Fluid and Electrolytes Balance Biochemistry Chapter 2 PDF

Fluid and Electrolytes Balance Dr. Mariam Alameri  Learning objectives  Learn about Body fluid compartments.  Learn about The interpretation of laboratory results regarding electrolytes, Variation in laboratory results, and Reference intervals.  Learn about Body fluid compart...

Fluid and Electrolytes Balance Dr. Mariam Alameri  Learning objectives  Learn about Body fluid compartments.  Learn about The interpretation of laboratory results regarding electrolytes, Variation in laboratory results, and Reference intervals.  Learn about Body fluid compartments, Osmolality, Water and sodium balance.  Learn about Hyponatraemia and Na+ loss: Pathophysiology, Water retention, Assessment and management  Learn about Hypernatremia and Na+ gain, Water loss, Assessment and management  Learn about Hyperkalemia, K+ balance, Treatment, and Hypokalemia.  Clinical Cases on Fluid and electrolytes balance Body fluid compartments Water is the chief constituent of human body. Water is the chief solvent of body. Total body water (TBW) comprises 60% of body weight in normal adult. Total body water (TBW) is divided into two basic compartments :  Intracellular water: 65% of total body water.  Extracellular water: 35% of total body water includes: 1- 20% Plasma 2- 80% Interstitial fluid.  Blood is 55% plasma , while water in blood plasma accounts for about 90% of its volume.  Water functions and role in the body:  1) Component of all body tissues providing structure and form.  2) Solvent for nutrients and body wastes and chemical reactions.  3) Provides transport for nutrients and wastes via the blood and lymphatic system.  4) Essential for hydrolysis and thus metabolism.  5) Lubricant of joints and in digestion.  6) Helps regulate body temperature by evaporation of perspiration. Body Water Input and Output Body Water Input Bodycan gain water by Ingestion of liquids and moist foods (2300mL/day). Metabolic synthesis of water during cellular respiration (200mL/day) Body Water Output  Body losses water through:  Kidneys (1500mL/day)  Evaporation from Skin (600mL/day)  Exhalation from Lungs (300mL/day)  Feces (100mL/day) Body fluid balance  A healthy adult individual always try To maintain water balance by the homeostatic mechanisms. Since Water balance is vital for human body  A body is said to be in water balance When the amount of water intake in the body is equal to the amount of water output.  Any fluid loss, retention or redistribution consider a clinical problems  The management of these condition is often urgent and requires biochemical examination.  Both internal and external balance must be considered.  The internal balance is the normal distribution between different body compartments, while the external balance matches input with output. The body’s state of hydration  a) Over-hydration: when the fluid accumulates in body compartments (water intake > water loss)  b) Dehydration: when the fluid is lost from body compartments (water loss > water intake).  1- Loss of ICF → cellular dysfunction, lethargy, confusion and coma  2- Loss of ECF (bleeding) → collapse and shock Factors causes dehydration:  1-Low water intake  2- High water loss  3- Diuresis (D.M, D.I, renal failure (failure to reabsorb water producing highly diluted urine)  4- Diarrhea  5- Excessive sweating and evaporation (via skin)  6- Hemorrhage The volume of body fluid compartments of a 70-kg adult man equals: A. 60 L B. 54 L C. 42 L D. 35 L BODY ELECTROLYTES  Electrolytes are substance when dissolved in solution dissociates into ions, these ions are able to carry an electrical current. So, an Electrolyte is a substance which develops an electrical charge when dissolved in water. CATION - Positively charged Electrolyte. ANION - Negatively charged Electrolyte.  Water molecules completely surround these dissociated ions, this prevents union of Cations and Anions. Cont… Salts like NaCl and KCl in aqueous solutions gets dissociated to Charged ions Na+ and Cl- called as Electrolytes. The concentration of these Electrolytes is expressed as mEq/L. ELECTROLYTES IN BODY FLUID COMPARTMENTS INTRACELLULAR EXTRACELLULAR Electrolytes Electrolytes POTASSIUM SODIUM MAGNESIUM CHLORIDE PHOSPHOROUS BICARBONATE 18 To Maintain Electrical Neutrality In Each Fluid Compartments Number Cations =Number Anions ECF Cations ECF Anions Na+ ( 140 Cl (103 - mEq/L) mEq/L) K+ HCO3- Ca+ HPO4-- Mg + SO4 -- Total Cations Total Anions 155 mEq/L 155 mEq/L Predominant Cations and Anions in ECF: Na and Cl HCO3 + -& - respectively.  