1. Chapter 24 Lecture Outline
24-1
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2. Balance
cellular function requires a fluid medium with a carefully controlled composition
three types of homeostatic balance
water balance
electrolyte balance
acid-base balance
balances maintained by the collective action of the urinary, respiratory, digestive, integumentary, endocrine, nervous, cardiovascular, and lymphatic systems
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3. Body Water newborn baby’s body weight is about 75% water
young men average 55% - 60%
women average slightly less
obese and elderly people as little as 45%
total body water (TBW) of a 70kg (150 lb) young man is about 40 liters
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4. Fluid Compartments major fluid compartments of the body
65% intracellular fluid (ICF)
35% extracellular fluid (ECF)
25% tissue (interstitial) fluid
8% blood plasma and lymphatic fluid
2% transcellular fluid ‘catch-all’ category
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5. Water Movement Between Fluid Compartments
fluid continually exchanged between compartments
water moves by osmosis
because water moves so easily through plasma membranes, osmotic gradients never last for very long
osmosis from one fluid compartment to another is determined by the relative concentrations of solutes in each compartment
electrolytes – the most abundant solute particles, by far
sodium salts in ECF
potassium salts in ICF
electrolytes key in governing body’s water distribution and total water content
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6. Water Movement Between Fluid Compartments
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Intracellular
fluid
Digestive tract
Bloodstream
Tissue fluid
Lymph
Bloodstream
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Figure 24.1 6

7. Water Gain
fluid balance - when daily gains and losses are equal (about 2,500 mL/day)
gains come from two sources:
preformed water (2,300 mL/day)
ingested in food and drink
metabolic water (200 mL/day)
by-product of aerobic metabolism and dehydration synthesis
C6H12O6 + 6O CO2 + 6H2O
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8. Fluid Balance Figure 24.2 Intake 2,500 mL/day Output 2,500 mL/day
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Intake
2,500 mL/day
Output
2,500 mL/day
Metabolic water
200 mL
Feces
200 mL
Expired air
300 mL
Food
700 mL
Cutaneous
transpiration
400 mL
Sweat 100 mL
Drink
1,600 mL
Urine
1,500 mL
Figure 24.2
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9. Regulation of Fluid Intake
thirst mainly governs fluid intake
dehydration
reduces blood volume and blood pressure
increases blood osmolarity
osmoreceptors in hypothalamus
respond to angiotensin II produced when BP drops and to rise in osmolarity of ECF with drop in blood volume
communicate w/ hypothalamus and cerebral cortex
hypothalamus produces antidiuretic hormone (ADH)
cerebral cortex produces conscious sense of thirst
intense sense of thirst with 2-3% increase in plasma osmolarity or 10-15% blood loss
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10. Thirst Satiation Mechanisms
long term inhibition of thirst
absorption of water from small intestine reduces osmolarity of blood
changes require 30 minutes or longer to take effect
short term inhibition of thirst
cooling and moistening of mouth quenches thirst
distension of stomach and small intestine
30 to 45 min of satisfaction
if water not absorbed into the bloodstream, thirst returns
short term response prevents overdrinking
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11. Dehydration, Thirst, and Rehydration
Renin
Angiotensin II
Thirst
Rehydration
Increased
blood osmolarity
Reduced
blood pressure
Stimulates
hypothalamic
osmoreceptors
salivation
Dry mouth ?
