Pathophysiology Study Guide PDF

A1 - UNIT 1 Learning objectives: 1. Analyze similarities and differences in etiology, pathogenesis, and clinical manifestations of immunosuppression disorders, hematopoietic disorders, infections, altered cellular metabolism and regulation including neoplasms, fluid and electrolyte imbalances, and...

A1 - UNIT 1 Learning objectives: 1. Analyze similarities and differences in etiology, pathogenesis, and clinical manifestations of immunosuppression disorders, hematopoietic disorders, infections, altered cellular metabolism and regulation including neoplasms, fluid and electrolyte imbalances, and acid/base imbalances. (CO 1, 4) Immunosuppressant disorders ○ HIV/AIDS Etiology (causes) HIV infection via bodily fluids Pathogenesis (how it develops) HIV targets and destroys CD4 WBC → altered immune function in persons → opportunistic infections, malignant tumors, nervous system manifestations, the wasting syndrome, and metabolic disorders Clinical manifestations Patients with HIV infection can be asymptomatic due to still circulating immune cells. The presentation of immunosuppressed cells does not develop until the number of circulating cells drops below the critical level (CD4 WBC Na+ → cells take in H20 and swell → cellular edema ○ Clinical manifestations  A distinguishing feature of renal loss hyponatremia is high urine sodium concentration Stupor/coma, anorexia, lethargy, tachycardia, muscle weakness, orthostatic hypotension, seizure, HA and stomach cramping Hypernatremia: ○ Etiology (causes) Intake of high-Na+ foods or drinks = hypertonic Na+ gain Excessive fluid loss through body system = pure water loss Insufficient fluid intake = hypotonic fluid loss ○ Pathogenesis (how it develops) Hypervolemia: increase Na+ and H20 in ECF → H20 moves out of cells → cells shrink Euvolemic hypernatremia: osmolality (concentration) of ECF increases → H20 moves out of cells to equalize ECF and ICF Hypovolemic hypernatremia: Na+ and H20 decrease from ECF → greater loss in ECF ○ Clinical manifestations Flushed skin, restlessness, anxiety, confusion, HTN, fluid retention, edema, decreased urine output, dry skin, agitation, low-grade fever and thirst Potassium (normal range 3.5-5.0) Hypokalemia ○ Etiology (causes) Poor dietary intake Excessive losses - renal and GI (n/v, suctioning) Fluid compartment shifts ○ Pathogenesis (how it develops) ECF K+ increases → kidneys excrete K+ by releasing aldosterone ○ Clinical manifestations N/v, EKG changes (flat or inverted T wave), decreased reflexes, hypotension, muscle weakness, shallow breathing and constipation Hyperkalemia ○ Etiology (causes) Metabolic acidosis Cellular injury DKA Potassium excretion - rarely diagnosed if ○ Pathogenesis (how it develops) K+ shifts from ICF to ECF K+ normally contained in the ICF is shifted to the ECF Inadequate insulin causes K+ to shift from ICF to ECF Impaired excretion when kidneys are not functioning normally ○ Clinical manifestations Muscle cramps/weakness, urine abnormalities, respiratory distress, decreased HR and BP, EKG changes (tall peaked T waves) and decreased deep tendon reflexes  Magnesium (1.1-3) Hypomagnesemia ○ Etiology (causes) Poor intake and/or absorption from GI tract Phytic acid, PPIs, calcium, phosphates and fats inhibit absorption Kidney disease with creatinine clearance 14 mg/dL encephalitis may develop >15 mg/dL life threatening and a crisis ○ Acid/base imbalances Respiratory - acidosis Etiology (causes) ○ Hypoventilation and increased physiological dead space Pathogenesis (how it develops) ○ pH < 7.35 and ↑CO2 → ↑ H+ concentration in the blood Clinical manifestations ○ Compensation = simulation of ventilation to normalize C02 and HCO3 levels ○ If respiratory acidosis is prolonged or severe → neurological changes, ↑ ICP, ↑ risk of herniation and death and life-threatening dysrhythmias Respiratory - alkalosis Etiology (causes) ○ Hyperventilation: decreased carbonic acid, cerebral vasoconstriction, less O2 to tissue and inhibited respiratory effort Pathogenesis (how it develops) ○ pH > 7.35 and ↓CO2 → ↓ H+ concentration in the blood Clinical manifestations ○ Compensation = excreting HCO3 through the kidneys Metabolic - acidosis Etiology (causes) ○ Renal and GI HCO3- loss, acid ingestion and alterations in acid production and excretion Pathogenesis (how it develops) ○ pH < 7.35 and ↓ HCO3 → ↑ H+ concentration in the blood Clinical manifestations ○ Compensatory mechanism = hyperventilation or Kussmaul breathing (a normal RR with long, deep breaths) Metabolic - alkalosis Etiology (causes) ○ Renal and GI loss of H+, intracellular shift of H+ and retention or addition of HCO3 Pathogenesis (how it develops) ○ pH > 7.35 and ↑ HCO3 → ↓ H+ concentration in the blood Clinical manifestations  ○ Compensatory mechanism = hypoventilation to increase partial pressure of C02 and increased excretion of HCO3 by the kidneys 2. Differentiate between the pathophysiological changes and identify regulatory and compensatory mechanisms for maintaining homeostasis, the cellular environment, nutrition, hemostasis, immunity, stress, and coping. (CO 2, 4) Maintaining homeostasis ○ Insufficient gas exchange Hypoxemia Etiology ○ Inadequate O2 in the air, respiratory disease, neurological system dysfunction and alterations in circulatory function Pathophysiological changes ○ Impaired diffusion of gases, inadequate circulation of blood through pulmonary capillaries and mismatching of ventilation and perfusion Compensatory mechanisms ○ Hypoventilation Hypercapnia Etiology ○ Hypoventilation or mismatching of ventilation and perfusion Pathophysiological changes ○ Acid-base imbalance (respiratory acidosis) and changes in kidney, nervous system and cardiovascular function Compensatory mechanisms ○ Renal and respiratory compensation The cellular environment ○ Pathophysiological changes - cell injury Physical agents: mechanical forces, extremes of temperature and electrical forces Biological agents: viruses, parasites and bacteria Nutritional imbalances: excesses and deficiencies Radiation: ionized RT, ultraviolet RT and non-ionizing RT Chemical injury: drugs, carbon tetrachloride, lead toxicity and mercury ○ Regulatory mechanisms Reversible cell injury = impairs cell function, but does not cause cell death Cellular swelling: impaired energy dependent NA+/K+ ATPase membrane pump normally from hypoxic cell injury ○ Etiology: not enough O2 in the air, respiratory disease, inability of cell to use O2, edema and ischemia ○ Pathogenesis: Cell does not have enough O2 → interrupts O2 metabolism and production of ATP → acute cellular swelling ○ Pathophysiology: longer cell goes without O2 the greater chance injury CANNOT be reversed → death Fatty change: linked to intracellular accumulation of fat Apoptosis = programmed cell death, aka suicide. When does it happen?: cell is worn out, too many cells were produced, cells were made improperly and cell has a genetic damage Necrosis = cell death Etiology: cell death in an organ or tissue that is still part of a living person Pathogenesis: interference in cell replacement and tissue regeneration  Pathophysiology: gangrene = tissue dies from lack of blood supply ○ Compensatory mechanisms - changes are due to stressors on the cell. If the stressor goes away, then the cell goes back to normal Alterations in size: Atrophy = decrease in cell size & Hypertrophy = increase in cell Hyperplasia = increase in number of cells Metaplasia = transformation of one cell type to another Dysplasia = abnormal cell growth of a specific tissue Nutrition ○ Pathophysiological changes Weight loss or gain Muscle wasting and weakness Changes in skin and mucous membranes Problems with wound healing Dehydration, diarrhea and abdominal pain ○ Regulatory mechanisms Signals regulating food intake and energy homeostasis: Ghrelin, insulin and leptin ○ Compensatory mechanisms Adjusted eating behaviors and/or metabolic processes Hemostasis - result of clotting process ○ Pathophysiological changes Formation of blood clot to stop bleeding and repair vessels ○ Regulatory mechanisms Constriction of the blood vessel Formation of a temporary “platelet plug" Activation of the coagulation cascade Formation of “fibrin plug” or the final clot ○ Compensatory mechanisms Nitric oxide prevents platelets from sticking to the endothelium and being recruited Platelet release bioactive molecules from their granules to help with hemostasis Platelet aggregation Prostacyclin inhibits platelet aggregation and causes vasodilation, while thromboxane A2 causes vasoconstriction Immunity ○ Pathophysiological changes Protects the body from invasion of microorganisms and other antigens Removes dead or damaged tissue and cells Recognizes and removes cell mutations that have demonstrated abnormal cell growth and development ○ Regulatory mechanisms 1st line