Systems Physiology Flashcards
1
Q
Homeostasis
definition
A
any self-regulating process by which an organism tends to maintain stability while adjusting to conditions that are best for its survival
2
Q
Feedback loops
A
- negative feedback loops that counteract changes of various properties from their target values, known as set points.
- positive feedback loops amplify their initiating stimuli
2
Q
Substance balance
A
- 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.
2
Q
Osmosis
A
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
3
Q
Reflection coefficient
A
describes how well solutes permeate the membrane. This coefficient ranges from 0 to 1. A reflection coefficient of 1 means a solute is impermeable
4
Q
Communication by chemical messengers
A
Endocrine
Paracrine
Autocrine
direct Cell-cell (gap-junctions)
5
Q
Net flux
A
represents the amount of substance moved in or out of the cell
6
Q
Transporters
A
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
7
Q
Specialized endocytosis
A
- 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
8
Q
GPCR - IP3/DAG
Pathway
A
Draw yourself
9
Q
GPCR - Adenylcyclase
Pathway
A
Draw yourself
10
Q
Ion channels
A
- 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
11
Q
Chemical messengers
A
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
12
Q
Cells of the central nervous system
A
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
13
Q
Action potential
A
- 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
14
Q
Graded potentials
A
- 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
15
Q
Divergence vs convergence
Neurons
A
- Convergence is where different neurons affect one neuron
- Divergence is where one neuron affects many different neurons
16
Q
Refactory period
Action potential
A
- 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
17
Q
Feedforward regulation
A
changes in regulated variables are anticipated and prepared for before they actually occur
18
Q
Reflex
A
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.
19
Q
Adaptation
homeostasis
A
denotes a characteristic that favors survival in specific environments.
- E.g. the ability of certain individuals to digest lactose in milk
20
Q
Acclimatization
Homeostasis
A
the improved functioning of an already existing homeostatic system
- Acclimatization is usually reversible
21
Q
GPCRs – cAMP
A
Draw
22
Q
A
23
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
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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.
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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.
26
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.
27
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.
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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.
29
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)
30
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).
31
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.
32
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
33
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.
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The retina
| structural
Light path ->
Ganglion cells -> Amacrine cells -> Bipolar cells -> horizontal cells -> Cones and Rods -> pigment epithelium
35
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
36
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.
37
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.
38
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.
2. 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.
3. 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.
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Types of contraction
| Skeletal muscle
- Isometric: muscle length is constant during activation
- Concentric: muscle shortens during activation
- Eccentric: muscle lengthens during activation.
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Load-velocity relation
| Skeletal muscle
- Shortening velocity is maximal when there is no load and is zero when the load is equal to the maximal isometric tension.
- At loads greater than the maximal isometric tension, the fibre will lengthen at a velocity that increases with load
NOTE: increase in muscle tension from successive action potential occurring during the phase of mechanical activity is known as summation
-contraction in response to repetitive stimulation is called tetanus
41
Length-tension relation
| Skeletal muscle
- Titin protein (attached to Z line and thick filament) is responsible for most of the passive elastic properties of relaxed muscle fibres.
- With increased stretch, the passive tension in relaxed fibre increases due to elongation of titin filaments.
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principal types of skeletal muscle fibres
- Slow-oxidative fibres (type 1) combine low myosin-ATPase activity with high oxidative capacity.
- Fast-oxidative-glycolytic fibres (type 2A) combine high myosin-ATPase activity with high oxidative capacity and intermediate glycolytic capacity.
- Fast-glycolytic fibres (type 2X) combine high myosin-ATPase with high glycolytic capacity.
43
Energy metabolism
| Skeletal muscle
- Phosphorylation of ADP by creatine phosphate provides a rapid ATP source at the start of muscle activity. Creatine phosphate breaks down into creatine and phosphate, quickly transferring energy to ADP.
