University of the Incarnate Word NURS 3312 patho_final_reviews 1,2 and 3 (A+ guide)

NUR 3125 Exam 1 Review  Review cellular components (lysosomes, nucleus, ribosomes, etc.): know function and associated disease if there is deficiencies or abnormal amounts o Plasma Membrane  Barrier against external environment  Protects organelles (mitochondria, lysosome, nucleus, etc.) Damaged plasma membrane could leave nucleus open which could cause DNA damage  Separates ICF from ECF  Semi permeable Phospholipid bilayer: allows lipid soluble substances such as oxygen and CO2 to diffuse thru  The proteins of the phospholipid bilayer do exchange w external environment via ion channels - when ion exchange occurs edema or dehydration can result  Outer surface of plasma membrane has glycoproteins (AKA Antigens) = surface markers If glycoproteins are altered – the immune system recognizes as non self and attacks o Mitochondria  Number of mitochondria depends on cell type- ex: muscles cell needs more energy, bone cells need less  Converts organic nutrients to ATP  When cellular hypoxia occurs- cells use anaerobic metabolism (glycolysis) which yields way less energy  Mitochondria are the only cell types that have DNA- subject to mutation by free radicals o Lysosomes  Degrades foreign substance and debris via digestive enzymes (proteases, lipase)  Autolysis- cell releases digestive enzymes to destroy cell that died  Heterolysis- macrophages engulf foreign material  Macrophages contain many lysosomes  Lack of lysosomes - harmful accumulation of non degraded substances Ex- Tay Sachs disease (accumulation of ganglioside)  Digestive enzymes: proteasomes/ peroxisomes  Proteasomes degrade polypeptide chains  peroxisomes break down long chains of fatty acid and free radicals  Adrenoleukodystrophy: disfunctional perioxisomes - long fatty acid chains accumulate in nervous system - dementia, paralysis, death o Endoplasmic reticulum  Network of tubules that act as a transport system Smooth ER: location of lipid production  Rough ER: protein synthesis  ER stress- protiens cant travel to their locations and are degraded - neurodegenerative disease, atherosclerosis, diabetes, cancer, obesity o Ribosomes  Organelles composed of rRNA – cellular protein factories  Different cells manufacture different protiens (ribosomes in pancreatic beta islet cells synthesis the protein that makes up insulin)  Ribosomes cant make protein during hypoxia o Golgi Apparatus  Ribosome synthesis protein - protein is transported via ER to the golgi to be processed, packaged, and secreted (converts into actual hormone) o Nucleus  Contains DNA (the bodies genetic material) which regulates all cell structure and function  Purine bases (a and g) and pyrimidine bases (thymine and cytosine)  Double helix forms individiuals genetic code  Review DNA replication, transcription, translation  Replication: DNA strand uncoils a begins to split into two separate strands o One strand becomes a template and the new nucleotides pair up with DNA template strand o Daughter strand forms alongside the original strand o At completion: two identical strands of DNA o Protein synthesis required for normal physiologic function o DNA directs cell to carry out protein synthesis through a two step process  Transcription- occurs in nucleus (RNA is tuned into DNA) o Two strands of DNA uncoil and sepreate o One strand is template for RNA synthesis (AG, UC) no guanine o RNA copies genetic info from the main DNA molecule and exits the nucleus  Translation- occurs in ribosomes (mRNA provides directions for protein synthesis) o Ribosome gets the message from the RNA (mRNA) o RNA transfers genetic info to the ribosome for synthesis of specific cellular proteins  Anaerobic vs. anaerobic processes  Aerobic: occurs at mitochondria requires oxygen, privdes max amount of energy for cellular function Net yield = 34 ATP Anaerobic: occurs outside mitochondria when no oxygen available, produces significantly less energy Net yield= 2 ATOP + pyruvic acid Lactic acid - lactic acidosis  Review types of cells (labile, permanent, stable) Three types of cells: -Labile: continually divide and replicate throughout life Skin, hair, nails, GI, GU, mucosal cells, cancer cells -Stable: Regenerates when needed; bone cells and hepatocytes -Permanent: Do not ever regenerate; neurons and cardiac cells  Review the Sodium-Potassium pump o K higher concentration inside cell, Na higher concentration outside cell (salt on ur skin, banana inside peel) o for every three sodium ions pumped out, two potassium ions are pumped in o membrane is more soluable to K, K leaks out easier = gradient of positivity (more positive outside cell0 o pump uses atp to more Na and K (ATPase Pump) – maintains resting potential and cellular fluid volume o can be pharmacologically altered via certain drugs (cardiac glycosides- improve the force of the hearts contractility) o Pharmacologic slowing of the ATPase pump keeps more calcium inside the heart muscle cell- strengthening force of contraction o Inotrophy= force of heart contractility) o Defects with pump can lead to Atrial Fibrilliation o Dysfunction of Na K Pump: when the cell is unable to produce Atp- physiologic functions are reduced -lack of Atp causes energy dependent calcium pump to not work - calcium accumulates - pathologic conditions (arteriosclerosis, aortic sclerosis, breast calcifications) -when pump cant pump sedum out- increased sodium causes cellular edema  Identify 6- types of cellular adaptation and relate them to clinical manifestations or disease processes  Adaptive changes = compensatory changes to try and regain homeostasis  Maladaptive= derangement of structure and growth (neoplastic growth)  Histology= study of cells and tissue, diagnostic info related to specific cellular change  Biopsy= extracts sample from and organ or tissue for histological evaluation  6 adaptive/maladaptive changes: HAHNMD  Hypertrophy: cells grow in size, results in enlargement of functioning tissueo Pathologic- cell size increases but supportive structures don’t -disease or compensatory maladaption -no associated angiogenesis- edema -Left ventricle hypertrophy results from hypertension o Physiologic- normal stimuli includes exercise, ex: biceps get larger from lifting -athletes get cardiac hypertrophy due to enlargement of cardiac muscle cell  Atrophy: cells shrink in size (in response to metabolic requirements) o Etiology- disuse or diminished workload, lack of nerve stimulation, inadequate nutrition, ischemia, aging  Hyperplasia: increase in number of cells, occurs only in cells capable of mitotic division (like eptithelium or glandular tissue, not cardiac or brain) o Stimulated by hormonal or compensatory cellular o Hormonal stimulation in pregnancy- estrogen stimulation results in mitotic division of breast gland cells (increase in number of breast gland cells) o Prostate gland cells increase in number bc of testosterone (benign prostatic hyperplasia) (maladaptive) o Keloid scars (maladaptive bc it overcompensates by exceeding the cell mass necessary for regeneration)  Metaplasia: replace of once cell type by another cell type o Occurs in response to chronic inflammation, environmental conditions from genetic programming o GERD causes squamus cell epitheluem of esophagus to turn into columnar stomach-like cells (greater acid tolerance)  Dysplasia o Deranged cellular growth (funky looking cells- vary in size shape and architecture) o Results from chronic inflammation - precancerous condition o Cervical dysplasia- precursor to cancer  Neoplasia: new growth o Proliferative cancerous cell growth o Benign neoplasm: well differentiated cells (resemble healthy cells of tissue origin) o Neoplastic/malignant: poorly differentiated (appears