Fluid Distribution within the body :

Total body water compromises 60% of the body weight.  Twenty percent of body weight is extracellular fluid while 40% of body weight is intracellular (20-40-60 rule).  The extracellular fluid is further divided into the intravascular space & the interstitial space.  Approximately 25% of the extracellular fluid is within the vascular space while the remainder (75% of extracellular fluid) is within the interstitium.  In terms of body weight, this calculates into 4.5% of body weight is fluid within the vascular space while approximately 15% of body weight is within the interstitium.

To understand the movement of fluid between the various fluid compartments within the body (intravascular, interstitial, and intracellular) one must be familiar with the behavior of solutions separated by a semipermeable membrane and the principles of OSMOTIC, ONCOTIC, and HYDRAUIC (hydrostatic) pressures.

  The movement of water down its concentration gradient is termed OSMOSIS.  This movement occurs when two solutions are separated by a semipermeable membrane that is permeable to water but not to the solutes within the water solutions.  The amount of hydrostatic pressure it takes to prevent water from moving from its higher concentration to its lower concentration is called osmotic pressure.  It is the total NUMBER of solutes within the solution, NOT the size or weight of the particles that determines the osmotic pressure of the solution.

An OSMOLE is the number of particles in 1 gram molecular weight of a substance in solution.  OSMOLALITY is the number of osmoles of solute dissolved in 1 Kg of water while OSMOLARITY refers to the number of osmoles dissolved in 1 liter of water.

  For body fluids, the difference between osmolality and osmolarity is negligible.  Tonicity is the comparision of the osmolality between two different solutions whether it is a comparison of normal saline verses plasma or extracellular fluid vs. intracellular fluid.  Hence, the terms : isotonic, hypertonic, and hypotonic.

     COLLOID OSMOTIC PRESSURE (COP) or oncontic pressure is the osmotic pressure generated by proteins.  Albumin and globulins are considerably larger than plasma electrolytes, urea, and glucose but the number of plasma proteins is substantially lower than the number of cyrstalloids in plasma.  It is the NUMBER of particles in solution NOT the size that determines osmotic pressure.  The osmotic pressure attributed to plasma proteins is substantially lower than that generated by crystalloids but colloid osmotic pressure still has major physiological importance in our patients because the vascular endothelium is relatively impermeable to proteins but permeable to crystalloids, glucose, urea, and water.  In a normal individual, the plasma and interstitial colloid osmotic pressures are not balanced with the interstitium and therefore are less because protein concentration in the plasma is higher.

Because of the impermeability of the vascular endothelium to the plasma proteins, the osmotic pressure generated by these proteins tends to be fully exerted but in many of our critically ill patients, vascular permeability to these proteins can be increased causing a decreased COP gradient between the intravascular space and the interstitium resulting in loss of fluid into the interstitial space.

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The Starling equation describes the forces that govern movement of fluid across the vascular endothelium.  Simply stated, the major forces involved are the differences in hydrostatic pressure between the intravascular space and the interstitium, and the permeability of the vascular endothelium.  Clinically, the only two forces that are readily measured are the intravascular hydrostatic pressure and the intravascular colloid osmotic pressure.

Fluid Balance:

            IN = OUT   à content is then redistributed between ICF and ECF

                        Fluid (H20) in GI,  out via urine excretion

                        Electrolytes in GI,  out via renal, sweat, respiratory, feces

                        Acid – Base (pH)   involves H+,   H+ “in” during metabolism

                                                                              H+ out via renal excretion

TO SUMMARIZE ::

Fluid compartments ::

ICF ....intracellular fluid, 2/3 of body fluids

ECF ....extracellular fluid, 1/3 of body fluids

1. Plasma --> fluid portion of blood

2. Interstitial --> fluid between tissue cells

3. lymph à fluid within the lymphatic vessels

4. Other compartments : CSF, eye humors, ear, sweat, sebum, Synovial, serous, saliva, semen

 

Movement of fluid between the compartments are selectively permeable and due to ::

            Hormones are the primary regulatory mechanisms that help fluid movement

                        1) ADH

                        2) Aldosterone

                        3) ANP

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Water is the universal solvent

Solutes consist of electrolytes and nonelectrolytes

Electrolytes have a greater osmotic power because they dissociate into two or more components  (Increases NUMBERS)

Will be measured in milliequivalent/liter (mEq/L) and reflects the number of electrical charges.

