module 1 studyguide interactions between cells and extracellular environment

Body fluids

In most people, approx. 67% of the total weight is water within cells, in the intracellular compartment.

The 33% of the total body water comprises the extracellular compartment.

~20% of this extracellular fluid is contained in the vessels of cardiovascular system, where it comprises the fluid portion of the blood (blood plasma)

Extracellular matrix

The extracellular environment fluids, as interstitial, or tissue, fluid, within a matrix of glycoproteins and proteoglycans. It consists of the protein fibers collagen and elastin. This fluid, derived from blood plasma, provides nutrients and regulatory molecules to the cells. The extracellular environment is supported by collagen and elastin protein fibers, which also form the basal lamina below epithelial membranes.

Integrins

Are a class of glycoproteins that extend from the cytoskeleton within a cell, through its plasma membrane, and into the extracellular matrix. By binding to components within the matrix, they serve as adhesion molecule between cells and the extracellular matrix.

Passive transport

net movement from higher to lower concentration

does not require ATP

includes simple diffusion, osmosis, and facilitated diffusion

Active transport

net movement goes against concentration gradient

requires ATP

involves specific carrier proteins

Primary active transport

Occurs against an electrochemical gradient (uphill)

Requires ATP

Is carrier-mediated and therefore exhibits stereospecificity, saturation, and competition

Examples:

• Na+ and K+ (pump)

  • inhibitors: cardiac glycoside drugs ouabain and digitals

• Ca2+ ATPase (or Ca2+ pump)

  • location: in sarcoplasmic reticulum (SR) or cell membrane

• H+, K+-ATPase

  • location: in gastric parietal cells transport H+ into lumen of the stomach

  • inhibitor: omeprazole

Secondary active transport

• The transport of two or more solutes is coupled

• One of the solutes (usually Na+) is transported downhill and provides energy for the uphill transport of the other solute(s)

• Metabolic energy isn’t provided directly, but indirectly from the Na+ gradient that is maintained across the cell membranes. Thus, inhibition of Na+, K+-ATPase will decrease transport of Na+ out of the cell, dec the transmembrane Na+ gradient, and eventually inhibit secondary active transport.

• If the solutes move in the same direction across the cell membrane, it is called cotransport, or symport

ex: Na+-glucose cotransport in the small intestine and Na+-K+-2Cl- cotransport in the renal thick ascending limb

• If the solutes move in opposite directions across the cell membane, it is called countertransport, exchange, or antiport

ex: Na+-Ca2+ exchange

Simple diffusion

Characteristics:

• is the only form of transport that is not carrier-mediated

• occurs down the electrochemial gradient (downhill)

• does not require metabolic energy and therefore is passive

Factors that inc permeability:

• high oil/water partition coefficient of the solute inc solubility in the lipid of the membrane

• dec radius (size) of the solute inc the speed of diffusion

• dec membrane thickness dec the diffusion distance

Small hydrophobic solutes have the highest permeabilities in lipid membranes.

Hydrophilic solutes must cross cell membranes through water-filled channels, or pores. If the solute is an ion, then its flux will depend on both the concentration difference and the potential difference across the membrane.

Facilitated Diffusion

The first molecule facilitates the second molecules transport.

ex: Insulin facilitates glucose entrance into target cell. Without insulin, glucose cannot enter into the target cell for production of ATP.

1. Insulin binds to its receptor on target cell’s membrane.

2. It activates target cell molecule (Glut-4 channels)

3. Glut-4 opens and acts as a channel for glucose, then glucose enters into target cell.

Deficiency of insulin leads to accumulation of glucose in blood (hyperglycemia or Type 1 diabetes)

Osmosis

The flow of water across a semipermeable membrane from a solution with low solute concentration to a solution with high solute concentration.

Osmotic Pressure

Osmotic pressure inc when the solute concentration inc.

The higher the osmotic pressure, the greater the water flow into it.

If solution is separated by semipermeable membrane with different effective osmotic pressures, the solution with higher pressure is hypertonic, and the one with lower pressure is hypotonic. Water flows from hypotonic to hypertonic solution.

Isosmotic

two solution that have the same calculated osmolarity

hyperosmotic

the higher osmolarity of two

hyposmotic

the lower osmolarity of two

Cystic fibrosis

Result of a genetic defect, abnormal NaCl and water movement occurs across wet epithelial membranes.

