Contractions have/has got, to be

Many of water’s biological functions stem from its chemical struc- ture. Recall that in the water molecule, H2O, the hydrogen and oxygen atoms share electrons to form covalent bonds. However, these atoms do not share the electrons equally. The oxygen atom has a greater ability to attract electrons to it because it pulls hydrogen’s electrons towards its nucleus. As a result, as shown in Figure 2-8, the region of the molecule where the oxygen atom is located has a partial negative charge, denoted with a , while the regions of the molecule where each of the two hydrogen atoms are located have partial positive charges, each of which are denoted with a . Thus, even though the total charge on a water molecule is neutral, the charge is unevenly distributed across the water molecule. Because of this uneven distribution of charge, water is called a polar compound. Notice also in Figure 2-8 that the three atoms in a water mole- cule are not arranged in a straight line as you might expect. Rather, the two hydrogen atoms bond with the single oxygen atom at an angle. SECTION 3 OBJECTIVES ● Describe the structure of a water molecule. ● Explain how water’s polar nature affects its ability to dissolve substances. ● Outline the relationship between hydrogen bonding and the different properties of water. ● Identify the roles of solutes and solvents in solutions. ● Differentiate between acids and bases. VOCABULARY polar hydrogen bond cohesion adhesion capillarity solution solute solvent concentration saturated solution aqueous solution hydroxide ion hydronium ion acid base pH scale buffer Copyright © by Holt, Rinehart and Winston. All rights reserved. (a) Electron cloud model (b) Space-filling model H H O The oxygen region of the water molecule is weakly negative, and the hydrogen regions are weakly positive. Notice the different ways to represent water, H2O. You are familiar with the electron cloud model (a). The space- filling model (b) shows the three- dimensional structure of a molecule. FIGURE 2-8 40 CHAPTER 2 Hydrogen bond H H H H H H H H H O O O O O O H H H H H – – – – – – – + + + + + + + + + + + + + + The dotted lines in this figure represent hydrogen bonds. A hydrogen bond is a force of attraction between a hydrogen atom in one molecule and a negatively charged region or atom in a second molecule. FIGURE 2-10 The positive region of a water molecule attracts the negative region of an ionic compound, such as the Cl portion of NaCl. Similarly, the negative region of the water molecule attracts the positive region of the compound—the Na portion of NaCl. As a result, NaCl breaks apart, or dissolves, in water. FIGURE 2-9 CI– Na+ H2O + + – – Solubility of Water The polar nature of water allows it to dissolve polar substances, such as sugars, ionic compounds, and some proteins. Water does not dissolve nonpolar substances, such as oil because a weaker attraction exists between polar and nonpolar molecules than between two polar molecules. Figure 2-9 shows how water dissolves the ionic compound sodium chloride, NaCl. In your body, ions, such as sodium and chloride, are essential to bodily func- tions, such as muscle contraction and transmission of impulses in the nervous system. In fact, dissolved, or dissociated ions, are pre- sent in all of the aqueous solutions found in living things and are important in maintaining normal body functions. HYDROGEN BONDING The polar nature of water also causes water molecules to be attracted to one another. As is shown in Figure 2-10, the positively charged region of one water molecule is attracted to the negatively charged region of another water molecule. This attraction is called a hydrogen bond. A hydrogen bond is the force of attraction between a hydrogen molecule with a partial positive charge and another atom or molecule with a partial or full negative charge. Hydrogen bonds in water exert an attractive force strong enough so that water “clings” to itself and some other substances. Hydrogen bonds form, break, and reform with great frequency. However, at any one time, a great number of water molecules are bonded together. The number of hydrogen bonds that exist depends on the state that water is in. If water is in its solid state all its water molecules are hydrogen bonded and do not break. As water liquifies, more hydrogen bonds are broken than are formed, until an equal number of bonds are formed and broken. Hydrogen bonding accounts for the unique properties of water, some of which we will examine further. These properties include cohesion and adhesion, the ability of water to absorb a relatively large amount of energy as heat, the ability of water to cool surfaces through evaporation, the density of ice, and the ability of water to dissolve many substances.