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ECF vs ICF :

Na+ is the primary cation in the ECF,  Cl- the primary anion

K+ is the primary cation in the ICF, proteins the primary anion along with HPO4-

     Exchanges between the two are due to :

Water ::  intake ....fluids, food, metabolic processes

   output ....Urine primarilty with insensible process occuring in the lungs, skin, and feces

Regulation of intake --> thirst center in the anterior hypothalamus contained in osmocreceptorsthat stimulate the magnocellular neurons of the supraoptic and paraventricular nuclei when the thirst threshold (~ 280 mOsm) is reached

Regulation of output --> renal, tied with Na+

Problems  ::
dehydration.........loss, decreased intake, decreased protein

        edema.............change in capillary pressure or permeability, decreased return

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Electrolyte Balance :

Electrolytes...salts, acids, bases

electrolyte balance is primarily due to salt and based on membrane permeability and fluid movement

e- = Na+, K+, Ca++, Mg++, Cl-, HCO3-

Abnormal loss :: vomiting, diarrhea

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Na+ salts (NaHCO3, NaCl) ::

90% of solute in ECF

regulation by the kidney

concentration :: 142 mEq/L

Na+ is the most abundant cation in the ECF

    is significant for osmotic pressure,  water follows salt

   Sodium must be actively transported

Regulation of Na+ balance ::

neural and hormonal

linked to blood volume and pressure

Aldosterone release is triggered by

Decreases in K+                                  

renin from JGA to activate angiotensin --> aldosterone in response to decreased Blood pressure, decreased filtrate osmolarity, and increased sympathetic stimulation

 

3. Heart :: baroreceptors --> hypothalamus --> sympathetic nervous system--> kidneys --> vessels dilate

Incr GFR --> Incr Na+/H2O output

   This process is called pressure diuresis

 

4. ADH :: Increased Na+ stimulates release (H2O reabsorption increases)

 

5. ANF :: will have an effect of decreasing BP and volume inhibits Na/H2O retention, & promotes excretion by suppressing the release of renin, aldosterone, & ADH

 

6. Hormones ::

Estrogen...enhance Na+ reabsorption

Progesterone ... decr Na+ reabsorption, blocks aldosterone

GCC .... enhance Na+ reabsorption

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Regulation of K+ ::

K+ is the primary cation in the ICF

   helps determine cell membrane potential excess in ECF creates excitability, depolarizes decrease causes hyperpolarization

   part of the buffer system to regulate pH, shifts with H+ to maintain (+) balance primarily maintained by renal mechanisms ::

therefore, regulation involves secretion

Summary -->

Rate and amount of secretion depend on

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Regulation of Ca++ ::

Primary amount in bones

Ca++ in ECF --> necessary for blood clotting, membrane perm, and secretory (for neurons)

Regulation to keep balanced at 9-11 mg/dl
Using hormones --> PTH, calcitonin

PTH....from the chief cells of the parathyroid stimulated by decreased blood Ca++ levels activated osteoclasts to release Ca++/PO4--

  S.I. absorption of Ca++ with Vit D activated by the kidneys

  Increase reabsorption by kidneys and decreased PO4-- reabsorption

Generally, most is reabsorbed at PCT & has a threshold, but with PTH, the active transport is inhibited

Calcitonin.... by parafollicular cells of Thyroid

         stimulated by increases in blood Ca++,deposits Ca++ in bone

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Regulation of Mg++

function to activate coenzymes for metabolism of CHO/Protein & involved in neuromuscular action

handled like K+

Regulation of ANIONS

Cl- follows Na+, will depend in pH, incr reabs when alkaline

HCO3- follows Na+, depends on pH, incr reabsorption when acid

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ACID BASE BALANCE

Normal metabolic process in the body result in the production of relatively large quantities of acids such as lactic acid, carbonic acid, sulfuric acid, beta-hydroxybutryic acid, and phosphoric acid.  These acids are transported to excretory organs, the lungs and kidneys, without causing any marked alteration in body pH.  Maintenance of pH is essential as many metabolic processes that occur within cells are pH dependent and will cease to operate if the pH is altered.