of defence, skin boundary surfaces = mucous membranes, enzymes, natural microbial flora and complement proteins The complement system aids 1st line of defence. It is essential for the activity of antibodies and increases bacterial aggregation making them more susceptible to phagocytosis. It is responsible for the dilation and ultimate leaking of fluid from the vascular system leading to redness and swelling during the inflammatory process ○ Vascular permeability: shift from ICF to ECF → hypovolemia and hypotension  ○ Nervous system: vasoconstricts and shunts blood from non-essential to essential organs (brain, heart and lungs) ○ Acute systemic hypoperfusion: ↑ HR and cardiac contractility to maintain CO. Inadequate tissue perfusion may → organ damage ○ Renal system: vasodilatory response of the glomeruli to maintain internal degree of pressure and continue filtration. Ongoing hypoperfusion → ↓ urine output → oliguria or anuria ○ Peripheral vasoconstriction: ↑ cardiac ventricular preload. If myocardium is compromised ↑ in ventricular afterload challenges the pulmonary vascular system → excess fluid in ventricles that cannot be ejected ○ Respiratory system: ↑ RR ○ Inadequate tissue perfusion (hypoxia) and hypercapnia: leads to CNS decompensation → seizures, stupor and coma ○ Multisystem failure: septic shock syndrome with multiorgan failure → inadequate tissue perfusion, overextended compensatory mechanisms, and hot cell damage leading to irreversible organ failure and death of host 2nd line of defence, innate, nonspecific immunity = phagocytes, natural killer T lymphocytes, granulocytes and macrophages 3rd line of defence, specific immunity = antibodies derived from B lymphocytes, the T lymphocytes resulting from learned or acquired specific immunity ○ Compensatory mechanisms Innate immunity (natural or native) = the immunity present at birth. It is nonspecific and involves inflammatory processes. Components: epithelial barriers, phagocytic cells, neutrophils, macrophages, NK cells, plasma proteins, opsonins, cytokines and acute phase proteins. Induction of inflammatory response. Adaptive immunity (artificial) = when the body is given immunity to a disease by intentional exposure to small quantities of it. It is gained after birth either actively or passively - active acquired immunity develops after the introduction of a foreign antigen resulting in the formation of antibodies or sensitized T lymphocytes. It is targeted to a specific antigen and involves T and B lymphocytes. Passive acquired immunity = occurs by the introduction of preformed antibodies. Example: transfusion of immunoglobulin (Ig) or naturally such as from a mother to fetus via the placenta or to her breastfeeding infant Stress ○ Pathophysiological changes Altered physiological function - cardiovascular, gastrointestinal, immune, neurologic systems Altered psychological factors - depression, accidents, suicide, chronic alcoholism, drug abuse, eating disorders ○ Regulatory mechanisms Alarm stage - generalized stimulation of the sympathetic nervous system and the HPA axis resulting in release of catecholamines and cortisol. Resistance stage - body selects the most effective and economic channels of defense. Exhaustion stage - resources are depleted and signs of “wear and tear” appear. ○ Compensatory mechanisms - Allostasis is how the body responds to stressors in order to regain homeostasis Activation of the SNS component of the autonomic nervous system  Activation of the RAAS system Activation of the endocrine system - growth hormone, thyroid hormone, reproductive hormones and ADH Coping ○ Mechanisms Emotional - techniques to regulate emotions and decrease stress Behavioral - conscious and voluntary response to stress 3. Differentiate between the causes and manifestations of inflammation, cellular injury and necrosis, types of dehydration, and types of shock. (CO 1-4) Inflammation ○ Causes Immunologic defense against tissue injury, infection, or allergy. Response to injury, not the agent causing the injury like infection Minimizes/removes pathologic agent or stimulus triggering the inflammation and promotes healing ○ Manifestations (4 potential outcomes) 1st – acute inflammation followed by restitution where the damaged tissue is replaced by identical function tissue. 