病理學 Exam 1 Study Guide PDF

**Study Guide Questions** **Exam \#1** **1) What is "normal" in terms of biological parameters? What are some examples of sources of variation on "normal."** **Sources of variation on "normal"** - Genetics - Age - HR for 3 y/o is tachycardic for an adult - Gender (Sex) - Ho...

**Study Guide Questions** **Exam \#1** **1) What is "normal" in terms of biological parameters? What are some examples of sources of variation on "normal."** **Sources of variation on "normal"** - Genetics - Age - HR for 3 y/o is tachycardic for an adult - Gender (Sex) - Hormone level -- testosterone, \[estrogen, progesterone\] - Testosterone = higher RBC count - Situational - Living at sea level (lower RBC count) vs high altitude (more RBC count) - Time - Hormone levels - Testosterone levels highest in morning - Female hormone levels diff based on ovulation cycle - Laboratory conditions - Every lab has their own reference values based on their tests There is no single value for any biological parameter that is normal. There is a distribution of normal within a population. **2) How has "race" been used in medicine as a source of variation in biological parameters? Why is this problematic?** **Race:** historically used as source of variation in normal values - Problematic because the way race is defined does not tie it to something biological - Race is self-identified with very broad categories (African American, non-Hispanic, Hispanic) - Does not translate to what people think it does - BELIEF: People THINK race = ancestry-related genes → r/t variation in biological parameters & disease - Ancestry-related genes correspond to only 0.1% of genes differences between ppl - Ancestry-related genes represent only minuscule part of genome - REALITY: race ≠ ancestry-related genes - Race = social category - Race is only used as a very poor substitute for ancestry-related genes - Medicine - Repeatedly weaponized throughout history to justify & rationalize enslavement of black people - Still used to obfuscate incidents of racial injustice - Used race as sorting tool w/ profound impacts on diagnostics & treatments of disease - Inaccurate, not true, and perpetuates idea that individuals in different racial categories are biologically different - When in fact, people from different racial categories are biologically the same - Reinforces racial stereotypes - Leads to bad medicine - Implicit bias - Use of harmful standards of care that have gone unexamined - When we find differences in disease incidence and health outcomes, it is a difference in social determinants (from oppression) → it shows disparities and NOT differences in genetics **3) What are the key concepts behind the biology of skin color? (**18 min documentary) Skin color primarily determined by amount & type of Melanin (pigment) produced by Melanocytes in skin **Melanin** - 2 types of melanin - Pheomelanin (reddish) - Eumelanin (black/brown) - Packaged into melanosomes that position themselves above nucleus of skin cells - Function: absorb UV light (esp. damaging UVB-(UV blue light emitted from the sun that has significant effects on living organisms) to prevent DNA damage - Type & amount produced by individuals indigenous to regions (around equator & high altitude) = correlated to amount of UV exposure endemic to that region - Individuals w/ more melanin = absorb less UVB = more prone to vitamin D deficiency **UVB** - Too much UVB = breakdown of folic acid in circulation = inc risk birth defects & poor reproductive success - Too little UVB = vitamin D deficient = can't absorb calcium = brittle bones - Vitamin D supplements can be taken **4) Define and explain: Etiology, Pathogenesis, and Clinical Manifestations** - **Etiology**: cause of a disease - **Pathogenesis:** development of the disease state - How the disease affected body function and how the body reacts to it - Factors of pathogenesis: - Time exposed to injury - Quantity - Location - Morphological changes **Etiology → pathogenesis → clinical manifestations** **5) What are the terms used to describe the clinical manifestations of disease....how are these terms different? Think of an example of each** **Clinical Manifestations**: clinical observations that are a result of the disease - 2 categories - **Signs**: objective; observable, measurable - **Symptoms**: subjective; reported **6) What are the terms used to describe the time course of a disease process? How are those terms different? Think of an example of each?