Patho unit 2

Intracellular fluid (ICF)

Extracellular fluid (ECF)

• interstitial fluid compartment
• intravascular fluid compartment

Sum of fluids within all compartments

• 1) high metabolic rate,
• 2) accelerated turnover of body fluids from greater body surface area in proportion to body size,
• 3) renal mechanisms that regulate fluid and electrolyte conservation may not be mature enough to counter fluid losses.

• 1) increased amount of body fat
• 2) decreased muscle mass
• 3) decreased ability to regulate sodium and water balances
• 4) kidneys are less efficient in producing concentrated urine and responses for conserving sodium become sluggish.

Osmotic forces

water channel proteins that provide permeability to water allowing for osmosis

ECF and is responsible for osmotic balance of the ECF

ICF

Hydrostatic pressure produced by cardiac contraction

Plasma proteins (albumin) generate plasma oncotic pressure because water, sodium and glucose readily move across the capillary membrane

Capillary hydrostatic pressure and interstitial oncotic pressure

plasma oncotic pressure (pressure of plasma proteins) and the interstitial hydrostatic pressure

• Net filtration = forces favoring filtration - forces opposing filtration
• It is the movement of fluid back and forth across the capillary membrane wall to maintain equilibrium between spaces. There is arterial filtration and venous reabsorption, therefore, the arterial end of the capillary has a greater hydrostatic pressure than cappillary oncotic pressure causing water to filter into the interstitial space. Likewise, at the venous end of the capillary, oncotic pressure exceeds hydrostatic pressure causing water to filter back into the circulation leading to equilibrium between the spaces.

• It is a problem of fluid distribution rather than fluid excess.
• 1) increased capillary hydrostatic pressure (fluid moves out of the capillary into the interstitial space)
• 2) decreased plasma oncotic pressure (decreased amount of fluid moving back into capillary)
• 3) increased capillary membrane permeability (permits the escape of plasma proteins into the interstititial space)
• 4) lymphatic obstruction (decreases amount of plasma proteins able to move into the lymphatics and return to the circulation - accumulates in the interstitial space)

It increases hydrostatic pressure of fluid within the capillaries and causes fluid to escape into the interstitial space

Increases hydrostatic pressure causing fluid to escape into the interstitium causing edema.

loss (nephrotic syndrome, hemorrhage, burns) or decreased production of plasma albumin (liver disease or protein malnutrition) causing decreased oncotic attraction of fluid within the capillary, thus fluid moves into the interstitial space.

Burns cause increase in capillary permeability due to the inflammatory immune response. This causes proteins to escape from the plasma and produce edema through the loss of oncotic pressure and a gain in interstitial fluid proteins. This makes it appear that the he is in a state of dehydration because the fluid is in the interstitial spaces and unavailable for metabolic processes or perfusion causing hypotension.

The renal effects of aldosterone from the adrenal cortex and natriuretic peptides.

antidiuretic hormone (ADH) fromthe posterior pituitary

Sodium

• 1) regulates osmolality (interstitial and intravascular fluid vol)
• 2) maintains neuromscular irritibility for conduction of nerve impulses along with K+ and Ca+.
• 3) regulates acid-base balance (NaHCO3 and NaPO4)
• 4) participates in cellular chemical reactions and membrane transport
• 5) indirectly regulates water balance thru regulation of extracellular osmotic forces with Cl- and bicarb.

• It is secreted when sodium levels are low, potassium levels are high, or renal perfussion is decreased.
• It is released form the adrenal cortex and increases the reabsorption of sodium and secretion of potassium by the distal tubules. This makes sodium concentration in ECF enhanced and potassium is excreted in the urine.

When circulating blood volume or BP decreases, renin is secreted by the kidney. Renin stimulates the release of Angiotensin 1 which is then converted to Angiotensin II. Angiotensin II then stimulates the secretion of aldosterone and causes vasoconstriction. Aldosterone promotes sodium and water reabsorption, conserving blood volume. The vasoconstriction increases BP and restores renal perfusion. This inhibits further release of renin.

hormones (ANP) produced by the myocardial atria, (BNP) produced by the myocardial ventricles, and urodilatin within the kidney.

They decrease blood pressure and increase sodium and water excretion. Therefore, they are natural antagonists to the renin-angiotensin system.

Increased glomerular filtration, aldosterone, and natriuretic peptides.

Chloride - it follows the active transport of sodium so that its changes are proportional to that of sodium.

Secretion of ADH and perception of thirst.

neurons located in the hypothalamus that are stimulated by increased osmolality. When released, they cause thirst which leads to drinking water to restore plasma volume and dilutes the ECF osmolality. Addionally, they cause release of ADH which then increases permeability of renal tubular cells to water and sodium. Water is then reabsorbed into the plasma causing increased urine concentration and decreased plasma osmolality.

They are stretch receptors located in the aorta, pulmonary arteries, and carotid sinus. When there is decreased atrial or aortic pressure, it stimulates release of ADH which inturn leads to reabsorption of water and promotes restoration of plasma volume.

