Physiology Flashcards
Outline properties and structure and role in cell functions of biological membrane
Structure:
- Basic unit: phospholipid (polar head, non-polar tails)
- Lipid bilayer (trilaminar under electron microscope)
- spontaneously forms in water
Properties:
- Selectively permeable
- Surface components modified with carbohydrates
- Cholesterol reduces flexibility
Functions:
- Separate cell from environment (protection)
- Signalling
- Cell adhesion
- synthesis
- Secretion and uptake
List major composition of cytosol and extracellular fluid
- Extracellular fluid (15L): Plasma (3L), Interstitial fluid (12L)
- Intracellular fluid (25L)
Osmolality balance is maintained between plasma, interstitial fluid, and intracellular fluid
- Water freely flows between compartments
- Can only directly alter osmolality of plasma
- Can NOT directly alter osmolality of interstitial fluid or intracellular fluid
Osmolality = osmoles/kg Osmolarity = osmoles/L
Define movement of material across a biological membrane as passive or active and the biological conditions under which each process is most likely to take place
Two driving forces for material movement:
- Concentration gradient
- Electrical gradient
Passive transport: substance moved with its gradient. No energy needed.
- Simple diffusion
- Channel-mediated
- Carrier-mediated
Active transport: substance moved against its gradient. Energy is needed
- Pumps
- Secondary active transport: one molecule moved with gradient, and one moved against:
1) Co-transporter (symport carrier): both molecules in same direction
2) Exchanger (antiport carrier): molecules go in opposite directions
List properties of common transporter: NaK-ATPase
Na pumped out, K pumped in, uses ATP
List properties of common transporter: NaH-exchanger
Na passively in, H+ actively out
List properties of H-ATPase
H+ out, uses ATP
List properties of NaK2Cl-cotransporter
Na, K, and 2 Cl into cell, no change in charge
List properties of SGLUT1 (cotransporter)
Na in passively, glucose in actively
List properties of aquaporin
H2O in or out (depending on transporter)
Describe the key structure and function of epithelia
Epithelia function
- Protective
- Secretory
- Absorptive
- Sensory
- Lubricating
Functional Epithelia Junctions
- Tight junctions: Selectively let molecules pass in the space between cells.
1) Forces molecules to be transported through the cell (allows cell to control transport) - Gap junctions: Easily allow ions and small molecules to pass between adjacent cell.
1) Gap junctions are always closed until lined up with a gap junction on the other side
2) Essential for coordinating actions of adjacent cell
Describe glucose recovery in proximal tubule as example of epithelial transport.
Apical side:
- SGLT transports 3 Na and 3 Glucose into cell (co-transport)
Basal side:
- GLUT channel lets glucose diffuse out
- NaK-ATPase pumps 3 Na out and 2 K in (active transport with ATP)
- K channel lets K diffuse out
Note:
- Since glucose can only enter cell through SGLT, high blood glucose can saturate transporter
- Glucose ends up in urine.
Describe chloride ion secretion in lungs as example of epithelial transport
Basal side:
- NaK2Cl co-transporter pumps 1 Na, 1 K and 2 Cl into cell
- K channel lets K diffuse out
- NaK-ATPase pumps 3 Na out and 2 K in (active transport with ATP)
Apical side:
- CFTR lets Cl diffuse out into lung air
Describe sweat production as example of epithelial transport
- Isotonic secretion: NaCl and water is secreted into coil
- NaCl absorption: Na+ and Cl- are resorbed only
Describe intracellular signalling in terms of the processes that take place in the target cell
- Chemicals or electrical signal affects cell surface
- Intracellular secondary messengers are release/created in the cytosol
- Additional proteins are affect.
Describe membrane potentials as a separation of charges
The membrane potential for a single ion is the electrical potential difference required to prevent diffusion of the ion across the membrane (assuming membrane is only permeable to that ion)
- Dependent on the difference in concentration in ECF and ICF, and membrane permeability
- e.g. Potassium:
1) Concentration is higher inside the cell, so membrane potential need to be negative to keep K+ in
2) Ek = -90mV
Describe membrane resting potential (Em)
It is the weighted average of the membrane potentials of all ions to which the membrane is permeable.