** - Time Course - **Latent period**: time between injury and time you see s/sx - **Prodromal period**: time when you first see s/sx (usually nonspecific, eg fever) - **Acute period**: time when clinical manifestations most severe. s/sx can be more specific (jaundice) **7) What is a differential diagnosis?** Differential diagnosis - Identifies list of possible conditions or diseased that be causing pt's s/sx then narrows down the list via testing analysis and evaluation to most likely or definitive diagnosis - **Clinical methods** - s/sx - **Laboratory methods** - Urinalysis (fecal analysis) - Blood analysis - Blood count - Blood chemistry - Blood culture - Serology - Tissue diagnosis - EKGs - Radiology **8) What is meant by the idea: interdependence of cells and systems? How does this relate to the idea of a "cellular basis of disease?"** - Function of entire organism depends on function of cells - Cells are also dependent on larger systems - Eg: circulatory system brings O2 to cell to function - Cell (smallest living unit) → tissues (epithelial, connective, nervous) → organs → organ systems → organism - Cells are found in ECF maintained by body systems because they don't have direct access to O2 **9) What is Total Body Water? What is it composed of? To what extent does it contribute to body weight?** **Total body water = ICF + ECF=60%** - **Intracellular fluid** (40% body weight) - Inside cells - Indirect maintained via direct maintained of ECF - **Extracellular fluid** (20% body weight) - Environment for cells to fxn - Plasma (intravascular; 5% body weight) - Intravascular =w/in blood vessels - Interstitial fluid (fluid between cells) -- third space (15% body weight) Inc Adipose tissue = dec total body water - (fat contains little water) - In reverse relationship **10) Explain the differences in Total body water in relation to body weight by age and gender. What factor contributes the most to these differences? Why?** - **Inc age** = lose muscle mass & inc fat = dec total body water - **Biological male** = more lean muscle mass, less fat = higher total body water - **Biological female** = less lean muscle mass, more fat = less total body water **11) How is cell volume controlled systemically? How is it controlled at the cellular level?** **Cell volume** - Swelling- volume to high - Shrinking- volume too low - **Both can cause cell death** - Controlled by water & osmolyte balance (sodium & potassium) - Water Balance - Any loss or gain of water - Primary Gains - Water- via consumption alone or w/ food - Metabolic processes - Primary Loses - Urine - Feces - Significant if person has diarrhea - Sweat - Controlled by ADH/thirst system (low blood volume = inc ADH) - Hypothalamus detects blood conc. As osmolarity ↑ ⇔↓BV⇔↑ blood conc. - Depending on if de- or overhydrate a signal will be sent to promote or decrease the sensation of thirst - Dehydration - ADH release from posterior pituitary gland water retention via kidneys restoration of normal water volume hypothalamus shuts off system - Overhydration - Opposite - Osmolytes (sodium & potassium) - Controlled by: - Renin-angiotensin system (**systemically**) - Maintains Na+ and K+ - Liver makes angiotensinogen SNS trigger by BP change, stress event, or Na fluctuation kidneys release renin to convert to A1 lungs and kidneys then release ACE to convert A1 to A2. - **Kidney** ↓ UO ↑ BP - **Posterior Pituitary**- ADH secreted ↑ water retention ↑ BP - **Vascular smooth muscle**- vasoconstriction ↑BP - **Hypothalamus**- stimulates water thirst↑ water intake ↑ BP - **Adrenal cortex**- aldosterone secretes (steroid hormone) ↑ water, ↑Na and ↓K+ ↑ BP - Sodium-potassium ATPase pumps (**intracellularly)** - ↑K inside and ↑Na outside cell - Accounts for 50% of cells energy production **12) What controls the distribution of fluids between ICF and ECF? What controls the distribution of fluids between the Intravascular and Interstitial compartments?** **ICF** **ECF (Plasma/Intravascular + Interstitial)** ---------- ----------------------------------------------- K^+^ Na^+^ Mg^+^ Ca^2+^ Proteins Cl^-^ [HCO~3~]{.math.inline}^-^ Major shift cell death Distribution of fluids between ICF & ECF - Controlled by osmolarity Distribution of fluid between intravascular and interstitial space - Controlled by Starling Forces **13) What is capillary bulk flow and starling forces? Explain how they work.