very different from healthy cells). Tumor= neoplasm  Review causes of cell injury (endothelial injury, hypoxia etc.)Causes of cell injury: o Hypoxic cell injury  Oxygen deprivation- blood cant deliver enough oxygen to cells bc of:  Diminished circulation (ischemia)  Anemia (lack of Hgb molecule)  Low concentration of oxygen (altitude)  Inadequate oxygen diffusion at alveoli (pneumonia)  Suffocation injury  Airway obstruction (FB or inflammation)  Hypoxia causes anaerobic metabolism- generates low ATP, pyruvic acid and 2 ATP  Pyruvic acid changes into lactic acid- alters cells biochemical activity o Free radical injury:  Reactive molecules that are a biproduct of oxidative phosphorolation  Oxidative stress: when free radical generation overwhelms the mechanism of removal and causes cell injury  EX: Reperfusion injury o Physical agents  Trauma- laceration, gsw, etc  Hyper/hypo thermia  Electric shock  Inflammation o Chemical agents  Endogenous, biological substances: Hyperglycemia, hypernatremia, etc  Exogenous, synthetic substances: drugs, pollutants, poisions, NSAIDS o Infectious agents- bacteria, fungi, virus, etc o Immunological- autoimmune o Nutrition imbalance:  Undernutrition, overnutrition and malnutrition cause cell injury  Ex: Low levels of albumin in protein starvation  Cell dysfunction occurs without specific vitamins, proteins, carbohydrates, minerals  Excessive fat stores place stress on heart and pancreas (heart disease, DM) o Endothelial cell injury  Blood vessels are lined by endothelium  Endothelia cells secrete VEGF (necessary for synthesis of blood vessels), nitric oxide (vasodialation), endothelin (vasoconstriction)  Glucose, epi, lipids, platelets, etc all act on endothelin!  Endothelium is injured by htn, hyperglycemia, free radicals, ldl, angiotensin 2 Endothelial injury is the intiator of CV disease and arteriosclerosis  HTN: shearing force, damages interior wall of arteries- can cause aneurysm  DM hyperglycemia: High blood glucose levels chemically injury membranes of endothelial cells, stimulates endothelin (vasoconstrictor)  Free radicals: Cigarettes are a major source (vasoconstriction)  Angiotensin II (potent vasoconstrictor): RAA product- arterial narrowing which increase BP causing high workload for heart  LDL: Generates atherosclerotic plaque  Two major forms of cell death: Apoptosis: Genetically programmed degenerative change that results in cell death o Organized process o Eliminates unwanted, unnecessary or damaged cells without inflammation o No adverse effects Cell Necrosis o Cells die due to stressors or insults that overwhelm the cell's ability to survive o Irreversible process o Infarction: death of a tissue due to prolonged ischemia  Selye’s General Adaptation Syndrome- what occurs during each stage?  Alarm o SNS: increased HR and respirations, decreased peripheral circulation, decreased blood flow to GI and GU, pupils dialate, catecholamines (norepinephrine) realeased from adrenal medulla - causes vasoconstriction o Hypothalamus: release ACTH which causes pituitary to release endogenous steroids (glucocorticoids), elevated blood glucose, elevated immunity- eventual immunosuppression o Aldosterone- sodium and water reabsorption o Posterior pituitary- ADH (vasopressin)  Resistance o Time limited- body relaxes (PNS) or stress takes over  Exhaustiono Systemic dysfunction if stressor doesn’t stop  Review mediators of inflammation (ex.: tumor necrosis factor, prostaglandins, histamine, bradykinin): What symptoms do they cause? o Histamine and bradykinin cause vasodialation (premits fluids wbcs and plateles to travel to sight of injury Histamine:  - released from basophils, platelets, and mast cells.  Physical injury, immune reactions, cytokines, and other inflammatory mediators stimulate histamine release.  Sneezing, rhinorrhea (runny nose), eye tearing, sinus inflammation, and pharyngeal irritation are consequences of histamine released in the upper respiratory tract. (Allergies) Prostaglandins:  released from WBCs  Phospholipase stimulated and acts on phospholipids (constituents of the WBC cell membrane)  Phospholipids broken down into arachidonic acid (AA)  Two enzymes involved to transform PGs into AA  Cox-1: (good)stimulates gastric mucous production, enhance renal perfusion, platelet aggregation  Cox-2: (bad) stimulates inflammation, causes pain, fever, swelling, muscle contraction -Leukotrines causes Bronchospasm and bronchoconstriction narrows airway, can lead to death very quickly Drugs can block leukotrines -Sepsis- blood stream infection. Early recognition; ELEVATED TNF which causes hypotension MAP- average of systolic and diastolic  IL-1, IL-6 major cytokines produced by macrophage Induces fever, loss of appetite, lethargy, weight loss, cachexia  Facilitates release of corticotropin and adrenal corticosteroids  Sepsis: TNF-alpha provokes hypotension, tachycardia, acidosis -Swollen Lymph nodes: Lymphadenopathy, or lymphadenitis  Review 3-stages of inflammation Stage 1: Vascular Permeability-Inflammatory mediators (histamine, bradykinin) cause blood vessels to dialate and become more permeable - permeability permits fluids WBCS and platelets to travel to the sight of injury -macrophages consume foreign material via phagocytosis -Patient has infection with edema: look if theres something draining from sight (exudate) Purulent- not clear, green or brown or other colors cloudy, smells bad Transudate- watery, can be light yellow liquid odorless. Ex; when you pop a blister -once fluid flows out of the blood vessels to the injures tissues -  Rubor (redness)  Tumor (swelling)  Calor (heat)  Dolor (pain)  Loss of function  Inflammation- inspect and look for redness, palapte to see if pain or warmth Stage 2- Chemotaxis  Chemical signal from microbial agents, endothelial cells, and WBCs attracts platelets and other WBCs to the site of injury- WBC’s line up at site of inflammation (margination)- release of inflammatory mediators that amplify, sustain or deactivate the process  Inflammatory mediators released: Cytokines  Tumor necrosis factor tnfa  Interleukins (ILs) il 1 and 6  Acute phase proteins released  C-reactive protein: crp and esr is commonly measure to assess if theres an inflammatory reaction  Fibrinogen Blood Counts -Cbc= complete blood count. Includes wbc, hgb, hct, plt -Normal- 4000 to 10000. wbc count greater than 10000 (Leukocytosis) = inflammatory reaction -Leukopenia/Neutropenia- low wbc count These proteins are indicative of inflammation:  C-reactive protein (CRP)  Erythrocyte sedimentation rate (ESR)  Leukocytosis with shift to left (bandemia) indicated big infection  90 percent neutrophils on differential= bacterial infection  90 percent lymphocytes= viral Types of WBCs  Neutrophils -immature= BANDS If theres a high level of bands that means all the mature neutrophils are used up. Signafies inflammatory reaction is really big-Shift to the left: high number of bands (Bandemia) Indicates acute inflammatory response -first responders (24-48 hours) -begin phagocytosis  Lymphocytes  Eosinophils- allergic reactions  Basophils- allergic reactions  Monocytes (macrophages) Neutrophils, basophils, eosinophils= Granulocytes  cytoplasmic granules that contain important enzymes and inflammatory mediators to fight infection.  After initial 24-48 hours, monocytes are activated Monocytes turn into macrophages - phagocytosis CBC with Differential  A WBC with differential measures the total number of WBCs and calculates the percentages of specific types of WBCs within the total.  