Chapter 26: Acid- Base

Question 1

Body Water Content:

Answer 1

o Infants: 73% or more water (low body fat, low bone mass).
o Adult males: ~60% water.
o Adult females: ~50% water (higher fat content, less skeletal muscle mass).
o Water content declines to ~45% in old age.

Question 2

Fluid Compartments:

Answer 2

o Total body water = 40 L (app 11 gal).
o 1) Intracellular fluid (ICF) fluid compartment = 2/3, or 25 L in cells = liquid found in cells.
o 2) Extracellular fluid (ECF) fluid compartment = 1/3,or 15 L.
o Plasma = 3 L.
o Interstitial fluid (IF): 12 L in spaces between cells.
o Other ECF = lymph, CSF, humors of the eye, synovial fluid, serous fluid, and gastrointestinal secretions.

Question 3

Composition of Body Fluids:

Answer 3

o Water: the universal solvent.
o Solutes: nonelectrolytes and electrolytes.
o Nonelectrolytes: most are organic.
o Do not dissociate in water: e.g., glucose, lipids, creatinine, and urea.
o Do not have an electric charge.
o Electrolytes:
o Dissociate into ions in water; e.g., inorganic salts, all acids and bases, and some proteins.
o Have an electric charge.
o Carry an electric current.
o Na+, K+, H+, HCO3-.
o Have greater osmotic power than nonelectrolytes, so contribute to fluid shifts (electochemical gradient).

Question 4

Electrolyte Concentration:

Answer 4

Expressed in milliequivalents per liter (mEq/L), a measure of the number of electrical charges per liter of solution.

Question 5

Electrolyte/ Non-Electrolytes:

Answer 5

o Osmolarity = the concentraton of molecules/ions per VOLUME of solution (mOsm/L).
o Osmolality = concentration of molecules per WEIGHT of solution (mOsm/Kg).

Question 6

Extracellular and Intracellular Fluids:

Answer 6

o	Each fluid compartment has a distinctive pattern of electrolytes
o	ECF: 
o	ECF is all body fluid out of cells, which includes blood plasma and interstitial fluid.
o	Higher protein content in plasma.
o	Major cation: Na+  (also Ca++).
o	Major anion: Cl–  (also HCO3-).
o	ICF: fluid in cells.
o	Low Na+ and Cl– .
o	Major cation: K+  (also Mg ++).
o	Major anion HPO42–  (also SO4--).
o	Proteins, phospholipids, cholesterol, and neutral fats make up the bulk of dissolved solutes
o	90% in plasma.
o	60% in IF.
o	97% in ECF.

Question 7

Fluid Movement Among Compartments:

Answer 7

o Regulated by osmotic and hydrostatic pressures
o Concentration of solutes in each compartment determines the DIRECTION of water flow. Water follows the particles (solutes) = osmosis.
o Anything above the osmotic gradient requires active transport or channels
o Electrolytes play the primary role in distribution of water and total fluid content of the body!!

Question 8

Water Balance and ECF Osmolarity:

Answer 8

o Water intake = water output = 2500 ml/day.
o Water intake: beverages, food, and metabolic water.
o Water output: urine, insensible water loss (skin and lungs), perspiration, and feces.

Question 9

Regulation of Water Intake:

Answer 9

o Fluid intake is regulated primarily by the hypothalamic THIRST CENTER
o The hypothalamic thirst center is stimulated by:
o Increased blood osmolarity picked up by central osmoreceptors in the hypothalamus
o Decrease aldosterone decreased blood volume.
o Dry mouth.
o Substantial decrease in blood volume or pressure.
o Drinking water creates inhibition of the thirst center and vice-versa.
o Inhibitory feedback signals include:
o Relief of dry mouth.
o Activation of stomach and intestinal stretch receptors.

