University of Texas | NURSING 6804 Pathophysiology Exam 1 study guide 2025/2026

University of Texas | NURSING 6804 Pathophysiology Exam 1 study guide 2025/2026 Exam 1 Blue Print 1. Cancer etiology – obesity, alcohol  Obesity/lack of exercise- poor nutrition; epidemic over the past 20yrs; linked to 13 distinct forms of cancer: liver, prostate, ovarian, gallbladder, kidney, colorectal, esophageal, breast (post menopause), pancreatic, endometrial, stomach, multiple myeloma, & meningioma; linked to both increased risk and increased progression of cancer  Alcohol- there is strong data linking alcohol with cancer of the mouth, pharynx, larynx, esophagus, liver, colorectal, and breast.; no “safe limit” of intake Other possible causes for cancer include: Smoking, Infectious agents (mold, bacteria, viruses, parasites), Environmental exposure to sunlight, ionizing radiation, non-ionizing radiation, air/water/soil carcinogens; carcinogens in the household (drugs; personal care items), Occupational exposure to chemical and physical carcinogens, Socioeconomic, racial, geographical, and ethnic factors also affect exposures, risk, detection, and treatment 2. Isotonic fluid – composition/maintenance  Isotonic = 0.9% normal saline  Hypertonic > 295 mOsm/kg o Can be due to water loss or solute gain, makes cells shrink. Most common cause is hypernatremia or a deficit in the ECF. o Water moves from ICF to ECF and causes hypervolemia in the vessels  Hypotonic < 275 mOsm/kg o Can be due to water gain or solute loss, makes cells swell. Most common causes are hyponatremia or excess of electrolyte-free water (water intoxication) o Water moves from ECF to ICF and leads to hypovolemia. o Normal Osmolality 275-295 mOsm/kg  Starling hypothesis – net filtration is equal to the forces favoring filtration minus the forces opposing filtration. Forces favoring filtration – capillary hydrostatic pressure (BP) & interstitial oncotic pressure (water pulling into interstitial spaces)  Forces opposing filtration – capillary oncotic pressure (water pulling into vessel) & interstitial hydrostatic pressure against vessel 3. Know about serum potassium and sodium and clinical features related to fluctuations in Na, K Sodium 135-145mEq  Hypernatremia = Na >145 o Hypovolemic hypernatremia – due to loss of sodium with a relatively greater loss of body water. Causes can be from loop diuretics, diuretic stages of renal disease, osmotic diuresis from diabetes mellitus, or mannitol use. o Isovolemic hypernatremia (most common) – due to loss of electrolyte-free water with a near normal body sodium level. Causes can be excessive sweating, inadequate water intake, fever with hyperventilation and increased water loss from lungs, burns, vomiting, diarrhea, lack of ADH or inadequate renal response to ADH. o Hypervolemic hypernatremia (rare) – due to and increase in TBW with a greater increase in sodium levels. Causes can be from infusion of hypertonic saline solutions, over secretion of adrenocortropic hormone (ACTH) or aldosterone from cushings syndrome or adrenal hyperplasia, deliberately high salt intake. Symptoms include weight gain, bounding pulse, increased BP, and lethargy. o Clinical Manifestations of Hypernatremia  Central nervous system signs are the most serious and are related to brain cell shrinking, brain dehydration, and alterations in membrane potential. Weakness, lethargy, muscle twitching, hyperreflexia, confusion, coma, and seizures can occur.  Dehydration signs and symptoms: thrist, headache, sudden weight loss, concentrated urine, hard stools, elevated body temp, soft eyeballs, sunken frontanels in infants, weak pulses, tachycardia to name a few.o Treatment  Iso & hypovolemic hypernatremia – give oral water or D5W until serum sodium levels are normal.  Hypervolemic hypernatremia – loop diuretics  Hyponatremia Na < 135 o Hypovolemic Hyponatremia – due to a loss of TBW with involves a greater loss of body sodium. Causes can be prolonged vomiting, severe diarrhea, inadequate secretion of aldosterone (adrenal insufficiency), and renal losses from diuretics. o Dilutional hypotonic hyponatremia (water intoxication) – occurs with large intake of electrolyte-free water or replacement of fluid loss with IV D5W. o Isovolemic hyponatremia – due to a loss of sodium without a significant loss of water (pure sodium deficient). Causes can be water retention secondary to SIADH, hypothyroidism, pneumonia, and glucocorticoid deficiency. o Hypervolemic hyponatremia – due to total body sodium increase and there is excess water. This leads to an increase in ECF volume, which causes the serum sodium concentrations to decrease. Causes can be heart failure, cirrhosis of the liver, and nephrotic syndrome, Edema is usually present. o Hypertonic hyponatremia – due to a shift of water from the ICF to the ECF, as occurs with hyperglycemia, hyperlipidemia, and hyperproteinemia. This dilutes sodiums and other electrolytes also called pseudohyponatremia. o Clinical Manifestations of Hyponatremia  Due to cell swelling the cells ability to depolarize and repolarize are decreased. This alters the action potential in neurons and muscle. This leads to impaired nerve conduction and neurological changes.  Nausea and vomiting are more common in less severe hyponatremia. In severe hyponatremia (<125), there can be lethargy, headache, confusion, apprehension, seizures, and coma. Cerebral edema!  In hypovolemic hyponatremia there can be hypotension, tachycardia, and decreased urine output.  In hypervolemic hyponatremia there can be weight gain, edema, ascites, and jugular vein distention. o Treatment  Restriction of fluids in the case of dilutional hyponatremia.  