Essentials of Pathophysiology CHAPTER 8 DISORDERS OF FLUID, ELECTROLYTE, AND ACID-BASE BALANCE PRE LECTURE QUIZ (TRUE/FALSE) F The extracellular compartment contains approximately two thirds of the body water in healthy adults, and is the larger of the two compartments. F Potassium is the most abundant cation in the body. F Edema of the brain, larynx, or lungs is not an acute, life-threatening condition. T Polydipsia is a term that means “excessive thirst.” F Decreased vascular volume would yield manifestations such as full and bounding pulses, venous distention, and signs and symptoms of pulmonary edema, such as shortness of breath, crackles, dyspnea, and cough. PRE LECTURE QUIZ ADH Diabetes insipidus is a condition that is caused by a deficiency or a decreased response to __________, also known as vasopressin. The most serious side effect of hyperkalemia is on ______________ function. Serum _______________ is directly or indirectly regulated by parathyroid hormone (PTH) and vitamin D. Respiratory acidosis is characterized by a decrease in __________, reflecting a decrease in ventilation and an increase in PCO2. Vomiting, removal of gastric secretions through the use of nasogastric suction, and low potassium levels resulting from diuretic therapy are the most common causes of _________________ alkalosis in hospitalized patients. Calcium Cardiac Metabolic pH FLUID DISTRIBUTION Intracellular compartment Extracellular compartment Interstitial spaces Plasma (vascular) compartment Transcellular compartment DISTRIBUTION OF WATER •Intracellular •Extracellular •Interstitial •Plasma •3rd Space SCENARIO An athlete ran a marathon even though he felt ill… After the race he collapsed. He was pale with a low blood pressure and sunken eyes. One knee and ankle were badly swollen, and his abdomen was distended with fluid. The doctor diagnosed appendicitis and dehydration. Question: What has happened to his: Blood osmolarity? Cell size? Transcellular fluid volume? Vascular compartment volume? Forces Moving Fluid In and Out of Capillaries and Cells OSMOSIS: WHICH WAY WILL WATER MOVE? Blood: (ECF) Few solutes Lots of water Cell: (ICF) Many solutes Less water Water Follows Solutes FORCES MOVING FLUID IN AND OUT OF CAPILLARIES Hydrostatic pressure Pressure created by the Heart i.e. Blood Presssure Forces water out of capillaries FORCES MOVING FLUID IN AND OUT OF CAPILLARIES Hydrostatic pressure generated by the heart Greatly reduced Hydrostatic pressure due to capillary resistance QUESTION What forces work to keep blood in the capillary? a. Capillary colloid osmotic pressure (COP) & tissue COP b. Capillary hydrostatic pressure & tissue COP c. Capillary hydrostatic pressure & tissue hydrostatic pressure d. Capillary COP & tissue hydrostatic pressure ANSWER Capillary COP & tissue hydrostatic pressure Hydrostatic pressure can be thought of as “pushing pressure,” and osmotic pressure can be thought of as “pulling” pressure. Pressure in the capillary that pulled/kept fluid in (capillary COP) and pressure pushing fluid out of the tissue (tissue hydrostatic pressure) would result in more fluid in the capillary. d. SODIUM Normal level is 135–145 mEq/L Regulates extracellular fluid volume and osmolarity Question: Why would “retaining sodium” cause high blood pressure? SCENARIO It’s a very hot day and you fall down the stairs on the way to see the doctor about your hepatitis and renal disease Explain why you have edema in your sprained ankle and foot CONTROLLING BLOOD OSMOLARITY High osmolarity causes: (Hypothalamic detection) Thirst increased water intake ADH release water reabsorbed from urine Low osmolarity causes: Lack of thirst decreased water intake Decreased ADH release water lost in the urine Negative _________________ Feedback QUESTION True or False: Increased levels of ADH decrease urine output. ANSWER True ADH