2nd – fibrous repair of the damaged tissue and the formation of scar tissue 3rd – the development of chronic inflammation 4th – initial death of tissue and ultimately death of the host Types of shock - syndrome not disease ○ Distributive Anaphylactic Causes ○ Vasodilating substances in the blood ○ System-wide inflammatory response to an allergen leading to overstimulation of the MAST cells resulting in a release of histamine, prostaglandins, etc Manifestations: severe edema in the upper airways blocking mechanical intake of O2 Neurogenic Causes: loss of sympathetic vasomotor tone from the brainstem to the thoracolumbar area (around T6) = no signal from the “cell phone towers” Manifestations: temporary loss of autonomic function below level of injury → cardiovascular injury Septic Causes: inflammatory mediators within the circulatory system respond to infection → ↑ permeability “leaky pipes” Manifestations: ↓ BP ○ Cardiogenic Causes: alterations in cardiac function → “pump problem” Manifestations: ↓ CO ○ Hypovolemic Causes: loss of plasma (dehydration, burns, diarrhea or vomiting) and hemorrhagic Manifestations: significant amount of fluid or blood loss ○ Obstructive Causes: obstruction of blood flow through circulatory system  Manifestations: ↓ BP, ↑ HR and SOB 4. Explore alterations in nutrition in connection with immunosuppression disorders and other aspects of inflammation and infection. (CO 1-4) Immune function ○ Alterations in immune function Host defense failure - antigenic variation, viral latency and immunodeficiency Primary immunodeficiency disrupted communication between B-cells and T-lymphocytes Autoimmunity - failure of immune system to distinguish itself from outers, B-cell hyperactivity, formation of autoantibodies that cause direct damage or combine with antigen to form tissue-damaging complexes. Hypersensitivity - 4 processes: autoimmunity, failure of self-tolerance, inflammation and disease development Allomunity - the body has a self versus non-self recognition activity of MHC molecules. Lymphocyte recognition is key. Must match MHC as closely as possible in organ transplants to avoid rejection via immune/inflammatory reactions Inflammation ○ Pathophysiological response: Acute inflammation - triggered by injury Increases blood flow to site, increases healing cell at site and prepares for tissue repair Chronic inflammation - recurrent or persistent, lasting several weeks or longer Monocytes, macrophages, and lymphocytes more prominently involved Can cause fatigue, malaise, body aches, insomnia, depression, anxiety, weight fluctuations or GI upset. Formation of granulomas and scarring often occur - may be due to a defect or an inability to resolve the damaged tissue or agent causing injury. As a protective measure to prevent tissue damage, thickened tissue forms at the site of inflammation made up of clusters of white blood cells. This is protective because it can surround a foreign body to prevent further damage. This is a reaction to the irritation that causes the inflammation Cellular response - controlled by cytokines, which send signals and organize the response Vascular response - induces vasodilation and increases capillary permeability to get more blood flow to the area Infection ○ Alterations Acute is an infection that resolves in a few days or weeks Chronic is an infection that usually lasts longer than 12 weeks or is incurable Localized is an infection limited to a specific body area Systemic describes an infection that affects the body as a whole, or has spread throughout the body Epidemic describes a situation in which there are more cases of an infectious disease than is normal for the population or geographic area Pandemic is a worldwide epidemic of a disease Healthcare-acquired (Nosocomial) infections occur when a secondary infection develops, transmitted by healthcare providers or care provided in a healthcare setting. Community-acquired infections occur when an infection is transmitted in a community setting CONCEPT MAPS Acid-base balance: closely related to fluid and electrolyte balance – changes in one of them can cause changes in the other Nutrition: greatly influences fluid and electrolyte intake Elimination: creates fluid and electrolyte output. Can greatly influence: Perfusion & Gas exchange (ECV imbalance) Cognition (osmolality imbalances) Mobility (electrolyte imbalances that cause muscle weakness) Pain- the ischemia from impaired tissue perfusion creates lactic acid that contributes to pain. Clotting- Impairs perfusion Inflammation- occurs