Where such membranes line the pancreatic ductules and small respiratory airways, they produce a dense, viscous mucus that cannot be properly cleared, which may lead to pancreatic and pulmonary disorders.

The genetic defect involves a particular glycoprotein that forms chloride channels in the apical membrane of the epithelial cells. This proteins is known as CFTR (cystic fibrosis transmembrane conductance regulator) is formed in the usual manner in the endoplasmic reticulum.

It does not move into the Golgi complex for processing, it doesn’t get correctly processed and inserted into vesicles that would introduce it into the cell membrane.

Regulation of blood osmolality

When a person becomes dehydrated, the blood becomes more concentrated as the total volume is reduced.

The inc blood osmolality and osmotic pressure stimulate osmoreceptors (neurons located in the hypothalamus).

Result of inc osmoreceptor stimulation: person becomes thirsty and drinks available water. With inc water intake, a dehydrated person excretes lower volume of urine.

1. Inc plrama osmolality stimulates osmoreceptors in the hypothalamus of brain.

2. Osmoreceptors in hypothalamus stimulate a tract of axons that terminate in the posterior pituitary; causes the posterior pituitary to release antidiuretic hormone (ADH) into blood.

3. ADH acts on kidneys to promote water retention, so a lower volume of more concentrated urine is excreted.

NORMAL OSMOLALITY IN PLASMA IS ABOUT 280-303 MILLI-OSMOLES/KG.

Edema

Water returns from tissue fluid to blood capillaries because the protein concentration of blood plasma is higher than the protein concentration of tissue fluid. Plasma proteins, in contrast to other plasma solutes, cannot pass from the capillaries into the tissue fluid.

Plasma proteins are osmotically active.

Person with abnormally low concentration of plasma proteins, excessive accumulation of fluid in the tissues will develop this.

This may occur when a damaged liver in the cirrhosis is unable to produce sufficient amounts of albumin, the major protein in the blood plasma.

Hyperglycemia

The kidneys transport a number of molecules from the blood filtrate which becomes urine, back into the blood.

Ex: Glucose in normally completely reabsorbed so that urine is normally free of glucose. If the glucose conc of the blood and filtrate is too high a condition, it is called hyperglycemia. However, the transport max will be exceeded. In this case, glucose will be found in the urine (glycosuria). This may result from the consumption of too much sugar or from inadequate action of the hormone insulin in the disease diabetes mellitus.

BG is over 120 mg/dl

Hypoglycemia

The rate of facilitated diffusion of glucose into tissue cells depends directly on the plasma glucose conc. When the plasma glucose conc is abnormally low.

BG is below 50 mg/dl

Oral rehydration

Effective for diarrhea:

1. Absorption of water by osmosis across the intestine is proportional to the absorption of Na+.

2. THe intestinal epithelium cotransports Na+ and glucose.

The glucose in the mixture promotes the cotransport of Na+ and the Na+ transport promotes the osmotic movement of water from the intestine into the blood.

Diffusion potential

The potential difference generated across a membrane because of a conc difference of an ion.

Can be generated only if the membrane is permeable to the ion.

The size of the diffusion potential depends on the size of the conc gradient.

The sign of the diffusion potential depends on whether the diffusing ion is positively or negatively changed.

Are created by the diffusion of very few ions and therefore, do not result in changes in conc of the diffusing ions.

Equilibrium potential

Is the diffusion potential that exactly balances (opposes) the tendency for diffusion caused by a conc differences. At electrochemical equilibrium, the chemical and electrical driving forces that act on an ion are equal and opposite, and more net diffusion of the ion occurs.

Approx values for equilibrium potential in nerve and muscle:

resting membrane

-70 mV

Approx values for equilibrium potential in nerve and muscle:

ENa+

+65 mV

Approx values for equilibrium potential in nerve and muscle:

E Ca2+

+120 mV

Approx values for equilibrium potential in nerve and muscle:

EK+

-85 mV

Approx values for equilibrium potential in nerve and muscle:

ECl-

-85 mV

Action potential

Is a property of excitable cells (nerve, muscle) that consists of a rapid depolarization, or upstroke, followed by repolarization of the membrane potential.

Have stereotypical size and shape, are propagating, and are all-or-none.

