Samenvatting voor het vak physiology. Alle pagina's die nodig zijn om te lezen voor het tentamen uit het boek zijn behandeld in dit document. Onderaan staan oefenvragen om je kennis te testen.
1 Introduction to physiology
Homeostasis: keeping the internal environment relatively stable (range of value, not a fixed value)
→ pathological condition (disease) caused when homeostasis cannot be contained
The internal environment of the body: the extracellular fluid (outside of the cells) → transition between
the intracellular fluid and the external environment
In a state of homeostasis, the body is in a steady state → not the same as equilibrium, because the
concentrations of certain substances can be very different in the ICF/ECF (stable disequilibrium)
- Regulated variables are kept at setpoint; control systems have three components: input signal,
integration center and response; control can be local or long-distance
Response loop: stimulus → input signal → integrating center → output signal → target → response
Feedback loop causes a regulated variable to oscillate around the setpoint
- Negative feedback loop: response opposes or removes signal + stabilize the regulated variable
- Positive feedback loop: response reinforces the stimulus, causing the regulated variable to be
further from the setpoint
- Feedforward control: predict that a change is coming and can start the feedback loop in
anticipation of the change
Circadian rhythm: daily biological rhythm
Acclimatization: the adaptation of physiological processes to a given set of environmental conditions
,6 Communication, integration, and homeostasis
6.1 Cell-to-cell communication
Two basic types of physiological signals: electrical (change in cell’s membrane potential) and chemical
(molecules secreted by cells into the extracellular fluid) signals → act as ligands that bind to proteins to
initiate a response). Target cells are the cells that respond to these signals.
Methods of cell-to-cell communication
- Local communication:
1. Gap junctions
Gap junctions are cytoplasmic bridges between adjacent cells → united connexins
create protein channel that can open and close; ions and small molecules can diffuse
2. Contact-dependent signals
Surface molecules from one cell membrane bind to a membrane protein of another
cell. Cell adhesion molecules (CAMs): act as receptors in cell-to-cell signaling
3. Autocrine/paracrine signals
- Paracrine signal: chemical that acts on cells in the immediate vicinity of the cell
that secreted the signal; restricted to adjacent cells
- Autocrine signal: chemical that acts on the cell that secreted it
- Long-distance communication:
4. Combination of chemical/electrical signals carried by nerve cells and chemical signals
transported in the blood
- Endocrine system: hormones; chemical signals secreted into blood and
distributed all over the body by circulation; receptors needed
Cytokines: can be excreted by any body cell; made on demand; intracellular
pathways are different
- Nervous system: electrical system travels along neuron → at end of cell:
translation into chemical signal (neurocrine molecules);
neurotransmitter: neurocrine molecule that diffuses from the neuron across a
narrow extracellular space to a target cell and has a rapid-onset effect.
neuromodulator: same as neurotransmitter, but slow effect
neurohormone: neurocrine molecule diffuses into blood for body-wide
distribution
6.2 Signal pathways
A cell can respond to a particular chemical signal only if the cell has the appropriate receptor protein to
bind that signal; common features of signal pathways:
- Signal molecule (ligand → any molecule/atom that irreversibly binds to a receiving protein
molecule; first messenger) binds to protein receptor
- Ligand-receptor binding activates receptor
- Receptor activates one/more intracellular signal molecules
- Last signal molecule creates response by modifying existing proteins/initiating synthesis of
proteins
The place where a signal molecule binds is based on:
, - Lipophilic: diffuse through bilayer; bind to cytosolic or nuclear receptors → activate/repress
gene activity by transcription; slow process
→ can also bind to receptors on membrane
- Lipophobic: bind to receptor proteins on membrane; rapid process
Signal transduction: process by which an extracellular signal molecule activates a membrane receptor
that in turn alters intracellular molecules to create a response; transducer is a device that converts a
signal from one form into a different form. The pattern of signal transduction:
- Extracellular signal molecule (first messenger) binds and activates membrane receptor