Three important, but independent variables regulate pH in blood plasma;

  This sensitive control of blood pH in the normal range of 7.3 - 7.45 is accomplished by combined effects of the blood buffer system, the kidney, and the respiratory system.  In addition to their role in controlling blood pH, these systems are also of significance in maintaining the normal cation-anion composition of the body.

Since blood and tissue pH usually does not change over time (i.e. stable), changes in pH can predict many disease states.

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In SUMMARY ::

ACID/BASE

pH :  blood is 7.35-7.45 (7.38-7.42); minium 7.00 to 7.70 maximum

H+ originates as a byproduct/end product of cellular metabolism such as HCl, lactic acid, ketone bodies

Regulation of Acid/Base is a regulation of [H+], remember that a proton is H+

Definitions ::

ACIDS :: sources :

Types of acids :

        Volatile acids : air         CO2, H2CO3

            Fixed acids :     metabolic byproducts excreted by kidneys:  phosphoric [PO4], sulfates [H2SO4]

            Organic acids:   metabolic byproducts used

                                                Amino acids

                                                Fatty acids

                                                HCl

                                                Uric

                                                Ketoacids : Kreb’s cycle acids, pyruvic acid

                                                Lactic acids

                                                Ketones

BASES :: sources : some fruits, vegetables, and metabolic processes

            Examples HCO3-, HPO4--, proteins (e.g. hemoglobin)

ALKALI :: alkaline metal with a hydroxyl ion (-OH)

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SRONG/WEAK ::

strong acid...very strong tendency to dissociate

discharge H+ into solution, e.g. --> HCL

Weak Acids .. partially dissociate, e.g H2CO3

Strong Base.. powerful removal of H+,  e.g -OH

Weak Base .. binds weakly with H+,  e.g.  HCO3-

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pH :

used to express the concentration of [H+] in solution

-log base 10 [H+]

therefore low pH means High H+ concentration, acidosis

and high pH means low H+ --> alkalosis

            recall from algebra that logarithmic formula comprises the following

                        y = log (base b) X çèb (to y exponent) = X

                                    where b > 0, b/= 1, X<0

                                                so that the log (base2) 8  = 3 

                                                             means that 2 ³ = 8

pH of venous blood is 7.35 (CO2 --> H2CO3)

pH of arterial blood is 7.4 and the limits are 6.8 - 8.0

To prevent acidosis/alkalosis is done by a control system ::

1. acid - base (chemical) buffer system.... seconds

2. respiratory (change CO2, monitored by resp centers in brain stem)  ..... minutes

3. Renal ....  hours to days

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CHEMICAL BUFFER SYSTEMS ::

A buffer is a mixture of a weakly dissociated acid and a salt of that acid.  As such, buffers prevent a major shift in pH by binding or releasing hydrogen ions.  HA (acid) <---> H+ + A- [base]

At equilibrium Ka = [H+] [A-] / [HA]

For example, in the bicarbonate buffer system, if a strong acid is added to a solution containing HCO3- and H2CO3, the H+ reacts with the HCO3- to form more H2CO3, which is a weak acid and causes only a slight increase in the H+ concentration.

  On the other hand, if a base is added to the same buffer system, the OH- reacts with the H+ of carbonic acid to form bicarbonate and water and the pH change is again small.

The Henderson-Hasselbalch equation is of assistance in understanding and explaining pH control of body fluids.  This formula is as follows :

    pH  =  pK + log salt/acid

  In this formula pK = the negative logarithm of the dissociation constant K, the salt is equal to the concentration of the ionized species, acid equals the concentration of the undisassociated acid, and pH is the negative logarithm of hydrogen ion.