Changes in TBW are accompanied by proportional changes in electrolytes and water. For example, if a person loses pure plasma (hemorrhage) or ECF (sweating), fluid volume is depleted, but the number and type of electrolytes (sodium) and osmolality remains within normal range.

the osmolality of the ECF is elevated causing water to move from intracellular space to extracellular space. This causes ICF dehydration/ECF overload leading to symptoms of hypervolemia.

Causes: 1) hypernatremia (from hypertonic IVF, hyperaldosteronism, cushing syndrome) which leads to osmotic attraction of water and symptoms of hypervolemia, 2) ECF free water deficit (from DI, hyperventilation) which leads to hypovolemia.

• 1) inadequate free water intake (causes ICF and ECF dehydration)
• 2) excessive administration of hypertonic saline solution (sodium bicarb)
• 3) hyperaldosteronism (causes conservation of sodium and reabsorption of water in the renal tubules)
• 4) cushing syndrome (caused by excess secretion of ACTH which also causes increase secretion of aldosterone)

• Serum sodium > 147 mEq/L
• Seizures, coma, pulmonary edema from primary hypernatremia
• Thirst, fever, dry mucous membranes, hypotension, tachycardia from hypernatremia secondary to water loss.

This is a hypernatremic state with dehydration possibly from water loss. It is treated with isotonic salt-free fluid (D5W) until the serum sodium level returns to normal. Additionally, attempt to stop the source of the water loss. Must be treated slowly to prevent rapid movement of fluid into brain cells causing cerebral edema, seizures and brain death.

When the osmolality of the ECF is less than normal causing fluid to shift from the ECF to the ICF (where osmotic pressure is greater) leading to cellular swelling.

Causes: 1) hyponatremia which causes osmotic pressure of the ECF to decrease and water moves into the cell. Plasma volume then decreases, leading to symptoms of hypovolemia. 2) Free water excess which causes both the ICF and ECF volume increase leading to symptoms of hypervolemia and water intoxication with cerebral and pulmonary edema.

• 1) pure sodium deficit: diuretics and extrarenal losses such as vomitting, diarrhea, GI suctioning, burns.
• 2) Inadequate intake of dietary sodium (rare)
• 3) Dilutional hyponatremias: with excess of TBW compared with total body sodium or a shift of water from the ICF to ECF (mannitol), excessive replacement with D5W, excessive use of hypotonic solutions like 0.45 NS, excessive sweating may stim thirst and lead to intake of large amounts of water.
• 4) Hypotonic hyponatremia: when TBW exceeds the increase in sodium as in renal failure
• 5) Hypertonic hyponatremia: when the shift of water from the ICF to ECF occurs with hyperglycemia, hyperlipidemia, and hyperproteinemia. Water is attracted to the ECF from the ICF compartment causing dilutional hyponatremia and other electrolytes.

She is in an isotonic hypovolemic state with hyponatremia, hypochloremia, metabolic alkalosis. She needs IVF replacement with hypertonic 0.9 NS until her sodium returns to normal, NPO, possibly give her bicarb suppliment. All this while taking care not to increase her sodium level too quickly.

• Conditions such as fear, pain, acute infection, brain trauma, surgery, drugs, ADH secreting tumor cells in the lung, pancreas, or other tissues cause increased ADH secretion which leads to increased renal reabsorption of water.
• Amount of ADH is inappropriate in relation to serum sodium levels. Serum sodium levels and osmolality are reduced from dilution. The kidneys continue to secrete sodium making urine sodium and osmolality elevated. Body fluid volume is increased because of reabsorption of water and urine volume is decreased.

serum and urine sodium will be decreased. Serum and urine osmolality are decreased because water is in excess of sodium therefore diluting the sodium. Hct will be reduced as well. Treatment would be to withhold water for 24 hours. For more severe forms showing CNS effects, hypertonic saline (3%) can be used. Arginine vasopressin receptor antagonist can be used for SIADH.

• 1) regulation of ICF osmolality
• 2) provides balance for intracellular electrical neutrality in relation to hydrogen and Na+
• 3) required for glycogen deposition in the liver and skeletal muscle cells
• 4) maintains resting membrane potential

• 1) the kidney
• 2) aldosterone levels
• 3) changes in pH and thus hydrogen ion concentration

• During acidosis: hydrogen is moving into the cell, therefore K+ moves out of the cell into the ECF. Decreased ICF K+ results in decreased K+ secretion by the kidneys leading to hyperkalemia.
• During alkalosis: hydrogen moves out of the cell causing K+ to move into the cell. Distal tubular cells increase their secretion of K+ into the urine leading to hypokalemia.

When potassium levels are increased , aldosterone is released stimulating secretion of potassium into the urine by the distal tubules of the kidney. Additionally, it increases the secretion of K+ from sweat glands.

aldosterone, insulin, epinephrine

it stimulates the Na+/K+ ATPase pump, thereby promoting the movement of potassium into the liver and muscle cells simultaneously with glucose transport after eating.

• Beta 1 adrenergics (epinepherine) stimulate movement of K+ into cells
• Alpha adrenergics shift K+ out of cells.