The cytoskeleton is a network of thin tubes and filaments that crisscrosses the cytosol. The tubes and filaments give shape to the cell from the inside in the same way that tent poles support the shape of a tent. The cytoskeleton also acts as a system of internal tracks, shown in Figure 4-18, on which items move around inside the cell. The cytoskeleton’s functions are based on several struc- tural elements. Three of these are microtubules, microfilaments, and intermediate filaments, shown and described in Table 4-2. Microtubules Microtubules are hollow tubes made of a protein called tubulin. Each tubulin molecule consists of two slightly different subunits. Microtubules radiate outward from a central point called the centrosome near the nucleus. Microtubules hold organelles in place, maintain a cell’s shape, and act as tracks that guide organelles and molecules as they move within the cell. Microfilaments Finer than microtubules, microfilaments are long threads of the beadlike protein actin and are linked end to end and wrapped around each other like two strands of a rope. Microfilaments con- tribute to cell movement, including the crawling of white blood cells and the contraction of muscle cells. Intermediate Filaments Intermediate filaments are rods that anchor the nucleus and some other organelles to their places in the cell. They maintain the inter- nal shape of the nucleus. Hair-follicle cells produce large quantities of intermediate filament proteins. These proteins make up most of the hair shaft. 84 CHAPTER 4 TABLE 4-2 The Structure of the Cytoskeleton Property Microtubules Microfilaments Intermediate filaments Structure hollow tubes made of two strands of intertwined protein fibers coiled into coiled protein protein cables Protein subunits tubulin, with two subunits: å actin one of several types of and ∫ tubulin fibrous proteins Main function maintenance of cell shape; cell maintenance and changing of maintenance of cell shape; motility (in cilia and flagella); cell shape; muscle contraction; anchor nucleus and other chromosome movement; movement of cytoplasm; cell organelles; maintenance of organelle movement motility; cell division shape of nucleus Shape Microtubules provide a path for organelles and molecules as they move throughout the cell. FIGURE 4-18 Microtubules Nucleus Endoplasmic reticulum Mitochondrion Ribosomes Copyright © by Holt, Rinehart and Winston. All rights reserved. Copyright © by Holt, Rinehart and Winston. All rights reserved. CELL STRUCTURE AND FUNCTION 85 1. Explain how the fluid mosaic model describes the plasma membrane. 2. List three cellular functions that occur in the nucleus. 3. Describe the organelles that are found in a eukaryotic cell. 4. Identify two characteristics that make mitochon- dria different from other organelles. 5. Contrast three types of cytoskeletal fibers. CRITICAL THINKING 6. Relating Concepts If a cell has a high energy requirement, would you expect the cell to have many mitochondria or few mitochondria? Why? 7. Analyzing Information How do scientists think that mitochondria originated? Why? 8. Analyzing Statements It is not completely accurate to say that organelles are floating freely in the cytosol. Why not? SECTION 3 REVIEW During cell division, centrioles organize microtubules that pull the chromosomes (orange) apart. The centrioles are at the center of rays of microtubules, which have been stained green with a fluorescent dye. FIGURE 4-20 Cilia and Flagella Cilia (SIL-ee-uh) and flagella (fluh-JEL-uh) are hairlike structures that extend from the surface of the cell, where they assist in movement. Cilia are short and are present in large numbers on certain cells, whereas flagella are longer and are far less numerous on the cells where they occur. Cilia and flagella have a membrane on their outer surface and an internal structure of nine pairs of micro- tubules around two central tubules, as Figure 4-19 shows. Cilia on cells in the inner ear vibrate and help detect sound. Cilia cover the surfaces of many protists and “row” the protists through water like thousands of oars. On other protists, cilia sweep water and food particles into a mouthlike opening. Many kinds of protists use flagella to propel themselves, as do human sperm cells. Centrioles Centrioles consist of two short cylinders of microtubules at right angles to each other and are situated in the cytoplasm near the nuclear envelope. Centrioles occur in animal cells, where they organize the microtubules of the cytoskeleton during cell division, as shown in Figure 4-20. Plant cells lack centrioles. Basal bodies have the same structure that centrioles do. Basal bodies are found at the base of cilia and flagella and appear to organize the devel- opment of cilia and flagella.

The endoplasmic reticulum (EN-doh-PLAZ-mik ri-TIK-yuh-luhm), abbre- viated ER, is a system of membranous tubes and sacs, called cisternae (sis-TUHR-nee). The ER functions primarily as an intracellu- lar highway, a path along which molecules move from one part of the cell to another. The amount of ER inside a cell fluctuates, depending on the cell’s activity. There are two types of ER: rough and smooth. The two types of ER are thought to be continuous. Rough Endoplasmic Reticulum The rough endoplasmic reticulum is a system of interconnected, flattened sacs covered with ribosomes, as shown in Figure 4-15. The rough ER produces phospholipids and proteins. Certain types of proteins are made on the rough ER’s ribosomes. These proteins are later exported from the cell or inserted into one of the cell’s own membranes. For example, ribosomes on the rough ER make digestive enzymes, which accumulate inside the endoplasmic retic- ulum. Little sacs or vesicles then pinch off from the ends of the rough ER and store the digestive enzymes until they are released from the cell. Rough ER is most abundant in cells that produce large amounts of protein for export, such as cells in digestive glands and antibody-producing cells. Smooth Endoplasmic Reticulum The smooth ER lacks ribosomes and thus has a smooth appear- ance. Most cells contain very little smooth ER. Smooth ER builds lipids such as cholesterol. In the ovaries and testes, smooth ER produces