OSUCOM Week 2
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What is PaO2?
Partial pressure of O2 in the blood. Normal is 80-100 mmHG.
What is FiO2?
Fraction of inspired air. Room air is 21% O2
What is SaO2?
Arterial O2 saturation. Normal is 95%-100%.
What is SpO2?
Oxygen saturation level (taken by pulse oximetry)
What is Low flow oxygen?
1-6 LPM (liters per minute) (used for 25%-45% FiO2). Rates above 4 LPM will require humidification to prevent drying out membranes. Oxygen masks require at least 5 LPM to prevent CO2 build up
What is High flow oxygen?
Up to 15 LPM (used for 57%-81% FiO2)
What are the risks of giving someone more oxygen than they need?
- Oxygen toxicity can damage the alveoli, eyes, and nervous system.
- Atelectasis (when oxygen replaces the nitrogen in the lungs) can cause the alveoli to collapse.
- O2 induced hypoxia occurs when the lack of CO2 removes the breathing stimulus. Occurs chiefly in COPD (chronic Obstructive Pulmonary Disease) patients
What effect will high levels of Methemoglobin have on a pulse oximetry reading?
Methemoglobin will result in a SpO2 reading of 85% regardless of the actual SpO2
What are the SpO2 estimated conversions to PaO2?
- 90% -> 60 mmHG (mild hypoxemia)
- 80% -> 50 mmHG (moderate hypoxemia)
- 70% -> 40 mmHG (severe hypoxemia)
- Just subtract 30 from the Sp02 values.
Describe the variables of Fick’s Law of Simple Diffusion and their impact on diffusion across a plasma membrane and their clinical relevance
- Fnet = KpA(ΔCs)/Δx.
- Fnet = net diffusion,
- Kp = membrane diffusion coefficient,
- A = area (cm2),
- ΔCs = solute concentration gradient,
- Δx = distance or thickness of the membrane.
- Think about it - a longer, wider membrane (more area), a bigger concentration gradient (more concentrated solute on one side), and a leakier membrane will result in more flux. A thicker membrane will result in less flux.
What is the effect of a pulmonary edema on membrane diffusion?
A pulmonary edema increases the distance between membranes, decreasing simple diffusion of oxygen.
What is the effect of a High altitude pulmonary edema (HAPE)?
Low oxygen pressure at high altitudes is compensated for by increased blow flow (pressure), which causes leakage from the capillaries.
Standard mM values of positive ions
- ion Intracellular Extracellular (plasma)
- K+ 140 4.0
- Na+ 5-15 140
- Ca+2 <0.00002 1-2
Standard mM values of negative ions and proteins
- ion Intracellular Extracellular 1
- Cl- 4-15 110
- HCO3- 12 22-30
- Protein 138 8-10
Standard values of osmolarity and pH
- ion Intracellular Extracellular (plasma)
- Osmolarity 287 mOsm 287 mOsm
- pH 7.1 7.4
How does secondary active transport work?
It uses the energy of other molecules (co-transport/symport and counter-transport/antiport) to transfer molecules across the membrane.
How does Water transfusion work?
- Water transfusion is both passive and facilitated (hence, some cells respond differently to different osmolar concentrations - RBC’s burst within seconds, frog eggs have no problems).
- Aquaporins are the first water channel proteins discovered. RBCs contain 200,000 AQP1 molecules.
Water transfusion equation
- Jv = LpΔP
- Jv = flow of water (volume),
- Lp = hydraulic conductivity (permeability),
- ΔP = pressure gradient (the difference between hydrostatic and osmotic pressure).
What is the simplified Nernst Equation for potassium (K+)?
Electrochemical gradient (mV) = -60 * log ([inside]/[outside])
What tests can be performed with urine dipsticks?
- bilirubin (component of heme - found in the body due to hemoglobin breakdown. May indicate liver disease, dehydration, or infectious hepatitis),
- specific gravity (1.010 - 1.020 normal, differences may indicate water overload, dehydration, high salt diet, infection, inability to concentrate urine, etc), blood (may indicate kidney, bladder, prostate, or vaginal infections),
- pH (normal 5-6), protein (may indicate bladder or kidney infection, or chronic kidney disease),
- urobilinogen (breakdown of hemoglobin - denotes a high rate breakdown of RBCs),
- nitrates (converted from nitrates by certain bacteria - may indicate infection),
- leukocytes (may indicate infection)
What are the types of urine test collections?
- Random void (any time, no requirements),
- first morning specimen (aka 8 hour specimen - contains the highest levels of cellular components),
- midstream catch,
- time specimen,
- suprapubic aspiration (from the bladder through the abdomen wall with a needle),
- pediatric specimen collected via bag
What are integral proteins?
Proteins that are closely associated with the membrane (ie, part of the membrane)
Tell me about transmembrane proteins.
Transmembrane proteins contain hydrophilic and hydrophobic (membrane spanning) regions (amphipathic) and may pass through the membrane one, or multiple, times.
Tell me about lipid linked proteins.