when there is tissue damage. In addition, damage to the endothelium of arteries leads to the development of inflammation that initiates atherosclerosis Gas exchange- results from the lack of oxygen being carried by the blood from the alveoli to cells and carbon dioxide away from cells to the alveoli for exhalation Elimination – elimination from the kidneys is an indirect indicator of cardiac output Cognition- altered due to the lack of neurons receiving adequate oxygen and glucose to maintain function Mobility – peripheral arterial disease reduces the mobility of patients because of the pain they experience Nutrition – lack of distribution of nutrients to maintain cellular function Patient education- the importance of walking and a healthy lifestyle behaviors to exercise the heart and improve central perfusion Anxiety – Excessive carbon dioxide is exhaled Acid-base balance- affected by gas exchange in several ways. Disease that retain carbon dioxide create increased levels of carbonic acid causing respiratory acidosis. When excessive carbon dioxide is exhaled, less carbonic acid is formed causing respiratory alkalosis. Hypoxia attributable to inadequate perfusion, causes lactic acid formation resulting in metabolic acidosis Perfusion – when inadequate, it causes lactic acid formation Nutrition – when a patient expends more than usual energy to breath, they require high-calorie, high-protein and nutritious foods in small servings to they do not tire which eating. Patients with anemia need food high in iron to maintain or increase their hemoglobin levels. Mobility – may be reduced with patients with impaired gas exchange become dyspneic when walking or climbing stairs Fatigue – related in two different ways: 1) When anemia is a cause of impaired gas exchange, fatigue may be a manifestation of the anemia; 2) when patients must use accessory muscles and work hard to breath, they exert significant energy to breath which contributes to fatigue. Fluid and electrolyte balances: changes in acid base balance and fluid & electrolyte closely related in that changes in one results in changes in the other. Oxygenation, Perfusion & Nutrition: facilitate optimal acid-based balance by allowing normal acid production. Alterations such as ischemia, hypoxia, starvation, and high-fat, low-carbohydrate diets can disrupt that process. Elimination: facilitates optimal acid-base balance through acid excretion, whereas changes such as oliguria and diarrhea can disrupt acid-base balance. Cognition: Disrupted acid-base balance can experience altered cognition. Perfusion: impaired when blood clots slow or stop blood flow or when the absence of clotting results in hemorrhage Gas exchange: impaired when pulmonary emboli reduced pulmonary capillary blood available to carry oxygen from alveoli to cells Intracranial regulation: affected either by blood clots or by hemorrhage, which produce disorders such as brain attack or communicating hydrocephalus Mobility: is reduced due to illness or recovery from surgery. Increases the risk for DVT. Pain: experienced from an arterial thrombus or constriction impairing perfusion to a lower extremity as well as by hemorrhage in a joint space Patient education: needed to help patients manage their bleeding or clotting disorders. Immune system - Provides a sentry level of alert for early identification of pathogens entering the body. - It is critical and the first line of defense against infection. - Inflammation is part of the body’s response to a foreign antigen. - Many of the symptoms of infection are those of the body's inflammatory response. Tissue integrity - Another critical concept, in that the skin is the largest component of the immune system. - Intact tissues form natural barriers to prevent pathogen entry. Stress (physical, emotional, or environment) - Challenges the immune system and is a trigger to inflammation. - This makes the body more vulnerable to damage. Nutrition - Is compromised when infection and inflammation is active. - The various disorders of the immune system can contribute to nutritional deficits. Cause: - Many of the pathophysiologic processes associated with inflammation are found in immunity and infection processes with the pathology from one overlapping those of the other two or one process triggering another. For example, the hypersensitivity reactions of the immune system triggering an inflammatory response or