1. blood + fluid compartments

Which of the following has a very high concentration in plasma, but a much lower concentration in the interstitial fluid?
1. Sodium
2. Proteins
3. Potassium
4. Bicarbonate

2. Proteins

blood makes up what % of the bodily fluids

8% of the bodily fluids

composition of blood

Hematocrit

% of blood volume composed of erythrocytes

Men = 45%

Women = 40%

formed elements

erythrocytes

no nucleus so not cells 

common plasma proteins

Albumin

Globulins

Fibrinogen & Clotting Factors

transthyretin

a1-antitrypsin

B- lipoprotein (LDL)

transferrin

complement proteins

Plasma proteins: Albumin

Most abundant plasma protein

Binds to many substances in plasma – important for transport

• steroids, bile, salts, fatty acids

Maintains osmotic (oncotic) pressure

oncotic pressure

osmotic pressure specific to plasma proteins 

Plasma proteins: Globulins

Carrier proteins

immunoglobulins (antibodies)

what type of immunity is antibodies (immunoglobulin)?

humoral immunity

plasma proteins: transthyretin

Binds T3/T4 and Vitamin A

plasma proteins: a1-antitrypsin

Protease inhibitor

plasma proteins: B- lipoprotein (LDL)

Binds lipid

plasma proteins: transferrin

Binds iron

plasma proteins: complement proteins

Innate immunity

To measure a specific compartment what are the conditions?

solute must be freely permeable throughout compartment, but confined to only that compartment

how to measure body fluid compartments: Total body water

3H2O (tritiated water)

how to measure body fluid compartments: Extracellular Fluid

22Na+, Inulin

how to measure body fluid compartments: Intracellular Fluid

Can't be measured directly
ICF = TBW – ECF

how to measure body fluid compartments: Plasma

125I-albumin, Evan's Blue dye

how to measure body fluid compartments: Interstitial Fluid

Can't be measured directly
ISF = ECF – plasma

other fluid compartments

Lymph

Bone and dense connective tissue fluids

Transcellular fluid

other fluid compartments: Lymph

Component of interstitial fluid

other fluid compartments: Bone and dense connective tissue fluids

~ 15% of total body water

other fluid compartments: Transcellular fluid

Fluids contained completely within epithelial-lined spaces

Synovial (joints), intrapleural, aqueous humor, peritoneal

OR

‘Functional’ ECF

• Cerebrospinal fluid, saliva, GIT secretions, sweat

Fluid ‘spaces’: First space

Intravascular fluid (plasma)

Fluid ‘spaces’: Second space

Interstitial and Intracellular fluid

Edema is accumulation in second space (interstitial)

Fluid ‘spaces’: Third space

Fluid compartments not easily exchanged with ECF

• Peritoneum

• Intrapleural

Patients with severe burns will often have ‘third spacing’ where fluid accumulates at the burn site, outside of interstitial fluid

ascites

Peritoneum Fluid accumulation

pleural effusion

Intrapleural Fluid accumulation

Ions balanced between ECF and ICF

Sodium is major cation in ECF

• Balanced with chloride and bicarbonate

Potassium is balanced with organic ions and proteins 

Fluid losses

Sweat

Insensible water loss

Gastrointestinal secretions

Fluid losses: Sweat

Variable: water loss of 100 – 8,000 mL/day

Fluid losses: Insensible water loss 

800 mL/day

Through skin (trans-epithelial) as well as through the respiratory tract

Cannot be prevented

Fluid losses: Gastrointestinal secretions

98% of water from secretions is reabsorbed

200 mL H2O lost in feces

Important factors in fluid balance

Osmolarity

Osmolality

Hydrostatic Pressure

Sodium balance

Water balance

Osmolarity VS Osmolality

Osmolarity = osmoles/L solution

Osmolality = osmoles/kg H2O

Similar (interchangeable) in dilute physiological solutions

Hydrostatic Pressure

pressure that pushes fluid through 

caused by plasma proteins → main reason for oncotic pressure 

Sodium balance

Primary osmolite in the ECF

Water + sodium balance

Together maintain ECF volume and osmolarity

Fluid exchange occurs at 

capillaries

Capillaries

consist of single layer of endothelial cells surrounded by basement membrane

Endothelial cells linked together by interendothelial junctions

• Adhering junctions or tight junctions

Effect of inflammation on capillary leakiness 

Endothelial tight junctions regulated by a variety of signaling mechanisms

• Cytokines, extracellular calcium, G proteins, etc.

