Clinical Chemistry 2 (Lecture) Module 3 - Electrolytes - Saint Louis University PDF

SAINT LOUIS UNIVERSITY SCHOOL OF NURSING, ALLIED HEALTH, AND BIOLOGICAL SCIENCES BS MEDICAL LABORATORY SCIENCE A.Y. 2022-2023...

SAINT LOUIS UNIVERSITY SCHOOL OF NURSING, ALLIED HEALTH, AND BIOLOGICAL SCIENCES BS MEDICAL LABORATORY SCIENCE A.Y. 2022-2023 CLINICAL CHEMISTRY 2 (LECTURE) MODULE 3 – ELECTROLYTES MODULE CONTENTS UNIT 1 — BLOOD VOL REGULATION; WATER & SODIUM UNIT 1 — BLOOD VOLUME REGULATION; WATER AND SODIUM BASIC CONCEPTS OF FLUID & ELECTROLYTE BALANCE UNIT 2.1 — POTASSIUM UNIT 2.2 — CHLORIDE AND BICARBONATE WATER UNIT 3.1 — CALCIUM UNIT 3.2 — MAGNESIUM  Plays a role in many physiological processes, including: UNIT 3.3 — PHOSPHATE o Transport of nutrients to cells o Determination of cell volume  transport into and ELECTROLYTES out of cells FUNCTIONS ELECTROLYTES INVOLVED o Removal of waste products  urine Maintaining electrical neutrality in the cells o Temperature regulation  body’s coolant through Na, K Cl sweating Blood volume and osmotic regulation Mnemonics: NaKO (view Cl as “O”) o Cushion of joints o Protection of tissues and organs from shock and Generation and conduction of action potentials Mg, Ca, K damage in the nerves and muscles o Digestion and absorption of food  regulation of Myocardial rhythm and contractility Mnemonics: Mag Ca-Kapatid body weight Blood coagulation Mg, Ca  Most compounds in the body must interact with an aqueous Production and use of ATP from glucose Mg, PO4 medium (e.g., water) in order to function Cofactors in enzyme activation  The body regulates a constant amount of water that is 60% OF Mg, Ca, Zn TOTAL BODY WEIGHT Mnemonics: Mag Ca-Zin  Located in the intra- and extracellular compartments, which is Acid-base balance then respectively termed as the ff: HCO3, K, Cl INTRACELLULAR WATER EXTRACELLULAR WATER GIBBS-DONNAN EQUILIBRIUM  Comprises majority of the  Comprises 1/3 or 40% of the total body water (about 2/3 or total body water GIBBS-DONNAN EQUILIBRIUM 60%)  2 solutions separated by semipermeable membrane establish an equilibrium so that all ions are distributed in body fluid ELECTROLYTE BALANCE compartments ELECTROLYTE BALANCE o STATE OF EQUILIBRIUM:  Total ions = total conc. of osmotically-  Note that there are differences among cells in various tissues in active particles their solute composition and concentrations (image below)  Water is balanced between 2 compartments through a semipermeable membrane o Diffusible ions will also balance between the 2 compartments o However, if 1 compartment has 1 non-diffusible component (e.g., proteins), it will not be balanced in the other compartment o Anions, such as chloride, are used to compensate for this imbalance  The concentrations of electrolytes within cells and in plasma are maintained by active transport and diffusion ACTIVE TRANSPORT DIFFUSION  Requires energy to move ions  The passive movement of ions across cellular membrane across a membrane NOTE  There are several factors which influences these processes, but the most important is the balance between the concentration of not only these substances, but also proteins, in these compartments © BANIÑA, NJ │ 3RD YEAR – 1ST SEM “Nothing worth having comes easy” 1 CLINICAL CHEMISTRY 2 (LEC) BODY WATER COMPARTMENTS  Constitutes the medium in which chemical reactions of cell metabolism occur TOTAL BODY WATER (TBW)  Characteristics:  Includes the ff: o Heterogeneous o Water both inside and outside of cells; and  Means that there is a difference in the o Water normally present in the GIT and GUT intracellular solute concentration between systems different cell types  Percentage in total body weight: o Discontinuous o Average adult man  65% of total body wt.  Means that the interior of every other cell is separated by a semipermeable cell o Women  55% of total body wt.  