Clinical Management 2 FINAL EXAM

Hypovolemic Shock

1. absolute hypovolemia: loss of intravascular fluid volume Causes: -hemorrhage -GI loss (vomiting, diarrhea) -fistula drainage -diabetes insipidus -hyperglycemia -diuresis 2. relative hypovolemia -results when fluid volume moves out of the vascular space into extravascular space (interstitial or intracavitary space) -third spacing Patho: -decrease in circulating volume -decrease venous return -decrease stroke volume and CO -decrease in cellular oxygen supply -decrease in tissue perfusion -IMPAIRED CELLULAR METABOLISM AND ORGAN FAILURE Response to acute volume loss depends on -extent of injury or insult -age -general state of health CM -anxiety -tachypnea -increase in C0, HR (initially) -(eventually leads to) decrease in SV, PAWP (swan catheter pressures), UO -if loss if >30%, blood volume is replaced.

Cardiogenic Shock

-systolic or diastolic function -compormised cardiac output Causes: -MI -cardiomyopathy -blunt cardiac injury -severe systemic or pulmonary hypertension -cardiac tamponade -myocardial depression from metabolic problems Patho: -all shock leads to impaired tissues perfusion leading to IMPAIRED CELLULAR METABOLISM and ORGAN FAILURE 1. systolic dysfunction -structural problems -dysrhythmias -primary ventricular ischemia 2. leads to decrease stroke volume and cardiac output 3. Diastolic dysfunction leads to ineffective filling which increase pulmonary pressures leading to pulmonary edema and a decrease in oxygenation 4. SPB & DBP lead to decrease in cellular oxygenation, tissue perfusion and IMPAIRED CELLULAR METABOLISM AND ORGAN FAILURE Early Manifestations -tachycardia -hypotension -narrowed pulse pressure -increase myocardial 02 consumption

Biochemical Changes in Cancer

1. Abnormal glycolysis 2. Loss of "self-antigen" 3. Loss of fibronectin and glycoproteins 4. Production of surface enzymes (allows for breaking and entering and other cells are imparied) 5. Production of tumor associated antigens

Trauma

- the 4th leading cause of death for ALL ages -nearly 1/2 of all traumatic incidents involve the use of alcohol, drugs, or other substance abuse -predominantly a disease of the young and carries potential for permanent disability -more males impacted than females Levels of Trauma Care -trauma center determined at STATE level, which sets criteria for categorization -facilities are designed as Adult and/or Pediatric Trauma Center. It is not uncommon for facilities to have different designations fro each group. -Level 1 is a comprehensive regional resource that is a tertiary care facility. They are affiliated with medical school, have everything and opened 24/7 -Level 2 is all to initiate definitive care for all patients but does not have all the specialties all the time -Level 3 has the ability to provide prompt assessment, resuscitation, surgery, critical care and stabilization of injured patients and emergency operations. Limited staff. Like a typical hospital -Level 4 has the ability to provide advanced trauma life support (ATLS) prior to transfer. -Level 5 boonies; enough to get the process going but not enough to keep the ball rolling. Trimodal Distribution of Death 1. first peak: seconds to minutes from time of injury to death -severe injuries, lacerations of the brain, brainstem, high spinal cord, heart/aorta, large blood vessels. 2. Second peak - minutes to several hours -subdural, epidural hematomas, hemos-pneumothorax, ruptured spleen, lacerated liver, pelvic fractures, other injures associated with major blood loss. 3. Third peak occurs several days to week after the initial injury -most often the result sepsis and multiple organ failure -at this stage, outcomes are affected by care previously provided. -The golden hour= 80% of trauma deaths int he first hour after injury -rapid trauma care has greatest level of impact in these patients. Pre-Hospital Care and Transport -the time from injury ton definitive care is a determinant of survival, particularly those with major internal hemorrhage. -Careful attention must be given to the airway with cervical spine immobilization, breathing and circulation. ABC + full spinal mobilization = primary survey -full spinal mobilization is being challenged and reexamined -Additonal interventions may include (occlusive dressings to open chest wound, needle thoracotocotomy to relieve tension pneumothorax (14 g in 4th and 5th intercostal), endotracheal intubation, criothyromy) Cricothyroidotomy - in-between the thyroid and cricoid cartilage, horizontal incision in the cricothyoidmembrane Traceomety - more long term placement Prehospital care and transport: Spine Precautions -protect the entire spinal cord until injury has been excluded by radiography or clinical physical exam in patients with potential spinal cord injury. Spinal Protection -rigi cervical spinal collar = cervical spine -long rigid spinal board or immobilization on flat surface such as a stretcher (literature is proving controversial) Clinical insight -treatment (immobilization) before diagnosis -return head to neutral position -do not apply traction -diagnosis of spinal cord injury should not precede resuscitation -motor vehicle crashes and falls are most common associated with spinal cord injuries -main foucs= prevention of further injuries Determine Transport method -travel time, terrain, availability of air or ground transport, capability of personnel, weather -need spinal precautions, C-collar, and spinal board.

Cell Immortality

-85-90% of cancer cells produce telomerase (enzyme). -Adds telomere segments to chromosomes (with every normal cell division, telomeres are shortened by 100 bases; when telomeres are gone, apoptosis occurs) -Cells divide without restraint -Accumulates additional mutations -Tumor becomes larger -Chemotherapy abolishes the telomere = multiple complications

Childhood cancer

-Acutely Chronic Condition -represents les than 1% of all cancers -80% cure rate -Leading cause of death from disease in children -approx. 1/1000 young adults is a survivor of childhood cancer Childhood cancer is not a single disease, but a group of diseases classified into two broad categories 1. Tumors of the blood and blood-forming tissues -leukemia -lymphoma 2. Solid tumors -bone tumors -neuroblastoma -retinoblastoma -CNS tumors -Wilms tumors (nephroblastoma /kidney cancer) Causes/Risks -Congenital malformations (renal abnormalities associated with increase risk of Wilms tumor) -Genetic alterations (trisomy 21, Rb gene that is a tumor suppressor gene, Li-Fraumeni Syndrome (mutation of p53 gene)) -Risk factors (ionizing radiation, carcinogenic drugs, infections (Epstein Barr aka Mono), race, male gender, older maternal age, siblings with cancer. Difference from Adult Cancers -childhood cancers are often the result of DNA changes in the cell that talk place very early (sometimes in utero) -childhood cancers are NOT strongly linked to lifestyle/environmental factors -Caucasians have a much higher incidence than African Americans -Peak ages are 2-5 (infants and young children are more susceptible to tumors involving embryonal tissue "-blastoma") and adolescence (more susceptible to bone tumors) because they -Usually affect deep tissues -related to peak growth periods -No screening or early detection available -usually very responsive to therapy!! 80% cure rate overall.

Cancer Genetics

-Cancer cell division continues, more mutations occur and apoptosis is not signaled leading to uncontrolled growth. Carcinogenesis 1. Initiation - Damaging of DNA (directly of indirectly) by agents or conditions resulting in percent alteration (genetic change) of gene expression that does not interfere with the altered cell's ability to reproduce. Causes - radiation, asbestos (insulation, mining), tabacco, alcohol, viruses (retroviruses- 25% of all cancers), bacteria 2. Promotion - enhancement of expression of the gene altered during initiation (cell multiplication). Usually increases the growth rate of the cells and is REVERSIBLE. 3. Transformation -refers to the process by which a normal cell becomes a cancer cell. This process is mediated by DNA mutations (genetic changes) and epigenetic changes. Cant stop, hard to stop. 4. Progression - the continuing change over time of a cancer cell population causing them to become more malignant, more aggressive, and less normal in appearance, function, and growth regulation. Results in further degrees of independence, invasiveness, metastasis. Metastasis -Spread of cancer cells from a primary tumor to a distant organ. If an individual has a tumor that has been identified as originating in the breast, but has evidence of additional tumors in the bone, then that have breast cancer with bone metastasis. - Removal of primary tumor often enhances growth of the metazoic tumors, therefore surgery is rarely an option when metastasis is present. 1. Cancer cells have direct access to venous blood via angiogenesis -lytic enzymes must degrade the wall of the capillary in order for cancer cells or tumor emboli to enter the blood stream. 2. Once in the venous circulation, they are able to drain into the lymphatics. -most common route of metastasis is through the lymphatics 3. Anatomic patterns of lymphatic/venous flow determine where cancer cells spread. 4. Specific receptors on the small blood vessels in different organs seem to attract certain cancer cell types to adhere to that organ during metastasis.

Histologic Classification This is CELL structure not cancer stages

-Dysplasia is pre-cancer: a lack of cell structure and uniformity in cell tissue 1. Grade 1 -well differentiated, cells vary slightly from norm 2. Grade 2 -moderately differentiated, cells are more abnormal 3. Grade 3 -poorly differentiated, cells vary abnormal (diagnosis and treatment of cancer begins) 4. Stage 4 -very primitive (anaplasia - cells lack differentiation); difficult to determine cell origin 5. Stage 5 -cannot assess origin or differentiation

Intracranial Regulation

-Maintaining a balance to promote an environment that is conducive to optimum brain functioning Assessing Neuro Function 1. mental status -level of consciousness -A/O x4 -Speech (asphagia, understanding, articulating) -Cognitive fucntion (memory, orientation, attention span, ability to focus, insight and abstract thinking) 2. Cranial Nerve Function 3. sensory function 4. motor function 5. reflexes (only done on patients suspected of neuro deficits) Glasgow Coma Scale (GCS) most common scoring system used to describe LOC following TBI. Measures ability to 1. open eyes (1-4) 2. verbal response (1-5) 3. motor response (1-6) Severe: 8 or less (7 or less is coma) "Less than 8, Intibate!" Moderate: 9-12 Mild: 13-15 Cranial Nerve Function -cranial nerve bodies lie within the brainstem & are good indicators of CNS function. 1. Optic (II) - visual acuity, most important 2. Oculomotor (III) - PERRLA 3. Trochlear (IV) - EMO 4. Abducens (VI) - EMO ***3 & 4 look for Horner's Syndrome (size, response, drooping)*** Unconscious Patients 1. assess brain stem function with OCULOCEPHALIC REFLEX (DOLL'S EYES) if able to turn head -the reflex is present/positive if the eyes move in the opposite direction from head movement -If awake, a normal patient will counteract this reflex; if unconscious and reflex is absent this indicates brain stem damage. 2. Assess brain stem function with OCULOVESTIBULAR REFLEX with cold-caloric test -Infuse ice water 10 mL/min into ear and the eyes should deviate TO the tested ear. Infuse warm water, eyes should deviate FROM the tested ear. -A positive response should dissipate in 5 mins and the opposite ear should be tested. -Ideally, both ears should be tested at the same time. Cold water in both = downward deviation (down at the cold snow) Warm water in both = upward deviation (up at the warm sun) Sensory Function -ability to detect stimuli (painful and light touch) -Touch all major dermatomes (fingers, shoulders, toes, thighs, trunk), first with sharp, then dull, then with light touch. -never ask "can you feel this" -close eyes Motor Function -ability of muscles to carry out motor commands -Move all extremities on command -Full ROM -assess balance and gait (stance, swing, stride) if appropriate Diagnostic Tests 1. Imaging Studies (CT) -views tissue density, does not define vasculature as well an angiography (lower risk for complications however) -Need contrast dye (ask about iodine or shellfish allergy/reaction) -New IV line of 20 g or higher -Test renal function prior -warn pt about metallic taste -monitor UOP up to 24 hours -increase fluid (PO or IV) intake to flush dye -metalic taste in the mouth 2. Spinal Scanning -assess herniated sick, spinal cord tumors, spinal stenosis 3. Brain scanning to detect -brain contusion or calcification -cerebral atrophy -hydrocephalus -inflammation -space-occupying lesions such as tumors or abscess -infarction or clot 4. MRI -view of soft tissue//superior to CT or x-ray -permits multiple plane views -useful for CNS study as shows structural and biochemical abnormalities associated with Transient Ischemic Attack (TIA), Tumors, Multiple Sclerosis (MS), Cerebral Edema, Hydrocephalus. -may need contrast dye (confirm no gadolinium allergy) -new IV line -remain still for 5-20 min periods over a 1.5 hr time span -NO METALLIC items -machine is enclosed & noisy, predicate for anxiety if desired & educate pt. -Increase IV flow rate to fluid intake to flush dye. 5. PET - positive emission tomography provides colorimetric information about the brain's metabolic activity by detecting how quickly tissues consume radioactive isotopes. Isotopes (emit positrons) combine with negative charge electrons in tissue cells and make gamma rays; the computer translates gamma ray as cerebral blood flow, volume & metabolism of NT. -Used to reveal cerebral dysfunction related to Tumors, Seizures, Head Trauma, TBI & stroke, Dementia, Effect of drug therapy or surgery. -can be given IV or gas 6. Skull and Spinal X-Rays -usually taken from ***anteroposterior and lateral angles***** -detects fractures, bony tumors, and unusual calcifications -used in suspected Spinal disease, Injury to the vertebrae, Spinal fracture or dislocation, Arthritic changes, Abnormalities such as kyphosis (hunching) or scoliosis. 7. Cerebral Angiography -contrast is injected into the brachial artery or femoral artery. -highlights vasculature to enhance detection of Stenosis or occlusion associated with thrombus, identify aneurysm and AVM (arteriovenous malformation), Locate vessel displacement associated with tumors, abscesses, cerebral edema, hematoma, herniation, Assess collateral circulation. 8. Electroencephalography (EEG) -records brain continuous electrical activity -used to identify Seizure disorders, Head injury, Lesions such as abscesses or tumors, TIA and stroke, Brain death. 9. Lumbar Puncture -a sterile need is inserted into the subarachnoid space, usually between L3 & L4, to draw out CSF. -used to detect blood in CSF, obtain CSF specimen for analysis, Inject dyes or gases for contract to radiologic studies, Administer drugs/anesthetics to relieve increased ICP by removing CSF.