ICF Cations ICF Anions Na+ Cl- K+ (150 mEq/L) HCO3 - Ca+ HPO4- - (140 mEq/L) Mg + SO4 -- Total Cations Total Anions 195 mEq/L 195 mEq/L Thus, the predominant Cations and Anions of ICF: K and HPO4 + --& protein respectively. The predominant Cations and Anions of ICF: A. K+ and HPO4-- & protein, respectively. B. Na+ and Cl- & HCO3-respectively. C. Li+ and l- & protein, respectively. D. None Movement of Water and Electrolytes Important definitions Diffusion – movement of particles down a concentration gradient. It also describes the random movement of particles in all directions through a solution. Osmosis: movement of water across a membrane from a less concentrated solution to a more concentrated solution. It reflects diffusion of water across a selectively permeable membrane. Active transport: Movement of solutes across membranes; Requires transporters and expenditure of energy Movement of particles is up a concentration gradient. Concentration and osmolality  Concentration: is a ratio of two variables (solute/solvent).  A concentration can be changed because either or both variables have changed.  Semipermeable membrane allow solvent but not solutes movement.  The factor that influence the distribution of the fluid between ICF and ECF is osmolality.  Osmolality: measures the overall number of solute particles in a solution Osmolality and Osmolarity  Osmolarity and osmolality are units of solute concentration that are often used in reference to biochemistry and body fluids. Both Osmolarity and osmolality are defined in terms of osmoles.  The osmole is related to osmosis and is used in reference to a solution where osmotic pressure is important, such as blood and urine.  Osmolality: osmoles of solute / Kg solvent  Osmolarity: osmoles of solute / L solution  Osmolality is convenient to use because the amount of solvent remains constant, regardless of changes in temperature and pressure, in contrast, Osmolarity considers the colligative properties of a solution; i.e., properties affected by the number of particles in the solution. Those properties include osmotic pressure, boiling point elevation, freezing point depression… Thus, osmolality is more accurate than osmolarity.  Osmolality  The major solute in normal plasma are Na+, K+, glucose and urea.  Calculated osmolality (mmol/kg) = 2[Na+]+2[K+] + [glucose]+[urea].  Na+ is the highest ions concentration in the plasma, it is responsible for the plasma osmolality.  osmolality (mmol/kg) = 2[Na+], when serum urea and glucose are normal  Osmolal gap osmolal gap is the difference between the measured osmolality and the calculated osmolality osmolal gap = measured osmolality - calculated osmolality. A normal osmol gap is < 10 mOsm/kg  The osmolal gap indirectly indicates the presence of osmotically active substances other than Na+, urea, or glucose, such as ethanol, methanol, plasma protein or lipid concentration. Tonicity  Tonicity: is the capability of a solution to modify the volume of cells by altering their water content. The movement of water into a cell can lead to hypotonicity or hypertonicity when water moves out of the cell.  Tonicity related to the non-diffusible solute.  Osmolality related to the diffusible and non-diffusible solute.  non-diffusible solute (e.g. Na)  diffusible solute (urea) Colloid pressure  Oncotic pressure, or colloid osmotic pressure is the osmatic pressure exerted by plasma protein such as albumin across plasma membranes. https://quizizz.com/admin/quiz/6500ed0 9503c424270bdfac0?searchLocale=  Normal water balance  Body water and electrolytes it contains, are in a state of constant flux. We drink and eat, we pass urine and sweat during all this, it is important that we maintain a steady state.  Several important homeostatic mechanisms exist to prevent any changes in the body fluid.  Normal sodium balance  75% of total body Na+ is exchangeable and 25% is non- exchangeable which means it is incorporated into the tissues such as bones.  Most of the exchangeable Na+ is in ECF (Reference range: 135 – 145 mmol/L).  - Sodium intake: is variable ranged from 100 – 300 mmol/day.  - Sodium losses are variable. Most Na+ excretion is via kidneys, and some is lost in sweat and faeces.  