Rapid correction of chronic hyponatremia can lead to osmotic demyelination syndrome with axonal damage in the brain leading to neurological disability or death.  Iso & Hypervolemic hyponatremia – ADH antagonists Potassium 3.5-5mEq o Regulation of potassium includes: o The action of aldosterone – stimulates the secretion of potassium into the urine by the distal renal tubules. Also increases the secretion of potassium from the colon and sweat glands. o The concentration gradient of K+ at the distal tubule and collecting duct – ECF potassium is detected in the peritubular capillaries and when concentrations are high more potassium is excreted to maintain homeostasis or vice versa. o The distal tubule flow rate and distal tubule sodium delivery – when flow is increased (diuretic use) the concentration of K+ is lower therefore more potassium will be secreted. o Changes in pH – hydrogen ions accumulate in the ECF creating a charge imbalance. To maintain ionic balance potassium shifts into the ECF. Acute acidosis can lead to hyperkalemia due to this. o Insulin – stimulates the Na+K+ ATPase pump, this promotes the movement of potassium into the liver and muscle cells and out of the ECF. Hypokalemia <3.5mEq o Causes: reduced intake of potassium, an increased entry of K+ into cells, and increase losses of K+, diarrhea, GI drainage tubes, laxative overuse, diuretic use, excessive aldosterone secretion, low plasma magnesium, kidney disease o Clinical manifestations: neuromuscular excitability decrease, skeletal muscle weakness, smooth muscle atony, cardia dysrhythmias, glucose intolerance, and impaired urinary concentrating ability. Cardiac muscle cell membrane potential becomes more negative, which requires a greater stimulus to trigger and action potential. Hypokalemia delays ventricular repolarization and can lead to sinus bradycardia, AB block, paroxysmal atrial tachycardia. Decreased insulin secretion and alters hepatic and skeletal muscle glycogen synthesis. o Treatment: replacement of potassium cand correcting the underlying issues. Promotion of high potassium foods may be necessary  Hyperkalemia >5.5mEq o Causes: acidosis, insulin deficiencies (DKA), whole blood admin, IV bolus of pen G, excessive replacement of K+, ACE inhibitors, ARBS, potassium sparing diuretics, aldosterone antagonists, decreased renal function. Hypoxia diminishes the efficacy of active transport and K+ can escape into the ECF. Addison’s disease decreased aldosterone secretion therefore not as much urine is being excreted so potassium can build up o Clinical Manifestations: restlessness, intestinal cramping, diarrhea, muscle weakness, loss of muscle tone, paralysis, narrow & tall T wave, short QT, depressed ST, wide QRS, ventricular fibrillation. Cells become more positive = hyperpolarized, this leads to more rapidly repolarization and hyper excitability. In extreme cases the cells can not repolarize and cannot respond to excitation stimuli. (Hypercalcemia counteracts the effects of hyperkalemia on resting membrane potential) o Treatment: calcium gluconate, glucose to stimulate insulin secretion, glucose with insulin for patients with diabetes, RASS inhibitors, potassium binders, dialysis for renal dysfunction.4. Know how to differentiate between neurofibromatosis I & II In NF1, the tumors occur in the small nerves of the skin and the large nerves inside your body, in NF2, tumors primarily affect the auditory nerves that connect the ears to the brain and control hearing. 5. Know nucleus, ribosomes, lysosomes, mRNA, rRNA, tRNA Nucleus Structure - Nuclear envelope - Nuclear pore complexes - Nucleolus - Ribonucleic acid (RNA) - Deoxyribonucleic acid (DNA) - Histone proteins Functions - Cell division and control of genetic information Ribosomes Structure: Ribonucleic acid (RNA) protein complexes; free vs. attached ribosomes Function: Synthesize proteins Lysosomes Structure• Saclike structures that originate from the Golgi • Primary vs. secondary lysosomes Functions • Intracellular digestion system • Role in autodigestion and autophagy RNA mRNA- messenger RNA; takes information from DNA in the nucleus out into the cytoplasm tRNA- transfer RNA; anticodon (3 base prong) undergoes complementary base pairing with mRNA to transfer information into the sequence of amino acids rRNA- ribosomal RNA; located in the ribosome along with protein (actual site of protein synthesis) 6. Transcription, translation DNA to RNA7. Mitochondria structure/functions/mutations importance Structure • Is surrounded by a double membrane. • Increased inner membrane surface area is provided by cristae. Functions • Is responsible for cellular respiration and energy production. • Participates in oxidative phosphorylation 8. Barr body Inactivated X chromosome (fixed); normal females (XX) have one barr body; normal males (XY) have no barr bodies Can be the X contributed by the mother or father Individuals that have an abnormal number of X chromosomes: XXY- Klinefelter Syndrome; males have barr body; Characteristics: Male appearance, Develop female-like breasts, Small testes—usually sterile, Sparse body hair, Long limbs XXX/XXXX- females that have multiple barr bodies (Trisomy X most common sex chromosome aneuploidy; Symptoms are variable: sterility, menstrual irregularity, and/or intellectual disability, Symptoms worsen with each additional X X- Turner syndrome; females have no barr body; Underdeveloped ovaries (sterile), Short stature (~ 4'7"), Webbing of the neck, Edema, Underdeveloped breasts; wide nipples, High number of aborted