This difference is largely a result of membrane difference in body fat  Certain features of most cell fluids are quantitatively similar  Theoretically divided into 2 MAIN COMPARTMENTS: MAJOR CATIONS OF ICW MAJOR ANIONS OF CELLULAR FLUIDS o ECW o ICW  Potassium  Sodium  Magnesium  Protein  Sodium conc. is low  Organic phosphates A. ECW  Sulfates  Chloride and bicarbonate conc. is EXTRACELLULAR WATER low  Includes all water external to cell membrane  Constitutes the medium through which all metabolic exchange REGULATION OF BODY FLUID COMPARTMENT: occurs OSMOLALITY AND VOLUME  Includes physiological ECW and transcellular water REGULATION OF BODY FLUID COMPARTMENT PHYSIOLOGICAL ECW  Normal metabolic functions require regulation of PHYSIOLOGICAL EXTRACELLULAR WATER osmolality/ionic strength, primarily in the ICW where most metabolic activities occur  The portion of the ECW whose volume and components are  ECW  has a role in regulating this osmolality mostly accessible for direct measurement in lab setting o Change in extracellular osmolality  results to a  Includes: change in intracellular osmolality o Plasma water (intravascular fluid)  Eventually leads to a change in the o Interstitial fluid (ISF) intracellular volume PLASMA  Composed of water, protein, lipid and other BLOOD VOLUME WATER macromolecules  The only compartment in which the composition is BLOOD VOLUME (BV) (INTRAVASCU LAR FLUID) directly measurable  One of the reasons why plasma is used as a sample  Importance: for measuring concentration of analytes in the blood o Maintain blood pressure o Ensure good perfusion to all tissues and organs INTERSTITIAL  Includes extravascular water into which ions and  OSMORECEPTORS FLUID (ISF) small molecules diffuse freely from plasma o Initially detect changes in BV  Although the concentrations of freely diffusible solute o Found in organs such as in the heart and kidneys in ISF might be expected to be equal to those in plasma, this is true only for uncharged solutes (e.g., urea) o Activate a series of responses that restore volume by  Difference with plasma: appropriately affecting the ff: o Absence of protein  Vascular resistance o Not normally sampled in amounts  Cardiac output sufficient for chemical analysis  Cavities and spaces in the body (pericardial, pleural,  Renal Na+ and water retention peritoneal and synovial) that are normally empty except for a few milliliters of viscous lubricating fluid SODIUM BALANCE AND WATER CONTENT are considered to be part of the ISF compartment  Normally, the ECW OSMOLALITY AND VOLUME is regulated by SODIUM BALANCE AND WATER CONTENT under the influence of the ff: o Hypothalamus TRANSCELLULAR WATER o RAAS o Atrial natriuretic factor (ANF) TRANSCELLULAR WATER o Kidneys  Any imbalance in sodium and water will result into a cascade of  Includes water enclosed by an epithelial membrane mechanisms to correct for that imbalance o Volume and composition of which are determined by the cellular activity of that membrane  Heterogeneous compartments that include: OSMOLALITY o Aqueous humor in the eye OSMOLALITY o CSF o Water within the GIT, GUT, and RT systems  Refers to the physical property of a solution  The volume of transcellular water portion of the anatomical ECW o Based on the total conc. of all dissolved molecules is not included in conventional measurements of ECW which include ions, organic metabolites, and proteins  When ECW osmolality ↑ by accumulation of effective osmols B. ICW  regulation of osmotic equilibrium as water shifts from the cell to the ECW  increases ICW osmolality to the same level INTRACELLULAR WATER as the ECW osmolality  Compartment in which solute concentrations cannot be o EFFEECTIVE OSMOLS directly determined  Solutes that are only found in the ECW  Includes all water within cell membranes  e.g., glucose and sodium © BANIÑA, NJ │ 3RD YEAR – 1ST SEM “Nothing worth having comes easy” 2 CLINICAL CHEMISTRY 2 (LEC)  ION CHANNELS hypothalamus through o Found in the semipermeable CM and allows water to ANGIOTENSIN II move freely LOCATION OF NEURON EFFECT MOVEMENT OF WATER STIMULATION Water intake Produces conscious area sensation of thirst  Water moves from a compartment with lower osmolality (i.e., with low  water intake conc. of solutes) to one with higher conc.  achieves equal osmolality on Water output Release of both sides of the membrane area antidiuretic  As water is lost from one fluid compartment, it is replaced with water hormone (ADH) from another compartment to maintain a near constant osmolality from the posterior pituitary gland  water reabsorption in the collecting ducts of ELECTROLYTES the kidney  formation of ELECTROLYTES hypertonic urine  ↓ output of free water (water  Refer to ions capable of electric charge, whose components without solute) dissociate in solution into CATION (+) and ANION (-)  Integration of all control  Imbalances in the conc. of these dissolved electrolytes affect the mechanisms governing water osmolality of blood intake and output ensures  SODIUM AND WATER METABOLISM is influenced by the ff: maintenance of appropriate water balance o Hypothalamus (Water metabolism) o RAAS o Natriuretic peptides B. RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM A. HYPOTHALAMUS SODIUM HYPOTHALAMUS SODIUM (Na+)  The regulatory centers for water intake and water output are  One of the most abundant electrolytes in the extracellular fluid located in separate areas of the hypothalamus in the brain o Accounts for the 90% of all the extracellular cations o Neurons (osmoreceptors) in each of these areas o Largely determines the osmolality of plasma respond to changes in plasma osmolality and plasma  Responsible for the ff: volume o Maintaining extracellular fluid volume  Water excess  ↓ plasma osmolality o Regulation of the membrane potential of cells  Water deficit  ↑ plasma osmolality  Active transport: exchanged with K+ across CM which involves Na+, K+-ATPase pumps HYPOTHALAMIC REGULATION OF WATER BALANCE SODIUM-POTASSIUM-ATPase PUMPS  Pumps three Na+ ions OUT of the cell in exchange for two K+ ions moving INTO the cell PI2SO3  2 Potassium In, 3 Sodium Out  Our body requires only 1-2 mmol/day of Na+ and the excess is excreted by the kidneys o Freely filtered o Actively reabsorbed in greater amounts in proximal tubules  Smaller amounts is reabsorbed in the loop of Henle along with chloride and water  Level of Na+ in the plasma is mainly regulated by: o Thirst o Water excretion  mainly affected by the release of INCREASED PLASMA VOLUME DECREASED PLASMA VOLUME AVP o Blood volume status ↑ PLASMA VOLUME  ↓ PLASMA ↓ PLASMA VOLUME  ↑ PLASMA o Sodium output (excretion through the GIT, skin, and OSMOLALITY OSMOLALITY urine)  BODY’S RESPONSE:  BODY’S RESPONSE: o Suppress thirst o Stimulates neurons RAAS ON SODIUM AND WATER METABOLISM o Suppress secretion of directly by causing ARGININE them to shrink  CONCENTRATION OF PLASMA Na+ is the routine marker for assessing VASOPRESSIN  EFFECTS: osmolality HORMONE (AVP)  o Reduction in the previously known as activity of distention ↓ TBW  ↑ Na+ conc.  Thirst sensation and secretion of AVP ANTIDIURETIC receptors located in  The secretion of AVP involves the osmoreceptors as a function of the HORMONE (ADH) the atria of the heart, hypothalamus  EFFECTS: inferior vena cava, and pulmonary veins o OSMORECEPTORS o Water is not  Immediately responds to small changes in osmolality reabsorbed but o Reduction in activity  A small increase or decrease will dictate the secretion of excreted of BP receptors in AVP the aorta of the heart and carotid arteries Suppression of AVP  Relay of these information to ↓ Na+ conc.  ↑ renal water excretion  secretion the CNS stimulates neurons in the water intake and water output areas of the © BANIÑA, NJ │ 3RD YEAR – 1ST SEM “Nothing worth having comes easy” 3 CLINICAL CHEMISTRY 2 (LEC)  Important in defending against salt-induce hypertension and congestive heart failure  Include: o Atrial natriuretic peptide (ANP) o Brain natriuretic peptide o C-type natriuretic peptide ATRIAL  Produced primarily from the atrium of the heart NATRIURETIC  EFFECTS: PEPTIDE o Reduces the increase in venous pressure (ANP) that occurs with a given increase in blood volume o Increases vascular permeability o Promotes NATRIURESIS (sodium excretion) and DIURESIS (increased urine output) as a result of increased glomerular filtration rate  The increased filtration rate allows more solute to be excreted in urine o In the brain, ANP inhibits:  Salt appetite  Water intake  Secretion of ADH and cortisol URODILATIN  Similar structure to ANP, but is formed in the kidneys  Its diuretic and natriuretic effects are known to be more potent than ANP BRAIN  Produced primarily from the ventricles of the heart NATRIURETIC  Just like ANP, is also has cardiovascular, natriuretic, PEPTIDE and diuretic effects C-TYPE  Produced in the brain, vascular endothelial cells, and NATRIURETIC renal tubules PEPTIDE  Minimal conc. in plasma  regulation is unclear  The MOST POTENT VENOUS VASODILATOR of the three, but has NO NATRIURETIC EFFECT RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM  The main hormonal system responisble for the regulation of renal Na+ excretion CLINICAL SIGNIFICANCE  RENIN o A proteolytic enzyme synthesized, stored, and secreted by the juxtaglomerular cells of the kidneys ↓ renal prefussion pressure (BP); ↑ secretion of renin ↓ plasma Na+ conc. 1 o Converts ANGIOTENSINOGEN to ANGIOTENSIN I  ANGIOTENSINOGEN  A polypeptide synthesized in the liver 2 o ANGIOTENSIN I is converted to ANGIOTENSIN II in the lungs and kidneys through the presence of ANGIOTENSIN- CONVERTING ENZYME (ACE)  ANGIOTENSIN II  Plays several roles to increase BP  Causes vasoconstriction of the vascular sys.  