In SUMMARY ::

Function of Acid/Base buffers::

solution that contains 2 or more chemical compounds that prevent marked changes in hydrogen ion concentration

Buffer systems that play a role in control of pH in the various fluid compartments are ::

also remember that hemoglobin can accept a H+ from H2CO3

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A. Bicarbonate Buffer System ::

H2CO3   --->  H+ + HCO3-

Location: ECF, very imporant in the CSF

The ration of dissociated to undissociated forms of an acid is considered constant (K)

K = [H+] [HCO3-] / [H2CO3]

When combined with the formula for pH (pH = -log [H+] m/L you get the following equation:

Henderson/Hasselbalch Equation ::

pH  = pK + log [HCO3-] / [CO2]

At normal plasma concentrations,

to measure the pH of the bicarbonate buffer system, will have pK of 6.1  ( the pK of H2CO3 is = 6.1 and the pK = - log K  =  [H+] x [HCO3]/ CO2

Therefore we have  pH  = 6.1 + log HCO3- / H2CO3 .

Thus, pH of plasma is dependent upon the RATIO of HCO3- to H2CO3

 The normal ratio is 20:1.  

As the log of 20 is 1.301, then 6.1 + 1.301 = 7.401 = normal pH of blood.

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As the bicarbonate buffer system is the most abundant in the body, it is the most easily controlled buffer system, the easiest one to measure, and it is clinically the most important since the body pH can be adjusted by changing the concentrations of HCO3- at the kidney and CO2 at the lungs or even carbonate from the bones if necessary.

A review follows  -->

Carbonic acid is formed when hydrogen from cell metabolism combines with bicarbonate

 (H+ + HCO3- --> H2CO3) or when carbon dioxide produced by cell metabolism is combined with water inside the RBC to form carbonic acid under the influence of cellular carbonic anhydrase.

Bicarbonate is formed when oxygen leaves oxyhemoglobin to form hemoglobin.  Hemoglobin then takes up the extra hydrogen ion from disassociation of carbonic acid and bicarbonate is formed and diffuses out of the RBC and into the plasma.  Oxygen removed in this fashion passes from RBC through plasma and into the tissue cells.

CO2 produced by normal metabolic processes of the body is carried to the lungs in the blood.
Remember that pCO2 is regulated by the respiratory centers of the brainstem and chemoreceptors in the arotic arch and carotid bodies.

 Because of continuous production of CO2 within tissue cells, there is a concentration differential for CO2 from cells to plasma and RBCs.  THis causes a shift of physically dissolved CO2 from tissue cells into the plasma and RBCs. 
The rest you should know from CO2 transport :

CO2  +  H20   <======>  H2CO3  <======>  H+  + HCO3-

so when increases in HCO3- will have an increase in pH and when increases in CO2 will decrease pH

**** The buffering power of the buffer system is greatest when the pH = pK and directly proportional to the concentrations of the buffer substances **********

A rise in HCO3- or a fall in CO2 resultst in alkalemia that can lead to alkalosis

A fall in HCO3- or a rise in CO2 results in acidemia that can lead to an acidosis

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2. Phosphate ::

Mixture of H2PO4- ( dihydrogen phosphate), HPO4--(monohydrogen phosphate)

             pK = 6.8                                                                                                        

a. Important in Renal Tubular Fluids

b. Important intracellular because increased concenttration and ICF pH is closer to pK

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3. Protein Buffer ::

Most plentiful,  in high concentration, primarily in the ICF, but also found in ECF

The amino acid Histadine is very important due to its imidazole ring, which results in proteins having a pKa = 7.0

pK is close to 7.4, therefore most powerful

In addition, the deamination of proteins releases an amine that is converted to ammonia (NH3). This in turn can be used as a base to accept addtional H+ to become ammonium (NH4+). This converstion takes place primarily in the kidneys to help buffer the urine when the phosphate buffer system becomes overloaded.

some amino acids act as acids :: R-COOH  --> R-COO-  + H+

some animo acids act as bases :: R-NH2 + H+  --> R-NH3+

some amino acids act as both, Example :: Hemoglobin, which had 36 histadine AA per molecule.

