NURS 208 Test 1- Pathology Concepts | graded A

Pathology Concepts Homeostasis • The tendency to maintain balance/stability internally • Self-regulating, give-and-take system • Compensatory mechanisms: strategies that make up for the chan ges and return the body to its normal state • Two feedback systems: - Positive feedback: formation of blood clot while bleeding, child birth - Negative feedback: control of elevated blood sugar by insulin Histology: cause or reason for a disease • May include infectious agents, chemicals, environmental influences, etc. • Idiopathic: unknown • Iatrogenic: unintended effect of a medical treatment - Predisposing: tendencies that enhances risk for developing certain diseases o Age, gender, health, diet/nutritional/activity status, genetics, etc. • Diagnosis: identification of the disease • Disease duration - Acute - Chronic • Clinical Manifestation: evidence of disease - Includes signs and symptoms - Syndrome: comprises a group of signs and symptoms that occur together • Remission: when the clinical manifestation of the disease disappears • Exacerbation: when clinical manifestation increases again • : likelihood of making a full recovery or regaining normal functioning • : death or death rate from a particular disease • : disease state or rate within a population • : new problems that arise because of a disease or condition • : strategies used to cure or manage a disease • : strategies to avoid the development of diseases (e.g., vaccination, lifestyle change, screening) Organelle Function Nucleolus Produces ribosomal RNA Endoplasmic reticulum (ER) SER is involved in the production of phospholipids and has many different functions depending on the cells; RER is the site of the synthesis of lysosomal enzymes and proteins for extracellular use Ribosomes Aid in protein production on the RER and polysomes Secretory Vesicles Store protein hormones or enzymes in the cytoplasm awaiting a signal for release Lysosome Recycling center. Combines with food vacuoles and digests materials engulfed by cells Mitochondria Complete the breakdown of glucose, producing nicotine adenine dinucleotide (NADH) and adenosine triphosphate (ATP). Cilia Propel materials along the surface of certain cells Centrioles Help organize spindle apparatus necessary for cell division Chapter 1: Cellular Function Cells • Basic membrane-bound functional unit of a living organism - In humans, cells form tissues, organs, and organ systems - Also basic unit of diseases • Understanding basic cellular function and dysfunction is essential to understanding pathophysiology Basic components: • Cytoplasm, nucleus, cell membrane • Eukaryotic cell: cells that contain a nucleus and cytoplasm (organelles), and are enclosed by plasma membrane → humans Cytoplasm • AKA protoplasm • Supports all internal cellular structures (organelles) - Organelles “little organs”, perform the work that maintains the cell’s life • Surrounds nucleus • Colorless, viscous liquid that fills the cell • Contains water, nutrients, electrolytes, glycogen, waste products Nucleus • Control center of cell • Regulates cell growth, metabolism, and reproduction • Contains all genetic information (DNA) Cell membrane • AKA plasma membrane • Protects the cell • Semipermeable boundary - Permeable to small hydrophobic molecules and small uncharged polar molecules - Impermeable to larger polar molecules and ions • Phospholipid bilayer (fatty double covering) • Exterior surface (polar head): charged, less fatty (hydrophilic) • Interior surface (nonpolar tail): uncharged, made up of lipids (hydrophobic) • Glycerol backbone: holds the head and tail together • Prefers lipid-soluble (hydrophobic) substances and small uncharged molecules to pass through • Allow small, uncharged polar molecules Cell Function • Selectively permeable membrane • Simple diffusion - Easy movement of solutes (e.g., gas exchange in the lungs) • Osmosis - Movement of a solvent from low solute concentration to high solute concentration - Helps regulate fluid balance in the body - Lysis: cell swell and burst - Crenation: cell shrinkage • Facilitated diffusion - Diffusion + channel or carrier protein - Energy NOT required - E.g., insulin transporting glucose into cell • Active transport - Requires carrier protein molecule and energy (ATP) - Lower concentration to an area of higher concentration, against a concentration gradient - E.g., Na-K pump: in order to move the ions (Na+ and K+) against their gradients, energy is required o Na-K pump moves potassium ions into the cell while simultaneously moving sodium ions out of the cell • Endocytosis - Cell membrane engulfs substances bringing into the cell • Phagocytosis - Cell eating, solid particles • Pinocytosis - Cell shrinkage • Exocytosis - Release of substances from the cell - Hormone secretion from glands Action Potential • Brief, long distance signals within a neuron (does not decay over distance) • Total amplitude of about 100mV (-70mV to +30mV) • Depolarization is followed by repolarization, and a short period of hyperpolarization • An AP or nerve impulses are generated only on axons - Changes permeability of neuron membrane by opening specific voltage-gated channels on axon - No voltage channel, no AP - Initially activated by graded potential current that spread toward axon along dendritic and cell body membranes Generating AP 1) Resting state: all voltage gates Na+ K+ channels are closed • Only leakage channels are open, maintaining resting membrane potential • Voltage gated Na+ channels have two gate and alternate between three different states: closed, opened, inactivated • Voltage gated K+ channels have one gate and two different states: closed or opened 2) Depolarization: voltage gated Na+ channels open • Depolarization is caused by rushed Na+ flowing into cell, producing sharp upward spike of AP • Depolarization reaches critical threshold level between -55 and -50 mV • Becomes self-generating, urged on by positive feedback • Positive feedback cycle: increase Na+ permeability due to increased channel openings leads to greater depolarization, which increases Na+ permeability and so on - Responsible for the rising (depolarizing) phase of AP 3) Repolarization: Na+ channel are inactivated, and voltage gated K+ channels open • As Na+ entry declines, voltage gated K+ channels open and K+ rushes out of cell, following its electrochemical gradient leading to repolarization • Both the abrupt decline of Na+ permeability and the increased permeability of K+ contribute to repolarization 4) Hyperpolarization: Some K+ channels remain open, and some Na+ channels reset • Hyperpolarization caused by K+ continuing to leave cell Threshold and the All-or-None Phenomenon • Not all local depolarization event produce AP, threshold must be reached to “fire” AP • Threshold is the membrane potential at which outward current created by K+ movement is equal to inward current of Na+ movement - Depolarization represents unstable equilibrium • Recall: local depolarization is graded potential and magnitude increase as stimuli becomes more intense • Critical factor is total amount of current that flow through membrane during stimuli - Strong stimuli depolarize membrane to threshold - Weak stimuli must be applied for longer periods to provide crucial current flow - Very weak stimuli do not trigger AP because current flow dissipates before threshold can be reached • All-or-None phenomenon: it either happens completely or not at all - If number of Na+ ions entering cell is too low to achieve threshold, then no AP will occur Propagating AP • In bare plasma membrane, voltage decays - Without voltage-gated channels, voltage decays because current leaks across membrane • In non-myelinated axons, conduction is slow (continuous conduction) - Voltage gated Na+ and K+ channels regenerate the AP at each point along the axon, so voltage does not decay - Conduction is slow because it take time for ions and for gates of channel proteins to move, and this