- Oxidative phosphorylation in mitochondria is fueled initially by muscle glycogen breakdown. After 5-10 minutes, blood-borne fuels, glucose, and fatty acids become dominant. Fatty acids become more crucial over time, reducing reliance on glucose.
- Phosphorylation of ADP by glycolysis in the cytosol quickly produces ATP, especially in anaerobic conditions. Increased muscle activity leads to elevated lactic acid levels.
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Regulation of whole muscle tension
| Skeletal muscle
- Individual fibre tension
- Fibre type dependent
- Muscle length
- Amount of fibres activated
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Local control of motor neurons
| Motor control
Most synaptic input to motor neurons comes from descending pathways and afferent neurons. Interneurons, acting as switches, integrate inputs and execute movement commands from higher centers.
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Co-activating Gamma Motor Neurons
| Motor control
Co-activating gamma motor neurons with alpha motor neurons prevents the central region of the muscle spindle from going slack during muscle shortening, ensuring continuous information about muscle length for ongoing and future movements.
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Length Monitoring Systems
| Motor control
Muscle spindles, with intrafusal and extrafusal fibers, monitor muscle length. Stretching muscle increases firing in stretch receptors, providing information about muscle length.
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Stretch reflex
- Monosynaptic Reflex (Path A): Activated stretch receptors in the thigh directly synapse onto motor neurons, causing contraction of the thigh muscles. This is a rapid, monosynaptic reflex.
- Inhibitory Interneurons (Path B): Afferent fibers activate inhibitory interneurons, inhibiting motor neurons to antagonistic muscles, inducing muscle relaxation.
- Activation of Synergistic Muscles (Path C): Afferent information activates motor neurons of synergistic muscles, aiding the intended motion.
- Information Ascending (Path D): Not part of the stretch reflex, but it demonstrates that information about changes in muscle length ascends to higher centers, crucial for slow, controlled movements.
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Brain Motor Centers:
- Cerebral Cortex: Primary motor cortex and premotor area plan and control voluntary movements. Anatomically distinct areas are interconnected and organized somatotopically.
- Subcortical and Brainstem Nuclei: Important for planning, monitoring movements, and learning skilled movements. Dysfunction contributes to conditions like Parkinson's disease.
- Cerebellum: Influences posture and movement indirectly, receiving sensory input and playing a crucial role in timing, coordination, and movement planning.
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Descending Pathways
- Corticospinal Pathways (Pyramidal Tracts): Originate in the cerebral cortex, most crossover in the medulla oblongata, influencing fine, isolated movements, particularly of the fingers and hands. Include corticobulbar pathways controlling facial muscles.
- Brainstem Pathways: Originate in the brainstem, remain mainly uncrossed, and affect muscles on the same side. Involved in coordinating large muscle groups for posture, locomotion, and head/body movements.
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Smooth Muscle Characteristics
- Structure: Lacks cross-striations found in skeletal and cardiac muscles, appears smooth. Smaller spindle-shaped cells with a single nucleus capable of division throughout life.
- Voluntary Control: Innervated by the autonomic division of the nervous system, not under direct voluntary control.
- Locations: Common in hollow organs like blood vessels, gut, bladder, and structures like hair follicles, radial muscles in the eye, and ciliary muscles.
52
Smooth Muscle Types
- Single Unit Smooth Muscle:
Responds as a single unit due to gap junctions.
Contains pacemaker cells generating spontaneous action potentials.
Found in the intestine, uterus.
- Multiunit Smooth Muscle:
Responds independently, lacks gap junctions.
Richly innervated by the autonomic nervous system.
Found in bronchi.
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Smooth Muscle Contraction and Control:
- Cross Bridge Activation: Controlled by calcium-regulated enzyme phosphorylating myosin, allowing cross-bridge formation. Dephosphorylation by myosin light-chain phosphatase relaxes the muscle.
- Calcium Sources: Sarcoplasmic reticulum and extracellular calcium entering through channels. Removal occurs through transport back into the SR or out of the cell.
- Activation Degree: Unlike skeletal muscle, only a portion of cross-bridges is activated in smooth muscle, allowing graded tension.