prevents diuresis by causing more water to be absorbed in the kidney tubules. If more water is absorbed, there is less water left to eliminate as waste, decreasing urine output. DEHYDRATION DUE TO HYPODIPSIA A common problem in elderly people Scenario: Dr. Bob thinks it could be treated with ADH given in a nasal spray Dr. Bill thinks renin injections would be better Question: What is your evaluation of these two theories? ADH IMBALANCES Diabetes insipidus (DI) Neurogenic Nephrogenic Syndrome of inappropriate ADH (SIADH) Which will cause hyponatremia? SODIUM IMBALANCES Hyponatremia (<135 mEq/L) Hypertonic Hypotonic (dilutional) Hypernatremia (>145 mEq/L) Water deficit Na+ administration SCENARIO A man with hypernatremia was severely confused. Question: The doctor said this was due to a change in the size of his brain cells. Why would this happen? A medical student suggested giving him a hypotonic IV. Why? The doctor said that might worsen the change in his brain cell size, and that his blood osmolarity should be corrected very slowly. Why? POTASSIUM Normal level is 3.5–5.0 mEq/L Maintains intracellular osmolarity Controls cell resting potential Needed for Na+/K+ pump Exchanged for H+ to buffer changes in blood pH WHAT WILL HAPPEN TO BLOOD K+ LEVELS WHEN THE CLIENT HAS: Hyperaldosteronism? Alkalosis? An injection of epinephrine? Convulsions? Loop diuretics? THE BASICS OF CELL FIRING Cells begin with a negative charge— resting membrane potential Stimulus causes some Na+ channels to open Na+ diffuses in, making the cell less negative, i.e. more positive Threshold potential Resting membrane potential stimulus THE BASICS OF CELL FIRING (CONT.) At threshold potential, more Na+ channels open Na+ rushes in, making the cell positive: depolarization Action potential: the cell responds (e.g., by contracting) Action potential Threshold potential Resting membrane potential stimulus THE BASICS OF CELL FIRING (CONT.) K+ channels open K+ diffuses out, making the cell negative again: repolarization Na+/K+ ATPase removes the Na+ from the cell and pumps the K+ back in Action potential Threshold potential Resting membrane potential stimulus BLOOD K+ LEVELS CONTROL RESTING POTENTIAL Hyperkalemia raises resting potential toward threshold Cells fire more easily Increased K+ can move resting potential to threshold, Na+ gates open and won’t close Threshold potential Hyperkalemia Normal resting membrane potential BLOOD K+ LEVELS CONTROL RESTING POTENTIAL (CONT.) Hypokalemia lowers resting potential away from threshold Cells fire less easily Threshold potential Normal resting membrane potential Hypokalemia QUESTION What effect does a potassium level of 7.5 mEq/L have on resting membrane potential (RMP)? a. RMP becomes less negative, and it takes a greater stimulus in order for cells to fire. b. RMP becomes less negative, and it takes less of a stimulus in order for cells to fire. c. RMP becomes more negative, and it takes a greater stimulus in order for cells to fire. d. RMP becomes more negative, and it takes less of a stimulus in order for cells to fire. ANSWER b. RMP becomes less negative, and it takes less of a stimulus in order for cells to fire. A potassium level of 7.5 mEq/L is considered hyperkalemic. In hyperkalemia, RMP is moved closer to the threshold (it becomes less negative). Because RMP is nearer to the threshold, a weaker stimulus will cause the cell to fire (a lesser distance must be overcome). CALCIUM Normal level is 8.5–10.5 mg/dL Extracellular: blocks Na+ gates in nerve and muscle cells Clotting Leaks into cardiac muscle, causing it to fire Intracellular: needed for all muscle contraction Acts as second messenger in many hormone and neurotransmitter pathways Calcium Regulation Blood Ca2+ can be increased by: 1. Increased intestinal absorption 2. Release from bones CALCIUM REGULATION Blood Ca2+ can be increased by: 1. Increased intestinal absorption 2. Release from bones SCENARIO: A man with metastatic cancer complains of bone pain and sudden weakness. Question: Why did the doctor measure: PTH? Calcium levels? Vitamin D levels? MAGNESIUM Normal level is 1.8–2.7 mg/dL Cofactor in enzymatic reactions Involving ATP DNA replication mRNA production Binds to Ca2+ receptors Can block Ca2+ channels EXTRACELLULAR CALCIUM CONTROLS NERVE FIRING Hypercalcemia Blocks more Na+ gates Nerves are less able to fire Hypocalcemia Blocks fewer Na+ gates Nerves fire more easily Which would cause Trousseau’s & Chvostek’s sign? Hypocalcemia because they indicate easy nerve firing CHVOSTEK’S SIGN &TROUSSEAU’S SIGN CHVOSTEK’S SIGN Elicitation: Tapping on the face at a point just anterior to the ear and just below the zygomatic bone Postitive response: Twitching of the ipsilateral facial muscles, suggestive of neuromuscular excitability caused by hypocalcemia TROUSSEAU’S SIGN Elicitation: Inflating a sphygmomanometer cuff above systolic blood pressure for several minutes Postitive response: Muscular contraction including flexion of the wrist and metacarpophalangeal joints, hyperextension of the fingers, and flexion of the thumb on the palm, suggestive of neuromuscular excitability caused by hypocalcemia QUESTION True or False: Both hyperkalemia and hypercalcemia cause cells to fire more easily. ANSWER False Recall that hyperkalemia cause cells to fire more easily by moving RMP closer to the threshold. Hypercalcemia, on the other hand, blocks more sodium gates. If less sodium enters the cell, it cannot depolarize as quickly (it is less likely to fire). Hypocalcemia blocks fewer sodium gates– cells depolarize more quickly (they are more likely to fire). Balance between blood pH, HCO3= and H2CO3 Normal Balance Metabolic Acidosis Respiratory Alkalosis Important Relationships Insert fig. 6-16 H2CO3 = .03 * PaCO2 ACID (H+) Normal value: pH = 7.35–7.45 Blocks Na+ gates Controls respiratory rate Individual acids have different functions: Byproducts of energy metabolism (carbonic acid, lactic acid) Digestion (hydrochloric acid) “Food” for brain (ketoacids) RESPIRATORY OR VOLATILE ACID CO2 + H2O H2CO3 (carbonic acid) H2CO3 H+ + HCO3- (bicarbonate ion) An increase in CO2 will cause Increases in CO2 (increased PCO2) Increases in H+ (lower pH) Increases in bicarbonate ion RESPIRATORY ACIDOSIS AND ALKALOSIS CO2 + H2O H2CO3 H+ + HCO3- (carbonic acid) (bicarbonate ion) Respiratory acidosis Respiratory alkalosis Increased PCO2 Decreased PCO2 Increased carbonic acid Decreased carbonic acid Increased H+ = low pH (<7.35) Decreased H+ = high pH (>7.45) Increased bicarbonate Decreased bicarbonate Respiratory distress may be an attempt to compensate for low serum pH QUESTION Tell whether the following statement is true or false: Serum levels of pH and CO2 levels are directly proportional. ANSWER False As blood levels of CO2 increase, pH becomes more acidic (decreases). RESPIRATION AND BUFFERS ADJUST BLOOD PH Scenario: A woman was given an acidic IV. Soon she began to breathe more heavily. Why? When her blood was tested, it had: Slightly lowered pH Low bicarbonate Low PCO2 Slightly increased K+ Her urine pH was slightly lowered Why? BUFFER SYSTEMS METABOLIC ACID IMBALANCES Metabolic acidosis Increased levels of ketoacids, lactic acid, etc. Decreased bicarbonate levels Metabolic alkalosis Decreased H+ levels Increased bicarbonate levels METABOLIC ACIDOSIS AND ALKALOSIS Increased metabolic acids raise H+ levels Some H+ combines with bicarbonate, decreasing it Breathing adjusts CO2 levels to bring pH back to normal Metabolic acidosis Metabolic alkalosis Increased H+ = low pH (<7.35) Decreased H+ = high pH (>7.45) Decreased bicarbonate Increased bicarbonate Heavier breathing causes Lighter breathing causes decreased PCO2 increased PCO2