the steroid hormones estrogen and testosterone. In skeletal and heart muscle cells, smooth ER releases calcium, which stimulates contraction. Smooth ER is also abundant in liver and kidney cells, where it helps detoxify drugs and poisons. Long-term abuse of alcohol and other drugs causes these cells to produce more smooth ER. Increased amounts of smooth ER in liver cells is one of the factors that can lead to drug tolerance. As Figure 4-15 shows, rough ER and smooth ER form an interconnected network. Copyright © by Holt, Rinehart and Winston. All rights reserved. reticulum from the Latin rete, meaning “net”; reticulum means “little net” Word Roots and Origins The endoplasmic reticulum (ER) serves as a site of synthesis for proteins, lipids, and other materials. The dark lines in the photo represent the membranes of the ER, and the narrow lighter areas between the dark lines show the channels and spaces (cisternae) inside the ER. FIGURE 4-15 Smooth ER Ribosomes Rough ER Cisternae 82 CHAPTER 4 GOLGI APPARATUS The Golgi apparatus, shown in Figure 4-16, is another system of flattened, membranous sacs. The sacs nearest the nucleus receive vesicles from the ER containing newly made proteins or lipids. Vesicles travel from one part of the Golgi apparatus to the next and transport substances as they go. The stacked membranes modify the vesicle contents as they move along. The proteins get “address labels” that direct them to various other parts of the cell. During this modification, the Golgi apparatus can add carbohydrate labels to proteins or alter new lipids in various ways. VESICLES Cells contain several types of vesicles, which perform various roles. Vesicles are small, spherically shaped sacs that are surrounded by a single membrane and that are classified by their contents. Vesicles often migrate to and merge with the plasma membrane. As they do, they release their contents to the outside of the cell. Lysosomes Lysosomes (LIE-suh-SOHMZ) are vesicles that bud from the Golgi appa- ratus and that contain digestive enzymes. These enzymes can break down large molecules, such as proteins, nucleic acids, car- bohydrates, and phospholipids. In the liver, lysosomes break down glycogen in order to release glucose into the bloodstream. Certain white blood cells use lysosomes to break down bacteria. Within a cell, lysosomes digest worn-out organelles in a process called autophagy (aw-TAHF-uh-jee). Lysosomes are also responsible for breaking down cells when it is time for the cells to die. The digestion of damaged or extra cells by the enzymes of their own lysosomes is called autolysis (aw-TAHL-uh-sis). Lysosomes play a very important role in maintaining an organism’s health by destroying cells that are no longer functioning properly. Copyright © by Holt, Rinehart and Winston. All rights reserved. The Golgi apparatus modifies many cellular products and prepares them for export. FIGURE 4-16 CELL STRUCTURE AND FUNCTION 83 Peroxisomes Peroxisomes are similar to lysosomes but contain different enzymes and are not produced by the Golgi apparatus. Peroxisomes are abundant in liver and kidney cells, where they neutralize free radicals (oxygen ions that can damage cells) and detoxify alcohol and other drugs. Peroxisomes are named for the hydrogen peroxide, H2O2, they produce when breaking down alco- hol and killing bacteria. Peroxisomes also break down fatty acids, which the mitochondria can then use as an energy source. Other Vesicles Specialized peroxisomes, called glyoxysomes, can be found in the seeds of some plants. They break down stored fats to provide energy for the developing plant embryo. Some cells engulf material by surrounding it with plasma membrane. The resulting pocket buds off to become a vesicle inside the cell. This vesicle is called an endosome. Lysosomes fuse with endosomes and digest the engulfed material. Food vacuoles are vesicles that store nutrients for a cell. Contractile vacuoles are vesicles that can contract and dispose of excess water inside a cell. Protein Synthesis One of the major functions of a cell is the production of protein. The path some proteins take from synthesis to export can be seen in Figure 4-17. In step , proteins are assembled by ribosomes on the rough ER. Then, in step , vesicles transport proteins to the Golgi apparatus. In step , the Golgi modifies proteins and pack- ages them in new vesicles. In step , vesicles release proteins that have destinations outside the cell. In step , vesicles containing enzymes remain inside the cell as lysosomes, peroxisomes, endo- somes, or other types of vesicles. 5 4 3 2 1 Copyright © by Holt, Rinehart and Winston. All rights reserved. Proteins are assembled by ribosomes on the rough ER. Vesicles carry proteins from the rough ER to the Golgi apparatus. Proteins are modified in the Golgi apparatus and enter new vesicles. Some vesicles release their proteins outside the cell. Other vesicles remain in the cell and become lysosomes and other vesicles. Nucleus

Chapter 22 Antihypertensive Drugs Hypertension Defined (JNC-8) Pharmacology Overview 7 main categories of drugs to treat HTN Adrenergic drugs (old friend) Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers (ARBs) Calcium channel blockers (CCBs) Diuretics Vasodilators Direct renin inhibitors A. Adrenergic Drugs: 5 Subcategories and where they act A1. Adrenergic neuron blockers (central and peripheral)- we won’t talk about this A2. Alpha1 receptor blockers (peripheral) A3. Alpha2 receptor agonists (central) A4. Beta receptor blockers (peripheral) A5. Combined α and β receptor blockers (peripheral) A2. Peripherally Acting Adrenergic DrugAlpha1 Blockers (we’ve met these) Doxazosin, prazosin, alfuzosin Block alpha1-receptors which causes BP to decrease Reduces peripheral vascular resistance and BP by dilating both arterial and venous blood vessels Main Use: benign prostatic hyperplasia (BPH) Alpha1 Blockers REMEMBER Tamsulosin (Flomax)* is an α1 blocker BUT *Tamsulosin is not used to control BP, just for BPH. A3. Centrally Acting Adrenergic DrugsAlpha 2 agonist Clonidine and methyldopa 1- Stimulate alpha2-adrenergic receptors. in the brain Decreases sympathetic outflow from the CNS which decreases NE production 