Primary Survey

-Most crucial assessment tool in trauma care (1-2 mins max) -designed to identify life threatening injuries accurately and establish priorities -ABCDEF of trauma Airway Breathing Circulation Neurologic deficit Exposure of patient (hypothermia; liver laceration + cold = coagulopathy) Full set of vitals -problems found during the primary survey are treated immediately -if the patient gets worse, the team will restart from the beginning of the primary survey. -some critical patients in the Emergency Department may not progress beyond the primary survey. Airway -loss of airway can result in death <3 minutes -prolonged hypoxia = inadequate perfusion, end-organ damage Assessment -vital signs = RR, O2 -Mental Status= agitation, somnolent, coma -Airway patency = secretions, stridor, obstruction -Traumatic Injury above the clavicles -Ventilation Status= accessory muscle use, retractions, wheezing. Clinical Insight -pts who are speaking normally generally do not have a needs for immediate airway management -hoarse or weak voice may indicate a subtle tracheal or laryngeal injury (may need intabation) -noisy respirations frequently indicates an obstructed respiratory pattern. Interventions 1. Maintenance of Airway Patency -suction of secretions -chin lift/jaw thrust -nasopharyngeal airway -definitive airway 2. Airway Support -oxygen -NRBM (100%) -bag valve mask -definitive airway 3. Definitive Airway ***endotracheal intubation*** - in line cervical stabilization -surgical crichothyroidotomy (last option) Breathing/ Ventilation -adequate gas exchange is required to maximize patient oxygenation and carbon dioxide elimination Assessment -exposure of chest 1. Genral inspection -tracheal deviation -accessory muscle use -retractions -absence of spontaneous breathing -paradoxical chest wall movement 2. Auscultation to assess for gas exchange -equal bilaterally -diminished or absent breath sounds 3. Palpation -deviated trachea -broken ribs -injuries to chest wall Identify Life Threatening Injuries 1. Tension Pneumothorax -air trapping in the pleural space between the lungs and chest wall -sufficient pressure builds up and pressure to compress the lungs and shift the mediastinum Physical Exam -absent breath sounds -air hunger -distended neck veins -tracheal shift 2. Open Pneumothorax -sucking chest wound -large defect of chest wall -leads to rapid equilibration of atmospheric and intrathoracic pressure -impaires oxygenation and ventilation Initial Treatment -three sided occlusive dressing -provides a flutter valve effect -chest tube placement remote to site of wound -avoid complete dressing, will create a tension pneumothorax. 3. Hemothorax (needs to replace blood) -blood collecting in the pleural space, common after penetrating and blunt chat trauma. -source of bleeding= lung, chest wall (intercostal arteries), heart, great vessels (Aorta), diaphragm. Physical Exam -absent or diminished breath sounds -dullness to percussion over chest -hemodynamic instabiltiy 4. Flail Chest -direct injury to the chest resulting in an unstable segment of the chest wall that moves separately from remainder of thoracic cage. -typically results from two or more fractures on 2 or more ribs -typically accomplished by a pulmonary contusion -physical exam = paradoxical movement of chest segment. crepitis = air leaking into SQ tissue Circulation 1. identification of shock- shock = inadequate organ perfusion 2. Clinical Signs of Shock -altered mental status -tachycardia (HR >100) = most common sign -arterial hypotension (SBP <120) -radial pulse - SBP >90 -carotis pulse - >60 3. Inadequate Tissue Perfusion -pale skin color -cool clammy skin -delayed cap refill (>3 seconds) -altered LOC -decreased urine output (UOP < 0.5 mL/kg/hr) Types of Shock in Trauma 1. Hemorrhagic -assume hemorrhage shock in all trauma patients until proven otherwise -results from internal or external bleeding 2. Obstructive -cardiac tamponade -tension pneumothorax 3. Neurogenic -spinal cord injury Sources of bleeding -chest -abdomen -pelvis -bilateral femur fractures Interventions General Treatment Principles 1. Stop the Bleeding -apply direct pressure -temporarily close scalp lacerations 2. Close open-book pelvic fractures -abdominal pelvic binder/bed sheet -never put in a foley 3. Restore circulating volume -crystalloid resuscitation (2L) -administer blood products 4. Immobilize fractures Responders vs Non-responders -Transient response to volume resuscitation = sing of ongoing blood loss -Non-responders = consider other source for shock state of operating room for control of massive hemorrhage. Neurologic Deficit -rapid assessment of neurologic status to identify life-threatening injury -pupil size and response -mental status (GCS) -motor and sensory exam *****Eye opening None = 1 To painful stimuli only = 2 To voice only = 3 Spontaneously open = 4 Verbal response None = 1 Incomprehensible sounds = 2 Incomprehensible words = 3 Confused = 4 Oriented = 5 Motor response None = 1 Decerebrate (extension) posturing = 2 Decorticate (flexion) posturing = 3 Withdraws to pain = 4 Localizes pain = 5 Follows commands = 6***** Exposure Head to toe examination of the patient for injury -remove clothing -check temperature -pitfalls -maintenance of spine = precautions -prevention of heat loss - under cervical collar -back and flanks Fracture -stabilize fracture -relocate dislocated joints (assess pulses before and after) *****reassess pulses**** Adjuncts to Primary Survey -exams during or after primary survey to aid in identifying life-threatening injuries -CXR -focused abdominal sonogram for trauma (FAST) -diagnostic peritoneal lavage (DPL) Passed out - Narcan and check FSBS for hypoglycemia Secondary Survey and Definitive Treatment -the secondary survey is a complete head to toe evaluation of the patient -adjuncts to the secondary survey include CT's, plain radiographs, blood tests, urinary bladder drainage. -treatment plans, especially for multiple injuries, based on clinical status and specific injurues FAST: focused abdominal sonography for trauma -Morrison's Pouch (right upper quadrant) -Pericardial sac -Splenorenal region (left upper quadrant) -pelvis (suprapubic region) Resuscitation -restoring organ perfusion -Assess HR, BP, UOP -May lead to compensatory shock (increased UOP, decreased BP, draw lactate) -Organ-specific indicators of perfusion (gastric tonometry) -Global indicators of perfusion -lactic acid, base deficit -cardiac output, oxygen delivery, oxygen consumption, mixed venous 02 saturation Damage Control Laparotomy -a shift from definitive management of abdominal injuries to stabilizing the patient for resuscitation -leave cavity opens dressing over to let swelling go down. Goals: stop bleeding control contamination temporary abdominal closure

Basics of a trauma assessment

1. Preparation -team assembly and equipment check -need to know mechanism of injury is VITAL 2. Triage -sort patients by level of acuity 3. Primary Survey -designed to identify injuries that are immediately life threatening and to treat them as they are identified -ABC + C spine (DONT MOVE PAST ABC UNTIL FIXED) 4. Resuscitation -rapid procedures and treatment to treat injures found in primary survey before completing the secondary survey -fluids, airway 5. Secondary Survey -full History and Physical (H&P) exam to evaluate for other traumatic injuries 6. Monitoring and evaluation, secondary adjusts -continual reassessment of primary and secondary survey 7. Transfer to definitive care -ICU or unit, Operating Room, Another facility Distracting injures!!!! Look at ABC before moving on. Preparation by receiving Trauma Team -trauma team at receiving hospital responds before arrival of patient -report has been transmitted that includes the history of traumatic event -identification of mechanism of injury is vital to the initial assessment and helps the team prepare appropriately.

Cancer Stages

1. Stage 1 -cancer confined to the organ of origin (In situ) 2. Stage 2 -cancer that is locally invasive, but has not metastasized 3. Stage 3 -cancer that has spread to regional lymph nodes 4. Stage 4 -cancer that has metastasized to distance organs of dame origin (lung cancer is now found in the brain) TNM (Tumor, Nodes, Metastases) - another system of staging T= primary tumor; the number equals the size of tumor and its local extent. 0-3 N= lymph node involvement; a higher number means more nodes are involved. 0-2 M= extent of distant metastases. 0-2

Kinetic Changes in Cancer Multiple Cell growth

1. Unrestricted cell growth - loss of tumor suppressor genes -loss of contact inhibition -loss of cell/cell recognition 2. Abnormal differentiation (ANAPLASIA) 3. Loss of contact inhibition -growth signals are not stopped when in cancer cell growth comes in contact with n organ or vessel; cells will pilled up, grow through, and overcrowd a boarder.

Morphologic Changes in Cancer

1. Variable Cell shape/size 2. Large Nucleus/ Cytoplasm Ratio 3. Aneuploidy - different # of chromosomes on a karyotype

Intracranial Regulation

Adequate brain function requires 1. consisted supply of oxygenated blood 2. Nutrients-primarily glucose This can be disrupted by -blockage of vessels -severe hypovolemia /hypotension -intracrainal hemorrhage -damage or excessive external pressure on a vessel Brain Function also depends on transmission of nerve impulses across synapses. This can be disrupted by -seizures -drugs or toxins (heroin binds to presynaptic endorphin to block pain)

Mechanisms of Injury: Penetrating Trauma

impalement of foreign object -Missiles or bullets that come into contact with internal structures that produce a change in pathway release more energy and result in more injury than a direct pathway. -injuries sustained from penetrating objects must be assessed for the potential for injection from the debris carried by the penetrating object.

Shock

shock occurs when the cardiovascular system is not able to perfuse organs and tissue, resulting in widespread impairment of cellular metabolism and tissue function. -systemic hypoxia leads to local ischemia damage -shock from any cause will result in impaired perfusion, which can progress to organ failure and death unless reversed Stages of Shock 1. Initial Stage -usually not clinically apparent -metabolism changes from aerobic to aerobic as perfusion decreases -lactic acid accumulates and must be removed by blood and broken down by liver -provess requires 02, which is unavailable due to poor perfusion. 2. Compensatory Stage -clinically apparent -neural, hormonal, biochemical compensatory mechanisms -attempts are made to overcome consequences of aerobic metabolism and maintain homeostasis 1. baroreceptors in carotid and aortic bodies active SNS in response to decreased BP -vasconstriction while blood to vital organs maintained 2. decreased blood to the kidneys activates the RAS -this increases venous return to the heart, CO, & BP 3. Impaired GI motility due to SNS response -risk for paralytic ileus 4. Cool, clammy skin from blood -except SEPTIC pt who will be warm and flushed 5. Shunting blood from lungs increases physiologic dead space to try to increase pt. breathing -decrease arterial 02 levels -increase rate/depth of respirations -V/Q mismatch 6. SNS stimulation increases myocardium 02 demands 7. If perfusion deficit corrected, pt recovers with no residual sequelae 8. if deficit not corrected, pt enters progressive stage 3. Progressive Stage - begins when compensatory mechanisms fail -aggressive interventions to prevent multiple organ dysfunction syndrome (MODS) -hallmarks of decreased cellular perfusion and altered capillary permeability 1. leakage of protein into interstitial space 2. increase systemic interstitial edema -Anasarca (whole body edema) 1. Fluid leakage affects solid organs and peripheral tissues 2. decrease blood flow to pulmonary capillaries 1. Movement of fluid from pulmonary vasculature to interstitum -pulmonary edema -bronchconstriction -decrease in residual capacity 2. Fluid moves into alveoli -edema -decrease surfactant -worsening v/q mismatch -tachypnea -crackles -increased work of breathing 3. CO 2 begins to fall bc tachypnea -decreases peripheral perfusion -hypotension -weak peripheral pulses -ischemia of distal extremities 4. Myocardial dysfunction results in -dysrhythmias -ischemia -myocardial infarction -end result: complete deterioration of cardiovascular system (increase in troponin) 5. Mucosal barrier of GI system becomes ischemic -ulcers -bleeding -risk of translation of bacteria -decreased ability to absorb nutrients 6. Liver fails to metabolize drugs and waste -jaundice -elevated enzymes -loss of immune function -risk for ***DIC** and significant bleeding 7. Acute tubular necrosis/acute renal failure due to hypo perfusion 4. Refractory Stage -exacerbation of aerobic metabolism -accumulation of lactic acid -increase in capillary permeability -profound hypotension and hypoxemia -tachycardia worsens -decreased coronary blood flow -cerebral ischemia -failure of one organ affects others -recover unlikely / death Clinical & Diagnosis Tests -H & P -no single study to determine shock -blood studies (elevation of lactate, base deficit) -12-lead ECG -chest x-ray -hemodynamic monitoring