** Capillary bulk flow - Movement of fluid between intravascular and interstitial space - Usually occur between capillaries - Caused by Starling Forces - Passive Forces determined by the sum of the forces between cap and interstitial spaces 1. **Capillary BP** i. Pressure that comes from inside the capillary ii. Pushing Ultrafiltration (out) 2. **Capillary Oncotic (Osmotic) Pressure** iii. Pressure exerted by plasma proteins in blood that can't get out cap. iv. Pulling Reabsorption (In) 3. Interstitial Hydrostatic Pressure v. Pressure that any fluid can exert against any container it is found in vi. PushingReabsorption (In) 4. Interstitial Oncotic (Osmotic) Pressure vii. Only occurs is plasma proteins leak into the interstitial spaces' b/c of break in capillary wall or acute inflammation 1. Usually, zero viii. Pulling Ultrafiltration (Out) **14) Explain the common causes of Edema. Explain third space fluid accumulation.** **Accumulation of fluid in the interstitial spaces** - Decreased plasma oncotic pressure → dec reabsorption - Caused by lost or diminished production of albumin - Increased interstitial oncotic pressure → inc ultrafiltration - Caused by increased capillary permeability or vascular injury → albumin escapes and pulls fluid - Increased capillary blood pressure → ultrafiltration - Caused by hypertension, venous obstruction (blockage or volume overload) - Lymphatic obstruction → impairs clearance of interstitial fluid causing lymphedema - Lymphatic capillaries are neat blood vessels to drain excess interstitial fluid to be redistributed into blood Water follows Albumin albumin has a higher pulling pressure Oncotic = pulling Plasma/Interstitial Oncotic what is doing the pulling force Third space fluid accumulation - Transcellular compartment (body cavities lines w/ serous membranes) - Eg: pericardial sac, peritoneal cavity, pleural cavity - Cause: imbalance in starling forces - Eg: - Ascites - Cause: hypoalbuminemia (liver failure, starvation) - pleural effusion **15) What is isotonicity, hypertonicity, and hypotonicity? Review common causes of each.** **[Conditions affecting ECF]** **Isotonic alterations:** alteration to ECF (fluid conc.) but osmolarity between ICF and ECF is same - Causes - Isotonic volume depletion: hemorrhage, severe wound drainage - Isotonic volume excess: excess IV fluids, hypersecretion of aldosterone **Hypertonic alterations:** osmolarity of ECF elevated due to increased conc of solutes - Causes - Hypernatremia: inadequate water intake, inappropriate administration of hypertonic saline - Water deficit: inadequate water intake, impaired renal conservation of water - Hyperchloremia: accompanies w/ excess of sodium or deficit of bicarbonate, excess ammonium chloride diuretic **Hypotonic alterations**: osmolarity of ECF less than normal due to decrease in solute conc. - Causes - Hyponatremia: diuretics, vomiting, diarrhea, burns, dilutional hyponatremia (inc \[glucose\] or \[cholesterol\] pulls water from interstitial space) - Water excess: decreased urine formation (eg renal failure), SIADH (excessive ADH) - Hypochloremia: accompanies any deficit of sodium or excess of bicarbonate, vomiting (loss of HCL) **16) What factors cause potassium to shift between ICF and ECF? What consequences can that have?** **Potassium Balance** - **Change in ECF/ECF pH** - **Acidosis**: H+ increases & enters cells → potassium swapped out from cell = inc potassium level (**hyperkalemia)** - **Alkalosis:** H+ leaves cell & K+ enters cells = dec potassium levels **(hypokalemia)** - **Insulin** - Inc insulin = K+ moves into cell (to produce glycogen) - Why? Insulin allows glucose to enter cell to form glycogen. K+ is cofactor needed to convert glucose to glycogen - Emergency drug for acute hyperkalemia (+ give glucose) - Dec insulin = K+ stays outside cell - **Catecholamines (dopamine, epinephrine, norepinephrine)** - Bind to B2 adrenergic receptors = K+ moves into cell - E.g.: epi pen shot - Bind to Alpha 2 adrenergic = K+ moves out cell **1) What is an acid? What is a base?** **Acid** - Compound that can donate an H+ to a solution - High concentration of free H^+^ ions **Base** - Compound that can absorb an H+ to a solution - Low concentration of free H^+^ ions **2) Explain the pH scale.** (Acidic) 0 -- 7 -- 14 (Alkaline) pH = - log \[H+\] Measure of relative acidity/alkalinity of a solution r/t \[H+\] in solution 7=neutral body fluids (Blood, CSF, interstitial fluids) **3) What is a buffer? What are the major buffering systems in the body?