Systems Physiology Flashcards
Homeostasis
definition
any self-regulating process by which an organism tends to maintain stability while adjusting to conditions that are best for its survival
Feedback loops
- negative feedback loops that counteract changes of various properties from their target values, known as set points.
- positive feedback loops amplify their initiating stimuli
Substance balance
- Net gain to body (eg. food intake)
- Distribution within body (eg. glycogenesis)
- Net loss from body (eg. metabolism)
The extracellular concentrations are predominantly fixed, in cotrast to intracellular
- Extracellular and intracellular fluids also differ in their composition of solutes such as sodium, potassium, calcium, magnesium, etc.
Osmosis
movement of water molecules from a solution with a high concentration of water molecules to a solution with a lower concentration of water molecules, through a cell’s partially permeable membrane
- Hypertonic - cell size decrease
- Isotonic - cell size stays the same
- Hypotonic cell size increase
Reflection coefficient
describes how well solutes permeate the membrane. This coefficient ranges from 0 to 1. A reflection coefficient of 1 means a solute is impermeable
Communication by chemical messengers
Endocrine
Paracrine
Autocrine
direct Cell-cell (gap-junctions)
Net flux
represents the amount of substance moved in or out of the cell
Transporters
Facilitates transport through the membrane passive or active:
Uniporter (passive) allows flow down the concentration gradient
Symporter, antiporter, ATP-powered pumps (active) allows flow agianst the concentration gradient.
- The symporter and antiporter is secundary active and the transport is facilitated by a co-transport of a molecule down the gradient
- ATP-powered pumps (P-class, V-class, F-class, ABC-class) are primary active
Specialized endocytosis
- clathrin-coated pit-mediated endocytosis (CME; clathrin and dynamin dependent),
- fast endophilin-mediated endocytosis (FEME, a clathrin-independent but dynamin-dependent pathway for rapid ligand-driven endocytosis of specific membrane proteins),
- clathrin-independent carrier (CLIC)/glycosylphosphatidylinositol-anchored protein enriched early endocytic compartment (GEEC) endocytosis (clathrin and dynamin independent),
- macropinocytosis
- phagocytosis
GPCR - IP3/DAG
Pathway
Draw yourself
GPCR - Adenylcyclase
Pathway
Draw yourself
Ion channels
- Metabotrophic ion channels; first messengers binds to receptors initiating intracellular signalling opening ion channels
- Ionotrophic ion channels; first messengers binds to ion channel directly and opnes it
Chemical messengers
First messengers; extracellular signaling molecules such as hormones or neurotransmitters that bind to cell-surface receptors and activate intracellular signaling pathways
Second messengers; small molecules and ions that relay signals received by cell-surface receptors to effector proteins
- Signal cascades are amplifications
Cells of the central nervous system
Neurons; electrical (connexon channels) and chemical neurons
- Afferent/sensory neuron: A single process from the cell body splits into a long peripheral process (axon) that is in the PNS and a short central process (axon) that enters the CNS
- Intermedia/interneurons: account for the majority of the neurons is concentrated entirely in the CNS & they communicate with each other
- Efferent/motor neurons: transmit signal away from the CNS to the effector such as muscle, gland or another neuron, most of its axon located in the PNS
Oligodendrites; myelinate axons
Astrocytes; regulates the brain mileu, stimulate blood/brain barrier, closes the synaptic cleft between neurons and take up neurotransmitters
Microglia; acts as the immunesystem of the brain, through phagocytosis
CNS - Glial Cells: Surround the axon and dendrites of neurons in the CNS. Provide physical and metabolic support
PNS – Glial Cells: Schwann Cells produce the myelin sheath of the axons in the periphery and Podocytes wrap around blood vessels to form the BBB
Action potential
- Resting State: Neurons maintain a resting membrane potential, typically around -70 millivolts (mV), due to the unequal distribution of ions across the cell membrane. Maintained by the sodium-potassium pump.