Sense of
thirst
Cools and
moistens mouth
Ingestion
of water
Rehydrates
blood
Distends
stomach
and intestines
Short-term
inhibition
of thirst
Long-term
Dehydration, Thirst, and Rehydration
Figure 24.3
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12. Regulation of Water Output
only way to control water output: variation in urine volume
kidneys can’t replace water or electrolytes
can only slow rate of water and electrolyte loss until water and electrolytes can be ingested
mechanisms:
a) changes in urine volume linked to adjustments in Na+ reabsorption
as Na+ is reabsorbed or excreted, water follows
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13. Regulation of Water Output
b) concentrate the urine through action of ADH
ADH secretion stimulated by hypothalamic osmoreceptors in response to dehydration
aquaporins synthesized in response to ADH
membrane proteins in renal collecting ducts whose job is to channel water back into renal medulla; Na+ is still excreted
concentrates urine
ADH release inhibited when blood volume and pressure is too high or blood osmolarity too low
effective way to compensate for hypertension
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14. Secretion and Effects of ADH
H2O
Elevates blood osmolarity
Dehydration
Na+
Increases water reabsorption
Thirst
Negative
feedback
loop
Water
ingestion
Reduces urine
volume
Increases ratio
of Na+: H2O
in urine
Stimulates distal convoluted
tubule and collecting duct
Stimulates posterior pituitary
to release antidiuretic hormone (ADH)
Stimulates hypothalamic
osmoreceptors
Figure 24.4
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15. Disorders of Water Balance
abnormalities of total volume, concentration, or distribution of fluid among the compartments are all bad
fluid deficiency – fluid output exceeds intake
volume depletion (hypovolemia)
water and Na both lost equally - osmolarity stays normal
hemorrhage, severe burns, chronic vomiting, or diarrhea
dehydration (negative water balance)
more water lost than sodium - osmolarity rises
lack of drinking water, diabetes, profuse sweating, overuse of diuretics
most serious effects:
circulatory shock due to loss of blood volume, neurological dysfunction due to dehydration of brain cells, infant mortality from diarrhea
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16. Fluid Balance in Cold Weather
body conserves heat by constricting skin blood vessels
raises blood pressure which inhibits secretion of ADH
increases secretion of atrial natriuretic peptide
urine output is increased and blood volume reduced
cold air is drier increases respiratory water loss also reducing blood volume
cold weather respiratory and urinary losses cause a state of reduced blood volume (hypovolemia)
exercise will dilate vessels in skeletal muscles
insufficient blood for rest of the body can bring on weakness, fatigue, or fainting (hypovolemic shock)
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17. Dehydration from Excessive Sweating
Sweat gland
Sweat pores
Skin
H2O 2 3 4 1 5
Water loss
(sweating)
Secretory cells
of sweat gland
Intracellular fluid
diffuses out of
cells to replace
lost tissue fluid.
Blood absorbs tissue
fluid to replace loss.
Blood volume
and pressure drop;
osmolarity rises.
Sweat glands
produce perspiration
by capillary
filtration.
1) water loss from sweating
2) sweat produced by capillary filtration
3) blood volume and pressure drop, osmolarity rises
4) blood absorbs tissue fluid to replace loss
5) tissue fluid pulled from ICF
6) all three compartments lose water
Figure 24.5
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18. Fluid Excess
fluid excess – less common than fluid deficiency b/c kidneys compensate for excessive intake by excreting more urine
renal failure can lead to fluid retention
two types of fluid excesses
volume excess
both Na+ and water retained - ECF remains isotonic
caused by aldosterone hypersecretion or renal failure
hypotonic hydration (water intoxication)
more water than Na+ retained or ingested
ECF becomes hypotonic
cellular swelling
pulmonary and cerebral edema
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19. Blood Volume and Fluid Intake
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Hypovolemia
Death 3
Blood volume (L) 2 1
Danger
Normal
Water diuresis 1 2 3 4 5 6 7 8
Fluid intake (L/day)
Figure 24.6
kidneys compensate very well for excessive fluid intake, but not for inadequate fluid intake
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20. Fluid Sequestration
fluid sequestration – a condition in which excess fluid accumulates in a particular location
total body water may be normal, but volume of circulating blood may drop to a point causing circulatory shock
most common: edema - abnormal accumulation of fluid in the interstitial spaces, causing swelling of the tissues
hemorrhage - another cause of fluid sequestration
blood that pools in the tissues is lost to circulation
pleural effusion – several liters of fluid can accumulate in the pleural cavity
caused by some lung infections
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21. ?