Antimetabolite Alkylating Agent

Methotrexate blocks synthesis of folic acid; inhibits mitosis (DNA replication) -profound neutropenia, thrombocytopenia, anemia, and crystalluria (alkalizes the urine) Cyclophosphamide moms bonds in DNA structure -profound neutropenia, thrombocytopenia, anemia and hemorrhagic cystitis -pre-medicate w MESNA (grabs metabolite in chemo and excretes it, coats the bladder)

Anaphylactic

Acute, life-threnting hypersensitivity reaction -massive vasodilation -release of mediators -increase capillary permeability Leaky vessels leads to throat, mouth, tongue sticking out aka angioedema CM -anxiety, confusion, dizziness -sense of impeding doom -chest pain -incontinence -swelling of lips and tongue, angioedema -wheezing, stridor -flushing, pruritus, urticaria -respiratory distress and circulatory failure Need Epi!!! (vasoconstriction) Benadryl (antihistamine)

Systemic Side Effects

Chemo works best on cells that proliferate quickly. -Hair = alopecia -Mucosa (mouth to anus) -Bone Marrow 1. Myleosuppression -results in neutropenia (risk for infection), thrombocytopenia (bleeding, brushing, extreme coughing, sneezing, or straining can increase ICP and can led to stoke), anemia fatigue, pale). 1. BMD -neutropenia, thrombocytopenia, anemia 2. Stomatitis -results in n/v, mucositis, diarrhea 3. Alopecia Additional Toxicities 1. Pulmonary - Bleomycin, Cytoxan, Methotrexate 2. Neurotoxic - Vinca alkaloids (central), platins (peripheral) 3. Renal - Platins, methotrexate 4. Bladder - Ifosphamide, cyclophosphamide (hemmoragic cyctisis) 5. Anaphylaxis- Asparaginase, bleomycin, platins, taxanes -stop infusion, run NS, give epi, hydrocortisone 6. Hepatotoxic - Mercaptopurine, thioguanine 7. Cardiotoxic - Antitumor antibiotics, antimetabolites 8. Ototoxic - Cisplatin 9. Reproductive - bank sperm and eggs

Monitoring Intracranial Pressure

Components of the Cranial Vault 1. Brain - 86% 2. CSF - 10% (cleans tissue, cements long term memory pathways, adequate sleep helps this process) 3. Blood - 3-4% **Fixed fluid volume, any changes leads to increased pressure contents, except in infants and children bc their skull bones are not fully fused yet** Volume Expanders -Increased content like tumors -Cerebral edema from inflammation due to trauma, stroke, infection -Excess CSF due to overproduction or decreased reabsorption -Hemorrhage -when stasis blood lysis, it causes inflammation and its irritative nature causes tissue damage. Monroe-Kellie Doctrine -the sum of the contents of the cranial vault (brain, CSF, blood) is constant. -an increase in one should lead to a decrease in one or both of the others. -ability to adapt is dependent on the RATE of change of the intracranial volume. -Small, slow changes can be compensated for -Large, rapid changes need evacuation to keep ICP down. The brain receives 20% of CO; cerebral arteries are able to auto regulate, vasoconstricting or dilating to maintain optimal blood flow. Like the kidneys, if systemic BP is decreased, vasodilation will occur; if BP is increased, vasoconstriction will occur. Increase BP = dilation Decrease BP = constriction Increased CO2 = dilation Decreased Co2 = constriction Hypoxia = dilation Cerebral perfusion Pressure -the pressure gradient that drives cerebral blood flow by auto regulation. - CPP = MAP - ICP - MAP = (SBP + (2 x DBP)) / 3 ICP Pressures Normal Adult: 5-15 Elevated: >20 CPP Pressures Normal Adult: 65-90 Ischemia Adults: <50 CPP @ death: <30 Normal Pediatric (1-12 yrs): >50 (>12) = >65 ***Hypotension in head injured pr is very bad; each episode increased their morbidity & mortality risk; don't want loss of brain tissue.*** 4 ICP Monitoring Systems 1. Ventricular catheter monitor ICP directly and is the most accurate, but has the highest risk for infection. 2. Subarachnoid bolt is eraser to place than a catheter, lower infection risk and damage as it does not penetrate the cerebrum. It is use for monitoring only, not draining. - Monitors are "zeroed" to the Foramen of Monroe (external auditory meatus) - ALWAYS close the stopcock to the drainage system pro to changing position bc system is gravity dependent.

Cancer & Genetics Terminology What is cancer? What is Neoplasm? What is a tumor and its classifications?

- Cancer involves the mutation and proliferation of normal cells into abnormal, deviant cells. -Neoplasm is new abnormal growth of tissue. -Depending on the size and location of the tumor, physiologic functioning of affected tissues, organs, or organ systems may become impaired. 1. Benign = not cancerous -grows slowly -well-defined capsule -well differentiated (normal size and shape) -not invasive to surrounding tissue 2. Malignant = cancerous -grows rapidly -not encapsulated -cells lack differentiation (anaplastic) -invasive to surrounding tissue "octopus arms" Tumors are named after the tissue from which they arise and are followed by the suffix -OMA (not exclusive to benign tumors) EX// adenoma - glandular cells, chondroma - cartilage cells, hemangioma - blood vessels, lipoma - adipose cells 1. Dysplasia - abnormal cell structure and a lack of uniformity amount cells in the tissue. 2. Carcinoma - epithelial cells 3. Adenocarcinoma - ductal or glandular epithelium 4. Sarcoma - connective tissue 5. Glioblastoma - glial cells 6. Lymphomas - lymph tissue 7. Leukemias - blood forming cells

Major Cancer Genes

-Oncogenes -Cancer suppressor genes -DNA (Mis-Match) repair genes All can result in a gain or loss of function. Oncogenes -gain of function aka "Accelerators" -Proto-oncogenes are normal genes that code for proteins that regular cell growth and proliferation. In most cases, proto-oncogenes code for growth factors, growth factor receptors, and signal-traducing proteins. When a photo-onccogene develops a cancerous mutation it becomes an oncogene; don't have regulation of cell growth. -activated by single allele -derive from proto-oncogenes and retroviruses -rarely inherited EX: 1. Growth Factor Genes -HST, SIS 2. Growth Factor Receptor Genes -RET, ERRB, NEU, MET, KIT 3. Signal Transduction Genes -HRAS, KRAS, ABL, CDK4, BRAF 4. Nuclear Transcription Factor Genes -NMYC, MYB, FOS ***Philadelphia Chromosome*** Translocation of Bcr-Abl genes// chromosome 9 &22. Cancer Suppressing Genes -loss of function aka Breaks -loss of function (cyclin dependent kinases) -stop cellular proliferation (transcription genes) -responsible for apoptosis -mutation may be inactive -both alleles must be inactive -more than 20 identified (RB-1, NF-1,2, APC, TP53) -both copies of the gene must be lost or damaged (heterozygosity) in order for this to occur. 1. Tumor suppressing genes -normal genes that code for proteins that regulate or halt cell proliferation 2. Care taker genes -normal genes that are responsible for maintenance of genomic integrity 3. Apoptosis genes -normal genes that are responsible for inducing apoptosis, or programmed cell death, in damage or mutated cells. p53 Gene -"Garden of the Genome" -stops the proliferation of damaged cells, helps to repair damaged DNA, and promoted apoptosis in irreversible damaged cells. -approx. 50% of all human cancers have a nutation of p53 gene. TP53 Gene (17 p) Mutation -linked to poor prognosis -p53 is transcription factor on 17p that halts cell cycle G-1 (CDK), higher levels of p53 in rapidly diving cells, allows time for repair, and apoptosis. We have 2 genes and elephants have 1 million; they have lower instances of cancer. DNA (Mis-Match) Repair Genes -DNA polymerase -6 mismatch repair genes identified -Mutation in these genes 1. active oncogenes 2. inactivate tumor suppressor genes 3. aneuploidy -Breakage in DNA EX: BRCA 1, BRCA 2, Xeroderma Pigmentosum Immune System -Natural killer cells -monocytes and macrophages -b cells and antibodies

Characteristics of Cancer Cells

-These can occur in any order; cancer cells have autonomy from normal cellular regulation. Normal, Dysplasia (abnormal cell structure and a lack of uniformity amount cells in the tissue), In situ Neoplasm (new abnormal growth of tissue), Invasive Neoplasm. 6 Hallmarks of Cancer 1. Self-suffiecncy of growth signals - some cancer's up-regulate own growth factors (RAS gene is a common example of a growth receptor mutated into the "on" position) -some cancers secrete growth factors that stimulate own growth (autocrine stimulation) 2. Insensitivity to antigrowth signals 3. Evasion of apoptosis -cancer cells become immortal -cancer cells hid their cell markers so natural killer cells can't find them and phagocytosis. 4. Limitless replicative potential -cancer cells produce telomerase; this maintains the telomeres, allowing cell division to occur over and over again will sustained telomere length. 5. Sustained Angiogenesis -cancer cells secrete factors that stimulate new blood vessel growth for its own blood supply (Cachexia - weight loss, muscle wasting, loss of appetite, general debility from chronic disease) 6. Tissue invasion and metastasis

Neurogenic Shock

-hemodynamic phenomenon that can occur within 30 minutes of a SPINAL CORD INJURY at the T5 vertebra or above and can last up to 6 weeks -can be in response to spinal anesthesia -results in massive vasodilation leading to pooling of blood in vessels Patho: Results in massive vasodilation (inhibition of SNS) leading to pooling of the blood in vessels -disruption of SNS and causes loss of sympathetic tone aka activates PNS (decrease HR) (vasodilation, decrease BP, decrease venous return, decrease SV & CO) -all leads to decrease cellular oxygen supply and tissue perfusion -IMPAIRED CELLULAR METABOLISM AND ORGAN FAILURE CM -hypotension -bradycardia -temperature dysregulation (resulting in heat loss) -dry skin -Poikilothermic (taking on the temperature of the environment)