- Activated membrane receptor turns on associated proteins and starts intracellular cascade
(stimulus converts inactive molecule A to an active form, which converts inactive molecule B
into active form, etc) of second messengers
- Last second messenger acts on intracellular targets to create response
Signal amplification turns one signal molecule into multiple second messenger molecules, because of
an amplifier enzyme that’s turned on by the receptor-ligand complex
Membrane receptors can be grouped into four categories:
1. Receptor channels
Rapid ion channels → upon binding of ligand to receptor-channel protein, channel gate
opens/closes → permeability to an ion is altered → change in membrane potential → electrical
signal that alters voltage-sensitive proteins
→ membrane ion channels do not have to be associated with membrane receptors
2. Protein-coupled receptors
G protein-coupled receptors (GPCRs): membrane-spanning proteins that cross the
phospholipid bilayer seven times; cytoplasmic tail linked to G protein (activated by exchange of
GDP for GTP → opens ion channel/alters enzyme activity on cytoplasmic side)
G protein-coupled adenylyl cyclase-cAMP system:
1. Signal molecule binds to G protein-coupled receptor, which activates G protein
2. G protein turns on adenylyl cyclase (amplifier enzyme)
3. Adenylyl cyclase converts ATP to cyclic AMP
4. cAMP activates protein kinase A
5. Protein kinase A phosphorylates other proteins, leading to a cellular response
G protein-coupled phospholipase C signal transduction
1. Signal molecule activates receptor and associated G protein
2. G protein activates phospholipase C (PLC), an amplifier enzyme
3. PLC converts membrane phospholipids into DAG, which remains in membrane, and IP3, which
diffuses in cytoplasm
4. DAG activates protein kinase C (PKC), which phosphorylates proteins
5. IP3 causes release of Ca2+ from organelles, creating Ca2+ signal
3. Receptor-enzymes
Two regions: receptor region on the extracellular side + enzyme region on the cytoplasmic side
4. Integrin receptors
, Integrins attach to cytoskeleton via anchor proteins → when a ligand binds, enzymes are
activated to alter the organization of the cytoskeleton
Calcium-dependent events that occur in the cell:
- Calcium binds to calmodulin, which alters protein activity
- Calcium binds to regulatory proteins → movement
- Calcium binds to regulatory proteins → exocytosis
- Calcium binds directly to ion channels to alter gating state
- Calcium entry into fertilized egg initiates development of embryo
6.4 Modulation of signal pathways
Different ligands with similar structures may be able to bind to the same receptor:
- Agonist: a competing ligand that binds and elicits a response from a receptor
- Antagonist: a competing ligand that binds and blocks the receptor activity
It is possible for one ligand to cause different effects in multiple receptors, because the target cell
response depends on its receptor or its associated intracellular pathways, not on the ligand (receptors
can have isoforms → protein that has the same function as another protein but is encoded by a
different gene)
When signal molecule is present in the body in abnormally high concentrations:
Enhanced response → target cells bring response back to normal by down-regulation: decrease in
receptor number (physically removing receptors by endocytosis)/desensitization: binding of chemical
modulator to receptor protein; up-regulation: insertion of receptors into membrane
The activity of ligand-receptor complex can be terminated by endocytosis, after which the ligand is
taken off and the receptors are put back on the membranes in exocytosis
6.5 Homeostatic reflex pathways
Cannon’s four postulates:
1. The nervous system has a role in preserving the ‘fitness’ of the internal environment
(parameter: a regulated variable)
2. Some systems of the body are under tonic control (instead of ‘on or off’; a moderate activity
that can be decreased or increased)
3. Some systems of the body are under antagonistic control (if a factor that shifts a homeostatic
state in one direction exists, a factor that shifts it in the other direction probably exists as well)
4. One chemical signal can have different effects in different tissues (antagonistic in one region,
cooperative in another)
Reflex pathway response loops:
- Input
1. Stimulus: disturbance/change that sets the pathway in motion
2. Sensor: sensory receptor that monitors its environment for a particular variable
Sensory receptors involved in neural reflexes:
- Central receptors: located in brain
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