Stimulates aldosterone secretion by the  NORMAL RANGE FOR PLASMA Na+ = 136-145 mmol/L adrenal cortex, thirst sensation in the brain, and ADH secretion  Diseases/pathologies involving blood Na+ levels include:  ALDOSTERONE o Hyponatremia o Hypernatremia Stimulates Na+ ↑ aldosterone ↑ plasma Na+; reabsorption in the distal secretion  Water is retained tubules  o NOTE: even if water is retained due to aldosterone action, plasma osmolality is better influence by Na+ conc. o Action of aldosterone establishes a balance between restoring Na+ conc. and increasing plasma volume SUMMARY ↑ blood ↑ urinary Na+ Na+ intake > Na+ excretion volume  excretion ↑ Na+ reabsorption  ↓ blood Na+ intake < Na+ excretion ↓ urinary Na+ volume  excretion C. NATRIURETIC PEPTIDES NATRIURETIC PEPTIDES  Dictates the balance between Na+ intake and excretion  Have reciprocal effects to the RAAS ↑ BP and plasma volume  Release of natriuretic peptides © BANIÑA, NJ │ 3RD YEAR – 1ST SEM “Nothing worth having comes easy” 4 CLINICAL CHEMISTRY 2 (LEC) A. HYPONATREMIA o In some instances, Na+ shifts into the cells to maintain osmotic balance  ↓ plasma HYPONATREMIA Na+  Na+ loss) TYPES OF HYPONATREMIA o Decreased water intake o Increased Na+ intake/retention HYPOOSMOTIC ↓ Na+ REABSORPTION due to either of the ff:  Categorized based on blood volume: HYPONATREMIA HYPOADRENALISM ↓ Na+ ↑ Na+ excretion o Hypovolemic Hypernatremia ↓ OSMOLALITY (low aldosterone) reabsorption  Frequent o Normovolemic Hypernatremia ↓ PLASMA Na+ EXCESSIVE USE ↓ Na+ conc. OF DIURETICS urination o Hypervolemic Hypernatremia SALT-LOSING Impaired renal ↑ Na+ loss in NEPHROPATHY funtion urine TYPES OF HYPONATREMIA Na+ is co- Defect in RENAL TUBULAR excreted to bicarbonate HYPOVOLEMIC CAUSES: ACIDOSIS maintain reabsorption  electroneutrality HYPERNATREMIA Tubules EXCESS WATER LOSS (WATER LOSS > Na+ LOSS) ↓ plasma K+  conserve K+ ↓ BLOOD VOL. HYPOKALEMIA and in exchange, ↑ PLASMA Na+  DIABETES INSIPIDUS (DI) Na+ is excreted o Hormonal disorder that happens when: Ketone are ↑ Na+ loss in  Tubules are UNABLE TO KETONURIA excreted in RESPOND TO ADH; or urine urine   There is IMPAIRED ADH SODIUM DEFICIT > WATER DEFICIT  ↓ PLASMA SECRETION o NEPHROGENIC DI OSMOLALITY  Normal production of ADH, but  Happens when there is: kidneys do not respond to it o ↑ loss of Na+ in sweat  This causes ↓ water  Observed in cases of CYSTIC reabsorption  water loss FIBROSIS o NEUROGENIC DI  Disease of the lungs  There is a problem in neural characterized by signals  ↓ production of increased sweat ADH production  This causes ↓ water  Sweat contains 50 reabsorption  water loss mEQ/L Na+  RENAL TUBULAR DISORDER o ↑ loss of Na+ in the GIT o Impaired water reabsorption  water  Observed in cases of SEVERE loss > Na+ loss DIARRHEA and EXCESSIVE INCREASED Na+ INTAKE/RETENTION VOMITING  Causes metabolic  Hyperaldosteronism (Na+ reabsorption) alkalosis where there  Excess ingestion of salt is ↑ bicarbonate  Dialysis fluid intake excretion accompanied with Na+ DECREASED WATER INTAKE INCREASED WATER RETENTION NORMOVOLEMIC  Occurs where there is insensible loss of water  Nephrotic syndrome HYPERNATREMIA through the skin and lungs o ↓ blood volume  stimulate production of ADH  ↑ thirst sensation NORMAL BV  Liver cirrhosis ↑ PLASMA Na+ o Prone to edema  ↑ thirst  dilute Na+  Congestive heart failure  Chronic polydipsia HYPERVOLEMIC  Occurs among px receiving hypertonic saline or  Cushing’s Disease HYPERNATREMIA sodium bicarbonate o ↑ cortisol in blood  production of ADH  ↑ H2O reabsorption ↑ BLOOD VOL.  Chronic renal failure ↑ PLASMA Na+  Syndrome of Inappropriate ADH Production o ↑ ADH production  ↑ thirst sensation  Hypothyroidism o Impaired H2O excretion SODIUM REFLUX  ↑ entry of Na+ into the cells  ↓ plasma Na+ HYPEROSMOTIC  Happens as a result of dilution in the presence of HYPONATREMIA osmotically active substances (e.g., glucose, mannitol) ↑ OSMOLALITY o Glucose causes SHIFT OF WATER from ↓ PLASMA Na+ the cells into the plasma © BANIÑA, NJ │ 3RD YEAR – 1ST SEM “Nothing worth having comes easy” 5 CLINICAL CHEMISTRY 2 (LEC) SIGNS & SYMPTOMS OSMOLALITY AND OSMOLAL GAP HYPONATREMIA HYPERNATREMIA OSMOLALITY Plasma Na+ >125 mmol/L will Plasma Na+ = 160-175 mmol/L  A colligative property