2. Stimulate alpha2-adrenergic receptors in kidneys remember alpha 2 opposes alpha 1 Dilates peripheral blood vessels → lowers peripheral resistance → Results in decreased BP So ….Clonidine (Catapres) Used primarily for its ability to decrease blood pressure in an urgent setting Also use in opioid withdrawal as previously discussed Oral (multiple times a day), and topical patch formulations Do not stop abruptly as it may lead to rebound hypertension In reality, Clonidine and methyldopa Not prescribed as first-line home antiHTN drugs High incidence of unwanted adverse effects: orthostatic hypotension, fatigue, and dizziness MIGHT be uses as adjunct drugs after other drugs have failed, in conjunction with other antiHTN such as diuretics A4. Adrenergic Drugs Selective Beta 1 Blockers Metoprolol, Atenolol Reduction of HR through β1 receptor blockade (remember adrenergic blocking of this receptor???) HR results in BP Cause reduced secretion of renin = BP A4. Adrenergic Drugs Selective Beta1 Blockers Nebivolol (Bystolic) Uses: hypertension and HF Action: blocks β1 receptors and produces vasodilatation, which results in a decrease in SVR High doses loses selectivity and blocks both β1 and β2 Less sexual dysfunction All BB- Do not stop abruptly; must be tapered over 1 to 2 weeks A4. Adrenergic Drugs NONSelective Beta Blockers Propranolol Acts equally on β1 and β2 Other uses include situational anxiety associated with public speaking, test taking As mentioned on previous slide, nebivolol at high doses becomes beta nonselective A5. Dual-Action Adrenergic Drugs α1 and β Receptor Blockers Dual antihypertensive effects of reduction in heart rate (beta1 receptor blockade) and vasodilation (alpha1 receptor blockade) Examples are carvedilol (common) and labetalol (not as common) A5. Dual-Action Adrenergic Drugs α1 and β Receptor Blockers Carvedilol (Coreg) Widely used drug that is well tolerated Uses: HTN, mild to moderate HF in conjunction with digoxin, diuretics, and ACE inhibitors Contraindications: severe bradycardia or unstable HF, bronchospastic conditions such as asthma, and various cardiac conduction problems Adrenergic Drugs Indications - HTN But also for Glaucoma (topical) BPH: doxazosin, prazosin, and terazosin (2 for 1) Management of severe HF when used with cardiac glycosides and diuretics Contraindications Acute HF- have to stabilize first MOAIs- yeah doesn’t everything interact with MAOIs? Peptic ulcers Severe liver/kidney disease Asthma (with beta blockers) Adrenergic Drugs: Adverse Effects Orthostatic hypotension 1st-dose syncope Rebound hypertension with abrupt discontinuation Most common: Dry mouth, drowsiness, constipation, sedation Interactions- always check for specific drug interactions Can cause additive CNS depression with alcohol, benzodiazepines, opioids Question #1 When administering an alpha-adrenergic drug for hypertension, it is most important for the nurse to assess the patient for the development of what response? Hypotension Hyperkalemia Oliguria Respiratory distress Answer A Hypotension This is a key point in patient education These drugs have strong vasodilating properties and may cause severe hypotension, especially at the beginning of therapy. B. Angiotensin-Converting Enzyme Inhibitorsaka ACE Inhibitors or ACEi Large group of safe and effective drugs Currently are 10 ACEi Often used as first-line drugs for HF and hypertension May be combined with a thiazide diuretic, loop diuretic, or Calcium Channel Blocker (CCB) You need to understand the basics ACE Inhibitors: Review RAAS ACE converts angiotensin I, formed through the action of renin, to angiotensin II Angiotensin 2 is a potent vasoconstrictor and also induces aldosterone secretion by the adrenal glands Aldosterone stimulates sodium resorption (H20 follows Na Both act to raise BP which causes kidneys to reduce renin production ACEi= Great drug to treat HTN BUT contraindicated in pregnancy (2nd,3rd trimester due to fetal renal damage) and breastfeeding first few weeks after birth B. ACE Inhibitors - PRIL Lisinopril (Prinivil) super common, often the 1st drug Enalapril (Vasotec) also common Captopril (Capoten) great if liver disease present Benazepril (Lotensin) Fosinopril (Monopril) Perindopril (Aceon) Quinapril (Accupril) Ramipril (Altace) Trandolapril (Mavik) Primary Effects of the ACE Inhibitors Prevent Na (and H2O) resorption by inhibiting aldosterone secretion (volume reduction) (GO BACK TO RAAS DIAGRAM) blood volume decreases work of the heart preload, or the left ventricular end-diastolic volume which is important in HF ACE SUMMARY OF ACTIVITY 1) Prevent vasoconstriction caused by angiotensin 2 (2) Prevent aldosterone secretion  less sodium and water resorption Cardioprotective Effects of ACEi They slow progression of left ventricular hypertrophy (ventricular remodeling) after MI so considered cardioprotective ACE inhibitors have been shown to decrease morbidity and mortality in patients with HF Renal Protective Effects of ACEi ACE inhibitors: reduce glomerular filtration pressure by volume reduction Cardiovascular drug of choice for patients with diabetes since it helps protect kidneys by reducing pressure. Sometimes used low dose for kidney protection with DM without HTN B. ACEi Enalapril (Vasotec) Only ACEi available in both oral and IV Enalapril IV does not require cardiac monitoring Oral enalapril: prodrug (metabolized in liver) Improves patient’s chances of survival after an MI Reduces the incidence of HF B. ACEi Captopril (Capoten) Uses: prevention of ventricular remodeling after MI; reduce the risk of HF after MI Shortest half-life Must be administered multiple times throughout the day so this limits its use Not a prodrug so good for patient with liver disease Question #2 A patient with diabetes has a new prescription for the ACE inhibitor lisinopril. She questions this order because her provider has never told her that she has hypertension. What is the best explanation for this order? The doctor knows best The patient is confused This medication has cardioprotective properties This medication has a protective effect on the kidneys for patients with diabetes Answer D ACE inhibitors have been shown to have a protective effect