Cellular Basis of Disease - Study Guide PDF

Study Guide Questions Week 2 - Cellular Basis of Disease Continued 1) What is an acid? What is a base?  An acid is a compound that can donate an H+ to a solution  A base is a compound that can absorb an H+ to a solution  Bases are...

Study Guide Questions Week 2 - Cellular Basis of Disease Continued 1) What is an acid? What is a base?  An acid is a compound that can donate an H+ to a solution  A base is a compound that can absorb an H+ to a solution  Bases are often the one with the negative charge  But if something were double negative, the base would be the double negative and the single negative is the acid 2) Explain the pH scale.  Measure of the relative acidity or alkalinity of a solution  pH is measuring the concentration of free hydrogen ions in the solution o The lower the number, the higher the acidity o The higher the number, the higher the alkalinity o 0-14, pH 7 = neutral (neither acid or base)  Most of our body fluids sit at pH 7  Normal pH = 7.35-7.45 (very small range)  pH = -log [H+] o Logarithmic scale = powers of 10 o Someone with pH 6 (acidotic) = blood acidity is ten times higher than that of pH 7  The higher [H+], the more acidic solution  The lower [H+], the more basic solution 3) What is a buffer? What are the major buffering systems in the body?  Any compound that can donate or absorb a H+ ion in a solution o Can go back and forth o Goal: prevent change in pH of that solution  Major buffering systems in the body o Proteins (Pr/HPr) – both intracellular and extracellular o Hemoglobin (Hb-/HHb) o Phosphate (HPO4-/H2PO4-)  Used in ATP, ADP   Bicarbonate buffer system (HCO3-/H2CO3) o Most important o Derives from CO2 – byproduct of metabolism, we exhale CO2 but also retain some in our bloodstream for the conversion of this buffer stream to occur o But there’s a limit to how much buffering can be done  If you add more acid than the system can handle, then blood becomes acidic o Is reversible: our body can shift rxn to make it go forward or backward  Controlling how much of reactants and products are available  If we want more carbonic acid = elevate CO2  If we want less carbonic acid = reduce CO2 o Manipulation of products and reactants of this reaction is regulated by two systems  Respiratory system  Increase respiratory rate = blow off CO2 = lower CO2 levels  Decrease respiratory rate = increase CO2 levels  Rapid effect (minutes to hours)  Renal system  Control HCO3- conservation (reabsorption) and H+ secretion (excretion)  Slow effect (hours to days) 4) What are the differences between and causes of respiratory vs. metabolic acidosis/alkalosis?  Respiratory acidosis/alkalosis = respiratory system is the cause of the acidosis/alkalosis o Solution = metabolic compensation o Lungs cannot be part of the compensation (the respiratory system’s messed up, so respiratory compensation will not help)  Metabolic acidosis/alkalosis = any other cause (other than respiratory) is the cause of the acidosis/alkalosis o Solution = Respiratory compensation o Kidneys cannot be part of the compensation  Causes of Respiratory Acidosis o Any respiratory change that causes CO2 levels to be retained   Hypoventilation (breathing too slow) or poor gas exchange (accumulation of CO2 and carbonic acid)  People with pulmonary disease (COPD)  Narrowing of airways – air trapping, hard to get air out of lungs  CO2 accumulates in lungs  They are persistently hypercapnic – too much CO2 in the blood  Causes of Respiratory Alkalosis o Any respiratory change that causes CO2 levels to drop  Hyperventilation – breathing too fast (depletion of CO2 and carbonic acid)  Causes of Metabolic Acidosis o Increased noncarbonic acids: ketoacidosis, uremia, ingestion, etc.  Ketoacidosis = body starts breaking down stored fat at an accelerated rate, byproduct is ketones  produces ketoacids  Occurs in Type I Diabetes (cannot produce own insulin)  Uremia = urine in the blood caused by renal failure  Kidneys stop producing urine  stop filtering out nitrogenous waste including uric acid  acid levels go up  Ingest large quantities of acidic products o Bicarbonate loss: diarrhea, renal failure, proximal tubule acidosis, etc.  Proximal tubule acidosis = proximal tubule of the nephron has a H+ excretion system  If excretion system stops = H+ retention = acidosis  Causes of Metabolic Alkalosis o Excess loss of non-carbonic acids: prolonged vomiting, GI suctioning, hyperaldosteronism, diuretic therapy, etc.  Prolonged vomiting = losing too much HCl = alkalosis  GI suctioning = remove too muc HCl = alkalosis  Hyperaldosteronism = overproduction of hormone aldosterone = promote H+ loss in proximal tubule = alkalosis  Diuretic therapy = diuretics block sodium retention  One of the mechanisms for sodium retention in the kidneys involves H+ secretion  Blocking that sodium retention can lead to too much H+ loss o Or excess bicarbonate intake  Ex. From treating stomach ulcers = consume bicarbonate to neutralize stomach acid = absorb too much = alkalosis 5) What data can be used to determine a patient’s acid/base balance? What are the normal ranges for these data? 6) Work through case study #1 (below) 7) What is the primary difference between aerobic and anaerobic metabolism?  