of a solution show neuropsychiatric symptoms:  Mental status alteration  A measure of solute concentration defined as:  Nausea  Lethargy o Moles of solute per kilogram of solvent (mOsm/kg)  Vomiting  Irritability  Affects the colligative properties  Muscular weakness  Muscle twitching  Headache  Increased thirst o Freezing point depression  Lethargy o Vapor pressure decrease  Seizures  Reference interval: 275-300 mOsm/kg  Coma  Respiratory depression  Solute conc. in plasma is directly proportional to the osmolality CAUSES OF ABNORMAL Na+ CONCENTRATIONS OSMOLAL GAP  Lab artifacts OSMOLAL GAP  Dehydration  Disorders of thirst and antidiuretic hormone  Difference between the measured osmolality with that of  Renal disorders calculated osmolality  Water redistribution due to osmotically active substances such as glucose  Drugs o Measured osmolality is usually determined by  Endocrine disorders freezing point depression or vapor pressure  Indicates the presence of other osmotically active substances CASE STUDY aside from Na+: o Glucose o BUN  Used to screen for the possible presence of exogenous toxic substances in px in an emergency dep’t or ICU  Calculated using the formula below: 𝒎𝒈 𝒎𝒈 𝒎𝒎𝒐𝒍 𝒈𝒍𝒖𝒄𝒐𝒔𝒆 ( ) 𝑩𝑼𝑵 ( ) 𝟐 𝑵𝒂 ( )+ 𝒅𝑳 + 𝒅𝑳 + 𝟗 𝑳 𝟏𝟖 𝟐. 𝟖 or  In the hypothetical case, the ff information were provided: o Renal function and organs producing hormone 𝒎𝒎𝒐𝒍 𝒎𝒎𝒐𝒍 𝒎𝒎𝒐𝒍 𝟐 𝑵𝒂 ( ) + 𝒈𝒍𝒖𝒄𝒐𝒔𝒆 ( ) + 𝑩𝑼𝑵 ( )+𝟗 significant in Na+ regulation is normal 𝑳 𝑳 𝑳 o Comorbidities are hypertension, hyperlipidemia and chronic depression ** 2 is multiplied to Na+ to consider the presence of chloride o Laboratory errors could be ruled out ** 9 is added to take into account the other osmotically active substances o That leaves us with potential drugs that could cause the condition What is important here is to identify the mechanisms of how that factor caused the decrease. Moreover, there is a need to rely on several clinical EVALUATE references. The given case depicts: TRUE OR FALSE SYNDROME OF INAPPROPRIATE AVP SECRETION AS A CAUSE 1. Antidiuretic hormone enhances water reabsorption in excess of solute from the collecting ducts of the kidney. TO HYPONATREMIA  Diagnosed when: RENAL OSMOLALITY > PLASMA 2. Renin secretion increases in response to a reduction in renal OSMOLALITY with normal renal, adrenal, and thyroid artery blood flow. function  How this condition would cause hyponatremia is shown below: 3. Aldosterone is secreted by the adrenal cortex to enhance sodium reabsorption. 4. Hypernatremia could result from increased water intake. 5. Sodium is the most abundant extracellular cation. © BANIÑA, NJ │ 3RD YEAR – 1ST SEM “Nothing worth having comes easy” 6 CLINICAL CHEMISTRY 2 (LEC) UNIT 2.1 — POTASSIUM INTAKE ENGAGE POTASSIUM INTAKE Identify which of the ff statements are “facts” about potassium.  Average dietary K+ intake: 2.4-4.4 g/d (60-120 mmol/d)  1. K+ burns with a bright yellow in a flame test. When in water, the flame body requirement for K+ takes on a lilac-colored hue.  K+ absorbed from the GIT is rapidly distributed, and a small 2. K+ vigorously reacts with water to form hydrogen gas. amount is taken up by cells 3. K+ has a low density for a metal. 4. K+ is the fifth most abundant element in the human body.  Normal intake, minimal need, and max tolerance for K+ is almost 5. Pure potassium metal will sink on water. the same as that for Na+ POTASSIUM HOMEOSTASIS POTASSIUM POTASSIUM HOMEOSTASIS FUNCTIONS  Extracellular K+ balance is controlled primarily by kidneys Include: o Also regulated by GIT to a lesser extent  Proper function of all cells, tissues, and organs in the human body  Cardiac, skeletal, and smooth muscle contraction A. POTASSIUM HOMEOSTASIS IN THE KIDNEYS o Important for normal digestive & muscular function POTASSIUM HOMEOSTASIS IN THE KIDNEYS  Homeostasis by maintaining H+ concentration (acid-base balance  electroneutrality)  Reabsorption: proximal tubules o Acidosis  ↑ H+ conc.  hyperkalemia  Secretion: distal tubules o Alkalosis  ↓ H+ conc.  hypokalemia  Excretion:  Neuromuscular excitability through the resting membrane o Urine  90% (5.0 mmol/L  ORAL DRUGS o Administered as K+ salts  Categorizes as due to: o DICOXINE  inhibits Na-K-ATPase pump o Decreased renal excretion  IV K+ THERAPY o Redistribution out of cells (cellular shift)  HIGH K+ DIET  CHRONIC ALCOHOL INTAKE o Increased intake  BLOOD PRODUCTS o Give rise to hyperkalemia esp. if using stored a. DECREASED RENAL EXCRETION