fetuses Observable in many interphase cells- highly condensed intranuclear chromatin bodies9. Monosomy – main issues  In autosomes- monosomy of any chromosome is lethal  In sex chromosomes- monosomy is not as lethal but can still cause serious problems  Turner Syndrome- monosomy X: 15-20% spontaneously aborted, sterile females; narrowing of the aorta; short stature; webbing of the neck; widely spaced nipples; swelling of the feet in newborns 10. Know Glycolysis – where, how, end products Occurs in the cytoplasm  Glucose is broken down through a series of biochemical reactions requiring ATP End products (per glucose molecule)= 2 pyruvate; net total of 2ATP (4 total but 2 used in the process of glycolysis)  With oxygen pyruvate can be processed to make more atp by going through the Kreb cycle  Glycolysis occurs during hypoxia, results in production of lactic acid and far less atp, less atp affects function of other parts of the cell such as cell atp channels (most important is Na and K pump). Lactic acid results in an acidic environment that can also activate lysosomes and result in more damage. All of it results in uncontrolled cell death with many reactive and damaging parts. 11. Anaerobic metabolism – products Process for producing energy (ATP) when there is not enough oxygen Produces a small amount of ATP (2 ATP per glucose molecule) and pyruvate which is converted to lactic acid if the cell does not receive enough oxygen12. Phenotype and genotype – what are the main differences? 13. Respiratory acidosis and alkalosis – know how to differentiate Anion Gap – normally 10-12 mEq/L, normal or elevated anion gap with metabolic acidosis may help determine the cause. 14. Local signs of inflammation – know well  Cardinal signs include redness, heat, swelling, pain, and loss of function.  Systemic: fever, leukocytosis, pyrogens in the blood  CELLS of inflammation / who gets there first: neutrophils first (6 or so hours), macrophages and T lymphocytes within 24 hours 15. inflammation  Cellular and chemical components, Nonspecific, rapidly initiated, no memory cells.  3 types of Plasma Protein Systems • Complement System • Clotting System • Kinin System  Complement System• Can destroy pathogens directly, activates or collaborates with other inflammatory responses. • There are 3 pathways within the complement system: classical for antibodies & antigens, lectin for mannosecontaining bacterial carbohydrates, and alternative for gramnegative bacterial and fungal cell wall polysaccharides. • Results in anaphylatoxin activity leading to mast cell degranulation, leukocyte chemotaxis, opsonization, and cell lysis.  Clotting System • Forms a fibrinous mesh at the site of inflammation. Made of mostly fibrin. • Prevents the spread of infection, stops bleeding, keeps microorganisms and foreign bodies at the site of inflammation for removal, and provides a framework for repair and healing. • Two pathways: Extrinsic for outside of the vessel and Intrinsic for the injured vessel wall.  Kinin System • Functions to activate and assist inflammatory cells. Kinin is mainly bradykinin. • Causes dilation of blood vessels, pain, smooth muscle contraction, vascular permeability, and leukocyte chemotaxis. • Kininases degrades kinin. 16. Vascular response – second line of defense  blood vessels dilate, increased vascular permeability and leakage, WBC adherence to the inner walls of the vessels, and migration through the vessels (diapedesis).  First line of defense includes physical, mechanical and biochemical barriers. o Skin, tight epithelial cells of GI tract, normal turnover of cells / “washing”, vomiting and urination, goblet cells that produce mucus, coughing and sneezing, low temp of skin and low pH of skin and stomach, sweat and saliva, etc.  Second line of defense: inflammation  Three characteristics of microcirculation response to injury: o Vasodilation causes slower blood velocity and increased blood flow to the injured site o Increased vascular permeability and leakage of fluid out of the vessel (exudation) cause swelling (edema) at the site of injury; as plasma moves outward, blood in the microcirculation becomes more viscous and flows more slowly, and the increased blood flow and increasing concentration of RBCs at the site of inflammation cause locally increased redness and warmth.o WBCs adhere to the inner walls of vessels, and they migrate through enlarged junctions between the endothelial cells lining the vessels into the surrounding tissue (diapedesis)  Within seconds, arterioles near the site constrict briefly to control bleeding. o Next, vasodilation sets in and causes slower blood velocity and increased blood flow to the site. 17. Cellular Mediators of Inflammation  Mast cells, neutrophils, eosinophils, basophils, monocytes, macrophages, natural killer cells, lymphocytes, platelets.  Biochemical mediators originate from the destroyed or damaged cell, it modulates the localization and activities of other inflammatory cells, and it helps tissue regeneration or repair.  