- Depolarization: In some smooth muscles, calcium ions, not sodium, bring in a positive charge during action potentials.
- Spontaneous Action Potentials: Some smooth muscle cells generate action potentials spontaneously, leading to rhythmic contractile activity known as pacemaker potential.
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Tonic vs. Phasic Contraction:
| Smooth muscle
- Tonic Contraction: Muscle can amplify force by entering a latch state, sustaining contraction with minimal ATP use. E.g., sphincters.
- Phasic Contraction: Alternating periods of contraction and relaxation, as seen in peristalsis.
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Autonomic Neurotransmitters and Receptors:
- Alpha Adrenergic Receptors: Stimulate contraction via GPCR Gαq.
- Beta Adrenergic Receptors: Activate cAMP and PKA, decreasing active myosin complex, leading to relaxation.
56
Regulation of Smooth Muscle Contraction
Inputs:
- Spontaneous electrical activity (action potentials).
- NTs released by autonomic nerves.
- Hormones (e.g., adrenaline).
- Local factors (pH, oxygen, osmolarity, ion concentrations, paracrine factors like prostaglandins, NO).
- NO (Nitric Oxide): Common paracrine compound causing smooth muscle relaxation.
- Stretch: Also regulates smooth muscle contraction.
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Erythrocytes (RBC)
- Biconcave shape, flexible for small capillaries.
- Hemoglobin binds oxygen and carbon dioxide.
- Iron homeostasis crucial for regeneration.
- Iron stored in RBC, released during destruction in spleen.
- Erythropoietin (EPO) stimulates RBC production.
- Causes of anemia: Iron deficiency, bone marrow failure, blood loss, inadequate erythropoietin secretion, excessive RBC destruction.
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Blood circulation
System Overview:
- Arteries and veins determined by direction, not oxygenation.
- Atrium (upper), ventricle (lower).
- Blood leaves left ventricle via aorta.
- Veins: Venules join to form veins, superior and inferior vena cava.
- Pulmonary circulation has separate vessels.
- Portal circulation (liver, anterior pituitary) passes through two capillary beds.
Blood Flow Equation: Flow = (Pressure Difference) / Resistance.
Determinants of Resistance:
- Viscosity, length, and radius of the tube.
- Small changes in radius affect resistance significantly in capillaries.
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Cardiac Contraction
Action Potential:
- Resting membrane potential close to -90mV.
- Depolarization by voltage-gated Na+ channels.
- Repolarization by K+ channels.
- Plateau phase: Ca2+ influx balances K+ efflux.
Calcium Activated Contraction:
- Troponin regulates cross-bridge formation.
- More Ca2+ released from sarcoplasmic reticulum strengthens contraction.
Cardiac Troponin in Blood:
- Indicates myocardial infarction (MI).
Innervation:
- Sympathetic (norepinephrine) and parasympathetic (ACh) fibers.
- Coronary arteries supply heart.
Cardiac Action Potentials:
- Long action potential prevents summation, aiding in filling during relaxation.
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Heart
Heart Wall Layers:
- Epicardium (outer), myocardium (muscular), endocardium (inner).
- Interventricular septum divides right and left sides.
Valves:
- Atrioventricular (AV): Tricuspid (right), bicuspid (left).
- Semilunar: Between ventricle and artery.
Cardiac Muscle:
- Striated, sarcomeres organized similarly to skeletal muscle.
- Cells connected via intercalated discs and adherence junctions.
- Gap junctions allow coordinated contraction.
- Nodal Action Potential: Pacemaker potential, calcium influx causes gradual depolarization.
Conduction System:
- Sinoatrial (SA) node: Pacemaker near vena cava.
- Atrioventricular (AV) node: Delays transmission to ventricles.
- Bundle of His, bundle branches, Purkinje fibers: Transmit action potential to ventricles.
ECG (Electrocardiogram):
- P wave (atria depolarization), QRS complex (ventricle depolarization), T wave (ventricle repolarization).