Lipid linked proteins have attached lipids that interact with the hydrophobic portion of the membrane.
Common Nernst potentials
- Na: +70 mV
- K: -98 mV
- Ca2+: +150 mV
- Cl: -30 mV to -65 mV
How do Nernst potentials predict ion flow across membranes?
Positive values indicate that the ion would likely enter the cell through a channel, negative values indicate that the ion would likely leave the cell.
What are Class I CFTR mutations?
(5%-10%) nonsense mutations, like G542X (“X” designates premature truncation or a nonsense mutation). These result in incomplete CFTR proteins.
What are Class II CFTR mutations?
(> 85%) Misfolded (although somewhat functional) proteins that are then recognized as misfolded and degraded, reducing the number of CFTR proteins available at the membrane. ΔF508 is the most common of all CFTR mutations.
What are Class III CFTR mutations?
- (2%-3%) Full length CFTR proteins that lack normal ion-channel activity. Regulation of activity by ATP and cAMP is not functional.
- G551D has FDA approved treatment!
What are Class IV CFTR mutations?
(< 2%) These exhibit only partial CFTR ion-channel activity, a feature that probably explains a less severe pulmonary phenotype.
What are Class V CFTR mutations?
(< 1%) These result in reduced numbers of CFTR transcripts (problems in protein synthesis or processing, resulting in fewer proteins).
What are Class VI CFTR mutations?
(< 1%) Mutations resulting in defective CFTR stability at the cell surface.
Define the cellular mechanism underlying the salty taste of a baby with cystic fibrosis.
Without a functioning CFTR protein, the chloride in salt ducts is unable to be reabsorbed, and the sodium follows, resulting in saltier skin.
What is autophagy?
When damaged or senescent organelles are surrounded by membrane and delivered to lysosomes for degradation
What is ED50?
The drug dose that is Effective or therapeutic for 50% of patients
What is TD50?
The drug dose that is toxic for 50% of patients
What is LD50?
The drug dose that is lethal for 50% of patients
What is the Therapeutic Index (TI)?
Therapeutic index = TD50/ED50. This is a comparison of toxicity to therapeutic values, indicating how safe it is. A higher index is better.
What is the Margin of Safety (MS)?
Margin of Safety = LD1/ED99
What does efficacy represent?
How big is the maximum effect (the greater the maximum effect, the greater the efficacy)
What does potency represent?
How little of a dose causes the maximum effect? The less needed, the stronger the potency.
What is an agonist?
An endogenous molecule or drug that activates a receptor (can be a full or partial agonist. A partial agonist produces a lower than maximal response at full receptor occupancy)
What is an antagonist?
A drug that prevents an agonist from activating a receptor.
What is an inverse agonist?
- A percentage of some receptors are in the active state in the absence of an agonist (causing a basal production level).
- An inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist, decreasing the basal rate.
- A basal rate must exist for an inverse agonist to exist.
What are Spare receptors?
Receptors that don’t need to be bound for a full response to occur. When spare receptors are present, additional antagonist will be needed to reduce the reaction.
Describe the structural subunits of the CFTR protein and what regulates its function.
There are 2 membrane spanning domains (each with 6 membrane spanning alpha helices), 2 nucleotide binding domains (one after each membrane spanning domain), a regulatory domain where phosphorylation occurs, and a carboxyl terminal where binding to the cytoskeleton, other ion channels, and signal transduction proteins occurs.
Activation is caused by phosphorylation through protein kinase A, and probably other kinases as well. A deletion in the first nucleotide binding domain is often related to the disease. (ΔF508)
Repeated administration of a drug results in reduced effect over time
Decreased ability of a receptor to respond to a drug or ligand. Can be homologous (affects one type of receptor) or heterologous (two or more types of receptors).
Complete loss of a receptor to respond to a drug or ligand.
effect of the drug on the body (drug site, interaction)
effectof body on the drug: absorption, distribution, metabolism, excretion
Describe the pathophysiology and clinical characteristics of cystic fibrosis
- Meconium ileus (abnormally thick and sticky bowel movements),
- Thick sticky mucus in lungs,
- salty sweat,
- blocked biliary ducts in the liver,
- blocked pancreatic ducts,
- intestines can't fully absorb nutrients,
- reproductive problems
What is VC? (Spirometry)
Vital capacity: The amount of air breathed out after the deepest inhalation
What is FVC? (Spirometry)
- Forced vital capacity: the determination of the vital capacity from a maximally forced
- expiratory effort
What is FEV1? (Spirometry)
Volume that has been exhaled at the end of the first second of forced expiration.
Repeated or persistent drug-receptor interaction results in removal of the receptor from sites where subsequent drug-receptor interactions could occur.
After a receptor is stimulated, a period of time is required before the next drug-receptor interaction can produce an effect.
Define ß-adrenergic receptor regulation:
Stimulation by an agonist results in phosphorylation. ß-arresting binds to the phosphorylation and prevents G proteins from attaching, reducing adenylyl cyclase activity. Continual agonist stimulation results in down regulation and eventual degradation.
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