2)o SO2 = % O2 saturationo PaO2 = partial P of O2 in plasma

- Ability of O2 to dissociate from Hb (oxyHb dissociation curve) determined by several conditionso Shift of curve to right (decr’d affinity for O2) helps O2 release to tissues – shift is caused

by incr’d 2,3-diphosphoglycerate [ ]’s in erythrocytes (RBCs), elevated temp, incr’d PCO2, and hydrogen ion [ ] (acidosis)

- Mixed vv O2 content by measuring ratio of Hb to oxyHb. Can be obtained from relative absorption of light by Hb and oxyHb at different wavelengths and reported as % saturation of oxyHb; SVO2 of 75% is usually quoted as nl value

o Range of 63%-77% is acceptable, while increases above this level relatively uncommono Prominent among causes for incr in SVO2 are decr’d peripheral O2 consumption and

incr’d peripheral shunting d/t sepsis. This L-R shunting of aa blood in periphery can also be found in conditions such as Paget’s dz of bone, cell poisoning as in CN toxicity assoc’d w/xcessive use of nitroprusside, and in pt suffering from hypothermia; probably most common cause of incr in SVO2 is wedged pulm aa catheter. When balloon at end of pulm aa catheter inflated, blood distal to balloon stagnates, absorbs O2 from surrounding ventilated alveoli and becomes closer in saturat’n to aa blood. SVO2 < 50% usually represents cardiac decompensation leading to lactic acidosis, onset of unconsciousness and permanent cellul’r damage when saturation below 20%

- Causes of decr’d SVO2:o Anemiao Lo COo Aa O2 desaturationo Incr’d O2 desaturation

Mixed venous O2 satur’n Condition77% Sepsis, R-L shunt, xcess inotrope, hypothermia,

wedged catheter66-77% Normal range60% Cardiac decompensation55% Lactic acidosis32% Unconsciousness

20% Permanent cell damage

Etiology of Shock after laparoscopic cholecystectomy (Greene and Ponsky, Endoscopic surgery, pp324-325, 447-455)

- On rare occasion, necessary to return pt to OR, either to deal w/suspected hemorrhage or hollow visceral injury leak after lap chole. Some of injuries noticed intraop and dealt w/at that time: trochar injuries to retroperitoneal vessels or intestines; diathermy burns to CBD or duodenum; bleeding from cystic a or R hepatic a; bile leak from cystic duct, CBD, or liver bed

- Some of injuries maybe over looked during procedure or manifest selves during postop period; manifestations of shock in immediate postop period (1st 24h) most likely from bleeding; clip falling off cystic a, liver bed, or missed sharp injury to liver, injury to R hepatic a, or anterior abd wall vessel; later manifestations of shock after lap chole (after 1st 24h) likely result from sepsis 2ndary to bile leak, perforated hollow visceral leak or 2ndary to accidental clip on CBD w/subsequent cholangitis

Fluid resuscitation in hemorrhagic shock (Sabiston 17E p98)

- tx of hemorrhagic shock depends on 2 factors: repletion of blood volume and cessation of hemorrhage. Adults in hemorrhagic shock receive 2L of isotonic fluid; kids receive up to 20 mL/kg. Assessment of hemodynamics to initial fluids should then be made. Pt’s who remain hypotensive maybe severely hypovolemic or have ongoing hemorrhage – these pt will req blood transfusion, many measures maybe used to guide resuscitative efforts, but pulm a catheter data provides most precise measures of response to interventions

- timing of resuscitation in active hemorrhaging pt also controversial – has been demo’d that attempts to restore blood vol during active hemorrhage useless and possibly harmful. Best tx in this pt popul’n is to achieve hemostasis

- composition of resuscitative fluid to use also debatable. Isotonic soln have been effective for many yrs. Admin of 3-4 mL of fluid req’d for each mL of shed blood. In effort to avoid hyperchloremic metab acidosis often occurs after resuscitation, isotonic soln w/alt anions to Cl (e.g. LR) often used

Hemodynamics of Cardiogenic Shock (Greenfield 2E)

- cardiogenic shock is result of hrt as effective pump, leading to inadeq CO, tissue perfusion, and O2 delivery. Intrinsic causes of cardiogenic shock include MI, cardiomyopathy, valvular hrt dz, and dysrhythmias. R-sided HF can result from pulm HTN or from massive PE which limits systolic ejection. Failure of L hrt leads to decr’d peripheral perfusion and may result in pulm congestion

- obstructive cardiogenic shock results from xtrinsic compression of hrt that limits diastolic filling limiting systolic ejection and CO. blood/fluid w/I pericardial sac may cause pericardial tamponade. Similarly, any cause of incr’d intrathoracic P (tension PTX, diaphragmatic hernia, etc.) can cause compressive cardiogenic shock. Reduction in cardiac filling often accompanied

by JVD and findings consistent w/hypovolemia (incr’d symp’c dischrg and diminished peripheral perfusion

- Physiologic characteristics seen w/cardiogenic shock are: increase in CVP and PCWP, incr in systemic vascular R, and decr in both CO and venous O2 saturation

Tx Traumatic Diaphragmatic Hernia (Schwartz 8E p167)

- Acute injuries repaired thru abd incision w/no. 1 monofilament permanent suture using simple running technique. Lrg avulsions or wounds w/xtensive tissue loss will req polypropylene mesh to close defect

- In blunt trauma, diaphragm injured on L 75% of time, as liver is thought to diffuse energy on R. Typically, blunt traumas result in tear in central tendon.

- Injury is suggested by abnormality of diaphragmatic shadow on CXR, which maybe subtle, esp w/penetrating injuries

Tx of Stab Wound to Chest (ACS Surgery 2006; ATLS Protocol)

- Perform primary survey and correct major problems w/airway, breathing, and circulation as they’re ID’d. These may include tension PTX, cardiac tamponade, or exsanguinating hemorrhage

- Penetrating objects that traverse mediastinum can injure major mediastinal structures – hrt, grt vessels, tracheobronchial tree, or esophagus. Transmediastinal injury dx’d when exam or CXR reveals entrance wound in one hemithorax and exit or missle lodged in contralateral hemithorax

- Hemodynamically unstableo Bilateral tube thoracostomy, cont primary survey and resuscitationo Resuscitative thoracostomy if pt has penetrating thoracic trauma and pulseless electrical

activityo Maneuvers can be accomplished include: evacuation of pericardial blood causing

tamponade, direct control of xsanguinating intrathoracic hemorrhage, open cardiac massage, x-clamping descending aorta

- Hemodynamically stableo Tube thoracostomy as indicated; r/o injury to thoracic aorta and its major branches

w/angiographyo CT of chest should be performed to eval status of hrt and pericardiumo H2O-soluble contrast esophagography and bronchoscopy should be performed. Immed

relief of tension PTX or surgical exploration for exsanguinating hemorrhage/pericardial tamponade maybe req’d. ID’d injuries should be repaired thru appropriate incisions. Local wound xploration no recommended w/wounds overlying ribs b/c of risk of causing PTX

- Hemodynamically unstable pt no req screening xray in ED. If hemodynamically stable w/penetrating trauma above umbilicus or suspected thoracoabd’l injury, upright CXR useful to xclude hemo- or PTX or to document presence of pneumoperitoneum

- Mediastinal emphysema raises suspicion for tracheoesophageal injury; mediastinal hematoma suggest grt vessel injury

Tx of Septic Shock (Schwartz 8E pp99-100)

- Initial tx begin w/airway and ventilation in obtunded or pt struggling to breathe. Hypotension d/t vasodilation and decr in total peripheral R maybe treated w/fluid resuscitation. Empiric Abx should be chosen selectively based on most likely pathogens

- Majority have hyperdynamic physio w/supranl CO’s and low SVRs and may req vasopressor support. Catecholamines are most often used. In pt’s that develop aa R, arginine vasopressin (potent vasoconstrictor) is beneficial

- Hyperglycemia and insulin resistance are common w/o underlying DM. mortality significantly lower in those w/tight FSBG (80-110)

- Use of CS controversial – observation that septic shock assoc’d w/adrenal insufficiency and glucocorticoid R resistance renewed interest in CS use

Tx Ventilatory Complications of Burns (Schwartz 8E pp192-193, 199)

- Any pt xposed to burning building or smoky fire should be placed on 100% O2 via nonrebreather mask if any suspicion of inhalation injury. If unconscious or in distress, itubate. Inhalation incr’s the fluid req’s for resuscitation by approx 1.5x. It incr’s magnitude of total body injury via disproportionate incr’s in systemic infl’n

- During resuscitation, careful monitoring of peripheral circul’n and ventilator needs must be made. Ventilation maybe compromised by chest wall inelasticity related to deep circumferential burn that’s restrictive. P’s req’d for ventilation incr and PCO2 rises. One must also assess for inhalation injury, PTX, and other causes

- Thoracic escharotomy seldom necessary even for circumferential burns. B/l incision made in anterior axillary lines. If extension noted onto abd wall, incisions should be xtended by transverse incision along costal margins

Adverse rxns of topical tx’s for burns (Sabiston 17E pp581-582)

- Silver sulfadiazine (Silvadene) – painless broad-spectrum anti-microbial topical tx used to treat burn wounds. Silvadene no treat some sp of pseudomonas and no penetrate eschar. Also been assoc’d w/transient leucopenia that develops b/w 3-5d after application. Use is assoc’d w/mild (-)’n of epithelization

- Mafenide acetate (Sulfamylon) – broad-spectrum anti-microbial topical tx used to treat burn wounds. Penetrates eschar. May cause metab acidosis w/wide application, use is assoc’d w/mild (-)’n of epithelization

Dx of neurogenic Shock (Schwartz, principles of surgery 6E pp139-140)

- Clinical picture of neurogenic shock assoc’d w/hypotension, low pulse rate and dry, warm, even flushed skin. Measurements taken during neurogenic shock indicate reduced CO, decr’d PVR, and decr’d venous tone. Appears to be normovolemic state w/grtly incr’d vasc capacity, reducing venous return to hrt w/reduction of CO

- Neurogenic shock seen w/clinical syncope, acute gastric dilation, and injury to SC. If no corrected, reduction in renal blood Q and brain damage may result. Tx is symptomatic in scope and may simply involve removing pt from stimulus; NG suction for acute gastric dilation; IV admin’n of fluid and vasopressor (ephedrine or phenylephrine (neo-synephrine) is given to counter effects of spinal anesthesia. This incr’s CO, restores venous tone, and incr’s systemic BP

- In SC trauma, invasive hemodynamic monitoring mybe req’d to guide Rx. In balancing 2 forms of Rx for spinal anesthesia, sl vol over-expansion is much less deleterious than xcessive vasopressor admin’n

Dx of abd compartment syndrome (Sabiston 17E pp320, 627-662)

- Abd compartment syndrome (ACS) – fundamentally defined as incr’d intra-abd P assoc’d w/adverse physiological consequences. Physio consequences include incr’d peak inspiratory P, decr’d UOP, hypoxia, hypercarbia, and hypotension d/t decr’d venous return. These findings assoc’d w/intra-abd P’s > 10mmHg and found in pt’s undergoing lengthy abd operations, rapid ascites accumulation, blunt abd trauma, rupture abd aorta, pelvic fx, intestinal ileus, obstruction, pneumoperitoneum, and septic shock

- Dx and Tx o Intravesicular P measured w/Foley catheter attached to manometer is most common

accepted dx’c tool. Grading system for ACS can be used to guide dx and tx, ultimate tx should be based on pt’s clinical condition

Grade Intra-abd P Tx1 10-14 mmHg None2 15-24 mmHg Hypervolemic resuscitation3 25-35 mmHg Decompression4 >35 mmHg Urgent

decompression/xploration

o Tx includes rapid abd decompression and is accomplished using temp’y abd closure system. Every effort should be made to achieve definitive closure w/I 4d. approx 1 wk after decompression primary closure generally not attainable and usually req’s skin grafting or mesh closure

Cancer

Rx and Prognosis Liver Met’s in Colon Ca (Sabiston 17E pp1554-1556)

- For pt w/isolated/resectable hepatic met’s, liver surgery allows for potential lng term survival. 5 yr survival rates range from 25-37%. In xperienced centers, mortality <5%. Approx ½ pt undergoing liver resection for colon ca will survive 3 yrs and 1 in 5 pt’s survive 10 yrs. Other colon ca stages w/respective tx listed below

- Stage I colon ca which are T1 (tumor invades submucosa) and T2 lesions (tumor invades muscularis propria) w/N0 and M0 that are tx primarily w/colon resection, adjuvant tx w/chemo or rad’n Rx no indicated

- Stage II colon ca are T3 and T4 lesions (T3 tumor invade thru muscularis propria and into subserosa and non-peritonealized pericolic/perirectal tissue. T4 tumors perforate visceral peritoneum or directly invade other organs/structures). Stage II tumors are N0 and M0. Surgical resection is primary Rx and chemo usual no recommended

- Stage III colon ca involve any T level tumor w/regional LNs (N1, 2, and 3 and no distant metastatic dz (M0)). Following resection of tumor, adjuvant chemo w/5-fluorouracil (5-FU) and levamisole or 5-FU and leucovorin are assoc’d w/incr’d survival when admin’d postop to selected pt w/no apparent residual dz

Gastrointestinal Stromal Tumors (GIST) – Px Factors (Cameron 9E pp111-113; Schwartz 8E pp1342-1343)

- Stromal tumors – MC GI mesenchymal neoplasm and GISTs constitute majority of GI sarcomas – uncommon w/annual incidence in US of approx 3,000-6,000/yr. There’s sl male prevalence and most commonly ID’d in pt in 7th decade of life. GIST have been ID’d thru-out alimentary tract, w/stomach being most frequent location (45-65%). In decreasing order of occurrence, also found in small bowel (15-25%), lrg bowel including rectum (5-10%), esophagus (5-10%), and duodenum (3-5%). Locations outside alimentary tract include omentum, pancreas, other retroperitoneal (RP) structures and GI mesentery. MC presenting sx of GISTs are GI bleeding, abd discomfort, and abd mass