- Threshold: To initiate an action potential, the neuron must receive a stimulus that brings the membrane potential to a critical threshold level, usually around -55 mV. If the stimulus is strong enough to reach this threshold, it triggers the opening of voltage-gated sodium channels.
- Depolarization: Voltage-gated sodium channels open rapidly, the influx of sodium ions causes a rapid and large depolarization of the cell membrane, resulting in a positive membrane potential.
- hyperpolarization of Na: As more sodium channels open, the positive feedback loop intensifies, causing a rapid increase in membrane potential. The membrane potential reaches its peak, usually around +30 mV. Voltage-gated sodium channels begin to inactivate.
- Repolarization: Voltage-gated potassium channels open.
Potassium ions move out of the cell, leading to the repolarization of the membrane. - Hyperpolarization: repolarization process overshoots the resting membrane potential, creating a temporary hyperpolarization of K. Na return to closed-state from inactivation, de-inactivates.
The relative refractory Period:
- Period in which Na+ channels de-inactivates and the charge needed for action potential decreases as more Na+ channels are de-inactivated.
Action potentials leaks over a distance, lambda is the distance at which 37% of the potential charge is lost
Graded potentials
- have a spatial distribution e.g. at an open cation channel there will be an area of depolarisation and the charge is concentrated at the site of depolarization and this determines how the potential moves along the neuron.
- as it moves farther from the site there is a dissipation or loss of charge as you move along: cable theory
- primarily generated by sensory summation input, causing a change in the conductance of the membrane of the sensory receptor cell
Divergence vs convergence
Neurons
- Convergence is where different neurons affect one neuron
- Divergence is where one neuron affects many different neurons
Refactory period
Action potential
- absolute refractory period: region of the membrane where Na channels are either already open or have proceeded to the inactivated state during the first action potential; during the action potential, a second stimulus will not be able produce a second action potential
- relative refractory period: following the absolute refractory period there is an interval in which a second action potential can be produced; some Na channels have returned to a resting
Feedforward regulation
changes in regulated variables are anticipated and prepared for before they actually occur
Reflex
A receptor detects the environmental change and is acted upon by a stimulus. The receptor relays a signal to an integrating center using the afferent pathway. This is then sent to the effector via the efferent pathway to elicit a response.
Adaptation
homeostasis
denotes a characteristic that favors survival in specific environments.
- E.g. the ability of certain individuals to digest lactose in milk
Acclimatization
Homeostasis
the improved functioning of an already existing homeostatic system
- Acclimatization is usually reversible
GPCRs – cAMP
Draw
Neuron structure
- Soma (cell body): contains the nucleus and ribosomes necessary for protein synthesis in this location
- Dendrites: outgrowths of the soma; typically receive incoming signals from another neuron; increase the surface area of the cell which increases capacity to receive signals from many other neurons
- Axon: carries outgoing signals to its target cells
- Collaterals: branches extending out of the axon; the greater amount of branching, the greater the cell’s influence on other neurons
- Axon Hillock: region where propagated electrical signals are generated; the neuron decides whether an action potential should be integrated, only if threshold is reached
- Axon Terminal: all branches end in this segment, release neurotransmitters from the axon
- Myelin sheaths: speeds up conduction of the electrical signals, conserves energy and cover the axon, are wrapped by:
Oligodendrocytes: glial cells that recruit myelin onto axons found in brain and spinal cord (CNS)
Schwann cells: glial cells form individual myelin sheaths at regular intervals along axons found in PNS
Nodes of Ranvier: spaces between myelin sheaths, exposes intervals of axon to extracellular fluid
Motor protein transport
Kinesin: anterograde transport; transports materials from soma to axon terminal; moves nutrient molecules, enzymes, mitochondria, vesicles, etc.
Dynein: retrograde transport in other direction; carry recycled membrane vesicles, growth factors, and other chemical signals.