Biochemical Factors Regulating Water And Electrolyte Balance 1. Neural Mechanism- Thirst Mechanism 2. Antidiuretic Hormone/Vasopressin 3. Renin Angiotensin System 4. Aldosterone 5. Atrial Natriuretic Peptide(ANP) 6. Kinins ( Increases Salt and Water excretion) 1.Neural Mechanism/Thirst Mechanism Regulate Low Body Water When the body water is lowered due to: No intake of fluids Body fluids lost through obligatory losses (Urine and Feces). This leads to decrease in volume of body fluids with respect to solutes and rise in osmotic pressure  The ECF volume decreases and becomes hypertonic. This tends to draw water from ICF causing cellular dehydration The cellular dehydration stimulates the thirst centre located in hypothalamus In response to the stimulus to thirst center dryness of mouth and Pharynx. Feeling of thirst makes drink water Water ingested orally quench the thirst to regulate the body water.  2.The regulation of blood osmolality by osmoreceptors and AVP (ADH)  Arginine vasopressin (AVP) (Anti-diuretic hormone (ADH) or vasopressin):  ↓ECF (↓B.P) → ↑ blood osmolality (↑ Na+ )→ hypothalamus senses blood osmolality → Posterior pituitary gland → ↑ ADH → ↑ water re-absorption + arterioles constriction → ↑ B.P.  ADH cause water retention by the kidney 3.The regulation of blood volume by RAAS 4. Aldosterone  5. Atrial natriuretic peptide (ANP):  ↑ ECF → Right atrium of the heart → ANP → ↑ Na+ excretion / ↓ angiotensin II → ↓ B.P.  6. Role of Kinins Kinins are proteins in the blood Kinins cause inflammation and affect blood pressure (especially lowers the blood pressure). Kinins increases Salt and Water excretion.  Hyponatremia  Reference range: 135 – 145 mmol/L.  Hyponatremia : serum sodium < 135 mmol/L.  Hyponatremia is the most common electrolyte disorder. ▪ Pathophysiology of hyponatremia: 1. Water retention (common): more water than normal is retained in the body compartment and dilutes the constituents of the ECF without a decrease in total body Na+ causing hyponatremia. 2. Sodium deficiency: when Na+ loss exceeds the water loss, hyponatremia may result. Initially Na+ loss is accompanied by water loss and serum so Na+ concentration remains normal. As Na+ loss proceeds, the reduction in ECF and blood volume stimulates ADH (non-osmotic control of ADH overrides the osmotic control) leading to water retention. Signs and symptoms of hyponatremia:  - Hyponatremia is asymptomatic if Na+ >125 mmol/L  - Hyponatremia is life-threatening when Na+ < 120 mmol/L  - Great risk when the decrease in sodium is very large or occurs rapidly (over hours)  - Symptoms resulting from brain over-hydration induced by hypo-osmolality, movement of water into brain:  1) Intracranial pressure  2) Headache and Malaise  3) Nausea and vomiting  4) Lethargy and loss of consciousness  5) Seizures and coma (< 110 mmol/L)  ▪ Laboratory assessment of hyponatremia: The laboratory assessment of hyponatremia consists of 3 steps: (O.V.U. system)  O= Osmolality assessment of plasma , V= Volume status assessment, U= Urinary sodium assessment a) Osmolality assessment of plasma Is the blood hypotonic, hypertonic or isotonic? 1) Hypertonic hyponatremia (> 295 mmol/kg)  Hyperglycaemia, mannitol therapy, or toxic alcoholism 2) Isotonic hyponatremia (280 - 295 mmol/kg)  Pseudo-hyponatremia from elevated lipids or protein (a low Na+ concentration is sometimes reported in patients with severe hyperproteinemia or hyperlipidemia.  These patients have in fact a normal Na+ concentration in their plasma water. However, the increased amounts of proteins or lipoproteins occupy a larger fraction of the plasma volume than usual, and the water occupies a smaller fraction. Normal Na concentration in plasma water while, hyponatremia in total + plasma volume  3) Hypotonic hyponatremia (< 280 mmol/kg) Water retention (common) or Sodium deficiency Further assessments are required (ECF volume and urinary Na+ concentration)  b) Volume status assessment  Is the patient’s ECF Hypervolemic, Hypovolemic, or Euvolemic?  c) Urinary sodium assessment  For hypotonic hyponatremia, Na+ concentration in urine must be assessed to determine renal or extra-renal causes Further assessment of hypotonic hyponatremia: assessment of hyponatremia:  Treatment of hyponatremia:  For treating hyponatremia, the underlying cause should be determined and treated, meanwhile, however, hyponatremia should be corrected using one of the following approaches according to blood volume status:  Hypovolaemic hyponatremia: sodium is depleted so give sodium (NaCl 0.9%)  Normovolaemic hyponatremia: water retention so restrict fluids.  