90% neutrophils: bacterial infection  90% lymphocytes: viral infection  High eosinophils = allergic reaction Stage 3: Systemic response  Fever -Pyrogens activate prostaglandins to reset the hypothalamic temperature-regulating center in the brain to a higher level- higher body temperature increases the efficiency of WBCs in their defense of the body. An antipyretic = drug that brings down fever -Chills with fever: Rigor; when hypothalamus sets tempuraturee higher than blood current temperature- body has sensation of feeling cold. Muscles contract to try and generate heat -fever can cause seizure in pediatric patients - keep fever below 102°F through the use of antipyretic medications such as aspirin, ibuprofen, or acetaminophen. These medications inhibit prostaglandin formation  Pain (could be for vascular permeability  General malaise (a general feeling of poor health)  Lymphadenopathy (swollen lymph nodes)  Anorexia  Sleepiness  Lethargy  Anemia Weight loss  Inflammatory mediators released from WBCS: -Prostaglandins -Leukotrienes -Tumor necrosis factor (TNF-alpha)-ENBREL Tnf is a cytokine Enbrel is given to autoimmune dieases (lupus) stops inflammatory response. Can cause immunosuppression -Interleukins (ILs)  Review principles of chronic inflammation  Chronic inflammation characterized by predominance of monocytes, lymphocytes and macrophages  Etiologic agents  Mycobacterium tuberculi (TB)  Treponema pallidum (syphilis)  Coal dust (black lung disease)  Autoimmune disease (rheumatoid arthritis)  Systemic lupus erythematosus  Granuloma: walled off section of the bacteria  What lab test indicate infection/inflammation: review WBC material  A WBC with differential measures total number of WBCs & calculates the percentages of specific types of WBCs within the total o 90% neutrophils: bacterial infection o 90% lymphocytes: viral infection o High eosinophils = allergic reaction  Review 3-processes of wound healing (primary, secondary, tertiary) Wound Healing 3 processes:  Primary intention: clean laceration, simple re-epithelization. Ex- surgical laceration  Secondary Intention: can’t close wound bc there is pieces of tissue missing. Regeneration of missing cells is not possible. May eventually heal but will have significant scar tissue; Myofibroblasts cause wound contraction. Ex- Decubitus ulcer- breakdown from skin pressure  Tertiary Intention: large gap of tissue missing, contaminated wound. Cleaned and left open for 4-5 days before closure  Pathophysiologic changes in the aging adult: changes in renal function, medication administration/metabolism, mental status, neurotransmitters, pulmonary, infection  Renal function:- GFR decreased= impaired renal function - Atrophy of the arterial blood vessels - blood flow to the kidneys decreased - Lower creatine clearance - Serum creatinine level and BUN rises (bun increases w dehydration) - (Kidneys normally filter blood and remove toxins and regulate bp Creatine clearance tell you how good GFR is - Patients can get volume overload and fluid and electrolyte abnormalities because they cant excrete - Hyperkalemia - Cant produce concentrated urine - dehydration - Diminished thirst response - will not feel thirsty even when signifcantlly dehydrated - Check serum creatine levels BEFORE admin meds that are excreted by kidneys. (to avoid toxicity)  Medication administration/metabolism o Watch out for polypharmacy o Influences on drug metabolism for older adults: decreased renal function, liver function, subcutaneous fat, body water, protein binding of drugs o Adjust medication dosages for older adults  Mental status o Behaviors related to sleep pattern and mild memory loss may be related to changes in neurotransmitters. o Vitamin B12 deficiency - demyelination of dorsal column of spinal chord - gait instability and paresthesias o Older adults may be unaware of injury because they have less pain sensitivity o Presbyopia: farsightedness; can see far better than near o Presbycusis: loss of ability to hear some high and low tones o Dementia  Neurotransmitters  Pulmonary o Stiff chest wall bc costal cartilage calcification o Kyphosis o Weakened cough reflex: risk for pneumonia o Barrel chest  Infectiono Harder to tell when there’s infection- less rise in WBCs, reduced fever and pain o Behavioral changes, such as confusion and disorientation, may be the only symptoms expressed during infection. o “Wind, water, wounds”  Sudden change in mental status?  Pulmonary infection  Urinary infection  Integumentary infection  Skin integrity: keloids, urticaria, dermatitis, lichenification, birth marks, differentiation between 3-types of skin cancer, changes seen with autoimmune disease (ex. lupus, scleroderma, etc.), macules vs. papules, nodules, bullae  Determine classification/depth of burn injury  Determine fluid volume resuscitation based on Parkland formula calculation  Determine TBSA % burn based on Rule of Nine calculation  Systemic pathophysiologic effects caused by burn injury. What happens pathophysiologically/what is the patient at risk for in the following system?: GI system, renal system, fluid loss/tissue edema (what vascular changes are seen?), pulmonary injury  Na k pump  Too much na = swelling  Tay sachs- sigmificant in pediatric  TNF= wide spread hypotension (low bp)  Leukotrienes- bronchoconstriction  Granulomatis disease- TB (chest x ray) Granuloma- encapsulated  Bradykinin= vasodialation  Prostaglandins are responsible for fevers  Weakened cough reflex  Hemangiomans- blood vessels  Port wine and Mongolian- patches  Autoimmune- alterations in immunoglobulins  Albumin keeps fluids from leaking. Burn pts loses albumin - leaky veins arteries - edema - reason for the parkland formula  Treat pt reverse zone of stasis to avoid necrosis  Pateints w burns get curling ulcersPathophysiology Exam 2 Pulmonary (Lane) Focus on pathophysiology · Pneumonia • Inflammation of the lung tissue in which alveolar air spaces fill with purulent, inflammatory cells, fibrin • Bacterial or viral • Lower respiratory tract disorder • Inhalation of droplets (droplet transmission) • Pathophysiology: • Acute inflammation spreads to the lower respiratory tract and alveoli- Mucus and exudative edema accumulate between the alveoli and capillaries • Alveoli attempt to open and close against the purulent exudate- sounds heard over the alveoli opening against the exudative fluid are crackles • Layer of infectious exudate at the capillary-alveoli interface that hinders optimal gas exchange • Symptoms: cough (may or may not produce sputum), fever, chills, pleuritic chest pain, dyspnea (difficult or labored breathing, hemoptysis (coughing up blood), decreased exercise tolerance, myalgia (muscle pain) · Tuberculosis • Can be found in other parts of the body (other than respiratory): • adrenal gland, vertebrae • lymph nodes • can spread within the bloodstream and cause multisystem disease • Spread by the inhalation of airborne droplets containing M. tuberculosis bacilli. • Risk factors: people with aids (20 times more likely than those who are immunocompetent), diabetics, IV drug users, people taking steroids • Endemic in Mexico, the Philippines, Vietnam, China • Leading cause of mortality among people who have HIV • Tubercle formation: tissue inflammation occurs as the bacilli multiply - pulmonary macrophages & WBCs migrate to the infected area - WBCs cannot kill the organism but wall off the infection • The lesion (tubercle) is a granulomatous accumulation of WBCs, bacilli, and fibrotic tissue - scar tissue grows around the tubercle, and the bacilli become inactive• Symptoms: chronic cough, purulent sputum, hemoptysis (coughing up blood), weight loss, anorexia (lack or loss of appetite), low grade fever, night sweats • Diagnosis: Mantoux tuberculin skin test- does not differentiate inactive disease from active disease (need chest x ray) • Check sight after 48 hours: An induration of 5 to 15 mm may be positive depending on other patient conditions. A reaction