- ECG shows electrical activity across multiple cardiac cells.
- Different leads may produce variations.
- ECG abnormalities: AV block examples.
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Cardiac Cycle
- The cardiac cycle consists of atrial and ventricular contractions and relaxations.
- Two main phases: systole (ventricular contraction and blood ejection) and diastole (ventricular relaxation and blood filling).
- Systole and diastole each have two phases.
- Isovolumetric ventricular contraction occurs when the ventricles contract, but the valves are still closed.
- Ventricular ejection follows isovolumetric contraction, and stroke volume is the amount of blood ejected.
- Diastole involves isovolumetric ventricular relaxation, AV valve opening, and atrial contraction.
- The cardiac cycle's left ventricle and aorta events include mid-diastole to late diastole, systole, and early diastole.
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Control of Heart Rate
- SA node regulates the heart rate.
- Parasympathetic activity (vagus nerve) decreases heart rate, while sympathetic activity increases it.
- Hormones like epinephrine from the adrenal medulla also influence heart rate.
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Control of Stroke Volume
- Stroke volume is influenced by end-diastolic volume, sympathetic nervous system input, and afterload.
- The Frank-Starling mechanism: Stroke volume increases as end-diastolic volume increases.
- Sympathetic stimulation increases contractility and stroke volume.
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Vascular System
- Endothelial cells line blood vessels, serving various functions.
- Arteries have compliance and contribute to pulse pressure. MAP is determined by a complex equation.
- Arterioles regulate blood flow and mean arterial pressure via vasodilation and vasoconstriction.
- Local controls and extrinsic controls, including sympathetic and parasympathetic influences, regulate arteriolar radius.
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Capillaries
- Capillaries allow efficient exchange between blood and tissues through diffusion.
- Bulk flow of protein-free plasma aids in fluid distribution.
- Starling forces (hydrostatic and osmotic pressures) determine net filtration and absorption.
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Venules and Veins
- Venules have a large blood capacity and facilitate leukocyte migration.
- Peripheral venous pressure is crucial for venous return to the heart.
- Veins have thin walls, high compliance, and valves to prevent backflow.
- Skeletal muscle pump and respiratory pump aid in venous return.
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Lymphatic System
- The lymphatic system consists of lymph nodes and vessels that carry lymph (interstitial fluid) back to the circulatory system.
- Lymphatic capillaries have large channels and play a role in fat absorption from the GI tract.
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General Circulation
- Mean Arterial Pressure (MAP) depends on Cardiac Output (CO) and Total Peripheral Resistance (TPR).
- TPR is also known as Systemic Vascular Resistance (SVR), representing the combined resistance of systemic blood vessels.
- Changes in MAP result from changes in CO and/or TPR, influencing the average volume of blood in systemic arteries over time.
- Total peripheral resistance is determined by total arteriolar resistance, with arterioles being major sites of resistance in the systemic circuit.
- Compensatory mechanisms, like vasoconstriction in less vital organs during increased perfusion to a specific organ, help maintain overall pressure.
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Arterial Baroreflexes
- Arterial baroreflexes, mediated by baroreceptors in carotid and aortic vessels, regulate mean arterial pressure.
- Baroreceptors detect pressure changes and relay information to the medullary cardiovascular center in the medulla oblongata.
- Neural pathways from the cardiovascular center influence sympathetic and parasympathetic outflow, controlling heart rate and vessel tone.
- Increased MAP leads to decreased sympathetic outflow and increased parasympathetic outflow, and vice versa.
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Hemorrhage and Compensation
- Baroreceptor reflex compensates for decreased blood pressure during hemorrhage.
- Baroreceptor reflex functions as a short-term regulator, responding almost instantly to blood pressure changes.
- Long-term regulation involves blood volume, influencing venous pressure, venous return, end-diastolic volume, stroke volume, and cardiac output.