- GI stromal tumors have distinctive immunohistochem and genetic features and thought to arise from pacemaker cell w/I GI tract called interstitial cell of Cajal. Both these cells and GIST cells xpress CD34 (a hematopoietic progenitor cell mrkr) and c-kit (transmembr glycopr R that’s prt of IC signaling pathway regulating cell growth and survival)

- Unlike other GI malignancies, behavior of GISTs is difficult to predict on path. ID’n of local/distant metastatic dz (to liver and lungs, MC’ly) is surest indicator of malignancy. Other characteristics that show some ability to predict how GISTs will behave include size, mitotic rate, DNA ploidy, cellular prolifer’n mrkrs, telomerase activity, and suppressor gene hypermethylation. 2 most important are size and mitotic rate. GISTs that generally xhibit b9 behavior are small tumors w/diameters less than 2cm and w/< 5 mitoses per HPF (hi powered field). Tumors that consistently demo malignant behavior are those that are lrg (diameters >10cm) and demo grtr than 10 mitoses per HPF. Both size and mitotic rate each serve as independent predictor of prognosis, neither small size or lo mitotic rate confirm b9 behavior

- Consensus conference on GISTs (2001) established criteria to delineate graded risk of malignant behavior based on size & mitotic rate. Based on these prediction of px and necessary f/u is determined:

Very low risk: <2cm <5 mitoses p50 HPFLow risk: 2-5 cm <5 mitoses p50 HPFIntmd risk: <5 cm 6-10 mitoses p50 HPF

5-10 cm <5 mitoses p50 HPFHi risk: >10 cm Any mitotic rate

Any size >10 mitoses p50 HPF

Ca w/grtst sensitivity to radiation Rx (Schwartz 8E pp286,596-597; Feig, The MD Anderson Surgical Oncology Handbook, 4E, pp513, 516)

- Xtent of DNA damage following radiation dependent on several factors. Most important of these is cellular O2. Hypoxic cells significantly less radiosensitive than aerated cells. Also contributing to efficacy of radiation is phase of cell cycle. Most radiation Sn phases are G2 and M, while G1 and S phases less Sn

- Ca’s w/grtst Sn to XRT include seminomas and lymphomas. After radical orchiectomy, stage I and IIA seminomas are typically treated w/XRT. Cure rate for stage I dz approaches 100%, while cure rate for stage IIA dz is approx 95%. Mediastinum is MC site for both hodgkin’s and NHL. Rad’n Rx w/ or w/o chemo results in cure rate of up to 90% w/early stage Hodgkin’s dz and up to 60% w/more advanced stages

Chemotherapeutic Agent in Pyrimidine Metabolism (Schwartz’s 8E pp279-280)

- Antimetabolites generally cell-cycle Sp chemotherapeutic agents that have major activity during S phase of cell cycle and have little effect in cells in G0. These drugs most effective in tumors that have hi growth fraction. Antimetabolites are structural analogues of naturally occurring metabolites involved in DNA & RNA synthesis interfere w/nl synthesis of NAs by substituting for purines or pyrimidines in metab’c pathway to (-) critical enz’s in NA synthesis. Antimetabolites include folate antagonists, purine antagonists, and pyrimidine antagonists

- E.g. of pyrimidine antagonists include capecitabine, cytarabine, floxuridine, and gemcitabine. 5-fluorouracil is pyrimidine analog. It’s thymidylate synthase (-)r interrupting action of enz req’d for synthesis of pyrimidine, thymidine – which is req’d for replication of DNA; Capecitibine is prodrug of 5-FU, meaning capecitabine is enzymatically converted to 5-FU in vivo

GI Lymphomas (Sabiston 17E pp1312-1313)

- Lymphomas constitute 10-15% of small bowel malignant tumors in adult and in kids <10yrs; they are most common intestinal neoplasm. Gastric lymphomas are isolated uncommon neoplasm

- 1/3+ pt w/lymphoma involvement of small bowel have generalized lymphoma. Small bowel lymphomas MC found in ileum. Grossly, these tumors usually lrg, >5cm and assoc’d w/diffuse infiltration of intestinal wall. Perforation occur in 25%. Tx of SB lymphoma is wide resection including regional LNs. XRT and chemo combined w/suregery provide best survival rates

- Gastric lymphoma may present as tumor mass or more commonly thickening of rugal folds. Tx is resection of bulky lesions…radiation alone provides lng-standing remission that may equal resection results

Germ Line Mutations Ca (DeVita, Cancer: principles and practice of oncology, 4E; Schwartz 8E p597)

- Germ Cell Tumors include:o Male: Seminomas, embryonal cell ca, teratocarcinoma, and mixed tumorso Female: dysgerminoma, teratoma, endodermal sinus/yolk sac tumor, mixed tumor,

embryonal carcinoma, and choriocarcinoma- Xtragonadal tumors most often found in anterior mediastinum, but can occur in pineal gland,

sacrococcygeal and paraaortic areas – these tumors thought arise from pluripotential primordial germ cells. When found in mediastinum, most effectively tx’d w/chemo and subsequent resection of residual masses

- Germ cell tumors commonly secrete AFP (alpha-fetoprotein) and HCG (human chorionic gonadotropin) result in elevated [ ] in blood; though non-Sp, lactate dehydrogenase (LDH) often elevated

- Various histolog’l types of germ cell tumors (seminomas, teratomas, embryonal cell ca, mixed tumors) shown have frequent chromosomal anomaly, an isochromosome for shrt arm of chromosome 12. Data limited this anomaly appears be more common in testicular tumors than in corresponding ovarian germ cell tumors

Characteristics of GISTs (Schwartz 8E pp1038-1042)

- GISTS as currently defined represent lrgst category of primary non-epithelial neoplasms of GIT. Arise from mesenchymal cells located in wall of organ and show remarkable variability in differentiation pathways. On basis of immunochem’l and ultrastructural studies, these neoplasms divided into several categories: leiomyomas, schwannomas, and less differentiated tumors referred to as GIST. The GIST tumors have mutation in c-kit gene and have aggressive clinical behavior and histolog’l features

- In small bowel, GIST uncommon. MC clinical presentation is GI bleeding. Other presentations: obstruction, intussusceptions or perforation

- w/complete resection, 5-yr survival is in 35-60% range. w/incomplete resection, <10% are living in 5 yrs. Risk of local & distant met’s is related to tumors w/>1 mitoses and tumor size >5cm. Neither XRT or chemo have demo’d any significant benefit w/these tumors

Tx of Malignant Fibrous Histiocytoma Leg (Schwartz 8E Ch18; Randal and Hoang, Current dx and tx in orthopedics 4E, ch6; Cameron 8E p1058)

- Malignant fibrous histocytomas (MFHs) are MC soft tissue sarcoma of later life usually occurring b/w ages of 50-70. Derived from fibroblasts and are hi-grade fibrosarcomas. Most common present w/pain, w/ or w/o palpable mass and radiographic studies show mass w/adj’t bone and soft tissue destruction. It’s lytic tumor of bone, affects metaphyseal-diaphyseal bone and periosteum no show response to blastic repair

- Tx is surgical resection w/wide margin of at least 2cm. which may include amputation of limb followed by multiagent chemo/XRT. Over 2/3 of pt will have local recurrence or distant met’s

and poor px. Current lit shifted to limb sparing surgery followed by chemorad’n. overall survival in amputation vs limb sparing are same. Local recurrence is sl higher in limb sparing surgery

Medical Rx of unresectable gastrinoma (Feig MD Anderson surgical oncology handbook 4E p399)

- Gastrinoma are endocrine tumor that secrete gastrin leading to acid hypersecretion and gastric ulceration. Most pt w/gastrinoma have serum gastrin levels >500 pg/mL. secretin provocative test usually done to confirm dx when serum gastrin is in range of 200-500 pg/mL

- Secretin Provocative Test: following 2 units/kkg secretin IV bolus, rise in serum gastrin level of 200pg/mL w/I 15 min or dbling of fasting gastrin level d/x’c of gastrinoma

- Tx:o Following confirm’n of dx (biochem’lly), tx involves following:

Omeprazole 20-200mg/d to induce achlorhydria Initiate studies to ID tumor location (CT scan, endoscopy, angiography, vv

sampling, somatostatin R studies) Abd xploration, enucleate pancreatic tumors (up to 2 cm) or pancreatectomy

- For unresectable gastrinomas, pt maintained on lng term omeprazole Rx (H2 R blocking agents) which highly effective. Octreotide can also be used as suppresses gastrin secretion. When surgery not option and liver met’s present then either hepatic a embolization w/trad’l chemo w/IFN-alpha and SS analogues can be used

- In pt found have inoperable dz chemo w/streptozotocin, doxorubicin, and 5-FU used. Other approaches (SS analogues, IFN, and chemoemboliz’n) have also been used w/some success

Characteristics of Stage IV Sarcoma (Sabiston 18E Ch31)

- Stage 4 sarcoma defined as tumor having spread either to LNs or to distant sites, independent of tumor size or histology

- Histology found be most important predictor of sarcoma deaths. Histologic grade based on cellularity, degree of mitosis, necrosis, stromal content, and differentiation

- Overwhelming majority of sarcomas spread hematogenously lymphatic spread rare (<3%). Xtremity lesions MC spread to lungs and visceral lesions most often spread to liver. Pt w/xtremity lesion need CXR (if lo grade) or chest CT (if hi grade). Pt w/visceral lesion need livers imaged by CT or MRI

Genetics:

Incr’d Ca Risk w/BRCA-1 Mutation (Schwartz 7E pp54-55; Robbins 7E)

- BRCA1 – tumor suppressor gene on Ch17q21. BRCA-2 similar fxn and located on Ch13q12-13. Fxn of these genes no been completely defined but pr products of both genes localized in nucleus and believed regulate transcription. BRCA-1 regulates estrogen R activity and co-activator at androgen R. Both involved in homologous recombination of DNA repair and bind

gene involved in dsDNA repair. Mutations usually frame-shift or nonsense mutations cause produc’n of truncated peptide though some are missense mutations

- Individual w/BRCA-1 mutation at hi risk (44%) of epithel’l ovarian ca and sl higher risk of prostate and colon ca. pt w/BRCA-2 mutation also at incr’d risk develop ovarian ca (27%) though less than BRCA-1 carriers. Male breast ca, melanoma, and pancreatic tumor also seen w/significantly higher freq’y in BRCA-2 individual

- Hereditary breast ca ID’d in approx 7% of those pt dx’d w/breast ca – have hi risk develop 2nd breas ca (50-70% by age 70)

- Found that OCP reduce ovarian ca risk by 60% and tamoxifen used reduce risk develop breast ca in carriers by as much as 50%. Pt present’g w/breast ca b4 age 45 w/1st degree relatives dx w/early breast ca or ovarian ca should be considered for genetic testing

Statistics & Research

Characteristics of Standard Deviation (SD) – O’Leary 4E pp283, 296

- SD = population & sample parameter; the sq root of variance; useful means of xpressing variability for normally distributed quantitative variable

- E.g. given set of numerical data pnts, mean/avg can be calculated. For each of these data pnts, there will be variability or deviation from this mean. ‘SD’ depicts variability for this given set of numerical data. When comparing variability amongst 2+ sets of numerical data, SD can be used to determine which set of data pnts more closely resemble its mean and therefore display less variability

Use of Meta-analysis (O’Leary 4E pp279-299)

- Meta-analysis = systematic method of eval’g statistical data based on results of several independent studies of same problem; often encountered in multi-center trials; meta-analysis incr’s sample size and improves power of study

Hernia:

Characteristics of Femoral hernia (Schwartz 7E pp1586-94; Sabiston 14E p1140)

- Femoral hernias are most commonly found in elderly women and are rare in men. Characteristically present as ‘mass about size of a walnut at medial base of Scarpa’s femoral triangle’. They are medial to femoral v. When palpated, mass appears irreducible d/t surrounding fat and LNs

- DDx of infra-inguinal mass medial to femoral v is: enlrgd LN, synovial cyst, saphenous v varix- Femoral hernias strangulate freq’ly d/t tight neck from which they arise. Occur twice as

frequently on the right than on the L b/c sigmoid colon protects entrance to canal on L side- Anatomic Boundaries of Femoral Hernias:

o Superiorly – Iliopubic tract and Inguinal Ligament

o Inferiorly – Cooper’s ligamento Laterally – femoral vo Medially – insertion of iliopubic tract into Cooper’s ligament (lacunar ligament)

Neck / Parotid / Larynx:

Anatomy of Posterior Cervical Triangle (Mastery of Surgery 5E pp270-273)

- Boundaries o Trapezius, SCM, clavicleo Floor: splenius capitis, levator scapula, middle scaleneo Covered by prevertebral fasciao Roof: investing layer of deep cervical fascia

- Subdivided by inferior belly of omohyoid into smaller triangles named for bv’s that run thru them:

o Superior: occipital triangleo Inferior: subclavian triangle

- Contents: Deep to Superficialo Below fascial carpet:

Occipital a Br’s of deep cervical plexus Brachial plexus trunks of C7 (C5+C6), C8, and T1

Dorsoscapular n Long thoracic n Suprascapular n Spinal accessory n – only motor br’s that run superficial to deep cervical

fasciao Superficial to SCM:

Ext’l jugular v Superficial cervical plexus – C2, C3, C4

Lesser occipital n Grt auricular n Transverse cervical n Supraclavicular nn

- ****Spinal accessory n is most superior of all the nn in triangle incisions should be made superior to this nerve in ‘carefree’ area, or risk injuring major structures beneath it in ‘careful’ area

Source of Bleeding after Tracheostomy (Greenfield 4E p1425; Sabiston 18E p1728)

- Classic complication of postop bleeding after tracheostomy is from innominate artery as it crosses over anterior trachea. This complication avoided by keeping tracheostomy above 4th tracheal ring

Pharynx & Esophagus:

Blood Supply to cervical esophagus (Skandalakis, Surgical Anatomy, Ch14)

- Cervical esophagus supplied by paired inferior thyroid aa..arise from thyrocervical trunk of subclavian a. inferior thyroid aa give off br’s 2-3cm long called tracheoesophageal aa. These travel caudal and medial on each side toward tracheoesophageal groove. Vessels of both sides joined along trachea and divide into 3-4 tracheal br’s w/2-3 br’s to esophagus. These in turn subdivide w/I periesophageal tissue b4 enter esophageal wall