The cells can have pattern recognition receptors (PRRs) on them to help them find the source of inflammation. o Toll-like receptors recognize pathogen-associated molecular patterns (PAMPs) o Complement receptors help recognize complement fragments o Scavenger receptors promote phagocytosis  Cellular Products o Chemokines or cytokines regulate innate or adaptive resistance by affecting other neighboring cells. They are either proinflammatory or anti-inflammatory and either synergistic or antagonistic. Actions are pleiotropic meaning the same molecule may have different biological activities, but it depends on the target cell it is acting on. Includes interleukins, interferons, and tumor necrosis factor. o Interleukins are made by macrophages and lymphocytes in response to microorganisms or other products of inflammation. These help regulate inflammation. o Interferons protect against viral infections, they are produced and released by the infected host cell, they do not kill viruses but prevent them from infecting additional healthy cells. o Chemokines are produced by macrophages, fibroblasts, and endothelial cells. Beta chemokines (CC) mainly affect monocytes, lymphocytes, and eosinophils. Alph chemokines (CXC) generally affect neutrophils. 18. Mast cells  Mast cells are cellular bags of granules located in loose connective tissues close to blood vessels. They are activated by physical injury, chemical agents, immunologic processes and TLRs. They can bereleased two different ways, degranulation or synthesis of lipid-derived chemical medicator.  Mast cells can be found in connective tissue and close to vessels near the body’s surfaces (Skin; GI; and respiratory tract) o Not found in the blood - basophils function like mast cells and circulate in the blood o They are also NOT found in areas of the body without blood vessels (CNS; cartilage; cornea; mineralized bone)  Mast Cell Degranulation  Releases histamine to cause large blood vessels to constrict and dilate postcapillary venules. o H1 receptor (proinflam) are present in the bronchi and induces bronchoconstriction. o H2 receptor (antiinflam) are present on the stomach mucosa and induces gastric acid secretion. 19. Most common immunoglobulins IgG: 80-85% of antibodies in the blood; provides the most protection against infections; crosses the placenta during pregnancy & protects the child for the first 6mo of life IgM: largest antibody; first one produced in the primary response to antigens; synthesized early in neonatal life (may increase in response to infection in utero); part of BCR complex in B cells IgA: found in blood and bodily secretions (secretory IgA) IgD: also part of BCR complex in B cells- part of the antigen receptor IgE: low concentration in circulation; specialized functions: mediate common allergic responses & defense against parasitic infection20. Type I hypersensitivity  IgE mediated  Against environmental antigens (allergens)  IgE binds to Fc receptors on surface of mast cells—“sensitized” -> Histamine release from mast cell degranulation o Manifestations:  GI allergy: Nausea, vomiting, diarrhea, abdominal pain  Skin manifestations: Urticaria (hives)  Mucosa allergens: Conjunctivitis, rhinitis, asthma  Lung allergens: Bronchospasm, edema, thick secretions 21. HPV - mechanism of transmission intercourse, oral sex, anal sex or other close genital contact. 22. Effect of booster doses – what does it do to the immune system?  Primary immune response from vaccination is generally short lived  Booster injections are used to push the immune response through multiple secondary responses Results in large # of memory cells & sustained protective levels of antibodies, T cells, or both  IgM levels similar to primary vaccination, IgG levels MUCH higher in booster than in primary vaccination  Pneumonic: Mom before grandma (just a helpful way to remember) In immune response IgM (mom) responds and is elevated first, in exposure following that IgG is elevated (grandma), so if a patient has high levels of IgG then they probably have been exposed to whatever antigen it is before. If patient has high IgM levels, this is their first exposure. 23. Clinical desensitization  May reduce the severity of the allergic reaction but could also cause anaphylaxis  Works best on common resp allergies and insect stings. Food allergies more difficult to suppress.  Desensitization is effective for people 5 years of age and older 24. Tumor cell markers  Substances produced by both benign and malignant cells.  Hormones, enzymes, genes, antigens, and antibodies Can be Used to:  screen and identify individuals at high risk for cancer. (example is PSA for prostate cancer screening)  help diagnose the specific kind of tumor (if certain cell marker abnormally elevated there maybe a cancer to blame)  follow clinical course of cancer  Estimate prognosis (medullary thyroid cancer)  measure how treatment is going (CA-125 with ovarian cancer)  Examples: ACTH, alpha fetoprotein (liver), PSA (prostate) catecholamines (adrenals), CEA (GI/ pancreas, lung, breast, etc), calcitonin, CA-125 (ovarian) 25. TNM system  T = tumor spread · T0= · T1= lesion <2cm · T2= Lesion 2-5cm · T3= invasion of skin and / or chest wall  N=node involvement · N0= no node involvement· N1=mobile nodes involved · N2 = fixed nodes involved  M = metastasis to distant site · M0= no metastases · M1= demonstrable metastases · M2=suspected metastases 26. Tissue regeneration in wound healing Wound healing 3 phases: inflammation; proliferation and new tissue formation; and remodeling and maturation  Inflammatory phase: o vascular and cellular responses o vasoconstriction, formation of fibrin clot, and coagulation help stop blood flow o Release of inflammatory mediators o Infiltration of neutrophils and macrophages that assist in clearing debris from the wound o Debridement (fibrinolytic enzymes dissolving fibrin clots); Inflammation then reversed (assists with permeability)  Proliferation and tissue formation phase: o invading macrophages release growth factors (promote angiogenesis and collagen formation) o Granulation tissue & epithelial stem cells grows into the wound from surrounding tissues o Epithelial stem cells create layers of epithelial cells o Wound closure- myofibroblasts contract to cause tension on attached cells  Remodeling and maturation phase: o usually complete within 2 years (dependent on patient comorbidities, type of wound, location, and if infection is present) o scar tissue is established and remodeled o fibroblasts continue to deposit and organize collagen o wound contraction continues; o New tissue will gradually reach its maximal strength and flexibility.  