Question 10

Regulation of Water Output:

Answer 10

o Obligatory water losses caused by:
o Insensible water loss: from lungs and skin.
o Feces.
o Minimum daily sensible water loss of 500 ml in urine to excrete wastes.
o Body water and Na+ content are coordinated by mechanisms that maintain cardiovascular function and blood pressure.
o Water reabsorption in collecting ducts is proportional to ADH release:
o Decreased ADH leads to dilute urine and ↓ volume of body fluids.
o Increased ADH leads to concentrated urine (caused by reabsorption of Na+ along with water).
o Hypothalamic osmoreceptors trigger or inhibit ADH release
o Other factors may trigger ADH release via large changes in blood volume or pressure, e.g., fever, sweating, vomiting, or diarrhea; blood loss; and traumatic burns. Hypoxia inducing factor (special proteins in cells). Renin from kidneys leads to angiotensin II. Aldosterone (adrenal cortex) leads to ADH.

Question 11

Hypernatremia (Dehydration):

Answer 11

o Negative fluid balance:
o ECF water loss due to: hemorrhage, severe burns, prolonged vomiting or diarrhea, profuse sweating, water deprivation, diuretic abuse.
o Signs and symptoms: thirst, dry flushed skin, oliguria.
o May lead to weight loss, fever, mental confusion, hypovolemic shock, and loss of electrolytes.

Question 12

Disorders of Water Balance (Hyponatremia):

Answer 12

o Cellular overhydration, or water intoxication.
o Occurs with renal insufficiency (chronic or acute) or rapid excess water ingestion.
o Too much aldosterone or cortisol.
o ECF is diluted leads to hyponatremia leads to net osmosis of water into tissue cells leads to swelling of cells leads to severe metabolic disturbances (nausea, vomiting, muscular cramping, cerebral edema) leads to possible death.

Question 13

Disorders of Water Balance (Edema):

Answer 13

o Edema = atypical accumulation of IF fluid leads to tissue swelling.
o Due to increase flow of fluid out of the blood and decrease return back into blood.
o Caused by increased blood pressure.
o Caused by increased capillary permeability (usually due to inflammatory chemicals = histamine).
o Caused by defective venous valves or localized blood vessel blockage.
o Caused by congestive heart failure, hypertension, and increased blood volume.
o Hindered fluid return to blood occurs with decreased (BCOP) blood colloid osmotic pressures.
o Hypoproteinemia = (decreased plasma proteins…specifically albumin)
o Fluids fail to return at the venous ends of capillary beds.
o Results from protein malnutrition, liver disease (less plasma proteins), or glomerulonephritis.
o Blocked (or surgically removed) lymph vessels:
o Causes leaked proteins to accumulate in IF since lymph system does not take them away.
o So Colloid osmotic pressure of IF goes up draws fluid from the blood.
o Results in low blood pressure and severely impaired circulation.

Question 14

Electrolyte Balance:

Answer 14

o Electrolytes are salts, acids, and bases.
o Electrolytic balance usually refers to salt balance in the body.
o Salts enter the body by ingestion and are lost via perspiration, feces, and urine.

Question 15

Central Role of Sodium:

Answer 15

o Most abundant cation in the ECF .
o Na+ leaks into cells and is pumped out (active transport) against its electrochemical gradient.
o ECF Na+ concentration remains stable due to osmosis.
o Changes in plasma sodium levels:
o Affects: Plasma volume, blood pressure (from osmosis)= osmolarity goes up leads to more water diffuses into blood plasma.
o Affects: Intra cellular fluid (ICF) and interstitial fluid (IF) volumes decrease= water diffuses into blood plasma from ICF/IF.
o Renal acid-base control mechanisms are coupled to sodium ion transport (antiporters) in kidney.
o Na+ actively transported into principal cells and H+ secreted into filtrate.