RBCs that release K+ down its conc. gradient o Risk is reduced by: RENAL  The kidneys may not be able to excrete K+ load when  Using relatively fresh blood (106 /μL) o Use of ANGIOTENSIN CONVERTING o LEUKOCYTOSIS (WBC count: >105 /μL) ENZYME (ACE) INHIBITORS © BANIÑA, NJ │ 3RD YEAR – 1ST SEM “Nothing worth having comes easy” 8 CLINICAL CHEMISTRY 2 (LEC) o EXCESSIVE FIST CLENCHING b. REDISTRIBUTION INTO CELLS (CELLULAR SHIFTS)  Involves muscular activity  Mild muscular activity  ↓ K+ level by METABOLIC  ↓ H+ conc. in the plasma  H+ inside cells move out ALKALOSIS into the plasma  K+ move inside cells  0.3-1.2 mmol/L electrochemical neutrality  Excessive muscular activity  ↓ K+ level by 2-3 mmol/L INSULIN  When insulin is given in the treatment of diabetic o PROLONGED TOURNIQUET APPLICATION THERAPY ketoacidosis  hypokalemia  Causes hemoconcentration  May cause anoxia  releases smaller REFEEDING  Occurs when previously malnourished patients (px molecules such as K+ into the plasma with anorexia nervosa, or alcohol dependents) are o Hemolysis fed with high CHO loads o Results to a rapid fall in PO43-, Mg, and K+, o Delayed sample analysis / unprocessed sample as mediated by a sudden increase in insulin as it moves glucose into cells SIGNS AND SYMPTOMS OF HYPERKALEMIA TREATMENT  MEGALOBLASTIC ANEMIA High intracellular K+ conc. may produce the ff symptoms: OF ANEMIA o Folic acid or Vitamin B12 often produce hypokalemia in the 1 st days of treatment  Mental confusion  This is due to the uptake of K+ by  Weakness / fatigue the new blood cells  IRON DEFICIENCY ANEMIA  Tingling sensation in the muscles o Its treatment results in a much slower rate of  FLACCID PARALYSIS of the extremities  due to lesser new blood cell production  thus, rarely muscle contraction implicated  Weakness of the respiratory muscles  BRADYCARDIA (decreased heart rate) and conduction defects HYPOKALE-  An autosomal dominant trait that can be precipitated o Evident on ECG/EKG MIC PERIODIC by rest after exercise PARALYSIS  Can also be acquired as a result of THYROTOXICOSIS  PROLONGED AND SEVERE HYPERKALEMIA (>7.0 o Due to increased sensitivity to mmol/L) catecholamines (e.g., epinephrine)  o Considered life-threatening promotes entry of K+ into cells o Must be dealt with as an absolute priority because peripheral vascular collapse and cardiac arrest OTHER  ACUTE LEUKEMIA CONDITIONS o WBCs take up K+  ↓ plasma K+ may be the 1st manifestation  HYPOTHERMIA  cells take up K+ c. INCREASED LOSSES/DECREASED INTAKE Conditions that cause increased K+ loss is referred to as TRUE POTASSIUM DEFICIT GIT LOSS  Common causes include VOMITING and DIARRHEA  CHOLERA o Assoc. with massive fluid loss from the GUT o >100 mmol/d is lost compared with 5 mmol normally  CHRONIC LAXATIVE ABUSE  MALABSORPTION SYNDROME URINARY DIURETICS LOSS  E.g., LOOP DIURETICS and THIAZIDE o Loop diuretics  interfere with K+ reabsorption in the loop of Henle  Mechanism include: o ↑ flow of H2O and Na+ to the site of distal K+ secretion o Secondary hyperaldosteronism induced by the loss of volume MINERALOCORTICOID EXCESS  Aldosterone increases Na+ reabsorption in the renal tubules at the expense of K+ and H+ o Means that in the presence of excess B. HYPOKALEMIA aldosterone, K+ excretion is increased HYPOKALEMIA HYPOMAGNESEMIA  Any cause of hypomagnesemia may lead to  Plasma K+ conc. 7.9) TEMPERATURE  Ideally, whole-blood specimens should be PHYSIOLOGIC VARIATION IN Ca2+ PLASMA CONC. AND analyzed within 15 to 30 minutes of sampling STABILITY o Although, free Ca2+ is reported to be stable PHYSIOLOGIC VARIATION IN PLASMA CALCIUM CONCENTRATION in whole-blood specimens for at least 1 hour at room temperature and for 4 hours at  Ca2+ conc. has been reported to vary with the ff: 4°C o Age  It has been reported that free Ca2+ was stable for at o Gender least 7 hours at room temperature in an evacuated blood collection tube o Season o During pregnancy FOR DELAYED ANALYSIS: o During a 24-hour period  Specimens can be collected in an ice-water slurry to o Posture minimize metabolism o Hyperventilation  Serum may be the optimal sample type because of o Exercise elimination of the anticoagulant and reduction in the occurrence of microclots o Nocturnal variation o Serum specimens can be collected in o Food ingestion evacuated gel tubes o These tubes should be filled completely and centrifuged to form an effective barrier AGE  Total and free Ca2+ have been reported to decline between