on the kidneys because they reduce glomerular filtration pressure. This property makes them the cardiovascular drug of choice for patients with diabetes. Question #3 A patient with a history of pancreatitis and cirrhosis is also being treated for hypertension. Which drug will most likely be ordered for this patient? Clonidine Prazosin Diltiazem Captopril Answer D Captopril Captopril is not a prodrug; therefore, it does not need to be metabolized by the liver to be effective. This is an advantage in patients with liver disease. ACE Inhibitors: Adverse Effects *Dry, nonproductive cough, which reverses when therapy is stopped. This is a class effect Dizziness- Note: First-dose hypotensive effect may occur Headache & Fatigue Possible hyperkalemia ** Angioedema: rare but potentially fatal Not safe in pregnancy-are contraindicated during the second and third trimesters of pregnancy because of increased risk of fetal renal damage C. Angiotensin II Receptor Blockers(ARB) Considered an alternative to ACEi Less likely to cause a dry cough and hyper K+ that is common with ACE inhibitors Angiotensin II Receptor Blockers: Mechanism of Action Go back to RAAS diagram! ARBs affect primarily 2 places 1. Vascular smooth muscle - blocks vasoconstriction 2. Adrenal gland -Selectively blocks the binding of Ang 2 to certain Ang 2 receptors inhibiting secretion of aldosterone Lowers volume retention and BP Angiotensin II Receptor Blockers -ARTAN Losartan (Cozaar)- very common Eprosartan (Teveten) Valsartan (Diovan) Irbesartan (Avapro) Candesartan (Atacand) Olmesartan (Benicar) Telmisartan (Micardis) Azilsartan (Edarbi) C. ARB Losartan (Cozaar) Beneficial in patients with HTN and HF Used with caution in patients with kidney or liver dysfunction and in patients with renal artery stenosis ***Not safe for breastfeeding women and should not be used in pregnancy (Cat C 1st trimester, Cat D 2nd-3rd trimester), potential fetal toxicity Appear to be equally effective for the treatment of hypertension and well tolerated ARBs less likely to cause cough and hyperK+ but can still happen Evidence that ARBs are associated with lower mortality after MI than ACE inhibitors Never take ACEi and ARBs at the same time* 5. Calcium Channel Blockers (CCB) Primary use: HTN, angina, some dysrhythmias Cause smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing muscle contraction Results in: Relaxed blood vessels to the heart Decreased peripheral smooth muscle tone Decreased SVResistance Decreased BP E. Diuretics First-line antiHTN in JNC 8 guidelines Decreases fluid volume The results from diuresis: preload, Peripheral resistance Overall effect  Decreased workload of the heart and decreased BP Thiazide diuretics are the most commonly used diuretics for HTN Ie hydrochlorothiazide (HCTZ), chlorthalidone We will discuss diuretics further in the chapter on diuretics F. Vasodilators Directly relax arterial or venous smooth muscle (or both) Results in: Decreased SVR Decreased afterload Peripheral vasodilation Indicated for treatment of HTN May be used in combination with other drugs F. Vasodilators Hydralazine (Apresoline) Orally: routine cases of essential hypertension Injectable: hypertensive emergencies BiDil: specifically indicated as an adjunct for treatment of HF in African-American patients F. Vasodilators Sodium Nitroprusside (Nitropress) *Sodium nitroprusside and IV diazoxide are reserved for the management of hypertensive emergencies. Contraindications: severe HF, known inadequate cerebral perfusion (especially during neurosurgical procedures) F. Vasodilators Adverse Effects Hydralazine: dizziness, headache, tachycardia, edema, dyspnea, N/V/D, vitamin B6 deficiency, rash Sodium nitroprusside: hypotension, bradycardia, decreased platelet aggregation, rash G. Direct Renin Inhibitors Aliskirin (Tekturna) Blocks the RAS pathway at the point of activation. Inhibiting renin production prevents the downstream production of Ang II (potent vasoconstrictor) Adverse effects: N/V, severe hypotension, hyponatremia, hyperkalemia… Contraindicated in patients with DM taking ACEi or ARB Miscellaneous Antihypertensives Eplerenone (Inspra) Newer class of drugs called selective aldosterone blockers (remember RAAS?) Reduces BP by blocking the actions of aldosterone at its corresponding receptors in the kidney, heart, blood vessels, and brain Indications: routine treatment of hypertension and for post-MI HF Contraindicated if serum potassium levels are high (above 5.6 mEq/L) A Special Form of HTNTreatment of Pulmonary Hypertension Sildenafil and Tadalafil Commonly used for erectile dysfunction Used for pulmonary hypertension but with different trade names Sildenafil: Revatio* (Viagra for ED) Tadalafil: Adcirca* (Cialis for ED)

Policy for Bloodborne Pathogen Exposure Incident as per OSHA regulation (29 CFR 1910.1030) Purpose: To ensure that ASC staff members are protected against potential exposure to bloodborne pathogens per OSHA regulations (29 CFR 1910.1030). Scope: This policy applies to all ASC staff members who may be exposed to blood or other potentially infectious materials during their duties. Policy: An exposure incident is defined as a specific eye, mouth, other mucous membranes, non-intact skin, or parenteral contact with blood or other potentially infectious materials that results from the performance of an employee's duties. Any spill or accident that results in an exposure incident must be immediately reported to the Infection Control Nurse, first-line leader, or another responsible person. The employer shall make available the hepatitis B vaccine and vaccination series to all employees who have occupational exposure and post-exposure evaluation and follow-up to all employees who have had an exposure incident. The employer shall provide a confidential medical evaluation and follow-up for the exposed employee, which shall include at least the following elements: • Documentation of the route(s) of exposure and the circumstances under which the exposure incident occurred. • Identification and documentation of the source individual, unless the employer can establish that identification is infeasible or prohibited by state or local law. The source individual's blood shall be