- Autotransfusion occurs in response to fluid loss, with intracellular fluid moving into vessels to increase plasma volume and restore arterial pressure.
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Blood Pressure Regulation in Various Conditions
- Hypotension can result from conditions like severe sweating, burns, diarrhea, vomiting, and others.
- Shock, denoting decreased blood flow to organs, can be hypovolemic, low-resistance, or cardiogenic.
- During exercise, CO increases, with arteriolar vasodilation in exercising muscles and vasoconstriction in other organs.
- Hypertension, chronically increased systemic arterial pressure, can lead to left ventricular hypertrophy and heart failure.
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Hemostasis
- Hemostasis is the stoppage of bleeding and involves the formation of a platelet plug and blood clot.
- Platelet plug formation includes platelet adhesion, activation, and aggregation.
- Blood coagulation leads to clot formation, involving the intrinsic and extrinsic pathways and the activation of thrombin.
- Anticlotting systems, including tissue factor pathway inhibitor, protein C activation, and antithrombin III, limit clot formation.
- Fibrinolytic system dissolves clots through the activation of plasmin.
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Blood-Brain Barrier and Cerebrospinal Fluid
- Cerebrospinal fluid (CSF) cushions the central nervous system (CNS) and is produced by ependymal cells in the choroid plexus.
- The blood-brain barrier controls the entry of substances into the brain's extracellular fluid, formed by cells lining small brain blood vessels.
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Lung Volumes and Capacities
- Tidal volume, inspiratory reserve volume, expiratory reserve volume, and residual volume are key lung volumes.
- Vital capacity is the maximum amount of air exhaled after maximum inhalation.
- Forced vital capacity (FVC) and forced expiratory volume (FEV) differentiate obstructive and restrictive diseases. Normally FEV is around 80% of FVC.
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Lung compliance
- Degree of lung expansion is proportional to the transpulmonary pressure (Palv-Pip).
- Lung compliance is defined as the magnitude of the change in lung volume divided by a change in transpulmonary pressure.
The greater the lung compliance, the easier it is to expand the lungs at any given change in transpulmonary pressure:
Pneumonia can reduce lung compliance due to stiffness.
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Principles of Ventilation
- Diaphragm and intercostal muscles are primary muscles of inspiration and expiration.
- Boyle's law describes the inverse relationship between gas pressure and container volume. Deadspace, is where the pressure corresponds to that of the atm, and is therefore inhaled agian. (negative pressure during inhalation and possitive during exhalation).
- Intrapleural pressure is negative during inspiration, keeping the lungs open against their inward recoil. There is always air in the lungs.
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Pulmonary Circulation:
| Lungs
Pulmonary arteries divert blood flow from damaged alveoli.
- Hypoxia in the lungs triggers vasoconstriction to avoid sending blood through poorly oxygenated alveoli.
Severe lung damage can lead to pulmonary edema due to increased capillary hydrostatic pressure.
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Alveoli and Gas Exchange
- Alveoli are connected through holes for air diffusion, allowing airflow even if some alveoli are occluded.
- Alveoli are primarily composed of type I cells, with type II cells producing pulmonary surfactants that lower surface tension.
Alveolar type II cells secrete a lipoprotein material called surfactant, whose primary function is to reduce the surface tension in the alveoli
The diffusion barrier consists of
1. Type I alveolar cells
2. Basal lamina
3. Capillary epithelial cells
- Very fragile
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Control of Conducting Zone
| Lungs
Smooth muscle cells in bronchi contract and dilate, expressing beta-adrenergic receptors that respond to norepinephrine.
- In anaphylaxis, inflammatory mediators like histamine can increase bronchial smooth muscle contraction.
- Asthma is treated with beta-adrenergic agonists like salbutamol to dilate bronchi.
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Organization of the Respiratory System and Respiratory Pathway
1. Air enters the pharynx, which branches into the esophagus (for food) and the larynx (for air and vocal cords).
2. Upper airways include the nose, mouth, and nasal concha, which increases surface area for air filtration, heating, and humidification.