Question 16

Regulation of Sodium Balance:

ANP (Atrial Natriuretic Peptide)

Answer 16

o Released by atrial muscle cells in response to stretch (↑ blood pressure) located in right atrium
o Brings about a decrease in blood pressure and blood volume:
o Decreased ADH, renin and aldosterone production
o Increased Excretion of Na+ and water
o Promotes vasodilation directly and also by decreasing production of angiotensin II.

Question 17

Regulation of Sodium Balance:

Aldosterone

Answer 17

o Na+ reabsorption =
o 65% is reabsorbed in the proximal tubules.
o 25% is reclaimed in the loops of Henle.
o Aldosterone leads to active reabsorption of remaining Na+ and H2O (concentrated urine) while K+ is secreted by the principal cells into tubules/collecting ducts.
o Renin-angiotensin mechanism is the main trigger for aldosterone release
o Granular cells of JGA secrete renin in response to:
o Sympathetic nervous system stimulation.
o Filtrate osmolarity increase (filtrate has too much Na+) so renin secretion: (vasoconstriction = afferent arteriole + ADH release + ADH = decreased filtrate).
o Decreased tubule filtrate causes less “stretch” from stretch receptors of the JGA and chemoreceptors of the macula densa (detect levels of NaCl).
o Renin causes the mesangial cells to contract:
o Means that the glomerular capillaries have less surface area = less filtrate made.
o Renin catalyzes the production of angiotensin II = aldosterone is released from the adrenal cortex and ADH from the pituitary gland.
o Aldosterone release is also triggered by elevated K+ levels in the ECF (causes the secretion of K+ into filtrate (urine).
o Diuretics for blood pressure dumps too much K+ = need a potassium supplement.
o Aldosterone brings about its effects slowly (hours to days).

Question 18

Influence of Other Hormones:

Answer 18

o Estrogens: increased NaCl reabsorption (like aldosterone), causes H2O retention during menstrual cycles and pregnancy.
o Progesterone: decreased Na+ / H2O reabsorption (blocks aldosterone release)
o Glucocorticoids: (cortisol from the adrenal cortex), edema with over-retention of Na+.

Question 19

Cardiovascular System Baroreceptors:

Answer 19

o	Baroreceptors (in carotid sinus) alert the brain of increases in blood volume and pressure which causes: 
o	Sympathetic nervous system impulses to the kidneys decline = renin decreases.  
o	Aldosterone / ADH release decreases = more water dumped.

Question 20

Regulation of Calcium:

Answer 20

o Ca2+ in ECF is important for:
o Neuromuscular excitability.
o Muscle contraction.
o Essential in Blood clotting.
o Cell membrane permeability and stability.
o Neurotransmitter release (exocytosis).
o Needed for the secretion of many hormones.
o Hypocalcemia leads to increased excitability and muscle tetany = acute laryngospasm.
o Hypercalcemia leads to inhibits neurons and muscle cells (sluggish) = decreases contractibility of heart and may cause heart arrhythmias can lead to death.
o Calcium balance is controlled by parathyroid hormone (PTH), calcitriol, and calcitonin.

Question 21

Regulation of Potassium Balance:

Answer 21

o Importance of potassium:
o Most abundant in the ICF and helps maintain normal ICF volume.
o Functions in membrane potentials, AP, nerve transmission, Na+/K+ ATP-ase pump.
o Necessary for normal insulin secretion.
o Helps regulate pH (often exchanged in renal tubules with H+ in opposite directions to maintain proper ion balance), remember antiporters!!
o K+ balance is controlled in the collecting ducts by changing the amount of potassium secreted into filtrate.
o High K+ levels in ECF triggers principal cell secretion of K+ .
o Low K+ levels in ECF triggers intercalated cells reabsorption of K+.
o Influence of aldosterone:
o Stimulates K+ secretion (and Na+ reabsorption and H20 follows) by principal cells
o So Increased K+ causes:
o Release of aldosterone (Na+ reabsorbed)
o Potassium secretion.
o In other words, Na+ in K+ secreted into filtrate (antiporters).