Hypervolemic hyponatremia: excess of both total body sodium and water so give diuretics to induce natriuresis and restrict fluids. e.g., Oedema: is an accumulation of fluid in the interstitial compartment due to reduced circulating blood volume (e.g., CHF) or reduced blood osmolality (e.g., hypoalbuminemia).  Sever hyponatremia so more aggressive treatment (hypertonic saline) may be indicated if symptoms persist, or the sodium concentration is less than 110 mmol/L. Which one of the following choices will be used to treat Hypovolaemic hyponatremia  A. water retention so restrict fluids  B. sodium is depleted so give sodium (NaCl 0.9%)  C. Give diuretics  D. None of the above  Clinical case  Case1: A 64-year-old woman was admitted with anorexia, weight loss and anaemia. Carcinoma of the colon was diagnosed. She was normotensive and did not have oedema. The following biochemical results were obtained shortly after admission. Serum osmolality was measured as 247 mmol/kg. What is the diagnosis? What is the best management?  What is the diagnosis?  A: Euvolemic Hypotonic hyponatremia due to SIAD These urea and electrolytes are typical of dilutional hyponatraemia. Her normal blood pressure and serum urea and creatinine concentrations make sodium depletion unlikely as the mechanism of her hyponatraemia. The absence of oedema excludes a significant increase in her total body water, and the absence of dehydration symptoms excluded hypovolaemia. The presence of carcinoma suggests SIAD. What is the best management? B: Euvolemic Hypotonic hyponatremia: restrict fluids.  Hypernatremia  Hypernatremia is defined as serum Na+ concentration above the upper reference value (>145 mmol/L).  Mild hypernatremia could be up to 150 mmol/L,  Severe hypernatremia is between 150-170 mmol /L,  Gross hypernatremia is at or above 180 mmol/L.  Hypernatremia is less commonly seen in hospitalized patients than hyponatremia.  Pathophysiology of hypernatremia: 1. Pure water depletion (relatively frequent finding in elderly people, as a result of inadequate water intake) 2. Combined sodium and water depletion with water loss predominating 3. Sodium excess (salt poisoning): the least common cause; high intake of Na+ or Na+ retention Pathophysiology of hypernatremia  Patients often become hypernatremic because they are unable to complain of being thirsty. In comatose patient is a good example, patient will be unable to communicate his needs, yet insensible losses of water continue from lungs/skin and need to be replaced.  Laboratory assessment of hypernatremia:  1. Na+ < 150 mmol/L with signs of dehydration → Mild hypernatremia (ECF is reduced due to loss of both Na+ and water). But water loss is more  2. Na+ 150-170 mmol/L with signs of dehydration → severe hypernatremia (Pure water loss).  3. Na+ > 180 mmol/L with no signs of dehydration → Gross hypernatremia (Salt poisoning).  o Symptoms of hypernatremia:  Symptoms most commonly involve the CNS as a result of the hyperosmolar state. These symptoms include altered mental status, lethargy, irritability, seizures, muscle twitching, fever, nausea or vomiting, difficult respiration, and increased thirst.  Treatment of hypernatremia:  Treatment is directed at correction of the underlying condition that caused the water depletion or Na_ retention. 1- Patients with hypernatraemia due to pure water loss should be given water, this may be given orally, or intravenously as 5% dextrose. 2 - If there is clinical evidence of dehydration that indicate loss of sodium and water, then sodium and water should be administered together. 3- The sodium overload (Salt poisoning). can be treated with Diuretics and intravenously as 5% dextrose are given. Clinical cases Case 2: 76-year-old man with depression was admitted as an acute emergency. He was clinically dehydrated. His skin was lax and his lips and tongue were dry. His pulse was 104/min, and his blood pressure was 95/65 mmHg. The following biochemical results were obtained on admission: What is the diagnosis? What is the best management? What is the diagnosis? A: He has severe hypernatraemia and the following observations would indicate that the patient is primarily suffering from water depletion. A diagnosis of pure water depletion was therefore established on the basis of the history, clinical findings and biochemical features. His skin was lax and his lips and tongue were dry. His pulse was 104/min, and his blood pressure was 95/65 mmHg High level of urea and creatinine, indicating pre-renal Azotaemia. What is the best management? A: Patients with hypernatraemia due to pure water loss should be given water, this may be given orally, or intravenously as 5% dextrose. Potassium homoeostasis  Potassium is the main intracellular cation (98%). Only 2% of the total body K+ is in the ECF (interstitial and plasma). Reference range is 3.5 – 5 mmol/L.  