Lecture 6- Cellular Environment

The largest single component of the body is

water

Continual intake and output of fluids in the body between various compartments are important for (2)

transporting nutrients and oxygen to the cells

removing waste and manufactured substances from the cells

Total Body Water (TBW)

the % of total body weight composed of water, can vary w age, gender, and body fat composition

Obese pts can be expected to have what TBW

less TBW with respect to body weight

Infant’s TBW

it is about 70-80% bc infants store less fats but bc they have high MR hey can be susceptible to TBW and potential evaporate fluid loss

With increasinf age, what happens to the TBW

declines due to increased fat and decreased muscle mass

Body fluid is contained in what 2 major compartments

Intracellular and extracellular

In all age groups most of the body fluid is

Intracellular (2/3)

The extracellular fluid is THEN broken down into 2 what compartments?

Intravascular and Interstitial

Intravascular-

Inside blood vessels

AKA PLASMA

one of the compartments that extracellular gets further broken down to

Interstitial-

environment btw cells and the capillary membrane

one of the compartments that extracellular fluid gets further broken down to

1L of water weighs

1kg

2.2 lbs

How does the typical 17L of extracellular fluid get distributed?

3L intravascular

8L interstitial

5L trapped in dense connective tissue and bone

1L transcellular water

Fluid Homeostasis has a net result of what 4 processes

Fluid Intake

Fluid Absorption

Fluid Distribution

Fluid Excretion

Fluid Intake-

entry into the body by any route: eating/drinking/cellular metabolism/ IV/ Feeding tubes

Fluid Absorption-

from the GI tract / from the Kidneys

Fluid Distribution

between vascular, interstitial, and intracellular compartments

Its fluid reaching the vasculature distributes between fluid compartments

Fluid Excretion-

urinary tract, skin, bowels, lungs

How does fluid intake get absorbed befpre reaching vascular compartment?

Fluid absorption from the GI tract depends on osmotic forces generated by absorption of electrolytes and other particles

What is fluid distribution the net result of?

Filtration across permeable capillary membrane

How does fluid distribution between the interstitial and intracellular compartment occur

by osmosis

Insensible fluid loss-

the amount of body fluid lost daily from skin, resp system, and bowel that is not easily measured

How is fluid excretion controlled?

primarily by the hormones Antidiuretic (ADH), Aldosterone, and Natriuretic peptides (NPs)

Filtration-

the process where fluid moves out of the capillaries into the surrounding tissue (interstitium) driven by hydrostatic forces

Osmosis-

The net movement of water caused by the osmotic concentration gradient

facilitates the movement of water between interstitial and intracellular fluid compartments across the cell membrane, driven by differences in solute concentration

Fluid Distribution between the vascular and interstitial compartments is the net result of…

filtration across permeable capillary membranes

what 2 forces move fluid from capillaries into the interstitial compartments at the capillary level?

Capillary hydrostatic pressure

Interstitial fluid colloid osmotic pressure

Capillary hydrostatic pressure-

outward push pf fluids against the capillary walls, it is important in that the blood is coming from the arteries deliveries oxygen and nutrients to the cells/tissues

Colloid osmotic pressure-

the pulling force of particles into the interstitial fluid

What provides nutrient and oxygen delivery to the cells?

water, sodium, and glucose that readily move across capillary membrane into the interstitial space

What DOES NOT cross the capillary membrane under normal circumstances?

plasma proteins bc they are too large to pass

What do the plasma proteins create then?

the plasma oncotic pressure:

“pulls” water, waste, and manufactured substances from cells back into circulation at the venous ends of the capillaries

How does the hydrostatic and colloid osmotic pressure in the INTERSTITIAL COMPARTMENT differ based on circumstances?

It is quite small in normal circumstances

During pathologic conditions like inflammation or injury, it caused plasma proteins to leak into the interstitial space, increasing excess fluid accumulation in the interstitial

During inflammation/injury, plasma proteins leak due to increased capillary membrane permeability, increasing excess fluid, what is this called?

EDEMA

what is our blood colloidal osmotic pressure?

25 mm Hg

Considering the 25 mmHg blood colloidal osmotic pressure, what happens during filtration and reabsorption?

In filtration, the hydrostatic pressure is greater, so fluid exits the capillary to balance

In reabsorption, the hydrostatic pressure is less so fluid reenters the capillary to balance

what are the things that can move across the plasma membrane (simple diffusion)?

water and small,uncharged lipid-soluble molecules

Can electrolytes move across the PM? How do they do it?