must occur before voltage can be regenerated • In myelinated axons, conduction is fast (salutatory conduction) - Myelin keeps current in axons (voltage doesn’t decay much) - AP generated only in myelin sheath gaps and appear to jump rapidly from gap to gap Refractory Period • Absolute refractory period follows stimulation during which no additional AP can be evoked - Begins with the opening of Na+ channels, and ends when Na+ channel reset to resting state - Ensure separate AP, all or none event - Enforce one-way transmission of AP, propagating AP away from origin • Relative refractory period follows the absolute refractory period; interval when threshold for AP is markedly elevated - Repolarization is occurring - Strong stimuli trigger more frequent Aps by intruding into the relative refractory period Multiple Sclerosis (MS) • Demyelinating autoimmune disease • Result of immune system’s attack on myelin protein and affects mostly young adults • Slowly ceases impulse conduction • Can cause visual disturbances and problems controlling muscles, speech disturbances, and urinary incontinence • High blood levels of vitamin D can reduce risk of developing MS Cell Energy Production • Cell obtains energy from two main sources—the breakdown of glucose (carbohydrate) and the breakdown of triglycerides (fats) • Food enters the gastrointestinal tract, where it is broken down into sugars, amino acids, and fatty acids • These substances then are either converted to larger molecules (e.g., glucose to glycogen, amino acids to proteins, and fatty acids to triglycerides and fats), stored until needed, or metabolized to make ATP Cell Replication and Differentiation • Cells replicate (S phase) and divide or proliferate (M phase) • Mitosis: - Most common form, cell divides into two separate identical daughter cells - Results in same number and kind of chromosomes as the parent cell • Meiosis: - Form of cell division that occurs only in producing sperm and ova (egg) cells - Results in four daughter cells each with half the number of chromosomes of the parent cell • Differentiation - A process by which cells become different and specialized in terms of cell type, function, structure, and cell cycle in order to perform a specific function - Begins in the embryo - E.g., cardiac cells, nerve cells, leukocytes, etc. - Normal cells = “well” differentiated cells Cellular Adaptation • Adaptation - Cells attempt to prevent their own death from environmental changes that can cause damage through adaptation - May modify their size, numbers, and/or types to maintain homeostasis - Modifications may be normal or abnormal, permanent or reversible - Types: o Atrophy ▪ Degeneration of cells ▪ Occurs due to decrease work demands on the cell → cells ↓ or ↑ in size and number → utilize less O2 → organelles ↓ or ↑ in size and number ▪ E.g., disuse of muscle, postmenopausal women ovary shrinkage o Hypertrophy (we like big sized trophies) ▪ Increase in the size of cells ▪ Occurs due to increase work demand ▪ E.g., cardiac and skeletal muscle o Hyperplasia (-plasia = “growth”) ▪ Increase in the number of cells ▪ Often occurs together with hypertrophy ▪ Usually a result of normal stimuli (e.g., menstruation, BPH, skin warts) o Metaplasia ▪ Cell replaced by another cell type ▪ Usually initiated by chronic irritation and inflammation (e.g., smoking) ▪ Does not necessarily lead to cancerous change o Dysplasia ▪ Cell mutation to a different size, shape, and appearance ▪ Abnormal, potentially reversible by removing trigger ▪ Often implicated as precancerous cells Cell Injury • Most diseases start with cell injury • Can be reversible up to a point • In normal states, it is balanced with cell renewal • Causes: - Physical agents: mechanical forces, extreme temperature - Chemical injury: pollution, lead, drugs - Radiation - Biologic agents: viruses, bacteria, parasites - Nutritional imbalances • When cell injury becomes irreversible, results in cell death Cell Death • Process of eliminating unwanted cells, called programmed cell death, usually occurs through the tosis mechanism - Programmed cell death occurs at a specific point in development - Apoptosis specifically occurs because of morphologic changes - Ischemia refers to inadequate blood flow to tissue or an organ. Can lead to necrosis - Necrosis: death of cells or tissues o Coagulative: usually due to interruption in blood flow (e.g., heart, kidneys) o Gangrene: form of coagulative necrosis that represents a combination of impaired blood flow and bacterial invasion ▪ Dry: skin dry, dark brown, or black appearance ▪ Wet: liquid wound ▪ Gas: most serious and fatal, foul-smelling gas released usually in the presence of Clostridium, infection spreads rapidly, gas released produce bubbles - In apoptosis, the cells condense or shrink; necrosis, the cells swell and burst Neoplasm (Tumor) • A new and abnormal cellular growth due to a mutation • Benign: non cancerous • Malignant: cancerous - Usually undifferentiated • Cancer is the disease state associated with rapid, uncontrolled cell growth with loss of differentiation - Second leading cause of death in the US - 78% of all cancer diagnoses are people ≥ 55 years - Overall incidence: men > women • : agents that initiate or promote malignant transformation or substances that can cause cancer (e.g., radiation, asbestos, tobacco, UV light etc.) • Other causes of cancer: oncogenes, age, lifestyle behaviors, nutritional status, hormonal balance, stress response, etc. • Carcinogenesis: process of cancer development - Initiation: exposure of the cell to a substance or event that causes DNA damage or mutation - Promotion: mutated cells’ exposure to factors that promote growth - Progression: tumor invades, metastasizes, and becomes drug resistant • Anaplasia: loss of differentiation that occurs with cancer Diagnosis • Grading system: 1 to 4 scale, in order of clinical severity • TNM staging system evaluates the tumor size, nodal involvement, and metastatic progress • Goal of treatment may be either: - Curative (eradicate the disease) - Palliative (treat symptoms to increase comfort) - Prophylactic (prevent the disease) • Remission refers to a period when the cancer has responded to treatment and is under control • Prognosis refers to the patient’s likelihood for surviving the cancer - Heavily dependent on the cancer’s ability to metastasize Genetic and Congenital Alterations • Genetic defect/diseases - A condition that is caused by an abnormality in genes - Inherited by biological parents - May or may not be recognized at birth • Congenital defect/diseases - Also called birth defects - A condition developed during the prenatal phase of life and present at birth or shortly thereafter - May or may not be genetic o May be from insult to the embryo or fetus which occurred at a very specific time during in utero development Genetics • A gene is a segment of deoxyribonucleic acid (DNA) that serves as a template of protein synthesis • DNA is a long double-stranded chain of nucleotides called chromosomes • Each nucleotide consists of a five-carbon sugar (deoxyribose), a phosphate group, and one of four nitrogen bases (cytosine, thymine, guanine, or adenine) • Chromosomes - Thread-like structure of tightly coiled DNA carries genetic information in the form of genes - 46 total chromosomes • Allosome: one pair of sex chromosome (XX, XY) • Autosomes: 22 paired chromosomes, numbered • Karyotype: a person’s unique set of chromosomes (count, appearance, male?, female?) • Allele: a variant form of a gene (e.g., eye color: blue, brown, green) • Genotype: actual set or specific combination of alleles for a given gene • Phenotype: the physical expression of the genes (e.g., blue eyes) Pattern of Inheritance • Alleles: variant forms of a gene, only two alleles are present in each gene copy (e.g., A, B, O blood type) • Homozygous: when both copy of alleles are identical for the gene (e.g., AA, BB, OO), may be dominant or recessive • Heterozygous: when the two copy