Potassium is the main cation inside the cell. It is involved in the regulation of neuromuscular excitability, heart contraction and H+ concentration.  In fact, potassium concentration should be tightly regulated in order to be maintained in the normal range. Both hyper- and hypo- kalemia can affect cardiac contractility and, in severe cases, may result in cardiac arrest.  Renal Regulation of potassium:  The kidneys are important in the regulation of K+ balance. Initially, the proximal tubules reabsorb nearly all the K+.  Then, under the influence of aldosterone, additional K+ is secreted into the urine in exchange for Na+ in both the distal tubules and the collecting ducts.  Thus, the distal nephron is the principal determinant of urinary K+ excretion.  Potassium balance  Most individuals consume far more K+ than needed; the excess is excreted in the urine under normal renal functions. K+ uptake from the ECF into the cells is important in normalizing an acute rise in plasma K+ concentration due to an increased K+ intake. Excess plasma K+ rapidly enters the cells to normalize plasma K+, the cellular K+ gradually returns to the plasma, to be removed by urinary excretion.  Hyperkalemia  Hyperkalemia is increased serum K+ level > 5 mmol/L. (Life-threatening if K+ > 7 mmol/L). It is the commonest and most serious electrolyte emergency.  Hyperkalemia causes cardiac arrest and muscle weakness that may be preceded by paraesthesia  Pseudu-hyperkalemia Due to hemolysis of RBCs ▪ Pathophysiology of hyperkalemia:  A) Increased K+ intake  1) Many oral drugs are administered as K + salts  2) IV infusion of K+ in treatment of hypokalemia (IV K+ should not be given faster than 20 mmol/hour)  3) Blood products transfusion especially with stored RBCs (due to the leakage of K+ from cells down its concentration gradient). this can be reduced by using fresh blood products less than 5 days B) Redistribution out of cells  1) Insulin deficiency: DM type 1 and 2  2) cathecholamines, such as epinephrine (β2- stimulator), promote cellular entry of K+, whereas propranolol (β-blocker) impairs cellular entry of K+.  3) K+ released from damaged cells: rapid turnover of cancer cells or break down of skeletal muscles (rhabdomyolysis).  4) K+ loss frequently occurs whenever the Na+/ K+ ATPase pump is inhibited by conditions such as digoxin overdose.  (5) Exercise : K+ is released from cells during exercise, which may increase plasma K+. These changes are usually reversed after several minutes of rest. 6) Plasma H+ concentration (Blood acidity):  Alkalosis – induced hypokalemia : As the concentration of hydrogen ions decreases, so potassium ions move inside cells in order to maintain electrochemical neutrality.  In metabolic acidosis – induced hyperkalemia: excess H+ moves intracellularly to be buffered → K+ moves from ICF to ECF to maintain electroneutrality → ↑plasma K+ (Hyperkalemia) [K+] increases by 0.2–1.7 mmol/L for each 0.1-unit reduction of pH. Effect of metabolic acidosis on serum K+ C) Decreased renal K+ excretion 1) Renal failure as GFR is very low. 2) Hypoaldosteronism: aldosterone stimulates Na+ reabsorption at expense of K + and H+. a. Deficiency: Addison’s syndrome b. Antagonism: ACE inhibitors c. Resistance: Angiotensin receptor blockers (ARBs)  The most common underlying causes are renal insufficiency, diabetes mellitus, or metabolic acidosis.  Various drugs may cause hyperkalemia, especially in patients with either renal insufficiency or diabetes mellitus. These drugs include:  captopril (ACEI),  nonsteroidal anti-inflammatory agents (NSAIDS) (inhibit aldosterone),  spironolactone (K+ - sparing diuretic),  digoxin (inhibits Na+/K+ pump),  cyclosporine (inhibits renal response to aldosterone),  and heparin therapy (inhibits aldosterone secretion). Symptoms of hyperkalemia.  