Usually remodeled tissues is not as good of quality as original tissue. And each injury increases risk for mutations and potential cancer, for example constant inflammation 27. Adaptive immunity – memory cells  Aka Acquired/Specific immunity Third line of defense- ex: vaccines (attenuated pathogens; recombinant viral proteins; toxoids)  Initiated when innate immune system signals cells of adaptive immunity (T lymphocytes, B lymphocytes, macrophages, and dendritic cells)  Delayed response after initial exposure but immediate response after secondary exposure  Memory cells- T and B lymphocytes (activated after initial exposure)  Future protection by activated T and B lymphocytes; cytokines; antibodies 28. Bradykinin functions  Part of the cellular inflammatory response  Causes dilation of blood vessels  Along with prostaglandins: o Induces pain o Triggers smooth muscle cell contraction o Increases vascular permeability 29. Proteins of the coagulation systems  The coagulation system consists of a family of plasma proteins that circulate in the blood in their inactive form (proenzymes)- All of these proteins are produced in the liver  May be activated by a variety of substances during injury/infection (ex: collagen; enzymes; bacterial toxins)  Cascade of proteolytic enzymes which activate downstream enzymes lead to fibrin clot formation  Protein names and functions: o Factor I (fibrinogen)- source of fibrin clot formation o Factor II (prothrombin)- source of thrombin that activates fibrinogen, other proteins (V,VII,XI,XIII,protein C), & platelets o Tissue factor (thromboplastin)- Cofactor for factor VII o Calcium- cofactor for binding phosphatidylserine o Factor V (labile factor)- cofactor in prothrombinase complex o Factor VII (Stable factor; proconvertin)- forms complex w/ tissue factor; activates factor IX and X o Factor VIII (Antihemophilic factor)- component of tenase complex o Factor IX (Christmas factor)- component of tenase complex; activates factor X o Factor X (Stuart-Prower factor)- component in prothrombinase complex; activates prothrombin o Factor XI (Plasma thromboplastin antecedent)- activates factor IX o Factor XII (Hageman/Contact factor)- activates factor XIo Factor XIII (Fibrin-stabilizing factor)- crosslinks fibrin  Vitamin K helps the liver produce clotting factors, which are proteins that cause blood to clot. Without vitamin K, the liver can't produce clotting factors II, VII, IX, and X, which means blood wouldn't clot 30. Endothelial cells – know functions  They participate in immune responses, inflammation, and angiogenesis.  Hemostasis: Endothelial cells initiate hemostasis by constricting blood vessels to reduce blood flow at the site of injury. They release substances like von Willebrand factor (vWF) and tissue factor to activate platelets, helping in blood clot formation. Endothelial cells promote platelet adhesion by exposing collagen and vWF, promoting platelet binding.  Prevention of Thrombosis: Endothelial cells prevent thrombosis through anticoagulant and antiplatelet mechanisms, ensuring clot formation only at sites of injury. These cells produce substances such as nitric oxide (NO) and prostacyclin, which inhibit blood clot formation and promote blood fluidity. Endothelial dysfunction can disrupt this balance, leading to bleeding or thrombosis, and contributing to several vascular complications.  Leukocyte Interaction: Endothelial cells facilitate the movement of leukocytes from the bloodstream into the surrounding tissues. This process is necessary for immune responses and inflammation. This involves leukocyte capture, rolling, firm adhesion, and migration across the endothelium. Endothelial adhesion molecules like selectins and integrins, along with their ligands on leukocytes, help these interactions.  Vascular permeability: Endothelial cells regulate the movement of substances, including fluids, electrolytes, and other molecules, between the blood and surrounding tissues. They form a selectively permeable barrier with tight junctions under normal conditions. They maintain the integrity of the vascular barrier, ensuring substances like nutrients and oxygen can pass while preventing the leakage of harmful substances into tissues.  Regulation of Vascular Tone: Regulation of vascular tone refers to the adjustment of the diameter of blood vessels to control blood flow and maintain blood pressure within a normal range. This process involves the contraction (vasoconstriction) or relaxation (vasodilation) of the blood vessels. Endothelial cells release various vasoactivesubstances that affect vascular tone, including vasodilators like nitric oxide and vasoconstrictors like endothelin. These molecules help regulate blood vessel diameter and blood flow.  Angiogenesis: Endothelial cells are also involved in angiogenesis, the process of formation of new blood vessels from pre-existing ones. Angiogenesis is essential for processes like wound healing and is involved in various pathological conditions, like inflammatory disorders and cancer. 