of alleles are different for the gene (e.g., AO, BO, or AB) • Dominant: the more powerful allele, more likely to be expressed in the offspring • Recessive: less influential allele, its expression is masked in the presence of a dominant gene, requires two copies of recessive allele to be expressed Chromosomal Disorders • Disorders caused by a missing, extra, or irregular portion of a chromosome • Usually occur when there is an error in cell division in the uterus • Monosomy X - Turners Syndrome - Deletion of part or all of an X chromosome - Affects females o Develop gonadal streaks instead of ovaries; no menstruation - Karyotype: 45X • Trisomy 21 - Down Syndrome - Three extra copies of chromosome 21 - Karyotype: 47XY +21 or 47XX +21 • Polysomy X - Klinefelter’s syndrome - Common abnormality that results from an extra X chromosome, creates XXY sex chromosomes - Affects males - Karyotype: 47XXY or 47XXXY Autosomal Dominant Disorders • Single-gene mutations that are passed from an affected parent to an offspring regardless of sex • Both homozygous and heterozygous allele pairs - In most cases, offspring with the homozygous pair will have a more severe expression of the disorder, as compared to offspring with the heterozygous pair, because the homozygous pair provides a “double dose” of the gene • Disease is dominant • Healthy is recessive • Marfans Syndrome - Inherited disorder that affects CT - Single-gene mutation (FBN1) on chromosome 15 o Mutation causes excess growth - Affects heart, eyes, blood vessels, bones - Tall, thin, with long arms, legs fingers and toes • Neurofibromatosis - Involving neurogenic (nervous system) tumors that arise from Schwann cells and other similar cell - Two types: 1. Type 1 Neurofibromatosis o Mutations in the NFI gene on chromosome 17 o NFI provides instructions for making a protein called neurofibromin that acts to suppress tumor development o Defect: cutaneous lesions that may include raised lumps, café au lait spots (brown pigmented birthmarks), and freckling 2. Type 2 Neurofibromatosis o Mutations in the NF2 gene on chromosome 22 o NF2 provides instructions for making a protein called merlin that acts to suppress tumor development o Defect: effects CN VIII hearing loss Autosomal Recessive Disorders • Single-gene mutation that are passed from an affected parent to an offspring regardless of sex • Occur only in homologous allele pairs; heterozygous pair are carriers only • Disease is recessive • Healthy is dominant • A person needs two copies of the diseased gene to develop the disorder • Disorders occur only in homozygous recessive allele pairs • Cystic fibrosis (CF) - Hereditary disease that affects the lungs and digestive system - The body produces thick and sticky mucus that can clog the lungs and obstruct the pancreas - Can be life-threatening, and people with the condition tend to have a shorter than normal life span • Phenylketonuria (PKU) - Deficiency of phenylalanine hydroxylase leading to toxic levels of phenylalanine in the blood, causing CNS damage - If untreated, PKU leads to severe intellectual disability - All newborns are screened for PKU by testing for high serum phenylalanine levels • Tay-Sachs Disease (TSD) - Mutation in the HEXA gene on chromosome 15 - HEXA is responsible for metabolizing lipids. Accumulation of these lipid can gradually destroy and demyelinate nerve cells - Nerve cell damage leads to progressive mental and motor deterioration, often causing death by 5 years old - Three forms based on symptom onset—infantile (most common), juvenile, and adult (extremely rare) - This genetic disorder is diagnosed by a thorough history and PE as well as deficient serum and amniotic HEXA level - No cure Sex-Linked Disorders • Occurs when genes located on the sex chromosomes cause genetic disorders • Mostly X-linked, may be dominant or recessive • Affected people are mostly males in X-linked disorders • Females are frequently carriers due to having two X chromosomes • Hemophilia - Condition where blood does not clot - Lacking Factor VIII • Fragile X Syndrome - The repeating FMRI gene o Affecting synapses, critical for nerve impulses - Causes intellectual disability Chapter 2: Immunity Stress • Physical, mental, or emotional strain or tension that can negatively affect the body’s homeostasis state • Universal experience • Result of both positive and negative experiences • May contribute directly to the development or exacerbation of disease and negative behaviors (e.g., smoking, drug abuse) Stress Adaptation • The body responds to stressors in attempt to cope and protect • Amygdala responsible for emotions responses  communicates with hypothalamus  release stress hormones epinephrine and dopamine • General adaptation syndrome, which is a cluster of systemic manifestations that represent an attempt to cope with a stressor • Three stages: 1. Alarm - Release of catecholamines and cortisol, also known as the fight-or-flight response 2. Resistance - Body chooses the most effective and advantageous defense - Fight or flight response symptoms disappear - Adapts or alters 3. Exhaustion - Body becomes depleted and damage may appear, as homeostasis can no longer be maintained through compensatory mechanisms - As the body’s defenses are utilized, disease or death result • Local adaptation syndrome: localized version of General adaption syndrome - Body’s attempt to minimize the damage of the stress to a small location - E.g., local inflammatory response • Individual variety exist according to conditioning factors - Genetics, age, gender, health status, nutrition, life experiences, social support, psychosocial factors • Positive coping strategies to deal with the stressor can minimize and eliminate negative stress effects and a good immune system is needed The Immune System • The body’s defense system that protects against disease • Leukocytes are the key blood cells of the immune response • Ability to recognize and respond to a foreign substance is essential - Pathogen: any foreign organisms that can cause diseases - Antigen: a protein on the surface of that can induce an immune response in the body producing specific antibodies, unique to a substance, may come from outside of body, body tissues or cells o MHC: glycoproteins that mark the cell as self, everyone has a unique set ▪ Class I: present endogenous antigens that originate from the cytoplasm (e.g., self-antigens and foreign proteins produced within the cell) ▪ Class II: present exogenous antigens that originate extracellular from foreign bodies such as bacteria, only present on professional antigen-presenting immune cells - Antibody: Y-shaped protein used by the immune system to identify and destroy Immunity • First-line of defense in the immune responses • Non specific • Provides immediate protection against all invaders Innate Defenses • Barriers - Physical: Skin, mucous membranes - Chemical: HCl stomach acid, saliva and tear (lysozymes—dissolve bacterial cell walls) • Inflammatory response - Response by the body to disease and injury - Mass cells release mediators including histamine, bradykinin, prostaglandins, and cytokines (messengers) → phagocytes activated → digest and destroy the invading pathogen - Physical effects: blood vessels dilate allowing increasing blood flow to the area → gaps appear in the cell walls → allows fluid and immune cells to pass out of capillaries → immune presence is strengthened - Redness, swelling, and pain • Pyrogens - Fever-producing molecules - Released by macrophages exposed by bacteria - Create an unpleasant environment for bacterial growth • Interferons - Type of a cytokine released from virus-infected cells - Bind to nearby uninfected cells - The uninfected cells release an enzyme that prevents viral replication - Named for their ability to "interfere" with viral replication • Complement system - Group of blood plasma proteins in the blood stream that enhance the ability to clear pathogens - Comes into effect only when activated by invasion