Question 22

Influence of PTH:

Answer 22

o Bones are the largest reservoir for Ca2+ and phosphates.
o PTH promotes increase in calcium levels by targeting bones, kidneys, and small intestine (indirectly through vitamin D).
o Calcitonin decreases calcium levels.
o Calcium reabsorption and phosphate excretion go hand in hand.

Question 23

Regulation of Anions:

Answer 23

o Cl– is the major anion in the ECF:
o Helps maintain the osmotic pressure of blood plasma and interstitial fluid.
o 99% of Cl– is reabsorbed under normal pH conditions.
o Makes up HCl in parietal cells digestion of proteins.
o Regulation of acid-base balance.
o CO2 gas transported in blood as HCO3- (Cl-shift important to electrochemical stability of the RBC).

Question 24

Acid-Base Balance:

Answer 24

o pH affects all functional proteins and biochemical reactions.
o Normal pH of body fluids.
o Arterial blood: pH 7.4.
o Venous blood and IF fluid: pH 7.35.
o ICF: pH 7.0.
o Alkalosis or alkalemia: arterial blood pH >7.45.
o Acidosis or acidemia: arterial pH H2CO3 HCO3- + H+
o Concentration of hydrogen ions is regulated by:
o Chemical buffer systems: rapid; first line of defense against pH fluctuations.
o Brain stem respiratory centers: acts within 1–3 min (blow off CO2).
o Renal mechanisms: most potent, but require hours to days to effect pH changes (kicking out H+ and keeping HCO3-.
o Strong acids (HCl) dissociates completely in water releasing lots of H+ àcan dramatically affect pH.
o Weak acids (carbonic acid) dissociates partially in water releasing some H+; are efficient at preventing pH changes.
o Strong bases (NaOH) dissociates easily in water; quickly ties up H+.
o Weak bases (HCO3-) accepts H+ more slowly.

Question 25

Chemical Buffer Systems:

Answer 25

o Chemical buffer: system of one or more compounds that act to resist pH changes when strong acid or base is added.
o Chemical buffer = a substance that binds H+ (removes H+ from solution) as the concentration of H+ goes up (and pH goes down) or, it releases H+ (puts it back into solution) as the H+ goes down (pH goes up).
o 1) Bicarbonate buffer system.
o 2) Phosphate buffer system.
o 3) Protein buffer system.

Question 26

Bicarbonate Buffer System:

Answer 26

o Mixture of H2CO3 (weak acid) and salts of HCO3– ( a weak base = e.g., NaHCO3).
o Regulates pH in the ECF.
o Transports CO2 in blood as HCO3-.
o If strong acid is added:
o HCO3– ties up H+ and forms H2CO3 = a weaker acid.
o Remember: CO2 + H2O H2CO3 H+ HCO3- .
o pH decreases only slightly, unless all available HCO3– (alkaline reserve) is used up.
o HCO3– and H+ concentrations is closely regulated by the intercalated cells of the DCT and collecting duct.
o If strong base is added: (e.g. NaOH)
o It causes H2CO3 to dissociate and donate H+.
o H+ ties up the base (e.g. OH–).
o NaOH + H2CO3 > NaHCO3 + H2O.
o pH rises only slightly.
o H2CO3 supply is almost limitless (from CO2 released by respiration) and is subject to respiratory controls.

Question 27

Phosphate Buffer System= Buffers Urine:

Answer 27

o Action is nearly identical to the bicarbonate buffer = H2PO4- > HPO4– + H+
o Components are sodium salts of:
o Dihydrogen phosphate (H2PO4–) = a weak acid.
o Monohydrogen phosphate (HPO42–) = a weak base.
o Effective buffer in urine and ICF, where phosphate concentrations are high (DNA, RNA, ATP).
o Tubular filtrate that is acidic (H+) combines with HPO4- to form H2PO4- = a weak acid so urine does not become too acidic.

