Biochemistry

Front 1

Osmolality

Back 1

Measures body electrolyte/water balance. It is proportional to the total concentration of all dissolved molecules. Sodium is the major influence of osmolality.
Normal Serum Osmolality: 280-300 mosmol/kg.
Serum levels dependent on Na, glucose and urea.
High osmolality - results in water moving out of the cell (ICF to ECF).
Ex. High blood glucose (hyperglycemia) results in water shift from ICF(neurons) to ECF. Dehydration occurs, can manifest coma.

Front 2

Osmotic Pressure

Back 2

Semipermeable membrane of cells allows water osmosis to occur between ECF and ICF. Plasma proteins do not cross the membrane and are responsible for osmotic pressure.

Front 3

Colloid Osmotic Pressure

Back 3

Role of albumin
Na+ is small and can exit from ICF to interstitial space, and carries with it water. To prevent loss of water, albumin binds to water. This results in colloid osmotic pressure.

Front 4

Edema

Back 4

Low albumin results in increased water in in interstitial space (between cells). Commonly seen when osmotic pressure of blood is low.
Burns - damage to capillaries (loss of albumin)
Low protein diet - protein responsible for osmotic pressure
Renal/Liver diseas

Front 5

Acids

Back 5

Are compounds that donate a H+ (hydrogen ion) to a solution/ accept electrons.
Strong acids tend to dissociate completely in solution, whereas weak acids dissociation is limited

Front 6

Bases

Back 6

Are compounds that accept a H+ ion/donate electrons.

Front 7

pH

Back 7

Plasma pH = 7.4
[H+] = 35-45 nmol/L

Front 8

Ka

Back 8

Dissociate constant of acid
Ka = [H+] [A-]/ [HA]
The larger the Ka, the stronger the acid, because most of the HA has dissociated. Smaller the Ka, weaker the acid.

Front 9

pKa

Back 9

= -logKa
Ka = acid dissociation constant, which is the measure of the strength of an acid in solution.

Front 10

Buffers

Back 10

Consist of a weak acid and its conjugate base.
They resist change in pH from addition of small quantities of acids (H+) or bases (OH-)

Front 11

Buffering Capacity

Back 11

When pH=pKa [weak acid] = [conjugate base].
Buffers in body fluids require pKa around 7.4 (arterial pH). The higher the buffer concentration, the higher its buffering capacity.

Front 12

Henderson-Hasselbalch Equation

Back 12

pH = pKa + log [A-]/[HA]
If the pKa of a weak base is known, the equation can be used to calculate the ratio of the weak acid to the conjugate base at any pH.

Front 13

Henderson-Hasselbalch in Pharmacology

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Most drugs are either weak acids or weak bases and are absorbed in their uncharged forms. Thus, a weak acid such as aspirin, the uncharged HA can pass through membranes and A- cannot.
For weak base, such as morphine, the uncharged form B can pass through and BH+ does not.

Front 14

Acid Drugs

Back 14

(pK<7) Are better absorbed in the stomach. They are often present in uncharged form and because the pH <pK, it will be better absorbed
Acidic drugs [HA] release a proton [H+], causing a charged anion to form [A-] (conjugate base)
HA <---> H+ + A-
Ex. Aspirin
(pH<pK) uncharged form R-COOH (stomach)
(pH>pK) charged (-) form R - COO - (intestine, will not absorb)

Front 15

Basic Drugs

Back 15

(pK<7) are better absorbed in the intestine. Because of pH of stomach is low (pH 1-2). Basic drugs will be present in their charged (+) forms and wont be absorbed. In the stomach it is present in the uncharged form.