** **Buffer** - Weak acids and weak bases that can absorb excess H+ or OH-, preventing fluctuations in pH - Primarily regulated by lungs & kidneys - But there are limits to this system **Major buffering systems in body** - Bicarbonate (HCO3^-^ / H2CO3) - **Primary buffer**- most CO2 in the blood is in this form - A black text and red letters Description automatically generated with medium confidence - **Respiratory**-Rapid minutes to hours - RR and depth effects PCO~2~ effects availability of CO~2~ for H~2~CO~3~ production - Tachypnea↑ CO~2~ release↓PCO~2~ ↓H~2~CO~3~↑pH alkalosis - Bradypnea ↓CO~2~ release↑PCO~2~ ↑H~2~CO~3~↓pHacidosis - **Kidneys**- Slow hour to days - Regulates plasma levels HCO~3~^-^ and H^+^ by controlling HCO~3~^-^ reabsorption and H^+^ excretion via the urine - Hemoglobin (Hb^-^ / HHB) - Proteins (Pr^-^ / HPr) (both intracellular & extracellular) - Phosphate (HPO4= / H2PO4^-^) - Form of energy (ATP) **Mass action**- the number of products on hand determine the direction of the reaction **4) What are the differences between and causes of respiratory vs. metabolic acidosis/alkalosis?** **Respiratory acidosis causes:** - Hypoventilation or poor gas exchange (accumulation of CO2 & carbonic acid) - Ex: COPD **Respiratory alkalosis** - Hyperventilation (depletion of CO2 & carbonic acid) **Metabolic acidosis** - Increased non-carbonic acids - Ketoacidosis, uremia, ingestion - Bicarbonate loss - Diarrhea, renal failure, proximal tube acidosis **Metabolic alkalosis** - Excess loss of non-carbonic acids - Prolonged vomiting (loss of HCl), GI suctioning, hyperaldosteronism, diuretics - Excess bicarbonate intake  **5) What data can be used to determine a patient's acid/base balance? What are the normal ranges for these data?** - **ABG- Arterial Blood Gas** - pH: 7.35-7.45 - pCO2: 35-45 - HCO3: 21-28 **6) Work through case study \#1 (below)** **7) What is the primary difference between aerobic and anaerobic metabolism?** - **Aerobic metabolism:** O2 is required - **Anaerobic metabolism:** O2 is not required **Cellular metabolism=** break down of proteins, fats, and carbs into ATP (energy for the cell) via 3 processes - **Glycolysis** - Occurs in the cytosol - **Citric/Krebs Cycle** - Mitochondria - **Oxidative Phosphorylation+ ETC** - Mitochondria - Yields the most ATP - Requires O~2~ to produce ATP ↓O~2~ ↓ATP productioncell death (if occurs long periods)  - Byproducts of ATP formation in mitochondria is ROS (Reactive Oxygen Species) normally neutralized and protect against oxidative damage by antioxidants (apart of cells defense mechanisms) - Theses species can interact will various cellular components if produced in excess can cause oxidative stress (cellular damage) - DNA - Proteins - Lipids - Benefits: - In moderate levels plays roles in: - Cell signaling - Immune responseto help kill pathogens - Regulation of cell growth **\*\*Slide NoteKnow These Forms of Cellular Transport** - **Passive** - Simple diffusion molecules move from high low conc - Osmosis- water molecule diffusion - Facilitated Diffusion- using proteins to help cross membrane - **Active** - Primary- uses ATP - Secondary- doesn't use ATP directly **8) Explain hypoxic and free radical cellular injury** **Hypoxic injury** - Caused by low O2 Glycolysis ramps up → lactic acid byproduct → acidosis - Ischemia- most common - Anoxia - Reperfusion injury blood supply return after a period of ischemia return of flow important but sudden influx of O2 can cause formation f ROS and free radicals which can cause damage to cell membranes proteins and DNA. A screenshot of a cell phone Description automatically generated **Free radical cellular injury** - Damaged causes by free radicals highly ROS unpaired electrons break bonds causing cellular dysfunction or death - Lipid peroxidation- steal electrons from membrane lipids 2. Membrane damage due to alter permeability and damage to enzymes and other protein 3. Protein damage 4. DNA damage - Disruption of polypeptide chains - DNA damage  Increases number of free radicals- A diagram of a substance Description automatically generated with medium confidence **9) What intracellular events lead to Hydropic swelling because of hypoxic injury?** **Hypoxia** - Lack of O~2~ oxidative phosphorylation not able to and ETC not able to operatecannot produce large amount ATP (normally produced) cells are not able to function without an energy source Na+/K+ ATPase pumps stop Sodium accumulates in cellwater followscell swells **10) What are the morphologic cellular changes that can be observed caused by cell stress or injury?