Lec2 Distribution of Water, pH, Buffers PDF

# What Water Does For Your Body... Water is the major component of most body parts. - Forms saliva (digestion) - Converts food to components needed for survival – digestion - Keeps mucosal membranes moist - Allows body's cells to grow, reproduce, and survive - Flushes body waste, mainly in ur...

# What Water Does For Your Body... Water is the major component of most body parts. - Forms saliva (digestion) - Converts food to components needed for survival – digestion - Keeps mucosal membranes moist - Allows body's cells to grow, reproduce, and survive - Flushes body waste, mainly in urine. - Lubricates joints. - Makes up 83% of Blood. - Composes 75% of the Brain. - Needed by the brain to manufacture hormones and neurotransmitters. - Regulates body temperature (sweating and respiration). - Acts as a shock absorber for the brain and spinal cord. - Helps deliver oxygen all over the body. - Accounts for 22% of Bones. - Makes up 75% Muscles # Biomedical Importance ## Physical Properties of Water - Universal Solvent - Water's dipolar structure and capacity for forming hydrogen bonds. - An excellent nucleophile, water is a reactant or product in many metabolic reactions. ## Regulation of Water Balance Depends upon hypothalamic mechanisms that control thirst, on antidiuretic hormone (ADH), on retention or excretion of water by the kidneys, and on evaporative loss. Nephrogenic diabetes insipidus, which involves the inability to concentrate urine or adjust to subtle changes in extracellular fluid osmolarity, results from the unresponsiveness of renal tubular osmoreceptors to ADH. ## Dissociation of Water Into hydroxide ions and protons, and pH AND BUFFERS - Bicarbonate and other buffers normally maintain the pH of extracellular fluid between 7.35 and 7.45 - Causes of acidosis (blood pH <7.35) include diabetic ketosis and lactic acidosis. - Alkalosis (pH >7.45) may follow vomiting of acidic gastric contents. # Your Patient - A 3-year-old child - The emergency department - Complaints of persistent vomiting and diarrhea for the past 24 hours. - On examination, the child appears lethargic and irritable. - His mucous membranes and skin look dry. - His skin turgor is decreased. - Vital signs reveal a heart rate of 150 bpm, blood pressure of 80/50 mmHg, and a temperature of 38.5°c. - Laboratory investigations: elevated serum sodium and hematocrit levels. # Look At Eyes For Dehydration - Shrunken Eyes: A picture of a baby with sunken eyes - Normal eyes: A picture of a baby with regular non-sunken eyes # Probable Diagnosis - Which of the following clinical findings is most indicative of hypovolemia in this child? - What is the primary mechanism leading to elevated serum sodium levels in this case? - What is the significance of the elevated hematocrit level in this child? - HYPOVOLEMIA – DEHYDRATION - MOST COMMON REASON OF DAIRRHEA - INFECTION, FOOD POISONING etc. # Sign And Symptoms Of Dehydration - A diagram with symptoms listed, showing a baby with sunken eyes and cheeks, a sunken abdomen, sunken fontanelles, a dry mouth and tongue, and few or no tears - A picture of a baby with sunken fontanelles # Edema - Hypervolemia/Volume Overload - A 7-year-old child - Pediatric clinic by her parents - Swelling of her face and lower extremities for the past week. - Swelling worsens during the evening and improves slightly after the child wakes up in the morning. - On examination, the child appears well-nourished. - Periorbital puffiness - Pitting edema in the lower extremities. # Which Of The Following Is The Most Likely Cause of Edema In This Child? - A) Nephrotic syndrome - B) Heart failure - C) Malnutrition - D) Allergic reaction # Water Balance Water is the solvent of life. Undoubtedly, water is more important than any other single compound to life. It is involved in several body functions. ## Function of Water - Water provides the aqueous medium to the organism which is essential for the various biochemical reactions to occur. - Water directly participates as a reactant in several metabolic reactions. - It serves as a vehicle for transport of solutes. - Water is closely associated with the regulation of body temperature. # Homeostasis Ability to maintain a steady state despite changing conditions. Water is important to this process because… - It makes a good insulator - Resist temperature change - Universal solvent - Coolant - Ice