E.g.: Histamine causes transitory gaps of 100 to 400 nm between adjacent endothelial cells

Increased endothelial permeability due to inflammatory response

Cytoskeletal contractility can change the shape of cells and pull individual endothelial cells apart

Breakdown or modulation of the intercellular junctions

Capillary exchange of solutes: transcellular

Gases and other small non-polar molecules

Capillary exchange of solutes: water-filled pores

Small, polar molecules can only traverse through water-filled pores

Low permeability

Capillary exchange of macromolecules

Molecules with a radius >1 nm (e.g., plasma proteins)

Cross through wide intercellular clefts, fenestrations, and gaps (when present and large enough)

Caveolae

Caveolae

facilitate transcytosis of macromolecules across endothelial cell

Capillary exchange of water

Fluid transfer across capillaries is convective

Through aquaporins and interendothelial clefts

Depends on net hydrostatic and osmotic forces

Plasma osmotic pressure “pulls” fluid back into capillary

• Much higher in capillary due to plasma proteins

Starling forces

At arterial end, hydrostatic pressure exceeds other forces → Favors filtration

At venous end, capillary oncotic pressure exceeds → Favors reabsorption

Regulation of Extracellular fluid (2 ways) 

Fluid movement between ECF and ICF is passive

Therefore, ECF must be tightly regulated

Two ways:

ECF fluid osmolarity is regulated by changing the amount of water

ECF fluid volume is regulated by changing the amount of sodium

• These two operate in tandem, but have some distinctions

Two mechanisms for sensing fluid abnormalities

1) Baroreceptors

2) Osmoreceptors

Two mechanisms for sensing fluid abnormalities: 1. Baroreceptors

Respond to increased hydrostatic pressure due to increased blood volume

Regulate sodium

Two mechanisms for sensing fluid abnormalities: 2. Osmoreceptors

Respond to the osmolarity of the ECF

Regulate water

The primary osmoreceptors are located in:
1. Medullary collecting duct of kidney
2. Aortic arch
3. Hypothalamus
4. Lungs

3. Hypothalamus ADH

Mechanisms for regulating plasma volume

Renin-Angiotensin-Aldosterone (RAAS)

Atrial Natriuretic Peptide (ANP)

Anti-diuretic hormone (ADH)

 

Mechanisms for regulating plasma volume: Renin-Angiotensin-Aldosterone (RAAS) effects + mechanism
 

Aldosterone causes Na+ to be reabsorbed

in response to low blood pressure (stimulus), low ECF volume kidney secretes renin → converts angiotensinogen to angiotensin 1 → ACE converts angiotensin 1 to angiotensin 2

angiotensin 2

causes massive vasoconstriction

causes aldosterone to be released from the adrenal cortex

aldosterone

acts on kidneys to increase the amount of sodium that is absorbed back into the blood → ECF + blood pressure increase

Mechanisms for regulating plasma volume: Atrial Natriuretic Peptide (ANP) effects

Opposite” hormone to aldosterone

↑BP stimulates release from atria

Causes excretion of sodium and water.

Mechanisms for regulating plasma volume: Anti-diuretic hormone (ADH) effects 

AKA Arginine Vasopressin

Vasoconstriction + Increased H2O reabsorption

where is ADH synthesized

in the hypothalamus

where + when is ADH released? 