** **[Morphologic cellular changes caused by cell stress/injury]** **Know the definition** **Metaplasia:** - Changes from terminal differentiated (mature) cells to less mature cells type changes but stability is maintained - Terminal differentiated cellsmature cellsmost functional and lose ability to divide when replacements are needed - Less mature cells divide faster and don't lose their ability to divide even after loss if function - Lead to pathology/problems - **Cause: chronic injury** - Smokers → no mature ciliated cells → smoker's cough - Common in epithelial cells (skin, GI, GU, respiratory) - Adaptive - Reversible (when injury goes away) **Dysplasia - precancerous** - Changes to diff cell type & divides rapidly (precancerous) tumors - W/ increased cellular division there is an increased risk for mutations - Cause: persistent severe cell injury - Not adaptive - Not reversible **Accumulations (Infiltrations) -- altered cellular storage** - **Water** → Hydropic swelling - Hypoxic injury - **Lipids** - Tay-Sachs Disease - deficiency in gene to digest certain type of lipid → accumulate in brain - Fatty liver disease - Chronic injury from ETOH exposure **11) What is the difference between hypertrophy and hyperplasia? Under what circumstances do you get one but not the other?** **Atrophy** - Decrease size of cells (not number) - **Causes:** - Decreased functional demand - Decreased hormonal stimulation - Examples: - Lack of hormonal stimulation - Protein/Calorie deficiency starvation **Hypertrophy** - Inc size of cells (not number) - **Causes:** - Increased functional demand - Increased hormonal stimulation - Can be performed by cells that don't divide - Eg: cardiac cells **Hyperplasia** - Inc number of cells (not size) - **Causes:** - Increased functional demand - Increased hormonal stimulation - Chronic injury/tissue repair - Often occurs w/ hypertrophy Cardiac muscle does not divide (no hyperplasia), but may get bigger (hypertrophy) **12) What are the visual signs of cellular (coagulative) necrosis?** General tissue death because of cellular necrosis Visuals: - Blebbing of plasma membrane - Cell & organelle swelling - Ribosomes detaches - Nuclear Changes 1. Pyknosis: nucleus shrinks 2. Karyorrhexis: nucleus in many pieces 3. Karyolysis: no nucleus **Types of Necrosis:** - **Liquefactive** - Tissue cells die and liquify - Occurs in tissue that has little to no connective tissue (like the brain) - **Caseous** - Occurs when cells die and there is a network of connective tissue holding it together - Looks like cottage cheese - **Fat** - Intracellular contents die and get released react with fatty deposits and undergo saponification - Soapy deposits of tissue - Cells have unique look - Occurs in tissues rich in fatty deposits (like pancreas or breast tissue) **13) Among the cellular responses to injury we learned in lecture (atrophy, hyperplasia, etc), which one is never adaptive and is considered "pre-neoplastic"?** **Dysplasia** - **"pre-neoplastic" = pre-cancer** **14) Compare and contrast cell necrosis vs. apoptosis.** **Cell necrosis** - Unintentional cell death - Look swollen & exploding **Cell apoptosis** - Cell death - Programmed cell death - **Look:** imploding (collapsing on itself); shrinkage - **Triggered by** - Viral infection - DNA damage - Certain kinds of membrane/mitochondrial damage - Cell stress (endoplasmic reticulum) - Induction by immune cells **Both:** - Versions of cell death Case Studies **Question 1:** A 66-year-old male with insulin-dependent diabetes mellitus, tobacco use, and COPD (FEV~1~ 1.65 L, 50% predicted) presents to the emergency department with a 3-day history of diarrhea, fatigue, and lightheadedness. He recently returned from a cruise and both he and his wife are ill. He reports minimal oral intake over the past 2 to 3 days. His serum glucose is 160 mg/dL, and his urinalysis shows no ketones present. He has a baseline creatinine level of 1.0 mg/dL. He is hypotensive on presentation with a blood pressure of 80/50 mm Hg, heart rate 110 bpm. ---------------------- ---------- --------------------------- ------- ----------- **Laboratory Data:** **ABG** **Basic Metabolic Panel** pH 7.22 Na 135 mEq/L PaCO~2~ 52 mm Hg K 3.0 mEq/L PaO~2~ 80 mm Hg Cl 102 mEq/L HCO~3~ 13 mEq/L CO~2~ 12 mEq/L BUN 44 mg/dL Cr 2.3 mg/dL ---------------------- ---------- --------------------------- ------- ----------- What is/are the primary acid-base disturbance(s) occurring in this case? **A** Metabolic acidosis only **B** Respiratory acidosis only **C** Metabolic acidosis and respiratory acidosis **D** Metabolic alkalosis and respiratory acidosis **1) What is a homeostatic feedback system? What do they do? Describe an example of one. What body systems serve as the "control systems of the body" and therefore control most homeostatic feedback systems?