tested as soon as feasible and after consent is obtained to determine HBV and HIV infectivity. • Collection and testing of blood for HBV and HIV serological status. • If the employee consents to baseline blood collection but does not consent to HIV serologic testing, the sample shall be preserved for at least 90 days. If, within 90 days of the exposure incident, the employee elects to have the baseline sample tested, such testing shall be done as soon as feasible • Post-exposure prophylaxis, when medically indicated, as recommended by the U.S. Public Health Service. • Counseling. • Evaluation of reported illnesses. The employer shall ensure that the healthcare professional evaluating an employee after an exposure incident is provided with the following: A copy of OSHA regulation 1910.1030 A description of the exposed employee's duties as they relate to the exposure incident Documentation of the route(s) of exposure and circumstances under which exposure occurred Results of the source individual's blood testing, if available. All medical records are relevant to the appropriate treatment of the employee, including vaccination status, which is the employer's responsibility to maintain. The employer shall obtain and provide the employee with a copy of the evaluating healthcare professional's written opinion within 15 days of the completion of the evaluation. The healthcare professional's written opinion for Hepatitis B vaccination shall include the following: Whether it is indicated for the employee If the employee has received such a vaccination The healthcare professional's written opinion for post-exposure evaluation and follow-up shall include the following: That the employee has been informed of the results of the evaluation That the employee has been told about any medical conditions resulting from exposure to blood or other potentially infectious materials which require further evaluation or treatment All other findings or diagnoses shall remain confidential and not be included in the written report. An employer must establish and maintain accurate medical records for each employee with occupational exposure. Records should include the employee's Name, hepatitis B vaccination status and dates, results of medical testing and follow-up procedures, healthcare professional's written opinion, and information provided to the healthcare professional. Records must be kept confidential and not disclosed without the employee's written consent, except as required by law. Records must be kept for at least the duration of the employee's employment plus 30 years. Form 7.041 Employee Consent Form for Testing for HBV and HIV Serological Status Following Accidental Exposure I, __________________________, understand that I have been involved in an accidental exposure incident and may be at risk for contracting Hepatitis B Virus (HBV) and Human Immunodeficiency Virus (HIV) under 29 CFR 1910.1030. Therefore, following OSHA standards, I am being offered the opportunity to be tested for these viruses. I understand that the testing will involve a blood sample and that the results will be kept confidential and will only be shared with authorized personnel. I also understand that testing is voluntary and that I have the right to refuse to test. By signing this form, I consent to be tested for HBV and HIV following the accidental exposure incident. Signed: __________________________ Patient's Name: __________________________ Form 7.042 Patient Consent Form for Testing for HBV and HIV Serological Status Following Accidental Exposure I, __________________________, understand that a staff member involved in an accidental exposure incident may be at risk for contracting Hepatitis B Virus (HBV) and Human Immunodeficiency Virus (HIV) following 29 CFR 1910.1030. Therefore, by OSHA standards, the staff member may be offered the opportunity to be tested for these viruses. I also understand that testing of my blood is necessary to determine if I am infected with HBV and HIV. The results will be kept confidential and only shared with authorized personnel. I understand that testing is voluntary and that I have the right to refuse to test. By signing this form, I consent to the staff member being tested for HBV and HIV and to my blood testing following the accidental exposure incident. Signed: __________________________ Form7.043 Refusal of Testing Patient/Employee (Circle One) I,_____________________________________, understand that I have the right to refuse testing for Hepatitis B Virus (HBV) and Human Immunodeficiency Virus (HIV) following an accidental exposure incident per 29 CFR 1910.1030. I understand that if I refuse to test, it may impact my ability to receive appropriate medical treatment and the healthcare facility's power to respond to the exposure incident. Following 29 CFR 1910.1030, The source individual's blood shall be tested as soon as feasible and after consent is obtained to determine HBV and HIV infectivity. The employer shall establish that legally required consent cannot be obtained if permission is not obtained. When the source individual's consent is not required by law, the source individual's blood, if available, shall be tested, and the results documented. Signed: __________________________

A solution is a mixture in which one or more substances are uniformly distributed in another substance. Solutions can be mixtures of liquids, solids, or gases. For example, plasma, the liquid part of blood, is a very complex solution. It is composed of many types of ions and large molecules, as well as gases, that are dissolved in water. A solute (SAHL-YOOT) is a substance dissolved in the solvent. The particles that compose a solute may be ions, atoms, or molecules. The solvent is the substance in which the solute is dissolved. For example, when sugar, a solute, and water, a solvent, are mixed, a solution of sugar water results. Though the sugar dissolves in the water, neither the sugar molecules nor the water molecules are altered chemically. If the water is boiled away, the sugar molecules remain and are unchanged. Solutions can be composed of various proportions of a given solute in a given solvent. Thus, solutions can vary in