Depolarization

Makes the membrane potential less negative (the cell interior becomes less negative).

MAKES THE INSIDE OF THE CELL LESS NEGATIVE (MORE POSITIVE) THAN THE OUTSIDE.

Repolarization

the phase of an action potential where the cell membrane's membrane potential returns to a negative value after being depolarized to a positive value

Hyperpolarization

Makes the membrane potential more negative (the cell interior becomes more negative).

Absolute refractory period

Is the period during which another action potential cannot be elicited, no matter how large the stimulus.

Relative refractory period

Begins at the end of the absolute refractory period and continues until the membrane potential returns to the resting level.

An action potential can be elicited during the period only if a larger than usual inward current is provided.

Conduction velocity (is inc by)

• inc fiber size. Inc the diameter of a nerve fiber results in dec internal resistance; thus, conduction velocity down the nerve is faster.

• Myelination. Myelin acts as an insulator around nerve axons and inc conduction velocity. Myelinated nerves exhibit saltatory conduction because action potentials can be generated only at the nodes of Ranvier, where there are gaps in the myeline sheath.

Neuromuscular junction

1. An action potential in the presynaptic cell causes depolarization of the presynaptic terminal.

2. Result of depolarization: Ca2+ enters the presynaptic terminal causing release of the neurotransmitter into the synaptic cleft.

3. Neurotransmitter diffuses across the synaptic cleft and combines with receptors on the postsynaptic cell membrane, causing a change in its permeability to ions and, consequently, a change in its membrane potential.

4. Inhibitory neurotransmitters hyperpolarize the postsynaptic membrane; excitatory neurotransmitters depolarize the postsynaptic membrane.

Neurotransmitters

Acetlycholine (ACh)

Functions in both the central and peripheral nervous systems. In the CNS, it supports memory, learning, and attention. In the peripheral nervous system, it signals voluntary muscles to contract and is a major neurotransmitter in the autonomic nervous system.

Synthesized by cholinergic neurons in the basal forebrain and the mesopontine tegmentum area of the brain, and in motor neurons.

Associated with Alzheimer's disease (linked to decreased ACh levels) and Myasthenia Gravis (an autoimmune disease where antibodies block ACh receptors). 

Neurotransmitters

Norepinephrine

Is the primary transmitter released from postganglionic sympathetic neurons.

Is synthesized in the nerve terminal and released into the synapse to bind with alps or beta receptors on the postsynaptic mebrane.

Is removed from the synapse by reuptake or is metabolized in the presynaptic terminal by monoamine oxide (MAO) and catechol-O-methyltransferase (COMT).

Neurotransmitters

Epinephrine

Is synthesized from norepinephrine by the action of phenylethanolamine-N-methyltransferase.

Is secreted, along with norepinephrine, from the adrenal medulla.

Neurotransmitter

Dopamine

Is prominent in midbrain neurons

Is released from hypothalamus and inhibits prolactin secretion

Neurotransmitter

Seretonin

Present in high conc in brain stem.

Formed trytophan.

Is converted to melatonin in the pineal gland

Neurotransmitters

Histamine

If formed from histidine

Present in the neurons of hypothalamus

Neurotransmitters

Glutamate

Is most prevalent excitatory neurotransmitter in the brain.

Has a kainate receptor, which is an ion channel for Na+ and K+

Neurotransmitters

GABA

inhibitory neurotransmitter

is synthesized from glutamate by glutamate decarboxylase

2 receptors: GABAa receptor inc Cl- conductance (site of action of benzodiazepines and barbiturates) and GABAb receptor inc K+ conductance.

Neurotransmitters

Glycine

Inhibitory neurotransmitter found primarily in the spinal cord and brain stem

inc Cl- condutance

Myasthenia gravis

Caused by presence of antibodies to the ACh receptors.

Characterized by skeletal muscle weakness and fatigability resulting from a reduced number of ACh receptors on the muscle end plate.

The size of EPP is reduced; therefore, it is more difficult to depolarize the muscle membrane to threshold and to produce action potentials.

Treatment: AChE inhibitors

Pheochromocytoma

rare adrenal medulla tumor that secretes excessive amounts of the stress hormones epinephrine and norepinephrine, leading to serious symptoms like rapid heart rate, severe headaches, high blood pressure, and sweating