Muscleweakness, tingling, numbness, and mental confusion by altering neuromuscular conduction.  Hyperkalemia disturbs cardiac conduction, which can lead to cardiac arrhythmias and possible cardiac arrest. Treatment of hyperkalemia  IV insulin + glucose (for severe cases)  IV Ca2+ gluconate (counteract K+ effect on nerve and muscle cells)  K+ binders: such as sodium polystyrene sulfonate (Kayexalate) enemas, which binds to K+ secreted in the colon. (Oral powder or rectal enema)  Loop diuretics: K+ may be quickly removed from the body by use of loop diuretics, if renal function is adequate.  Hemodialysis: can be used if other measures fail.  Patients treated with these agents must be monitored carefully to prevent hypokalemia as K+ moves back into cells or is removed from the body. Hypokalemia  Hypokalemia is decreased serum K+ level < 3.5 mmol/L. Hypokalemia caused by: a) Reduced K+ intake (rarely in severely hypocaloric diets in rapid weight loss program). b) Redistribution inside cells: 1) Metabolic alkalosis 2) Treatment with insulin 3) Refeeding syndrome (high CHO diets → insulin) 4) Treatment of anemia (folic and B12 for megaloblastic) 5) β-2 agonists (salbutamol for asthma) c) Increased loss: 1) From GIT (vomiting and diarrhea) e.g: cholera 2) Urinary loss: a. Diuretics: both loop and thiazide due to secondary hyperaldosteronism b. Hyperaldosteronism (Conn’s syndrome) c. Cushing’s syndrome  Symptoms of hypokalemia:  Symptoms of hypokalemia include weakness, hyporeflexia, constipation, tachycardia and in severe cases, paralysis and cardiac arrest. Symptoms often become apparent as plasma K+ decreases below 3 mmol/L. Treatment of hypokalemia:  Depends on the severity of hypokalemia. May involve:  Intravenous administration (I.V): the rate of i.v administration should be carefully monitored since giving K as a high rate can result in cardiac arrest. Should not exceed 40 mEq/hr.  Potassium substitutes (KCl).  Diet: potassium in food is ubiquitous. Rich dietary sources of potassium include fruits (especially dried fruits), vegetables IV Fluid therapy  Colloids and Crystalloids Intravenous fluids may be divided into  Crystalloid solutions - clear fluids made up of water and electrolyte solutions; Will cross a semi-permeable membrane e.g Normal, hypo and hypertonic saline solutions; Dextrose solutions; Ringer’s lactate and Hartmann’s solution (compound sodium lactate (CSL).  Colloid solutions – Gelatinous solutions containing particles suspended in solution. These particles are largely unable to cross a semi-permeable membrane. e.g. Albumin, Dextrans, Hydroxyethyl starch [HES]; Plasma…  IV Fluid therapy  a) Plasma, whole blood, or plasma expanders: Replace deficiency in the vascular compartment only. Because these solutions contain colloids particles that cannot pass through semipermeable membrane.  b) Isotonic saline (0.9 % NaCl) Replace deficiency in the ECF (vascular and ISF) they contain crystalloid particles that can pass through semipermeable membrane.  c) 5% dextrose (H2O): If pure H2O were infused, it would hemolyze RBCS. Instead, it should be given as 5% dextrose (isotonic). The glucose is rapidly metabolized the H2O that remains is distributed through all body compartments both ECF and ICF. Clinical cases…H.W  Case 1: A 42-year-old man was admitted with a 2-day history of severe diarrhoea with some nausea and vomiting. During this period his only intake was water. He was weak, unable to stand and when recumbent his pulse was 104/minute and blood pressure was 100/55 mmHg. On admission, his biochemistry results were:  What is the diagnosis?  What is the most appropriate treatment for this patient? Case 2  Patient R is a man, 56 years of age, with diabetes and hypertension. He is currently being treated with metformin 1 g twice per day, lisinopril 40 mg/day, and amlodipine 10 mg/day. His blood pressure is 146/83 mm Hg, and lab work reveals the following abnormalities: BUN 83 mg/dL, serum creatinine 4.1 mg/dL, and potassium 7.3 mEq/L. He is rushed urgently via emergency medical services to the local hospital, where an ECG is obtained immediately. Blood gases are sent to rule out lactic acidosis due to use of metformin in acute renal failure. The ECG shows widening of the QRS wave, and Patient R is showing signs of muscle weakness.  What is the diagnosis?  What is the most appropriate treatment for this patient?