** Homeostatic feedback system - Negative feedback loops - Controls some biological parameter that is important in the body - E.g. body temp - Involves brain (hypothalamus), body receptors (thermoreceptors from skin) - **Control systems of the body: nervous system, endocrine system**  **2) Describe the structure of the Nervous system: Central vs. Peripheral, Afferent vs. Efferent. Etc.** **CNS -- brain & spinal cord** **Peripheral** -- nerves that branch from brain & spinal cord - Afferent nerves (carries sensory info to CNS) - Somatosensory stimuli - Conscious stimuli from body -- touch, heat, pain - Visceral stimuli - Autonomic - BP, blood volume, blood osmolarity, HR - Efferent nerves (carries commands from CNS to body) - Somatic efferent - motor neurons → skeletal muscle (voluntary motor function) - Autonomic nervous system -- involuntary visceral function - Sympathetic Fight-or-flight - Parasympathetic Rest and digest - Control: smooth muscle, cardiac muscle, glands → feedback loop **3) Describe the general structure of a neuronal cell. What is myelination?** Neuronal cell - **Soma: cell body** - Nucleus - Organelles - Protein synthesis originates - **Dendrites & dendritic tree** - Received info from other cells (stimulatory or inhibitory) - **Axon Hillock** - Where AP begins - **Axon** - Fiber that connects soma & cells that the axon contacts - **Myelination** insulation covering (high in lipids) increases conduction speed of AP down axon, prevents loss of signal - Schwann cells (in PNS) - **Nodes of Ranvier**: exposed axon between Schwann cells, where AP occurs by jumping nodes - Oligodendrocytes (in CNS) - Form of glial cell - **Axon Terminal** - Final point that contacts other neuronal cells **4) Compare and contrast the three basic types of neuronal cells: afferent, efferent, & interneuron.** **Efferent neurons** - Command Neurons - Cell body located in CNS - Axon extends into PNS → effector organ/cell **Afferent neurons** - Sensory Neurons - Cell body in PNS, but close to spinal cord (CNS) - Somatosensory afferent neurons don't have dendrites. They have a specialized receptor at organ - Receptor turns signal to AP → PNS → CNS **Interneuron** - Connect & communicates between afferent/efferent neurons - Found in CNS only **5) Define and explain equilibrium potential. In what direction will an ion move when a cell is at that ion's equilibrium potential? Why?** **Equilibrium Potential** - An ion is the electrical potential difference across a cell membrane at which there is no net movement of that specific ion across the membrane. - No net movement concentration and electrochemical gradients are equal and opposite - Chemical driven by the concentration difference of the ion across the membrane - Electrochemical force exert by membrane potential ions move towards the side of the membrane where the opposite charge exists - Inside of cell mostly negatively charged (more amino acids & proteins) - Outside of cell mostly positively charged (sodium) **K+ equilibrium potential = -90 mV** - Greater concentration drives from K+ inside cell → out of cell - Electrical gradient (negative intracellular charge) pulls K+ from outside cell → inside cell **Na+ equilibrium potential = +60** - Greater concentration Na+ outside cell → moves inside cell **6) What factors determine resting membrane potential?** **Resting membrane potential= -86 mV** - Determined by: - **Ions present** (K+, Na+, Cl-, Ca2+) - **Ions' equilibrium potential** - Electrical graduation = concentration gradient - Ions' **permeability** - Most permeable ion pulls cell closer to its equilibrium potential (K+ b/c there's more leak channels for K+) **7) Review the changes in membrane potential that occur during an action potential. What are the underlying events involved?