22. Electrolyte Balance physiological functions of electrolytes
chemically reactive and participate in metabolism
determine electrical potential across cell membranes
strongly affect osmolarity of body fluids
affect body’s water content and distribution
major cations
Na+, K+, Ca2+, and H+
major anions
Cl-, HCO3- (bicarbonate), and PO43-
different concentrations in blood plasma and intracellular fluid (ICF)
but same osmolarity (300 mOsm/L)
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23. Electrolyte Concentrations
145
300
103 4 5 4
(a) Blood plasma
150
300 75 12 4
< 1
Figure 24.7
Na+ K+
Cl–
Ca2+ Pi
Osmolarity
(mOsm/L)
24-23
(b) Intracellular fluid 23

24. Sodium - Functions
main ions responsible for resting membrane potentials
inflow of sodium through membrane gates causes depolarization that underlies nerve and muscle function
principal cation in ECF
sodium salts accounts for % of osmolarity of ECF
most significant solute in determining total body water and distribution of water among the fluid compartments
Na+ gradient a source of potential energy for cotransport of other solutes such as glucose, potassium, and calcium
Na+- K+ pump generates body heat
NaHCO3 has major role in buffering pH in ECF
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25. Sodium - Homeostasis adult needs about 0.5 g of sodium per day
typical American diet contains 3 – 7 g/day
primary concern - excretion of excess dietary sodium
sodium concentration coordinated by:
a) aldosterone - “salt retaining hormone”
aldosterone receptors in ascending limb of nephron loop, the distal convoluted tubule, and cortical part of collecting duct
aldosterone, a steroid, binds to nuclear receptors
activates transcription of a gene for the Na+ -K+ pumps
10 – 30 minutes to insert enough Na+ -K+ pumps in the plasma membrane
tubules reabsorb more Na and secrete more H and K
water and Cl passively follow Na
primary effects: urine contains less NaCl, more K and a lower pH
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26. Sodium - Homeostasis
b) ADH – modifies water excretion independently of sodium excretion
high Na in the blood stimulates the pituitary to release ADH
kidneys reabsorb more water
slows down any further increase in blood sodium concentration
drop in sodium inhibits ADH release
c) ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide )
inhibit Na and water reabsorption, and the secretion of renin and ADH
kidneys eliminate more Na and water, lowering blood pressure
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27. Sodium - Homeostasis d) others:
estrogen mimics aldosterone and women retain water during pregnancy
progesterone reduces sodium reabsorption and has a diuretic effect
sodium homeostasis is also achieved by regulating salt intake
salt cravings in humans and other animals
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28. Sodium - Imbalances hypernatremia hyponatremia
plasma sodium concentration greater than 145 mEq/L
loss of water faster than sodium (diarrhea), not drinking
results in water retention, hypertension and edema
hyponatremia
plasma sodium concentration less than 130 mEq/L
person loses large volumes of sweat or urine, replacing it by drinking plain water
quickly corrected by excretion of excess water
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29. Potassium - Functions most abundant cation of ICF
big effect on intracellular osmolarity & cell volume
produces (with sodium) the resting membrane potentials and action potentials of nerve and muscle cells
Na+-K+ pump
co-transport and thermogenesis
essential cofactor for protein synthesis and other metabolic processes
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30. Potassium - Homeostasis
closely linked to that of sodium
90% of K+ in glomerular filtrate is reabsorbed by the PCT
rest excreted in urine
DCT and cortical portion of collecting duct secrete K+ in response to blood levels
Aldosterone stimulates renal secretion of K+
