Download Cellular Processes and Pathologies and more Exams Advanced Education in PDF only on Docsity!
NURS 5315 Advanced Pathophysiology
Ovarian cancer site of metastasis? - Peritoneal surfaces, omentum (fold of peritoneum connecting the stomach with other abdominal organs), liver The increased NADH/NAD+ ratio in the liver from ethanol causes: - 1. Pyruvate --> lactic acid, causing lactic acidosis
- Oxaloacetate --> malate. This prevents gluconeogenesis and leads to hypoglycemia
- Glyceraldehyde-3-phosphate --> glycerol 3- phosphate and combines with fatty acids to form triglycerides in the liver, known as hepatosteatosis
- Decreases citric acid cycle production of NADH and leads to using Acetyl-CoA for ketogenesis and lipogenesis What can Reactive Oxygen Species cause? - Heart disease, Alzheimers, Parkinsons, Amyotrophic Lateral Sclerosis (ALS), CV disease, HTN, HLD, DM, ischemic heart disease, HF, OSA. Lipid perioxidation, damage proteins, fragment DNA, less protein synthesis, chromatin destruction, damage mitochondria What is the body's defense against ROS? - Antioxidants (Vitamin E, Vitamin C, cysteine, glutathione, albumin, ceruloplasmin, transferrin) How are free radicals produced? - 1. Normal cellular respiration
- Absorption of extreme energy sources (radiation, UV light)
- Metabolism of exogenous chemicals, drugs, and pesticides
- Transition of metals
- Nitric oxide acting like a chemical mediator and a free radical action potential - Process of conducting an impulse. Activates the neuron --> the neuron depolarizes --> then repolarizes Threshold potential - Point at which depolarization must reach in order to initiate an action potential
Hypokalemia and action potentials - HYPERpolarized (more negative, ex. -100). Less excitable. Decreased neuromuscular excitability: weakness, smooth muscle atony, paresthesia, cardiac dysrhythmias Hyperkalemia and action potentials - HYPOpolarized (more positive, ex: closer to 0). More excitable. Peaked T waves. When resting membrane potential=threshold potential, it is BAD = cardiac standstill, paresthesia, paralysis Hypocalcemia and action potentials - Increased permeability to Na+. More excitable. Tetany, hyperreflexia, circumoral paresthesia, seizures, dysrhythmias. Hypercalcemia and action potentials - Decreased permeability to Na+. Less excitable. Weakness, hyporeflexia, fatigue, lethargy, confusion, encephalopathy, depressed T waves Atrophy - Occurs as a result of decrease in work load, pressure, use, blood supply, nutrition, hormonal stimulation, or nervous stimulation. Once the cell has decreased in size, it has now compensated for decreased blood supply, nerve supply, nutrient supply, hormonal supply, and has achieved new homeostasis. Cells are alive but have diminished function and may lead to cellular death. Atrophy examples - Physiologic atrophy- shrinking of the thymus gland during childhood. Disuse atrophy- someone that ends up being paralyzed Hypertrophy - Increase in SIZE of cells, which will lead to increase in size of organ. Caused by hormonal stimulation or increased functional demand. Hypertrophy examples - physiologic hypertrophy- skeletal hypertrophy when a person does heavy work or weight lifting / when a kidney is surgically removed, the other kidney increases in size pathologic hypertrophy- cardiomegaly results from an increased workload in hypertensive patients / left ventricular hypertrophy Hyperplasia - Increase in NUMBER of cells. Results from increased rate of mitosis. Can ONLY happen in cells that are capable of mitosis (cell division).
- Increased troponin (heart) Reperfusion injury - Oxygen supply is restored to ischemic tissues. Triggers oxygen intermediates which causes cell membrane damage and mitochondrial calcium overload. Xanthine dehydrogenase --> xanthine oxidate. This makes large amounts of free radicals, superoxide, and hydrogen peroxide. Causes cell membrane damage and mitochondrial calcium overload Reperfusion injury clinical manifestations - White blood cell count is impaired. Seen in tissue transplantation, ischemic syndromes of the heart, liver, intestines, kidneys, and cerebrum. Free Radical - Molecules that have an unpaired electron on its outer shell. This makes the molecule unstable. Cause cellular injury, aging, and disease to occur. Reactive Oxygen Species (ROS) - Produced as a normal byproduct of ATP production in mitochondria. ROS can overwhelm the mitochondria and exhaust intracellular antioxidants. Also produced by absorption of high energy sources like radiation or UV light. Ethanol - Acute affects in the liver include inflammation, fatty infiltration, hepatomegaly, acute liver necrosis, suppressed fatty acid oxidation. Chronic ethanol use is mainly seen in the stomach and liver, and is caused by free radicals. Elevated anion gap and osmolar gap >10 is diagnostic Infarct - Form of necrosis that is a SUDDEN insufficiency of arterial blood flow. (ie: heart attack, cold leg, MI) Apoptosis - Programmed cell death (normal). Needed to prevent cellular proliferation that would result in a large body. Clinical implications: neurodegenerative disease, ischemic injury, death of virus infected cells
Autophagy - Autodigestion of the cell. When cells lack nutrition, autophagy is triggered. During times of metabolic stress, autophagy provides ATP and other macromolecules for energy and cell survival. When stress progresses, it leads to cell death Aging - Body released more cytokines and proinflammatory substances which results in chronic inflammation What lab values are elevated as we age? - Interleukin 1, tumor necrosis factor-alpha, and C-reactive protein Role of hepatocytes - Acetyl CoA is processed by hepatocytes and transforms to 3 ketone bodies:
- Acetoacetate
- Acetone
- B-hydroxybutyrate Role of mitochondria - Ketogenesis: occurs mostly in the hepatocytes What triggers ketogenesis? - Unavailability of glucose. Keto diet = no sugar. Starvation and Type 2 DM can lead to this. Role of Acetyl-CoA - Returns to citric acid cycle and combines with oxaloacetate to form citrate. Also transforms into ketone bodies by hepatocytes Oxaloacetate - Used in gluconeogenesis (process of getting sugars from carbs). During starvation or uncontrolled diabetes, oxaloacetate levels are insufficient because it has been completely used by gluconeogenesis. Depletion of oxaloacetate increases amount of Acetyl CoA. Normal cells - Will not grow unless attached to a firm surface. Normal cells have a limited life span and divide 10-50 times. Uniform in size and shape. Cancer cells - Cells continue to crowd and eventually pile over. Immortal and divide for years. Divide rapidly and are parasites. Must grow in a hypoxic or acidic environment.