Since it is a state of acidosis, H+ moves into the cell in exchange for K+ moving out of the cell in attempt to accomodate the acidotic state. Normal level of potassium is maintained in the plasma, but continues to be lost in the urine causing a deficit in total body K+. If insulin is given for treatment of DKA, the insulin will drive the potassium into the cells and causing severe hypokalemia. K+ replacements must be given as well.

• 1) decreased po intake
• 2) increased movement of K+ into cells from ECF (as with alkalosis).
• 3) loss of total body K+ stores (as with GI and renal disorders)
• 4) increased aldosterone secretion (as with stress, dehydration and hyponatremia, etc)
• 5) increased renal K+ excretion (diuretics or low Mag)

• decreased hepatic and skeletal muscle glycogen synthesis,
• impaired renal function
• polyuria (increased urine with low spec grav)
• polydipsia (increased thirst with dehydration)
• neuromuscular excitability
• skeletal muscle weakness,
• cardic dysrhythmias

SB, AV block, PAT, depressed T-wave, U-wave increases, ST depression, peaked P-wave, prolonged QRS

* slows the Na/K pump

correction of acid-base balance is first and foremost

• 1) increased intake
• 2) shift of K+ from ICF to ECF
• 3) decreased renal excretion of K+

cell trauma or change in cell membrane permeability, acidosis, insulin deficiency, cell hypoxia, burns, crush injuries

Since Addison's results in decreased production and secretion of aldosterone, there will be a tendency toward hyperkalemia. Aldosterone promotes the movement of K+ from the ECF to ICF with hyperkalemia so that the plasma K+ can then be filtered out by the kidneys and K+ can be secreted in the urine.

Muscle weakness, restlessness, diarrhea, muscle paralysis, cardiac arrythmias: narrow and peaked T-waves, shortened QT interval, depressed ST segment, prolonged PR interval, widened QRS, VF, cardiac arrest. it also causes hypopolarized cell (increased excitability).

• It influences the threshold potential by augmenting or overriding the effects of hyperkalemia. for example, hypocalcemia makes the threshold potential more negative thereby enhancing the neuromuscular effects of hyperkalemia (more muscle weakness). Hypercalcemia makes the threshold potential less negative, thereby counteracting the effects of hyperkalemia on resting membrane potential.
• K+ effects resting membrane potential versus Ca+ effects threshold potential.

• 1) Calcium gluconate: retores normal neuromuscular irritibility.
• 2) glucose: stimulates insulin secretion
• 3) glucose and insulin: facilitates cellular entry of potassium
• 4) Sodium bicarb: corrects metabolic acidosis and lowers serum potassium

• Located primarily in the mitochondria.
• 1) major cation for the structure and function of bones and teeth
• 2) enzymatic cofactor for blood clotting
• 3) hormone secretion and function of cell receptors
• 4) membrane stability and permeability

2.5 - 4.5 mg/dl

acts as an intracellular and extracellular anion buffer in the regulation of acid-base balance, provides energy for muscle contraction in the form of ATP

• 1) PTH (secreted in response to low calcium - causes reabsorption of calcium and inhibition of phosphate reabsorption leading to increase in serum calcium and urinary excretion of phosphate.)
• 2) Vitamin D (secreted in response to low phosphate levels, low calcium, and PTH secretion to further enhance absorption of calcium in the small intestine, bone, and renal tubules of the kidney)
• 3) calcitonin (decreases calcium levels by inhibiting osteoclasitic activity in bone)

8.5 - 12mg/dl

• 1) inadequate intestinal absorption
• 2) deposition of ionized calcium into bone or soft tissue
• 3) blood administration
• 4) decreases in PTH and vit. D.

Calcium binds with it making absorption of calcium and phos by the body impossible or difficult.

the citrate in the blood products binds to the calcium so it is unavailable for absorption

Pancreatitis leads to the release of lipases into soft tissue spaces and free fatty acids are formed which bind the calcium.

Bone mets inhibit bone resorption and increase calcium deposits into bone, thereby decreasing serum calcium levels.

Calcium would be low due to decreased intestinal absorption of calcium (vit D) and the loss of PTH.

• Hypocalcemia because the increase in pH enhances protein binding of iCa.
• Low protein levels decrease the amount of bound calcium in the plasma.

Hyperreflexia due to increased neuromuscular excitability from a lower threshold potential approaching resting membrane potential.

Hypocalcemia

• Positive Chvostek: tapping on facial nerve just below the temple to elicit twitch of the nose or lip
• Positive Trousseau: contraction of the hand and fingers when the arterial blood flow in the arm is occluded for 5 minutes.

Hypercalcemia

Decreases serum binding of calcium to albumin which increases ionized calcium thus causing hypercalcemia.

• intestinal malabsorption
• increased renal excretion of phosphate

hypoxia, bradycardia, heart arrhythmias (especially heart block) due to decreased ATP levels which diminish release of oxygen to the tissues. May also show muscle weakness, respiratory failure, irritibility, confusion, coma, convulsions.

2 - 4.5 mg/dl

small intestine and kidney

1.8 - 2.4

Mg inhibits potassium channels, therefore, hypomagnesemia causes movement of K out of the cell. The kidneys then excrete the potassium and it results in hypokalemia.