** - **Resting Potential**: K⁺ leak channels maintain the resting potential. - **Depolarization**: Voltage-gated Na⁺ channels open, allowing Na⁺ to rush into the cell. - **Repolarization**: Voltage-gated Na⁺ channels close, and K⁺ channels open, allowing K⁺ to exit the cell. - **Hyperpolarization**: K⁺ channels stay open slightly longer, causing the membrane potential to overshoot. - **Return to Resting**: K⁺ channels close, and the Na⁺/K⁺ pump restores the resting potential. **8) What purpose does the myelin sheath serve?** - Increases conduction speed of AP down axon, prevents loss of signal **9) What is a synapse? What types of synapses exist?** - Contact between presynaptic cell and postsynaptic cell - 2 types: - **Chemical synapse (most)** - Via excitatory or inhibitory neurotransmitters (amino acids, monoamines, catecholamines) - **Electrical synapse** - 2 cells that are electrically coupled via gap junctions (allow ions & small molecules to pass from one cell to the other -- direct electrical spread) - Example: - NMJ: axon terminal between voluntary neuronal cells & skeletal muscle - Neurotransmitter: acetylcholine - Receptor: nicotinic receptors **10) What are the steps involved in synaptic transmission at a chemical synapse?** **Steps of chemical synaptic transmission** 1. Neurotransmitter molecules synthesized & stored in vesicles in presynaptic cell 2. AP reaches presynaptic terminal 3. Voltage gated Ca2+ channels open; Ca2+ enters presynaptic cell terminal 4. Rise in Ca2+ triggers fusion of vesicles w/ presynaptic membrane 5. Neurotransmitters diffuse across synaptic cleft → bind to specific receptors on postsynaptic cell 6. Bound receptors activate postsynaptic cell 7. Neurotransmitter breaks down, taken up by presynaptic terminal, or other cells, or diffuses away from synapse **11) What is the difference between a neurotransmitter and a neuroactive peptide?** **Neurotransmitter** - Chemical messenger released by presynaptic cell that produces either excitation/inhibition of postsynaptic cell **Neuroactive peptides** - Peptides co-released w/ neurotransmitters - Function: Modify response to NT - Usually changes responsiveness of postsynaptic cell to neurotransmitter - Stimulate postsynaptic cell to make more receptors → inc sensitivity/response to neurotransmitter; or vice versa **12) Describe, compare, and contrast the following categories of neurotransmitters: Amino acid, monoamines, and catecholamines.** - **Amino Acids (Building blocks of protein)** - Fast-acting, often influencing ion channels directly. - Localized, rapid effects on excitability or inhibition - Glutamate (aka glutamic acid) -- excitatory; CNS - GABA -- inhibitory, CNS - Glycine -- inhibitory, CNS - **Monoamines (NT derived from single AAs)** - Modulatory effects, influencing mood, alertness, and sleep patterns, and they often act through G-protein coupled receptor - Acetylcholine (modification of choline) - Serotonin (modification of tryptophan) - Histamine (modification of histidine) - **Catecholamines (Derived from AA tyrosine)** - Derived from tyrosine, modulate physiological functions like the stress response and reward. - Slower, more modulatory effects. - Critical for motor control, attention, and autonomic functions - Dopamine - Norepinephrine - Epinephrine - Primarily a hormone **13) What are the predominant excitatory and inhibitory neurotransmitters found in the central nervous system?** - Glutamate (aka glutamic acid) -- excitatory; CNS - GABA -- inhibitory, CNS - Glycine -- inhibitory, CNS **Case Study** Jean was a 54-year-old woman recently hospitalized and diagnosed with congestive heart failure. Upon discharge from the hospital, she was given a prescription for Lasix (furosemide) 20 mg PO daily. After 1 week at home, she had lost 3 pounds of water weight. She was very excited about this weight loss and decided "*If 1 pill is good, 2 pills are better*" and so she began to take 40 mg of furosemide daily. A week later she presents to the emergency room with generalized weakness, leg cramps, constipation, and "strong" heartbeats. 1\. What was the likely cause of Jean's symptoms? 2\. What is the major intercellular cation, and what is its role in the action potential of neurons and muscle cells? 3\. What were the effects of Jean's electrolyte imbalance on the resting membrane potential of her neurons and muscle cells and on the threshold for an action potential? 4\. Relate what was occurring in Jean's cells to her musculoskeletal and gastrointestinal symptoms. 5\. How do cardiac and muscle cells respond differently to alterations in serum potassium levels?