Fluids Lecture 2

three fluid compartments in the body

intracellular fluid, plasma, interstitial fluid

what 2 fluids make up the ECF

plasma and interstitial fluid

capillary wall is permeable to

salts, solutes, water

Interstitial Steady-State

Rate of fluid exit from capillary = Rate of fluid drainage into lymphatic vessels

The Distribution of ECF is Determined by

Starling Forces

lack of gradient due to IF and plasma shared property

Because IF and plasma are the same solution, there is no osmotic gradient due to salts and solutes

starling forces: hydrostatic pressure

Blood pressure squeezing plasma out of capillaries into the IF space

From plasma to capillary wall (IF)

can plasma proteins (albumin) leave the capillaries

no

Plasma proteins act as

osmolytes

oncotic pressure

Force exerted specifically by blood plasma proteins on water movement

From IF to capillary wall on plasma

net filtration pressure equation

Net filtration pressure = (P_c - P_i) - (π_c-π_i)

+NFP

capillary → interstitial space

-NFP

interstitial space → capillary

If the balance of Starling Forces is disturbed

the ratios of plasma and interstitial fluid will be changed

alterations in starling forces: effect on plasma

any change in volume is dealt with by the volume homeostatic feedback loop

alterations in starling forces: effect on interstitial fluid

changes in extracellular fluid volume outside of the circulation cannot be sensed and are beyond primary homeostatic control

Fluid build up in tissue (or body spaces) outside of the circulation (edema) can only be remedied by treatment of

the underlying cause

Edema

Interstitial fluid build-up in tissue increases the diffusion distance over which nutrients, oxygen, and wastes must travel to and from circulation

Insufficient perfusion can cause cell injury, death, and lead to necrosis

localized edema

Localized to a specific site (e.g., sprained finger) or organ (e.g., pulmonary edema

generalized edema

More uniform distribution of fluid in interstitial spaces

generalized edema: dependent/pitting edema

A manifestation of generalized edema that is gravity-dependent (i.e., fluid accumulates in lowest part of the body, which depends on position)

Causes of Edema: Increased capillary hydrostatic pressure (Pc)

Induced by:

Increased plasma volume (Na+, water retention)

Local accumulation of fluid (prolonged standing, congestive heart failure)

Decreased vascular volume (tight clothing, inflammation of veins)

Causes of Edema: Decreased capillary oncotic pressure (πc)

Induced by:

Loss of plasma proteins (into urine: kidney disease)

Loss of plasma proteins (into IF: increased capillary permeability: burns, allergic reaction)

Decreased production of plasma proteins (liver cirrhosis, malnutrition)

Causes of Edema: Blockade of lymphatic ducts that drain interstitial fluid (lymphedema)

Induced by:

Surgical removal (Secondary lymphedema: cancer treatment)

Physical block (Secondary lymphedema: tumor or injury)

Rare genetic condition (primary lymphedema)

Treatment of Generalized Edema

Lowering capillary hydrostatic pressure, promotes fluid movement from IF back into circulation, where the additional volume can be sensed and corrected

Lower dietary salt intake

Treat with diuretics to increase urine output and lower plasma volume

Treatment of Dependent Edema

Compression stockings to increase interstitial hydrostatic pressure (Pi)

Push excess ECF back into circulation

Kwashiorkor

Affects children from 1-5 years old.

Secondary complications are usually the cause of death

Characterized by dependent edema (feet, abdomen) and undernutrition fueled by a diet composed almost entirely by carbohydrates

Kwashiorkor: how does diet induce disorder

Insufficient dietary protein → low levels of albumin → low πc

Kwashiorkor: disorder consequences

hypovolemia and edema

how does hypovolemia exacerbate edema

Hypovolemia → increased ADH, ANGII to promote Na+ and H2O reabsorption → exacerbates edema

Kwashiorkor: treatment

Correcting electrolyte imbalance, hypoglycemia, and macro and micronutrient deficiency

osmolality

a measurable property of a solution based on the amount of dissolved particles it contains

tonicity

the ability of a solution to draw water out of or into cells

ecf and icf osmolality

the same; iso-osmotic

An ECF solution that does not cause cells to alter volume is said to be

isotonic

If plasma osmolality rises above 294, it is said to be

hyper-osmotic

An ECF solution that causes cells to shrink is said to be

hypertonic

If plasma osmolality falls below 280, it is said to be

hypo-osmotic

An ECF solution that causes cells to swell is said to be

hypotonic

Water is not responding to [Na+] specifically, but to

an osmotic gradient

major osmotically active (water attracting) particle in ECF

Na+

normal plasma osmolality

280-294 mOsmol/kg

NaCl: % of plasma osmolality

242 mOsmol/kg (~85%)

only ECF component abundant enough that small % changes can substantially alter osmolality

NaCl

effect of swollen cells

Swollen cells can occlude circulation and lymph drainage

Swollen cells can even burst, releasing cytotoxins

effect from shrunken cells

Shrunken cells can release K+, affecting activity of excitable cells

ICF volume changes in response to alterations in

ECF salt concentrations

The ECF/ICF barrier is the

cell membrane

cell membrane permeability

freely water permeable due to aquaporin H2O channels but, unlike the capillary wall, are poorly salt and solute permeable