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31. Secretion and Effects of Aldosterone
Hypotension
H2O
Hyperkalemia K+
Hyponatremia
Na+
Renin
Angiotensin
Stimulates
adrenal cortex
to secrete
aldosterone
Negative
feedback
loop
Stimulates renal
tubules
Increases Na+
reabsorption
Increases K+
secretion
Less Na+
and H2O in urine
More K+
in urine
Supports existing
fluid volume and
Na+ concentration
pending oral intake
Secretion and Effects of Aldosterone
Figure 24.8
24-31 31

32. Potassium - Imbalances
most dangerous imbalance of electrolytes
hyperkalemia - effects depend on whether the potassium concentration rises quickly or slowly
if concentration rises quickly (crush injury), sudden in extracellular K+ over-excites nerve & muscle cells
slow onset inactivates voltage-regulated Na+ channels; nerve and muscle cells become less excitable
can produce cardiac arrest
hypokalemia
rarely results from dietary deficiency
from sweating, chronic vomiting or diarrhea
nerve and muscle cells less excitable
muscle weakness, loss of muscle tone, decreased reflexes, and arrhythmias from irregular electrical activity in the heart
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33. Potassium & Membrane PotentialsK+ mV + –
(a) Normokalemia
(b) Hyperkalemia
(c) Hypokalemia
RMP
K+ concentrations
in equilibrium
Equal diffusion into
and out of cell
Normal resting
membrane
potential (RMP)
Cells more excitable
Elevated extracellular
K+ concentration
Less diffusion of K+
out of cell
Elevated RMP (cells
partially depolarized)
Cells less excitable
Reduced extracellular
Greater diffusion of
K+ out of cell
Reduced RMP (cells
hyperpolarized)
Figure 24.9
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34. Chloride - Functions most abundant anions in ECF
major contribution to ECF osmolarity
required for the formation of stomach acid
hydrochloric acid (HCl)
chloride shift that accompanies CO2 loading and unloading in RBCs
major role in regulating body pH
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35. Chloride - Homeostasis
strong attraction to Na+, K+ and Ca2+, which chloride passively follows
primary homeostasis achieved as an effect of Na+ homeostasis
as sodium is retained, chloride ions passively follow
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36. Chloride - Imbalances hyperchloremia hypochloremia primary effects:
dietary excess or administration of IV saline
hypochloremia
side effect of hyponatremia
sometimes from hyperkalemia or acidosis
primary effects:
disturbances in acid-base balance
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37. Calcium - Functions lends strength to the skeleton
activates sliding filament mechanism of muscle contraction
serves as a second messenger for some hormones and neurotransmitters
activates exocytosis of neurotransmitters and other cellular secretions
essential factor in blood clotting
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38. Calcium - Homeostasis
calcium homeostasis is chiefly regulated by PTH, calcitriol (vitamin D), and calcitonin (in children)
these hormones affect bone deposition and resorption
intestinal absorption and urinary excretion
cells maintain very low intracellular Ca2+ levels
to prevent calcium phosphate crystal precipitation
cells must pump Ca2+ out
or sequester Ca2+ in smooth ER and release it when needed
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39. Calcium - Imbalances hypercalcemia – hypocalcemia –
from alkalosis, hyperparathyroidism, hypothyroidism
reduces membrane Na+ permeability, inhibits depolarization of nerve and muscle cells
muscular weakness, depressed reflexes, cardiac arrhythmias
hypocalcemia –
vitamin D deficiency, diarrhea, pregnancy, acidosis, lactation, hypoparathyroidism, hyperthyroidism
increases membrane Na+ permeability, causing nervous and muscular systems to be abnormally excitable
very low levels result in tetanus, laryngospasm, death
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40. ?