an infection stimulating an inflammatory response. Effect: - Tissue integrity is at risk along with impaired mobility and pain because of the consequences (swelling) of an inflammatory response associated with an initial injury. - The impact on thermoregulation depends on the severity of the inflammatory response to tissue injury. - In the presence of inflammatory-induced pleural effusion, adequate gas exchange can be compromised. - Microvascular clotting may be a consequence of inflammation, especially if it is chronic resulting in alterations in hemostasis. - The concepts of Fatigue and Stress are associated with both injury and recovery, whether it is an acute inflammatory response or chronic inflammation from an autoimmune hypersensitivity reaction. TOPICS TO FOCUS ON! Thrombocytopenia ○ What is it: results from a decrease in platelet production, increased sequestration of platelets in the spleen, or decreased platelet survival ○ Compensation mechanism:The bone marrow (where platelets are produced) detects the low platelet count and compensates by increasing the production of megakaryocytes (the precursor cells to platelets). This process is stimulated by the release of thrombopoietin, a hormone mainly produced by the liver and kidneys.Thrombopoietin stimulates the bone marrow to produce more megakaryocytes, which then release platelets into the bloodstream. In some cases, the bone marrow may release large platelets (which are usually immature but may be more effective in clotting), but the increase in production may not always be enough to fully compensate for the loss. Fluid Volume Deficit (FVD) ○ Dehydration: pure water loss, results in hypernatremia to maintain homeostasis Compensation mechanism: secretion of ADH from pituitary gland (promotes reabsorption of water) and stimulation of thirst center (when stimulated, thirst center sends a signal to increase water intake). ○ Volume Depletion: occurs when there is a loss of water and sodium which results in deficit of ECF volume = decrease in blood volume circulation Compensation mechanism: activation of body systems and processes (sympathetic nervous system stimulation, release of ADH, atrial receptor suppression, and RAAS activation) to retain water and sodium. Complement System and Shock ○ What: complement system is found in the blood and is essential for the activity of antibodies ○ Pathophysiology: increases and allows for the shift of fluid from the intravascular compartment to the extravascular/extracellular spaces in the tissues leading to hypovolemia and hypotension (vascular permeability), attempts to compensate for the hypotension with peripheral vascular constriction and shunting of blood from nonessential to essential organs (brain, heart & lungs) (nervous system), results in increased heart rate and cardiac contractility to maintain cardiac output despite a hyperdynamic cardiovascular state, inadequate tissue perfusion may cause organ damage (acute systemic hypoperfusion), attempts to compensate by creating a vasodilatory response of the glomeruli to maintain an internal degree of pressure to continue filtration and continued hypoperfusion of kidneys leads to decreased urine output to retain cardiovascular volume resulting in oliguria or anuria (renal system), peripheral vasoconstriction, respiratory system increases RR then leads to inadequate tissue perfusion (hypoxia) and hypercapnia then multisystem failure (shock) Marasmus and Kwashiorkor ○ Key Differences Between Marasmus and Kwashiorkor: Feature Marasmus Kwashiorkor Cause Severe calorie and Adequate calories but severe protein protein deficiency deficiency  Appearan Very thin, wasted Swelling (edema), especially in the ce muscles, and abdomen body Swelling No edema (due to Edema (swelling from fluid (Ede lack of protein) retention) ma) Fat Stores Low or absent fat Fat stores may be present but the stores protein deficiency causes fluid retention Immune Weakened, more Weakened, more prone to infections Syste prone to m infections Inflammat Increased due to Increased inflammation, ion infections and contributing to swelling and tissue tissue damage breakdown Primary Lack of calories Lack of protein, but enough energy Nutrit (energy) and (calories) ional protein Issue ○ Antibody-mediated and Immune complex-mediated hypersensitivity ○ Type II hypersensitivity response (antibody-mediated reaction): reaction against