Head and neck cancer site of metastasis? - Lymphatics, liver, bones Sarcoma site of metastasis? - Lungs Melanoma site of metastasis? - Lymphatics, lung, liver, brain, GI Origin of cancer from adeno? - Glandular Epithelial TNM Staging System - T= tumor spread TX= main tumor not measured T0= tumor cannot be found T1=T4=size or extent of main tumor. Higher the number, larger it is N= node involvement NX= cannot be measured N0=no cancer in lymph nodes N1-N3= number of lymph nodes. Higher the number, the more lymph nodes that contain cancer M= presence of metastasis MX=cannot be measured M0=cancer has not spread to other parts of body M1=Cancer has spread to other parts of body BRCA gene - Increases risk for developing ovarian, breast, and prostate cancer Paraneoplastic syndromes - Triggered by cancer but aren't caused directly from a tumor/mass. Commonly caused by hormones released by a tumor or an immune response triggered by a tumor. May be earliest S/S of unknown cancer
Cachexia - Imbalance between amount of energy intake vs. energy used. Wasting syndrome = catabolic process. Increase in apoptosis and impaired ability to regenerate cells. Necrosis - Cell death, irreversible cell injury. Clinical implications: fever, increased heart rate, increase number of leukocytes, pain, presence of cellular enzymes (LDH, CK, AST, ALT, ALT, Amylase, aldolase) Coagulative necrosis - Occurs primarily in the kidneys, heart, and adrenal glands. Commonly results from hypoxia caused by severe ischemia or hypoxia from chemical injury (especially ingestion of mercuric chloride) Liquefactive necrosis - Commonly results from ischemic injury to neurons and glial cells in the brain What does T3N2M0 in cancer staging mean? - large, with local nodes but no evidence of metastasis What kind of genetics does a person with cystic fibrosis have? - Autosomal recessive Which type of cellular injury can cause Alzheimers? - Free radical/ROS Well differentiated vs undifferentiated cancer cells - Well-differentiated cancer cells look more like normal cells and tend to grow and spread more slowly than poorly differentiated or undifferentiated cancer cells. What is the main plasma protein? - Albumin (negative charge). Buffers H+ (positive charge). Binds calcium (about 40%). What does a decreased plasma oncotic pressure mean? - Results from losses or diminished production of plasma albumin. Causes fluid to move into the interstitial space, resulting in EDEMA. AST and ALT are related to which organ? - Liver Valve malfunction can cause what? - Ventricular hypertrophy
How does a hypertonic solution alter osmolality? - Increases solute concentration, causing INCREASED osmolality. Causes cells to SHRINK. How does a hypotonic solution alter osmolality? - Intravascular space to become more dilute, causes cells to SWELL. Fluid volume deficit (dehydration) clinical manifestations - Poor skin turgor, dry mucous membranes, sunken eyes, sunken fontanels (in babies), decreased urine output, fatigue Fluid volume excess (fluid retention) clinical manifestations - Edema, tight skin, puffiness of eyes, rales or wet breath sounds Edema is an accumulation of fluid where? - Interstitial space Edema pathophysiology - 1. Increased hydrostatic pressure
- Decreased oncotic pressure
- Increased capillary membrane permeability
- Lymphatic channel obstruction Edema clinical manifestations - Pitting, swelling, puffiness, limited movement in affected area Liver disease and protein malnutrition can result in what? - Decreased oncotic pressure Glomerular disease, trauma victims, hemorrhage, burns, and cirrhosis of the liver can result in what? - Decreased oncotic pressure How does edema cause increased hydrostatic pressure? - Venous obstruction --> increased hydrostatic pressure --> fluid is pushed out of the vascular space into the interstitial space
How does edema cause decreased oncotic pressure? - Decreased plasma protein production --> decreased oncotic pressure and osmotic pressure --> fluid moves into the interstitium How does edema cause increased capillary permeability? - Results from times of inflammation (trauma, crushing injuries, burns, neoplastic diseases, allergic reactions, infections). Increased capillary permeability allows large amounts of fluid to escape and enter the interstitial space. How does edema cause lymphatic channel obstruction? - Lymphatic channels are blocked because of infection or tumor. Proteins and fluids are not reabsorbed and accumulate in the interstitial space, causing lymphedema. Hypovolemic