41. Acid-Base Balance one of the most important aspects of homeostasis
metabolism depends on enzymes; enzymes sensitive to pH
slight shift from normal pH can shut down entire metabolic pathways
also can alter the structure and function of macromolecules
7.35 to 7.45 is normal pH range of blood and tissue fluid
challenges to acid-base balance:
metabolism constantly produces acid
lactic acids from anaerobic fermentation
phosphoric acid from nucleic acid catabolism
fatty acids and ketones from fat catabolism
carbonic acid from carbon dioxide
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42. Acids and Bases
pH of a solution is determined by its hydrogen ions (H+)
acids – any chemical that releases H+ in solution
strong acids like hydrochloric acid (HCl) ionize freely
gives up most of its H+
markedly lower pH of a solution
weak acids like carbonic acid (H2CO3) ionize only slightly
keeps most H+ chemically bound
does not affect pH much
bases – any chemical that accepts H+
strong bases - big effect on pH (OH-)
weak bases - small effect on pH (HCO3-)
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43. Buffers buffer – any mechanism that resists changes in pH
convert strong acids or bases to weak ones
physiological buffer - system that controls output of acids, bases, or CO2
urinary system buffers greatest quantity of acid or base
takes several hours to days to exert its effect
respiratory system buffers within minutes
cannot alter pH as much as the urinary system
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44. Buffers
chemical buffer – a substance that binds H+ and removes it from solution as its concentration begins to rise, or releases H+ into solution as its concentration falls
restore normal pH in fractions of a second
function as mixtures called buffer systems composed of weak acids and weak bases
three major chemical buffers : bicarbonate, phosphate, and protein systems
amount of acid or base neutralized depends on the concentration of the buffers and the pH of the working environment
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45. Bicarbonate Buffer System
bicarbonate buffer system – a solution of carbonic acid and bicarbonate ions.
reversible reaction important in ECF
CO2 + H2O  H2CO3  HCO3- + H+
lowers pH by releasing H+
CO2 + H2O  H2CO3  HCO3- + H+
raises pH by binding H+
functions best in the lungs and kidneys
to lower pH, kidneys excrete HCO3-
to raise pH, kidneys excrete H+ and lungs excrete CO2
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46. Phosphate Buffer System
phosphate buffer system - a solution of HPO and H2PO4-
H2PO4-  HPO42- + H+
as in the bicarbonate system, reactions that proceed to the right liberate H+ and decrease pH, and those to the left increase pH
more important buffering the ICF and renal tubules
where phosphates are more concentrated and function closer to their optimum pH of 6.8
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47. Protein Buffer System
proteins are more concentrated than bicarbonate or phosphate systems, especially in the ICF
protein buffer system accounts for about three-quarters of all chemical buffering in the body fluids
protein buffering ability is due to certain side groups of their amino acid residues
carboxyl (-COOH) side groups which release H+ when pH begins to rise
others have amino (-NH2) side groups that bind H+ when pH gets too low
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48. Respiratory Control of pH
the addition of CO2 to the body fluids raises the H+ concentration and lowers pH
the removal of CO2 has the opposite effects
neutralizes 2 to 3 times as much acid as chemical buffers
CO2 is constantly produced by aerobic metabolism
normally eliminated by the lungs at an equivalent rate
CO2 + H2O  H2CO3  HCO3- + H+
lowers pH by releasing H+
CO2 (expired) + H2O  H2CO3  HCO3- + H+
raises pH by binding H+
increased CO2 and decreased pH stimulate pulmonary ventilation, while an increased pH inhibits pulmonary ventilation
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49. Renal Control of pH
the kidneys can neutralize more acid or base than either the respiratory system or chemical buffers
renal tubules secrete H+ into the tubular fluid
most binds to bicarbonate, ammonia, and phosphate buffers
bound and free H+ are excreted in the urine, actually expelling H+ from the body
other buffer systems only reduce its concentration by binding it to other chemicals
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50. Acid-Base Balance Figure 24.12 pH Normal Alkalosis Acidosis 7.35 7.45
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Figure 24.12 pH
Normal
Alkalosis
Acidosis
7.35
7.45
8.0
6.8
Death
Death
H2CO3
HCO3–
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51. Disorders of Acid-Base Balance