the serum and the clot with its discreetly and to remain unchanged in the elderly cellular elements o Once centrifuged, specimens are stable for hours at 25°C and for days at 4°C, provided DURING  ↓ Total Ca2+; free Ca2+ unchanged the tube remains sealed PREGNANCY,  The fetal circulation is relatively hypercalcemic, as evidenced by higher total and free Ca2+ in cord blood than in maternal plasma CATIONS AND  Modern electrodes have high selectivity for calcium  Ca2+ concs. decline after birth in healthy term ANIONS over Na+, K+, Mg2+, H+, and Li+ ions neonates during the first few days, but soon increase o At normal concentrations, these cations have to concs. slightly greater than those observed in little effect on the accuracy of free Ca2+ adults measurements o However, high concentrations of Mg2+ and Li+ may influence the apparent POSTURE  Changes in posture cause fluid shifts within 10 concentration of free Ca2+ minutes  alter the concs. of cells and large  Many physiologic anions including protein, molecules, including albumin and total Ca2+ (as part phosphate, citrate, lactate, sulfate, and oxalate form of it is protein bound), in the vascular compartment complexes with calcium ions  Standing o Although these anions reduce the o Decreases intravascular water concentration of free Ca2+ by complex o Increases the total Ca2+ conc. by 0.2 to 0.8 formation, they do not directly interfere mg/dL (0.05–0.2 mmol/L) with measurement of the Ca2+ that is free  Recumbency/lying down o Has smaller effect for free Ca2+ © BANIÑA, NJ │ 3RD YEAR – 1ST SEM “Nothing worth having comes easy” 19 CLINICAL CHEMISTRY 2 (LEC) o One partial explanation (along with UNIT 3.2 — MAGNESIUM hypoalbuminemia) for the mild hypocalcemia observed in many hospitalized CALCIUM AND MAGNESIUM patients may be the hemodilution associated with recumbency Calcium and magnesium are 2 of the essential minerals of the bone with  This effect can be observed during a recommended calcium-magnesium ratio of 2:1. 24-hour sampling of normal individuals  If the human body adult contains about 1200 grams of Ca2+, the total body  Prolonged immobilization and Mg content is also about 25 g, predominantly found in bone or skeleton. bed rest  increase bone resorption  ↑ total and free Ca2+ MAGNESIUM HYPERVEN-  ↓ Free Ca2+ conc. Attributed to the possible MAGNESIUM TILATION changes in plasma pH  4TH MOST ABUNDANT CATION IN THE BODY  ↓ pH  ↑ free Ca2+  2ND MOST PREVALENT INTRACELLULAR CATION EXERCISE  ↑ Free Ca2+ conc.  ↑ pH  ↓ free Ca2+ o Comes next to K+ in terms of intracellular dominance o Also found extracellularly NOCTURNAL  Both plasma free Ca2+ con. and Ca2+ excretion are  Its conc. in cells (nucleus, mitochondria, and ER) varies from 2.4- VARIATION decreased during the night 7.3 mg/dL (1-3 mmol/L)  Generally, the ↑ the metabolic activity of a cell, the ↑ is its Mg FOOD  Has been reported to have various effects, but usually INGESTION causes a mild ↑ in plasma Ca2+ content  Ingestion of Ca2+ salts  ↑ plasma Ca2+ DISTRIBUTION RI FOR TOTAL AND FREE Ca2+ IN SERUM AND PLASMA TISSUE DISTRIBUTION OF MAGNESIUM REFERENCE INTERVALS (based from the discussion)  Bone: 55%  Muscle and other soft tissue: 43% TOTAL Ca2+  Child (300 enzymes, colorimetric measurement of calcium in blood. including those important in glycolysis  The breakdown of glucose  releasing energy and pyruvic acid o Mg is an allosteric activator to many enzyme systems  Neurotransmission o Mg competitively inhibits the entry of Ca2+ into presynaptic nerve terminals  This influences neurotransmitter release at neuromuscular junctions  neuromuscular excitability o ↓ plasma Mg conc.  ↑ neuromuscular excitability  Muscle relaxation © BANIÑA, NJ │ 3RD YEAR – 1ST SEM “Nothing worth having comes easy” 20 CLINICAL CHEMISTRY 2 (LEC)  Other functions include: A. HYPERMAGNESEMIA o Transcellular ion transport HYPERMAGNESEMIA o Synthesis of CHO, CHONS, lipids, and nucleic acids  ↑ plasma Mg  Nutritionists suggest to increase intake of  Aka MAGNESIUM INTOXICATION Mg over Ca2+  ↑ levels of Mg or Mg intoxication is not a frequently encountered o Release of and response to hormones clinical problem  Symptomatic hypermagnesemia o Always caused by excessive intake resulting from the ff:  Antacids  Enemas  Parenteral fluids containing Mg  Conditions resulting to ↑ plasma Mg levels include: o Hypothyroidism o Dehydration o Renal failure CONDITIONS RESULTING TO HYPERMAGNESEMIA HYPOTHYRO- DEFICIENCY OF