Management of Shock

-identification of pt's at risk for shock -integration of the pt's history, physical examination, and clinical findings to establish a diagnosis -interventions to control or eliminate the cause of the decreased perfusion -protection of target and distal organs from dysfunction -provision of multi system supportive care General management strategies -ensure patent airway -maximize oxygen delivery Cornerstone of therapy for volume-related shock= Volume Expansion -isotonic crystalloids (NS/LR) for initial resuscitation of shock -if pt does not respond to 2-3 L of crystalloids, blood administration and central venous monitoring may be instituted Complicaitons -hypothermia -coagulopathy Primary goal for drug therapy = correction of decrease tissue perfusion 1. Vasopressor drugs (epi) -achieve/maintain MAP >60 to 65 -reserved for pt unresponsive to other therapies 2. Vasodilator therapy (nitro for cardiogenic shock) -achieve/maintain MAP >60 to 65 **Nutrition is vital to decreasing morbidity from shock** -initiate enteral nutrition (Preffered feeding method) within the first 24 hours -initiate parenteral nutrition if neutral feeding contraindicated or fail to meet at lest 80% of caloric requirements -monitor protein, nitrogen balance, BUN, glucose, electrolytes Management of Cardiogenic Shock 1. Restore blood flow to the myocardium by restoring the balance between 02 supply and demand -thrombolytic therapy -angioplasty with stenting -emergency revascularization -valve replacement 2. hemodynamic monitoring 3. Drug therapy (diuretics to reduce preload) 4. Circulatory assist devices (intra-aortic balloon pump, ventricular assist device) Management of Hypovolemic Shock -focuses on stopping the loss of fluid and restoring the circling volume -***fluid replacement is calculated using 3:1 rule (3 mL of isotonic crystalloid for every 1 mL of estimated blood loss)*** Management of Neurogenic Shock In spinal cord injury: spinal stability -treatment of the hypotension and bradycardia with vasopressors and atropine -fluids used cautiously as hypotension is generally NOT related to fluid loss -Monitor hypothermia Management of Anaphylactic Shock 1. epinephrine, diphenhydramine (Benadryl) 2. maintaining a patent airway -nebulized bronchodilators -endotracheal intubation or cricothyroidotomy may be necessary -aggressive fluid replacement -intravenous corticosteroids if significant hypotension persists after 1-2 hours of aggressive therapy Management of Septic Shock 1 hour bundle -Measure serum lactate (Normal 0.5-1) -Obtain blood culture prior to antibiotic therapy -administer broad spectrum antibiotics -administer 30 mL/kg crystalloid for hypotension or lactate >4 -vasopressors if pt is hypotensive during or after fluid resuscitation to maintain MAP>65 HOUR ONE BUNDLE: INITIAL RESUSCITATION FOR SEPSIS AND SEPTIC SHOCK (BEGIN IMMEDIATELY): 1) Measure lactate level.* 2) Obtain blood cultures before administering antibiotics. 3) Administer broad-spectrum antibiotics. 4) Begin rapid administration of 30ml/kg crystalloid for hypotension or lactate ≥4 mmol/L. 5) Apply vasopressors if hypotensive during or afterresuscitation to maintain a mean arterial pressure ≥ 65 mm Hg. *Remeasure lactate if initial lactate elevated (> 2mmol/L). Other -maintain glucose between 70-150 -adminster IV corticosteroids Other Specimens to Culture -Sputum -Stool -Wound? Assess SEPSIS IN CHILDREN -Assess LOC, CRT, BP, pulses, temperature, UOP >1ml/kg/hr -Give O2 and gain IV access -Draw ABG, lactate, glucose, ionized calcium, cultures, CBC -Correct hypoglycemia (< 60 in children) or hyperglycemia (>180) -Give 20 ml/kg isotonic boluses and monitor response over 5-10 min -Administer antibiotics even if cultures could not be obtained - WITHIN 1 HR!!!! -Consider hydrocortisone

Diabetic Keto Acidosis (DKA)

-is a serious complication of Type 1 DM & is the leading cause of death among young adolescents/adult diabetics. -is caused by SEVERE insulin deficiency leading to severe HYPERGLYCEMIA -DKA can also occur inn Type 2 diabetes bc eventually type 2 leads to beta cell destruction and insulin deficiency. Etiologies -in some cases, type 1 DM are diagnosed for the first time when they develop DKA (this can be life-threatening if not treated quickly) -20-30% of causes of DKA in type 1 DM have no obvious trigger; quick onset 1. One common cause is omission of insulin -missing one dose on insulin will probably NOT cause DKA, but failure to take multiple doses will results in a rapid onset of sxs. -those at the highest risk of failing to follow insulin regimes include alcoholic and drug abuses, as well as individuals without access to health care and diabetic education. These individuals may have a history of uncontrolled hyperglycemia. (Be careful w type 1 DM undergoing surgery; sometimes insulin omission is accidental and occurs when theft is under medical/nursing care) 2. Acute illnesses/infection and trauma are most commonly associated with DKA 3. Physiological or psychological stress leads to the release of stress hormones (primarily cortisol) -the brain requires glucose when under stress so it increases cortisol secretion; cortisol will increase glucose uptake in the CNS and decrease glucose uptake in all of the other tissues (bc the brain is a glucose hog). Other cells use different metabolic pathways like fatty acid and amino acids bc all of the glucose is going to the CNS. The liver then gets involved performing gluconeogenesis, more FA and AA, all to promote a raise in blood glucose. This is all about preserving the brain which can only use glucose (and eventually ketone) as a full source. -one of the main consequences of cortisol secretion is a rise in blood glucose -there is evidence that psychological stress can induce DKA, especially in children. 3. There are many insulin-antagonist medications that raise blood glucose levels - systemic corticosteroids (minic the action of cortisol) Patho: -without insulin, the body breaks down fats for energy -rapid breakdown of fats leads to development of ketones, resulting in a severe metabolic acidosis. -Acidosis impacts potassium levels (for every change 0.1 change in pH, there is o.6 change in K+, this occurs when buffers in the body aren't enough to reduce H+, H+ then moves into the intracellular space and K+ leaves the cell into the extracellular space) -as acidosis worsens, blood glucose levels increase and hyperkalemia worsens -as with diabetes, the liver is responding to lack of cellular fuel (thinks its in a SNS state, cell starvation, increased serum cortisol) by converting glycogen to glucose to release into circulation (excess glucose molecules trigger osmosis (glucose is an osmotic diuretic) and fluid shift occurs//correct dehydration!) CM 1. Severe Hyperglycemia -blood glucose can be extraordinarily high in DKA. Most sources list a glucose level of >300 mg/dl, but in many cases it is much higher. 700-1000 is not unusual. 2. Polyuria leading to hypotension and shock -osmotic diuresis leads to increased urine output which leads to volume depletion and eventually hypovolemic shock. -Polydipsia is a fairly early sign of polyuria -hypovolemia manifests w postural hypotension and tachycardia at first -hypovolemia eventually manifests with signs of tissue dehydration becuase fluid shift from the extravascular spaces into the blood stream in an effort to maintain blood volume and pressure -sxs of tissue depletion and severe volume depletion include dry mucus membranes and poor skin turgor. 3. Electrolyte imbalances Potassium: in early stages, potassium can be elevated due to insulin deficiency and metabolic acidosis. However with diuresis (hyperglycemia is an osmotic diuretic) we see potassium loss in the urine. Potassium levels must be checked frequently bc they are difficult to predict and can change rapidly. Sodium: first, hyperglycemia causes water to shift out of cell and interstitial fluid into the bloodstream. This fluid shift dilutes plasma sodium resilient gin a hyperglycemic hyperosmolar hyponatremia. Osmotic diuresis then causes a total body deficit of sodium and chloride. Phosphate, magnesium, and calcium: osmotic diuresis generally leads to a deficit of these electrolytes 4. CNS alterations (20% of CO) -hypotension leading to decreased cerebral perfusion, metabolic acidosis from elevated ketones, and sodium alterations all contribute to generalized dysfunction of the CNS neurons. -the patient with DKA may first have headaches and double vision, then becoming confused and eventually losing consciousness. 5. Kussmaul Respirations -metabolic acidosis in DKA stimulates hyperventilation to compensate for the lowered blood pH -during hyperventilation with prolonged exhalations (Kussmaul respirations), CO2 is blown off, thus raising the pH of the blood. -the effects of respiratory compensation are limited, but Kussmaul respirations are an important signs of metabolic acidosis, and should not be confused with respiratory distress. 6. Acetone breath -the liberation of ketones (ketosis) and the presence os ketones in the blood can sometimes be detected by smelling a patient's breath. Ketones have similar structure to acetone and have a fruity, but pungent odor. 7. GI and abdominal symptoms -in the early signs of DKA, patients often present with anorexia, nausea, and vomiting. These appear to be caused by gastroparesis (delayed gastric emptying) related to hyperglycemia and hyperosmolarity. -abdominal pain (generalized or epigastric) is likely due to the metabolic acidosis that develops in DKA. Lowered pH can cause cell injury and the stimulation of pain neurons. Diagnostics -serum glucose: 200-800 -Increased serum ketone levels -postive urine acetone test -ABG results indicating metabolic acidosis -increased serum osmolality -initial K+ in normal range; hyperkalemia depending on level of acidosis; hypokalemia in later stages -ECG with changes related to hyperkalemia (tall, tented t waves, and wide QRS complex) or hypokalemia (Flattened T wave and possible U wave) Treatment 1. in DKA, INITIAL intervention is to expand extracellular volume and stabilize cardiovascular system with non-dextrose IV fluids (depending on level of dehydrations 10-20 ml/kg/hr bolus of NS or LR) 2. Correction of potassium deficit -this will depend one K+ levels (<3.3 should give until in range and if over range don't give) -once you start insulin therapy K+ will go down 3. Low dose of IV regular insulin if K+ levels are above 3.3 4. As blood glucose nears 250 mg/dL give D5 fluids to prevent hypoglycemia -blood glucose must be lowered slowly bc too rapid of a drop can cause a fluid shift, in a hyperglycemic state the cells are shrinking but if you drop glucose rapidly the cells will see and cause cerebral edema. Leading cause of death in children with DKA -as blood glucose levels normalize, add K+ to IV fluids to prevent hypokalemia -want a target blood glucose of 14-180 -this level avoids extreme hyperglycemia but minimizes the risk of hypoglycemia -Short acting REGULAR INSULIN is preferred to main glycemic control -monitor ABG for decreased in acidosis -in some cases bicarbonate may be used to increase pH, although this is controversial as the evidence of benefits is lacking. -as bicarbonate levels rise, serum K+ may fall, requiring more aggressive KCL replacement -frequently assess LOC and ability to maintain airway, respiratory status (including breath sounds) and cardiac rhythms -monitor vital signs and changes, indicate in hydration status

Mechanisms of Injury: Blunt Trauma

-most often results from vehicle accidents, but may occur in assaults, falls from heights, and sport related injuries -may be caused by accelerating, decelerating, shearing, crushing, and compressing forces. -coup-countra- coup injuries -body tissues respond differently to kinetic energy...low density porous tissues and structures, such as lungs, often experience little damage because of their elasticity. -the heart, spleen, and liver are less resilient often rupturing or fragmenting. -often, overt external signs are not apparent...making the mechanism of injury most important to the practitioner performing the physical examination.

Drugs Used in Cancer

Cancer Characteristics -high growth fraction -high mitotic index -1 mL cancer has 1 billion cells -drugs with 99% efficacy still leaves 10 million cancer (mutated cells) "Remission" until 5 years of no cancer, then "Cured" Tumor Heterogenicity -limitless growth -insensitive to anti-growth signals -produces own growth signals -sustained angiogenesis -evades apoptosis Clonal Therapy - immortality is an ability we should focus on because it greatly affects how we decide to treat the cancer. Gompertzian Curve - tumors grow with characteristic growth kinetics called Gompertizian kinetics; from its origin in a single cell, there is long lately periods between the beginning of growth to clinical detection because symptoms don't usually occur till later, don't become palpable till later, and can be first visualized on an x-ray till later in tumor development. These kinetics are essential for designing strategies used in chemotherapy and radiation. Treatment -surgery (non-matastisized) -radiation therapy (palliative) -chemotherapy -hormone modulation (block receptors so hormones can't trigger growth of tumor) -immunotherapy (manipulating own immune system with cytokines) -disruption of intracellular signals (TNF, interferon, interleukin, genetic modified T cells, turn back on PD1 & CDLA to stimulate immune responses bc cancer turned these off) Molecular Targeted Therapy can block certain areas of the 6 hallmarks of cancer in order to simplify signals that promoted tumor growth and longevity. Variable Treatment Times Admitted to the unit if comorbidities and treatment is unsafe to handle at home (mouth sores, mucositis, diarrhea)

Drugs Effecting Cell Cycle

Cell-Cycled Specific Drugs -Chemotherapy is best delivered as small divided doses or continuous infusion. ***Timing and schedule is most important*** G1 : First growth phase responsible for growth and normal metabolic roles -steroids, nitrosureas, asparginase S : synthetic phase responsible for DNA replication. -antimetabolites, antifolates, pruine inhibitors, topoisomerase inhibitors G2 : Second growth phase responsible for growth and preparation for mitosis -bleomycin, etoposide M : mitotic phase response for prophase, metaphase, anaphase, telephase -vinca alkaloids, taxanes Cell Cycle NON- specific -effective even when the cell is at rest -Chemo is best delivered as a BOLUS dose; can get cells on any cell cycle -total amount/dose is most important NON-Specific Agents 1. Alkylating Agents -nitrogen mustard -cisplatin -cyclophosphamide 2. Antitumor Antibiotics -omycin -rubicin (cells can't replicate) -these agents/chemo will inserted an alkyl group into the DNA that causes cross linking and breaks in DNA; so during development the DNA breaks and destroy the cancer cell.

Note about solid tumors

DONT PALPATE ANY SOLID TUMOR!!!!