Dx of perforated esophagus (Schwartz 8E Ch24)

- Clinical features: cervical/thoracic pain, difficulty swallowing, respiratory distress, fever, L pleural effusion

- Abnl’s on CXR can be variable and shouldn’t be depended upon to make dx – b/c abnl’s dependent on 3 factors: (1) time interval b/w perforation and radiographic exam’n, (2) site of perfor’n, and (3) integrity of mediastinal pleura

- Mediastinal emphysema, strng indicator of perfor’n, takes at least 1hr to be demo’d and present in only 40% of pt’s. Mediastinal widening 2ndary to edema no occur for several hrs

- Dx confirmed w/contrast esophagogram which will demo extravasation in 90% of pt – use of H2O soluble medium (gastrograffin) preferred. Of concern is there’s 10% FN rate. Studies should be done w/pt in R lat decubitus position. In this position contrast material fills entire length of esophagus, allow actual site of perfor’n and its interconnecting cavities to be visualized in almost all pt’s

Zenker’s diverticulum of Esophagus (Greenfield 2E pp670-674)

- Dx: zenker’s diverticulum arise from natural zone of weakness in post’r hypopharyngeal wall. Retention of food & saliva for several days gives rise to halitosis and regurg’n of undigested food is common. Aspirat’n and pulm abscess may occur

- Tx: o Recent lit concerning tx of zenker’s diverticulum insist all pt can benefit from

cricomyotomy which reduce outflow R at upper esoph’l sphincter thought cause zenker’s diverticulum

o If diverticulum still visible after cricomyotomy suspension to prevertebral fascia or xcision of diverticulum performed. Suspension is more conservative approach w/little to no change of wound infection or fistula formation

o Either approach eliminates stagnation of food w/I diverticulum which cause both sx’s and probably malignancy

Esophageal Leiomyoma (Sabiston 17E pp1116-1117)

- Form of GIST d/t mesenchymal cell origin. Virtually all GISTs arise from mutation of c-kit oncogene

- Esophageal leiomyomas occur in pt from 20-50 yoa. More than 80% tumors occur in mid and lower 1/3 of esophagus. Majority as/x’c lrg tumors (usually >5cm) produce sx’s (dysphagia, vague retrosternal P or pain)

- Dx based on barium swallow, CXR, or endoscopy. Barium swallow appearance is distinctive b/c well-localized mass has sm surface w/distinct margins and no circumferential

- EUS confirms dx of leiomyoma as hyperechoic lesion located in submucosa or muscularis propria- Tx based on size and sx’s – as/x’c or smaller tumors (<5cm) can be observed and followed; lrgr

tumors (>5cm) or sx’c tumors req xcision

Stomach:

Gastric Acid Secretion (Schwartz 8E pp941-943)

- Parietal cell secretes acid when 1+ of 3 membr R types stimulated by Ach (from vagal n fibers), gastrin (from D cells), or histamine (From ECL cells). Histamine binds to histamine 2 (H2) receptor which stim’s adenylate cyclase via G-pr-linked mech’n. activation of AC results in incr in IC cAMP which activates pr kinases, leading to incr’d levels of phosphopr’s and activation of proton pump

- Gastrin binds to type B cholecystokinin (CCK) R’s and Ach bind to M3 muscarinic R’s – both stim phospholipase C (PLC) via G-pr linked mech’n lead to incr’d production of inositol triphosphate (IPe) from membr bound Phospholipids (PLs). IP3 stim’s release of Ca++ from IC stores which leads to activ’n of pr kinases and activ’n of H/K ATPase

- Enzyme H/K ATPase is proton pump – when parietal cell stim’d there’s cytoskeletal rearrangement and fusion of tubulovesicles w/apical membr of secretory canliculus. Heterodimer assembly of enz subunits into microvili of secr’y canaliculus results in acid secretion w/EC K being xchanged for cytosolic H. electroneutral this is E-req’g process since H secreted against gradient…during acid production, K and Cl also secreted into secretory canaliculus thru separate channels, providing K for H/K-ATPase and Cl for secreted H

- PPI (proton pump (-)r) drugs irreversible interfere w/fxn of H/K ATPase molecule. SS from mucosal D cells bind membr R’s and (-) activation of AC thru inhibitory G pr

MC Metabolic Complications in Roux-en-Y Bypass (Schwartz 8E pp32, 1006)

- MC metabolic (-)y assoc’d w/Roux-en-Y gastric bypass (RYGB) is vit B12 (-)y – manifested in 26-70% pt undergoing procerdure…deficiency manifest self as pernicious anemia, neuropathy, myelopathy, and glossitis

- Other assoc’d (-)y include:o Fe – 20-49% (microcytic anemia 18-35%) – can also present as general fatigue and

dyspneao Folate: 9-18%, deficiency can closely resemble B12 deficiencyo Ca++ - profound deficits can result in dementia, encephalopathy, and tetanyo Thiamine – classic sx of dry beriberi (AMS, peripheral neuropathy) or Wet Beriberi (hrt

failure)

Re-Bleeding peptic ulcer (Sabiston 18E pp1205-1207)

- Peptic gastric and duod’l ulcers are MCC of acute upper GI bleeding. Dx / Rx endoscopy is standard approach unless emergency surgery is req’d for profuse bleeding. Appearance of ulcer on endoscopy can predict risk of re-bleeding

- Forrest Classification of endoscopic findings & Rebleeding risks in PUD

Classification Description Rebleeding RiskGrade Ia Active, pulsatile bleeding High Grade Ib Active, nonpulsatile bleeding HighGrade IIa Nonbleeding visible vessel HighGrade IIb Adherent clot IntmdGrade IIc Ulcer w/black spot LowGrade III Clean, nonbleeding ulcer bed Low

- Endoscopic Rx includes monopolar/bipolar electrocoagulation, heater probe Rx, laser/argon plasma coagulation, or injection Rx using epinephrine ias highly effective in controlling bleeding. Endoscopic Rx fails in about 20% of pt’s. repeat endoscopy maybe effective in controlling re-bleeding. Role of hemoclips is less clear & can be difficult to apply but can be particularly effective in dealing w/spurting vessel to provide immediate hemorrhage control

Effects of Truncal Vagotomy (Sabiston 17E pp1295-1297)

- Vagal nn enter abd in close assoc’n w/esophagus. d/t axial rotation of stomach, R vagus becomes post’r vagus nd L become ant’r vagus. Ant’r vagus gives several gastric br’s in proximal stomach and hepatic br to hepatic plexus. Ant’r vagus continues a ‘The nerve of Laterje’ to pre-pyloric area of stomach where it terminates in ‘crow’s foot’

- Post’r vagus n innervates proximal stomach w/multiple gastric br’s and gives off lrg celiac n. this br often follows L gastric a and relocates post’r vagus medially into gastro-hepatic omentum or adjac’t to R crus of diaphragm. R vagus rarely reaches pyloric area of stomach

- Division of both vagal trunks at esophageal hiatus denervates acid producing fundic mucosa + remainder of vagally supplied viscera. Truncal vagotomy should be combo’d w/gastric emptying procedure d/t (-)n of gastric motor activity

- Vagotomy reduces cholinergic stimul’n of parietal cells, also diminishes parietal cell responsiveness to gastrin and histamine. Basal acid secretion reduced by about 80%, gastrin levels incr’d postop

- Gastric denervation abolishes vagally mediated receptive relaxation . intragastric P rise is higher than nl…emptying of liquids & solids acceler’d after vagotomy combo’d w/gastric emptying procedure. Removal of efferent vagal innervations result in diminished exocrine pancreatic secretion w/decr’d bicarb and enz outputs – biliary secretion decr’d, and GB distension noted; fecal fat content incr’d and CCK/secretin decr’d. most instances these xtragastric alter’ns in digestive fxn subclinical

- MC side effect of vagotomy is diarrhea, which is fairly well controlled w/somatostatin (SS). Cholelithiasis d/t reduced emptying capacity of GB is common.

Site Intrinsic Factor Secretion (Schwartz 7E p1187)

- Parietal cells of stomach secrete intrinsic factor (IF) – important factor in hematopoiesis- IF is essential for ileal absorp’n of vit B12. vitB12 stored in lrg quantities – pt who undergoes

total gastrectomy at risk for vit B12 (-)y and will develop megaloblastic anemia pt who has total gastrectomy should receive vit B12 injections regularly, i.e. monthly following total gastrectomy

Small Bowel:

Gastrin & Secretin Relationship (Schwartz 8E Ch25)

- Passage of acidic chime from stomach into duod marks beginning of intestinal phase of digestion (in this phase, there’s (-)n of gastric acid secretion + stimul’n of pancreatic/biliary secretions)

- Acidification of duod stimulates secretion of secretin from S cells of intestinal mucosa. Secretin (-) release of gastrin and (+) release of bicarb from pancreas. Acidific’n of duod also (+) rlease of entergastrones (including gastric (-)y peptide – GIP that (-)’s gastric acid secretion)

Tumor Most Likely to Metastasize to SB (Sabiston 16E pp904-905; Cameron, Current Surgical dx and tx 12E Ch29)

- Metastatic tumors involving SB much MC than primary tumors. MC met’s to SB are those arising from other intra-abd organs – ovaries, kidneys, stomach, colon, pancreas. Colon and pancreatic ca are MC primary sites for direct invasion. Peritoneal seding may arise from any intra-abd malignancy including gastric, hepatic, ovarian, appendiceal, and colonic primary tumors

- Hematogenous met’s from xtra-abd tumors are rare but found w/breast, skin, and lung ca. cutaneous melanoma is MC xtra-abd source to involve SB and is found in 50% of pt dying of malignant melanoma

Etiology of Dumping Syndrome (Schwartz 8E Ch25)

- Appearing after meals, is characterized by tachycardia, diaphoresis, hypotension, light-headedness, abd pain, and diarrhea. Sx believed to result after abrupt delivery of hyperosmotic chime into small intestine causing peripheral and splanchnic vasodilatation. Sx’s occur 15-30min after meal and can be treated w/recumbence and IVFs

- Clinically significant dumping occur in 5-10% pt after pyloroplasty, pyloromyotomy, or distal gastrectomy. Dumping can also occur in upto 25% pt following truncal vagotomy w/most resolve spontaneously and <5% causing long term morbidity

- Tx includes dietary manipulation w/small meals and SC injections of octreotide 30 min prior to meals shown alleviate dumping syndrome

- Although unpredictable, conversion of Billroth II to Billroth I, conversion of Billroth to Roux-en-Y, pyloric reconstruction, gastrojejunostomy takedown and interposition of reversed intestinal segment b/w stomach and duodenum have been used to manage disabling dumping syndrome

Anatomy of Foramen of Winslow (Mastery of Surgery 5E pp817-837)

- Foramen of Winslowo Superior: Livero Inferior: Duodenumo Anterior: Portal triado Posterior: IVC

Acidification Duodenum (Schwartz 8E pp941-945, 1025-1026)

- Passage of acidic chime from stomach into duodenum marks beginning of intestinal phase of digestion. In this phase, there’s inhibition of gastric acid secretion + stimulation of pancreatic/biliary secretion. This phase poorly understood – thought be mediated by hormone yet to be discovered that’s released from proximal SB mucosa in response to luminal chime

- Acidification of duodenum stimulates secretion of secretin from S cells of intestinal mucosa. Secretin (-) release of gastrin and stim release of bicarb from pancreas. Acidification of duodenum also stimulates release of GIP which (-) gastric acid secretion

- Xposure of intestinal mucosa to free AAs and lng-chain FAs stim CCK release by CCK cells. Circulating CCK then stimulate secretion of pancr’c enz’s + contraction of GB

- Representative Regulator Peptides produced in small intestine (aThis table indicates which enteroendocrine cell types located in intestinal epithelium produce these peptides. These peptides also widely xpressed in nonintestinal tissues)

Hormone Sourcea ActionsSomatostatin D cell (-) GI secretion, motility, and

splanchnic perfusionSecretin S cells Stimulates exocrine pancr’c

secretion; stimulates intestinal secretion

CCK I cell Stimulates pancreatic exocrine secretion; stim GB emptying; (-) sphincter of Oddi contraction

Motilin M cell Stimulates intestinal motilityPeptide YY L cell (-) intestinal motility & secretionGlucagon-like peptide 2 L cell (+) intestinal epithelial

proliferationNeurotensin N cell (+) pancreatic & biliary secretion;

(-) SB motility; (+) intestinal mucosal growth

Characteristics of Shrt Bowel Syndrome (Schwartz 8E pp1051-1052)

- Group of S/S that result from total SB length that is inadequate to support nutrition, arbitrarily defined as <200 cm. clinical findings include diarrhea, fluid and electrolyte abnl’s, dehydration, & malnutrition

- Resection of < 50% of SB well tolerated. Clinical significant malabsorption occur when >50-80% resected. In those who lack fxnal colon, lifelong TPN likely if <100cm remain. w/fxnal colon, lifelong TPN likely if <60 cm remain

- Length alone no sole determining factor of lifelong dependence on TPN. Intact colon has capacity to absorb lrg amnts of fluids & electrolytes and small role in absorbing shrt chain FAs. Intact ileocecal valve assoc’d w/decr’d malabsroption b/c delays transit of chime from SB to colon slowing transit time for grtr absorption. Healthier the remaining bowel, the less malabsorption. Resection of jejunum tolerated better than ileum as bile salt and vit B12 absorption sp to ileum

- After massive SB resections, program for tx maybe divided into early & late phaseso Early tx is primarily directed at control of diarrhea, replacement fluid & electrolytes and

TPN (total parenteral nutrition). Vol losses can xceed 5L/d and stringent monitoring of I&O must be done; judicious use of antimotility agents (loperamide or diphenoxylate) may delay small intestine transit; octreotide may help reduce vol of GI secretions, assoc’d w/delayed adaption in animal models

o Diets should be begun at isoosmolar [ ]’s and w/small volumes; H2 R antagonists or PPIs may diminish diarrhea cause by early, transient acid hypersecretion

Dx Study of Gallstone Ileus (Schwartz Principles of Surgery 6E p1381)

- Gallstone ileus occurs when gallstone obstructs SB, which most commonly occurs at terminal ileum