Question 28

Protein Buffer System:

Answer 28

o Intracellular proteins are the most plentiful and powerful buffers and in ICF and ECF. Provides about ¾ of the body’s buffering.
o Protein molecules are amphoteric (can function as both a weak acid and a weak base).
o When pH rises, organic acid or carboxyl (COOH) groups à release H+.
o When pH falls, amino groups (NH2 )groups à bind with H+ to form NH3à down the hatch.

Question 29

Physiological Buffer Systems:

Answer 29

o Respiratory and renal systems =
o Act more slowly than chemical buffer systems.
o Have more capacity than the chemical buffer systems.

Question 30

Respiratory Regulation of H+:

Answer 30

o Respiratory system eliminates CO2
o A reversible equilibrium exists in the blood:
o CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3– requires carbonic anhydrase (found in RBCs and surface of capillary epithelial cells).
o The addition of CO2 to body fluids (increased pCO2) will raise the concentration of H+ and decrease pH.
o The removal of CO2 will drive the equation above to the left, decreasing free H+ and increasing pH.
o Hypercapnia (too much CO2) activates chemoreceptors in the medulla oblongata due to resulting acidity.
o Rising plasma H+ (decreasing pH) activates peripheral chemoreceptors leads to.
o To becomes less acidic, more CO2 is “blown off” from the blood (increased rate and depth of ventilation).
o H+ concentration is reduced per equation and pH goes up.
o Decreased pH is caused by decreased ventilation, and the release of H+ (= more CO2 accumulates).
o Hence hyperventilation causes respiratory alkalosis and depresses the CNS = pCO2 45mm Hg.

Question 31

Renal Mechanisms of Acid-Base Balance:

Answer 31

o Most important for acid-base balance is renal mechanisms
o By conserving (reabsorbing) or generating new HCO3– , Kidneys make new HCO3- by breaking down the amino acid glutamine .
o By secreting HCO3–.
o Generating or reabsorbing one HCO3– is the same as losing one H+ .
o Secreting one HCO3– is the same as gaining one H+.
o Renal regulation of acid-base balance depends on secretion of H+.
o H+ secretion occurs in the DCT and in collecting duct via type A intercalated cells:
o The H+ comes from H2CO3 produced in reactions catalyzed by carbonic anhydrase inside the cells.

Question 32

Steps of Acid-Base Balance:

Answer 32

o 1) CO2 combines with water within the tubule cell forming H2CO2.
o 2) H2CO2 is quickly split forming H+ and bicarbonate ion (HCO3-).
o 3) H+ is secreted into the filtrate.
o 4) For each H+ secreted a HCO3- enters the peritubular capillary blood either via symport with Na+ or via antiport with Cl-.
o 5) The H2CO3 formed in the filtrate dissociates to release CO2 and H20.
o 6) CO2 diffuses into the tubule cell, where it triggers further H+ secretion.

Question 33

Reabsorption of Bicarbonate:

Answer 33

o Tubule cell apical (or luminal) membranes are impermeable to HCO3–.
o CO2 combines with water in PCT cells, forming H2CO3.
o H2CO3 dissociates to HCO3- and H+.
o H+ is secreted, and HCO3– is reabsorbed into capillary blood.
o Secreted H+ unites with HCO3– to form H2CO3 in the filtrate, which generates CO2 and H2O.
o HCO3– enters the peritubular capillary blood and H+ secreted.

Question 34

Metabolic Acidosis and Alkalosis:

Answer 34

o Causes of metabolic acidosis:
o Ingestion of too much alcohol (leads to acetic acid).
o Excessive loss of HCO3– (e.g., persistent diarrhea).
o Accumulation of lactic acid, shock, ketosis in diabetic crisis, starvation, and kidney failure.
o Metabolic alkalosis is much less common than metabolic acidosis:
o Indicated by rising blood pH and HCO3–.
o Caused by vomiting (emesis) of the acid contents of the stomach or by intake of excess base (e.g., antacids).