Stroke

Defined as a decrease in blood flow to a localized area of the brain that results in brain tissue hypoxia. General CM 1. Loss of CNS function in infarcted area (loss of sensation or motor functioning) 2. contralateral deficits (deficits are typically on the side of the body opposite of the side where brain injury occurred) 3. Loss of consciousness 4. Vision cut can affect both eyes, cut may affect only one FAST - face - arm (eyes have to be close) - speech - slurred - time ACT NOW Ischemic Stroke - artery -interruption (occlusion) of cerebral blood supply due to a thrombus, embolus, or vascular stenosis. -every minute the brain loses 1.9 million neurons, 14 billion synapses, 7.5 miles of myelinated fibers. Transient Ischemic Attack TIA - mino stroke -intermittent occlusion of small arteries and arterioles in the brain -neurological deficits resolve within 24 hours Lunar Infarct -interruption (occlusion) of blood supply in the perforating arteries typically occurring in deeper portions of the brain -deeper in the brain CM -neurological deficits are typically either purely motor or sensory. Hemorrhagic Stroke -rupture of a cerebral blood vessel leading to intracranial hemorrhaging due to trauma or a ruptured or leaking intracranial aneurysm CM 1. headache w severe sudden onset 2. sis of increased ICP -altered LOC -hemiparesis progressing to hemiplegia (paralysis on one side of the body) -abnormal motor responses (decorticate to decerebrate posturing) only stroke w this becuase you are increasing ICP -altered vision (blurry, decreased acuity, diplopia, sluggish pupil response) Diagnostics -Radiologic Imaging (white=blood, dark=tumor, old blood, infarction) 1. CT should be obtained within minutes of patient arrival -shows structural abnormalities, edema, lesions (non-hemorhagic infarction or aneurysm), and differentiates stroke from tumor or hematoma. -CT scan usually normal for patient with TIA -hemorrhagic stroke visible immediately, ischemia stroke within 72 hours. -this will indicate thrombolytic therapy. 2. MRI is used to show area of infarct or ischemia, and cerebral swelling -cerebral angiography shows vascular disruption or displacement of cerebral circulation -carotid duplex scan (ultrasound) shows blood flow through carotid arteries and stenosis due to atherosclerosis plaque or clots -Lumbar puncture with bloody CSF may indicate hemorrhagic stroke -EEG to identify damage area, and to differentiate stroke from seizure activity General Brain Attack Protocol -Document when patient last seen normal -secure patient safety -titrate o2 to maintain SP02 over 95% -establish and record VS q15 minutes -Labs: CBC, Chem 14, Coags, Tox Screen, Troponin, LFTs, B Hcg -Bedside glucose check (low blood glucose can mimic signs of stroke) -record pt's weight -stat EKG -NIHSS exam Q15 vitals Treatment 1. Supportive- begin treatment within 60 minutes of patient arrival -Thrombolytic therapy -aspirin as anti-platelet RECTAL -benzodiazepines for seizure prevention -stool softeners to minimize staining (decrease ICP) -corticosteroids to minimize secondary injury -analegesics 2. Surgical -depending on the cause and extent of the stroke, pt may undergo: -craniotomy to remove hematoma -carotid endarterectomy to remove plaque from inner arterial walls -extracranial bypass to circumvent blocked artery

Diabetes Case study

Diagnosing 1. A1C >6.5% -considered diabetic when over 6.5 -long tern glycemic control is determined though A1C -shows glycemic control over the span of 3 months -Normal is 4-6 -Anything below 9 for a diabetic is good 2. Fasting Plasma glucose >126mg/Dl (7.0) 3. 2-h plasma glucose >200 mg/dL (11.1) during an OGTT 4. Randoma plasma glucose >200 mg/dL New DM 1 w DKA 1. Fluid Resuscitation -immediately start 0.9 NS IV fluid, u to 1 L/hr for 2-3 hours 2. Management of hyperglycemia -adminster regular insulin vis IV drip (rate and bolus dependent on protocol) -at the same time start IV potassium 3. Monitor blood glucose hourly VS Q1 Physical Assessment Labs ABG Glucose Monitoring Type 2 DM w HHNKS 1. Fluid Resuscitation -immediately start 0.9 NS IV fluid resuscitation -monitor fluid volume ro prevent fluid overload, heart failure and dysrthymias in older patents. 2. Management of hyperglycemia -administer regular insulin VS often Physical Assessment Labs Glucose Monitoring Kidney damage or UTI = blood and leukocytes in urine High blood sugar in females = high risk for developing UTI Education 1. Self monitoring of blood glucose -for those on insulin therapy, testing is recommended 2-4 times a day -usually it is with meals, and/or with the peak of intermediate-acting insulins NPH Glucometers Insulin injection -outer arm, abdomen, hip area, thigh -need to rotate spots to minimize the risk of lipodystrophy Insulin Pumps -change every 3-5 days -Humalog and nova log (RA) -want to work like normal pancreas -even when not eating there is a basal rate -not seen in children often Insulin -keep spar vial of insulin available -inject room temperature helps to reduce local irrigation (no clump) -store in refrigerator -can be kept at room temp if used within a month form first opening Sick Day Guidelines -take insulin/oral anti diabetic agents -FSBS Q3-4 HRS -Report BS >300 -Supplemental usual meal plan as needed with sift foods, 6-8 times/day -Ensure adequate hydration (if N/v, diarrhea, fever) Exercise -lowers blood glucose levels -improves circulation and increases metabolic rate -increases HDL and decreases total cholesterol and triglycerides -those on insulin therapy should eat 15 g carbohydrate snack before engaging in modern exercise Nutrition -1 unit of insulin for 15 g of carbohydrates -encourage low glycemic foods or combine starchy foods with protein -educate about serving labels Type 1 Diabetics: Hypoglycemia For the Conscious -15 g of a fast-acting concentrated carb -3-4 glucose tablets -4-6 oz of fruit juice/soda -6-10 hard candies -2-3 tablespoons of sugar or honey For the Unconscious -call for assistance and take measures to ensure ABC -draw blood sample if possible -Give 25mL OF DW50 or 0.5 to 2 mg IM glucogon Type 1 DM Hypoglycemia Causes -overdose of insulin or anti-hyperglycemia agents -delayed or omitted meals -increased exercise -alcohol Patho: SNS response to low blood sugar levels triggers the adrenal medulla to release epinephrine (BB decrease the body's SNS response to hypoglycemia) Early CM -shakiness, tremors -tachycardia, palpitations -diaphoresis -anxiety Late CM (due to decreases CNS function) -headache -changes in affect/behavior and cognition -weakness, dizziness -visual disturbances -if untreated, eventually you will see seizures and loss of consciousness DM 1 Hypoglycemic Unawareness -occurs when a diabetic does not perceive the early sympathetic warnings signs of hypoglycemia Patho: -repeated episodes of hypoglycemia causes injury to autonomic centers in the brain -normal sympathetic warning signs are not activated -avoidance of hypoglycemia for a few weeks can restore partial awareness Happens in older patients, patient with frequent hypoglycemic episodes, patients with diabetic autonomic neuropathy Alcohol -is absorbed first and does not require insulin for absorption -hypoglycemia resulting from alcohol consumption is associated with those taking insulin, resulting from altered gluconeogenesis.

Diagnosis & Classification of Cancer

Diagnosis 1. Health history -risk factors -family history -clinical manifestations 2. Physical Assessment 3. Diagnostic studies -imaging -labs -biopsy 4. Diagnostic testing -scans = x-ray, CT, MRI -tumor markers = substances produced by cancer cells or by non-cancer cells in response to cancer -biopsy = collected by exfoliation, aspiration (of fluids or solid tissue), excision Clinical Manifestations VARY DEPENDING ON 1. Location - increased pressure and/or decreased blood supply to surrounding tissue, organs, and nerves 2. Loss of function - due to death/damage of healthy tissue 3. Rate of growth - severe and dramatic onset of symptoms with fast growing, particularly within the skull. 4. Excess of function -hormone producing tumors C.A.U.T.I.O.N - 7 early warning symptoms of cancer from ACS to promote awareness C- change in bowel or bladder habits A- a sore that does not heal U- unusual bleeding or discharge T- thickening or lump in breast or elsewhere I- indigestion or difficulty swallowing O- obis change in mole or wart N- nagging cough or hoarseness

Dosing Schedules

Effective dose against cancer Safest toxicity risk to patient "enough to kill cancer, not enough to kill Pt" BALANCE Dose intensity: dose over total delivery time Relative Dose intensity: ratio of deliver dose ad planned dose Dose Density: reducing time between standard doses Dose Escalation: increasing the dose per cycle Combination vs single Agent -Combo therapy with different MOA's increases proportion of cells killed at any one time due to heterogeneous (6 hallmarks) cell populations 1. increase proportion of cell kill 2. Reduce drug resistacne

CM of increased ICP

General: HA, N/V (projectile) Decreased LOC is the earliest and most important symptom and relates to area of brain involved -Confusion: cerebrum dysfunction -Lethargy -Obtundation/Stupor: midbrain dysfunction -Coma: pons, medulla dysfunction Motor Signs 1. DeCORticate posturing -abnormal flexion, pulls towards core -cerebrum, thalamus, hypothalamus 2. DEcErEbrate posturing -arm extension and adduction -midbrain, pons 3. Contralateral hemiparesis -one arm extension, one arm flexion towards core, both hands adduction postion -medulla Respiratory Changes 1. Cheyne-Stokes -hyperventilation and apnea 2. Central Neurogenic Hyperventilation - pressure on sensors. 3. Apneustic - prolonges inspiratory pause 4. Ataxic - completely irregular Pupillary Changes -often sluggish w increased ICP -impending herniation (fixed and dilated >5 mm) Other Signs 1. Loss of gagging and swallow reflexes (compression of cranial nerve X - vagus); even unconscious will have a gag reflex if ICP is within limits. 2. Loss of corneal reflexes (go to poke eye, you will back up and blink) 3. Seizures 4. Vital Sign Changes LATE -widening pulse pressure aka increased SBP, decrease DBP -bradycardia 5. Herniation -intracranial contents shift (or herniate) from the compartment of greater pressure to one of lesser pressure. -Uncal (lateral) herniation is the result of a lesion in the temporal lobe; will present with -decreased LOC, dilation of pupil on side of compression, posturing, bilateral babinski, cushion's triad. Cushing's Triad -HTN -Respiratory irregular/ apnea -Bradycardia CM of Increasing ICP in Infants & Children -Increase in Occipital-Frontal Circumference -High-pitched, piercing cry (neuro cry) -Seizures, tremors, twitching, repetitive movements -setting-sun eyes: only see top half of eyes -MacEwan sign -Bulging Fontanels -Combativeness, irritability -Postive Babinski reflex: fanning of toes