THYROXINE DISM  ↓ thyroxine  ↓ renal excretion of Mg  accumulation of Mg  ↑ Mg plasma conc. MAGNESIUM-RICH FOODS DEHYDRATION  Can cause PSEUDOHYPERMAGNESEMIA Spinach, cooked Swiss chard, cooked o Can be corrected with rehydration Dark chocolate Pumpkin seeds, dried Almonds Black beans Avocados Figs, dried RENAL  Hypermagnesemia is common in px with: Yogurt or kefir Bananas FAILURE o END STAGE RENAL DISEASE o UNDERGOING DIALYSIS o ACUTE RENAL FAILURE REGULATION OF MAGNESIUM o CHRONIC RENAL FAILURE  Serum Mg conc. is usually REGULATION OF MAGNESIUM maintained until the GFR falls below 30 mL/min  KIDNEYS control the overall regulation of body Mg  Severe hypermagnesemia may result, esp. if Mg-containing o Deficiency state  kidneys reabsorb Mg medications are used o Overload state  kidneys readily excrete excess Mg  Renal failure  ↓ reabsorption of Mg in the kidneys  LOOP OF HENLE o Major renal regulatory site of Mg o It is where 50-70% of filtered Mg is reabsorbed SIGNS AND SYMPTOMS OF HYPERMAGNESEMIA  PROXIMAL CONVOLUTED TUBULES (PCT) Include: o Passively reabsorb 25-30% of Mg  SMALL INTESTINES  Symptoms of hypermagnesemia typically do o About 20-65% of dietary Mg is absorbed not occur until the serum level exceeds 27  e.g., Mg from raw nuts, dry cereal, mg/dL (1.5 mmol/L) vegetables, meats, fruits  Depression of the neuromuscular  Parathyroid hormone (PTH), aldosterone, and thyroxine system regulates the absorption, reabsorption, and excretion of Mg o The most common manifestation of Mg intoxication  Deep tendon reflexes PTH ALDOSTERONE & THYROXINE o May disappear when plasma Mg conc. is >5-9 mg/dL Increases renal REABSORPTION Have the opposite effect of PTH in the  Depressed respiration and apnea (shortness of breath) of Mg kidney o May occur at concs. >10-12 g/dL Enhances the ABSORPTION of Mg Increases the renal EXCRETION of  Cutaneous Flushing / Facial Flushing (refer to image above) in the intestine Mg o A subjective sensation of warmth that is accompanied by reddening of the skin anywhere on the body Mg INTAKE, REABSORPTION, AND EXCRETION o Favors the face, neck, and upper torso o Commonly observed in menopausal women Mnemonics: Do Not F*** Up  Other symptoms:  Daily dietary intake: 360 mg o Hypotension  Daily net uptake: 100 mg o BRADYCARDIA  Daily fecal output: 260 mg o SOMNOLENCE  Daily urinary output: 100 mg o Nausea o Vomiting CLINICAL SIGNIFICANCE o Cardiac arrest o Coma Include the ff diseases/conditions:  Hypermagnesemia TREATMENT FOR HYPERMAGNESEMIA  Hypomagnesemia Include:  Discontinuation of Mg source  HEMODIALYSIS  for px with renal failure  DIURETIC & IV FLUID  for those w/ normal renal function © BANIÑA, NJ │ 3RD YEAR – 1ST SEM “Nothing worth having comes easy” 21 CLINICAL CHEMISTRY 2 (LEC) B. HYPOMAGNESEMIA CELLULAR SHIFT (PLASMA INTO THE CELL) HYPOMAGNESEMIA REFEEDING  Previously and fully starved patients who are SYNDROME suddenly fed with a full meal  ↓ Mg levels  ↓ serum Mg levels  Most frequently observed in hospitalized individuals in ICU HUNGRY BONE  Seen in the ff cases:  MODERATE TO SEVERE MAGNESIUM DEFICIENCY SYNDROME o After parathyroidectomy o Usually due to loss of Mg from GIT or kidneys o Px with diffuse osteoblastic metastases o Can be seen among px receiving diuretic therapy  Mg shifts intracellularly, particularly in the bone cells (i.e., ↑ uptake of Mg into the bones) GIT LOSS VOMITING AND  May deplete body stores of Mg ACUTE  Hypomagnesemia is seen in 20% of px with acute NASOGASTRIC  More commonly assoc. with losses in the lower PANCREATITIS pancreatitis SUCTION intestine  This is probably due to deposition of Mg in areas of necrosis OTHER  Malabsorption syndromes CONDITIONS  Surgical procedures among neonates CATECHOLAMINES  ↑ Catecholamine concs.  intracellular shift  Diarrhea  Promotes cellular entry of Mg into the cell  May be one of the factors contributing to RENAL LOSS hypomagnesemia which is seen in the ff cases: o During or after cardiac surgery HYPERTHY-  Thyroid gland disorder characterized by ↑ o Congestive heart failure ROIDISM thyroxine levels  ↑ renal excretion of Mg  May also cause intracellular shift of Mg OTHER  Treatment of metabolic acidosis CONDITIONS HYPOCALCEMIA  May decrease Mg levels due to impaired AND ↑ Na+ secretion of PTH EXCRETION OR  Although the acute effect of extracellular Mg on PARENTERAL PTH secretion is similar to that of Ca2+, in Mg COMPLICATIONS OF HYPOMAGNESEMIA FLUID THERAPY deficiency, there is impaired PTH release