concentra- tion. The concentration of a solution is the amount of solute dis- solved in a fixed amount of the solution. For example, a 2 percent saltwater solution contains 2 g of salt dissolved in enough water to make 100 mL of solution. The more solute dissolved, the greater is the concentration of the solution. A saturated solution is one in which no more solute can dissolve. Aqueous (AY-kwee-uhs) solutions—solutions in which water is the solvent—are universally important to living things. Marine microorganisms spend their lives immersed in the sea, an aqueous solution. Most nutrients that plants need are in aqueous solutions in moist soil. Body cells exist in an aqueous solution of intercellu- lar fluid and are themselves filled with fluid; in fact, most chemical reactions that occur in the body occur in aqueous solutions. Copyright © by Holt, Rinehart and Winston. All rights reserved. Liquid water Solid water Ice (solid water) is less dense than liquid water because of the structure of ice crystals. The water molecules in ice are bonded to each other in a way that creates large amounts of open space between the molecules, relative to liquid water. FIGURE 2-12 solvent from the Latin solvere, meaning “to loosen” Word Roots and Origins CHEMISTRY OF LIFE 43 ACIDS AND BASES One of the most important aspects of a living system is the degree of its acidity or alkalinity. What do we mean when we use the terms acid and base? Ionization of Water As water molecules move about, they bump into one another. Some of these collisions are strong enough to result in a chemical change: one water molecule loses a proton (a hydrogen nucleus), and the other gains this proton. This reaction really occurs in two steps. First, one molecule of water pulls apart another water molecule, or dissociates, into two ions of opposite charge: H2O ∏ H OH The OH ion is known as the hydroxide ion. The free H ion can react with another water molecule, as shown in the equation below. H H2O ∏ H3O The H3O ion is known as the hydronium ion. Acidity or alkalin- ity is a measure of the relative amounts of hydronium ions and hydroxide ions dissolved in a solution. If the number of hydronium ions in a solution equals the number of hydroxide ions, the solution is said to be neutral. Pure water contains equal numbers of hydro- nium ions and hydroxide ions and is therefore a neutral solution. Acids If the number of hydronium ions in a solution is greater than the number of hydroxide ions, the solution is an acid. For example, when hydrogen chloride gas, HCl, is dissolved in water, its mol- ecules dissociate to form hydrogen ions, H, and chloride ions, Cl, as is shown in the equation below. HCl ∏ H Cl These free hydrogen ions combine with water molecules to form hydronium ions, H3O. This aqueous solution contains many more hydronium ions than it does hydroxide ions, making it an acidic solution. Acids tend to have a sour taste; how- ever, never taste a substance to test it for acidity. In concentrated forms, they are highly corrosive to some materials, as you can see in Figure 2-13. Bases If sodium hydroxide, NaOH, a solid, is dissolved in water, it dissociates to form sodium ions, Na, and hydroxide ions, OH, as shown in the equation below. NaOH ∏ Na OH Copyright © by Holt, Rinehart and Winston. All rights reserved. Eco Connection onnection Acid Precipitation Acid precipitation, more commonly called acid rain, describes rain, snow, sleet, or fog that contains high levels of sulfuric and nitric acids. These acids form when sulfur dioxide gas, SO2, and nitrogen oxide gas, NO, react with water in the atmosphere to produce sulfuric acid, H2SO4, and nitric acid, HNO3. Acid precipitation makes soil and bodies of water, such as lakes, more acidic than normal. These high acid levels can harm plant and animal life directly. A high level of acid in a lake may kill mollusks, fish, and amphibians. Even in a lake that does not have a very elevated level of acid, acid precipitation may leach aluminum and magnesium from soils, poisoning water- dwelling species. Reducing fossil-fuel consump- tion, such as occurs in gasoline engines and coal-burning power plants, should reduce high acid levels in precipitation. Sulfur dioxide, SO2, which is produced when fossil fuels are burned, reacts with water in the atmosphere to produce acid precipitation. Acid precipitation, or acid rain, can make lakes and rivers too acidic to support life and can even corrode stone, such as the face of this statue. FIGURE 2-13 44 CHAPTER 2 This solution then contains more hydroxide ions than hydronium ions and is therefore defined as a base. The adjective alkaline refers to bases. Bases have a bitter taste; however, never taste a substance to test for alkalinity. They tend to feel slippery because the OH ions react with the oil on our skin to form a soap. In fact, commercial soap is the product of a reaction between a base and a fat. pH Scientists have developed a scale for comparing the relative con- centrations of hydronium ions and hydroxide ions in a solution. This scale is called the pH scale, and it ranges from 0 to 14, as shown in Figure 2-14. A solution with a pH of 0 is very acidic, a solution with a pH of 7 is neutral, and a solution with a pH of 14 is very basic. A solution’s pH is measured on a logarithmic scale. That is, the change of one pH unit reflects a 10-fold change in the acidity or alkalinity. For example, urine has 10 times the H3O ions at a pH of 6 than water does at a pH of 7. Vinegar, has 1,000 times more H3O ions at a pH of 3 than urine at a pH of 6, and 10,000 times more H3O ions than water at a pH of 7. The pH of a solution can be measured with litmus paper or with some other chemical indicator that changes color at various pH levels. Buffers The control of pH is important for living systems. Enzymes can function only within a very narrow pH range. The control of pH in organisms is often accomplished with buffers. Buffers are chemi- cal substances that neutralize small amounts of either an acid or a base added to a solution. As Figure 2-14 shows, the composition of your internal environment—in terms of acidity and alkalinity— varies greatly. Some of your body fluids, such as stomach acid and urine, are acidic. Others, such as intestinal fluid and blood, are