protects against temperature extremes (insulates frozen lakes) # Distribution of Body Water - A Diagram showing the distribution of water within the body. ## ECF - Intravascular: plasma-arteries, veins, capillaries - Intestinal: spaces between cells - Transcellular: Cerebrospinal fluid, Pleural spaces, Synovial spaces, Peritoneal fluid spaces ## ICF - Intracellular: Essential for normal cell function - Provides medium for metabolic processes # Total Body Water - A diagram showing water distribution between the intracellular and extracellular compartments of the body. - Intracellular fluid (63%) - Extracellular fluid (37%) - Interstitial fluid - Plasma - Lymph - Transcellular fluid # Major Compartments For Fluids * Intracellular Fluid (ICF) * Inside cell * Most of body fluid here – 63% weight * Decreased in elderly * Extracellular Fluid (ECF) * Outside cell: 37% * Interstitial fluid – between cells & blood vessels (25%) * Intravascular fluid – within blood vessels (5~8%) * Transcellular fluid – cerebrospinal, pericardial, synovial, gastrointestinal tract fluid (1~2%) # Distribution of Water - A diagram showing a woman and a man, each divided into sections. - The top section shows the percentage of solids - The bottom section shows the percentage of fluids and the distribution between intracellular fluid and extracellular fluid. ## Woman - Solids: 45% - Fluids: 55% - Intracellular fluid (ICF) 2/3 - Extracellular fluid (ECF) 1/3 ## Man - Solids: 40% - Fluids: 60% - Intracellular fluid (ICF) 2/3 - Extracellular fluid (ECF) 1/3 - Intestinal: 80% # Water Steady State Amount Ingested = Amount Eliminated - A diagram showing the flow of water in and out of the body with the volume or rate of each process listed. ## Water Gain - 2.2 L/day - Food and drink ## Water Loss - Skin: Insensible water loss: 0.9 L/day - Lungs - Urine: 1.5 L/day - Feces: 0.1 L/day ## Total Intake and Output - Intake: 2.2 L/day - Metabolic production: 0.3 L/day - Output: (0.9 + 1.5 + 0.1) L/day # Electrolytes Composition Of Body Fluids - Normal Values (Serum) - Cation: - Sodium (Na+): 135 - 145 mEq/L - Potassium (K+): 3.5 - 5.50 mEq/L - Calcium (Ca++): 8.5 - 10.5 mg/dL - Ionized Calcium: 4.5 - 5.5 mg/dL - Magnesium (Mg++): 1.5 - 2.5 mEq/L - Anion: - Bicarbonate (HCO3): 24 - 30 mEq/L - Chloride (Cl--): 95 - 105 mEq/L - Phosphate (PO4--): 2.8 - 4.5 mg/dL # Mechanisms Controlling Fluid And Electrolyte Movement - **Diffusion:** type of passive transport that allows substances to cross membranes with the assistance of special transport proteins - **Facilitated diffusion:** - **Active transport:** physiologic pump that moves fluid from an area of lower concentration to one of higher concentration. - **Osmosis:** the process by which fluid moves across a semi-permeable membrane from an area of low solute concentration to an area of high solute concentration - **Hydrostatic pressure:** the pressure created by the weight of fluid against the wall that contains it. - **Oncotic pressure:** Osmotic pressure exerted by proteins # Fluid Exchange Between Capillary And Tissue - A diagram showing the movement of fluid between the capillary and tissue. - Capillary: - Arterial end: Hydrostatic pressure 40 mmHg - Venous end: Oncotic pressure 25 mmHg, Hydrostatic pressure 10 mmHg - Tissue: - Interstitial hydrostatic pressure 1 mmHg - Interstitial oncotic pressure 1 mmHg # Electrolyte Composition Of Body Fluids - **Electrolytes are well distributed** - **Maintain the osmotic equilibrium and water balance.** - **There is a marked difference in the concentration of electrolytes between the ECF and ICF.** - Na⁺ is the principal extracellular cation while K+ is the intracellular cation. - **This difference in the concentration is essential for the cell survival which is maintained by Na+ + ATPase** # Regulation Of Electrolyte Balance - **Electrolytes and water balance are regulated together and the kidney play a critical role.** - **The regulation is mostly achieved through the hormones and certain mechanisms:** - Aldosterone - ADH (Antidiuretic hormone) - Renin-angiotensin system # Dehydration Is a condition characterized by water depletion in the body. It may be due to insufficient intake or excessive water loss or both. ## Two Types of Dehydration - Due to loss of water alone. - Due to deprivation of water and electrolytes. ## Causes of Dehydration - Diarrhea - Vomiting - Excessive sweating - Adrenocortical dysfunction - Kidney disease - Deficiency of ADH # Characteristic Feature of Dehydration - A diagram showing the movement of water and solutes out of the intracellular compartment to the extracellular compartment. ## Features of Dehydration - **The volume of ECF decrease, electrolytes concentration and osmotic pressure increase.