31. Process of phagocytosis 1. Recognition: the phagocyte recognizes the target particle 2. Signaling: the phagocyte activates a signaling cascade to induce particle internalization. 3. Phagosome formation: the phagocyte forms a phagosome by closing the phagocytic cup around the particle. 4. Phagolysosome maturation: the phagosome matures into a phagolysosome, which in an acidic and hydrolytic environment that degrades the particle. 32. Histamines and Leukotrienes  Both are proinflammatory mediators that are released during an alergic inflammation and can cause a number of symptoms. o Histamine: responsible for many symptoms of allergic rhinitis, including sneezing, nasal itching, and rhinorrhea. o Leukotrienes: cause increased vascular permeability and nasal airway resistance. They also cause bronchoconstriction in both healthy people and those with asthma.33. Down syndrome and testing in pregnancy  Trisomy 21 – mentally challenge, low nasal bridge, low-set ears, protruding tongue, and poor muscle tone  Risk increases with maternal age >35  Prenatal testing – quad screening (blood test), ultrasound, chorionic fluid sampling, amniocentesis 34. Marfan syndrome  Autosomal dominant disorder affecting connective tissues of the body:  Affects chromosome 15  Eye problems- bilateral dislocation of the lens (most common); myopia; retinal detachment  Cardiovascular problems- mitral valve prolapse; progressive dilation of aortic wall ring; weakness of aorta and other arteries-- can lead to aneurysm (which can rupture leading to premature death); risk of aortic dissection much higher in pregnant women  Musculoskeletal system issues- long thin body with exceptionally long extremities; long tapering fingers; hyper-extensible joints; spinal deformities; concave/convex chest 35. Klinefelter syndrome characteristics  XXY- male appearance; female-like breasts; small testes- usually sterile (testicular dysgenesis); sparse body hair; long limbs (bar bodies visible) 36. Active transport – why is it different from passive transport?  Passive transport-does not use energy (ATP); moves down the concentration gradient Active transport-Requires life, biological activity, and energy (ATP) expenditure; Uses energy to move particles across a membrane against the concentration gradient  If you don’t have ATP this can no longer function properly  Example of an active transport pump is Na and K pump 37. Know the process of Osmosis, diffusion, filtration and active transport  Passive Transport (no ATP used)  Osmosis- movement of water across a semi-permeable (must be permeable to water) membrane down the concentration gradient (dependent on hydrostatic pressure and solute concentration)  Diffusion- movement of solute (w/ or w/o a semi-permeable membrane) down a concentration gradient  Filtration- movement of water and solute d/t a greater force on one side of the membrane than the other (ex: hydrostatic pressure)  Active Transport- uses ATP; transport proteins (the Na+/K+ pump) to move against the concentration gradient 38. Hypertrophy, hyperplasia, dysplasia – differentiate  Hypertrophy- increase in cell size  Hyperplasia- increase in cell number (abnormal multiplication) o You can check if patient has hypertrophy vs hyperplasia by doing a biopsy and looking at cells under microscope  Dysplasia- change in size; shape; organization of cells  Minor dysplasia associated with chronic irritation/inflammation o Most frequently found in respiratory tract; uterine cervix o Precursor for cancer 39. Hypoxic cell injury - mechanism  Interrupts oxidative (aerobic) metabolism-  diminishes ATP production  Anaerobic metabolism produces lactic acid  Acid damages cell membranes; intracellular structures; DNA Amount of damage depends on degree of O2 deprivation & metabolic needs of the cell  Can be from ischemia (most common cause of cell death) 40. Lead poisoning  High blood levels of lead  If untreated will result in lead encephalopathy- serious and irreversible neurological damage  Young children living at or below the poverty line at greatest risk (older housing; compromised nutrition)  Lead exposure increases risk of- damage to the brain/CNS; slowed growth/development; learning and behavioral problems; hearing and speech problems  Commonly found in old homes with lead paint, also found in medical equipment like old tooth implants 41. Apoptosis – importance  Programmed cell death- if this did not occur, endless cell proliferation would result encouraging the survival of abnormal/mutated cells, predisposing the individual to cancer &/or autoimmune disease  Cancer cells turn this function off to allow endless proliferation 42. Neoangiogenesis  Process of cancer cells establishing new blood vessels to supply themselves with blood and nutrients to grow.  Normal non pathological system is angiogenesis, neoangiogenesis is pathologic. May also allow for cancer to metastasize by traveling through blood. 43. Paraneoplastic syndromes – what is it?  Symptom complexes triggered by cancer but not caused by direct local effects of the tumor mass  Caused by biological substances (hormones) released from the tumor or by an immune response triggered by the tumor  May appear as other signs and symptoms at random (ex is fever, malaise that is unexplained)  Caused by cancer cells releasing hormones in excess as they proliferate and leads to general feeling of unwellness44. Cells of immunity – especially in parasitic infections  Eosinophils take care of parasites  Neutrophils: These are the most abundant white blood cells, acting as the first line of defense against infection by rapidly engulfing and destroying bacteria through phagocytosis.  