of pathogen - Stimulates the activation of cytokines, stimulate vasodilation - Opsonization: identifying the invading particle to the phagocyte → phagocytosis - Create membrane attack complex (MAC): forms channels which disrupts the cell membrane of target cells, leading to cell lysis (burst) and death • Macrophages (WBC) - Natural killer cells: cytotoxic, react nonspecifically and destroy primarily tumor cells and virus-infected cells, releases granzyme and perforins to induce apoptosis - Dendritic cells: sensor and antigen presenting cells, enhance the uptake of antigens and present it on the MHC II complex to activate T cells Adaptive (acquired) Immunity • Antigen-specific defense mechanism • Has to be created • Created in response to exposure to antigens • Mediated by T and B cells Adaptive Defenses • Cellular immunity - Defense approach that is mediated by T cells, which recognize the presence of the antigen, bind to the antigen, and trigger a response by other immune cells - T cells work to protect the body against viruses and cancer cells, and they are responsible for hypersensitivity and transplant rejection - Two types of T cells: 1. Regulator cells o (Helper T cells) + (Suppressor T cells) o Helper cells activate B cells to produce antibodies o Suppressor cells turn the antibody production off 2. Effector cells (Killer cells) o Killer (cytotoxic) cells destroy cells infected with viruses by releasing lymphocytes that degrade cell walls • Humoral Immunity - B cells mature in bone marrow - B cells differentiate into memory cells or antibody-secreting plasma cells o B cells = plasma cells o Antibody (Ab) = Immunoglobulin (Ig) o These cells eliminate bacteria, neutralize bacterial toxins, prevent viral reinfection, and produce immediate inflammatory response - B cells have receptor sites for a specific antigen and are activated when in contact with the antigen; B cells multiply into antibody-producing cells or memory cells  reaction resulting in acquired immunity Acquired Immunity • Active acquired immunity - Gained by actively engaging with the antigen - Longer process - Getting the varicella infection and does not have it again and the case in which a person receives the varicella vaccine and never has the condition • Passive acquired immunity - Gained by receiving antibodies made outside of the body - Immediate protection - Mother-to-fetus transfer of antibodies Altered Immune Response • Hypersensitivity - Exaggerated immune response to an antigen - Reactions may be immediate or delayed, B cell or T cell involved - Four types (ACID): - Allergens activate T cells, which bind to mast cells, in type I hypersensitivity - The target cell is destroyed by an antibody directed, cell surface antigen in type II hypersensitivity - In type III hypersensitivity, circulating antigen antibody complexes accumulate and are deposited in the tissue - Macrophages perform delayed processing of the antigen in type IV hypersensitivity • Transplant - Four Types 1. Allogeneic transplants are those in which the tissue used is from the same species and is of similar tissue type, but is not identical o Most transplants use allogeneic tissue 2. Syngenic transplants use tissue from the identical twin of the host 3. Autologous transplants use host and donors are the same person o Someone storing up his or her own blood prior to a scheduled surgery 4. Xenogenic transplants use tissue from another species o Use of pig heart valves to replace diseased valves in a human - Types of Rejection 1. Hyperacute tissue rejection o Occurs immediately to 3 days after transplant o Recipient has antibodies against the donor tissue o Triggers a systemic inflammatory reaction o The response is so quick that often the tissue has not had a chance to establish vascularization; as a result, the tissue becomes permanently necrotic 2. Acute tissue rejection o Most common o Occur between 4 days and 3 months following transplant o Cell mediated and result in transplant lyses or necrosis o Patient exhibits manifestations of the inflammatory process including fever, redness, swelling, and tenderness at the graft site and impaired functioning of the transplanted organ 3. Chronic tissue rejection o Occurs 4 months to years after the transplant o Most likely due to an antibody-mediated immune response o Antibodies and complement molecules become deposited in the transplanted tissue vessel walls o Resulting in decreased blood flow and ischemia - Rejection reaction classifications: 1. Host vs Graft rejection  host fighting graft 2. Graft vs Host rejection  graft fighting host ▪ Life threating ▪ Occurs only in bone marrow transplants • Autoimmune - Immune system loses the ability to recognize self and becomes self-destructive - Affect women more often than men - Can affect any tissue or organ in body - Characterized by frequent, progressive periods of exacerbations and remissions - Systemic lupus erythematosus o Chronic autoimmune disorder o Cause is unclear, but it’s thought that B cells are overactivated to produce autoantibodies and autoantigens that combine to form immune complexes which attack the body’s own tissues o Result in inflammation of connective tissues in any body organ o Tx: symptom management, immunosuppressant, anti-inflammatory agents o 11 criteria used for diagnosing (SOAP BRIAN MD) ▪ Serositis (inflammation of the serous membranes that line the lungs [pleura], heart [pericardium], and inner abdomen [peritoneum]) ▪ Oral ulcers ▪ Arthritis ▪ Photosensitivity ▪ Blood disorders (low counts of white or red blood cells, or platelets) ▪ Renal involvement (abnormal amounts of urine protein or clumps of cellular elements, called casts, which are detectable with a urinalysis) ▪ Immunologic phenomena ▪ Antinuclear antibodies ▪ Neurologic disorder (e.g., brain irritation manifested as seizures or psychosis) ▪ Malar rash (“butterfly” rash over the cheeks of the face) ▪ Discoid rash (patchy redness that can cause scarring) • Immunodeficiency - A diminished or absent immune response - Increase susceptibility to infections - Primary cause: reflecting a defect with the immune system o Genetic or congenital - Secondary/acquired cause: reflecting an underlying disease or factor that is sup- pressing the immune system o Infection, drug therapy, stress, malnutrition - Increase risk of opportunistic infections - How do you ↓ risk of infection: o Reverse isolation precautions: hand washing, limiting visitors, and avoiding fresh flowers to limit the person’s exposure to pathogens • HIV/AIDS - Acquired immunodeficiency syndrome - Deadly, sexually transmitted disease caused by human immunodeficiency virus (HIV) - HIV is a retrovirus - Retrovirus single-stranded RNA viruses that uses reverse transcriptase to convert the viral RNA to DNA, replicate through B cell (CD4+) by Attacking and destroying it, uses CD4 to gain entry into B cell - HIV-1 is the most prevalent strain in U.S. - Transmission: ▪ Bodily fluids, Blood products, sharing needles and syringes, needle- stick exposure, during pregnancy, delivery - Category 1 refers to a CD4 cell count ≥ 500 cells/mm - Category 2 of HIV infection progression refers to a CD4 cell count of 200 to 499 cells/mm3 - Category 3 refers to a CD4 cell count < 200 cells/mm3 - Asymptomatic HIV infection is one of the categories in another HIV classification system based on symptom presentation Immune-building Strategies • Acquired Eating a well-balanced diet • Increasing antioxidants and protein intake • Getting adequate sleep • Avoiding caffeine and refined sugar • Reducing stress Chapter 3: Hematopoietic Function Functions • Transport functions - Delivers O2 from lungs and nutrients from digestive tact to entire body - Transport metabolic waste products from cells to elimination sites (lungs CO2, kidneys nitrogenous waste in urine) - Transport hormones from endocrine organs to target organs • Regulation functions - Maintain body temperature, pH, and adequate fluid volume in circulatory system • Protective function - Prevent blood loss by clotting - Prevent infection with leukocytes Blood consists of plasma and formed elements • Blood is specialized CT • Consists of the formed elements: - Plasma o 55% of whole blood o Least dense component - Buffy coat o < 1% of blood o Leukocytes—fight infection ▪ Only true cell that has nuclei o Platelets (thrombocyte)—stop bleeding - Erythrocytes (hematocrit) o 45% of whole blood o Most dense component Plasma vs. Serum • Serum - Liquid that remains after blood has clotted • Plasma - Liquid that remains when clotting is prevented with the addition of anticoagulant Physical characteristics • pH 7.4 [7.35 – 7.45] • Color depends on amount of oxygen - Scarlet red: Oxyhemoglobin (oxyHb) - Deep red: Deoxyhemoglobin (deoxyHb) • Erythrocytes are a major factor for blood viscosity • Blood accounts for about 8% of body weight - Males: 5-6 L - Females: 4-5 L • Arteries carry blood away from heart • Veins carry blood toward heart Composition of Plasma • Water - 90% of plasma volume; dissolving and suspending medium for solutes of blood; absorb heat • Solutes - Electrolytes o Cations Na+, K+, Ca+, Mg2+ o Anions Cl-, HCO3- o Help maintain osmotic pressure and normal blood pH - Plasma proteins o Albumin ▪ Main contributor to osmotic pressure o Globulins ▪ Alpha, beta—transport protein that bind to lipids ▪ Gamma—antibodies o Fibrinogen ▪ Clotting factor • Non-protein nitrogenous substances - By-products of cellular metabolism such as urea, uric acid, creatinine, and ammonium salts • Nutrients (organic) - Material absorbed by digestive tracts and transported throughout body - Glucose, amino acids, fatty acids, glycerol and triglycerides, cholesterol, and vitamins • Respiratory gasses - Oxygen and carbon dioxide • Hormones - Steroid and thyroid hormones carried by plasma membrane Osmosis • Movement of water through a semipermeable membrane from less concentrated to more concentrated solution Blood Smear: Erythrocyte Structure and Function • Anuclear • RBC are confided to bloodstream, and carry out their function in blood • Spectrin a cytoskeletal membrane permitting membrane flexibility and bioncave shape in order to be carried passively through capillaries • Three structural characteristics contributing to gas transport functions 1. Small size and shape provide huge surface area relative to volume 2. Over 97% hemoglobin, the molecule that binds to and transports respiratory gases 3. Efficient oxygen transporters • An erythrocyte’s job is to transport oxygen and carbon dioxide • Hemoglobin binds easily and reversibly with oxygen • Hemoglobin consists of globin (2 alpha and 2 beta polypeptide chains) and four heme groups • Each heme group carries iron - Fe2+ carries O2, Fe3+ does not carry O2 like in liver Production of Erythrocytes • Blood cell formation AKA hematopoiesis, which occurs in red bone marrow • Erythropoiesis is RBC formation - Hormonally controlled - Three phases 1. Production of ribosomes 2. Synthesis of hemoglobin 3. Ejection of nucleus and organelles - Leave bone marrow as reticulocyte - Mature in blood to an erythrocyte Regulation and Requirements for Erythropoisiderinesis • Having too few erythrocytes can lead to tissue hypoxia, and having too many makes the blood viscous • Hormone control helps ensure erythrocytes in blood remains in homeostatic range by rapidly producing new cells and depends on the adequate supply of iron, amino acids, and certain B vitamins • It is not the number of erythrocytes in blood that controls rate of erythropoiesis, but their ability to transport oxygen to meet tissue demand Hormonal control • Erythropoietin (EPO)—a glycoprotein hormone—stimulates the formation of erythrocytes - Kidneys produce EPO • Drop in blood oxygen levels that trigger EPO formation can result from: - Decreased RBC count - Decreased amount of hemoglobin - Decreased availability of oxygen • EPO stimulates red bone marrow • As EPO increases, RBC count increases • Oxygen-carrying ability of blood rises EPO Dietary requirements • Nutrients—amino acids, lipids, carbohydrates are essential for synthesis of all cells • Two B-complex vitamins—b12 and folic acid are necessary for normal DNA synthesis • Iron—essential for hemoglobin synthesis - Free iron ions (Fe2+, Fe3+) are toxic - Iron is stored as ferritin or hemosiderin, and binds to transferrin Erythrocyte Life Cycle 1. Low oxygen levels in blood stimulate kidneys to produce EPO 2. EPO levels rise in blood 3. EPO and necessary raw materials in blood promote EPO in red bone marrow 4. New erythrocytes enter bloodstream; function about 120 days 5. Aged and damaged RBC are engulfed by macrophages of spleen, liver, and bone marrow; the hemoglobin is broken down 6. Raw material are made available in blood for erythrocyte synthesis Hemoglobin Breakdown (through liver) • Heme - Iron o Stored as ferritin or hemosiderin o Bound to transferrin and released from liver as needed for EPO - Bilirubin o Picked up by liver and secreted into intestine in bile where it is metabolized to urobilinogen (yellow urine) or stercobilin (brown feces) • Globin - Amino acids  circulation Erythrocyte disorders • Most are classified as anemia or polycythemia Anemia • Lacking blood—lacking blood oxygen capacity is too low to support normal metabolism • Its is a sign of some disorders rather than a disease itself • Leads to decrease in oxygen delivery to other body tissues • S/sx: fatigue, weakness, pallor, dyspnea, tachycardia • Diagnosis: (hemoglobin concentration/hematocrit) - M: H/H < 13.5 g/dL/41% - F: H/H < 12 g/dL/37% • Causes: - Decrease in erythrocytes: blood loss, decreased production - Destruction of erythrocytes: hemolytic or sickle cell anemia • Three groups: 1. Blood loss 2. Not enough RBC produced 3. Too many RBC destroyed Blood loss Anemia Hemorrhagic anemia • Acute blood loss is rapid - Stab wound • Chronic hemorrhagic anemia is slight but persistent blood loss - Due to hemorrhoid or undiagnosed ulcer, etc Not enough RBC produced • Several causes for decrease erythrocyte production such as iron deficiency or complete failure of red bone marrow Iron deficiency • Erythrocytes produced under these conditions are microcytes • Microcytes are small and pale because they cannot synthesize their normal complement of hemoglobin • Treatment: increase Fe intake through diet or supplements Pernicious anemia • Autoimmune disease mostly affecting elderly • Low gastric intrinsic factor (IF) • IF must be present for B12 to be absorbed in intestinal cells • Without Vitamin B12, developing erythrocytes grow but do not divide leading to the development of macrocytes • Low Vitamin B12 in diet can lead to anemia—common in vegetarians since meats, poultry and fish provide ample vitamin B12 Renal anemia • Caused by lack of EPO, the hormone that control RBC production • Treated with EPO injection Aplastic anemia • Red bone marrow suppression by certain drugs or chemicals, ionizing radiation or viruses Too many RBC destroyed Hemolytic anemia • Erythrocytes rupture prematurely • Hemoglobin abnormalities, transfusion of mismatched blood, and certain bacterial and parasitic infections are possible causes • Abnormal hemoglobin usually genetic • Two examples 1. Thalassemias 2. Sickle cell anemia Thalassemias • Mediterranean ancestry • One globin chain is absent or faulty, and erythrocytes are thin, delicate, and deficient in hemoglobin • Monthly blood transfusions required Sickle Cell Anemia • Point mutation • Form sickle “C” shape • Homozygous dominant (HbA, HbA) - Normal hemoglobin • Homozygous recessive (HbS, HbS) - Abnormal hemoglobin - Sickle cell anemia • Heterozygous (HbA, HbS) - Normal and abnormal hemoglobin - Sickle cell trait - Normal hemoglobin more abundant • Fetal Hb (HbF) - Does not sickle - High affinity for O2 • Glycosylated Hb (HbA) - Plasma glucose level blood bests for diabetics Polycythemia • Abnormal excess of erythrocytes increase blood viscosity causing it to flow sluggishly • Primary (congenital) - P.vera