Different types of receptors
- Mechanoreceptors: respond to mechanical stimuli such as pressure or stretch. The receptors adapt at different rates – some adapt rapidly as the stimulus is changing which gives sensations of touch, whereas slowly adapting receptors give rise to sensation of pressures. Some has small receptive fields that can provide precise information(fingers) and some wide (back).
- Thermoreceptors: detect sensations of cold of warmth. Different TRP isoforms will open at different temperature ranges to allow influx of cations to generate action potential
- Photoreceptors: respond to particular ranges of light wavelengths.
- Chemoreceptors: respond to binding of particular chemicals to the receptor membrane, provides senses of smell and taste.
- Nociceptors: general detectors of pain due to actual or potential tissue damage. Can be activated by a variety of stimuli.
Adaptation
Sensory
decrease in receptor sensitivity, which results in a decrease in action potential frequency in an afferent neuron despite the continuous presence of a stimulus.
- Rapidly adapting receptors (phasic) are quick to produce action potentials at onset of stimulus but very quickly cease responding.
- Slowly adapting receptors (tonic) maintain a persistent or slowly decaying receptor potential during a constant stimulus and hence can initiate action potentials for the duration of the stimulus.
Receptive fields
Neuron
Branches that belong to one afferent neuron, originating from a single afferent neuron with all its receptors endings makes up a sensory unit and peripheral end of an afferent neuron divides into many fine branches, each of which will have a sensory receptor.
Receptive fields of neighbouring neurons tend to overlap so stimulation of a single point activates several sensory units
- Strength of stimuly can affect adjacent branches resulting in summation and therby increase the frequency of action potential.
- more action potentials in the associated afferent neuron if it occurs at the centre of the receptive field.
lateral inhibition
Neuron
information from afferent neurons with receptors at the edge of a stimulus is strongly inhibited compared to information from afferent neurons at the centre.
The pathways can ‘talk’ so that central neuron is firing at highest frequency, it inhibits the lateral neurons (via inhibitory interneurons) to a greater extent than the lateral neurons inhibit the central pathway.
- enhances the contrast between the centre and periphery of a stimulated region, thereby increasing the brain’s ability to localise a sensory input.
Descending pathways
Neurons
influence sensory information by directly inhibiting the central terminals of the afferent neuron or via an interneuron that affects the ascending pathway by inhibitory synapses.
- down from the brain
Descending neurons can stimulate opiod release, which inhibits exitatory neurons
Ascending pathways (act upon signals going up to the brain)
Afferent sensory pathways
Neuron
formed by chains of three or more neurons connected by synapse. Central processes of afferent neurons enter the brain or spinal cord and synapse to interneurons. Central processes may diverge to terminate on several interneurons (A); or can converge so that the processes of many afferent neurons terminate upon a single interneuron (B).
Referred pain
due to the convergence of visceral and somatic afferent neurons onto ascending pathways, this is why people having heart attack can feel pain in their arms.
- Information about somatic sensation enters both specific and nonspecific ascending pathways. The specific pathways cross to the opposite side of the brain.
On- and off-pathway
neurons
It is intrinsic for the bipolar cell, it either depolarizes (on) or hyperpolerizes (off). Lateral inhibition and the clear edge between ON and OFF areas increases the contrast between areas.
- On reduces inhibition
- Off reduces exitation
The eye
The eye processes light through the cornea and lens, focusing it on the retina. Refraction and shape changes in the lens adjust focus. The retina contains layers of cells, with photoreceptors (rods and cones) at the back. Cones detect colors and have fewer discs than rods (active in the dark).
- Photoreceptors have photopigments that absorb light. Rhodopsin is the photopigment in the retina for rods. Photopigments have membrane bound proteins called opsins which are bound to a chromophore (retinal) molecule.
- In the absence of light, guanylyl cyclase converts GTP to cGMP (secondary messenger) which can keep the outer segment ligand-gated cation channels in open state allowing influx of cations hence when it is dark the cell is maintained in depolarised state.
