Control Systems, Membranes, Cell Volume

homeostasis

ability of body to maintain a constant internal environment, Claude Bernard mid 1800s

Water B. Cannon

made a list of variables that are controlled through homeostasis

1. ionic composition of fluids

2. body temperature

3. pH of body fluids

4. plasma glucose concentration

5. blood pressure

6. hormones

control systems

physiological mechanisms that control the regulated variables in the body

set point

optimal value of a variable, example: body temperature at 98.6 F

sensor

receptors that measure the controlled variable, detects changes of variable, receives an input signal

integrating center

compares the sensor value to the setpoint value, sends an output signal onto the effector, example: brain

effector

mechanism that responds to an output signal, adjusts the controlled variable

error signal

the output signal if the sensor value is not at the set point

normal set point variation

caused by biological rhythms, example: body temperature fluctuates with time of day

abnormal set point adjustment

can occur during disease states or infection, example: fever induction

types of sensors

1. mechanoreceptors (mechanical distortion)

2. osmoreceptors

3. nociceptors (noxious/painful stimuli)

4. chemoreceptors

5. thermoreceptors

6. proprioceptors (changes in muscle length)

system gain

how sensitive the effector is in response to a change in the variable, higher gain = higher sensitivity, more narrow range of variable

system lag

the time it takes to create a response to a change in a variable

types of physiological control systems

1. negative feedback (common)

2. positive feedback

3. feed forward systems (anticipatory)

4. open loop systems (disordered)

negative feedback

keeps a system at the set point by bringing it back to normal, shuts itself off, examples: hormone release, blood pressure, stretch reflexes

positive feedback

does not maintain homeostasis, increases the initial stimulus, requires an outside factor to shut it off, examples: blood clotting, labor, action potentials, LH surge in ovulation, congestive heart failure, hemorrhagic shock, inflammation

feed forward system

anticipatory, the body predicts that a change will occur and starts the response prior, example: rise in heart rate before exercise, salivating before eating

open loop systems

when a negative feedback loop has been disrupted, loss of feedback causes the variable to increase or decrease in one direction, examples: parkinson’s disease, hyperthermia from sun stroke

cell membrane

a thin phospholipid bilayer that separates the intra and extracellular fluids

1. isolates and compartmentalizes functions

2. regulates exchange

3. communicates between the cell and the environment

4. structural support

5. generation of gradients

cell membrane macromolecules

percentages of protein, lipid, and carbohydrates differ between different types of cells

phospholipids

can form bilayers, micelles (droplets involved in lipid digestion), or liposomes (have aqueous center)

phospholipid head and tail

polar head (hydrophilic) and nonpolar fatty acid tail (hydrophobic)

fluid mosaic model

cholesterol inside the lipid bilayer creates fluidity, proteins throughout serve as receptors and channels

glycolipids and glycoproteins in cell membrane

structural stability, cell recognition, immune response

total body water volume

40 L, 60% body weight

intracellular fluid volume

25 L, 40% body weight

extracellular fluid volume

15 L, 20% body weight, made up of interstitial fluid and plasma

interstitial fluid volume (15% overall)

12 L, 80% of ECF

plasma volume (5% overall)

3 L, 20% of ECF

transcellular fluid

“forgotten volume”, not usually counted in measuring body water, examples: CSF, fluid in bladder and GI tract

dilution principle

a tracer is added to the body and allowed to distribute, then compartment volumes are calculated by measuring the tracer

dilution principle formula

volume of compartment = (amount of tracer added - amount of tracer excreted) / (concentration of tracer)

properties of an ideal tracer

1. non toxic

2. rapidly distributed

3. can’t be metabolized

4. not excreted during equilibration period

5. easily measured

6. can’t interfere with body fluid distribution

dilution principle formula units

volume = mL or L

mass = g or mg

mass per volume = g/L or mg/mL

tracer for total body water TBW

antipyrine and tritiated water

tracer for intracellular fluid ICF

none

tracer for extracellular fluid ECF

mannitol and inulin

tracer for interstitial fluid ISF

none

tracer for total blood volume TBV

radioactive RBCs

tracer for plasma volume

Evan’s blue and radioactive albumin

hematocrit formula

hematocrit = (volume of RBCs) / (volume of blood)

volume of blood formula

volume of blood = (volume of plasma) / (1 - hematocrit)

Na+ intra- and extracellular concentrations

intracellular: LOW (10 mM)

extracellular: HIGH (140 mM)

K+ intra- and extracellular concentrations

intracellular: HIGH (150 mM)

extracellular: LOW (4 mM)

