INB 365S - Exam 1

Simple Transport across the cell membrane stops when…

there is no concentration gradient anymore, usually goes from high to low.

Functions of the cell membrane

1. Physical isolation

2. Regulation of exchange with the environment

3. Communication between the cell and the environment, endocrine cells release hormones while neurons release neurotransmitters.

4. support and structure.

Cholesterol

4 ring structure that fills up gaps between phospholipids in the cell membrane. It increases flexibility and makes the membrane stronger. Hormones made from this easily go past cell membranes through simple diffusion.

Permeancy of molecules depends on…

lipid solubility, size, polarity and charge.

• solubility in lipids is needed

• small size is needed/preferred

• uncharged and nonpolar molecules easily pass through.

Passive transport

type of transport across the cell membrane that does not need ATP and gets its energy from a concentration gradient and the potential energy stored in it.

Insulin and Glut 2 and Glut 4 - everything about it

1. Glut 2 is triggered by skeletal muscle and exercise, decreases blood glucose levels, recommended for Diabetes 2 patients who have insulin insensitivity.

2. Glut 4 is sensitive to insulin and it turns glucose into ATP and glycogen so that blood sugar levels decrease. If Glut 4 is triggered a lot by insulin due to constant blood sugar levels, the receptors for glut 4 will become less and less sensitive.

3. constant high blood sugar levels can harm the kidneys and its filters.

Simple Diffusion

Type of passive transport that does not require ATP or external energy, uses own energy generated by a concentration gradient (potential/kinetic energy in that).

• Temperature increases it directly

• molecular size and weight has inverse relationship

• distance from initial site has inverse relationship.

• additional factors: surface area, thickness, etc

Stops when there is no concentration gradient.

Fick’s Law of Diffusion across a membrane

Rate is proportional to (surface area x concentration gradient x permeability)/membrane thickness

Depends on the lipid solubility of a molecule, available surface area, and membrane thickness.

Flux is equal to concentration gradient x membrane permeability.

Channels

Transmembrane proteins that have no binding site, are very quick to transport molecules, won’t become saturated, only go from high to low.

• most remain closed because if they remain open, this can mess up a cell’s physiology.

• majority are ion channels

• They can be gated: voltage gated, mechanically gated, or ligand gated.

• exhibit specificity

THere are no glucose channels because it is so big, a channel so big to accommodate it would lead to the cell dying because of a bigger opening in the bilayer.

Carriers

Transmembrane proteins that engage in both active and passive transport and make no direct connection between the ECF and ICF. They operate slower than channels due to a possibility of saturation and they can go in both directions.

They are similar to enzymes in that they catalyze the transport process, have substrate specificity, undergo conformational change, are affected by temperature and pH change, are subject to saturation and competition, and have allosteric sites that can inactivate or activate these proteins.

Active transport

type of cell transport that requires ATP or external energy. The proteins don’t always have a binding site for ATP but the CELL needs the ATP or energy from another concentration gradient happening.

Active transport/ATPases

proteins that have direct binding sites for ATP and are called pumps. These work against the concentration gradients of the ions. 1st active transport happens with these. These can become saturated and have all the properties of carriers.

Secondary active transport

type of active transport that takes energy from another concentration gradient. Uses a symporter or antiporter. These don’t have direct binding sites for ATP.

Vesicular transport

Vesicular active transport that is for large molecules. It requires vesicles and ATP (cell needs ATP to cause conformational change to excrete or take in larger molecules. Pinocytosis is for cell drinking. Phagocytosis is the process of cell eating usually with bacteria in immune cells. Receptor mediated endocytosis takes place in coated pits of the bilayer where ligands bind to receptors and are taken in.

teleological approach - not for this course

thinking about a physiological event in terms of its adaptive significance. (RBCs transport oxygen because cells need it and RBCs bring it to them)

Mechanistic Approach - for this course

The “how” of a system that examines a process deeply. “RBCs bring oxygen to cells because oxygen bind to hemoglobin on the RBCs”

Homeostasis

the regulation of the body’s internal environment. Not static and unchanging but rather there are some values for equilibrium. The composition of the body compartments is identical.

Diabetes Mellitus

metabolic disorder characterized by abnormally high blood glucose concentrations

ECF

the watery internal environments that surrounds cells

ICF

the fluid inside cells and they both make up the the body’s internal environment.

Local Control

control restricted to the tissue or cell involved. A nearby group of cells senses a change and the other cells nearby immediately respond, releasing a chemical and a response occurs.

Long distance reflex control

Control that uses changes that are widespread in the body. There is a response loop that has the three primary components and a feedback loop.

• stimulus → sensor → input signal → integrating center → output signal → target → response.

Feedback loops

Loops where the response feeds back to influence the input portion of the pathway.

• Negative loops keep systems at a setpoint and stable, they restore the normal state but cannot prevent the initial disturbance

  • feedforward controls are anticipatory responses that predict a change and start the response loop in anticipation of change.

  • long loop negative feedback happens when endocrine gland hormones feed back to suppress initial hormones

  • short loop negative feedback is when pituitary hormones feed back to decrease hypothalamus hormone secretion.