** - **Water is drawn from the ICF, shrunken cells and disturbed metabolism.** - **ADH secretion is increased.** - **Plasma protein and blood urea concentration increased.** - **Loss of electrolytes from the body (Na+, K+, etc.).** <start_of_image> - Skin with decreased turgor remains elevated after being pulled up and released # Clinical Symptoms Of Severe Dehydration - Increased pulse rate - Low blood pressure - Sunken eyeballs - Decreased skin turgor - Lethargy - Confusion - Coma - **Treatment:** Intake plenty of water, 5% glucose solution. # Overhydration Overhydration or water intoxication is caused by excessive retention of water in the body. It may be due to excess intake or large volumes of salt-free fluids, renal failure, or overproduction of ADH. ## Clinical Syndromes - Headache - Lethargy - Convulsions ## Overhydration Treatment - Stop water intake - Administration of hypertonic saline # Other Interactions ## Van Der Waals Forces Are the weak forces which contribute to intermolecular bonding between molecules. Van der Waals forces are the sum of the attractive and repulsive electrical forces between atoms and molecules. These forces differ from chemical bonding because they result from fluctuations in charge density of particles. - Examples: - Hydrogen bonding - Dispersion forces - Dipole-dipole interactions ## Hydrophobic Interactions - The tendency of nonpolar compounds to self-associate in an aqueous environment. - This self-association is driven by mutual attraction nor by "hydrophobic bonds." - Self-association minimizes the disruption of energetically favorable interactions between the surrounding water molecules. ## Electrostatic Interactions - Interactions between charged groups help shape biomolecular structure. - Electrostatic interactions between oppositely charged groups within or between biomolecules are termed salt bridges. - Salt bridges are comparable in strength to hydrogen bonds but act over larger distances. - They facilitate the binding to charged molecules and ions to proteins and nucleic acids. # Nucleophiles Metabolic reactions often involve the attack by lone pairs of electrons residing on electron-rich molecules. - **Water:** whose two lone pairs of sp3 electrons bear a partial negative charge. - **Water is an excellent nucleophile. Other nucleophiles of biologic importance include the oxygen atoms of phosphates, alcohols, and carboxylic acids; the sulfur of thiols; and the nitrogen of amines and the imidazole ring of histidine.** - **Nucleophilic attack by water typically results in the cleavage of the amide, glycoside, or ester bonds that hold biopolymers together. This process is termed hydrolysis.** # Electrophiles - **Electron-poor atoms called electrophiles** - **Common electrophiles include the carbonyl carbons in amides, esters, aldehydes, and ketones and the phosphorus atoms of phosphoesters** # Dissociation of Water One water molecule dissociates into a hydrogen ion (H+) and a hydroxide ion (OH-). $H_2O \iff H^+ + OH^-$ - **Hydrogen ion - Acid** - **Hydroxide ion - Base** # Henderson-Hasselbalch Equation ## Derivation According to the Brønsted-Lowry theory of acids and bases: - An acid (HA) is capable of donating a proton (H+) - A base (B) is capable of accepting a proton. - After the acid (HA) has lost its proton, it is said to exist as the conjugate base (A-). - Similarly, a protonated base is said to exist as the conjugate acid (BH+). ## Henderson-Hasselbalch Equation $pH = pK_a + log ( \frac{[A^-]}{[HA]} )$ # pH - p means "puissant" and H means "Hydrogen." - It is the French word, which means strength/power of hydrogen. - It was introduced by Sorenson in 1909. ## Definition It is defined as the negative log of the hydrogen ion concentration. # pH and Buffers - pH is the negative log of [H+]. A low pH characterizes an acidic solution, and a high pH denotes a basic solution. - The strength of weak acids is expressed by pka, the negative log of the acid dissociation constant. Strong acids have low pka values and weak acids have high pka values. - Buffers resist a change in pH when protons are