greater than 15 mm of induration is interpreted as positive in all persons. • In other countries people receive BCG vaccine. They will test positive on Mantoux skin test · Emphysema · Alveolar wall destruction (become like over extended balloons) → retention of air bc alveoli can't recoil · Patient cannot get air OUT of lungs · Barrel shaped chest bc excessive air in lungs · Chronic hypercapnia (buildup of CO2 in lungs) · Overdistention of alveoli with trapped air- creates obstruction to expiratory airflow, loss of elastic recoil of the alveoli and high residual volume of carbon dioxide · Hyperreactive airways to irritants- leads to bronchoconstriction · Chronic bronchitis • Chronic bronchitis is diagnosed when a patient reports a history of bronchitis for 3 months out of the year for at least 2 years • Productive cough, airway inflammation • Inflammatory changes cause permanent remodeling (leukotrienes, cytokines, interleukins, TNF (tumor necrosis factor ) • Poor ventilation and oxygenation causes pulmonary arterial vasoconstriction- Pulmonary HTN, right ventricular enlargement (Cor Pulmonale) • Hypersecretion of mucus and edema inhibit ventilation • Patient cannot get air INTO lungs · Asthma · Bronchial hyperresponsiveness triggered by allergens, infection, etc (Hyper-reactive obstructive airway disease) · Chronic inflammatory disorder · Reversible airway constriction · Triggers: allergens, pollutants, upper respiratory infection, exercise, cold air, GERD (Gastroesophageal reflux disease) aspirin, nsaids · Symptoms: wheezing, cough, dyspnea, chest tightness, use of accessory muscles, eczema · IgE elevated· FEV1 decreases · Decreased overall FEV1/FVC · The FEV1 and FEV1/FVC ratio should then be reassessed after a bronchodilator is administered to diagnose and evaluate the severity of asthma. · Mild intermittent asthma: o Occurs fewer than two times a week during waking hours o Occurs less than twice a month at night · Mild persistent: o Occurs than twice a week, but not daily o Occurs less than twice a month at night · Moderate persistent: o Every day, quick relief inhaler daily, interferes with activity · Severe persistent: o Continuous, severe limitations Status asthmaticus: Persistent bronchoconstriction that endures despite attempts to treat the attack with various medications.  Uneven distribution of ventilation results from generalized severe bronchoconstriction, leading to a dramatic fall in arterial oxygenation  Status asthmaticus can be fatal · Pneumothorax · Collapsed lung · Presence of air in the pleural cavity- causes collapse of large section or all of lung tissue · Primary spontaneous: absences of lung disease, inciting event (Marfan syndrome) · Secondary spontaneous: underlying pathological process occurs in the lung (TB, pneumonia, CF (Cystic fibrosis, mucus blocks airway) · Traumatic: penetrating wound (rib fracture, GSW (gunshot wound) · Tension: Closed, penetrating injury- causes buildup of air within the pleural cavity that compresses lung, cardiac structures and vena cava (life-threatening) · Iatrogenic (from doctor), relating to illness caused by medical examination or treatment. · Pleural effusion • A pleural effusion is an abnormal collection of fluid within the pleural cavity that compresses lung tissue and inhibits lung inflation • Pathophysiology: disruption of balance between hydrostatic and oncotic forces causes fluid to leak out of pulmonary capillaries and into the pleural space • Edematous fluid accumulates within the pleural space • Causes: • heart failure • severe pulmonary infection• neoplasm • Fluid may be an exudate or transudate, purulent, lymph, or sanguineous (bloody) Transudate is fluid pushed through the capillary due to high pressure within the capillary. Exudate is fluid that leaks around the cells of the capillaries caused by inflammation. • Transudative: Cirrhosis, CHF, Nephrotic syndrome • Exudative: Malignancy, pancreatitis, tuberculosis, trauma, infection • Thoracentesis: relieves pressure on lungs and provides for fluid analysis • Symptoms: dyspnea, tachypnea, pleuritic chest pain, dullness to percussion, diminished breath sounds, flat dull sound with percussion · Pulmonary embolism • PE: clot that has traveled to the pulmonary arterial circulation & caused obstruction of arterial blood flow through the lungs • Usually the embolism originated in the venous circulation as a deep vein thrombosis in the leg or in the right side of the heart as an atrial thrombus • Thrombi also often form around central venous catheters and travel to the right side of the heart into the pulmonary artery • Leading cause of death: vague presentation • Can be avoided by using compression stockings · Acute respiratory distress syndrome (ARDS) (wet lung??) · Pulmonary dysfunction characterized by diffuse alveolar injury, pulmonary capillary damage, bilateral pulmonary infiltrates, and severe hypoxemia. · It occurs in critically ill patients and is commonly a sequela to trauma, sepsis, drug overdose, massive transfusion, acute pancreatitis, or aspiration · The most common risk factor for ARDS is sepsis · Other causes: direct lung injury (aspiration), indirect injury (systemic illness) · Sudden progressive pulmonary edema- not related to cardiac disease · A defining feature of ARDS is arterial hypoxemia that does not improve with administration of oxygen · ABG levels demonstrating a Po2 of 50 mm Hg or less and Pco2 of 50 mm Hg or more are diagnostic · Non-compliant lung: difficult to ventilate · ARDS is a major cause of death Infectious Disease (Kayla)Terminology - Pathogen: Specific microorganisms that are capable of causing infectious disease; they are categorized as viruses, bacteria, fungi, and parasites - Host: the term used to describe the human or animal invaded and colonized by a pathogen - Colonization: indicates that a pathogen is living within the host but does not mean infection exists. MRSA, Streptococcus - Infection: describes the invasion, colonization, and multiplication of pathogens within the host; diagnosed when there is isolation of a pathogen or evidence of its presence and pathogen-related host symptoms Virulence - Different pathogens have varying disease-producing potential, which is called VIRULENCE - VIRULENCE FACTORS that enhance the pathogen’s ability to infect the host; pathogenic toxins that destroy host cells adhesion factors that enhance attachment of the pathogen to the host cells - the SEVERITY OF INFECTION depends on the virulence of the pathogen and the strength of the host defenses at the time of infection Reservoir - a reservoir is a source of a pathogenic organism that may or may not be suffering from the disease caused by the pathogen o EX: a child suffering from chickenpox would be considered a reservoir because he or she harbors the transmittable organism o FOMITE: Environmental objects can also act as reservoirs of microorganisms EX. An unsanitary bathroom or desktop Bacteria  Advantageous or harmful  Colonized with normal flora  Categorized according to shape AND aerobic/ anaerobic respiratory capability and lab staining o CATEGORIES  Cocci= ROUND  Bacilli= ROD SHAPED  SPIROCHETES= SPIRAL o Bacteria can either be gram positive or gram negative  Gram positive: Bacteria have a thick, peptidoglycan-rich cell wall that turns purple with the staining procedure  Gram negative: Bacteria have a thin cell wall that contains less peptidoglycan and takes on a pink-colored staino Review the specific bacteria that we discussed in class · Review virulence, adhesion, colonization Viruses  Consist of a deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) genome surrounded by a protein coat  A virus enters a human cell and reprograms the infected cell to synthesize viral particles