- Dx of gallstone ileus determined thru combo of clinical findings and radiographs. Air fluid levels on upright or decubitus abd x-rays suggest SBO and air in biliary tree pathognomonic of gallstone ileus

- Hx will reveal past sx of cholelithiasis that suddenly resolved or hx of gallstones. Findings on PE support gallstone ileus are sx of SBO: abd pain, obstipation, vomiting, abd distension

- Tx = enterotomy removing stone, palpation of entire SB to eliminate possibility of 2nd gallstone in transit and if possible concomitant cholecystectomy w/closure of duodenal fistula

Colon & Rectum:

Dx Test of LGIB (Sabiston 17E pp1258-1259)

- Controversy surround initial investigative test for LGIB and dependent upon xpertise and availability. 3 options for dx testing – colonoscopy, selective visceral angiography, and Technicium 99m-labeled RBC scintigraphy

- Colonoscopy: indicated when significant hemorrhage ceased and resuscitation complete; performed as early as possible since most episodes of bleeding stop spontaneously. Pos findings include active bleeding site, nonbleeding visible vessel, clot adherent to diverticular ulcerated orifice or to discrete focus of mucosa, or fresh blood localized to colonic segment

- Selective injection of contrast into SMA or IMA can ID hemorrhage at rate of 0.5cc/min or grtr. The study can accurately ID bleed in 45-75% pt who actively bleeding at time of contrast injection

- In technetium 99m-labeled RBC scintigraphy, pt RBCs labeled w/technetium isotope and reinserted into circulation. As bleeding occurs, labeled blood enters colonic lumen and isotopic focus created – this focus can then be imaged w/whole body scintigraphy. Bleeding as low as 0.1cc/min can be detected if bleeding present at time of injection, test can accurately ID bleeding in 85% of cases

Highest Risk Colon Ca (Schwartz 8E pp1084-1085)

- ID of RFs which predispose individual to development of CRC essential to development of useful, appropriate screening modalities. Those factors that have been shown to impart risk to developing CRC include:

o Aging – been ID’d as dominant RF predisposing individual to developing CRC. Steady rise in risk after age 50 has been well documented. This correlates w/American recommendations for routine screening after age 50

o Hereditary RFs – 20% of CRC appear have some hereditary relationo Environment/dietary factors – diets hi in animal fat and lo in fiber ID’d as CRC RFs.

Obesity + sedentary lifestyle incr mortality assoc’d w/CRCo IBD – chronic, on-standing infl’n predispose individual to this dzo Other factors – cigarette smoking, acromegaly, pelvic irradiation + many others can

predispose individual to CRC

Fecal Occult Blood (Sabiston 17E pp1465-1466; Lawrencce, Current surgical dx and tx, pp718-719)

- Fecal occult blood testing (FOBT) – inexpensive and easy to use

- Studies show screening annually w/3 consecutive stools that where pos had 33% risk reduction for CRC. Using FOBT alone has unacceptably hi FN rate w/only 30-50% ca’s detected. When combined FOBT w/flex sig combo missed 24% of proximal ca’s. colonoscopy is gold standard for screening but still miss 20-24% of all polyps but there are very few missed >1cm if FOBT is post then colonoscopy is single best f/u study.

Spleen:

Etiology of Hypotension after ITP Tx (Sabiston, Txtbook of Surgery 15E pp1196; Fischer, Mastery of Surgery 6E pp1659)

- Idiopathic thrombocytopenic purpura (immune thrombocytopenic purpura – ITP) is acquired d/o caused by destruction of plt xxposed to circulating IgG antiplt factors. Spleen is source of said factors – also major site for sequestering sensitized plts

- Term ITP should be reserved for hemorrhagic d/o characterized by subnl plt count in presence of BM containing nl or incr’d megakaryocytes and in absence of any systemic dz or hx of ingestion of drugs capable of inducing thrombocytopenia

- Female pt’s outnumber males at ratio of 3:1. Plt counts generally reduced to 50K or less and at times approach zero. Acute ITP has xcellent px in kids under 16yoa. Approx 80% of these will recover completely w/o sp Rx

- Generally accepted protocol for managing pt w/dx’d ITP include initial 6wk-2mos period of CS Rx. If pt no respond, splenectomy performed. If pt does respond, CS Rx tapered off and if thrombocytopenia recurs, splenectomy carried out. Any manifestations suggestive of intracranial bleeding demand emergency splenectomy. In one series, 5/6 pt w/ITP and life-threatening intracranial bleed were saved by splenectomy. Plt should be available for procedure but only admin’d in pt who continue bleeding following removal of spleen

- Hypotension following splenectomy 2ndary to hemorrhage. Early postop bleeding closely monitored. Coagulopathy needs be corrected and any decr in hct warrants reexplor’n early to evacuate potential hematomas and reduce incidence of subphrenic abscess. MC site of bleeding is shrt gastric vessels

Tx of post-splenectomy bleeding, ITP (Cameron, Current Surgical Rx 8E pp533-536)

- ITP – MC indication for elective splenectomy; spleen usual avg size in ITP and laparoscopic removal possible; ITP in kids resolves 70% of time w/o therapy; in adults surgical and medical Rx indicated. Many pt present w/plt count <10,000/mm3 and PO CS are needed. IVIG may also be given for very lo plt counts or w/persistent purpura. Splenectomy indicated for failure of medical therapy, intolerance of CS/need for prolonged CS, or after 1st recurrence

- Splenectomy causes changes in peripheral blood smear including Howell-Jolly bodies and siderocytes. Rate of transfusion is 3-5% for all indications of splenectomy – pt undergoing lap splenectomy more likely have bleeding problems. Bleeding complications include intraop bleeding req’g transfusion, postop bleeding req’g transfusion, abd wall hematoma formation,

and hemothorax. Pt should be given prophylaxis of meningococcal, streptococcal, and haemophilus influenza vaccinations 1wk prior to splenectomy

Pancreas:

Pancreatic Divisum (Schwartz 8E Ch6; Simmons and Steed, Basic Science Review for Surgeons, pp257-259; O’Leary pp63-65)

- Pancreas appears at about 5th or 6th wk of gestation; composed of ventral and dorsal anlage. Both anlage possess ducts, ventral duct related to CBD and dorsal duct empties more proximally into duodenum. Both ducts (when present) empty into 2nd prt of duodenum. At about 7 wks gestation, anlage fuse 2ndary to asymmetric gut rotation. Ventral anlage forms uncinate process and prt of head; dorsal component forms body, tail, and remainder of head

- Fusion of dorsal & ventral ductal elements produce major duct of Wirsung. Patency of dorsal duct beyond site of fusion forms accessory duct of Santorini – occurs in 70% individuals; in other 30%, proximal aspect of dorsal duct (Santorini) regress after anastomosis w/ventral duct (of Wirsung)

- In 4-10% individuals there’s failure of fusion of dorsal & ventral ducts – termed pancreatic divisum. Drainage of dorsal & ventral aspects of pancreas remain separate and majority of pancreatic exocrine secretion exit via accessory duct – in this case ‘main’ pancreatic duct empty thru minor papilla. Only pancr’c drainage from uncinate process drain thru ampulla of Vater. Felt by many authors pancreatitis can result from relative outflow obstruction as minor papilla no able adequately accommodate such lrg volume

Diagnosis of Glucagonoma (Sabiston 17E p 1016-1017)

- Glucagonoma – tumor of islet alpha cell, cause syndrome of skin rash, DM, anemia, wght loss, elevated level of glucagons. Skin lesion is dx’c characteristic, necrolytic migrating erythema

- Parenteral AAs will eliminate skin rash as lo levels are ID’d w/this syndrome. Glucagon tumors are malignant and aggressive resection of tumor usually arising in tail/body is tx. Cure rate is only 30% and octreotide may provide sx’c relief if unresectable or for reoccurrence.

- Dx is made from characteristic skin lesion, elevated levels of glucagon, and presence of pancreatic tumor. Glucagon has upper limit of 150-190 pg/mL, in pt w/a glucagonoma, glucagon levels range from 200-2000 pg/mL. Tumor maybe demo’d by enhanced CT or MRI or by selective angiography

Pancreatic enzymes – characteristics of secretion (O’Leary 2E pp452-455)

- Digestive enzymes synthesized and stored in pancreatic acinar cells and released in response to CCK and vagal stimul’n. pancreatic enz’s are:

o Proteoolytic – trypsin, chymotrypsin, carboxypeptidase, ribonuclease, deoxyribonuclease, elastase

o Lipolytic – lipase, colipase, phospholipase A2o Amylolytic – amylase

- Lipase and amylase secreted in their active form – proteolytic enz’s and PLA2 secreted as inactive ‘zymogens’. Activation of trypsinogen to trypsin occurs when zymogen xposed to duodenal enz enterokinase. Trypsin then converts other zymogens to their active forms. In intestine, proteolytic enz’s digest pr’s into peptides, lipase breaks fat into glycerol and FAs, PLA2 catalyze conversion of biliary lecithin to lysolecithin, and amylase convert starch to disaccharides and dextrins

- Secretin is principal stimulant of pancr’c H2O and electrolyte secretion. H2O and electrolytes originate from central acinar and intercalated duct cells. At basal secretory rate of 0.2-0.3 mL/min, [Cl] and [bicarb] ions equivalent to plasma; w/neurohumoral stim’n bicarb component incr’s in [ ] while Cl [ ] falls. End product is clear, isotonic, sol’n w/pH of 8

- CCK and vagal stim’n (Ach) are principal stimulants for secretion of pancr’c enz’s

Palliative tx for pancr’c ca (Schwartz 7E p1491)

- Palliation tx for ca of head of pancreas is directed toward relief of obstructive jaundice, gastric outlet obstruction, and pain. In adv’c dz, 70% of pt w/pancr’c ca will develop obstructive jaundice and 1/3 of pt w/ca in this area will eventually develop gastric outlet obstruction

- Cholecystojejunostomy and choledochojejunostomy are both safe and procedure of choice for relief of biliary obstruction. Gastrojejunostomy should be considered in pt who xpected to survive more than few mos

- Pain is major sx in up to 80% of pt w/pancreatic ca. problem best managed by chem’l destruction of celiac nn and achieved by percutaneous injection of 50% EtOH into region of ganglia under CT guidance. Can also be done at operation. Pain relief is possible in up to 80% pt’s. pain often recurs – repeated percutaneous injections can be performed w/xpected good results

Biliary & Liver:

Site Absorption Bile Salts (Lawrence, current surgical dx and tx 12E Ch25)

- Bile salts remain in intestinal lumen thru-out jejnum where participate in fat digestion & absorpt’n. upon reaching distal SB, reabsorbed by active transport system located in terminal 200 cm of ileum

- Over 95% of bile salts arriving from jejnum are xferred by this process into portain v blood, remainder enter colon, where converted to 2ndary bile salts. Entire bile salt pool of 2.5-4g circulates 2x thru enterhepatic circulation during each meal, and 6-8 cycles made each day. Nl daily loss of bile salts in stool amounts to 10-20% of pool and restored by hepatic synthesis

GB emptying post fatty meal (Schwartz 8E Ch31)

- GB filling occurs by tonic contraction of sphincter of Oddi, creating gradient b/w bile ducts and GB. Process mediated in prt by hormone motilin. During meal GB empties by coordinated motor response of GB contraction and relaxation of sphincter of Oddi

- Neurohormonal regulation of GB contraction coincides w/gastric emptying. In response to meal, duodenum triggers release of series of neurohumoral messengers that incr GB tone. CCK released from cells line duod’l lumen bind directly to CCK-A receptors on GB sm mm cells. In addition, CCK activates vagal afferents in wall of duod and these in turn initiate vago-vagal reflex that release Ach at GB synapse, further increas’g contractile activity

Anatomy of Liver (Cameron 8E p293; Schwartz 8E p1140)

- Classic description – liver characterized as having 4 lobes…R, L, caudate, and quadrate. These trad’l lobes no describe true segmental anatomy of liver

- True division into R and L lobes is Cantlie’s line (plane b/w GB fossa and suprahepatic IVC posteriorly)

o R segmental fissure or R hepatic v divides R lobe into ant (seg V and VIII) and post (segments VI and VII) section but no extern’l landmarks. Falciform ligament divides L lobe into medial (segment IV) and lateral (segments II and III) segments

o Caudate lobe consist of segment I and lies ant to IVCo True segmental divisions can be observed only in cast specimen of live where hepatic a,

portal v, and bile ducts have been injected – this divides liver into its 8 true segments in relation to vascular supply and bile drainage

Bile [ ] in the GB (Schwartz 8E p1191)

- Primary purpose of GB is storage and [ ] of bile. GB mucosa has grtst absorptive power per unit area of any structure in body and able to concentrate secreted bile up to ten times (tenfold) – approx 90% of H2O in GB bile is absorbed in 4hr much higher density of bile salts, bile pigments and chol’l. absorption of fluid is E dependent thru active transport of Na and Cl and passive movement of H2O against significant [ ] gradients

- Mucous secreted from GB at 20cc/hr and protects mucosa from damaging effects of [ ]’d bile and facilitates passage of bile thru cystic duct. Glycopr and H ions secreted by epithelial cells. H ions decr bile pH which promotes Ca solubility. Mucosal glands in infundibulum and neck secrete mucus glycopr’s, producing white bile seen in hydrops

Characteristics of bile flow (Schwartz 8E, pp1142-6, 1188-1190)

- Bile ducts follow segmental anatomy of intrahepatic vasculature. At cellular level, bile duct arise from hepatocyte membr that when merge w/adjacent hepatocytes, form canaliculi. These then merge to form canal of Hering. Lrgr collections form small ducts…confluence of L and R hepatic ducts maybe intrahepatic and gives rise to common hepatic duct (duct b/w confluence and cystic duct takeoff) – common hepatic and cystic duct join to form common bile duct (CBD) which ends at ampulla of Vater. Intact sphincter of Oddi directs bile into GB

- Anomalies of xtrahepatic biliary tree exist in 1/3 of pt. small ducts (of Luschka) may drain directly from liver into body of GB. Accessory R hepatic ducts exist in 5% of pt