All of the above buffer systems work together and a change in [H+] affects all buffer systems.

The buffer systems buffer  each other by shifting H+ from one to another.

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Respiratory Control of Acid-Base balance

The respiratory center found in the ventrolateral surface of the medulla oblongata near CN XII is sensitive to blood levels of PCO2. 

If blood PCO2 increases above normal, there will be an increase in the respiratory rate.

  This increase has a tendency to return PCO2 and consequently H2CO3 towards normal.  This respiratory center will also respond to pH changes and even if PCO2 is normal and pH drops, the respiratory rate will increase and PCO2 will be reduced.

            Conversely, if PCO2 is low or blood pH is increased, the respiratory rate will decrease.  Thus regulation of the rate of pulmonary ventilation in response to changes in PCO2 and pH serves as a basis for pulmonary compensation in alkalosis and acidosis.

TO SUMMARIZE Respiratory Regulation ::

CO2 constantly being formed, will be eliminated by the lungs during alveolar ventilation

CO2 + H2O  --> H2CO3  -->  H+  + HCO3-

* changes in CSF pH by excess accumulation of CO2 causes

            changes in respiratory rate to regulate CO2 to correct the blood pH

* provides a physiological buffer system that is 2x the power of the chemical buffers

* increases in CO2 will decrease pH  (see formula)

* changes in blood pH from incr/decr ventilation so that increased ventilation will increase pH and decreased ventilation will decrease pH

    remember : alveolar ventilation will affect CO2 and vice versa

* stimulated by the medulla/pons respiratory center

  Impairment of respiratory system function causes an acid/base imbalance

increases in CO2  --> acidosis

decreases in CO2  --> alkalosis

if pH changes due to respiratory problem will be called :: respiratory acidosis, respiratory alkalosis

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Renal Control ::

kidneys remove metabolic acids such as : phosphoric, uric, ketone bodies

control of [H+] by excreting acidic/basic urine

a. Tubular secretion of H+

1) Secondary active transport : PCT, Asc L.H., DCT

   start with CO2 + H20 --> H2CO3  -->  HCO3- + H+

H+ : countertransport with Na+ by carrier protein will go down its concentration gradient Na+ into cell, H+ out

b. Primary active transport :

 [H+]  in late distal tubules and collecting ducts [I cells] secrete H+ by primary active transport

  ATP to move H+ with carrier against its concentration gradient

  H+ generated from CO2 + H20 -->  etc

c. Rate of secretion ::

             Based on ratio of CO2 :: HCO3- in ECF

d. Reabsorbtion of HCO3- ::

Kidney adjustment of pH ::

acidosis... ratio of CO2 : HCO3 is increased

alkalosis... ratio of HCO3- : CO2 is increased

Excess H+ secreted into tubules must be carried by buffer system

phosphate and ammonia  (also urate & citrate)

Ammonia Buffer System :  NH3 (ammonia), NH4+ (ammonium)

Some Cl- will combine with H+ to form HCl (strong acid)

Kidney slow to act (days), but more powerful and has the ultimate capability of regulating pH. 
Urine pH is approx 6.0 : more acid excreted due to slightly more formation (metabolism) therefore,
HCO3- is shuttled back and forth
so it is retained in ECF if acidosis is occurring and removed if alkalosis is occurring,
Movement of HCO3- also affects Cl- movement

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Renal Acid / Base transport summary

            Na+/ H+          counter transport

            Na+/HCO3-    co-transport

            H+ ATPase      primary active transport

            H+ /K+            counter transport

            Na+ / K+         active transport

            Cl-                   diffusion

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Abnormalities in acid/base will create acidosis/alkalosis and can be caused by

1. respiratory: alterations in pCO2 due to altered CO2 elimination

2. metabolic: alterations in [H+] or [HCO3-]

and can also be compensated and uncompensated as well as simple or complicated acid base abnormalitites.