Macrophages: These large phagocytes engulf and digest pathogens, dead cells, and cellular debris, also playing a role in antigen presentation to activate T cells.  Dendritic cells: These antigen-presenting cells capture pathogens, process them, and migrate to lymph nodes to activate T cells, initiating the adaptive immune response.  Natural Killer (NK) cells: These lymphocytes recognize and kill virusinfected cells and cancer cells without needing prior exposure to the specific pathogen.  B lymphocytes (B cells): When activated by an antigen, B cells differentiate into plasma cells that produce antibodies specific to that antigen, which neutralize pathogens.  T lymphocytes (T cells): These lymphocytes mature in the thymus and include different types with distinct functions:  Helper T cells (Th cells): Coordinate the immune response by activating other immune cells like cytotoxic T cells and B cells through signaling molecules.  Cytotoxic T cells (Tc cells): Directly kill infected cells by releasing cytotoxic substances.45. Prions  Composed of misfolded proteins; can self-replicate causing springform encephalopathy  Crutchfield jacobs disease- progressive, fatal, dementing neurologic illness caused by prions (fatal at ~8mo after symptom onset)  Transmission- consumption of meat from infected animals  Diagnosis- clinical evaluation; MRI; EEG; spinal fluid analysis; may also be detected in blood, urine, &/or olfactory epithelium  Definitive diagnosis: autopsy  No treatment  A miss-formed piece of protein that causes nerve degeneration (also known as mad cow disease), not a living organism. 46. HIV staging, testing, and treatment options  Stages: o Acute HIV- 2 to 4wks after infection; can be asymptomatic or have flu-like symptoms; viral titers are high (antigens can be measure in blood) and individual is highly contagious o Clinical latency- chronic HIV infection; virus continues to replicate but body is able to replace infected cells; immune defenses decline very slowly; may last 10-11yrs in untreated individuals or decades if therapy is successful in keeping titers low; often asymptomatic or have low levels of infection (ex: thrush) o AIDS- significant immune compromise  Diagnostics for AIDS: o Th cells <200cells/mm^3 o Western blot analysis o Presence of antibodies against HIV o Atypical or opportunistic infections and cancer (ex: Kaposi Sarcoma; Non-Hodgkin’s Lymphoma; Cervical Cancer)  Treatment: o antiretroviral therapy (ART)- combination of reverse transcriptase inhibitors; protease inhibitors; integrase inhibitors; fusion inhibitors; CCR5 antagonist o For children during/shortly after pregnancy- IgG therapy to help prevent perinatal infection; C-section; no breastfeeding (if untreated, child will likely die by age 2) 47. Childhood cancer – etiology and prognosis  Most originate from the mesodermal germ layer.  Multifactorial etiology- genetic risk factors; congenital conditions; environmental factors  Prognosis- nearly 85% of children/adolescents diagnosed with cancer are cured48. Carcinoma in situ – know well - specific characteristics  Preinvasive epithelial tumors (only in the original tissue) -glandular and squamous origin,  Localized to the epithelium- have not penetrated the local basement membrane or invaded surrounding stoma  May remain stable for a long time, progress to invasive/metastatic cancers, or regress and disappear  High grade- higher likelihood of becoming invasive 49. Naming of tumors – benign vs malignant  Benign tumors- usually encapsulated w/ connective tissue; contain fairly well-differentiated cells; well organized surrounding, supportive tissue (stroma); do NOT spread beyond their capsule; mitotic cells rarely seen  Malignant tumors- lack a capsule; more rapid growth rates; loss of differentiation; absence of normal tissue organization; variable in size/shape; disorganized stroma; grow to invade nearby blood vessels, lymph, and surrounding structures; mitotic cells common 50. Philadelphia chromosome  Reciprocal chromosomal translocation resulting in an abnormal gene product responsible for a clinical disorder- Chronic Myeloid Leukemia 51. Most common tumor suppressor genes  TP53 (the guardian of life genome)- regulates cell division by restricting cells from growing and dividing too fast or in unusual ways; plays a role in whether damaged cell DNA will be repaired or die from apoptosis; missense mutations are the most common mutation in human cancers (loss of function in both alleles to increase cancer risk)  Caretaker genes- activated by TP53 to repair damaged cell DNA/aid in chromosome stability; mutation causes increased chromosome instability & increased rates of mutation  Tumor suppressor gene and cancers syndromes associated with loss of function: o RB1- retinoblastoma o TP53- Li-Fraumeni syndrome o CDKN2A- familial melanoma o Neurofibromin (NF1)- Neurofibromatosis o APC- Familial adenomatous polyps o BRCA1/BRCA2- Breast cancer o WT1-Wilms tumor (childhood kidney cancer) 52. Metastasis  The spread of cancer cells from the site of the original tumor to distant tissues/organs Metastatic cells must be able to withstand stress of travel in the blood/lymph and must then survive in a new environment 53. Types of necrosis in gangrene  With hypoxia, bacterial invasion can result in gangrenous necrosis  Dry gangrene o lack of arterial blood supply o venous flow can carry fluid out of the tissue o coagulative necrosis o line of demarcation- skin dry; shriveled; dark brown/black  Wet gangrene o lack of venous flow o fluid accumulates in the tissue o more lethal o caused by necrotizing bacteria (gram + cocci, gram - rods, or