produced or consumed. Maximum buffering capacity occurs ± 1 pH unit on either side of pka. - Physiologic buffers include bicarbonate, phosphate, and proteins. # pH Is A Unit Of Measure - It describes the degree in acidity or alkalinity (basic) of a solution. - It is measured on a scale of 0 to 14. - Low pH values correspond to high concentrations of H+ and high pH values correspond to low concentrations of H+. # The pH Value Of A Substance - It is directly related to the ratio of the hydrogen ion and hydroxyl ion concentrations. - If the H+ concentration is higher than OH-, the material is acidic. - If the OH- concentration is higher than H+, the material is basic. - 7 is neutral, < is acidic, >7 is basic. # The pH Scale - A scale from 1-14 showing acid (strong and weak) neutral, and alkali (strong and weak) with a color bar - pH value as shown by different color in universal indicator # Bases - Strong bases have a pH of 11 to 14. - Contain lots of OH- ions and fewer H+ ions. - A diagram showing the pH scale from 7-14, with corresponding everyday examples. # Measurement of pH - The pH can be measured by: - pH strips - pH indicators - pH meter # Buffers - Weak acids or bases that react with strong acids or bases to prevent sharp, sudden changes in pH (neutralization). - Two pictures are included: - Heinz Vinegar - Dawn Dish Soap # Buffer - A buffer solution is a solution which resists changes in pH when a small amount of acid or base is added. - Typically a mixture of a weak acid and a salt of its conjugate base or a weak base and a salt of its conjugate acid. - The resistive action is the result of equilibrium between the weak acid (HA) and its conjugate base (A-) or vice versa. $HA_{(aq)} + H_2O_{(l)} \iff H_3O^+_{(aq)} + A^-_{(aq)}$ # Types of Buffers - Two types: - Acidic buffers - Basic buffers ## Acidic Buffers Solution of a mixture of a weak acid and a salt of this weak acid with a strong base. E.g. $CH_3COOH$ + $CH_3COONa$ (weak acid) + (Salt). ## Basic Buffers Solution of a mixture of a weak base and a salt of this weak base with a strong acid. e.g. $NH_4OH + NH_4CI$ (Weak base) + (Salt) # How Buffers Work - Equilibrium between acid and base. - Example: Acetate Buffer $CH_3COOH \iff CH_3COO^- + H^+$ - If more H+ is added to this solution, it simply shifts the equilibrium to the left, absorbing H+, so the [Ht] remains unchanged. - If H+ is removed (e.g. by adding OH-) then the equilibrium shifts to the right, releasing H+ to keep the pH constant. # Buffer capacity Or Buffer action - It is defined as the number of moles of an acid or a base required to be added to one litre of the buffer so as to change its pH by one. *Buffer capacity = (No. of moles of the acid or base added to 1 litre of buffer) / (Change in pH)* - NOTE: Buffer capacity of a buffer is maximum when the concentration of the weak acid and its salt or weak base and its salt are equal. # Buffer Systems In Body Fluids - A diagram showing the buffer systems in ICF and ECF, along with their components and where they are found. - ICF: - Phosphate buffer system - Hemoglobin buffer system (RBCs only) - Amino acid buffers (all proteins) - ECF: - Carbonic acid-bicarbonate buffer system - Plasma protein buffers # The Carbonic Acid Hydrogen Carbonate Buffer System - The carbonic acid-hydrogen carbonate ion buffer is the most important buffer system. - Carbonic acid ($H_2CO_3$) acts as the weak acid. - Hydrogen carbonate ($HCO_3-$) acts as the conjugate base. - Increase in $H^+ (aq)$ ions is removed by $HCO_3^- (aq)$. - The equilibrium shifts to the left and most of the $H^+ (aq)$ ions are removed. # Phosphate Buffer System - The phosphate buffer system ($HPO_4^2-/H_2PO_4^-$) plays a role in plasma and erythrocytes. $H_2PO_4^- + H_2O \iff H_3O^+ + HPO_4^2-$ - Any acid reacts with monohydrogen phosphate to form dihydrogen phosphate. - The base is neutralized by dihydrogen phosphate $H_2PO_4^- + H_2O \iff HPO_4^2- +H_3O^+$ $H_2PO_4^- + OH^- \iff HPO_4^2- +H_3O^+$ # Proteins As A Buffer - Proteins contain –COO- groups, which, like acetate ions ($CH_3COO^-$), can act as proton acceptors. - Proteins also contain –$NH_3^+$ groups, which like ammonium ions ($NH_4^+$), can donate protons. - If acid comes into blood, hydronium ions can be neutralized by the –COO- groups: $-COO^- + H_3O^+ \iff -COOH + H_2O$ - If base is added, it can be neutralized by the —$NH_3^+$ groups: $-NH_3^+ + OH^- \iff -NH_2 + H_2O$