Management of Cancer across the Lifespan

Goals of Cancer Therapy -Prevention -Cure -Control -Palliation -Minimize overlapping toxicities Chemotherapy has the greatest impact on rapidly dividing cells (oral mucosa, hair, bone marrow (neutropenia (7-12 hours), thrombocytopenia (7-8 days), anemia (90-120 days)), reproductive organs) Hematopoiesis -all stem cells arise from a pluripotent stem cell -stem cells are capable of proliferation, differentiation, and maturation to maintain homeostasis. Side effects of treatment -n/v -diarrhea -skin irritation -hair loss -myelosuppression #1 Myleosupression -a decrease in he bone marrow's production of blood cells as a result of cancer itself or cancer treatment. Suppression of the myeloid line (neutropenia (increase his for infection), thrombocytopenia (increase risk of hemorrhage), anemia (increase risk of hypoxic injury due to lack of 02 transportation). NADIR is the period of lowest blood cell counts. -sooner and more severe with multi-modal therapy -most at risk for infection and feel the crummiest -typcially occurs between 7-14 days flowing the first dose of chemotherapy Anemia Assessment -suppression of healthy RBC that carry adequate 02 to the body's tissues -cold intolerance, pallor, headaches, fatigue, irritability, poor concentration, increased 02 demand, palpitations, tachycardia, angina Medical Management blood transfusion, Epogen (controversial due to increase in clotting) Nursing Interventions -rest periods, group activities/ "cluster care", safety precautions, nutrition (high protein and calories), exercise, symptom management, supplemental oxygen, monitor lab values (CBC, total iron binding capacity, transferrin saturation) Thrombocytopenia Assessment -suppression of healthy platelets that assist with clotting -petechiae, bruising, hepato/splenomegaly, occult or over blood in stool/urine, HEADACHES, HYPOTENSION (both can be suspected of brain bleed), tachycardia. -less than 10,000 is potential for serious hemorrhage Medical Management -Platelet infusion -Safety precautions -avoid increased ICP (coughing, vomiting, sneezing, straining) -patient education (avoid NSAIDS, birth control to prevent heavy menstrual, stool softeners to prevent straining) Neutropenia Assessment -neutrophils (granulocytes) are the first line of defense against bacteria -Assess for signs of infection like: redness, swelling, puss, fever >38, chills/rigors -neutropenic patient may not present any of the classic sis bc their body may no be able to manifest the usual clues. -Assess for feeling dizziness or weak, urinary sxs, a sore throat, stuffy nose/cough, difficulty swallowing, temperature. Risk for infection -age -indewlling devices -incontinence -poor hygiene -poor mobility -skin alterations Neutropenia + infection = sepsis = sepsis shock = high mortality rate Degree of Neutropenia Absolute Neutrophile Count ANC= WBC x total neutrophils (bands +segs) x10 -less than 500 is high risk for infection/ dangerous ****the greatest risk factor for infection is prolonged neutropenia***** Medical Management -identify infection source (blood//2 sets one PIV and one CVC, urine, sputum, stool, oral lesions, CXR) -platelets, antibiotics (prophylaxis or confirmed infection), colony stimulating factors in order to prevent infection (filgrastim - neupogen, peg-filgrastim - neulasta) Nursing Interventions -strict hand hygiene, personal hygiene -immunosuppressed diet (wash all foods, cook meals throughly, no salad bars or buffets) -avoid invasive procedures -no stagnant water (flowers, dentures), careful pet care, avoid sick contacts/visitors, avoid crowds & construction, no attenuated vaccines, private hospital room. Nutritional Alterations -change in oral intake resulting in weightless or gain Risk factors - n/v -alterations in taste or smell -cancer treatment chemo/radiation -glucocorticoids -pain -metastatic or recurrent disease Management -monitor h & w -identity source of inadequate intake (pain, n/v, altered taste sensation) -promote oral hygiene -promote adequate intake (high calorie, high protein) -use nutritional supplements -enteral or parenteral feeding as indicated Mucositis -an inflammatory and ulcerative process of the mucous membranes, resulting in severe discomfort that can impair patients' ability to eat, swallow, and talk. -accompanied by a risk for life threatening bacteremia and sepsis Management -pre-treatment dental evaluation -orla hygiene (set and soda) -cryotherapy (sucking on ice prior, during, and post chemo infusion) -oral cavity assessment -pain management -avoid irritant (mouth wash, spicy foods) -flossing only recommended is pt is already a flosser. Sexual and Reproduction Alterations CM -erectile dysfunction -loss of libido -vaignal dryness -fatigue -body image changes -infertility Management -give pt permission to talk about concerns -fertility preservation -fatigue management w moderate exercise -symtom management (minimise dryness and irrigation with lubricant) Psychosocial Issues -higher rates of depression and anxiety as a result of the emotional, physical, social, and financial toll RF -advanced stage of cancer -uncontrolled cancer pain -fatigue -being unmarried -taking certain medications (corticosteroids, IL2) -previous or family history of anxiety/depression Altered Body image -alopecia -mastoectomy -invasive devices -removal of colon,uterus, internal organs -weight loss or gain -limb amputation Spiritual Distress -questioning existence, purpose in life, existence of afterlife -real possibility of death Care Giver Strain -physical, emotional, spiritual, financial Survivorship -is a survivor from time of diagnosis Palliative & end of Life Care Palliative - goal is to improve quality of life and can be used in conjunction with curative treatments End of life - goal is not to be cured but comfortable

HHNKS

Hyperosmolar Hyperglycemia Nonketotic Syndrome is a serious complication of hype 2 DM. This complication was formerly called HHN coma, because some patient lose consciousness for a variety of reasons. -caused by factors there precipitate severe hyperglycemia and dehydrations. The path is similar to that of type 2 DM. -this complication occurs most frequently in type 2 diabetics over age 60. Etiologies 1. Failure to take hyperglycemia agents PROFOUND DEHYDRATION -skipping one dose of a hyperglycemic agent probably won't lead to HHNKS, however routinely missing doses of failure to take anti hyperglycemic agents over a number of days could precipitate the condition. Drugs: 1. those that decrease insulin secretion and increase dehydration (thiazides, loo diuretics) 2. those that increase insulin resistance (corticosteroids) 2. Illness -many cases of HHNKS occur during or flowing an acute illness -the release of stress hormones during an acute illness causes a rise in blood sugar -illnesses that result in dehydration are common precipitating factors because fluid and electrolyte imbalance is component of HHNKS. Dehydration from a lack of fluid intake in an otherwise healthy type 2 diabetics can also lead to HHNKS. Patho: -in type 2 DM, glucose production and release is increased or glucose uptake by cells is decreased. -when cells don't receive glucose as fuel, the liver responds by converting glycogen to glucose for release. -as all excess glucose molecules remain in the pasta, osmosis causes fluid shift (water form cells to go into the vasculature, shrinking cells) -the cycle continues until fluid shifts in the brain cause coma and death. It can be weeks before they go into the hospital. CM unlike DKA, most cases of HHNKS develop slowly over days and weeks. The onset of symptoms is gradual and by the time it is recognized, serious complications have often developed. Mortality rates for HHNKS are around 10-20%. 1. Signs of profound dehydration -dehydration is often more severe in HHNKS than in DKA 2. Severe Neurological deficits -profound dehydration and hyperglycemia/hyperosmolarity lead to neuronal dehydration and generalized CNS dysfunction. Approximately 10% of patients present in a coma. 3. Absence of ketosis -the patho of HHNKS is similar to DKA, except that in HHNKS there is not ketosis -in HHNKS, the type 2 diabetic has enough of an insulin response in the adipose tissue to prevent significant lipolysis -this is evidenced by the absence of ketones in the urine. 4. DVT and formation of thromboembolism -HHNKS results in profound volume loss that often develops over the course of days or even weeks. -by the time the condition is detected, the individual may be severely dehydrated which increases the risk of blood clotting in the arteries or veins. Individuals with HHNKS often present with DVT's, stroke, and organ dysfunction. 5. Oliguria and Renal Function (LATER SIGN) -the kidneys are often the first to experience dysfunction related to hypovolemia and hypotension (receive 25% CO). Severe dehydration in HHNKS reduces renal blood flow and can lead to renal failure. -hypovolemia activates the mechanism for renal compensation (aldosterone and ADH secretion) Renal retention of fluids manifests with oliguria. If the patient has progress to renal failure, then urine output will further reduced and labs will show an elevated serum creatinine and BUN. Diagnostics -Serum Glucose: 800-2000 -Ketones are absent, so there is no acidosis, and urine and serum ketones results are negative -Urine glucose are positive -Serum osmolarity is increased -Serum sodium levels are elevates (increased NA from dehydration, neurological problems), but potassium levels are usually normal (not in acidosis) Treatment 1. Isotonic or half-normal saline IV fluids are given to correct dehydration -when the patient's blood glucose level approaches 250 mg/dL add dextrose to the fluid to prevent hypoglycemia. 2. IV insulin and electrolyte replacement are delivered -as blood glucose levels normalize, so do sodium levels. 3. Administer IV insulin and titrate dosage based on patients blood glucose levels -HHNKS its have severely elevated glucose levels, but LESS insulin is usually needed than for DKA, because its typically secrete at least some insulin and may be sensitive to additional doses. 4. Monitor LOC and ability to maintain airway, respiratory status 5. Monitor vital signs for hydration status.

Classifications of Shock

Low blood flow -cardiogenic -hypovolemic Unequal distribution of blood flow -septic -anaphylactic -neurogenic

Oncology emergencies

Metabolic 1. Sepsis -whole body inflammatory state caused by severe infection 2. Disseminated Intravascular Coagulation DIC -over stimulation of coagulation and a rapid consumption of clotting factors leads to bleeding 3. Hyperglycemia -increased bone reabsorption of calcium and/or inadequate renal clearance 4. Syndrome of inappropriate Anti-Diuretic Hormone SIADH 5. Hypersensitivity & Anaphylaxis -produced by normal immune response to exposure or antigen or allergen -typically related to chemotherapy and immunotherapy 6. Tumor Lysis Syndrome 1. Tumor Burden 2. Treatment induced - chemotherapy, radiation, biotherapy, hormonal agents, surgery, spontaneous occurrence -increased serum potassium, prosperous, nucleic acid from cell lysis and the body is unable to clear tumor debris form renal insufficiency or failure. CM 1. Hyperkalemia -most life threatening consequences -depression, fatigue, muscle weakness, hypoactive bowel sounds, nausea, ileum, peaked T waves, arrhythmia, v-tach, v-fib/arrest Prevention: avoid heparin, potassium sparing diuretics, ACE inhibitors, radiographic dyes block tubular reabsorption of uric acid, avoid food high in K. 2. Hyperphyosphate w HYPOcalcemia -anxiety, depression, confusion, hallucinations, ventricular arryhmias, heart block, cardiac arrest, twitching, paresthesia, muscle cramps, carpopedal spasms, tetany. 3. Hyperuricemia @10-15 mg/dl -fatifue, malaise, weakness, n/v, flank pain and compromised renal function, prutitis in peritoneal, gout. @>20 mg/dl -hematuria, crystaluria, azotemia, anuria, renal failure, edema, hypertension. Management -correction of electrolyte imbalances -Q6H labs monitoring (CBC, BMP, BUN, Cr) -aggressive hydration and diuresis -phosphate binders aka TUMS -hemodialysis (last resort) -Allopurinol to decrease uric acid and gout by inhibing xanthine oxidase. Structural 1. Increased ICP -caused by metastases, tumors 2. Cardiac Tamponade -abnormal collection of fluid around the heart or between the pleura, sometimes containing cancer cells 3. Spinal Cord Compression -when cancer cells grow in or near the spine and press on the spinal cord and nerves 4. Superior Vena Cava Syndrome -compromised venous drainage of the head, neck, upper extremities, and thorax through SVC. -prognosis is cerebral anoxia, laryngeal edema, bronchial obstruction and death. -Compression or obstruction of the vessel from tumor, enlarged lymph nodes, thrombus Mechanisms of Compression 1. extrinsic mass 2. direct tumor invasion through vessel wall 3. thrombus around CVC 4. thrombus within SVC: hyper coagulable state, intimal damage from CVC, or venous stasis from compression. CM 1. EARLY SXS - more pronounced in the am or bending over -facial swelling, erythema, fullness in head, peri-orbital redness and edema, swelling in neck, arms, hands (Stroke-difficulty buttoning collar) -DSYPNEA!!! most common (ask if the breathing has gotten worse) -nonproductive cough, hoarseness, cyanosis of upper torso, venous distention (JVD), visible collateral veins in chest 2. LATE SXS -sxs of ICP (headache, irritability, visual disturbances, dizziness, syncope, MS changes) -Horner syndrome: unilateral ptosis (drooping eyelid), miosis (constricted pupil), anhibrosis (decreased in sweating on the same side) -dysphagia, hemoptysis, CHF, stridor, tachycardia, hypotension, progressive, cyanosis and facial edema. More CM SXS - worse in the morning after hours of lying down. keep HOB elevated!! Plethora - an excess of blood, red appearance in head and neck Horner Snydrome Stroke Sign- facial and neck swelling early in the am, difficult button shirt EMERGECNY 1. Decrease in Cardiac filling and CO 2. cerebral edema 3. respiratory distress Management 1. Radiation (gold standard for lung cancer) 2. Chemotherapy 3. Surgery - debulk or remove 4. Thrombolytic for Clots 5. Intravascular Stent Placement - contraindicated when tumor invaded the vessel wall 6. Medication: opioids: pain management but be careful with respiratory distress and neurological changes, steroids: decrease swelling MORE 1. Supportive Cares (02 & diuretics) 2. Positioning - elevated HOB 3. Promote energy conservation - shower at the end of the day 4. Vigilant I &O's 5. Avoid upper extremity venipuncture and blood pressures With all Oncologic emergencies you must treat underlying disorder CANCER