NO, they require specific channels such as Facilitated Diffusion or Active transports

Facilitated Diffusion is..

passive transport

Water passes through…. in the cell membrane

aquaporins

Osmolality-

difference in particle concentration inside and outside the cell

Number of dissolved particles in a solution

What created an osmotic pressure gradient ?

when there is a difference in particle concentration inside and outside the cell = osmolality

Osmosis moves water from an area of … solute concentration, to an area of … solute concentration, so this means water moves into a….

low to high

so water moves into a MORE concentrated solution

water moves down its concentrated gradient from high to low concentration of water

Osmotic concentration of a solution depends on..

only on the number of particles without regard to their size, charge, or mass

What are examples of solute particles?

crystalloids or colloids

to be an effective osmole, the particle must be largely confined to one particular compartment

What are the osmoles of Extra and Intracellular?

Sodium- Extracellular

Potassium- Intracellular

Understanding Osmosis is key to understanding what conditions?

cirrhoris = decreased protein production

Volume depletion from DKA/HHS= too many effective osmoles in the extracellular space

Inflammatory conditions= lead to fluid sequestration=pancreatitis

Isotonic solution

Hypotonic Solution

Hypertonic solution

iso- normal

hypo- swollen RBC “hypo=hippo”

Hyper- shrunken RBC “hyper=skinny”

Ions are made of…. What 2 types is there?

electrolytes that form electrically charged particles (electrolytes dissociate into ions when dissolved in water)

Cations- (+) “ my cat makes me happy +

Anions- (-) “ ah no" -”

Electrolyte solutions conduct an..

electric current

it imports excitable cells like nerve and muscle cells

Ions are measured in

Milliequivalents

Nonelectrolytes:

solutes that do not dissociate (ionize) in solution and do not carry an electrical charge

so when they are dissolved in water, they do not break down into anything smaller than

Nonelectrolytes that play a role in homesostasis include:

Glucose, Proteins, Urea, Lipids, Organic molecules (hormones, neurotransmitters)

How are nonelectrolytes significant in maintaining intravasuclar volume?

the ionic composition of interstitial and intravascular fluid is similar, the main different is that INTERSITIAL fluid contains less protein = affects osmotic pressure”

most abundant EXTRACELLULAR ions are

Cations- Sodim and Calcium

Anions- Chloride and Bicarbonate

Plasma membrane is impermeable to

charge particles

so ion exchange occurs through channels

Electrolyte composition in homeostasis is maintained through

pumps or ion channels located in the cell membrane

Electrolytes have a greater…

osmotic pull than nonelectrolytes

Bc they dissociate into ions when dissolved in water, it increased their total solute concentration= larger osmotic gradient

Explain composition and osmolality between intraceullar and extracelluar compartments

composition of electrolytes is different

osmolality is the same (280-290 mOsmol)

Fluid imbalance/changes in electrolyte concentration will affect

movement of water across the plasma membrane

In clinical situations, what concentration of an electrolyte is measured?

the plasma (intravascular fluid) concentration

What are the 4 processes that work together to maintain electrolyte concentrations as a result of normal # electrolytes in plasma?

Electrolyte Intake

Electrolyte absorption

Electrolyte distribution

Electrolyte excretion

Electrolyte Intake

Occurs through food and drink

Oral medications

Feeding tubes or IV nutrition

Electrolyte Absorption

Depends on if intake occurs orally:

GI tract and Kidneys contents/abnormalities

Availability of binding proteins (calcium)

Concentration gradients (potassium)

Electrolyte Distribution factors that affect it:

Concentration gradients

Cell membrane permeability

Kidney function

Hormones

Acid Base Balance

Fluid Intake

Diet and nutrition

Electrolyte Excretion

through urine, feces, and sweat

urinary excretion is influenced by Aldosterone hormone

Electrolyte Loss

some pt lose it through abnormal routes that cause imbalances, so they exit body via

vomiting

nasogastric suction

paracentesis

fistula drainage

Electrolyte abnormalities may be due to

increase/decrease electrolyte intake or absorption

Shift of electrolytes between body fluid compartments

Increase/decrease of electrolyte excretion

Electrolyte loss through abnormal routes

Electrolyte concentrations need to be maintained at a …

very narrow range!