A solution is composed of a solute dissolved in a solvent. In the sugar water described in Figure 5-1, the solute was sugar and the solvent was water, and the solute molecules diffused through the solvent. It is also possible for solvent molecules to diffuse. In the case of cells, the solutes are organic and inorganic compounds, and the solvent is water. The process by which water molecules diffuse across a cell membrane from an area of higher concentration to an area of lower concentration is called osmosis (ahs-MOH-sis). Because water is moving from a higher to lower concentration, osmosis does not require cells to expend energy. Therefore, osmosis is the passive transport of water. Direction of Osmosis The net direction of osmosis depends on the relative concentra- tion of solutes on the two sides of the membrane. Examine Table 5-1. When the concentration of solute molecules outside the cell is lower than the concentration in the cytosol, the solution outside is hypotonic to the cytosol. In this situation, water diffuses into the cell until equilibrium is established. When the concentration of solute molecules outside the cell is higher than the concentration in the cytosol, the solution outside is hypertonic to the cytosol. In this situation, water diffuses out of the cell until equilibrium is established. Observing Diffusion Materials 600 mL beaker, 25 cm dialysis tubing, funnel, 15 mL starch solution (10 percent), 20 drops Lugol’s solution, 300 mL water, 100 mL graduated cylinder, 20 cm piece of string (2) Procedure 1. Put on your disposable gloves, lab apron, and safety goggles. 2. Pour 300 mL of water in the 600 mL beaker. 3. Add 20 drops of Lugol’s solution to the water. CAUTION: Lugol’s solution is a poison and eye and skin irritant. 4. Open the dialysis tubing, and tie one end tightly with a piece of string. 5. Using the funnel, pour 15 mL of 10 percent starch solution into the dialysis tubing. 6. Tie the other end of the dialysis tubing tightly with the second piece of string, forming a sealed bag around the starch solution. 7. Place the bag into the solution in the beaker, and observe the setup for a color change. Analysis What happened to the color in the bag? What happened to the color of the water around the bag? Explain your observations. Quick Lab www.scilinks.org Topic: Osmosis Keyword: HM61090 mb06se_homs01.qxd 11/27/07 8:52 AM Page 98 HOMEOSTASIS AND CELL TRANSPORT 99 When the concentrations of solutes outside and inside the cell are equal, the outside solution is said to be isotonic to the cytosol. Under these conditions, water diffuses into and out of the cell at equal rates, so there is no net movement of water. Notice that the prefixes hypo-, hyper-, and iso- refer to the relative solute concentrations of two solutions. Thus, if the solution outside the cell is hypotonic to the cytosol, then the cytosol must be hyper- tonic to that solution. Conversely, if the solution outside is hypertonic to the cytosol, then the cytosol must be hypotonic to the solution. Water tends to diffuse from hypo- tonic solutions to hypertonic solutions. How Cells Deal with Osmosis Cells that are exposed to an isotonic external environment usually have no difficulty keeping the movement of water across the cell membrane in balance. This is the case with the cells of ver- tebrate animals on land and of most other organ- isms living in the sea. In contrast, many cells function in a hypotonic environment. Such is the case for unicellular freshwater organisms. Water constantly diffuses into these organisms. Because they require a relatively lower concentration of water in the cytosol to function normally, unicel- lular organisms must rid themselves of the excess water that enters by osmosis. Some of them, such as the paramecia shown in Figure 5-2, do this with contractile vacuoles (kon-TRAK-til VAK-y ̄ ̄o ̄ ̄o-OL), which are organelles that remove water. Contractile vacuoles collect the excess water and then contract, pumping the water out of the cell. Unlike diffusion and osmosis, this pumping action is not a form of passive trans- port because it requires the cell to expend energy. Copyright © by Holt, Rinehart and Winston. All rights reserved. (a) (b) Vacuole filling with water Vacuole contracting TABLE 5-1 Direction of Osmosis Condition External solution is hypotonic to cytosol External solution is hypertonic to cytosol External solution is isotonic to cytosol Net movement of water into the cell out of the cell none H2O H2O H2O H2O H2O H2O The paramecia shown below live in fresh water, which is hypotonic to their cytosol. (a) Contractile vacuoles collect excess water that moves by osmosis into the cytosol. (b) The vacuoles then contract, returning the water to the outside of the cell. (LM 315) FIGURE 5-2 100 CHAPTER 5 (a) HYPOTONIC Cell walls (b) HYPERTONIC (a) ISOTONIC (b) HYPOTONIC (c) HYPERTONIC Other cells, including many of those in multicellular organisms, respond to hypotonic environments by pumping solutes out of the cytosol. This lowers the solute concentration in the cytosol, bring- ing it closer to the solute concentration in the environment. As a result, water molecules are less likely to diffuse into the cell. Most plant cells, like animal cells, live in a hypotonic environ- ment. In fact, the cells that make up plant roots may be surrounded by water. This water moves into plant cells by osmosis. These cells swell as they fill with water until the cell membrane is pressed against the inside of the cell wall, as Figure 5-3a shows. The cell wall is strong enough to resist the pressure exerted by the water inside the expanding cell. The pressure that water molecules exert against the cell wall is called turgor pressure (TER-GOR PRESH-er). In a hypertonic environment, water leaves the cells through osmosis. As shown in Figure 5-3b, the cells shrink away from the cell walls, and turgor pressure is lost. This condition is called plasmolysis (plaz-MAHL-uh-sis), and is the reason that plants wilt if they don’t receive enough water. Some cells cannot compensate for changes in the solute con-

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