- The more permeable the membrane is to an ion, the greater influence that ion’s membrane potential has on the resting potential.
- Cell membranes are more permeable to K+ than Na+, so Em is closer to Ek.
Explain the process by which action potentials can propagate along a membrane
- Membrane depolarizes past threshold
- Voltage-gated Na+ channels open -> Na+ rushes in
- Membrane depolarizes
- Na+ channels close
- Voltage-gated K+ channels open slowly -> K+ rushes out
- Membrane repolarizes
- K+ channels remain open longer
- Membrane hyperpolarizes
- K+ channel closes
- NaK-pump restores resting potential.
Describe Ca2+ signalling
- glucose sensing in pancreatic beta-cells
- Glucose enters cell
- ATP produces in cell
- K+ channels close
- Cell membrane depolarizes
- Ca2+ channels open
- Insulin vesicles exocytosis - sarcoplasmic reticulum
- Action potential in T-tubules causes DHP confirmation change.
- RyR in sarcoplasmic reticulum releases Ca2+
- Ca2+ binds to troponin (on actin) and allows contraction
Describe IP3 signalling
- G-protein Coupled receptor (GPCR) receives signal
- G-protein activates phospholipase C
- Phospholipase C cleaves membrane phospholipid to IP3 and DAG.
1) IP3 releases Ca2+ from ER
2) DAG activates Protein Kinase C
Describe cAMP signalling
- G-protein coupled receptor (GPCR) receives signal
- G-protein activates Adenyl Cyclase
- Adenyl cyclase converts ATP to cAMP
- cAMP activates Protein Kinase A
Describe Ras/MAPK
- Receptor Tyrosine Kinase (RTK) activate Ras
- Ras activates MAPKKK, MAPKK, MAPK cascade
Distinguish between electrical and chemical signals
- Electrical signals: conductance between muscles; passage of charged molecules
- Chemical signals: neurotransmitter, signal molecules
Define neurotransmitter
Chemical secreted by neuron axons that diffuse across the synapse to elicit an action potential in the target cell
Describe neuron-to-neuron synaptic transmission:
- Action potential comes down the nerve axon
- depolarization of pre-synaptic axon
- Influx of Ca2+ into axon
- Release of neurotransmitters into synaptic cleft
- Neurotransmitters attach to receptors on postsynaptic neuron
- Action potential starts on postsynaptic neuron (if threshold met)
- Neurotransmitter is broken down.
Describe tetrodotoxin function
Blocks voltage-gated Na+ channels to inhibits APs
Describe neuromuscular junction
Between motor neuron axon and motor end plate
- Action potential comes down the nerve axon
- Depolarization of presynaptic axon
- Influx of Ca2+ into axon
- Release of ACh into synaptic cleft
- ACh attach to Nicotinic receptors on motor end plate
- Action potential starts on motor end plate
- Neurotransmitter is broken down by Acetylcholinesterase (AChE)
Describe Botulinum Toxin (botox)
Prevents ACh secretion
Describe organophosphate poisoning
Inhibits Acetylcholinesterase (AChE); constant contraction
Describe myasthenia gravis
Autoimmune disease where antibodies block and destroy ACh receptors (i.e. nicotinic receptors)
Describe the features of intercellular chemical signalling
- Autocrine signalling: cell secretes signal that acts on itself
- Paracrine signalling: cell secretes signal that acts on local cells
- Endocrine signalling: Hormones secreted into bloodstream and acts on distant cells
Outline the HPT axis
HPT axis = hypothalamic-pituitary-thyroid axis
Hypothalamus: important link between nervous system and endocrine system. Produces hormones
Posterior pituitary:
- Neurosecretory neurons in hypothalamus produce Vasopressin (ADH) and oxytocin
- Hormones are released into capillaries in posterior pituitary
- Hormones go straight to target tissue
- Negative feedback goes straight to hypothalamus
Anterior pituitary:
- Anterior pituitary produces hormones
- Hypothalamus releases releasing hormones into hypothalamic-hypophyseal portal system
- Releasing hormones cause anterior pituitary to release its hormones
- Many anterior pituitary hormones stimulate other endocrine glands
- Negative feedback goes to both hypothalamus and anterior pituitary
Describe homeostasis
The tendency for the body to maintain a stable, relatively constant internal environment
Describe factors under homeostatic regulation
Concentration of:
- Nutrients
- Oxygen
- Carbon dioxide
- Waste
- Water
- Salts
pH, Temperature, blood volume/pressure.