self, inflammation, opsonization, lysis of cells causing autoimmune disorders (Grave’s disease, Hashimoto’s thyroiditis, etc.) Pathophysiology: antibodies (IgG/IgM) bind directly to cell surfaces or extracellular matrix components, causing cell damage via complement activation, phagocytosis, or cytotoxicity ○ Type III hypersensitivity response (immune complex-mediated reaction): disposition of insoluble antigen-antibody complex into vascular epithelium or extravascular tissue causing systemic lupus erythematosus Pathophysiology: formation of antigen-antibody complexes (immune complexes) that deposit in tissues, causing inflammation and tissue damage via complement activation and recruitment of inflammatory cells. Staging lymphomas and Solid malignant tumors ○ Staging solid malignant tumors T = size and extent of spread, the # indicates the progressive extent of the malignant disease TX = Primary tumor can not be assessed T0 = no evidence of primary tumor Tis = Carcinoma in situ T1, T2, T3, T4 = increase size and/or location extent of the primary tumor  N = absence or presence in lymph nodes, the # indicates the # of lymph nodes involved NX = can not be assessed N0 = no regional lymph node metastasis N1, N2, N3 = increased involvement of reginal lymph nodes M = absences or presence of secondary spread of the tumor MX = can not be assessed M0 = no distant metastasis M1 = Distant metastasis ○ Staging lymphomas ○ Shock ○ Disruption in cellular process: during shock, reduced blood flow leads to hypoxia, causing cells to switch from efficient aerobic metabolism to less efficient anaerobic metabolism, which produces lactic acid and can result in metabolic acidosis. Without adequate oxygen, the mitochondria can't generate enough ATP, disrupting essential cellular functions like ion transport and protein synthesis, leading to cell swelling and death. Additionally, damage to the endothelial cells lining blood vessels increases their permeability, allowing fluid to leak into surrounding tissues, causing edema and worsening the buildup of waste products like lactic acid, which further harms cellular processes and contributes to organ dysfunction. Pernicious anemia and folate-deficiency anemia ○ Pernicious anemia: B12 deficiency affects DNA synthesis because intrinsic factor is attack, leading to megaloblastic formation (abnormal rbc in bone marrow) and neurological symptoms Factors: autoimmune disease, genetic disorders ○ Folate-deficiency anemia: Folate (B9) deficiency also disrupts DNA synthesis (production of rbc) but lacks neurological effects Factors: poor diet, alcohol use, pregnancy, certain medications  Edema ○ Definition: excess interstitial fluid in the tissues ○ Development: imbalance of any of the factors that control movement of water, disproportionate increase in capillary fluid pressure (capillary hydrostatic pressure - pushes fluid out) or permeability, decreased capillary colloid osmotic pressure (pulls water back in), impaired lymph flow Hypocalcemia ○ Pathogenesis: inhibits PTH (causing parathyroid hormone deficiency) which leads to decreased calcium release, preventing osteoclast function leading to reduce calcium reabsorption by kidneys and lost into abdomen Factors: decreased PTH (injury or removal), hypomagnesemia, alkalosis (enhances binding of calcium to albumin), low vitamin D (stimulate absorption of calcium), calcitonin (prevents osteoclast function), pancreatitis (deposits into abdomen) Hypermagnesemia and Hypomagnesemia ○ What: primarily absorbed in the GI tract, metabolism influenced by renal function ○ Hypomagnesemia: an electrolyte that serves many functions within the body including assisting with cellular function and nerve conduction Factors: poor intake/absorption of GI tract, phytic acid, PPI’s, calcium, phosphates, and fats inhibit absorption, can cause cardiac dysrhythmias, kidney disease with creatinine clearance less than 20 mL/min ○ Hypermagnesemia: influences the cardiovascular system by affecting electrophysiological function and hemodynamic stability, influences neurological functioning by inhibiting the release of acetylcholine, uncommon but fatal Factors: causes cardiac and neurologic dysfunction, levels affected by Na+, Vitamin D, growth hormone, parathormone, and thyroid hormone, primarily seen in renal disorders (acute/chronic) Stress ○ Cellular adaptation: cells adapt to stressors such as size (atrophy/hypertrophy), number (hyperplasia), and