- Production of bile by hepatocytes is active process that occur at level of canalicular membr – secretion responsive to neurogenic, humoral, and chemical stimuli. Vagal stimul’n incr flow; splanchnic stimul’n decr flow, HCl, partly digested pr and FA in duod stim release of secretin from duod that in turn incr bile flow and production

- Bile similar to plasma in electrolyte composition. Cholic acids and chenodeoxycholic acids are primary bile acids. Deoxycholic and lithocholic acids are 2ndary bile acids formed by intestinal bacteria. d/t enterohepatic circul’n, 95% of bile acids actively transported and returned back to liver via portal circul’n

Characteristics of CCK (Schwartz 8E pp1026,1191,1227)

- CCK is produced by I cells in SI epithelium. Released endogenously from duod’l mucosa in response to a meal. Highest [ ]’s are in duodenum; released into bloodstream by acid, fat, and AAs in duodenum. Stimulates pancr’c exocrine secretion, stim GB emptying, and (-) sphincter of Oddi contraction

- Gastric hydrolysis of pt yields peptides that enter intestine and stim intestinal endocrine cells to release CCK-releasing peptide, CCK, and secretin, which then + pancreas to secrete enz’s and bicarb into intestine

- CCK is main stimulus to GB emptying; plasma ½ life of 2-3 min and metabolized by liver and kidneys

- CCK acts directly on sm mm R’s of GB and (+) GB contraction; relaxes terminal bile duct, sphincter of Oddi, and duod’m – its stim’n mediated by cholinergic vagal neurons

- s/p vagotomy, response to CCK diminished and size/volume of GB incr’d

Lithogenic Bile Characteristics (Schwartz 8E p1196)

- in US, cholesterol stones 80% gallstones and black pigmented stones acc’nt for remaining 15-20%; brown stones are small %age. Pigmented stones primarily found in Asia

- chol stones are >70% chol, multiple, radiolucent, variable in size, hard, faceted/irregular, and various colors. Formation dependent on 3 factors: supersaturation of bile w/cholesterol, nucleation, and stone growth

o maintenance of chol in soln dependent on presence of sufficient amnts of bile salts and phospholipids

o alterations which result in relative incr in chol predispose to stone formationo 30% of cholesterol carried in micelles and remaining 70% carried in vesicles in lipid

bilayer arrangemento Stability of these vesicles thought be key determinant in satur’n and stone formation.

Nucleation is an unclear event that may be ppt’d by Ca, stasis, abnl GB wall absorption, mucous, or glycopr’s or maybe d/t lack of antinucleation substances; once nucleation occur’d further precipitation enhanced by stones themselves

o Pigmented stones <20% chol and are drk b/c of Ca bilirubinate. Black stones are small, brittle, sometimes speculated…formed in GB in individuals w/hemolytic dz (hereditary spherocytosis, sickle cell) where bile becomes supersaturated w/unconjugated BRN and then ppt w/calcium

o Brown stones are <1cm, brownish-yellow, soft, and mushy…they form in GB and ducts, 2ndary to bact’l infection and parasites causing stasis. Stone comprised of ppt’d Ca bilirubinate and bact cell bodies

Monitoring hepatic fxn after liver resection (Schwartz 8E pp1146-1148)

- Liver tests after liver resection can be broken down to tests of liver fxn (PT/INR, factors V & VII, BRN, albumin), parenchymal injury (AST, ALT) and biliary obstruction (ALP, GGT, BRN) more important than any individual test result is pattern of liver test abnl’s

- AST & ALT initially incr’d postop but should decr thereafter. INR sl incr’d postop, rise until postop day 2 and then decr; progressive incr in AST, ALT, or INR should initiate eval of patency of vessels in and out of liver w/duplex U/S or contrast CT

- Alkaline phosphatase (ALP) will be sl incr’d postop, rise until POD3 or 4, then decr. Contin’d rise in ALP may signify biliary obstruction. Incr in BRN levels w/o rise in ALP may indicate bile leak

Best Tests of hepatic biosynthesis (Sabiston 17E p1533)

- Liver is responsible for many bio fxns include bile formation, reprocessing of biliary salts thru enterohepatic circulation, and b/d and metab of Hb to BRN. Other major metabolic fxns of liver have to do w/CHO, lipid, and pr metabolism

- Pr synthesis is most common measure used determine hepatic synthesis. At least 17 of major human pr synthesiz’d/secret’d by liver. Albumin is most abundant serum pr (15% of total hepatic synthesis), ½ life of albumin (45d) limits ability determine active hepatic synthesis of pr

- Tf is pr commonly used assess hepatic synthesis – ½ life is 4-5d pos anabolic state can be determined by rise in serum transferrin (Tf) levels

- Other pt that mrkrs of hepatic biosynthesis include coagul’n pr. Of these factors, 7 has shrtst ½ life of 5-7hr and b/c it’s vit K dependent pr, absence of vit K or blockage of gamma-carboxylation by Coumadin can be assessed by monitoring PT (this test dependent on adeq amnts of fxnal factor 7)

- Liver synthesize hepatic glycogen after eating, responsible for burning lactic acid to pyruvate which subsequently convert back to glc, these synthetic fxns difficult monitor. Lipid metabolism which generate TGs from FAs, ketones (acetoacetate), lipopr’s, and chol are synthesized by liver but difficult to monitor

- Acute phase pr produced by liver in response to systemic infl’y state initiate sudden transient rise in C reactive pr, compliment in coagul’n pr’s while albumin synthesis decr’d

Pulmonary:

Characteristics of P Support Mech’l Ventilation (Marino ICU Book 3E pp480-481)

- P support ventilation is P-augmented breathing that allows pt to determine inflation volume and resp’y cycle duration. This mode is to augment spontaneous breathing. At beginning of each spontaneous breath, neg P generated by pt opens valve that delivers inspired gas at preselected P (usually 5-10 cm H2O). the pt’s inspiratory flow rate is adjusted by ventilator as needed to keep inflation flow rate constant

- When pt’s inspiratory flow rate falls below 25% of peak inspiratory flow, supplemented breath terminated. P support ventilation allows pt to dictate duration of lung inflation and inflation volume, by recognizing pt’s inherent inspiratory flow rate

Etiology Hypoxemia (Sabiston 17E pp622-624)

- Hypoxemia represents inadequate xchange or delivery of O2 to pulmonary vascular bed. Causes may include hypoventilation 2ndary to inadequate CNS drive (head injury) or drug OD (narcotics, BZDs). Other causes of hypoventilation should be considered including oral pharyngeal intubation, rather than tracheal intubation, and inadequate volume ventilations or ventilation w/inadequate O2 [ ]’s

- After adequate O2 [ ] delivery has been ascertained, primary causes is vent’n perfus’n mismatch – commonly d/t ARDS (pulm blood shunted to collapsed alveoli or alveoli filled w/transudates). The ‘wet lungs’ d/t transudates reduce compliance which add to V/Q mismatch

- Falling P/F ratio (P =arterial PO2; F = FIO2) – the ratio of arterial PO2 to %age of inspired O2 (FIO2) has nl ratio of approx 400. Pt w/pulm problems have ratio <350 (e.g. arterial PO2 of <140 w/FIO2 of 0.40), ratio of <250 indication for vigorous pulm’y Rx and not necessarily indication for incr’g inspired O2 [ ]

Effects of Smoking on Pulm Fxn (Sabiston 17E pp1765-1769; Mason, Murray & Nadel’s textbook of resp medicine, 4E)

- Pulm dz from smoking includes overlapping syndromes of chronic bronchitis (cough & mucus secretion), emphysema, and airway obstruction. Lung pathology produced by cigarette smoking includes loss of cilia, mucous gland hyperplasia, incr’d # of goblet cells in central airways, infl’n, goblet cell metaplasia, squamous metaplasia, mucus plugging in small airways, destruction of alveoli, and reduced # of small aa effects on pulm fxn are those consistent w/obstructive pattern (decr’d DLCO, decr’d FEV1/FVC) – poor ventilation w/CO2 retention occurs when FEV1 becomes < 1 L. eventually, emphysematous changes cause diminished compliance and oxygenation becomes poor as well

Fluid turnover nl pleural space (Schwartz Principles of Surg 6E pp660-663)

- Pleura are dynamic serous membr of flat mesothelial cells – overlies thin layer of CT. portion overlying lung called visceral pleura and prt over chest wall is parietal pleura

- Normally there’s balance of hydrostatic and colloid osmotic factors. Generally 5-10L of pr free fluid traverse from systemic capillary in parietal pleura to pleural space and into pulmonary

capillary. Any alteration in this movement develop fluid collection called transudate (which is pr poor ultrafiltrate, or exudates which is pr rich)

Operative Risk w/pulmonary resection (Mastery of Surgery 5E p582)

- Xtent of surgery necessary for complete resection of lung ca often uncertain b4 operation assessment should be made as to whether pt may tolerate pneumonectomy, lobectomy, or limited resection. Determination of preop status including smoking hx, coexistent emphysema or COPD, pulm reserve, and cardiac fxn is mandatory. Cessation of smoking at least 2 wks but ideally 6 wks prior to surgery decreases risk of postop PNA

- Forced expiratory volume in 1 sec (FEV1) and diffusion capacity of carbon monoxide (DLCO) used to estimate postop pulmonary fxn. Following eqn is applied to preop pulm fxn test results:

o % predicted postop FEV1 = % preop FEV1 – (preop FEV1 x no. segments removed/18)- Postop FEV1 and DLCO should be >35% predicted. Pt w/predicted postop VO2 (O2

consumption) maximum > 12 mL/kg/m2 tolerate resection; 10 mL/kg/m2 or less are at very high risk

O2 Dissociation (Levitsky, Pulmonary Physiology, 2E, pp139-151; Ganong, Review of Mediccal Physio, 12E, pp543-544)

- 3 predominant conditions affecting oxyHb dissociation curve are blood pH, temperature, and [ ] of 2,3-diphosphoglycerate (2,3-DPG). Rise in temp or fall in pH shifts curve to R; when curve shifted to R, higher PO2 req’d for Hb to bind given amnt of O2; fall in temp or rise in pH shifts curve to L and lower PO2 req’d to bind given amnt of O2

- Convenient index of such shifts is P50 (PO2 at which Hb is ½ saturated w/O2) – higher the P50, the lower the affinity of Hb for O2; lower P50, higher affinity of Hb for O2. If oxyHb dissociation curve shift to R, P50 incr’s; if it’s shifted to L, P50 decreases

- Typical ‘normal’ adult oxyHb dissociation curve for blood at 37C w/pH of 7.4 and PCO2 of 40 torr. P50 is partial P of O2 at which Hb is 50% saturated w/O2

- Lo pH’s or hi PCO2’s both shift curve to R. hi pH and lo PCO2’s both shift curve to L. b/c hi PCO2’s in blood often assoc’d w/lo pH – these 2 effects often occur concurrently

- Hi temps shift curve to R; lo temps shift curve to L

- 2,3-DPG produced by erythrocytes and normally present in relatively hi [ ]’s w/I RBCs – higher [2,3-DPG] shift curve to R, lower [2,3DPG] shift curve to L. more 2,3-dpg produced during chronic hypoxic conditions, shift curve to R and allow more O2 to be released from Hb at particular PO2. Blood deficient in 2,3-dpg does not upload grt deal of O2, xcept at very lo PO2’s. blood stored in blood banks for as little as 1 wk have very lo levels of 2,3-dpg unless steps taken restore nl levels of 2,3-dpg

- CO shifts curve to L b/c of profoundly grtr affinity CO has for Hb when compared to O2- b/c lo pH, hi PCO2, more 2,3-dpg, and higher temp all shift curve to R, they all can help to unload

O2 from Hb upon its arrival at tissues…hi pH, lo PCO2, less 2,3-dpg, lower temps and CO make it more difficult for O2 to unload from Hb at tissues b/c of affinity O2 has for Hb incr’s

Pulmonary Fxn (Sabiston 17E pp1765-1769)

- Tidal volume – amnt of air xpired during normal respiratory excursions- Fxnal residual capacity (FRC) – amnt of gas contained in lung at end of xpiration- Vital capacity (VC) – amnt of gas xhaled following maximal inspiration and forced expiration – VC

decreases w/age- Residual volume (RV) – amnt of air remaining in lungs after maximal expiration- Forced expiratory volume at 1 second (FEV1) – volume of air exhaled in 1 sec w/maximum

xpiratory effort- Pulm comorbidities assoc’d w/incr’d operative risk include smoking, age, COPD, asthma, and

obesity; FEV1 of 1-2L is no assoc’d w/incr’d operative risk; w/FEV1 <800 cc, there’s assoc’d risk of severe pulm complications; those w/<500 cc have grtst risk. Presence of CO2 retention is mrkr for pt w/dramatically incr’d risk; hypercapnia (>43 mmHg – nl range is 38-42 mmHg CO2) indicates severe dz representing fxnal loss of >50% of lung

Tx of ARDS (ARDSNet – NIH/NHLBI ARDS Network http://www.ardsnet.org/; Civetta, Critical Care, 2E, pp1237-1247)

- Acute resp distress syndrome (ARDS) is severe, often fatal, infl’y dz of lung characterized by sudden onset of pulmonary edema and resp failure, usually in setting of other acute medical conditions resulting from local (PNA) or distant (multiple trauma) injury. Acute lung injury (ALI) is term used to describe pt’s w/milder form of ARDS

- Progression of ALI or pulm edema to ARDS req’s supportive mgmt geared toward global resuscitation. Early endotrach’l intubation and initiation of pos P ventil’n recommended w/mgmt strategies directed at minimizing barotraumas and preventing incr’g levels of CO2 retention

o FIO2 of 0.5 or less preferred, as well as tidal volumes of no more than 4-6 cc/kg; tidal volumes may have to be decreased if need for PEEP incr’s, to avoid mrkd incr’s in peak inspiratory and mean airway P’s. peak plateau P should be maintained under 35 cm H2O, peak end-inspiratory P should be adjusted to inflection pnt, and hypercapnea up to a pCO2 of 90 mmHg or pH of 7.20 can be permitted. P-limiting ventilator modes should be used to achieve these goals

Ventilation Perfusion Abnl’s (Schwartz 7E p456; ICU Book 2E pp340-350)