Name three elements of feedback control
- sensor
- control centre
- Effector
Describe thermoregulation
- Homeothermy: Core body temperature is maintained within 2C
- Periphery of body will be sacrificed if needed to maintain core temperature.
- Fever results in an increase in the set-point for body temperature. Negative feedback tries to maintain body temperature at new elevated point.
- Heat stroke occurs when decrease in blood volume due to sweating causes the sweating to stop, and body overheats
- Anaesthetics disable the hypothalamus, so body can’t compensate for temperature. Patient will shiver when anaesthetics wear off to compensate
Describe feedback control in body temperature
- Sensors:
a. Peripheral thermoreceptors in skin
b. Central thermoreceptors in hypothalamus - Control centre:
a. hypothalamus - Effectors
a. Skeletal muscles (shivering)
b. blood capillaries (vasodilation/vasoconstriction)
c. sweat glands
Describe osmolarity and extracellular fluid volume regulation
- ECF volume is regulated to maintain blood pressure
- ECF osmolarity is regulated to maintain cell volume
- High osmolarity is related to lower blood volume/pressure
- Osmolarity is decreased by increasing water in plasma
- Vasopressin (ADH): hormone released by hypothalamus which increases permeability of collecting duct, thus increasing water resorption (decreases plasma osmolarity)
Describe feedback control in osmolarity and ECF volume
- Sensors:
a. Osmoreceptors in hypothalamus
b. Baroreceptors in aorta and carotid artery - Control centre:
a. Hypothalamus - Effectors
a. Thirst
b. vasopressin (ADH) -> kidneys
Compare difference between ‘cell growth’ and ‘cell proliferation’
Cell growth: Increase in cell mass
Cell proliferation: Increase in cell number
List the cell cycle phases
- G1-phase: cell growth and monitoring
- S-phase: DNA synthesis
- G2-phase: Monitoring
- M-phase: Mitosis and cytokinesis (division)
List checkpoints:
- G1 checkpoint: checks for cell size, DNA damage, nutrients, and growth factors
- G2 checkpoint: checks if DNA replicated properly
- M Checkpoint: Checks if chromosomes are attached to spindle fibres
Describe Cdk and cyclins:
- Cdk activation controls the cell phases
- Cdk is activated three criteria are met:
1. cyclin present
2. Activating phosphate added
3. Inhibitory phosphate NOT added - synthesis and degradation of cyclins coordinate the cell cycle (Cdk’s usually always present in cell)
Define mitogen
Any substance that stimulates cell division (i.e. progression through cell cycle)
- e.g. cytokine, growth factors, and hormones
- Activated proto-oncogenes
- Inhibit tumour suppressors
Describe mitogens and its functions in cancer
- Cancer cells are self-sufficient or independent of mitogens for cell proliferation
- Some cancer cells can synthesize mitogens themselves
- Some cancer cells upregulate mitogen receptor expression
- E.g. mutation in Ras and Wnt signalling pathways
Describe p53 and cell escape from apoptosis
- p53 = tumour suppressor gene that triggers apoptosis in cells that have over-expressed mitogens, DNA damage, or chromosome abnormalities
- Mutations (inactivation) of p53 allow tumours cells to escape apoptosis and proliferate
- 50% of tumours have mutated p53 gene.