form - type of cell, replacement of adult cells (metaplasia). Differentiation gene alters, functional genes remain unaffected. ○ Pathophysiology: allostasis is the processes by which the body responds to stressors in order to regain homeostasis by activation of the Sympathetic Nervous System component of the Autonomic Nervous System, activation of the RAAS system, activation of the Endocrine system Carcinoma ○ Cellular communication in carcinoma is disrupted by genetic mutations that affect signaling pathways and regulatory mechanisms. ○ Autocrine signaling (self-stimulation) and paracrine signaling (communication with surrounding cells) are often altered to support tumor growth and invasion. ○ Key growth factor receptors on the surface of carcinoma cells may be overexpressed or mutated, leading to continuous growth signaling. ○ Signal transduction pathways inside the cells become aberrant, leading to uncontrolled cell division and survival. ○ Carcinomas often involve the escape from growth suppressors (e.g., p53) and resistance to apoptosis, allowing damaged cells to survive and proliferate. Protein deprivation ○ Pathophysiology: Protein deprivation leads to the breakdown of muscle tissue and other organs to release amino acids for vital functions, causing muscle wasting (cachexia) and affecting overall health. Without sufficient protein, the body cannot produce essential enzymes, hormones, antibodies, and structural components, impairing growth, immune function, and tissue repair. The  immune system becomes suppressed, making the body more susceptible to infections and delaying wound healing. Additionally, low protein levels lead to fluid imbalances and edema, especially in the abdomen and lower extremities, due to reduced albumin. Enzyme deficiencies disrupt metabolic functions, and hormonal imbalances, such as impaired thyroid hormone synthesis, result in symptoms like fatigue and weight gain. A negative nitrogen balance further exacerbates muscle wasting, while the lack of protein also contributes to fatigue and weakness. In children, protein deprivation causes growth retardation, developmental delays, and reduced immune function, while severe deprivation can lead to fatty liver. Type III hypersensitivity and Systemic Lupus Erythematosus (SLE) ○ What is SLE: is an autoimmune disease where the body's immune system mistakenly attacks its own cells and tissues. This results in inflammation and damage to various parts of the body, including the skin, joints, kidneys, heart, and lungs. ○ Pathophysiology: Autoimmune Response: in SLE, the body’s immune system starts attacking its own cells. Normally, the immune system defends against infections, but in autoimmune diseases like SLE, the immune system mistakes healthy cells for harmful ones and launches an attack on them. Involves Responses by the Innate and Adaptive Immune Systems: the innate immune system (the body’s first line of defense) and the adaptive immune system (which includes B cells and T cells) both become involved in SLE. ○ Innate immune system: The innate immune system cells (like macrophages) recognize immune complexes and promote inflammation. ○ Adaptive immune system: B cells produce autoantibodies, and T cells increase inflammation and help activate B cells. Chronic Disease Due to Persistent Antigen: SLE is a chronic disease because the immune system keeps producing autoantibodies against the body’s own cells and tissues. This causes persistent inflammation and damage to organs over time. The immune system never "shuts off" its attack, which is why SLE can last for a lifetime. Activation of B Cells, Producing Antibodies: B cells are part of the adaptive immune system. In SLE, B cells produce antibodies that mistakenly attack the body’s own tissues (called autoantibodies). These antibodies then form immune complexes that can cause further tissue damage and inflammation. Activation of T Cells, Promoting Inflammation: T cells play a role in promoting inflammation in SLE. They help activate B cells (which make the autoantibodies) and also release signals that recruit other immune cells to cause further inflammation and tissue damage. Systemic Condition: since SLE can affect many different parts of the body (like skin, joints, kidneys, heart, lungs, and brain), it is considered systemic. Symptoms can vary widely and often come and go in flare-ups, where the disease becomes more active.