- Xchange of O2 and CO2 in lung req’s open airways to facilitate ventilation of pulm alveoli. Perfusion of ppulm cap’s w/mixed venous blood deficit in O2 and carrying hi quantities of CO2 must accompany alveolar ventilation

- Mismatch of ventil’n to perfus’n, or V/Q mismatch is designated ‘shunt fraction’ or fraction of cardiac output that represents intrapulm’y shunt. In nl subjects, shunt fraction < 10% cardiac output

- Shunt fraction incr when small airways are occluded (asthma, chronic bronchitis); alveoli filled w/fluid (edema, PNA), alveoli collapse (atelectasis) or capillary flow xcessive (nonembolized regions of lung w/PE). Hi shunt fraction commonly ID’d as ARDS, where pulm alveoli collapsed and blood gas xchange mrkdly reduced d/t mismatch of ventil’n to non-perfused areas and perfusion of pulm alveoli which are collapsed and/or filled with transudates

- Arterial O2 tension falls progressively as shunt fraction incr, but aa CO2 tension remains constant until shunt fraction xceeds 50%. As intrapulmonary shunt incr from 10-50%, an incr in FIO2 produces less of increment in arterial PO2. When shunt fraction xceeds 50%, arterial O2 tension is independent of changes in FIO2. b/c of diminished influence of impaired O2 on arterial O2 tension in conditions w/hi shunt fraction, FIO2 can often be reduced to levels considered nontoxic w/o compromising oxygenation

- In normal lung, decr in vv PO2 have little effect in aa PO2. As shunt fraction incr, changes in vv PO2 begin to affect aa PO2. If shunt fraction reaches 100%, vv PO2 is sole determinant of aa PO2 in conditions w/hi shunt fraction, mixed vv PO2 is important in eval of hypoxemia

Nitric Oxide Inhaled Effect (Sabiston 16E pp98-99; Schwartz 7E p461)

- Nearly every cell type has capacity to synthesize NO from NO synthetase; L-arginine is sole substrate for NO synthetase. Effect of NO is thru guanate cyclase resulting in relaxation. NO has shrt ½ life of few sec’s or less d/t instability of molecules

- Small amnts of NO may act as NT and regulate relaxation of sphincters in GIT and (when released by vascular endothelium) results in vasodilatation thru relaxation of sm mm

- Inhalation of NO in small doses (0.01-20 ppm) has reduced pulm’y HTN and improved oxygenation in variety of pt’s. use of NO in ARDS pt’s has suggested response rate of 60-70%

Characteristics Extra Pulmonary Sequestration (Dail and Hammar, Pulmonary Pathology, 1988, pp53-55; Schwartz 7E p722)

- Xtralobar pulm sequestration is mass of pulm parenchyma (usually single pyramidal to round/ovoid lesion ranging from 0.5-15 cm in lrgst diameter) not connected to tracheobronchial tree that lies outside nl investment of visceral pleura. Felt develop from aberrant outpouching of foregut separate from nl lung outpouching

o Age: most freq’ly seen in 1st 6 mos of life (61%)o Sex: more freq’ly in males (3 or 4:1)o Location: in thorax (85%); b/w diaphragm and lower lobe (63%)

o Arterial supply: systemic aa (95%); aorta (80%); pulm a (5%)o Venous drainage: primarily systemic drainage (>80%); partial/complete pulmonary v

drainage (25%)o Associated anomalies (in 65%):

Diaphragmatic hernia (16%) Pulmonary hypoplasia (>25%) Bronchogenic cyst CV malformations Bronchopulmonary foregut connection Pectus excavatum

Characteristics Pulm Sequestration (Sabiston 17E pp2122-2123)

- Pulm sequestrations are lung malformations in which bronchial communic’n no exist; intralobular if w/I lung parenchyma; xtralobular if surrounded by separate pleural covering; frequently assoc’d w/abnl systemic blood supply, primarily systemic vessel arising from infradiaphragmatic aorta and located w/I inferior pulmonary ligament – true in 85% of intralobular sequestrations

- Aa supply often run w/I inferior pulmonary ligament and this is important when xcision considered

- Xtralobular sequestrations also have systemic blood supply, but aa usually arise from thoracic aorta or celiac axis

Conditions assoc’d w/hi O2 saturations (Sabiston 17E pp95-96)

- Long debated that pt in shock had better outcome if supernal O2 delivery achieved. w/o O2, these cells developed ‘debt’ and by hyperoxygenating the cells, they would work overtime to restore deficit. Based on eqn for delivery of O2, pt should be resuscitated w/blood transfusions and ionotropes should maximize CO. the studies testing effectiveness of supernormal delivery of O2 benefits have been inconclusive

- Clearly pt in shock needs their O2 satur’n maximized. Certain situations may req higher O2 sat’s as pulse ox is unreliable or falsely elevated (CO poisoning, methemoglobinemia). Any situation that shifts oxyHb dissoc’n curve to L which prevents O2 from being delivered at tissue level may require higher O2 saturation

CARDIAC:

Definition O2 Delivery (Sabiston 17E p619)

- O2 delivery (DO2) is volume of O2 delivered from hrt each min and calculated as product of CO and aa O2 content. O2 content of blood is sum of amnt of O2 bound to Hb plus amnt dissolved

in plasma O2 content is related to [Hb] and saturation of Hb w/O2 (SaO2). The amnt of O2 dissolved in plasma depends on O2 tension

- Thus in order incr O2 delivery an adequate Hb w/concentration above 10g will be advantageous and icnr’g O2 tension (incr’d FIO2) will be helpful. Similarly incr’g CO thru vol loading or inotropes may provide incr’d O2 delivery in situations where O2 demand maybe great

Dx Lo Cardiac Output (CO) – Schwartz 8E p97

- Clinical signs of low CO: hypotension, cool/mottled skin, depressed mental status, tachycardia, and diminished pulses. Cardiac exam may include dysrhythmia, precordial heave, or distal hrt tones. EKG and echo are confirmatory for dx

S/S of Aortic Stenosis (Sabiston 17E pp1890-1893)

- Acquired idiopathic AS is most common – assoc’d w/advanced age related calcification of aortic valves and immobility of leaflets. Rheumatic fever results in adhesion of commissures and leaflets leading to regurgitation and stenosis. Congenitally bicuspid aortic valves prone to develop AS in early adulthood

- These structural changes cause compensatory LV hyperplasia, loss of ventricular wall compliance, higher systolic ventricular P’s and longer ejection time…w/these changes, coronary blood flow is compromised and myocardial ischemia occurs. Sx’s may no occur until aortic valve area is about 1 cm^2 after which progression is rapid

- Principal sx’s of AS are:o Angina is usually earliest sx and assoc’d w/mean survival of 4-7yrso Syncope indicates survival < 3yrso Congestive hrt failure w/mean survival of 1-2 yrs

- Dx is confirmed by LVH on exam w/systolic murmur from base of hrt radiating into carotids, EKG notable for LVH and ischemia, CXR w/enlarged cardiac silhouette, and echo or cardiac cath demonstrating P gradient across aortic valve

Pulmonary Catheter Findings in RHF (ICU Book 2E pp160-164; Schwartz 7E p846; Schwartz 8E pp364-367)

- L-sided HF can result in fluid retention and pulm congestion, subsequently lead to pulm HTN and progressive RHF. Primary RHF occasionally results from RV injury and dysfxn or from primary tricuspid valve dz. RAP, normally <5-8mmHg, maybe elevated up to range of 15-30mmHg and sometimes higher; retention of >7-10lbs of fluid results in visible edema of BLE which almost always symmetrical. Jugulovenous distension (JVD) and hepatomegaly develop w/severe RHF. w/chronic severe failure, generalized fluid retention maybe acute, w/marked deformities from accumulation of 20+ lbs of edema fluid, ascites, and massive hepatomegaly

- Relationship b/w central vv P (CVP) and pulm cap wedge P (PCWP) can be used to distinguish LHF from RHF. Relationship b/w vascular filling P, CO (or stroke vol (SV)) and vasc resistance can provide similar info

- RHF: CVP above 10 mmHg; CVP > PCWP (or CVP = PCWP); high RAP (right atrial P); low CI (cardiac index = CO x BSA); high PVRI (peripheral vasc resistance index)

- LHF: PCWP >12mmHg; PCWP > CVP; hi PCWP; lo CI; hi SVRI (systemic vasc resistance index)

Tx of atrial fibrillation (Andreoli, Cecil Essentials of Clinical Med, 6E, pp121-124)

- A fib is MC sustained supraventricular tachyarrhythmia. Multiple reentrant loops circle thru both atria, create chaotic atrial depolarization and ineffective atrial contraction – results in ‘irregularly irregular’ ventricular contraction rate of 120-170 bpm. Classic EKG finding is loss of P waves w/irregular ventricular pattern – may occur as only cardiac abnl, but more common in presence of other cardiac dz (including HF, valvular hrt dz, and ischemic hrt dz)

- Roughly 1/3 of pt undergoing cardiac surgery will post op develop a fib. Pt w/persistent (paroxysmal or chronic) a fib are at risk for thromboembolic events as blood becomes static in atrial appendages and subsequently embolizes to rest of body

- 3 parts to tx of a-fib: (1) rate control, (2) prevention of complications from thromboembolus , (3) restoration and maintenance of normal sinus rhythm (NSR)

o HR can usually be controlled w/digoxin, beta-blockers, or calcium-channel blockers. Thromboembolic events can be prevented w/anticoagulation therapy (warfarin to maintain INR b/w 2 and 3)

o Restoration of NSR can be obtained either pharmacologically or electrically and is most effective/safest in pt w/less than 48-72h of sustained a-fib. Pharmacologic methods include class IA antiarrhythmics, class IC, and class III. Electric means of rate control include catheter ablation of AV node and pacemaker implantation

VASCULAR:

Blood Flow control peripheral vessels (Schwartz 8E pp88-90)

- Hemodynamic physiology based on Ohm’s law, which describes relationship of P, flow, and resistance: P = flow x resistance

- Clinically, this law can be translated into following eqn: MAP = CO x SVR perfusion necessary to provide adequate tissue oxygenation is based on cardiac output and systemic vascular resistance (SVR)

- Effects of blood flow on peripheral vessels best demonstrated in microcirculation. Shock causes profound changes in tissue microcirculation – 2 examples seen in hemorrhage and sepsis. After hemorrhage, lrgr arterioles vasoconstrict d/t sympathetic stimulation while smaller, distal arterioles dilate, d/t local cellular mech’ns

- In sepsis, these same microcirculation changes occur. Difference b/w hemorrhage and sepsis is correction of hemodynamic parameters and O2 delivery and consumption restores tissue oxygenation; however in sepsis tissue dysoxia persists

CV Effects of Nitric Oxide (NO) – Schwartz 8E pp20-23

- Endogenous NO acts thru stimulation of soluble guanylate cyclase (enz which forms cyclic GMP) – cGMP then activates pr kinases which lead to dephosphorylation of myosin light chains and mm relaxation. This rxn dependent on presence of L-arginine and occurs in variety of cell types (endothelial cells, neutrophils, M0’s, cerebellar neurons, renal cells, and Kupffer cells)

- NO release leads to release of EDRF (endothelium derived relaxation factor) – this sequence countered by potent endothelial products (known as endothelins). Prostacyclins synergistically enhance vasodilatory effects of EDRF and NO

- NO serum [ ] elevated in endotoxin mediated sepsis (condition characterized by lo SVR). b/c NO is produced in so many diff’nt cell types, believed serve wide spectrum of cellular fxns – currently known that NO mediates hepatic cell pr synthesis and electron transport w/I hepatocellular mitochondria

Characteristics Blood Circulation (Schwartz 8E p88)

- Preload o Majority of blood vol is w/I vv system at rest. Venous return to hrt generates ventricular

end-diastolic wall tension. When decr’d aa inflow occurs, there’s active contraction of vv sm mm and passive elastic recoil in thin walled systemic vv. This results in incr’g vv return to hrt and maintaining ventricular filling

o Normal circulating blood vol maintained w/I anrrow limits by kidneys. Kidney’s ability to manage salt and water balance thru local hemodynamic changes and hormonal effects of renin, ANG, and ADH will maintain circulating blood vol

- Ventricular contraction: frank starling curve describes F of ventricular contraction as fxn of preload; curve based on myocardial fiber length and strength

- Afterload: resistance against which hrt mm contracts. Aa P is major component of afterload influencing ejection fraction; vascular R is based on precapillary sm mm sphincters and blood viscosity

Dx of Neointimal Hyperplasia (Rutherford, Vascular Surgery, 6E, pp149-165)

- Intimal hyperplasia defined as abnl migration/proliferation of vasc sm mm cells w/assoc’d deposition of EC CT matrix which is followed by remodeling of this new tissue; macroscopically, intimal hyperplasia appears firm, pale, and homogenous. Involved area is smooth and uniformly located b/w endothelium and internal elastic lamina of aa. Surgical pathology and dopler U/S are vascular modalities for dx

Enz MC Assoc’d w/AAA (Schwartz 8E p733)

- AAAs frequently involve atherosclerotic plaque, but mounting research currently supporting multifactorial etiology; of note, there has been shown xpanding loss of elastin fibers in AAAs (abd aortic aneurysms). Typical aorta composed of approx 12% elastin, but aneurysmal aortas

contain 1%. Proteolysis and infl’n have been deemed predominate F’s in this elastin loss. Proteolysis has been linked to incr’d metalloprotease activity

Etiology of Renovasc’r HTN (Rutherford 6E pp1766-1767; Sabiston 17E pp2017-2019)

- Renovasc HTN (RVHTN) is entity in which BP elevation caused by hypoperfusion of kidney. Over 90% of cases d/t atehrosclerosis of renal a followed by fibromuscular dysplasia. When occlusion xceed 60% diameter of main renal a, changes in P and flow distally result in incr’d secretion of renin and subsequent shifts in peripheral vasoconstriction and ECF vol causing HTN. <3% of HTN can be attributed to this etiology