is bone marrow cancer - Characterized by dizziness and exceptionally high RBC count o Hematocrit may be as high as 80% and blood volume may double causing vascular system to be engorged with blood and severely impairing circulation • Secondary (induced) - Result when less oxygen is available or EPO production increases - Acute o Blood doping ▪ Stimulating production of RBC ▪ Used to treat patients with anemia ▪ Healthy athletes who inject EPO increase stamina due to increase oxygen-carrying capacity due to a higher hematocrit ▪ High hematocrit and high blood viscosity can cause clotting, stroke or heart failure - Chronic o Hypoventilation/respiratory disease o High altitude living Blood Testing Hematocrit (Hct) % • % of RBC • People with a high blood volume of plasma may be anemic if their blood count is normal because the blood cells have become diluted • Like hemoglobin, (reduce in HCT indicate Anemia) a normal hematocrit % depends on age and gender • General results - Male: 40.7-50.3% - Female: 36.1-44.3% • Interpretation: - Low HCT cause of anemia - High HCT cause of Polycythemia • Calculation: - HCT = Length of RBC column / total length of blood column Pulse Oximetry • Measure % saturation of Hb (SpO2) Blood typing • Prevents transfusion reactions • Antigen (Ag) - Antibody generator - Agglutination - Receptor on the RBC • Antibody - Agglutinin o Immune system protein binding to receptor • If blood cell clumps (Agglutination), the antibody has bound to the appropriate antigen on cells • Your blood type matches whatever antibody caused agglutination • E.g. if your blood agglutinates in anti-B, you have the antigen and are Type B • Blood types are indicated by both the ABO and Rh antigens present Leukocytes structure and function • WBC are complete cells with nuclei and usual organelles • <1% of blood volume • Crucial to our defense against disease • Diapedesis is the ability for WBC to slip out of capillary vessels • WBC through tissue spaces by amoeboid motion—form cytoplasmic extensions that move them along • By following chemical trail of molecules released by damage cells or other or other WBC, aka positive chemotaxis, they pinpoint areas of tissue damage and infection and fight • Leukocytosis, WBC count over 11,000cells/ul when in action to fight off infection • Two categories 1. Granulocytes 2. Agranulocytes • Leukocytes from most abundant to least abundant • Never Let Monkey Eat Bananas (neutrophils, lymphocytes, monocytes, eosinophils, basophils) Granulocytes (“B.E.N.2”) • Neutrophil - Phagocytize bacteria, release cytokines - Neutropenia o Lifespans about 6 hours o Low absolute neutrophil count < 1500, decreasing ability to fight infection o Causes: increase usage, drug suppression,, radiation, bone marrow cancers • Eosinophil - Kill parasitic worms; complex roll in asthma and allergy • Basophil - Release histamine and other mediators of inflammation; contain heparin, an anticoagulant Agranulocytes • Lymphocyte - Mount immune response by direct cell attack or via antibodies o T lymphocytes ▪ Function in the immune response by acting directly against virus-infected cells and tumor cells o B lymphocytes ▪ Give rise to plasma cells, which produce antibodies (immunoglobulin) that are released to the blood • Monocyte - Phagocytosis; develop into macrophages in the tissue - Crucial in the bodies defense against viruses, certain intracellular bacterial parasites, and chronic infections such as tuberculosis Mononucleosis • AKA “mono” or “kissing disease” • Most commonly caused by Epstein-Barr virus (EBV) → targets and infects B cells → produce heterophile antibodies • Most frequent in adolescents and young adults • Transmission: person-to-person contact • Incubation: 4-6 weeks • S/sx: fatigue, sore throat, fever, enlarged spleen, enlarged lymph nodes • Diagnosis: (+) heterophile antibody test (monospot test) - B cell morphed to look like monocyte • Lab: ↑ lymphocytes • Self-limiting Leukemia • A group of malignant disorders affecting the blood and blood-forming tissues (bone marrow, lymph system, and spleen) • Proliferation of dysfunctional WBC because of loss of cell division regulation • Adults > children • Etiology: - No single cause - Genetics: oncogenes o HPV can trigger oncogene causing cancer—oncogene usually suppressed unless triggered - Environment: chemical agents, radiation, viruses, immunodeficiency • When the cell becomes a leukemia cell, it no longer matures normally • Unregulated proliferation of immature leukocytes in the bone marrow • Infiltrates splenomegaly, hepatomegaly, lymphadenopathy, bone pain, meningeal irritation Lymphoma • Malignancy of the lymphatic system (lymphocytes) that usually starts in the lymph nodes, but may involve other lymphatic organs • More common than leukemia • Broadly classified into two categories: - Hodgkin - Non-Hodgkin Hodgkin Lymphoma • Less common • Men x2 > Women • Most frequent in 15-30 and above 50 years of age • Originates in a single location (80% cervical lymph nodes) - Most often starts in the upper body lymph nodes • Proliferation of abnormal giant, multinucleated cells, Reed-Sternberg cells—B cells • Etiology: exact cause unknown - Epstein-Barr virus, genetics, exposure to occupational toxins • Signs and symptoms: - Enlargement of lymph nodes: cervical, axillary, inguinal, mediastinal - Painless and hard nodes - Fever, night sweats, unintentional weight loss (B symptoms), fatigue, weakness - Cough, dyspnea, dysphagia (mediastinal) - Hepatomegaly, splenomegaly (advanced) • Diagnosis: lymph node biopsy Non-Hodgkin Lymphoma • Non Reed-Sternberg cells • Includes malignancy of B, T, and NK cell origin but not Reed-Sternberg cell - Many different subtypes • Etiology: exact cause unknown - Viruses, bacteria, genetics, environmental, immunodeficiency states • May originate from outside of the lymph nodes • Signs and symptoms: various - Painless lymph node enlargement - Fever, night sweats, unintentional weight loss, fatigue, weakness - Hepatomegaly, neurologic sx (CNS involvement), GI complaints, airway obstruction • Diagnosis: excisional lymph node biopsy, BM examination, peripheral blood analysis, CT, PET, LP (CNS), endoscopy (GI) • More difficult to treat than Hodgkin Multiple Myelloma • Cancer of plasma cells • Effects older adults, Male > female • Characterized by excessive numbers of abnormal plasma cells in bone marrow crowding blood-forming cells and causing Bence Jones proteins to be excreted in urine - Bence Jones protein = immunoglobulin light chains • Multiple bone tumors develop and bone destruction occurs leading to hypercalcemia and then renal impairment and neuromuscular issues Production and lifespan of Lymphocytes • Leukopoiesis—production of WBC stimulated by chemical messengers, which will act as paracrines or hormones • Two chemical messenger factors 1. Interleukins 2. Conoly-stimulating factors (CSF) Leukocyte Differentiation • Hematopoietic stem cell give rise to formed elements of blood (hemocytoblasts) • Early branching 1. Myeloid stem cell give rise to formed elements Myeloblast  promyelocyte  myelocyte  band cells  granular leukoctyed (eosinophils, basophils, and neutrophils) Monoblast  promonocyte agranular leukoctye (Monocyte)  macrophages (tissues) 2. Lymphoid stem cell give rise to lymphocytes B lymphocyte precursor  B lymphocytes  plasma cells T lymphocyte precursor  T lymphocytes  effector T cells Platelets (megakaryocytes) • Fragment s that help stop bleeding (blood clotting) • Anucleate • Causing platelets to age quickly • Thrombopoietin protein regulates the formation of platelets - Liver Hemostasis • Prevents blood loss “plugs the hole formation” • Response is fast, localized, and carefully controlled • Three steps: 1. Vascular spasm 2. Platelet plug formation 3. Coagulation Vascular Spasm • Smooth muscle contracts, causing vasoconstriction • Trigger factors - Injury to vascular smooth muscle - Chemicals released by damaged endothelial cells and activated platelets - Reflexes