• Positive loops reinforce the stimulus and send the variable even farther from the normal value (breastfeeding, labor, and blood clotting) the breastfeeding example is below:

  • sensory detectors detect baby suckling

  • message is transmitted to the hypothalamus

  • hypothalamus signals to posterior pituitary to release the hormone oxytocin

  • oxytocin stimulates the mammary gland to eject breast milk

  • cycle repeats as long as the baby suckles.

How to calculate total body compartments and volumes and osmolarity

1. convert lbs to kgs and TBW (60% of total weight) TBW is also called D2O

   1. Women have less total body water and after you age to 60, your TBW starts decreasing.

2. ECF is 1/3 of TBW and 2/3 is ICF, ECF is also called inulin

3. Plasma is 25% of ECF and interstitial fluid if 75%. Evan’s blue is plasma

4. Osmoles is the vant hoff factor times the moles, always do mOsM

5. water goes through simple diffusion so plasma osmolarity for all body compartments are the same.

osmolarity

number of particles in solution - mol x dissociation factor / L = molarity x dissociation factor. Osmolality is osmoles of solute per kilogram of water.

tonicity

tells us the nature of the solute, how the cell behaves. Takes into account the nature of the particles in solution. It always describes the solution, not the cell. Penetrating particles follow water movement and water only moves based on nonpenetrating particles.

• hypotonic → cell swells (D-5-Water, ½ normal saline, D-5-1/2 normal saline)

• hypertonic → cell shrinks

• isotonic → cell doesn’t change size (normal saline, D-5-Normal saline)

osmosis

movement of H2O across a selectively permeable membrane towards the area of higher solute concentration. Osmotic pressure is the pulling pressure due to difference in solute concentration across the membrane.This can cause bulk flow which is when a pressure gradient causes fluid to flow from regions of higher pressure to those of lower pressure.

lumen

the interior of any hollow organ, may be partially or wholly filled with air or fluid. An extension of the external environment and material in the lumen is not truly part of the body’s internal environment.

Absorption and secretion in terms of ECF and lumen

1. secretion is the process by which a cell releases a substance into the lumen.

2. absorption is the process by which a cell takes a substance from the lumen and releases it into the ECF.

integral proteins

proteins that are tightly bound to the membrane - transmembrane or lipid-anchored proteins. Help in movement.

cytoskeleton functions

1. cell shape - mechanical strength to cell

2. internal organization - stabilizing position of organelles

3. intracellular transport - helps move organelles and material

4. assembly of cells into tissues - linking cells to one another and providing mechanical strength to tissue

5. movement - cell movement through cilia and flagella and motor proteins (convert stored energy into directed movement)

Lipophilic signal molecules

ligands that diffuse through the cell membrane and bind to cystosolic or nuclear receptors, have a part in gene transcription and protein production. These are usually steroid or thyroid hormones and act as transcription factors. Also amine hormones can do this.

Lipophobic signal molecules

ligands that can not diffuse into the cell and instead bind to receptors on the surface of the cell membrane, inducing a signal transduction pathway usually. These are usually integral membrane proteins that bind to lipophobic signal molecules. THey bind peptide hormones and others. These usually activate a second messenger (cAMP, cGMP, IP3, calcium) and can trigger release of calcium from stores, open/close ion channels, or modulate enzyme activity.

g proteins

a type of membrane receptor protein that is inactive when it is bound to GDP and active when it is bound to GTP.

Cannon’s Postulates

1. role of autonomic nervous system in homeostasis

2. tonic activity (constant like HR)

3. antagonistic control is moving something up or down

4. effects of chemical signals based on receptors.

components of a homeostatic mechanism

1. stimulus: the disturbance or change that sets the pathway in motion

2. sensor/receptor (all have a certain threshold that needs to be met to set the reflex response in motion)

3. afferent signal - activated by change

4. control center = integrating center, sees whether the input signal is outside the desired range and if it is, there is an output signal.

5. efferent signal - goes to target cells or in some cases to another integrating center (also labeled afferent 2 then)

6. effector or target cells

7. response from the effectors

8. result = outcome.

can be localized (paracrine) or systemic (nervous and endocrine)

Simple Neural Reflex - gas stove example

1. stimulus → pain from burning

2. receptor → pain receptor

3. afferent → sensory neuron

4. integration center → spinal cord/CNS

5. efferent → motor neurons

6. effector → skeletal muscle

7. response → move hand back from stove

more specific than endocrine reflex as it goes to a single or limited amount of target cells, rapid speed, very short, signals are identical in strength.

simple endocrine reflex - blood sugar too high example

1. stimulus → blood glucose levels too high

2. receptor → glucose receptor

3. integrating center → beta cells

4. efferent → insulin

5. effector → skeletal muscle and adipose tissue

6. response → more GLUT 4 receptors on cells in these tissues, blood glucose level decreases.

there is no afferent here because the glucose receptors are on the beta cells themselves so the signal does not need to travel anywhere else to the integrating center. These are broad range and target any cells that have receptors for the hormones, distributed through blood, have a slow onset and last longer than neural responses, and stimulus intensity is correlated with the amount of hormone secreted.