Release from posterior pituitary is increased by:

• High plasma osmolarity (MAIN)

• Low central blood volume

Alterations in sodium and water balance (3 types) 

Isotonic alterations

hypertonic alterations

hypotonic alterations

Alterations in sodium and water balance: Isotonic alterations

Gain or loss of ECF volume but osmolarity is normal (280-294 mOm)

Isotonic fluid loss or isotonic fluid excess

Isotonic alterations: Isotonic fluid loss (results in, caused by, treated with)

Results in dehydration and hypovolemia

Caused by hemorrhage, diaphoresis (sweating), inadequate fluid intake

Treated with 0.9% NaCl (i.v. fluids)

Isotonic alterations: Isotonic fluid excess (results in, caused by, treated with)

Results in increased BP, pulmonary edema, heart failure

Caused by excessive iv. fluid administration, abnormal aldosterone secretion

Treated with diuretics

Alterations in sodium and water balance: Hypertonic alterations Consequence

Osmolarity of ECF greater than normal

Hypernatremia → Cell Shrinkage

Hypernatremia is caused by

Loss of H2O: hyperosmotic dehydration

OR

Gain of NaCl: hyperosmotic overhydration

Hypertonic alterations: hyperosmotic dehydration

Loss of H2O

Most common – could result from vomiting, diarrhea, inadequate water intake

Diabetes insipidus – lack of ADH

Hypertonic alterations: hyperosmotic overhydration

Gain of NaCl

Rare – results from oversecretion of aldosterone or hyperosmotic iv. fluid

Rarely due to excess salt consumption in healthy individuals

Alterations in sodium and water balance: Hypotonic alterations types + Consequence

Osmolarity of ECF below normal

Hyponatremia → Cell Swelling

Hyponatremia is caused by

Loss of Na without loss of water: hypoosmotic dehydration

OR

Loss of water, but greater loss of Na

OR

Gain of pure water: hypoosmotic overhydration (water intoxication)

Hypotonic alterations: hypoosmotic dehydration

Loss of Na without loss of water

Syndrome of inappropriate ADH (SIADH)

Rarely due to low-sodium diet

Hypotonic alterations: Loss of water, but greater loss of Na

Adrenal insufficiency (aldosterone deficiency)

Hypotonic alterations: hypoosmotic overhydration (water intoxication)

Gain of pure water

Interstitial ‘Gel fluid’

resists volume change

Interstitium

Fluid-filled interstitial space identified because of improved fixation and microscopy techniques

In dermis and many submucosal tissues

• “Pre-lymph

Lymphatic circulation

Filtration at capillaries exceeds absorption by ~ 2 L per day

Lymphatics remove excess fluid and protein from interstitium

Keeps interstitial colloid pressure low

Drains back into circulation at inferior vena cava

Flow into lymphatics 

Lymphatic capillaries are a type of ‘pressure release valve’

Series of one-way valves ensures lymph moves in one direction only

Edema

excess fluid in body tissues

Intracellular edema causes 

Intracellular edema is particularly problematic for CNS

1. Hyponatremia

2. Reduced tissue metabolism or lack of nutrition

• Na-K pump slows and Na+ builds up inside cell (water follows)

3. Inflammation → Increases membrane permeability
   

Extracellular edema causes 

most common

1. Increased capillary pressure

2. Decreased plasma proteins

3. Increased capillary permeability

4. Blockage of lymph return

Increased capillary filtration is caused by

Increase filtration coefficient

Increase hydrostatic pressure

Decrease colloid osmotic pressure

Extracellular edema causes: Increased capillary pressure

leads to increased hydrostatic pressure

Increased blood volume (hypernatremia)

High venous pressure

• due to Heart failure or venous obstruction/failure

Decreased arteriolar resistance

• due to Impaired sympathetic nervous system or vasodilator drugs

Extracellular edema causes: Decreased plasma proteins

leads to decrease in colloid osmotic pressure

Loss of proteins in urine

Liver failure

Extracellular edema causes: Increased capillary permeability

leads to increase filtration coefficient

Immune reactions

Bacterial infections/toxins

Extracellular edema causes: lymphedema

Failure of lymphatic system → blockage of lymph return

Cancer or infection

Surgery or congenital absence

Which of the following are forces that favor filtration in
systemic capillaries? (Check all that apply)
1. Capillary hydrostatic pressure
2. Interstitial fluid hydrostatic pressure
3. Plasma osmotic pressure
4. Interstitial fluid osmotic pressure

1. Capillary hydrostatic pressure
2. Interstitial fluid hydrostatic pressure