How can we look for electrolyte imbalances?

measuring electrolytes via plasma on blood draws

What are the charges of the IC and EC compartments?

it is different so it created an electrical gradient

What does plasma serve as?

a barrier for electrolytes to move from one compartment to another

Specific protein channels allow…

for electrolyte exchange and return to homeostasis

Potassium balance is regulated bc of its role in

neuromuscular function

increased serum potassium lvl activates mechanisms that

move potassium into the cell and excrete excess from the body

Insulin-

causes activation of and increases the number of Na/K ATPase pumps

Epinephrine-

causes activation of Na/K ATPase pump via secondary messenger

Aldosterone-

promotes renal excretion of potassium in the distal convoluted tubules of kidneys

90-95% of K excretion is via Aldosterone promotion!!

Ratio of ICF potassium to ECF concentration is

the major determinant of the resting membrane potential

resting membrane potential is the

electrical charge difference across the PM of a resting, non-stimulated cell

necessary for transmission and conduction of nerve impulses + normal cardiac rhythms + contraction of skeletal and smooth m.

At rest the inside of the cell is

negatively charged, which is maintained by the action of Sodium Potassium ATPase pump and potassium leak channels

Resting membrane potential is about

-70 mV to -90 mV

When an action potential is initiated, an influx of ….. occurs leading to..

cations (sodium) leading to a more positive IC environment

What is threshold? and what happens if it is reached?

-55 mV

voltage gated sodium channels open and causes depolarization

Depolarization:

shift in a cells membrane potential, making the inside of the cell less negative compared to its resting state

what happens AFTER depolarization?

repolarization occurs when voltage gated potassium channels open and potassium LEAVES the cell creating a more (-) internal environment

Potassium leak channels:

membrane bound channel that stay lightly open, allowing K to flow down its concentration gradient

Hypokalemia:

serum lvl drops to <3.5

Caused by decreased intake, shift of K from plasma, Increased K excretion via kidneys, diarrhea, loss through vomit/drainage/suction

Clinical manifestation of Hypokalemia:

loss of EC K= more IC K to move down its concentration gradient (goes from in to out) →

Creates a (-) IC environment= not RMP ): →

Fewer anions (P,P) will be neutralized= Cell interior is NEGATIVE →

Cell is less responsive so you need a stronger stimuli for it to react →

Cell is Hyperpolarized= more (-) than RMP = Muscle Weakness!! →

Muscle weakness causes:

skeletal m weak/paralysis

decreased GI activity

postural hypotension

→ Ends w Cardiac arrythmias! (develop U wave in EKG)

Hyperkalemia

Potassium lvl goes up to >5.0

caused by Increased intake, Shift of K into ECF, Decreased K excretion via kidneys, Drugs that decrease renal excretion, Laboratory error

Clinical manifestations of Hyperkalemia

Increased EX K decrease IC K movement out of cell →

More (+) IC environment- less K leaving cell = neutralizes the - anions →

Cell inside is LESS - = increased excitability →

Cell is Hypopolarized, goes to AP threshold →

Muscle weakness:

skeletal m weak/paralysis

intestinal cramp and diarrhea

tingling lips/fingers/restlessness

→ Leads to cardiac arrythmias! (peaked T waves on EKG)

Magnesium is stored in

40-60% in muscle and bone

30% in cells

Magnesium ions exist in blood as

bound (phys inactive) and unbound (phys active) forms

Regulation of Magnesium occur in

small intestine and kidney

Hypomagenisemia causes:

Chronic alcoholism!!

Malnutrition

Malabsorption syndromes

Pancreatitis

Ileal resection

Hypercalcemia

Diuretic, DKA

emesis, gastric suction, fistula drainage

Causes of Hypermagnesemia

lvl goes up to >3

rare but associated w renal failure!

magnesium containing antacids can exacerbate this in pts w chronic renal failure

Magnesium controls the release of

Acetylcholine at the motor endplate

Hypomagnesemia: excessive ACh release- cramps, twitch, insomnia, Torsades

Hypermagnesemia: decreased ACh release- lethargy, hypotension, resp depression, paralysis, - tendon reflexes

Clinical manifestation of Magnesium

It is cofactor of IC enzymatic rxns: DNA/RNA synthesis + Protein synthesis

Muscle function and relaxation - Pregnancy!!

Regulates the release of neurotransmitters at junction

Low mag lvls decrease activity of enzyme that drives Na/K pump

(-) mag in myocardium= cardiac dysrhythmias- Torsades de Pointe

Phosphate groups enable

enzymes to catalyze specific biochemical reactions

Phosphate in pH regulation

acts as an IC buffer