Signal Transduction and all the parts

This is the process by which an extracellular signal molecule activates a membrane receptor that in turn alters intracellular molecules to create a response.

1. transducer is a device that converts a signal from one form into a different form.

2. signal amplification turns one signal molecule into multiple second messenger molecules

3. amplifier enzymes are turned on by the receptor ligand complex and they activate several molecules as the cascade proceeds.

4. receptor channels are activated and initiate the most rapid intracellular responses of all receptors, channel gates open and close altering the cell’s permeability to an ion and can change the cell’s membrane and electrical potential.

5. G protein coupled receptors are large and complex family fo membrane spanning proteins that cross the phospholipid bilayer seven times.

down regulation

a decrease in receptor number. The cell physically removes receptors through endocytosis. This desensitizes the cell and leads to a diminished response rate from the target cell. Happens usually when ligand concentration usually increases.

Up regulation

an increase in receptor number on a target cell’s membrane so the target cell becomes more sensitized. Used when ligand concentration usually decreases.

steroid hormone

hormone that is made from cholesterol and are released from the adrenal cortex (cortisol and aldosterone), gonads (sex hormones), and placenta.

• synthesized on demand from precursors as they cannot be stored

• travel through simple diffusion out of the cell as they are lipophilic

• bound to carrier proteins throughout the plasma

• their half life is long

• receptors are in the cytoplasm or the nucleus

• activate genes for transcription and translation and help to start new protein synthesis

amine hormones (synthesized from tyrosine or tryptophan) can also have these same qualities

Peptide hormones

Most hormones are this type, they are synthesized by linking amino acids.

• made in advance and stored in secretory vesicles

• released from parent cell through exocytosis or active transport

• dissolve in plasma easily and transported through blood

• half life is short

• receptors are in cell membrane

• activate secondary messenger systems that involve signal transduction to modify existing proteins

amine hormones (synthesized from tyrosine or tryptophan) can also have these same qualities

synergism

effect of 2 or more hormones on same parameter is greater than additive (testosterone and growth hormone). 1+1 >2

permissiveness

one hormone is needed for another to exert its full effect (first hormone has no direct effect on parameter → thyroid hormone and GH). Can be though of as allosteric or needs “permission” from first hormone to function fully. (1+1 = 1)

antagonism

hormones have opposing effects (1+1 = 0 → insulin and glucagon)

oxytocin

hormone released from the posterior pituitary that is triggered with milk release and birthing/labor.

vasopressin/adh

hormone that is released by the posterior pituitary and is linked to increased blood pressure and pressing blood vessels and also keeping water in the body.

Hypophyseal portal system

a portal system of capillaries that connect the hypothalamus, posterior, and anterior pituitary. Neurohormones released by the hypothalamus go into the portal system, going to the anterior pituitary, triggering it to release hormones into the body/blood.

• neurons originate in the hypothalamus and release trophic hormones into the capillaries

• portal vessels carry the trophic hormones from the capillaries to the anterior pituitary and then to the body.

• posterior pituitary does not have veins and trophic hormones don’t leave through there

posterior pituitary

neural tissue that is a down growth/extension of the hypothalamus. This releases neurohormones.

Anterior pituitary

endocrine/glandular tissue that is an outgrowth of the roof of the mouth. It releases classic hormones.

trophic hormones

hormones released by an integrating center that is not the last one in a reflex response, it causes another hormone’s release.

Endocrien pathologies

There can be hyposecretion, hypersecretion, and abnormal tissue responsiveness.

1. 1st degree pathology begins in the final endocrine gland in the pathway.

2. 2nd degree pathology begins in the tissue producing trophic hormones, 1st or 2nd integrating center before the final one in the reflex response system.

Breast milk production hormone pathway

Dopamine (hypothalamus) and TRH (hypothalamus - actually stops the production of next hormone) → prolactin (ant pit) → breast milk production

Thyroid hormone production pathway

TRH (hypothalamus) → TSH (ant pit) → thyroid gland (endocrine tissue) → T3 and T4 released → targets many tissues.

cortisol hormone production pathway

CRH (hypothalamus) → ACTH (ant pit) → adrenal cortex (endocrine tissue) → cortisol released → targets many tissues

growth hormone/factors hormone production pathway

GHRH and Somatostatin (hypothalamus, somatostatin inhibits next hormone production) → GH (ant pit, can go to many tissues by itself also) → liver (endocrine tissue) → insulin like growth factors released → targets many tissues.

Gonad Hormones production pathway

GnRH (hypothalamus) → FSH and LH (ant pit) → gonadotropins that can target germ cells of gonads directly → endocrine cells of gonads → androgens and estrogen and progesterone released → goes to many tissues and germ cells of gonads.

hormone

chemical secreted by a cell or group of cells into the blood for transport to a distant target, where it exerts its effect at very low concentrations. They act by binding to receptors.

• steroid hormones made only in a few organs, cells that secrete these have a lot of smooth ER.

• hypersecretion is excess hormone secretion caused mostly by tumors, causes trophic level hormones to decrease

• hyposecretion is caused by atrophy of glands and causes trophic hormone levels to rise.