ICF volume change is the result of

water being driven across cell membranes by osmosis

An increase in [Na+] in the extracellular fluid

draws water out of cells: Cell shrinkage

A decrease in [Na+] in the extracellular fluid

allows water to be drawn into cells: Cell swelling

Homeostasis of ECF Tonicity: Rise is plasma osmolality

ECF becomes hypertonic

Tonicity-sensing cells in the hypothalamus shrink, activating the pituitary gland, results in the release of antidiuretic hormone (ADH) from the pituitary

ADH acts in the kidneys to increase water retention

Plasma (and ECF) is diluted to isotonic set point (any consequent volume disturbance is handled by volume homeostatic feedback loop)

hypotonic alteration

water excess or salt deficit

isotonic alteration

volume excess or deficit (salt and water)

hypertonic alteration

salt excess or water deficit

Darrow-Yannet Diagrams

Device for visualizing changes in osmolality and volume, because terms like ‘dehydration’ are not definitive

Can be used to depict all six classic types of fluid disturbance

what form of fluid disturbance cannot be visualized using darrow-yannet diagrams

edema, because it is a redistribution of fluid within ECF

Isotonic Alterations: ecf, tonicity, and icf

Changes in ECF volume, no change ECF tonicity: therefore no effect on ICF

2 isotonic alterations

isotonic hypovolemia and isotonic hypervolemia

Isotonic Hypovolemia (Fluid Loss): Cause, sign, resolution

Causes: Hemorrhage, excessive sweating, vomiting, diarrhea

Signs: Weight loss, dryness of skin and mucous membranes, decreased urine output, maybe decreased BP

Resolution: Oral or I-V administration of electrolytes and glucose solution

Isotonic Hypervolemia (Fluid Excess): causes, signs, resolution

Causes: Excessive administration of IV fluids, hypersecretion of aldosterone

Signs: Weight gain, distended neck veins, increased bp, diluted hematocrit, protein and edema

Resolution: Diuretics

Hypersecretion of Aldosterone: type of fluid alteration

isotonic hypervolemia

Aldosterone hypersecretion may be caused by

a tumor in the adrenal glands

effect of constitutive ALDO signal

decreases urine output by promoting Na+ reabsorption; Water follows salt: water is reabsorbed along the osmotic gradient

Treatment of Hypersecretion of Aldosterone

Surgical removal of the adenoma (if possible), or K+ sparing diuretics (Spironolactone is a competitive inhibitor of the ALDO-R)

Hypertonic Alterations (ICF Shrinkage): ECF, tonicity, ICF

Changes in ECF volume, with an increase in ECF tonicity: therefore ICF shrinkage

Hypertonic Alterations: 2 forms

pure water deficit and salt excess

Hypernatremia/Pure Water Deficit (ICF Shrinkage): Respective causes

Cause +Na: dietary, infusion of hypertonic saline

Cause –H2O: (rare) impaired water access or intake (but elderly, infants), excess water loss (hyperventilation, fever, diabetes insipidus)

Hypernatremia/Pure Water Deficit (ICF Shrinkage): ECF signs

hypo (pure water deficit) or hypervolemia (hypernatremia) depending on cause

Hypernatremia/Pure Water Deficit (ICF Shrinkage): ICF signs

Cell shrinkage, which alters cell excitability causing twitching, confusion, convulsions, coma

Hypernatremia/Pure Water Deficit (ICF Shrinkage): Resolution

Infusion with salt free but isotonic (5% glucose) fluid… Note: infusion with hypotonic solution risks red blood cell lysis and cerebral edema.

Diabetes insipidus: what form of fluid alteration

hypertonic alteration due to pure water deficit; ICF Shrinkage

Diabetes insipidus

Characterized by dilute urine production >10-15L/day and intense thirst

Diabetes insipidus: loss of what secretion

ADH

Diabetes insipidus: effect of no ADH

No ADH → ADH-receptor in kidney no activated → H2O channels (aquaporins) are not mobilized to nephron tubule

Diabetes insipidus: treatment

Consuming water to match urine output, and desmopressin (ADH analog)

Hypotonic Alterations (ICF Swelling): ECF, tonicity, and ICF

Changes in ECF volume, with a decrease in ECF tonicity: therefore ICF swelling

Hypotonic Alterations (ICF Swelling): 2 forms

salt loss and pure water excess

Hyponatremia/Pure Water Excess: respective causes

Cause -Na: Dietary, typicall in the elderly in a hospital setting; Vomiting, diarrhea, diuretic treatment

Cause -Na: Dilutional hyponatremia following infusion with 5% glucose saline

Cause +H2O: Water intoxication, ADH excess (SIADH)

Hyponatremia/Pure Water Excess: signs ECF

Hyper (pure water excess) and hypovolemia (salt loss)

Hyponatremia/Pure Water Excess: signs ICF

Cell swelling alters Vm of neurons and muscle, lethargy, confusion, seizures, coma

Hyponatremia/Pure Water Excess: Resolution

Hypertonic (3% salt) fluid replacement, but slowly to prevent osmotic demyelination syndrome

Water intoxication: type of fluid alteration

hypotonic fluid exces

Water intoxication

Drinking excessive amounts of water

Outpaces the filtration rate of the kidney (~1L plasma / hour)

Water accumulates in the brain (cerebral edema), altered excitability and pressure; can cause brain damage, coma, and death