Chapter 24Lecture Outline

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24-1

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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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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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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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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Water Movement Between Fluid Compartments

Figure 24.1

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Digestive tract

Bloodstream BloodstreamTissue fluid Lymph

Intracellularfluid

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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 + 6O2 6CO2 + 6H2O

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Fluid Balance

Figure 24.2

Intake2,500 mL/day

Output2,500 mL/day

Metabolic water200 mL

Feces200 mL

Expired air300 mL

Cutaneoustranspiration

400 mL

Sweat 100 mL

Urine1,500 mL

Drink1,600 mL

Food700 mL

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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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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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Dehydration, Thirst, and Rehydration

Figure 24.3

Dehydration

Renin

Angiotensin IIDehydration

Thirst

Rehydration

Increasedblood osmolarity

Reducedblood pressure

Stimulateshypothalamic

osmoreceptors

Reducedsalivation

Stimulateshypothalamic

osmoreceptors

Dry mouth?

Sense ofthirst

Cools andmoistens mouth

Ingestionof water

Rehydratesblood

Distendsstomach

and intestines

Short-terminhibitionof thirst

Long-terminhibitionof thirst

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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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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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Secretion and Effects

of ADH

Figure 24.4

H2O

Elevates blood osmolarity

DehydrationNa+ Na+

Increases water reabsorption

Thirst

Negativefeedback

loop

Negativefeedback

loopWateringestion

Reduces urinevolume

Increases ratioof Na+: H2O

in urine

Stimulates distal convolutedtubule and collecting duct

Stimulates posterior pituitaryto release antidiuretic hormone (ADH)

Stimulates hypothalamicosmoreceptors

H2O

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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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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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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

Sweat gland

Sweat pores

Skin

H2O

2

3 4

1

5

Water loss(sweating)H2O

H2O

Secretory cellsof sweat gland

Intracellular fluiddiffuses out ofcells to replacelost tissue fluid.

H2O

H2O

H2O H2O

Blood absorbs tissuefluid to replace loss.

Blood volumeand pressure drop;osmolarity rises.

Sweat glandsproduce perspirationby capillaryfiltration.

Dehydration from Excessive Sweating

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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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Blood Volume and Fluid Intake

kidneys compensate very well for excessive fluid intake, but not for inadequate fluid intake

Figure 24.6

5

4

3

2

1

00

Blo

od

vo

lum

e (L

)

1 2 3 4 5 6 7 8Fluid intake (L/day)

Death

NormalDanger

Hypovolemia

Water diuresis

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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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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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Electrolyte Concentrations

Figure 24.7

145

4

103

5 4

300

(a) Blood plasma

12

150

4 < 1

75

300

(b) Intracellular fluid

Osmolarity(mOsm/L)

Na+ K+ Cl– Ca2+ Pi

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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 90 - 95% 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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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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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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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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Sodium - Imbalances

• hypernatremia– 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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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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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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Secretion and Effects

of Aldosterone

Figure 24.8

HypotensionH2O

HyperkalemiaK+

Hyponatremia Na+ K+

Renin

Angiotensin

Stimulatesadrenal cortex

to secretealdosterone

Negativefeedback

loop

Stimulates renaltubules

Increases Na+

reabsorptionIncreases K+

secretion

Less Na+

and H2O in urineMore K+

in urine

Supports existingfluid volume and

Na+ concentrationpending oral intake

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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

K+

mV

+

–

mV

+

–

mV

+

–

(a) Normokalemia

(b) Hyperkalemia

(c) Hypokalemia

RMP

K+ concentrationsin equilibrium

Equal diffusion intoand out of cell

Normal restingmembranepotential (RMP)

Cells more excitable

Elevated extracellularK+ concentration

Less diffusion of K+

out of cell

Elevated RMP (cellspartially depolarized)

Cells less excitable

Reduced extracellularK+ concentration

Greater diffusion of K+ out of cell

Reduced RMP (cellshyperpolarized)

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Potassium & Membrane Potentials

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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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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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Chloride - Imbalances

• hyperchloremia – 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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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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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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Calcium - Imbalances• hypercalcemia –

– 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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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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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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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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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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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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Phosphate Buffer System

• phosphate buffer system - a solution of HPO42-

and H2PO4-

• H2PO4- HPO4

2- + 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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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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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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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

pH

7.457.35Alkalosis

Acidosis

8.06.

8

Normal

Death

Death

H2CO3 HCO3–

24-50

Acid-Base Balance

Figure 24.12

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24-51

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

Figure 24.13

H+ K+ Protein

Proteinleading to Hyperkalemia

leading to Hypokalemia

K+ H+

(a) Acidosis

(b) Alkalosis

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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

Figure 24.13

H+ K+ Protein

Proteinleading to Hyperkalemia

leading to Hypokalemia

K+ H+

(a) Acidosis

(b) Alkalosis

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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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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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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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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

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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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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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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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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

END

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