anaerobic microorganisms) o tissue is cold, swollen, pulseless, moist, black, has a foul odor (no line of demarcation)  Gas gangrene o a type of wet gangrene caused by Clostridium infection (widely present in soil and proliferate under low oxygen tension) o Clostridium produce hydrolytic enzymes/toxins that destroy tissue and produce hydrogen sulfide bubbles o if untreated, death results in the next 12 hours- sepsis, shock, renal shutdown 54. Edema – Interstitial (what contributes to it)  Increased capillary hydrostatic pressure- volume of interstitial fluid exceeds lymphatic capacity to return fluid to the vascular system o Caused by: Venous obstruction- thrombophlebitis; blood clots; hepatic venous obstruction; R sided heart failure; tight clothing & Sodium & water retention o Predisposing factors- heart failure; oliguric kidney disease; cirrhosis  Decreased capillary oncotic pressure- More fluid to leaks into the interstitial space than is reabsorbed through the capillaries o Caused by: Plasma protein (albumin) loss- glomerular diseases of the kidney (nephrotic syndrome); hemorrhage; significant drainage from wounds/burns; protein-losing enteropathies & Diminished plasma protein production- severe liver disease or protein malnutrition  Increased capillary membrane permeability- allows significant amounts of proteins to escape into the interstitial space o occurs with inflammation and immune responseso often a result of trauma (burns; crushing injuries), neoplastic disease, allergic reaction, and infection  Lymph channel obstruction- proteins and fluids not reabsorbed and accumulate in the interstitial space (lymphedema) o Often occurs after the removal of lymph nodes (axillary; femoral) o Associated with the surgical treatment of cancer Treatment for edema can be elevate edematous limbs, use compression stockings, avoid prolonged standing, restrict salt intake, and take diuretic. 55. Radiation therapy – systemic use  Used to kill cancer cells while minimizing damage to normal structures  Well suited for cancer in local areas hard to reach surgically (ex: brain; pelvis)  Most effective with good local delivery of oxygen (not always present in large cancers)  Each tissue is given the maximum lifetime amount of radiation it can tolerate  Several delivery methods- external beam; brachytherapy(radiation seeds); etc. 56. Mechanism of ionizing radiation in cell injury  Ionizing radiation is any form of radiation capable of removing orbital electrons from atoms resulting in free electrons and positively charged ionizing atoms- causes molecular damage (especially to DNA)  3 types: x-radiation; gamma radiations; neutrons  Biological effects depend on rate of delivery; cell proliferation; oxygen effects/hypoxia; vascular damage (not all cells have the same sensitivity to IR) o Cell damage can be  Lethal  Potentially lethal- cell severely affected--modifications in environment will cause cell death  Sublethal- cell can substantially repair itself  High doses of radiation cause substantial cell death; result in detectable tissue reaction within days(early) or months to years(late)  Can cause large spectrum of genetic changes because all phases of cell cycle can be affected o IR during mitosis- chromosomal aberrations o DNA can be damaged directly or indirectly  Bystander effects- effects on cells not directly in the radiated field  Genomic instability- generations of cells derived from irradiated cell appear normal but mutations appear in distant offspring57. Patho of SLE  Systemic lupus erythematosus- chronic multisystem immune disease more common in females  Autoantibodies against: nucleic acids; erythrocytes; coagulation proteins; phospholipids; lymphocytes; platelets; etc  Deposition of circulating immune complexes containing antibody against host DNA  Clinical manifestations: remission/flare ups; arthralgias/arthritis (90%); vasculitis & rash (70-80%); renal disease (40-50%); hematologic changes (50%); cardiovascular disease (30-50%) Eleven common findings: Facial rash (malar rash) Discoid rash Photosensitivity Oral or nasopharyngeal ulcers Nonerosive arthritis Serositis Renal disorder Neurologic disorder Hematologic disorders Immunologic disorders Presence of antinuclear antibodies (ANA)  Diagnosis- presence of at least four of the above findings; labs-- positive ANA screen  Treatment- no cure; control symptoms and suppress the autoimmune response o Protection from UV light; NSAIDs; corticosteroids; immunosuppressive drugs (hydroxychloroquine) 58. Acute graft rejection  Cell-mediated immune response against unmatched HLA antigens  Hyperacute rejection o Occurs within minutes or hours after transplantation, and is usually caused by specific antibodies against the graft.  Acute rejection o Occurs within the first few months after transplantation, and is caused by the body's immune system attacking the new organ. The risk of acute rejection is highest in the first three months.  Chronic rejection o Occurs months or years after transplantation, and is the leading cause of long-term graft loss. 59. Ploidy – types – what is it? Euploidy- cells have a multiple of the normal number of chromosomes Haploid and diploid cells are euploid Polyploidy- cells have more than the diploid number Triploidy-zygote has three copies of each chromosome (fetus cannot survive) Tetraploidy- zygote has four copies of each (fetus cannot survive)Aneuploidy- cell that does not contain a multiple of 23 chromosomes Trisomy-cell contains three copies of one chromosome Monosomy- presence of only one copy of any chromosome (lethal- better to have extra than less)