o RHINOVIRUS o INFLUENZA VIRUS o HEP B  Example: Varicella zoster causes chickenpox that consists of a blister like rash and upper respiratory infection - after the illness VIRUS REMAINS DORMANT within the DORSAL GANGLIA of the SPINAL CORD Portal of Entry  The portal of entry for microorganisms o SKIN o RESPIRATORY SYSTEM o GI SYSTEM o UROGENITAL TRACTS  SKIN: Portal of Entry o The skin surface has normal flora (bacteria) that consists of  Staphylococcus epidermidis (S. EPIDERMIDIS)  Staphylococcus aureus (S. AUREUS)  Corynebacterium and Candida albicans (yeast fungal infection) o *The skin is most vulnerable to infection when the surface breaks*  EX: DECUBITUS ULCERS  RESPIRATORY: Portal of Entry o Droplet infection o Droplets of fluid emitted from SNEEZING and COUGHING of infected people contain LARGE inoculums of pathogens  EX  PNEUMONIA  CONSOLIDATION on CXR  Defenses of the respiratory system  Mucocillary defense: respiratory tract cilia and mucus  Sneezing and coughing for defense  The alveoli in the lungs  Respiratory epithelial cells also secrete interferon: body’s natural antiviral cytokine  Immunoglobulin A (IgA) is found in LARGE amounts of B lymphocytes of the respiratory tract  Cervical lymph nodes within the oropharyngeal region: store WBCs to defend against inhaled INFECTIOUS agents Gastrointestinal Infection Fecal-oral route indicates transmission of gastrointestinal pathogens occurs because of ingested matter that was contaminated by FECAL MATTER o Ex  Escherichia coli (E. COLI)  Enterococcus faecalis (E. FAECALIS)  HEP A  Salmonella Genitourinary Infection  Urogenital infections commonly originate from entry of pathogens into the URETHRA- urine outflow is a protective mechanism that constantly flushes microorganisms out of the body Bloodborne Infections  Blood transfusion is the most common method of transmission of bloodborne infections o Needlestick or lacerating injury with a sharp instrument contaminated with infected blood o Intravenous drug users: shared needles o Eye, oral, skin  *THE NURSE is at risk for HIV because of the direct contact* Infection in a Pregnant Woman can be transmitted two ways 1. Infection passes from the maternal bloodstream INTO the placenta INTO the fetal circulation 2. Infection transmitted during childbirth - vaginal secretions - membranes in contact with newborn (congenital infection) 5 stages of Infection  1. Incubation period (this can be weeks, days, hours)  2. Prodromal stage (when the person feels the sick coming on)  3. Acute stage  4. Convalescent stage  5. Resolution phase Bacterial Infections  Staphylococcal infections o Gram-positive round bacteria that form clusters o Staphylococcus aureus (S. AUREUS) colonizes the skin, vagina, nares and oropharynx as normal flora o Leading cause of nosocomial infection and surgical wound infection  Resistant Staph o S. aureus has developed resistance to many antibiotics o Strains commonly encountered in clinical settings:  Methicillin-resistant S. aureus (MRSA)  Vancomycin - resistant S. aureus (VRSA)  Streptococcus o Group A beta hemolytic streptococcus (GABHS) also called streptococcus pyogeneso Gram positive o Secretes large numbers of toxins that facilitate the spread of infection through tissues: DNAases, proteases, and exotoxins  S. pneumoniae: CAP  E. faecalis: UTI Bacterial Pneumonias  Streptococcus pneumoniae: community acquired pneumonia o Gram-positive diplococci bacteria o Influenza o Smoking: changes ciliary function o Clinical signs  Mycoplasma Pneumonia o Atypical pneumonia o 40 years o Crowded areas  Acute onset of high fever: rigers (violent shakes) productive cough, pleuritic chest pain, dyspnea, tachypnea, tachycardia, dyspean, sweats, malaise & fatigue  Auscultation crackles  Diagnostic tests: o Chest x-ray o Sputum culture o Pneumococcal vaccine every 5 to 10 years  Legionella Pneumophila Bacteria o These bacteria are found most often in the warm, moist, air conditioning systems of large buildings, though they have been found in water delivery systems o The microbe is transmitted via aerosolized mist in the air: NOT person- toperson transmission Pseudomonas Infection Gram negative rod  Soil, water, plants  P. aeruginosa  Common in patients hospitalized 1 week  Nosocomial  IV lines, severe burns, trauma, surgery, catheters Haemophilus Influenza: Meningitis  Gram negative  Bacteremia, meningitis, pneumonia  5 - 10% cases of meningitis  Droplet inhalation  Bacterial or viral  Inflammation of the meningeal layers that surround and protect the brain and spinal cord  Bacterial: very serious  Viral: “aseptic” usually milder disorder Meningitis  Streptococcus pneumonia (pneumococcus)  Neisseria meningitidis (meningococcus) o Meningococcal vaccine  Haemophilus influenzae o Hib vaccine  Clinical Manifestations o Nuchal rigidity  Diagnosis o Lumbar puncture (LP) Gastrointestinal Bacterial Infections  Salmonella  Shigella  E. Coli  Campylobacter o All of these are bacterial causes of gastroenteritis worldwide o Causes severe diarrheal illness E. Coli  Gram negative, rod-shaped bacteria  Inhabit the intestines  Can cause cholecystitis, bacteremia, UTI, pneumonia o A specific strain called E. Coli causes severe gastroenteritis and can cause hemolytic- uremic syndrome o Fecal- oral route Tetanus  Neurological disorder caused by Clostridium tetani (C. tetani) = a toxinproducing, spore- forming anaerobic bacteriao Found in soil o Occurs after a penetrating injury such as a puncture wound or laceration  C. tetani toxin blocks inhibitory neurotransmitters, causing hyperactivity of neurons o Muscle spasms (tetany), particularly in masseter muscles and jaw= lockjaw Tdap Vaccine  Adults should receive Tdap vaccination every 10 years because it offers the best prevention against pertussis, tetanus, and diphtheria Clostridium difficile (C. difficile)  C. difficile: spore-forming, toxin- secreting anaerobic bacteria  Toxins disrupt the intestinal mucosa - erode the intestinal epithelial cells - forms pseudo membranes that contain necrotic tissue, white blood cells (WBCs) and mucus  Common predisposing factor: o Long-term antibiotic use o Alteration of the normal flora in the gut  Patient to patient transmission: nosocomial infection Lyme disease is caused by a bacterial spirochete called Borrelia burgdorferi (B. burgdorferi) o Found in forest animals such as squirrels, rodents, and the white-tailed deer  A tick that feeds off one of these animals can harbor the microorganism o Neither the reservoir (deer) nor vector (tick) becomes ill because of the microorganism o Incubation period of 3 to 32 days - a rash known as erythema migrans begins as a painless red macule that expands slowly to form a target like lesion o Cranial neuritis: inflammation of the nerve cause one side of the face to be paralyzed aka bell's palsy o 60% of patients develop arthritis Immune System (Kayla) Immune system responses  Infection stimulates immune system to defend against pathogens o ADAPTIVE: defends the body upon preexposure to pathogen o INNATE: defends regardless of previous exposure Innate (first response) o Toll-like receptors (TLRs) on cells of innate immune system stimulate immune response o Complement system mediators attach pathogens o Anatomic barriers block entry of foreign substanceso Macrophages provide constant surveillance WHICH stimulate inflammatory response AND destroy bacteria and undergo apoptosis  Mediated by cytokines - produced by WBCs - promote leukocyte recruitment and acute inflammation  Natural killer cells - granular lymphocytes which destroy tumor cells and viruses Adaptive (second response) o A more specific form of protection: it is developed after exposure to antigens o This immune mechanisms act rapidly, specifically, destructively