- Swallowing involves the soft palate, uvula, larynx, epiglottis, tongue, and pharyngeal muscles.
The larynx opens into the trachea, which further branches into bronchi and bronchioles. (conducting zone, which defends agianst bacteria, heats and moisture air and ensures a low resistance)
- Bronchioles are the first airway branches without cartilage, and the respiratory zone contains alveoli for gas exchange.
- Conducting zone lacks alveoli but has cilia defending against foreign matter.
Gas exchange occurs at the alveolar-capillary membrane, with oxygen entering cells and carbon dioxide exiting cells.
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Convection vs. Diffusion
| Gas exchange
Convection is the mass movement of molecules in the same direction, while diffusion is the movement of a fluid from an area of higher concentration to an area of lower concentration.
- Boyle's Law states that the pressure of a given mass of an ideal gas is inversely proportional to the volume it occupies.
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Gas Exchange
- The respiratory quotient (RQ) represents the ratio of CO2 produced to O2 consumed.
Oxygen and CO2 exchange occurs between the atmosphere, lungs, blood, and tissues.
Alveolar partial pressure of oxygen is influenced by atmospheric air, alveolar ventilation rate, and total-body oxygen consumption.
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Transport of CO2 and O2 in Blood
- CO2 is transported in plasma (7%), bound to hemoglobin (23%), and as bicarbonate (70%). Bicarbonate is crucial for maintaining blood pH.
- Oxygen is transported dissolved in plasma (2%) and reversibly combined with hemoglobin (98%). Hemoglobin can bind four oxygen molecules, reaching equilibrium between free and bound oxygen.
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Control of and affects on Breathing
Breathing is controlled by the autonomic nervous center (medulla oblongata) but can be voluntarily influenced. Negative feedback regulates rhythmic, involuntary breathing.
Innervation of the diaphragm and intercostal muscles is through somatic motor nerves
Chemoreceptors monitor CO2, H+, and O2 levels.
- Peripheral chemoreceptors in arteries monitor CO2 concentration, O2 concentrations in blood and feed back on respiratory centers.
- central chemoreceptors in the medulla monitor CSF CO2 concentration.
Stretch receptors in the lungs and chest wall monitor the amount of stretch in these organs
- Stretch receptors, higher brain centers, and chemical factors (pH) influence breathing.
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Hypoxia
Four types of hypoxia:
- hypoxic (Low oxygen in the inhaled air)
- anemic (Reduced oxygen-carrying capacity of blood)
- circulatory (Reduction in blood circulation)
- histotoxic (Reduced ability of tissue cells to consume oxygen)
High-altitude exposure triggers hyperventilation, tachycardia, and pulmonary responses to adapt to decreased oxygen levels.
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Hypoventilation and Hyperventilation
- Hypoventilation occurs when alveolar ventilation can't keep up with CO2 production.
- Hyperventilation occurs when alveolar ventilation is excessive for the amount of CO2 being produced.
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Control of Ventilation During Exercise:
Major stimuli to ventilation during exercise include reflex input from mechanoreceptors, increased body temperature, central command from exercising muscles, plasma epinephrine concentration, and increased plasma K+ concentration.
- Ventilation changes occur rapidly at the onset and end of exercise.
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Acute hypoxic exposure
A) Hyperventilation: Decrease arterial pO2 -> stimulation of
peripheral chemoreceptors -> increased rate & depth of
breathing -> increased pH -> Respiratory alkalosis
B) Tachycardia: Also stimulate peripheral chemoreceptors ->
increase sympathetic activity -> increase Cardiac Output ->
increase oxygen delivery to the tissues.
C) Decreased pO2 -> vasoconstriction of pulmonary vasculature -> Increased pulmonary capillary pressure -> fluid filtration ->
Capillary stress and failure -> increased permeability -> HAPE
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Mouth and Salivary Glands
| Digestion and secretion
- The mouth receives food and initiates mechanical digestion through mastication.