Ca++ intra- and extracellular concentrations

intracellular: LOWer (3 mM), 99.9% bound

extracellular: LOW (5 mM), 50% bound

Cl- intra- and extracellular concentrations

intracellular: LOW (2 mM)

extracellular: HIGH (105 mM)

calcium as a biological signal

second messenger molecule that is tightly regulated

1. metabolic regulation

2. muscle excitation

3. building block for bone and teeth

4. blood clot formation

bulk flow

when fluids and gases move from higher pressure to lower pressure regions, amount moving per unit time

diffusion

movement of molecules from regions of higher concentration to lower concentration

diffusion conditions

1. passive

2. occurs until concentration is equal everywhere

3. fast over short distances, slow over longer distances

4. directly related to temperature

5. inversely related to molecular weight and size

6. takes place in open system or across partition

functions of diffusion

1. delivery of nutrients

2. deliver/removal of gases

3. removal of waste products

flow formula

flow = A*P*C

A = membrane area (cm²)

P = permeability (cm/s)

C = solute concentration

flow units = moles/second

net flow formula

net flow = A*P*(C1 - C2)

C1 and C2 = concentration of compartments

driving force for net flow

concentration difference across the membrane (C1 - C2)

einstein’s relationship for speed of diffusion

x² = 2Dt

x = distance (cm)

D = diffusion constant (cm²/s)

t = time (s)

diffusion constant proportionality

D is inversely proportional to molecule size

molecule size and speed of diffusion

the smaller the molecule the faster the diffusion

where is diffusion best utilized?

across short distances, examples: across cell membranes and compartments, across capillaries

fick’s law of diffusion

diffusion rate is proportional to (membrane area * D * concentration gradient) / membrane thickness

D is proportional to (solubility) / (radM * W)

factors that affect diffusion through cell membrane

1. lipid solubility

2. molecular size

3. concentration gradient

4. membrane surface area

5. composition of lipid layer

membrane permeability formula

P = (D * Beta) / l

D = diffusion constant

beta = partition coefficient

l = membrane thickness

units of permeability = cm/sec

types of transport across membrane

1. simple diffusion (no channel needed)

2. facilitated diffusion

3. primary active transport

4. secondary active transport

5. water transport

simple diffusion

hydrophobic molecules that move freely across membrane, examples: lipids, alcohols, carbon dioxide and oxygen

facilitated diffusion

passive process where solute moves through a transport protein on the membrane

channel proteins

gated: can be opened or closed in response to signals

open: pores

types of carrier proteins

uniport carriers: transport 1 substrate

symport carriers: transports multiple substrates in the same direction

antiport carriers: transports multiple substrates in opposite directions

transport maximum

the maximum rate at which a solute can be transported across a membrane even when the concentration gradient increases, saturation

competitive inhibition

when 2 substrates compete for a binding site, example: glucose transport is reduced when galactose is competing

primary active transport

solute is moved from an area of low concentration to high concentration using energy (ATP) through a protein on the membrane

cyanide

inhibits primary active transport by working upon the ETC

primary active transport pump examples

1. Na/K ATPase

2. calcium pumps

3. proton pumps

4. H+/K+ exchange pumps

Na/K ATPase

maintains ionic gradients that drive action potentials

calcium pumps

maintains low intracellular calcium concentrations

proton pumps

eliminates H+ from the kidney to achieve pH balance

H+/K+ exchange pumps

secretes gastric acid in stomach

secondary active transport

dependent on another solute moving down its concentration gradient to move another solute up its gradient, does not directly require ATP, example: glucose and sodium via SGLT protein

aquaporins

allows water to be permeable through cell membrane

osmotic equilibrium

the body is in osmotic equilibrium, water concentrations are equal throughout the body

osmosis

the movement of water across a membrane in response to a solute concentration gradient

osmotic pressure

the minimal amount of force that needs to be applied to prevent the flow of solutes through a semipermeable membrane

molarity

number of moles of dissolved solute per liter of solution (mol/L)

1 osmole

1 mole of a fully dissociated substance dissolved in water

osmolarity concept

the concentration of osmoles in a mass of solvent

osmolarity formula

osmolarity = molarity * (particles/molecule)

osmolarity units: osmol/L or OsM

osmolarity of 1 mole of glucose in 1L of solution

1 osm/L

osmolarity of 1 mole of NaCl dissolved in 1L of solution

2 osm/L

osmolality

osmoles of solute per kg of water (clinical usage)

maintenance of electroneutrality

cells must be electrically neutral at all times

cell electroneutrality

1. inside mOsm = outside mOsm

2. leakage of ions is one-for-one exchange

3. role of Na+/K+ ATPase

osmolarity of solutions

describes the number of particles in solution

cell in hypoosmotic solution

cell immediately swells

cell in isosmotic solution

no immediate change in cell

cell in hyperosmotic solution

cell immediately shrinks

formula to calculate cell volume change from change in osmolarity

(final volume) / (initial volume) = (initial concentration) / (final concentration)

tonicity

describes how a solution would affect cell volume if placed in the solution and allowed to reach equilibrium, dependent on impermeable solutes

osmolarity vs tonicity

osmolarity determines immediate impact on water movement, tonicity determines long-term impact on water movement