and with memory for every individual antigen it has encountered o Antigen specific o CD4= T helper cells  The CD4 cell influences all other cells of the immune system including other T cells, B lymphocytes, macrophages and NK cells  Cells are involved in cell-mediated immunity and antibody mediated adaptive immunity o CD8= cytotoxic T cells  Directly attack the antigen o T LYMPHOCYTES: cell- mediated immunity or T- cell immunity (thymus and bloodstream) o B LYMPHOCYTES: humoral immunity or B cell immunity (bone marrow) o IMMUNOGLOBULINS (look at table 10.5)  Every human has surface antigens called MAJOR HISTOCOMPATIBILITY COMPLEXES (MHCs) aka HUMAN LEUKOCYTE ANTIGENS (HLAs). *IMPORTANT FOR TRANSPLANT AND BLOOD TRANSFUSIONS* o The adaptive allows body to tell difference from antigens that belong and antigens that are invaders Prevention/ Eradication of Infection  Prevention of infectious disease through administration of vaccines in the most efficient method of controlling CONTAGIOUS disease within a population o ANTIBIOTICS o IMMUNOLOGICAL BOOSTING AGENT o SURGERY ANTIGEN- Presenting Cells (APCs)  T cells cannot be activated by antigen alone: APCs process the antigen first and induce cell- mediated immunity  APCs are also referred to as DENDRITIC CELLS - located in epidermis and mucous membranes where antigens enter the body - release cytokines B cells - Plasma Cells: IgS  B lymphocytes (B cells) are naive or immature until they encounter antigens  After exposure to an antigen, B cells are stimulated to further mature into plasma cells  As plasma cells, they have the ability to produce specific proteins called immunoglobulins (Igs) also called antibodies which attack the antigenImmunoglobulins IgM: first responder IgG: second exposure to the same antigen IgA: secretions IgD: hypersensitivity IgE: allergies  Antibody- mediated immunity involves five subtypes of immunoglobulins: IgM, IgG, IgA, IgE, and IgD  Ig= plasma cell derived from a B lymphocyte  Igs inactive until antigen presented - attacks antigen and binds to it so that it cannot infect any other cell  Primary and secondary phases The Body’s Antibody- Mediated Response to an Antigen Consists of Two Phases: 1. Primary phases occurs when the host cell is exposed to an antigenic invader and proliferation of immunoglobulins to neutralize the invader 1. The primary immunoglobulin IgM marks the primary response 2. A second exposure to the same antigen initiates a secondary immune response - amnestic response 1. Stimulates a quick increase in levels of IgG immunoglobulins Hypersensitivity Reactions 1. Type 1: IMMEDIATE HYPERSENSITIVITY 2. Type 2: CYTOTOXIC 3. Type 3: IMMUNE DEPOSITION 4. Type 4: DELAYED HYPERSENSITIVITY Type 1 Hypersensitivity  Rapidly developed immune reaction after IgE binds to mast cells  “Allergy or atopic disorder”  Mast cells are key components - contains histamines (potent vasodilator) Anaphylaxis  Severe type 1 hypersensitivity reaction o Bee sting allergy  Hives (urticaria) Bronchospasm  Angioedema (severe facial edema, tongue, lips, eyelids): THIS CAUSES AIRWAY ISSUES  Severe hypotension - syncope  Emergency treatment required  USE EPINEPHRINE o ANTIHISTAMINES: Benadryl o CORTICOSTEROIDS: solumedrol - *YOU WANT TO GIVE THESE PATIENTS VASOCONSTRICTORS BC HISTAMINE WILL CAUSE THE VESSELS TO DILATE* Type II Cytotoxic Hypersensitivity  Mediated by Igs directed toward antigens present on cell surfaces o Ex: exogenous antigen such as a drug metabolite o Cytotoxic hypersensitivity reaction (Ex. transfusion reaction)Type III Immune Complex Hypersensitivity  Antigen combines with Ig within circulation and then are deposited in tissues - cause organ dysfunction o SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) o RHEUMATOID ARTHRITIS (RA) TYPE IV DELAYED HYPERSENSITIVITY  Initiated by T lymphocytes that have had previous exposure to an antigen  T lymphocytes are sensitized - delayed inflammatory reaction (contact dermatitis) o Ex: transplant rejection - donor tissue has MHCs on its cells that differs from recipients MHCs - destroys the donor’s foreign MCH- bearing transplant cells o Ex: PPD testing Selected Autoimmune Disorders  AUTOIMMUNE o Body forms antibodies against itself and cause organ dysfunction o Body forms antibodies to an antigen as well as antibodies to body tissue mistaken for antigen  Example: In rheumatic heart disease, the body forms antibodies against the streptococcus organism (GABHS) and also reacts with heart valve tissue SLE  Formation of autoantibodies (antinuclear antibodies)o Anti-double stranded DNA antibodies (anti-dsDNA) o Anti-smith bodies o Antinuclear antibodies (ANA)  Deposition of immune complexes triggers inflammatory reaction and damage organ membranes Rheumatoid Arthritis (RA)  Chronic autoimmune inflammatory disorder - affects joints, may be systemic  Etiology: unknown (genetic, infections)  More common in females  Clinical presentation: symmetrical, tender, swollen joint, worsen in the morning or after rest  Results in permanent destruction  DIAGNOSIS: Rheumatoid factor (RF), ESR, CRP RA PATHOPHYSIOLOGY  Autoimmune response destroys cartilage, bone, tendons and ligaments  Antigenic stimulus provokes APC to begin inflammatory cascade  APC activate T cells - T cells secrete cytokines, which recruit WBCs to synovial regions  WBCs (macrophages and monocytes) secrete antibodies called rheumatoid factor (RF) IMMUNODEFICIENCY DISORDERS -HIV  Causes acute infection followed by lengthy asymptomatic period  Can progress to acquired immune deficiency syndrome (AIDS)  1981 - 1984 CDC involvement  1.1 million affected in US  Epidemics  ETIOLOGY o Infects CD4 cells (helper T cells) o Virus fuses with CD4 surface receptors and inserts its RNA into cell o Reverse transcriptase enables viral RNA to transform into DNA and inserted into CD4 cells genome o CD4: factory of HIV particles, can remain inactive o CD4 cells have specific surface receptors for HIV - destroyed after replication - cells can no longer function within cell mediated immune responsesHIV Pathophysiology  Presents as flu-like viral syndrome (no initial rise in antibodies)  Development of antibodies to HIV requires from 2 weeks to 6 months  Asymptomatic period of HIV replication and CD4 cell destruction - LATENT period (6 months- 10 years) - able to transmit the disease  As virus replicates CD4 cell counts begin to show decline o CD4 500: susceptible to opportunistic infection o CD4 200: diagnosis of AIDS is made, death is imminent  Clinical Presentation o Mild, flu like illness (Acute antiretroviral syndrome) - lymphadenopathy, pharyngitis, GI symptoms x 2 weeks o High risk behaviors: unprotected sexual activity, anal intercourse, IVDA, MSM (men who have sex with men) o At risk population: heterosexuals who engage in unprotected sex, STD, frequent transfusions, pregnancy/breastfeeding, tattooing, dental  HIV Diagnosis o HIV RNA assay: earliest and most sensitive  HIV RNA level: measurement of viral load= how many viral particles are present in the blood  Antibody negative status - antibody positive status  On average, occurs between 2 weeks to 6 months o CD4 to CD8 ratioo If ELISA test is positive, then the patient will be asked will be asked to take the Western Blot Test to confirm HIV Opportunistic Infections and Infections and Illnesses That Occur with HIV Infection  Tuberculosis  Candida  Pneumonia  Kaposi sarcoma  Toxoplasmosis  Cryptococcus  Histoplasmosis  Hep A, B & C Hematologic System (Bailey) 1. Differentiate between classification of anemia (decreased RBC mass, RBC maturation defects, lack of production, etc.). This means you must fully understand the differences between things like hemolytic anemia vs. acute blood loss vs. folic acid deficiency. A. Anemia caused