- Salivary glands produce saliva containing amylase (enzymes for carbohydrate digestion).
- Parasympathetic stimulation triggers saliva production, and there are three major salivary glands: parotid, submandibular, and sublingual.
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Stomach
| Digestion and secretion
- The stomach receives, mixes, and propels food to the small intestine.
- Gastric glands produce gastric juices containing mucus, pepsinogen, and HCl.
- Stomach motility involves receptive relaxation and peristaltic waves.
- Gastrin and acetylcholine stimulate gastric secretions.
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Pancreas
| Digestion and secretion
- The pancreas produces pancreatic juice with digestive enzymes.
- Pancreatic enzymes are activated in the small intestine.
- Secretin and cholecystokinin regulate pancreatic secretion.
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Liver and Gallbladder
| Digestion and secretion
- The liver secretes bile, while the gallbladder stores and releases bile.
- Bile emulsifies fat, increasing its surface area for digestion.
- Bile salts are reabsorbed in the enterohepatic circulation.
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Small Intestine
| Digestion and secretion
- Consists of the duodenum, jejunum, and ileum.
- Villi and microvilli increase the surface area for absorption.
- Carbohydrates, proteins, and fats are digested and absorbed in the small intestine.
- Mixing movements (segmentation) and propelling movements (peristalsis) aid digestion.
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Large Intestine
| Digestion and secretion
- The large intestine absorbs water and electrolytes.
- Intestinal flora synthesizes vitamins and uses cellulose for raw materials.
- Defecation involves the rectum, internal anal sphincter, and external anal sphincter.
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Absorption in the Small Intestine
| Digestion and secretion
- Active transport and facilitated diffusion absorb monosaccharides and amino acids.
- Fats are emulsified by bile salts, digested by lipase, and absorbed as fatty acids.
- Water and electrolytes are absorbed through the small intestine's villi.
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Types of Secretion
| Principles of hormonal control system
- Constitutive secretion is continuous, while regulated secretion is stimulated.
- Exocrine secretion goes into ducts, and endocrine secretion goes into the bloodstream.
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Hormones
| Principles of hormonal control system
- Amine hormones: synthesized from tyrosine, including catecholamines (e.g., norepinephrine, epinephrine) and iodine-containing hormones (T3, T4).
- Peptides/Proteins: synthesized in the endoplasmic reticulum, stored in vesicles, and released upon stimulation. Protein-bound hormones have an equilibrium between free and bound forms, with the free fraction exerting effects.
- Steroids: derived from cholesterol, including cortisol, aldosterone, testosterone, and estradiol. Steroid and thyroid hormones bind to intracellular receptors, influencing gene transcription.
Peptide hormones and catecholamines have a short half-life due to rapid breakdown. Steroid hormones have a longer half-life due to protein binding.
Major controllers include ions, nutrients, neurotransmitters, and other hormones.Hormone secretion can vary throughout the day, influenced by factors like circadian rhythms.
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Endocrine Disorders:
| Principles of hormonal control system
Classified by hormone amount (hyposecretion/hypersecretion), source (primary/secondary), and response (hypo/hyperresponsiveness).
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Hormonal glands
| Principles of hormonal control system
- Hypothalamus and Pituitary Gland:
Hypothalamus regulates the anterior pituitary through hypophysiotropic hormones. Posterior pituitary releases oxytocin and vasopressin.
- Thyroid Gland:
TSH stimulates T3 and T4 production, iodine is crucial in hormone synthesis. Hypo/hyperthyroidism can lead to thyroid disorders.
- Adrenal Gland:
Produces aldosterone and cortisol, influenced by the renin-angiotensin-aldosterone system. Adrenal medulla releases norepinephrine during the fight-or-flight response.
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Metabolic Processes:
| Principles of hormonal control system
- Absorptive state involves nutrient storage, while the postabsorptive state focuses on energy release.
- Insulin promotes nutrient storage, while glucagon, cortisol, and GH stimulate energy release.
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