Weak bases [BH+] also release H+, however the protonated form of basic drugs is usually charged and loss of a proton produces an uncharged B:
BH+ <--> B + H+
Ex. Morphine

(pH<pK) charged form R-NH4+ (stomach)
(pH >pK) uncharged form R-NH3- (intestine)

Front 16

Metabolic Production of Acids

Back 16

-Metabolism produces 22,000 mmol/day of acid
Volatile - CO2 (major 22,000)
Noncolatile - sulfurice, phosphoric and ketone bodies (40-80 mmil/day)

Maintained by buffer, respiratory and kidney systems

Front 17

Body buffers

Back 17

Plasma pH is maintained at 7.36 - 7.44 and intracellular at 7.1 (lower because of metabolic acids)
Major Buffer systems:
Bicarbonate-carbonic acid - (ECF buffer)
Hemoglobin (histidine)
Phosphate (ICF)

Front 18

Bicarbonate Buffer

Back 18

CO2 + H20 <---carbonic anhydrase--> H2CO3 (carbonic acid)
Carbonic Acid dissociates --> H+ + HCO3- (bicarbonate)
pKA of bicarbonate buffer = 6.1

Front 19

Normal [HCO3-] and Arterial PCO2

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[HCO3] = 22-25 mEq/L (regulated by renal system)
Arterial PCO2 = 40 mmHG (regulated by respiratory)
Because these two levels are regulated independently, the bugger system is the most important in eCF.

Front 20

Transport of C02 (Tissues to lungs)

Back 20

1) O2 unloads from Hb because of low O2 in the cells, and readily passes across cells.
2) CO2 in cells is high, so diffuses out into RBC
3) With water (H20) and carbonic anhydrous --> becomes carbonic acid (H2CO3)
4) Carbonic acid dissociates to produce H+ ions and bicarbonate anion [HCO3-]
5) Hb acts as buffer and attaches to H+ ions

Front 21

Transport of CO2 (at the lungs)

Back 21

1) O2 passes from alveoli to RBC
2) HHb dissociates to form H+ ions and Hb, which binds with O2 from lungs to for HbO2
3) HCO3- (bicarbonate anion) binds with H+ to from carbonic acid
4) Carbonic acid with help of carbonic anyhydrase dissociates into water and C02,
5) CO2 diffuses into alveoli of lungs and is expelled

Front 22

Acidosis

Back 22

When the blood pH falls.
Respiratory center is stimulated resulting in increased respiration (hyperventilation). There is an increased washout of CO2, lowering PCO2 (arterial).

Front 23

Alkalosis

Back 23

When the pH increases.
The respiratory system is inhibited, resulting hypoventilation. Increases retention of CO2, increasing PCO2.

Front 24

Hyperventilation

Back 24

Increase respiration.
Decrease in CO2 and PCO2

Front 25

Hypoventilation

Back 25

Decrease in respiration
Increase in CO2 and PCO2

Front 26

Reabsorption of filtered bicarbonate

Back 26

1) CO2 + water and carbonic anhydrase convers into carbonic acid
2) Carbonic acid dissociates into bicarbonate and H+ ions. Bicarbonate enters the blood
3) H+ enters the tubular lumen and binds with filtered bicarbonate and converts to carbonic acid
4) Carbonic Acid dissociates into CO2 and enters back into long

NO FILTERED BICARBONATE IS LOST

Front 27

Acetazolamide

Back 27

Inhibits carbonic anhydrase.
Used to treat metabolic or respiratory alkalosis.
Interferes with bicarbonate (HCO3) reabsorption, thereby reacidifying the blood.

Front 28

Role of Phosphate buffer in formation of new bicarbonate

Back 28

For every H+ that is excreted into the tubular lumen, one bicarbonate is gained in the blood. You need new bicarbonate because you loose bicarbonate through buffering. Filtered phosphate HPO4 acts as buffer and binds with H+ and is converted to H2PO4 which is excreted in the Urine

Front 29

Role of Ammonia in Formation of new bicarbonate

Back 29

Glutamine is broken down into ammonia by glutaminase.
Ammonia is then filtered in the tubular lumen and binds with H+ ions for dissociation of carbonic acid.
- Ammonium chloride is excreted in urine NH4Cl
-Ammonia has MORE capacity than phosphate