- Diminished mean aa P (MAP) sensed by renal baroR’s in afferent arteriole causes renin release by juxtaglomerular apparatus; renin hydrolyzes angiotensinogen in liver to form ANG-I; ANG-I converted to ANG-II via ACE in lungs. ANG-II acts directly on vasc sm mm as potent vasoconstrictor and facilitate formation of aldosterone in adrenal cortex. Aldosterone stim conservation of salt&water by kidney

- ANG-II mediated Na retention incompletely counteracted by icnr’d GFR and natriuretic response by opposite intact kidney; HTN progresses over time b/c of sustained incr in PVR. Hemodynamic and hormonal responses stim’d by ANG-II + its direct effects on vascular endothelium, result in LVH and vasc hyperplasia

- Absence of R kidney or bilateral renal a stenosis eliminates compensatory P-induced natriuresis. This condition results in severe HTN from combined effects of vol xpansion and peripheral vasoconstriction

Hypoxemia-Assoc’d changes in vasc tone (Fishman, Pulm Dz and D/o 3E p1245; Simmons and Steed, Basic Science Review for surgeons, pp169, 217-218)

- Acute hypoxemia stim vasoconstrictor center in upper medulla and lower pons. Epinephrine and NE released from hypoxic tissue as well as adrenal medulla; this symp response selectively restricts blood Q to non-vital areas (skin, splanchnic bed, and to lesser xtent mm) Blood Q to hrt, brain, and kidney preserved. Pulm vasc bed constricts in response to acute hypoxemia

MC Location Of Splanchnic Artery Aneurysm

- Splanchnic a aneurysms are uncommon, but 8.5% result in death. Involved aa and their relative frequencies are splenic (60%), hepatic (20%), SMA (5.5%), others < 5% each

- Splenic a aneurysms occur most freq’ly in females – MC etiology being degenerative atherosclerosis; hi splenic a flow is important etiology frequently result of portal HTN. Medial dysplasia assoc’d w/renovasc HTN and polyarteritis nodosa another cause; pancreatitis and septic emboli are most freq’nt causes of mycotic false aneurysms

- Aneurismal rupture is most frequent complication and can present w/hypotension, hemorrhagic shock, and LUQ pain. May initially be contained w/I lesser sac, though can occur in peritoneal cavity proper, GIT, pancreatic duct, or splenic v; women of child-bearing age particularly hi risk of death from rupture during pregnancy and should undergo elective repair

o Aneurysm >2cm and sx or ruptured aneurysms warrant immed repair

- Percutaneous emboliz’n of splenic a is most frequently applied therapy. Open surgical splenectomy is rarely needed, but prox and distal surgical ligation w/open surgery or laparoscopy are good tx options

Pathophysio of renovasc HTN (Sabiston 18E p1969)

- HTN occurs when renal a diameter is decr’d by grtr than or equal to 60%. Renal baroR’s in afferent arterioles sense decr in P, which stimulate juxtaglomerular apparatus (JGA) to secrete renin. Renin then hydrolyzes angiotensinogen (liver) to form ANG I. ANGI then converted by ACE to ANG II in lungs

- ANG II has 2 important effectso Alone it’s potent vasoconstrictor on vasc sm mm (which incr BP)o Stimulates aldoseterone in adrenal cortex incr in aldosterone encourage Na and H2O

retention which works to incr intravascular fluid volume, worsening HTN

Site of Lowest O2 Saturation of Blood (Sabiston 18E; Miller, Modern Surgical Care, 2E)

- Coronary circulation possesses 2 unique features:o Hi degree of O2 xtraction at baseline so hrt can adjust to changing O2 needs by only

small increment in O2 xtractiono Incr’g O2 req’s must be met by proportionate incr in coronary Q

- Myocardial O2 xtraction in particular that of LV is grtr than any other tissue in body- Network of vv drain coronary circulation and vv circulation can be divided into 3 systems:

coronary sinus and its tributaries, ant RV vv, and thebesian vv- Coronary sinus predominantly drain LV and receives 85% of coronary vv blood. At 20-30%,

coronary sinus O2 saturation lowest in blood circulat’n

Non-Disabling Claudication (Schwartz pp961-963)

- Non-operative mgmt indicated in pt w/mild claudication and tx regimens include cessation of tobacco use and institution of daily program of regular exercise. Vasodilators including CCBs, have been used w/limited success. Pentoxifylline may reduce sx’s of claudication by improving tissue perfusion, although randomized studies yet to be completed

HAND & ORTHOPEDIC:

Anatomy Anterior Compartment Calf (Schwartz 8E p763)

- Anterior compartment of lower xtremity includes following:o Anterior tibial a and vo Deep peroneal no Peroneus tertiuso Extensor digitorum longus

o Extensor hallicus longuso Tibialis anterior

- Clinically this compartment is important b/c ant compartment is most commonly affected in compartment syndrome. Numbness in web space b/w 1st and 2nd toes is d/x’c d/t compression of deep peroneal n

Carpal Tunnel Syndrome (CTS) – Schwartz 8E pp1766-1770

- CTS results from incr’d P w/I rigid carpal canal causing median n ischemia and dysfxn. Incr’d P can be attributed to tenosynovitis, collagen, amyloid, edema, and space-occupying lesions (lipomas), bone abnl’s of radius or carpals, and posttraumatic hematomas

- Sx’s include paresthesias and numbness in radial 3 ½ fingers and later in course hand weakness/awkwardness from thenar atrophy. Focal wrist and hand pain are NOT prt of CTS, while nocturnal sx’s as listed are hallmarks

- Dx of CTS is clinical. PE will elicit carpal tunnel sx’s w/direct P over median n in carpal canal w/I 30 sec. Phalen test (gravity induced wrist flexion) will induce sx’s w/I 1 min and Tinel’s sign (percussion of n) produce paresthesias in distribution of median n. electrophysiologic studies provide confirmatory info and should be performed b4 surgery

- Tx includes splints, NSAIDs, and operative division of transverse carpal ligament

Etiology of Wrist Drop Assoc’d w/upper xtremity fx (Sabiston18E p554; Greenfield 4E p1994; Chapman, Orthopedic Surgery 3E p464)

- w/distal-third humeral fx, radial n is at risk, its injury can cause wrist drop as radial n supplies xtensor mm to wrist

Dx Scaphoid fx (Greenfield 2E pp2158-2159)

- carpal bones are 8 in number and arranged in 2 rows. Proximal row consist of scaphoid (navicular), lunate (semilunar), and triquetral bones; distal row consist of trapezium (grtr multiangular), trapezoid (lesser multiangular), capitates, and hamate

- scaphoid is most common fx’d carpal bone and can often be complicated by nonunion and avascular necrosis d/t its distally based blood supply

- dx of this fx should be suspected in individuals who have fallen on outstretched hand and present w/pain localized to radial aspect of wrist. Initial xrays often neg mgmt of suspected scaphoid fx should include placement of lng arm thumb cast and repeat xrays in 2wks to confirm/dispute presence of fx

Dx Compartment syndrome in xtremity (Schwartz 7E p206)

- compartment syndrome can occur anywhere in xtremities and pathophysiology is an acute incr in P in closed space which impairs blood flow to structures within. Causes of compartment syndrome include arterial hemorrhage into compartment, vv ligation or thrombosis, crush injuries, infections, and mm swelling following lng periods of ischemia followed by reperfusion

- Pain is prominent sx in conscious pt. active/passive motion of involved xtremity incr pain. Progression to paralysis can occur. The most frequent site is anterior compartment of leg, early signs of which are paresthesias and numbness b/w 1st and 2nd toes caused by P on deep peroneal n

- In unconscious pt, compatible hx, firmness of compartment to palpation, and diminished/absent pulse should suggest compartment syndrome. Compartment P’s can be measured using small handheld Stryker manometer. P’s >45mmHg usually req operative intervention; P b/w 30 and 45mmHg should be carefully eval’d and watched closely

- A 4-compartment fasciotomy req’d in lower xtremity, which is most freq’ly involved w/compartment syndrome

NEUROLOGY:

Glasgow Coma Score in Closed Head Injury (Sabiston 18E p483)

- Be able to calculate a pt’s GCS in clinical scenario- Eye Opening

o 1 no responseo 2 to painful stimuluso 3 to verbal stimuluso 4 spontaneous

- Best Verbalo 1 no responseo 2 incomprehensible speecho 3 inappropriate wordso 4 disoriented, inappropriate contento 5 oriented and appropriate

- Best Motoro 1 no responseo 2 abnl xtension (decerberate)o 3 abnl flexion (decorticate)o 4 withdrawalo 5 purposeful movemento 6 obeys commands

- TOTAL = 3-15- Motor is most important determinant of prognosis- GCS ≤ 8 intubate

Signs of Incr’d Intracranial P (ICP) – Cameron 8E pp922-925; Sabiston 18E pp485-487, 2093-2094

- Neurological exam includes GCS, which ID’s pt level of consciousness

o Mild injury considered GCS 14-15o Mod injury GCS 9-13o Severe injury GCS 3-8o GCS exam should be repeated serially, as decrease of even 1 or 2 pnts in GCS score

indicate change in neurological statuso Most important factor in GCS scoring is motor fxn, which correlates most strongly w/pt’s

prognosis- ‘lateralizing signs’ or unilateral/asymmetric signs also indicator of decr’g intracranial fxn.

Unequal pupil size is mrkr of intracranial injury. Usually side of lrgst pupil is side of brain injuryo Also check for lateralized motor fxno Any of above makes emergent CT scan of head necessary

- As ICP increase even more, pt will lose brainstem reflexes such as corneal reflex, vestibule-ocular and oculocephalic reflexes. Pt will progress from flexor posturing to extensor posturing

- w/even further increase in ICP pt’s will lose their respiratory drive and show Cushing’s reflex (bradycardia, widening of pulse P, incr’d SBP). This will then progress to foramen magnum herniation

GENITO/URINARY:

Metastasis in Germ cell Tumors of Testis (Wein, Campbell-Walsh Urology Online, 9E, Ch29; Sabiston 18E p2282)

- germ cell tumors account for 95% of testicular ca’s and of germ cell tumors seminomas are most common

- tumors present as nodule or painless swelling of one testicle…check AFP and beta-HCG- 1st place of met’s is retroperitoneal LNs (periaortic)

Characteristics of Testicular Ca (Sabiston 17E pp2311-2314)

- Testicular ca is MC malignancy in men 15-35 yoa. Testicular tumors present as nodule or painless swelling of 1 testis.30-40% of pt c/o dull ache or heavy sensation in lower abd, perianal area, or scrotum. 10% present w/acute pain and 5% of men have gynecomastia

- Mrkrs of testicular ca include AFP and b-HCG and should be measured by radioimmunoassay b4 surgery in all pt w/testicular ca

o Embryonic cell components will elevate AFP levels while choriocarcinomatous elements secrete b-HCG. In non-seminomatous tumors, 1 or both of these mrkrs will be elevate in approx 90% pt’s. in seminoma, b-HCG will be hi in approx 10%. These mrkrs best used to monitor recurrence after tx w/orchiectomy, retroperitoneal node dissection, or chemo

o f/u should be at 3 mos intervals for 3 yrs and should include CXR, AFP levels, b-HCG levels, and PE

o hi mrkrs at presentation (b-HCG > 8000, AFP >1000) and failure of markers to normalize are ominous px’c signs

OBSTETRICS & GYNECOLOGY:

RFs Endometrial Ca (Schwartz 8E p1586)

- RF for endometrial ca: obesity, DM, HTN, lo parity, early menarche, estrogen replacement or supplementation w/o concurrent progestational agents, and late menopause

C-Diff Colitis in Pregnancy (Mandell, Bennett, and Dolin, Principles and Practices of Infectious Disease 6E pp423, 1258)

- Vanco maybe used treat C diff colitis during preg’y- PO form is most effective delivery mech’n – can be given PR in cases of severe ilieus. Only small

fraction of PO vanco is absorbed leading to lo levels of transmission to fetus- Parenteral or PO metronidazole is considered 2nd line Rx

SKIN & LYMPHATICS:

Anatomy Thoracic Duct (Sabiston 17E pp1093-1094)

- Thoracic duct forms at confluence of cisterna chili at level of T12 and L2 and on R side of abd aorta. Duct enters post mediastinum thru aortic hiatus at level of T10-12; continues cephalad on ant surface of vertebral column b/w aorta and azygous v and behind esophagus.