- When light shines, retinal molecules change conformation and dissociate from opsin so the shape of opsin also changes promoting an interaction between opsin and transducin. Transducin belongs to G protein family and can activate enzyme that degrades cGMP so the cation channels can close and there is loss of depolarising current to the membrane potential hyperpolarises. Retinal molecule changes back to resting shape and binds to opsin.
The eye’s complexity enables the conversion of light into electrical signals for vision, with the final image inverted on the retina. Eyeball length variations can cause near-sightedness or far-sightedness. The proximity of photoreceptors to the pigmented epithelium prevents blurring and back scattering.
The retina
structural
Light path ->
Ganglion cells -> Amacrine cells -> Bipolar cells -> horizontal cells -> Cones and Rods -> pigment epithelium
Muscle
Types
- Skeletal; voluntary, anatomically around skeleton and is striated
- Cardiac; involuntary, anatomically in the heart and is striated
- Smooth muscle; involuntary, anatomically surronding organs and bloodvessels and is smooth
Skeletal muscle
structure
The muscle is build up by sarcomers consisting of a Z-line, thin- and thick filaments and a M-line in the middle. (striated pattern of skeletal muscle is due to arrangement of thick and think filaments)
- Thin filaments also have troponin and tropomyosin. Each actin has binding site for myosin.
- Thick filaments are made from myosin, myosin heavy chain has two globular heads which generate movement.
Sarcoplasmic reticulum forms a sleeve around each myofibril, at the end of each segment are the lateral sacs which have a calcium binding protein
Transverse tubule (t-tubule) is continuous with the extracellular fluid surrounding the muscle fibre, and allow action potentials propagating along the surface membrane to also travel into the muscle fibre interior.
Skeletal muscle contractions
Alpha neurons innervate skeletal muscle fibres.
Depolarization and opening voltage-sensitive calcium channels triggers the release of acetylcholine (ACh) into the extracellular cleft. ACh diffuses to the motor end plate, binding to nicotinic receptors, leading to sodium and potassium influx and depolarization, creating the end-plate potential (EPP). Initiating an action potential that propagates along the muscle fiber surface and T-tubules, facilitating muscle contraction.
- Neuromuscular junctions are typically centrally located, enabling bidirectional propagation of action potentials.
- All neuromuscular junctions are excitatory hence there are never any inhibitory signals.
Calcium binding to troponin induces a conformational change, allowing tropomyosin to move, enabling cross-bridge formation between myosin and actin. Cross bridge activity is calcium-dependent.
In resting muscle, low cytosolic calcium blocks cross bridge activity. Calcium release from the sarcoplasmic reticulum (SR) via T-tubule action potential occurs. The DHP receptor induces a conformational change in the ryanodine receptor, allowing calcium release. Calcium ATPases in the SR membrane pump calcium back, taking longer than release, sustaining cytosolic calcium concentration and prolonging contraction.
Sliding filament mechanism
Skeletal muscle
Sliding filament theory as the distance between the Z discs shortened but the A band length was unchanged. The cross-bridge cycle is responsible for this movement:
1. Ca2+ binds to troponin C, troponin I realease actin, which displase the actin and reveal bindingsite for myosinheads.
- Myosin releases Pi during the binding to bindingsite, triggering the release of the strained conformation of the energised cross-bridge which produces the movement of the bound cross-bridge aka power stroke, which release ADP.
- Binding of new ATP molecule to myosin breaks the link between actin and myosin. This dissociation is an example of allosteric regulation of protein activity as the binding of ATP at one site on myosin decreases myosins affinity for actin bound at another site.
- Note: at this step ATP is not acting as an energy source, it is simply an allosteric modulator that weakens binding between myosin and actin.
4 Once actin and myosin have dissociated, ATP bound to myosin is hydrolysed by myosin-ATPase, thereby reforming the energised state of myosin and returning the crossbridge to its pre-power stroke.
Types of contraction
Skeletal muscle
- Isometric: muscle length is constant during activation
- Concentric: muscle shortens during activation
- Eccentric: muscle lengthens during activation.