initiated by local pain receptors • Efficiency increases as damage increases • More effective in smaller blood vessels • Spasm response is valuable because a strongly constricted artery can significantly reduce blood loss, allowing time for the next two steps to occur Platelet Plug Formation • Intact endothelium cells release nitric oxide and prostacyclin prevent platelet aggregation in undamaged tissue and restrict aggregation to site of injury • Injury to endothelium lining the vessel exposes underlying collagen fibers; platelets adhere • Von Willebrand factor stabilizes bound platelets by forming a bridge between collagen and platelets - Platelets become activated: swell, form spike process, and stick - Release chemical messengers o ADP—aggregating agent causing more platelets to stick and release content o Serotonin and thromboxane A2—enhance vascular spasm and platelet aggregation • Platelets aggregate forming plug Coagulation (blood clotting) • Reinforce platelet plug with fibrin protein that traps RBC and platelets, forming clot • Most clotting factors (procoagulants) are plasma proteins synthesize by liver • Three phases: 1. Two pathways to prothrombin activator o Intrinsic pathway - Clotting factors found within blood - Triggered by (-) charged faces such as platelets, collagen, or glass - Slower because it has many intermediate steps o Extrinsic pathway - Tissue factor required is found outside of blood - Triggered by exposing blood to tissue factor (factor III) - Faster because it bypasses several steps of intrinsic pathway o Phase 1 ends with formation of prothrombin activator 2. Common pathway to thrombin o Prothrombin activator catalyzes conversion of plasma protein prothrombin into active enzyme thrombin 3. Common pathway to fibrin mesh o In the presence of calcium thrombin activates factor XIII (fibrin stabilizing factor) the fibrin mesh o Fibrin mesh traps blood cells and seals hole for repair o Cross linking strengthens and stabilizes clot, sealing hole until blood vessel is permanently repaired Post Clot Events • Clot retraction - As platelets contract, fibrin strands squeeze serum from mass compacting clot and drawing ruptured edges of blood vessel closer together • Healing - Platelet-derived growth factor (PDGF) released by platelets stimulate smooth muscle cells and fibroblasts to divide and rebuild vessel wall - As fibroblasts form endothelial cell patch over injured area to restore endothelial lining stimulated by endothelial growth factor (VEGF) • Fibrinolysis - Cleanup unneeded clots when healing has occurred - Without fibrinolysis, blood vessels would eventually become completely blocked - Plasminogen produces plasmin “clot buster” - The presence of a clot in and around blood vessel causes endothelial cells to secrete tissue plasminogen activator (tPA) - Activated factor XII [Hageman factor] and thrombin released during clotting also activate plasminogen Thromboembolic Disorders • Thrombus - Clot that develops and persists in an unbroken blood vessel • Embolism - A thrombus that breaks away from vessel wall and floats freely in bloodstream is a called an embolus - Embolism—obstruction of blood vessel - Pulmonary embolism can dangerously impair body’s ability to obtain oxygen - Cerebral embolism can cause stroke Anticoagulants • Aspirin - Prevents platelet plug formation by inhibiting thromboxane A2 (TxA2) - Taking low dose aspirin over several years can reduce incidence of heart attack • Heparin - Antithrombin, secreted by basophil granules or given by injection - Like most clotting factors, heparin inhibits the intrinsic pathway - Most used in hospitals (for patients undergoing procedures and to prevent or treat venous thrombosis) • Warfarin - Oral administration; inhibits Vitamin K- dependent clotting enzymes - Outpatient treatment to reduce risk of stroke Dissembled Intravascular Coagulation (DIC) • Widespread clotting and severe bleeding - Clotting occurs in intact blood vessels and residual blood becomes unable to clot - Blockage of blood flow accompanied by severe bleeding follow • Occurs during complications in pregnancy or a result of septicemia or incompatible blood transfections • Can be fetal Hemophilia A • Inherited bleeding disorder in which the ability of the blood to clot is severely reduced • Caused by lack in coagulation factor VIII (antihemophilic factor) • X-linked recessive bleeding disorder, so most affected people are males • Also called “classic hemophilia” • Main clinical manifestation: bleeding • Treatment: replacement of factor VIII concentrates (IV) • Bleeding precautions: electric razor, soft-bristle toothbrush, fall and injury prevention, avoid invasive procedures (e.g., IM injection, rectal temperature) Idiopathic Thrombocytopenic Purpura (ITP) • Originally termed idiopathic thrombocytopenic purpura • An autoimmune disease that causes abnormal destruction of circulating platelets • Antiplatelet antibodies develop in the blood and bind to platelets → recognized as foreign object and destroyed by macrophages in the spleen • Platelet count in the bone marrow is usually normal • Survival of platelets is shortened (nl: 8-10 days) • Clinical manifestations: asymptomatic in many cases • Most common: bleeding (usually mucosal or cutaneous) - Mucosal: epistaxis, heavy menses, gingival bleeding, large bullous hemorrhage (wet purpura) - Cutaneous: petechiae, purpura (dry), superficial ecchymosis (bruising) - Heavy bleeding internally or externally may be fatal (e.g., brain) - Prolonged bleeding after venipuncture or IM injection • Platelet level <150 • Treatment: corticosteroid—prednisone - If asymptomatic, therapy may not be used unless < 10,000 platelets/µL Chapter 6: Fluid, Electrolyte and Acid-Base Homeostasis Body Fluid • Body fluid: all liquids inside the human body (~60 % of body wt in adults) - BF = water (solvent) + solute (blood cells, electrolytes, nutrients, etc.) • Two body fluid compartments 1. Extracellular: Fluid found outside cells o Interstitial (between cells) o Intravascular (inside blood vessels) o Transcellular (fluid in the peritoneal, pleural, and pericardial cavities, cerebrospinal fluid, fluid in the joint spaces, lymph system, eyes, and gastrointestinal tract) 2. Intracellular: fluid found inside cells Fluid Movement • Fluid constantly moves among compartments to maintain homeostasis • Water moves passively across cell membrane • Movement of water depends on hydrostatic and osmotic pressures in the capillaries • Hydrostatic pressure (push): the pressure created by the weight of fluid against the wall that contains it • Osmotic pressure (pull): - Pressure required to stop osmosis across the semipermeable membrane - Pressure that must be applied to prevent osmosis from actually taking place - Water gets pulled in to the higher solute concentrated or higher osmotic pressure solution - Pressure of solutes in the water • Osmolality - The concentration of fluid that affects the movement of water between fluid compartments by osmosis - Measures the solute concentration per kilogram in blood (mOsm/kg) - Serum osmolality: primarily reflects the concentration of Na (nl: 275 to 295 mOsm/kg) • Tonicity - Osmotic pressure of two solutions separated by a semipermeable membrane - Ability of an extracellular solution to make water move into or out of a cell by osmosis - Affected by solutes that cannot cross the membrane → water shift occurs - Intravenous (IV) solutions are described in relation to tonicity o Intracellular vs plasma (intravascular) solute concentration o Three classifications of tonicity 1. Hypotonic ▪ E.g. 0.45% saline ▪ Lower [solute] to those in intravascular compartment 2. Isotonic ▪ E.g. 0.9% saline and lactated Ringer’s solution ▪ [solutes] equal to intravascular compartment 3. Hypertonic ▪ E.g. 5% dextrose in 0.9% saline, 3% saline ▪ Higher [solute] to those in intravascular compartment ▪ Cause fluid to shift from intracellular compartment to intravascular space • Example: cerebral edema → tonicity of the IV fluid? - Hypertonic—out of intracellular to extracellular • Decreased fluid volume or increase osmolarity (solute concentration) triggers thirst mechanism in hypothalamus • Antidiuretic hormone (ADH) regulates fluid volume by controlling water losses in the urine - Released from the pituitary gland in times of decreased fluid volume and increased osmolarity, ADH promotes reabsorption of water into the blood from the renal tubules • The hormone known as aldosterone is released to conserve more water when necessary (e.g., when a person has low blood pressure) by increasing reabsorption of sodium and water in the renal tubules • Atrial natriuretic peptide released when the atria of the myocardium becomes overstretched, indicating increased fluid volume - This peptide stimulates renal vasodilation, increasing urinary output - Suppresses aldosterone secretion, further increasing urinary output Fluid Excess • Fluid excess in the transcellular space = third spacing (e.g., ascites, pleural effusion) • Fluid excess in the interstitial space = edema - Occurs when hydrostatic > osmotic pressure in the IV compartment - Localized or generalized (anasarca) • Fluid excess in the intravascular space = hypervolemia or fluid volume excess • Fluid excess in the intracellular space = water intoxication - May lead to cell rupture (lysis) • Causes: - Excessive water and sodium intake - Inadequate water and sodium elimination (e.g., renal failure, heart failure, SIADH, Cushing’s syndrome) • Signs and symptoms: acute weight gain, peripheral edema, ascites, cerebral edema, distended jugular veins, SOB, ↑ RR, crackles, bounding pulse, increase BP • Lab findings: decrease serum osmolality • Management: depends on the cause - Restrict sodium and water intake - Administer diuretics - Maintain patient in Fowler’s position (patient seated with HOB elevated to 45- 60°) - E.g., Edema: hypertonic solutions to shift water out to the intravascular space Fluid Deficit • Dehydration • Fluid deficit in the intravascular space = hypovolemia or fluid volume deficit • Fluid deficit in the intracellular space = cell shrinkage • Causes: - Inadequate fluid intake - Fluid and sodium loss from vomiting, diarrhea, GI suctioning, sweating, hemorrhage, diabetes insipidus (DI, lack of ADH), excess use of diuretics, burns - Third-space fluid shift (hypovolemia, e.g., ascites, effusion) • Signs and symptoms: acute weight loss, thirst, ↓ skin turgor, dry oral mucous membrane, oliguria, concentrated urine (except in DI), decrease BP, increase HR, weak pulse • Lab findings: increase serum osmolality • Management: depends on the cause • Fluid replacement: oral, IV - Isotonic or hypotonic Electrolytes • Electrolytes: active chemicals in the body fluid, electrically-charged ions • Cations: positively charged • Anions: negatively charged • Concentration in body fluids is expressed in (mEq/L) - Electrolyte concentrations differ in fluid compartments - ICF: main cation (K+) main anion (PO 3-) - ECF (plasma): main cation (Na+) main anion (Cl-) - Sodium (Na) prefers to stay in the ECF and potassium (K) prefers stays in the ICF • Blood test examines only compartment electrolytes Sodium • Primary cation in ECF (plasma)—135-145 mEq/L • Regulated by kidneys and aldosterone produced by adrenal glands - High serum osmolality or low blood volume, aldosterone is released and kidney retain sodium - Low serum osmolality and fluid volume increases, kidneys release sodium • SNS help kidneys regulate sodium - Increasing the glomerular filtration rate increases sodium excretion - Decreasing the glomerular filtration rate decreases sodium excretion • Renin–angiotensin–aldosterone mechanism also manipulates sodium in the kidneys - Triggered in times of decreased renal perfusion (hypovolemia and hypotension) - Renin  angiotenisinogen to angiotensin I  angiotensin II kidneys release Na • Functions: - Controls fluid volume and serum osmolality - Facilitates muscle and nerve impulses through Na-K pump • Primarily obtained through dietary intake (e.g., table salt) - Recommended daily allowance: 2-4 grams — <2300mg = 1tsp • Sodium loss mostly occurs during urination and sweating Hypernatremia • Result from high serum Na levels (>145 mEq/L) • Causes: - Deficient water or water loss: ↓ water intake, vomiting, diarrhea, DI, heat stroke - Excess sodium: ↑ intake, hypertonic IV solutions, corticosteroid use, Cushing’s syndrome • Signs and symptoms: depends on the cause and severity - Manifestations are primarily the result of water shifting out of ICF into ECF - Change in mental status (brain cell dehydration: agitation, restlessness, confusion, lethargy, seizures, coma), intense thirst, BP changes • Lab findings: ↑ serum Na, ↑ serum osmolality • Management: treat underlying cause - Offer and encourage water, restrict sodium intake, isotonic (mild) - Severe: Administer IV hypotonic solution - avoid correcting too rapidly→ may lead to cerebral edema - Assess level of consciousness - Monitor Na level Hyponatremia • Serum sodium level < 135 mEq/L • Causes: - Deficient/loss of sodium: dietary sodium restriction, excess sweating, GI loss, diuretic use, adrenal insufficiency (Addison’s disease) o Addison’s disease - Water retention: ↑ water intake, SIADH, renal failure, heart failure • Signs and symptoms: depends on the cause and severity - Manifestations are primarily due to cellular swelling, first appears in the CNS (cerebral edema, headache, confusion, irritability, vomiting, seizures, difficulty concentration, coma), muscle weakness • Lab findings: ↓ serum Na, decrease serum osmolality • Management: treat underlying cause - If loss of sodium: replacement (oral, NGT) - If water excess: fluid restriction - If cerebral edema, administer hyoertonic solution – administer slowly to prevent overcorrection - Assess level of consciousness - Monitor Na level Potassium • Primary ICF cation (3.5-5mEq/L) • Functions: - Regulates electrical conduction in the heart and neuromuscular function o Serum potassium should not fluctuate – may cause serious heart issues - Plays a role in acid-base balance • There is an inverse relationship between Na and potassium reabsorption in the Kidneys • Primarily obtained through dietary intake (e.g., bananas, oranges, raisins, green leafy vegetables) - Recommended daily allowance: 40-60 mEq (One medium size banana ~12 mEq) Hyperkalemia • Serum potassium level > 5 mEq/L • Causes: - Deficient excretion: kidney disease, potassium-sparing diuretics, hypoaldosteronism (Addison’s disease) - Excess intake (e.g., salt substitute) - Increased release from cells: acidosis (diabetic ketoacidosis), tissue damage (burn, MI) • Signs and symptoms: depends on the cause and severity - ↑ K concentration outside the cell changes normal ECF : ICF ratio → ↑ cell excitability and changes in impulse transmission to the nerves and muscles (↑ depolarization) - ECG changes (cardiac dysrhythmias), increased bowel motility (diarrhea), vomiting, irritability • Management: treat underlying cause - Monitor ECG, K level - Restrict dietary potassium - Administer: sodium polystyrene sulfonate (Kayexalate) orally or enema o K exits—increase excretion  diarrhea - IV sodium bicarbonate (if acidosis), IV calcium gluconate (antagonizes action of hyperkalemia on the heart), regular insulin and hypertonic dextrose IV, dialysis Hypokalemia • Serum potassium level < 3.5 mEq/L • Causes: - Excessive loss: potassium-losing diuretics, GI loss (NGT suction, vomiting, diarrhea), Cushing’s syndrome - Deficient intake - Increased shift into the cell: alkalosis • Signs and symptoms: depends on the cause and severity - Alters resting membrane potential→ ↑ negative charge within the cell and delays the depolarization and repolarization → impaired nerve signals & muscle contraction - ECG changes (shallow T wave, prominent U wave), hyporeflexia, muscle weakness, paresthesia (numbness or tingling), loss of muscle tone (respiratory arrest), decreased bowel motility (constipation) or i