Genetic Exemplars Cancer

Multi-factoral Disease -modifier genes -response to DNA damage -carcinogens -hormonal/reproduction factors Accumulation of injuries- It takes several mutations, acquired over time, to transform a cell into cancer. This is why incidences of cancer increase greatly with age. Somatic vs Hereditary Cancer Somatic -mutation arises in single cell -not transmittable to offspring -accounts for 80-95% of cancers -single-organ disease -late onset Hereditary -mutation is constitutional -transmitted to offspring (mutation must be present in sperm or oocyte) -accounts for 5-15% of cancers -80-100% affected will develop cancer Clinton suspicious of familial link if: -early onset (before the age of 35) -tow or more close relatives diagnoses with the same cancer -multiple or bilateral tumors (bc all cells inherited the mutated gene) Hereditary Cancer Syndromes -Transmitted in autosomal dominant pattern -carriers have much increased risk for getting cancer Familial Adenomatous Polyposis Colorectal Cancer -multiple polyps in colon by second decade of life -polyps are precursors to colorectal cancer -tumor suppressor genes (Adenomatous polyposis coli (APC-gene), TP-53 gene (Li-Fraumeni syndrome - inherited familial predisposition to rare cancers because of p53 mutation to tumor suppressing genes; this does not necessarily determine you will get cancer but your risks are higher than the general population. This is important to identify in order to screen and detect cancer growth early. Hereditary Nonpolyposis Colorectal Cancer -Lynch Syndrome ( inherited disorder that increases your risk of developing colon cancer, uterine/endometrial cancer) -DNA repair-gene (genetic instability that leads to cancer) BRCA -1 -mutation in chromosome 17 -DNA repair-gene BRCA- 2 -chromosome 13

Treatment

Often used in combination -surgery -chemotherapy -radiation -Bone Marrow Transplant (BMT) -Immunotherapy 1. Surgery -precise local treatment -may be a method of obtaining specimens (Diagnostic) -may removed all of the primary tumor (Curative) or a portion of it (Debunking) -May be the only treatment a patient requires -may be preceded or followed by other modalities -May be used in the palliative setting to alleviate or lessen intolerable symptoms (Palliative) -DIAGNOTIC = performed to obtain a tissue sample for analysis of cells suspected to be malignant -CURATIVE = removal of tumor and margin o surrounding healthy tissue to increase chat e of complete cancer removal. -DEBULKING = used when it is not possible to remove all of the cancerous tumor bc doing sow would severely harm an organ. -PALLIATIVE = goal of treatment is to make the patient as comfortable as possible and to promote quality of life as defined by patient and his or her family. -RECONSTRUCTIVE = restore function and/or appearance with grafts, tissue expanders, flaps, and prosthetics. -PROPHYLACTIC = surgery to remove an organ or glans that show no signs of cancer, in attempt to prevent development of cancer of that organ or gland. 2. Chemotherapy -based primarily on TBSA (some drugs based on Kidney function or ideal body weight) -may change throughout treatment Routes -oral, IV, arterial (liver), subQ, IT/intraventricular, intraperitoneal, intrapleural, intravesicular, intranasal, creams. -Central venous access is ideal RN Concerns -this is a hazardous drug especially to those who don't need it; it is carcinogenic, teratogenic, reproductive toxic, organ toxic, genotoxic. -worried about own exposure to spills and patient body fluids. -we can absorb it, inject by needle sticks, inhalation (cover up toilet when flushing urine), ingestion (wash hands). Extravasation - escape of chemotherapy drug into he extravascular space, either by leakage from a vessel or by direct infiltration. Manifestations: pain, erythema, swelling, resistance to flow, and lack of blood return. ****Need to asses catheter before starting chemo and frequently check patentcy during infusion**** Prevent of Extravasation -CVC preferred -flush catheter, check for resistance, swelling, tenderness, redness -check for blood return from catheter -educate patient and family on symptoms to report -monitor site throughout infusion If Extravasation is suspected 1. STOP administration immediately 2. apply ice or heat (depending on chemo agent) 3. notify the physician, who may order a neutralizing agent or attempt to aspirate any remaining drug. 3. Radiation -the use of high energy electromagnetic waves or particles to shrink tumors and kill cancer cells. -used for curative or palliative treatment in combination with chemotherapy. -Goal is to deliver adequate dose to tumor volume with minimal damage to surround tissue. -this will 1. stop or limit the cell's ability to divide, 2. affects both healthy and cancerous cells, 3. healthy cell have the ability to repair. Types 1. Internal -pt will emit radiation, need protection plan -brachytherapy/pellets (low or high dose) -systemic (IV, PO) 2. External -beam radiation (pt will need to be in the exact same position every time) Adverse Effects 1. EARLY/ACUTE -skin reactions (external beam radiation) -head/neck -alopecia -dry mouth -anorexia/n/v -urinary problems 2. CHRONIC/LATE -fibrosis -lymphedema -intestinal damage -infertility -secondary cancer (RARE) Safety Considerations -pt will only emit radiation when there is a source present (brachytherapy and systemic) -need to consider TIME, DISTANCE and SHIELDING -private room, dosimeter badges, maintain 6 foot distance when possible, no children or pregnant visitors or staff, limit visitors to 30 minutes a day. 4. Bone Marrow Transplant -Goal is to 1. treat hematologic cancers and 2. to treat effects of aggressive chemotherapy treatment for cancer that destroy some marrow cells. -transplant contain immature cells known as hematopoietic or blood-forming stem cells. Sources 1. Autologous/Syngeneic -receive own stem cells (before chemotherapy treatmemt) or identical twin stem cells 2. Allogeneic -receive HLA matches stem cells 3. Umbilical Cord Blood -cells are immature, less of a concern that there will not match. Preparation of Transplant Donor: give peripheral blood, bone marrow or umbilical cord Recipient: may get chemo and radiation or both!! before BMT Adminsitation -hematopoietic cells delivered to blood stream via IV infusion -stem cells travel through the blood until they reach the bone marrow; doner's bone marrow cells repopulates recipient bone marrow. -Engraftment (is the process in which the transplanted stem cells find their way to the bone marrow spaces in the centre of the large bones of the body. Only then can the transplanted stem cells begin to produce new blood cells) This typically takes 2-4 weeks. You will see a rise in WBC, platelets at the 2 week mark and eventually a rise in RBC. Compilations and Risks GVHD: Graft vs Host Disease -immune response elicited by donors T lymphocytes against recipient tissues -causes infection, bleeding, anemia 5. Immunotherapy -manipulating own immune system with cytokines. Interferon alfa-2a (Roferon) MOA: enhances phagocytosis and cytotoxic T cell effects Interleukin-2 Aldeskeukin (proleukin) -dont really use as much anymore but was foundation of immunotherapy. MOA: activated and proliferates T&B cells, enhances antigen/antibody binding, flu-like symptoms, capillary leak syndrome Monoclonal Antibodies!!! take antigen from human body, implant it into animal or human to develop specific antibodies against specific antigen then insert monoclonal antibodies back into patient. SE: All cause anaphylaxis, BMD (CD-antigen attacking like Rituximab (Rutuxan) & Alemtuzumab (Campath), Rashes and Diarrhea (GF receptor targeting like Bevicizumab (Avastin), and cardiac complications in Trastuzumab (Herceptin)

Traumatic Brain Injury

Open head injury -brake in the dura caused by focal brain injury, usually involving skull fracture -highest infection risk Closed head injury -caused by blunt injury from impact of rapidly moving object, or if head hits a hard surface -dura radians intact -less infection risk than open head injuries -increased ICP -more common Focal Brain Injury -injuries confined to ONE AREA of the brain, resulting from an impact to the head -many focal brain injuries cause ruptured vessel that result in bleeding in the intracranial vault. -included contusions, epidural hemorrhage, subdural hematoma, and intracranial hematoma. Defuse brain Injury -rotational acceleration and deceleration produces shearing, tearing, or stretching of nerve fibers resulting in diffuse (or wide spread) axonal damage. -organ donors // brain dead // not come back Coup/Contrecoup Injuries -injuries caused by the sudden acceleration or deceleration of the head (with out without impact) -coup, or the initial injury, occurs at the site of impact -contrecoup, or the subsequent injury, occurs on the side opposite of the site of impact -both can result in bleeding and contusions due to the force of injury Secondary Injury -brain injury resulting from pathologic processes occurring after the initial injury that negativity impact the outcome. Cortical Contusions -small tear in vessels or surface of brain results in area of infarction, necrosis, hemorrhage, edema -peak effects 18-36 hours after injury. CM -immediate, brief loss of consciousness -***changes in attention and memory, the worse the injury the worse the memory and attention*** Epidural Hemorrhage (arterial) -result of direct impact injury causing bleeding which dissects the dura away from the skull Classical Sxs -immediate LossOC, lucidity, rapid decrease in LOC -arterial blood is main source in 85% of pt -often middle meningeal artery in temporal fossa Subdural Hematoma -most common type of intracranial bleed, usually a venous bleed at the top of the skull Classical SXS -slow decrease in LOC without LossOC Acute Subdural Hematoma -symptoms develop within 48 hours post injury CM -symptoms of increase ICP (will need medical intervention and surgical evacuation of the hematoma) -herniation possible -type of herniation dependent on location of hematoma -In the elderly, acute subdural hematoma can occur as a result of a fall -In pediatrics, they can result from a fall, bike accident, abuse (if the mechanism of injury for not match the severity of the injury, one should always suspect abuse, whether it be child or adult) Chronic Subdural hematoma -typically, occurs in smaller veins, with the hematoma progressing over weeks to months Causes: -most common among the elderly (who have greater risk for aneurysms due to weakening of blood vessels over time) or alcoholics (due to decreasing clotting capabilities) -in children, chronic subdural hematoma may indicate potential child abuse or non-accidental trauma (NAT) such as SHAKEN BABY SYNDROME or violent blows to the head. CM -headache, drowsiness -confusion-appears like slow onset dementia -herniation possible Intracerebral Hematoma -trauma or tearing of small vessels that bleed into eh parenchyma (brain tissue) -typically causes by high impact forceful injuries, but may be due to the spontaneous rupture of an aneurysm -hematoma acts as expanding mass inside the cerebrum (similar to tumor) which may delay sis for 3-10 days. -MRI - need the full view planes Subarachnoid Hemorrhage -bleeding into the subarachnoid space (The space between the arachnoid membrane and pia mater that is filled with cerebrospinal fluid and contains the large blood vessels that supply the brain and spinal cord) results in a mixing of blood with CSF, causing an inflammation response in the meninges (3 membranes covering the brain and spinal cord). Causes: -ruptured aneurysm -arteriovenous malformation (AVM) -head trauma (particularly basilar skull fractures and injuries around the CIRCLE OF WILLIS) Patho: -blood into the subarachnoid space -blood irritates the meninges causing inflammatory reactions -edema from inflammation and hemorrhage can lead to an increased ICP with associated consequences. -scarring of the arachnoid villi can occur which impairs CSF absorption (CSF cleans tissue; serous fluid builds up in cranium) -leads to hydrocephalus CM 1. signs of increased ICP -headache, change in mental status, n/v, focal neurological changes 2. signs of meningeal irrigation -positive Kernig (lift leg and it bends) and Brudzinski (lift neck knees bend) -neck stiffness -photophobia, blurred vision -irritability, restlessness -low grade fever Mild Concusison -Grade I-III -disturbed electrical activity (transient) due to temporary anoxic disturbances -no loss of consciousness -possible momentary amnesia -visual disturbances, headache Classic Concussion -grade IV -diffuse disconnection from brain stem RAS -loss of consciousness <6 hours -headache, drowsiness, confusion, dizziness, visual disturbances, vomiting, amnesia -concussion may have cumulative effect Post-Concussion Syndrome -psychological and social problems for up to 1 year after concussion -children who have suffered from a concussion should not participate in contact sports until 7 days after symptoms subside. -repeated concussion have an accumulative effect -if you have >2, they should consider not paying high contact sports due to the high damaging brain effects. Diffuse Axonal Injury -widespread dysfunction caused by acceleration/deceleration forces and sharing injury (tearing of axons) -coma or loss of consciousness >6 hours -best seen on an MRI, should still suspect DAI if pt's CM do not match CT scan. -Usually take longer than expected to wake up or they have a prolonged coma. -typically become organ donors Path: -microscopic injury to axons and vessel -also results in scarring, demyelination -cerebral edema common Diagnostics 1. Radiologic Imaging -x-ray will identify skull fracture -CT shows fracture of cranial vault and any hemorrhage, cerebral edema, or herniation -MRI may show intracranial hemorrhage from ruptured blood vessels 2. Cerebral angiography shows location of vascular damage due to internal pressure or injury. Treatment 1. surgical -evacuation of hematoma, bone fragments or foreign matter -craniotomy to relieve intracranial pressure (neeeedddsss a helmet) 2. Supportive -close observation for signs of change in neurological status Neuro checks -cleaning and debridement of wounds -diuretics - mannitol -analgesics -anticonvulsants -respiratory support -prophylactic antibiotics if indicated