by decreased RBC mass:  Acute & chronic blood loss o Adult can usually lose 500 mL of blood w/o serious or lasting effects, lose 1000 mL=hypovolemic shock/cerebral hypoperfusion can occur o Insufficient RBCs to carry oxygen  RBC loss from hemolysis (sickle cell disease, blood transfusion reaction) Sickle Cell Anemia: SCA gene mutation changes the normal hemoglobin molecule HgB A into Hgb S- concave hemoglobin B. Structural fragility of sickle cell anemia RBCs → exposure to hypoxia/stress, RBC contorts to sickle shape → (painful VASO-OCCLUSIVE CRISES) shape can lead to thrombosis bc the sickle shape can’t go through capillaries → ischemia, tissue hypoxia, organ damage, infarction B. Chest, abdomen, long bones B. Splenic dysfunction bc surplus RBC death → decreased immunity B. RBC breakdown → hyperbilirubinemia → jaundice B. Anemia caused by lack of RBC synthesis (RBC maturation defects):  Iron, vitamin B12 or folic acid deficiency (necessary nutrients used to synthesize RBCs) o B12/folic acid: for DNA synthesis  Any lack of these leads to decreased RBC production, thus anemia  Could be nutritional deficiency Iron Deficiency Anemia: need iron to make HgB, not enough = poor O2 transport Hgb, Hct ↓MCV: ↓ microcytic (small) MCH: ↓ (mass) MCHC: ↓ hypochromic (pale color) Low serum iron Pernicious Anemia: (B12 deficiency) Malabsorption secondary to gastric atrophy Antibodies to intrinsic factor develop B12 needed for DNA synthesis: negatively affects hematopoiesis → necessary for folic acid metabolism Folic Acid Deficiency: required for DNA synthesis, necessary for neural tube defects, prevention of cardiovascular disease RISK for Folic Acid Deficiency:  Elderly susceptible  Lack of meat in diet  Lack of Hcl in the tummy  Intrinsic factor deficit caused by autoimmune destruction  Gastric bypass  Alcoholism Clinical Manifestations: a lot of neuro stuff + fatigue, dyspnea, exercise intolerance, tachycardia RISK for Pernicious Anemia: vegans, heavy menstrual bleeding, pregnant women, chronic GI bleeds Clinical Manifestations: hair loss, glossitis, coldness/numb fingertips, pica (craving for non-food substances) Aplastic Anemia: complete disruption of bone marrow function inhibits manufacture of all blood cells  Pancytopenia  Life threatening can be caused by: cancer, sepsis, drugs, radiation exposure  Bone marrow contains fat instead of blood cells, early forms of hematopoietic cells greatly diminished, stem cell pool is reduced Anemia of Chronic Disease: results from cancer, heart failure, DM, stroke, RENAL FAILURE (ONE OF BIGGEST CAUSES)  Secondary to long-term disorders  Decrease in RBC survival time blunted erythropoietic response in bone marrow & impaired iron metabolism G. Hemoglobinopathies:Hemolytic anemia: erythrocyte destruction outpaces RBC synthesis by the bone marrow  Abnormal Hgb structure -- deficient oxygen carrying  RBC hemolysis occurs from: o Autoimmune disease, transfusion reaction, medications (drug reactions), mother/fetus incompatibility (ABO or Rh factor), hemoglobinopathy (sickle cell anemia), prosthetic heart valves  Caused by autoimmune disorders: o Warm and cold agglutination interferes with anesthesia Clinical Manifestations: fatigue, jaundice, pallor, dark urine, enlarged spleen MCV: volume of one RBC MCH: average amount of HgB in an average RBC (mass) MCHC: average concentration of HgB in a given volume (color) Polycythemia: opposite of anemia --- thick viscous blood  Overabundance of RBCs  Primary: hyperproliferation of all blood cells, viscous, needs periodic phlebotomy  Secondary: more common, hyperproliferation of RBCs in response to chronic blood hypoxia (COPD) 2. Distinguish between the classifications of blood cancers (ALL, CLL, AML, CML)-- what are specific features that make each one stand out? ALL (Acute Lymphocytic Leukemia): children→ esp with down syndrome, previous chemo or radiation, T or B lymphocytes don’t mature in the bone marrow, the immature cells become numerous, thus less room for the healthy blood cells in the marrow o Lymph nodes house the lymphoblasts (nonfunctional), thus crowding healthy lymphocytes  Anemia (pancytopenia)  Susceptibility to infection/frequent infections  Full feeling due to enlarged liver & spleen  Bone pain  Unexplained bruising  Bleeding gums/nose  Suppressed clotting  Splenomegaly  CLL (Chronic Lymphocytic Leukemia): Most common type in U.S., median age of 70 o B cell lymphocyte malignancy (fail to differentiate from precursor to mature) these immaturities are called B-CLL lymphocytes  B-CLL’s have excess proto-oncogenes, giving them a long life  The long life leads to proliferation in the bone marrow, lymph nodes, & spleen  Lymphocytosis: too many B & T cells  This proliferation of non functional B-CLL’s decreases the good stuff like RBC/WBC/platelets o RISK: agent orange, advanced age, Caucasin male, genetics o Presence of Igs that are: low, mutated, or non-existent o Clinical manifestations:  Lymphadenopathy (abnormal sized lymph nodes)  Enlarged spleen  Night sweats  Weight loss  Pancytopenia  AML (Acute Myelogenous Leukemia): caused by proliferation of undifferentiated (blast) myeloid cells in the bone marrow (don’t worry about this one too much) o Genetic mutation in abnormal myeloid cells changes normal apoptosis o Proliferation of myeloid blasts → reduces production of normal blood cells in bone marrow o RISK: previous chemo/radiation o Clinical Manifestations:  Anemia (lack of RBC)  Bleeding disorders (thrombocytopenia) Infections (neutropenia)  Rash  Raised nodules  pancytopenia  CML (Chronic Myelogenous Leukemia): characterized by overproduction of mature myeloid cells in bone marrow o Arises from oncogene mutation in hematopoietic stem cell o Median is 50 years (middle age) o RISK: ionizing radiation o 95% have Philadelphia chromosome- genetic mutation on that chromosome  3 phases: o Third phase: blast crisis phase, where myeloid blast cells do not differentiate at all; will bring pt to hospital o Manifestations of Blast Crisis: bone pain due to excessive proliferation of blasts stretching bone marrow, fever, fatigue, weakness, bleeding, pancytopenia  Clinical manifestations of CML: fatigue, abdominal fullness (enlargement of organs), night sweats, low-grade fevers 3. Distinguish between lymphomas (Hodgkin and Non-Hodgkin) Hodgkins: Develops from specific abnormal B lymphocyte line  Reed Sternberg cells in lymphoid tissue (multinucleated cells)  Reed Sternberg wants to get in the NHL but he can’t because he's on the B team  17% of lymphoma cases  Young adults/children (not ready for the National Hockey League)  Etiology o EBV, carcinogen exposure, viruses, genetic & immune mechanisms proposed Non-Hodgkins (NHL): Develops from either abnormal B, T, or NK cells  83% of lymphoma cases (consists of over 20 different lymphomas)  Middle age (National Hockey League is for adults to play in)  Etiology: o Chromosomal translocations o HBV, HIV, H.pylori, hepatitis C, herpes virus (viruses) Clinical manifestations: pancytopenia, spleen/liver enlargement, decreased Hct & Hmg Risks: exposure to chemo before, viruses 4. Extrinsic vs. intrinsic pathways and substances involved (don’t worry about) Extrinsic pathway: Stimulated by trauma to vessel/external injury (ex: laceration) o Factor II activated → comes into contact with tissue factor & fibroblasts, leukocytes → activates prothrombin to thrombin → conversion of fibrinogen to fibrin o The pathway is measured by a diagnostic test → prothrombin time (PT)  Intrinsic pathway: Stimulated by tissue damage (ex: arteriosclerosis/inflammation) o Stasis of blood o Factor XII activated → factor X activates conversion of prothrombin to thrombin → fibrinogen to fibrin o The pathway is measured by a diagnostic test → aPTT 5. Review