In the critically ill, acidosis is usually more of a problem then alkalosis with common causes of metabolic acidosis including disorders of chloride homeostasis, lactate, and other anions. Metabolic acidosis or alkalosis are catergoirized by the ions that are responsible for the shift away form the normal pH state. In chemistry, normal neutral pH = 6.8-7.0, so human blood [normal pH = 7.35-7.45] is slightly alkaline. Human urine pH can vary, but ranges from 5-8, with normal pH around 6.0.

Acidosis means an acidic pH compared to normal pH of 7.4. Acidosis may result from starvation diets, severe diarrhea, DM, and respiratory disease.
Metabolic acidosis is produced by an increase in free [H+] which can happen through production of organic anions (lactate, ketones), loss of cations (diarrhea), disruption of ion management (renal tubular acidosis), or by addtion of anions (poisonings). Metabolic acidosis is a raised H+ concentration with normal pCO2. The high [H+] causes a reciprocal fall in the [HCO3-], to maintain equilibrium. Respiratory compensation occurs quickly via shallow, rapid breaths or panting. This lowers the pCO2, reducing both the [H+] and the [HCO3-].
Respiratory acidosis (high pCO2) results in the formation of carbonic acid from CO2 and water. H2CO3 ionizies to increase both [HCO3-] and [H+]. [H+] changes only slightly due to the buffering effect of hemoglobin. At this pCO2 level, the kidney compensates by reducing [H+]. The concentration of HCO3- rises further to maintain chemical equilibrium.

Alkalosis may result from excess alkali ingestion, severe vomiting, and respiratory hyperventilation.
Metabolic Alkalosis occurs as a result of a large strong ion difference that can be caused by the loss of anions in excess of cations (vomiting, diuretics), or by the transfusion of a large volume of banked blood.

Respiratory acidosis/alkalosis ::

decreased pulmonary ventilation --> increases pCO2 due to reduced CO2 elimination

increased pulmonary ventilation --> decreases pCO2 caused by increased CO2 elimination

Respiratory acidosis is due primarily to pathology ::

Respiratory alkalosis is due to over breathing (seen in high altitudes, anxiety, anesthesia, pregnancy, fever, heart attack, pain)

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Metabolic Acidosis/Alkalosis

all other abnormalities of acid/base balance besides those caused by excess/insufficient CO2

Acidemia that is allowed to progress will result in Metabolic acidosis :: 

 

Acidosis is determined by calculating the Anion Gap (AG)

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Alkalemia that progresses will result in metabolic alkalosis

Summary of causes: Increases in base [HCO3-] or loss of an acid [H+]

1. diuretics or genetic diseases that result in a loop diuretic defect by causing an increased flow thru tubules, increased Na+ reabsorption, incr H+ secretion

2. alkaline drugs

3. loss of Cl- (HCl) from vomiting stomach contents

4. Excess aldosterone :: incr Na+ reab, due to exchange mechanism will have H+ secretion

5. Excessive Sweating :: Cl- loss

6. Secretory Diarrhea :: Cl- loss

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Analyzing Acid Base Disorders is important since

Metabolic Acidosis if HCO3- < 24 mM

Respiratory Acidosis if pCO2 >40 mmHg

Metabolic Alkalosis if HCO3- > 24 mM

Respiratory Alkalosis if pCO2 <40 mmHg

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Compensation ::

1. Respiratory Compensation

Compensation in metabolic acidosis when pCO2 < 40 mmHg
Compensation in metabolic alkalosis when pCO2 > 40 mmHG

2. Renal compensation :  of respiratory change

Compensation in respiratory acidosis when HCO3- < 24 mM

Compensation in respiratory alkalosis when HCO3- > 24 mM

Mixed Acid Base Disorders:

Common:

TREATMENT OF ABNORMALTIES ::

Drugs to neutralize excess

Chemical analysis of abnormalities uses

AGING CHANGES to affect fluid and acid/base ::

1. changes in water

2. decreased homeostasis regulation

3. diseases that lead to e- change such as

a. congestive heart failure  (CHF)

b. diabetes mellitus (DM)

c. chronic renal failure (CRF)