Define hormone
chemical signal that is secreted directly into the blood by specialized cells. They act on distant target cells. Minute amount of hormone can elicit a response.
List the three types of hormones:
Steroids:
- bind to intracellular receptors (diffuse through cell membrane): intracellular receptors then bind to specific DNA sequences in the nucleus.
- based on cholesterol
- e.g. cortisol
Peptides:
- Bind to cell-surface receptors
- e.g. Insulin and glucagon
Thyroid hormones:
- Bind to intracellular receptors (diffuse through cell membrane)
- T3 has potent effect on cell
- T4 is mostly found in blood
- T4 is converted into T3 in the cell
Describe feedback system regulates hormone release:
- Hypothyroidism: low amounts of thyroxine (T4) in blood
- Assume measured low T4 in blood, how can you check what’s wrong?
- Measure TSH: low or normal = anterior pituitary problem, high = thyroid problem
- Rarely a problem with hypothalamus
Explain how resting membrane potential in axon is maintained
Resting membrane potential is -60mV (more negative charges INSIDE cell)
- Em is maintained by 3 factors:
1) Na/K-pump established concentration gradient
2) K+ leakage channels let K escape but leave anions behind (explains negative potential)
3) Na+-leakage channels let Na in (less impactful than K so keeps Em just above Ek) - E(k) = -75mV ->More impactful to overall Em since membrane is more permeable to K
- E(Na) = +55mV
Explain the generation of action
- membrane is depolarized above threshold by external source
- Hodgkin cycle:
- Sodium channels open
- Sodium rushes in
- Membrane depolarizes - Delayed opening of K-channels
- K rushes out
- Repolarization and hyperpolarization
- Inactive period for Na-channels
Describe unmyelinated axons
- AP propagated via continuous propagation
- 1 m/s speed
- Na rushing in triggers neighbouring voltage-gated Na channel to open
Describe myelinated axons
- AA propagated via saltatory propagation
- 100m/s speed
- Voltage-gated Na channels are concentrated at Nodes of Ranvier
- Myelin insulated axon and allows current to pass from node to node.
Describe effects of myelin
- Electrical properties
- Increase membrane capacitance in internode regions
- Increase ion permeability at nodes - Signal properties
- Reduce amplitude of depolarizing signal
- Maintains signal amplitude
Describe the structure of Neuromuscular junction and discuss arrangement of vesicles and ACh receptors
- Pre-synaptic membrane:
- ACh synaptic vesicles near surface
- Voltage-gated Ca2+ channels - Post-synaptic membrane:
- Nicotinic ACh receptors (with associated Na+ and K+ channels)
- Voltage-gated Na+ channels
Describe the sequence of events for Neuromuscular Action Potential transmission
- Nerve depolarizes near nerve terminal
- Voltage-gated Ca2+ channels open
- ACh vesicles releases into synaptic cleft
- ACh diffuses
- Nicotinic ACh receptor binds ACh; associated Na and K channels open
- Voltage-gated Na+ channels open to start muscle AP
Define ‘safety factor’
There is a minimum threshold needed before a muscle AP is initiated
Define ‘miniature end plate potential (mEPP)
Depolarization of end plate due to release of one vesicle (one quanta) of ACh into synaptic cleft
Define ‘endplate potential (EPP)’
mEPP multiplied by the number of ACh vesicles released
Describe myasthenia gravis
Autoimmune antibodies bind to nicotinic ACh receptor
- Reduction in mEPP resulting in reduction of EPP
- Threshold for muscle AP not met
- Compound muscle action potential (CMAP) decrease rapidly (i.e. repeated stimulation decreases)
- Treatment:
1) Acetylcholinesterase inhibitor -> ACh stays longer in synapse
2) Immunosuppressants -> reduce autoimmune antibodies