diseases associated with coagulopathy: hyper or hypocoagulation (Ex. DIC, hemophilia)  Immune Thrombocytopenia Purpura (ITP): Antibody destruction of platelets triggered by antigen; hypocoagulation  immune system mistakenly attacks platelets o Antigenic target is platelet GPIIB/IIIa complex which gets attacked by IgG antibodies  The GpIIB/IIIa receptor is usually stimulated by platelet adhesion which enhances clotting process further o More common in children o Transient usually (short time) o Immunologic piece  Disseminate Intravascular Coagulation (DIC): Disorder of clot formation & bleeding episodes in critically ill patients; hypocoagulation; clot and bleed at same time o Suppressed anticoagulant mechanisms → abnormal fibrinolysis (a clot mechanism) o Persistent activation of clotting factors, and the clot factors run out, so this leads to further bleeding o 30-50% of septic pts o Not much we can do for them besides supportive care o Doubles mortality rate  Bleeding disorders from decreased platelet number/activity: aplastic anemia, cancer in bone marrow, renal failure, various meds  Bleeding disorders from defective coagulation: cirrhosis, hemophilia, vitamin K deficiency, Von Willebrand Disease  Conditions associated with hypercoagulability:o Increased platelet activity: atherosclerosis, diabetes, elevated lipids/cholesterol, smoking, splenectomy, o Enhanced coagulation factor formation: atrial fibrillation (irregular heart rhythm that causes stasis of blood in the atrium), cancer, immobility, postsurgical state, pregnancy, oral contraceptives, heart failure Renal/Urologic System (Kortnie) 1. Differentiate between pre-intra-post renal failure Kidney → ureters → bladder → urethra Prerenal dysfunction: above the kidney; caused by decreased blood flow and perfusion to the kidney.  Decreased blood flow & perfusion to kidney causes ischemia/hypoxia  Reduced cardiac output, not enough blood to kidney o Any condition that directly or indirectly decreases renal perfusion may lead to prerenal dysfunction. o Prerenal dysfunction occurs because of reduced cardiac output or severe hypovolemia (low blood volume). YOU NEED TO FIGURE OUT WHY  Large blood loss from the body, as in hemorrhage, is a common cause of prerenal kidney injury because of ischemia.  SHOCK!  Reversible: typically :)  Diuretic= makes the patient pee/lose fluid ****CAN CAUSE PRERENAL**** Intrarenal dysfunction: (kidney itself) develops secondary to actual injuries to the kidney itself.o Any condition that directly harms the kidney tissue  trauma to the kidney, infection of kidney, nephrotoxic drugs, obstruction (myoglobinuria) *Contrast induced or dye from lab testing can cause damage to the kidneys*  Nephrotoxic drugs o NSAIDs, aspirin o ACE inhibitors, angiotensin-receptor blockers (ARBS), aminoglycoside antibiotics o Statin drugs that cause rhabdomyolysis (anticholesterol) → myoglobin involved, causes BLOCKAGE  Infections o Pyelonephritis: infection of kidney o Autoimmune diseases Postrenal dysfunction: related to obstruction of urine outflow from the kidneys. o Caused by obstructive uropathy, a problem that prevents urine outflow from the kidney  kidney stone, prostate gland hyperplasia, bladder disorders, strictures o In postrenal kidney dysfunction, urine backs up within the ureter and into the kidney, which can lead to hydronephrosis, a fluidfilled swollen kidney. 2. Pathophysiology of Renal calculi  Nephrolithiasis is the formation of stones, also called calculi in the kidney.  Stones can travel down the ureter or bladder.  Risk factors: o Genetic susceptibility o Dehydration o Hypercalcemia: excessive calcium intake o Gout/Hyperuricemia o Urinary tract infection Nephrolithiasis Pathophysiology (KIDNEY *STONES*)  Factors resulting in nephrolithiasis: o Dietary & intestinal absorption factors o Endocrine abnormalities o Crystalline components in blood o pH or urine  Types of stones o Calcium oxalate: 75% (hyperabsorption) o Struvite: 15% (Chronic UTI) o Uric acid: 6% (Gout, malignancy) o Cystine: 2% (failure to reabsorb cystine) **PEE THROUGH STRAINER WANT YOUR STONE!** Three theories 1. Supersaturation of urine by stone forming constituents 2. Deposition of calcium phosphate- plaque becomes a calculi 3. Deficiency of one or all proteins that inhibit stone formation  Clinical Manifestations: Pain (colic); abdominal, flank, radiation into groin, N/V, cool, clammy 3. Features/clinical manifestations associated with acute kidney injury and end stage renal disease Acute Tubular Necrosis (ATN)  Ischemia and hypoxia can damage the renal tubules and result in **Acute Tubular Necrosis** (ATN), the most common cause of acute kidney injury (AKI).  With ischemia, there is sloughing of the cells of nephron tubules into the tubular lumen. The lumen becomes blocked, preventing fluid from flowing through them, thereby reducing urine formation.  Unless this process is reversed, renal failure will occur. **Acute Kidney Injury (AKI) Pathophysiology**  Decreased GFR leads to azotemia (high BUN), high serum creatinine and fluid retention.  **Acute Tubular Necrosis** (ATN), the most common cause of acute kidney injury (AKI). 4 Phases:  Initial: time from precipitating insult to time of initial manifestations  Oliguric: decreased in GFR, elevated potassium, fluid volume excess (low urine output) o *Anuria: no urine output at all  Diuresis: beginning to recover, increased urine output (doesn’t always mean they are improving)  Recovery: final repair, healthy nephrons compensate for damaged nephrons (Pts. may not return to previous state) AKI Clinical Manifestations  **Metabolic acidosis**  Volume overload- pulmonary edema (lots of fluid in the lungs, pts gets short of breath really quick, frothy sputum they cough up)  Encephalopathy: is a general term that means brain disease, damage, or malfunction  Hyperkalemia: excessive amount of K levels *(levels 8, 9, 10)  Thrombocytopenia: Low blood platelet count o Platelets (thrombocytes) are colorless blood cells that help blood clot  Costal-vertebral area (CVA) tenderness  Hematuria: blood in urine  Proteinuria: protein in urine  An inadequate amount of urine  *Oliguria* is an amount lower than 400 mL of urine output per day or lower than 20 mL of urine per hour (adult is normally 30 mL) o cc’s=mL Diagnosis: urinalysis, labs: BUN/GFR/Creatinine  Studies: CT, ultrasound- avoid IV contrast, dehydration WHAT GOES IN MOST COME BACK OUT → I’s & O’s ... IN’s & OUT’s Chronic Kidney Disease (CRF)  CRF is an irreversible, progressive disease process. (GETS WORSE!)  Gradual in onset, the disease may develop over months to years, with 90% to 95% of the nephrons affected  CRF usually progresses to ESRD; as CRF progresses, kidney function deteriorates to the point that the kidney is unable to excrete waste products or control volume status  Hemodialysis or kidney transplant are the only options to support life. End-Stage Renal Disease (ESRD)  In the past, ESRD was called UREMIA (meaning urine in the blood)  Kidney is dysfunctional; numerous nephrons damaged; blood not being filtered  Very low GFR Complications of ESRD: END STAGE RENAL DISEASE  insufficient filtration of blood waste; nitrogen buildup causes RBC & platelet lysis → hemolysis, thrombocytopenia, & confusion/stupor o encephalopathy: no longer responsive pt.  kidney does not develop a concentrated urine  kidney secretes excess renin to raise BP = hypertension  kidney does not secrete erythropoietin to manufacture RBCs = anemia  kidney does not maintain acid-base balance = metabolic acidosis  kidney does not excrete excess K+ = hyperkalemia  kidney does not synthesize a component of vitamin D; decreases Ca++ absorption = hypocalcemia  uremic fetor and uremic frost (salt looking) (saliva and pers