acidosis – pH below 7.35
H+ diffuses into cells, drives out K+, elevating K+ conc. in ECF
membrane hyperpolarization, nerve and muscle cells are hard to stimulate; CNS depression - confusion, disorientation, coma, and possibly death H+ K+
Protein
leading to
Hyperkalemia
Hypokalemia
(a) Acidosis
(b) Alkalosis
Figure 24.13
24-51 51

52. Disorders of Acid-Base Balance
alkalosis – pH above 7.45
H+ diffuses out of cells and K+ diffuses in, membranes depolarized, nerves and muscles overstimulated
a person cannot live for more than a few hours if the blood pH is below 7.0 or above 7.7 H+ K+
Protein
leading to
Hyperkalemia
Hypokalemia
(a) Acidosis
(b) Alkalosis
Figure 24.13
24-52 52

53. Disorders of Acid-Base Balances
acid-base imbalances fall into two categories:
respiratory and metabolic
respiratory acidosis
occurs when rate of alveolar ventilation fails to keep pace with the body’s rate of CO2 production
CO2 accumulates in the ECF and lowers its pH
emphysema - severe reduction of functional alveoli
respiratory alkalosis
results from hyperventilation
CO2 eliminated faster than it is produced
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54. Disorders of Acid-Base Balances
metabolic acidosis
increased production of organic acids such as lactic acid (anaerobic fermentation), and ketone bodies seen in alcoholism, and diabetes mellitus
ingestion of acidic drugs (aspirin)
loss of base due to chronic diarrhea, laxative overuse
metabolic alkalosis
rare, but can result from:
overuse of bicarbonates (antacids and IV bicarbonate solutions)
loss of stomach acid (chronic vomiting)
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55. Compensation for Acid-Base Imbalances
compensated acidosis or alkalosis
either the kidneys compensate for pH imbalances of respiratory origin, or
the respiratory system compensates for pH imbalances of metabolic origin
uncompensated acidosis or alkalosis
a pH imbalance that the body cannot correct without clinical intervention
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56. Compensation for Acid-Base Imbalances
respiratory compensation – changes in pulmonary ventilation to correct changes in pH of body fluids by expelling or retaining CO2
hypercapnia (excess CO2) - stimulates pulmonary ventilation, eliminating CO2 and allowing pH to rise
hypocapnia (deficiency of CO2) reduces ventilation and allows CO2 to accumulate, lowering pH
24-56 56

57. Compensation for Acid-Base Imbalances
renal compensation – adjustment of pH by changing rate of H+ secretion by the renal tubules
slow, but better at restoring a fully normal pH
in acidosis, urine pH may fall as low as 4.5 due to excess H+
renal tubules increase rate of H+ secretion, elevating pH
in alkalosis as high as 8.2 because of excess HCO3-
renal tubules decrease rate of H+ secretion, lowering pH
kidneys cannot act quickly enough to compensate for short-term pH imbalances
better for pH imbalances that lasts for a few days or longer
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58. Fluid Replacement Therapy
one of the most significant problems in the treatment of seriously ill patients is the restoration and maintenance of proper fluid volume, composition, and distribution among fluid compartments
fluids may be administered to:
replenish total body water
restore blood volume and pressure
shift water from one fluid compartment to another
restore and maintain electrolyte and acid-base balance
drinking water is the simplest method
does not replace electrolytes
broths, juices, and sports drinks replace water, carbohydrates, and electrolytes
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59. Fluid Replacement Therapy
patients who cannot take fluids by mouth
enema – fluid absorbed through the colon
parenteral routes – sites other than digestive tract
intravenous (I.V.) route is the most common
subcutaneous (sub-Q) route
others
excessive blood loss
normal saline (isotonic, 0.9% NaCl)
raises blood volume while maintaining normal osmolarity
can induce hypernatremia or hyperchloremia
correct pH imbalances
acidosis treated with Ringer’s lactate
alkalosis treated with potassium chloride
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60. Fluid Replacement Therapy
plasma volume expanders – hypertonic solutions or colloids that are retained in the bloodstream and draw interstitial water into it by osmosis
used to combat hypotonic hydration by drawing water out of swollen cells
can draw several liters of water out of cells within a few minutes
patients who cannot eat
isotonic 5% dextrose (glucose) solution
has protein sparing effect – fasting patients lose as much as 70 to 85 grams of protein per day
I.V. glucose reduces this by half
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61. END