Management of Increased ICP

Overall goal of treatment is to maintain ICP below 20 and CPP greater than 70. 1. Maintain a patent airway and adequate respiratory functioning -suction judiciously (hyper oxygenate before and after) -assess breathing patterns and lung sounds frequently -endotracheal intubation recommended for GCS<8 or CT scan suggesting increased ICP. 2. Ensure proper positioning -maintain neutral neck position and avoid extreme hip flexion. -Elevate HOB to 30 degrees or Reverse Trendelburg 35-45 degrees. 3. Fluid Management -avoid hypotonic fluids, use iso -provide osmotic diuretics (mannitol) and monitor CVP -provide hypertonic solutions and monitor serum sodium q6h. 3. Maintain normal body temperature and prevent fever -provide acetaminophen, indomethacin, cooling blankets to keep temp >38.3 4. Minimize stimulation -avoid unnecessary stimulation and maintain a calm, quiet, dimly lit environment -PREVENT activities that cause vagal nerve stimulation (no straining) Surgical Interventions -to prevent recurrence, restore blood flow, repair vessels (aneurysms) or malformations -Burr holes -Craniotomy - helmet

Targeting Hormones

SERM Raloxifene (Evista); Tamoxifen (Nolvadex) activated estrogen receptors, decreasing bone reabsorption; block estrogen receptors in breast & uterus. Aromatase Inhibitors Anastrozole (Arimidex); Letrozole (Femara) block conversion of androgen to estrogen Androgen antagonists Gonadatropin Analogs Blocking testosterone Hormones in Cancer Therapy Prednisone, Dexamethasone, estrogen, testosterone, progesterone

Immunotherapy Supportive medications Supportive Therapies Transfusions

See above Anti-emetics, gastrointestinal, opioids Antibiotics, antifungals, antivirals, TPN, growth factors (Filgrastim (Neupogen); Peg-filgrastim Sargramostim (Leucine) Packed RBC's (once HbG is 6-8), Platelets

Seizures

Seizure- malfunction of the brain's electrical system resulting from cortical neuronal discharge Epilepsy- condition characterized by two or more unprovoked seizures Etiology -most seizures are idiopathic 1. Genetic factors may be involved -children with congenital defects and genetic disorders at increased risk -epilepsy runs in families 2. Hormonal Factors -in women with epilepsy, seizures often increase in frequency during menstruation 3. Acquired Seizure Disorder -brina injury may result in an acquired seizure disorder Patho 1. Epileptogenic focus -area in brain where seizure starts 2. Characteristics of electric discharge -may arise from central areas in the brain -may be restricted to one area of the cerebral cortex -may be in a localized area of the cerebral cortex and spread 1. Physiologic states associated with seizure development 2. Dehydration 3. Hypoglycemia 4. Hyponatremia 5. Fever 6. Fatigue 7. Emotional Stress Types of Seizures -generalized seizures involve both hemispheres 1. Tonic-clonic - most common type 2. Absence -"lights are on w nobody home", seen a lot in children 3. Infantile spasms -partial seizures involve specific area of the brain 1. simple partial 2. complex partial - often begin with "aura" CM 1. "Aura" -most common with simple and complex partial seizures -current thought is that it is part of the seizure itself 2. Ictal phase - event of the seizure 3. Post-Ictal phase - tired & difficult to rouse -may feel tired and complain of sore muscles and HA -sore, tired, difficult to arouse Diagnostic Tests 1. Laboratory analyses -CBC, CMP 2. EEG -24 hour, provoked or sleep deprived, hyperventilation (absence) 3. MRI Management DURING a witnessed seizure 1. Take measures to maintain patient saftey -padding on side rails -protect patient = no restraints -do not attempt to pry the mouth open or place anything in the mouth (may loose finger lol) -loosen restrictive clothing 2. GIVE 02 3. Clear Secretions -side-lying -suction if needed 4. Vitals, monitors 5. Document Management AFTER a witnessed seizure 1. Take measures to provide for client safety -confusion, agitation afterwards is common 2. Provide supplemental oxygen as needed 3. Clear secretions (suction if needed) 4. Vitals, monitors 5. Side-lying (recovery position) 6. Provide quiet environment/ non-stimulating -often tired afterwards 7. Document Treatment 1. Pharmacolotherapy 2. Vagal Nerve Stimulation 3. Diets - ketogenic 4. Seizure-alert dogs 5. Surgery Status Epilepticus 1. Acute Prolonged seizure activity -seires of seizures in a row w/o full recovery of consciousness -longer than 30 minutes -can lead to brain damage Management -maintain airway, breathing -assessment, vitals -administer IV diazepam, lorazepam, fosphenytoin.

Septic Shock

Systemic inflammatory response to documented or suspected infection Severe Sepsis: sepsis + organ dysfunction Septic Shock: presences of sepsis with hypotension despite fluid resuscitation + presence of tissue perfusion abnormalities Mortality rates as high as 50% Primary causative organisms -gram -&+ bacteria -endotoxin stimulates inflammatory response Patho: IMPAIRED CELLULAR METABOLISM AND ORGAN FAILURE CM 1. increase coagulation and inflammation DIC 2. decrease in fibrinolysis -formation of micro thrombi -obstruction of microvasculature 3. Hyper-dynamic state: Increased CO and decreased SVR -tachypnea/hyperventilation -temperature dysregulation (flush and warm skin) -decrease UOP -altered neurologic status -GI dysfunction -respiratory failure is common Early: Widening pulse pressure Peripheral edema Dyspnea Late: SEVERE HYPOTENSION Generalized edema Respiratory distress Severe hypoxemia Oliguria/anuria Other s/s of organ dysfunction

Intracranial Regulation Pharmocology

What is the primary inhibitory neurotransmitter in the brain? -GABA Anti epileptic Drugs -clients suffering from seizures on CNS depressants should never stop cold-turkey; long term therapy can result in co-morbid depression as a side effect. Heavily metabolized by the liver, drug interactions can be common. 1. Benzodiazepines -increase frequencies that the calcium channel is open, increases CNS depression -class of choice for sleep and anxiety disorders -should be avoided in hepatic insufficient (Look at LFT's!!) and depressed -all bento's have amnesic effects; this is valuable in a surgical client bc they are unlikely to remember unpleasant experiences; valuable to chemo patient bc feel horrible on chemo and can decrease anxiety -SCHEDULE 4!!!! -Antidote: Flumazenil (Romazicon): good for extreme overdose situation but not for CNS-depression medication dependent seizure patients -long 1/2 life; can bottom out a low blood pressure -Lorazepam is the safest in HI -Alprazolam (Xanax): anxiety disorders -Chlordiasepoxide (Librium): ETOH withdrawal -Clonazepam (Klonopin): seizure types -Midazolam (versed):conscious sedation 2. Barbiturates -increase the length of time they are open, increases CNS depression -greater risk for respiratory and cardiac depression and hepatotoxicity compared to benzo -DOC for febrile seizures in kids -interfere with absorption of fat soluble vitamins and folic acid (concern for pregnancy and children) -Category D pregnancy -Schedule 2 Drugs -Nurse is concerned about growth patterns, nutrition, child's safety (CNS depressant) and LASTLY dependence (weaning off drug will be carefully monitored) -Primidone (Mysoline): tonic/clonic seizures -Thiopental Sodium (Pentathal): no longer available -Methohexital (breivital): 3. Gaba Agonist Gabapentin Pregabalin - prodrug that is concerted into gabapentin via CYP enzymes -neuropathic pain commonly in diabetics -biggest concern is sedation and tolerance (develops in 1-2 weeks) -for seizure activity, needs to be tapered off. -Category C -SE: gingivitis- educate dental hygiene, sedation will go away; don't stop mediation 4. Hydantoins -used more for maintenance; bento's can actively break a seizure Phenytoin (Dilantin) -only stable with NS give slow Cerebrex: only used for SE -can give faster bc not as hurtful to the veins -can be given with dextrose or NS -not used for long term Both -most common of all AED -delays influx of sodium across neuronal membrane (and heart, can cause brady/block) -works on all seizures except absence and hypoglycemic (give glucose) -low hepatotoxicity but still check LFT's -like barbiturates, interferes with fat-soluble vitamin and folic acid absorption -Category D pregnancy -Monitor children growth patterns; occasionally CBC for BMD if showing infection, bleeding -most common AED associated with hyperplasia of gums (gingivitis): educated oral hygiene -in type 2 DM, monitor glucose; this can cause hyperglycemia -AED's increase CYP = metabolized faster -ataxic & slurred speech & HA can indicate overdose, this drugs has a slim therapeutic range. 5. Hydantoin-Like drugs (all are more hepatotoxic than phenytoin and SJS) -delaying sodium influx -Carbamazepine (Tegretol): likely to cause BMD (CBC, anemia, infection), promotes secretion of ADH (risk for CHF) -Valproic Acid- mood stabilizer (bi-polar), treat nerve damage, increased risk for pancreatitis. Lamotrigine - SJS 6. New Agents- lower seizure threshold, neuroprotective, pt's can go home on these -Topiramate (Topamax) Levitiracetam (Keppra) Oxcarbazepine (Trileptal) 7. Carbonic Anhydrase Inhibitor Acetazolamide (Diamox) -sulfa drug -diuretic (dehydration, hypokalemia, sun sensitivity) and creates cranial acidosis to change action potential of GABA receptors Assessment for CNS depressant administration -RR and mental status -most AED have slim therapeutic ranges due to CYP enzymes; monitor toxicity and drug levels -monitor LFT -CBC for most (sxs of BDM/infection) AED= CYP enzyme activation -this causes a fast metabolism and drug intolerance -DMII also taking OHA will be metabolized faster and cause hyperglycemia -all overhear drugs are less therapeutic ***DILEMMA*** Anti seizure + CNS depressants = depression Antidepressants are CNS stimulants = induce seizures Hypertensive Emergency Vasodilators (given IV) 1. Calcium Channel Blockers Nicardipine -prevents vasospasm 2mg/min =15mg max Clevidipine 2. Beta Blocker Esmolol (BreviBloc) - goal is to decrease HR first, risk for block and brady 3. Ace Inhibitor Enalaprit - prodrug, converts to enalapril Stroke 1. Antihypertensives Diuretics ACE Inhibitors Angiotensin 2 Receptor Blockers Calcium Channel Blockers Beta Blockers -brady Alpha-1 Blockers Alpha-2 Agonists Direct-Acting Vasodilators SE: syncope, reflex tacky, rebound HTN 2. Stroke Prevention -Antilipemics: these mostly control hyperlipidemia Statins Fibrates (Fibric Acid Inhibitors) Bile Acid Sequesterants Niacin 3. Antidiabetics Insulin -risk for hypoglycemia Sulfonylureas -risk for hypoglycemia (Gly-, gli-, Tol-) Biguanides: risk for lactic acidosis (Metformin (Glucophage) Alpha-glucosidase inhibitors: prevents complex carbohydrate metabolism 4. Atrial fibrillation Cardiac Digoxin Beta Blockers or CCBs Anticoagulants LMWH Warfarin 5. Aspirin Non-selective COX binding Inhibits synthesis of TXA-2 Irreversibly binding Single 325 mg dose affects platelets for 5-7 days 6. Antiplatlet agent: Clopidrogrel Bisulfate (Plavix) -risk for bleeding Active Stroke 1. Thrombolytic Reteplase Aletplase -used during non hemorrhagic stokes -rapid 1/2 life 2. Mannitol -maintains BP to kidney in surgery -only use in ARF never CRF 3. Calcium Channel Blockers Nicardipine (Cardene) -decreases peripheral vascular resistance working just in arterial smooth muscle, with minimal effects to the heart 4. Glucocordtcoid Dexamethasone -used in increasing ICP -monitor blood sugars -adrenal insuffienciy (taper off) -thin skin (prevent bed sores) Adjuvant Drugs 1. CNS Depressants opioids propofol dexmedetomidine (precedex) -can decrease respiratory drive and increase CO2 accumulation which can increase ICP 2. Pituitary Hormone Desmopressin -HI or Stroke pt can develop DI -can increase VWF production; monitor for sxs of clots 3. CNS Stimulant Methylphenidate (Ritalin) increases NE/dopamine in RAS (reticular activating system located in brain stem) 4. Other stimulants Atomoxatine (Adderall) Dextroamphetamine (Dexedrine) Modanafil (Prodigal)- helps stay awake w no jitters 5. Stool Softeners Docusate -SE: hyperkalemia prevention of staining = increase ICP, triggering dysrthymia 6. Additional Drugs Heparin Anti-emetics - projectile vomiting Laxatives Antidepressants