Cells need energy in the form of ATP, attained via cellular metabolism  Anaerobic metabolism = O2 is not involved  Aerobic metabolism = O2 is being consumed o 3 stages: Glycolysis, Krebs Cycle, and Electron Transport Chain and Oxidative phosphorylation  Oxygen primarily needed for the last stage  Cells not getting enough oxygen  cannot form enough ATP  cannot do work  slowly die 8) Explain hypoxic and free radical cellular injury  Reversible cell injury vs irreversible cell injury  Hypoxic injury o Low oxygen content o Ischemia = reduced blood flow to the area o Anoxia = no oxygen delivery due to obstruction  no blood flow to the area  leads to cell/tissue death o Reperfusion injury = blood flow is recovered to an area  Any time there is cell/tissue injury, there will be inflammation  When blood flow RETURNS to an area, inflammatory cells/mediators come along with it o Reversible hypoxic injury  Obstruction/cessation of blood flow  ischemia  less mitochondrial oxygenation  less ATP  more glycolysis  more lactate acid (byproduct of glycolysis)  pH acidotic   nuclear chromatic clumping + increased swelling of lysosomes  (when lysosomes pop) increased release of lysosomal enzymes (hydrolases, digestive enzymes)  cell death via autodigestion  Free radical injury o Free radical = unpaired electron in outermost shell  Dangerous because they will break bonds and steal electrons to satisfy the unpaired electron  cause damage to anything it encounters o Reactive oxygen species  Oxygen-containing compound that have a free radical  Superoxide anion (O2-), peroxide (O2--), hydroxyl radical (·OH), hydroxyl ion (OH-) o Types of free radical injuries  Lipid peroxidation  Damage lipids, including structural lipids of the cell  Disruption of polypeptide chains in proteins  DNA damage o Any organism that engages in aerobic metabolism deals with reactive oxygen species  But cells produce endogenous antioxidants that neutralize these reactive oxygen species before they do any damage o UV light, smoking, air pollution, inflammation, and radiation also deals with reactive oxygen species 9) What intracellular events lead to Hydropic swelling because of hypoxic injury?  Hydropic swelling = water accumulates in the cell o Not enough ATP  Na/K pump can’t operate (intracellular mechanism that controls cell volume)  increased intracellular Na+, increased extracellular K+, intracellular Ca++  water accumulates (water follows salt)  increased acute cell swelling  organelles start swelling  cell death  Hypoxic injury can quickly turn into cell death 10) What are the morphologic cellular changes that can be observed caused by cell stress or injury?  Morphologic changes = functional changes  Atrophy = same number of cells but its intracellular contents and the functional capacity is reduced  Hypertrophy = same number of cells but they’re bigger and increased in functional capacity  Hyperplasia = cell is the same size as normal cell, but increased number of cells o In many tissues, hypertrophy and hyperplasia will happen together  Metaplasia = tissue transforms from one cell type to another (less differentiated cell type), generally adaptive (reversible)  o Metaplasia of tracheal epithelium in a smoker  Pseudostratified columnar epithelial cells line our airway  Cilia important to move mucus and prevent buildup  In smokers, these cells are replaced with simple squamous epithelial cells due to chronic injury to the airway  Flat, not functionally mature but divide rapidly (so they’re able to withstand the smoker’s airway/more hostile environment), and don’t have cilia  Results in smoker’s cough  lack cilia to move mucus  Dysplasia = deranged cells that are growing out of control non-adaptive (pre- cancerous, irreversible) o Wrong cell type, not uniform, rapidly dividing, too many of them 11) What is the difference between hypertrophy and hyperplasia? Under what circumstances do you get one but not the other?  Hyperplasia = increased number of cells  Hypertrophy = increased size of cells  Both caused by same sources of stimulation o Increased functional demand – tissue is being asked to overperform o Increased hormonal stimulation – tissue is being directed to increase its number/size because of hormones o Often happen together  You get hypertrophy but not hyperplasia with cardiac muscle o Cardiac muscle cells do not divide or make new cells o They can get bigger or smaller (trophy) but not hyperplasia 12) What are the visual signs of cellular (coagulative) necrosis?  Necrosis = tissue death  Cytoskeleton starts to breaks down  Lysosomes have exploded  digestive enzymes are causing protein clumping  Cells look amorphous (weird in shape)  plasma membrane bleb  Cell swelling, organelle swelling (endoplasmic reticulum, mitochondria, disaggregated ribosomes)  Cell nuclei shriveled up (pyknosis) or shattered cell nuclei (karyorrhexis), or nucleus is no longer discernible as if it’s not there at all (karyolysis) 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-cancerous 14) Compare and contrast cell necrosis vs. apoptosis  Both are forms of cell death  Cell necrosis = cell death caused by unintentional injury o Cells are swollen and look like they’re exploding  Cell apoptosis = programmed cell death o Every cell has self-destruct gene sequence that dies when triggered, cells produce proteins/enzymes that start chopping up DNA o Cells look like they’re imploding, collapsing into itself  Cell shrinkage chromatic condensation  nuclear collapse  apoptotic body formation (shattered pieces)  lysis of apoptotic bodies o Conditions that may trigger apoptosis  Cell recognizes it’s infected/damage in some way  eliminates itself to prevent cancer/harm to body  Viral infection  DNA damage  Certain kinds of membrane/mitochondrial damage  Cell stress (endoplasmic reticulum)  Induction by immune cells Case Studies Question 1: A 66-year-old male with insulin-dependent diabetes mellitus, tobacco use, and COPD (FEV1 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 Acidotic Na 135 mEq/L PaCO2 52 mm Hg Acidotic K 3.0 mEq/L PaO2 80 mm Hg Cl 102 mEq/L HCO3 13 mEq/L Acidotic CO2 12 mEq/L BUN 44 mg/dL Cr 2.3 mg/dL Mixed cause acidosis, uncompensated 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