- At T4/T5, duct crosses to L of spine, pass under aortic arch, and continue along L side of esophagus to ascend into neck post’r to L subclavian a. thoracic duct enters vv system at jxn of L subclavian and L internal jugular vv

Precursors Skin Malignancy (Sabiston, Textbook of Surgery 15E; Rose LC. Recognizing Neoplastic Skin Lesions: A Photo Guide. Am Fam Physician 1998 Sep 15; 58(4): 873-84)

- These are several known precursors of cutaneous malignancieso Melanoma: nevi, especially in dysplastic nevus syndromeo SCC: actinic keratosis, keratoacanthoma, Bowen’s dz (SCC in-situ)o BCC: none

Characteristics of Toxic Epidermal Necrolysis (TEN) – Habif, Clinical Dermatology 4E

- Fever is MC prodromal sx; sx’s suggestive of URI preceding skin lesions by 1-2 wks and stomatitis, conjunctivitis, and pruritus occurring 1-2d b4 rash. TEN begins w/diffuse, hot erythema that becomes painful and ultimately results in epidermal separation from dermis. Infl’n and blistering of mucosal membr’s is characteristic

- Conjunctival involvement is constant feature and bronchial involvement (occur in 27% pt’s) is poor px factor

ENDOCRINE:

Tx of Gastrinoma (Fauci Harrison’s Principles of Int Med 17E Ch344; Sabiston 17E pp1014-1015)

- Gastric acid hypersecretion d/t gastrinomas can be usually controlled by PO gastric antisecretroy drugs. b/c of lng duration of action and potency, slowing 1-2x per day dosing, PPIs are drugs of choice; histamine H2-R blockers are also effective – higher/more frequent dosing (q4-8h) often req’d

- In pt w/MEN I w/hyperparathyroidism correction of hyperparathyroidism incr Sn to gastric antisecretory drugs and decr basal acid output

- w/incr’d ability to control acid hypersecretion, >50% of pt’s who are not cured (>60% of pt’s) will die from tumor-related causes. 1/3 of pt present w/hepatic met’s and in <15% of those w/hepatic met’s the dz is limited so surgical resection maybe possible. Surgical cure is possible in 30% of pt w/o MEN-1 or liver met’s (40% all pt’s)

- in pt’s w/MEN-1, lng-term surgical cure rare b/c tumors multiple, freq’ly w/LN met’s all pt w/gastrinomas w/o MEN-1 or medical condition limiting life expectancy should undergo surgery

- if surgery is indicated the highest yield in search for gastrinoma is in gastrinoma triangle. Entire pancreas should be thoroughly eval’d by mobilizing spleen to visualize tail and mobilizing head w/wide Kocher maneuver

Mech’ns of Gastrin Suppression (Schwartz 8E Ch25)

- Gastrin produced by antral G cells and is major hormonal stimulant of acid secretion during gastric phase of digestion. Luminal peptides and AAs are most potent stimulants of gastrin release and luminal acid is most potent (-)r of gastrin secretion. (-)n of gastrin predominantly mediated in paracrine fashion by SS released from antral D cells. Gastrin-stimulated acid secretion is significantly blocked by H2-antagonists, suggesting that principal mediator of gastrin-stimulated acid production is histamine from mucosal enterochromaffin-like (ECL) cells

Anatomy of Parathyroid glands (Sabiston 18E p957)

- Usually 4 parathyroid glands, lie on posterior surface of thyroid. Superior glands normally near tracheoesophageal groove and inferior Parathyroids below inferior thyroid a (or ectopic)

- Superior PTs arise from 4th branchial pouch and inferior PTs descend from 3rd branchial pouch together w/thymus – classically all PTs receive blood supply from inferior thyroid a

- Ectopic PTs can be found: tail of thymus, superior thyroid poles, trachea-esophageal space, and carotid sheath

Primary Hyperparathyroidism (Sabiston 17E pp987-989)

- MCC of hypercalcemia in non-hospitalized pt- In hospital setting, it’s 2nd MCC of hypercalcemia – only pt w/ca w/met’s to bone have grtr

prevalence of elevated serum calcium [ ]’s. most pt w/primary hyperparathyroidism are ID”d d/t common use of multiphasic chemical blood screen tests – many of these pt have subtle or even profound sx’s of fatigue, weakness and depression, polyuria, polydipsia, arthralgia, and constipation when questioned in detail

- Pt’s w/renal stones, bone dz (osteitis fibrosis cystic), peptic ulcer, pancreatitis, and in pt w/MEN syndrome and HTN should be closely assessed for hypercalcemia

- Dx: dx of primary hyperparathyrodism is usually made by findings of persistent elevated serum calcium levels assoc’d w/elevated PTH concentrations

- Special note:o Hypercalcemia assoc’d w/malignancy and bone met’s has been shown be d/t osteoclast

mediated bone reabsorption – mech’n occurs in myeloma and metastatic breast cao Ectopic PTH causing hyperparathyroidism – MC source is SCLC and SCC of lung or H&N

and hypernephromas – in add’n to PTH secretion, these tumors often secrete other humeral factors (PGE2) – ectopic hyperparathyroidism more likely when serum calcium concentration xceed 14 mg/dL when serum alk phosphates activity increased and when there’s significant degree of anemia

Pheochromocytoma, Dx of (Sabiston 17E pp1052-1057)

- Dx of pheo is commonly initiate b/c of uncontrolled HTN – HTN is episodic and assoc’d w/anxiety attacks, paroxysmal HAs, palpitation, and diaphoresis

- Dx established w/24h urine collection for catecholamines, metanephrine, and vanillylmandelic acid (VMA) – VMA has grtst Sp (97%) and best Sn (91%). 24h urine collections more SN than plasma levels d/t episodic release of catecholamines from tumor. NE more commonly found w/xtra adrenal pheo’s whereas epinephrine more common w/adrenal tumors. Clonidine suppression test can be helpful establishing dx when catecholamines only mildly elevated

- CT scan and MRI effective in localizing tumor. The I-labeled metaiodobenzylguanidine (MIBG) scan is safe noninvasive nuclear medicine imaging study which can be used for localization of the pheochromocytoma (pheo)

Serum values in primary hyperparathyroism (HPT) – Sabiston 17E pp987-989

- Dx of primary HPT made in conjxn w/elevated serum Ca concentration in add’n to elevated serum intact PTH. Elevated serum intact PTH no establish dx alone – evaluated as fxn of serum Ca concentration in that elevations in both serum Ca and PTH establish dx of HPT – ½ of these pt’s also have hypophosphatemia – d/t effect of PTH on bicarb xcretion in kidney, pt will also have hypochloremic metab’c acidosis. 10-40% of pt will have elevated alk phos which indicate some element of bone dz

Dx and Tx of Thyroiditis (Sabiston 17E pp957-958)

- Acute suppurative thyroiditis

o Xtremely rare and usually result of severe pyogenic infection of upper airwayo Assoc’d w/severe localized pain and usually unilateralo Tx involves abscess drainage and Abx w/minimal lng term effects on thyroid fxn

- Subacute Thyroiditiso Also known as granulomatous thyroiditiso Occurs in yng women following URI or viral infectiono Sx of malaise, pain, and thyroid enlrgmnto Thyroid is tender to palpationo Dx studies are unnecessaryo Dz is self limiting w/a few wkso Tx consists of salicylates for sx’c relief

- Hashimoto Dzo Chronic lymphocytic thyroiditiso Commonly found in middle aged womeno Assoc’d w/defective thyroid hormone synthesis which results in goitero Goiter is as/x’c and rubbery hard to palpationo Tx consists of thyroid hormone replacement*o Occasionally thyroidectomy indicated to relieve tracheal compression or for cosmetic

reasonso MCC of spontaneous hypothyroidism in adults

- Reidel Strumao Rare fibrotic process which involves thyroid gland and strap mm of necko Process maybe assoc’d w/pain d/t compression of adjacent tissueso Tx may require resection of thyroid isthmus and as much of fibrotic process as possible

while preserving recurrent laryngeal nno Thyroid hormone replacement freq’ly needed

- *Hashitoxicosiso Mild thyrotoxicosis assoc’d w/Hashimoto’s dz – rare finding and especially noted in

acute phase of dz when there maybe xcessive release of thyroid hormoneo This phase self-limiting and can be managed w/antithyroid drugs or propranolol

Mech’n of Calcitonin (Hedge, Clinical Endocrine Physiology, 1987)

- Calcitonin is hormone produced by parafollicular cells or C cells of thyroid gland – calcitonin is a 32 AA polypeptide and all 32 AAs req’d for significant activity

- Action of calcitonino On bone

Acutely it decreases plasma calcium levels by decreasing calcium efflux across osteoblast-osteoclast bone membr

Chronically it (-)s bone resorption by (-)g osteoclastso On GIT

(-) gastrin secretion- Metabolism – kidneys are primary site of metabolism, but it’s also metabolized by liver

o Hypercalcemia calcitonin release decrease in serum calciumo Elevated serum calcitonin levels assoc’d w/medullary thyroid carcinoma occurring

sporadically or familial (MEN-II syndrome)

BREAST:

Anatomy of Axillary Dissection (Sabiston 18E pp851, 878)

- Node levels:o I = lateral to pec minor mmo II = under pec minor mmo III = medial to pec minor (include subclavicular nodes)o Rotter’s Nodes: b/w pect major and pec minor

- Ideally level I and II nodes taken during axillary dissection

Histology assoc’d w/subsequent breast ca (Sabiston 17E p881)

- Breast ca occurring subsequent to initial dx of breast ca typically will present as same histological type as original ca – w/ductal carcinoma in situ (DCIS), subsequent breast ca usually present as invasive ductal ca. breast ca developing subsequent to dx of lobular carcinoma in situ (LCIS) will be histologically invasive ductal ca (50-65%) or invasive lobular ca (35-50%). LCIS is not breast ca but rather histologic mrkr for incr’d breast ca susceptibility

- Fibrocystic changes are spectrum of histologic changes – include mild-mod hyperplasia which no appear to increase woman’s risk of breast ca – proliferative lesions can be divided into atypical epithelial hyperplasia or those w/o atypia. RR of pt w/atypical ductal or lobular hyperplasia is 4.4x risk of developing breast ca as control population

Characteristics of Phylloides Tumor Breast (Sabiston 17E p914)

- Phylloides tumor = MC neoplasma of non-epithelial origin in breast, comprises <1% of all breast neoplasms

- Phylloides tumor present as painless mass – pt may have hx of recent enlrgmnt of stable nodule which may attain huge size w/prominent vascularity and thinning of overlying tissue. Skin fixation, edema, and axillary involvement are rare. This tumor is encountered most often in women b/w 30-40 yoa but may occur at any age

- b/c it arises in lobar elements, it’s nonexistent in males – it’s well circumscribed and looks much like fibroadenoma on mammogram and can’t be distinguished from fibroadenoma by U/S. met’s occur in 20% of malignant lesions and in <5% of b9 lesions clinical behavior difficult to predict

- pathologically tumors are well circumscribed brownish in color. Differentiation of b9 from malignant by histology maybe difficult but metastatic dz develops only rarely

- tx consist of xcision w/1 cm margin of nl breast tissue. Formal axillary dissection unnecessary. Most phylloides tumors spread hematogenously. Total mastectomy reserved for lrg lesions which can’t be excised w/o cosmetic deformity or for recurrences following previous local xcisions

Px factors in breast Ca (Doherty Current Surgical dx and tx 12E p320-321)

- stage of breast ca is most reliable indicator of px- most favorable px is seen in dz localized to breast w/no regional spread- axillary LN status is best px factor and correlates w/survival at all tumor sizes- estrogen and progesterone R are px variables in that pt w/hormone R neg tumors have much

higher recurrence rate than pt w/hormone R pos tumors- flow cytometry of tumor cells to analyze DNA index and S phase frequency also aid in px in add’n

to HER-2/neu oncogene amplification, epidermal growth factor Rs, can cathepsin D- no marker is as strong px factor as LN met’s

Px factors in tx of invasive breast ca (Sabiston 17E p890, Doherty Current Surgical dx and tx 12E p309)

- breast ca arise from either epithelial lining of lrg or intmd sized ducts or from epithel’m of terminal ducts of lobules. Histologic subtypes of invasive breast ca only sl px indicator – these parameters include invasion of bv’s, tumor differentiation, invasion of breast lymphatics, and tumor necrosis – these histologic parameters seem to have very little px value compared w/accurate staging

- infiltrating ductal ca is MC form of ca and carries w/it worst outcome. Infiltrating lobular and pure medullary ca’s carry intmd px. Tubular and mucinous ca’s are least clinically aggressive ca’s. factors like tumor size, grade, and R status are what help determine px of invasive breast ca. there are many xceptions

PEDIATRICS:

MC type of esophageal atresia (Schwartz 8E Ch38)

- 5 major varieties of esophageal atresia (EA) and tracheoesophageal fistula (TEF)o Isolated EA (type A)o EA w/TEF b/w proximal segments of esophagus and trachea (type B)o EA w/TEF b/w distal esophagus and trachea (type C)o EA w/fistula b/w both proximal and distal ends of esophagus and trachea (type D)o TEF w/o EA (H-type fistula) – Type E

- Most commonly seen variety is EA w/distal TEF which occurs in approx 75-85% of the timeo Next most frequent is pure EA (type A) – occur in 8-10% of pt’s followed by TEF w/o EA

(type E), this occurs in 5-8% of cases and also is referred to as an H-type fistula based on anatomic similarity to that letter

o EA w/fistula b/w both prox and distal ends of esophagus and trachea (type D) is seen in approx 1-2% of cases and type B (EA w/TEF b/w prox segments of esophagus and trachea) is seen in approx 1% of all cases

MISCELLANEOUS:

Next of Kin and Legal Consent (Sabiston 17E p22)

- Consent – defined as permission, granted by pt to surgeon to make dx or therapeutic intervention on pt’s behalf. Consent must be informed to be valid all relevant info must be provided to pt. moreover it must be voluntary (as free from coercion as possible) noting that pt’s condition may in itself be inherently coercive. Surgeon’s role is to provide pt sufficient info to make decision about what course to follow – this includes risks, benefits, and alternative, while avoiding extraneous details. To be able to differentiate b/w what’s pertinent and what’s not requires sound judgment

- Next of kin – pt’s closest relatives. Although usually defined by state law, most states recognize spouse and immed blood relatives as next of kin

Source of Medication Error (Schwartz 8E pp335-336; Medmarx, USP Quality Review, No 81, Issued September 2004)

- Communication failures/losses – most important component when errors/complications occur in health care. Documentation now considered essence of hi quality pt care. Orders need to be promptly and clearly written in order to minimize confusion. Any unclear orders shouldn’t be interpreted or carried out w/o further clarification

- MEDMARX along w/FDA and US Pharmacopeia is nat’l reporting system for medication errors – last looked at data in report produced in 2004 and found that #1 cause of medication error is improper dose/quantity

Tx of Elder Abuse (Andreoli, Cecil Essentials of Clinical Medicine, 6E, p1104)

- Elderly pt often dependent on their social support resources for daily care and tx of their medical needs – these support services range from spouses to kids and other fam members, friends, to residential communities and nursing homes

- Social work referrels can help doc plan for and meet needs of elderly pt’s and can also help ID cases of elder abuse & neglect. These suspicions must be reported to local investigational organizations (adult protective services). Doc’s should consider warning signs of elder abuse including multiple rib fx’s in diff’nt stages of healing, burn marks, and laceration/abrasions

Characteristics of PET scan (Braunwald, harrison’s principles of internal medicine, 16E, pp1506, 2355)

- Positron emission tomography (PET) detects positrons emitted during decay of radionuclide that has been injected into pt. analogue of glc (2-[18F] fluoro-2-deoxy-D-glc (FDG)) is most freq’ly

used moiety – taken up by cells competitively w/2-deoxyglc. After 45-60 min, multiple images of glc uptake activity formed. Images reveal differences in regional glc activity among nl and malignant cells. Tumor cells have incr’d uptake and metabolism of glc and will therefore light up on PET scan

- PET scanning being used w/incr’g freq’y to eval and detect solitary tumors and metastatic dz