hypernatremia - Occurs as a result of sodium and water loss. Clinical manifestations: volume depletion, orthostatic hypotension, hypotension, tachycardia, lack of organ perfusion Hypervolemic hypernatremia - Uncommon, but most common cause is administration of hypertonic sodium salts. Infants: erroneous preparation of dietary formula Outpatient adults: ingestion of salts Inpatient adults: iatrogenic (hypertonic IV solutions) Clinical manifestations of mild, moderate, and severe hyponatremia? - Mild: anorexia, apathy, restlessness, nausea, lethargy, muscle cramps Moderate: agitation, disorientation, headache Severe: seizures, coma, incontinence, death Insulin effects on potassium - Shifts K+ intracellularly Acid base balance effects on potassium - Alkalosis shifts K+ into cells --> hypokalemia Acidosis shifts K+ out of cells --> hyperkalemia
Metabolic acidosis - Causes: Excess H+ ions (renal disease), bicarb deficiency (diarrhea, renal tubular acidosis), increased acid production (ketoacidosis, lactic acidosis). Clinical Manifestations: myocardial contractility, decreased cardiac output, hyperkalemia, headache, lethargy, coma Patho: Body will compensate by hyperventilation or Kussmaul respirations, increased ionized calcium Metabolic alkalosis - Causes: Excess of bicarbonate, deficiency of H+ (gastric suctioning, excessive vomiting, diuretic use) Clinical Manifestations: Hypokalemia, cardiac arrhythmias, hyperactive reflexes, hypocalcemia weakness, slow shallow respirations Patho: Hypokalemia, decreased ionized calcium Respiratory Acidosis - Causes: Hypoventilation, respiratory depression, impaired respiratory musculature from Guillian Barre or multiple sclerosis, OSA, asthma, ARDS, COPD, PNA Clinical Manifestations: Headache, restlessness, blurred vision, apprehension, lethargy, muscle twitching, tremors, convulsions Patho: Hypoventilation (mechanical ventilation may be required) Respiratory Alkalosis - Causes: Hyperventilation, hypoxemia, PE, CHF, high altitudes, fever, sepsis, anemia, anxiety, hepatic failure, salicylate overdose Clinical Manifestations: dizziness, confusion, paresthesias, convulsions, seizures, coma Chronic metabolic acidosis will enhance resorption of what? - Ammonium What are the 4 nitrogenous bases of DNA? How do they pair up? - Adenine, cytosine, guanine, thymine Thymine <--> adenine Guanine <--> cytosine How does DNA replication occur? - Consists of breaking the weak hydrogen bond between the bases, leaving a single strand with each base unpaired. The consistent pairing of TA and GC is key to accurate
replication. DNA polymerase travels along a single DNA strand, adding the correct nucleotides to the free end of each new strand. What is RNA? - Responsible for transcription, translation, protein formation from DNA. Uracil <--> adenine Guanine <--> cytosine Transcription - RNA is synthesized from DNA resulting in creating of mRNA Translation - RNA directs synthesis of polypeptides. mRNA interacts with tRNA and ribosomes to create amino acids Gamete cell - Mature sperm or egg cell. Haploid, contain 23 chromosomes. Reproduce through meiosis. When the sperm and egg join, the two sets of 23 chromosomes form a complete set of 46 chromosomes. Somatic cells - All other cells in the body. Diploid, 46 chromosomes or 23 pairs of chromosomes. Reproduce through mitosis. 23 pairs of chromosomes or 46 chromosomes total. Polyploidy and its clinical manifestations - When a cell has more than 46 chromosomes Ex: Liver, bronchial and epithelial tissues are normally polyploid. A zygote having 3 or 4 copies of each chromosome, rather than 2 has triploidy or tetraploidy which almost always results in spontaneous abortion/stillborn. Aneuploidy and its clinical manifestations - Cells that do not contain multiple of 23 chromosomes (can contain more or less, like 45 or 47). Caused by nondisjunction (failure for the chromosomes to divide properly). Ex: Spontaneous abortion, still born, birth defects Autosomal aneuploidy and its clinical manifestations - Autosomal chromosomes are all chromosomes which do not have any relation to gender. Ex: Trisomy 13, 18, 21 (can survive, others don't survive). Trisomy 21 causes down syndrome (low IQ, low nasal bridge, poor muscle tone, short stature, lower life expectancy)
Clastogens - Harmful agents which damage chromosomes. Ex: radiation Hypoxic injury pathophysiology - Lack of O2 --> decrease in mitochondrial function --> decreased ATP --> increases anaerobic metabolism. Also causes cessation of protein synthesis.
