Cell physiology Flashcards
What is the water distribution breakdown of a 70kg man?
60% of man is water
40% ICF- cannot be measured-> measure TBW with deuterium oxide
20% ECF (14litres)
of ECF; 25% vascular, 75% interstitial
ECF is isosomotic with ICF at osmotic equilibrium
ECF best measured using insulin, a polysaccharide, MW5200
Transcellular water= component of ECF that has been processed by cells into special compartments eg.CSF
What are the key facts about total body water?
60% of body weight Higher in men than women Reduces with age Used to measure ICF Inversely proportion to fat-> decreased in Cushing's disease
What is osmosis?
The diffusion of a solvent into a region where there is a higher concentration of a solute to which the membrane is impermeable
What are the fundamental properties of the plasma membrane?
Semipermeable; permeable to H20, K+, Na+ etc
Preferential permeability to lipid soluble substances
Low surface tension
High electrical resistance-> impermeable to organic ions
What are the 4 ways a substance can cross a membrane?
Diffuse freely Endocytosis Exocytosis Via transport proteins How well a substance crosses membrane depends on ; size, electrical charge, fat solubility
What is the Donnan effect?
When an ion on one side of a membrane cannot diffuse across, the other ions which are permeable will move to balance the charge.
This effect means that:
1. there are more osmotically active particles in cells than in interstitial fluid, hence Na-K+ ATPase is essentially to prevent cell swelling
2. an electrical difference exists across the membrane
3. there are more proteins in plasma than interstitial fluid, there is Donnan effect ion movement on capillary walls
what is the equilibrium potential of a membrane?
There is no net passive movement of ion across the membrane
NOT related to concentration being the same on both sides or potential difference being zero
What is the normal resting membrane potential in the cell membrane of nerve and muscle?
-70 to -90mV
Potassium permeability is greater than sodium permeability
Insulin causes an increase in resting membrane potential (hyperpolarization)
What role to Na/K+ ATPase play in maintaining the cell membrane potential/
The concentration gradient of K+ facilitates its movement out of the cell via K+ channels, however its electrical gradient is in the opposite direction
Na/K+ATPase pumps 3 Na+ out and 2K+ into the cell, which keeps the intracellular concentration of sodium low and acts and a electrogenic pump
What are the key facts about the capillary membrane?
Different tissues have differing permeability
Liver capillaries are permeable to plasma proteins
Glucose transfer across capillary wall occurs by passive diffusion
How much sodium and potassium is there in the body?
More total Na than K
Total exchangeable Na is 3000ml (70% of total body Na)
Total body K is 3000ml (90% exchangeable)
What is normal serum osmolality and pH of ECF?
Serum osmolality is 300mmol/kg
pH of ECF 7.36-7.44
What are the main cations in intracellular fluid?
K, Mg, Na
K concentration 150-160
Organic phosphates are present in high concentrations
More H ion intracellular than extracellular
Describe the concentration of ions in plasma
Higher sodium concentration than in interstitial fluid
Higher magnesium concentration than in interstitial fluid
Higher protein concentration than in interstitial fluid
Chloride concentration is LOWER in plasma due to Donnan’s effect
What happens to a cell when extracellular K+ is reduced to 3.0?
K+ will diffuse out
H+ will diffuse in
Intracellular net charge=unchanged due to Donnan’s effect
What are the key functions of tight junctions?
Surround apical margins of cells in epithelia
Restrict molecular movement across epithelium
Facilitate cell to cell adhesion (NOT communication)
Found just below luminal surface
What are the functions of gap junctions?
Spanned by corresponding connexons
Connexons line up and are the only way things can pass between cells without entering ECF
Allows ions, sugars, amino acids and other small molecules
Facilitates cell to cell communication
Allows synchronous contraction of cardiac+smooth muscle
Defective connexin gene in Charot-Marie Tooth
What are the 4 ways cells communicate through the ECF?
Autocrine
Paracrine, endocrine and neural (all use chemical messengers that bind to receptors)
How do receptor numbers get downregulated in the case of an excessive hormone?
Ligand binds to receptor->ligand receptor complex gets endocytosed-> decreased number of available receptors
Alternatively gets chemically desensitized so they are less sensitive
What is an example of a stimulus that acts to open or close ion channels in a cell membrane?
ACh on nictonic receptor
Noradrenaline on K+ channel in heart
What is an example of a stimulus that acts via cytoplasmic/nuclear receptors to increase transcription of mRNAs?
Thyroid hormones
retinoic acid
Steroid hormones
What is an example of a stimulus that acts to increase phospholipase C?
ANGII
Noradrenaline via alpha adrenergric receptor
ADH via V1 receptor
What is an example of a stimulus that acts on adenylyl cyclase to modify intracellular levels of cAMP?
Noradrenaline via B1 receptor (increases cAMP)
Glucagon
ADH
Noradrenaline via A2 receptor (decreases cAMP)
Which 2 substances increase cGMP in a cell?
ANP
Nitric oxide
Which hormones increase tyrosine kinase activity?
Insulin
EGF
PDGF
M-CSF
Which things increase the action of Na-K ATPase?
High levels of intracellular Na Thyroid hormones Insulin Aldosterone Uses lots of energy: 24% of cell energy expenditure, 70% in neurons
Which things decrease the action of Na-K ATPase?
Decreased TP Dopamine Ouabain Digoxin Intracellular oedema may occur in areas where local blood flow is depressed because inadequate oxygenation depresses cell membrane ionic pumps and allows Na to leak into cells.
What are the functions of calcium within a cell?
Proliferation, nerve signalling, contraction, secretion pretty much everything etc
Describe the concentrations of calcium and describe its movements across cell membrane
Intracellular Calcium=100nmol/L, most bound to ER
Extracellular calcium= 12000x higher, calcium always wants to move into cells
Does this via; voltage gated, ligand gated and stress activated. Voltage gated can be either transient or long standing..
Cells get rid of calcium via Calum-H ATPase (2 hydrogens) or Ca-Na ATPase (3 Na)
When a cell is activated and more calcium needs to enter cell how is this achieved?
Intracellular calcium increased by increased store operated Calum channels. Calcium inside a cell needs to bind to a protein (troponin, calmodulin and calbindin)
Describe the function and structure of microtubules
Composed of tubulin and make up part of cytoskeleton Make up filaments of spindle at mitosis Fix the shape of platelets Assist transport of material within cell are NOT part of Golgi complex
Describe the function and structure of lysosomes
Found in granulocytic WBCs
May be involved in gouty arthritis
Merge with intracellular membrane lined vacuoles containing exogenous substances forming a phagocytic vacuole
Are released intracellulary (not extra cellularly) in normal host response to infection
Describe an action potential in terms of membrane potential
Resting membrane potential= -70mV
Stimulus raises it to -55mV, then if this threshold is reached it overshoots up to +35mV (via sodium influx)
Then K+ channels open and a slower depolarisation occurs
If threshold not reached, nothing happens, but does not get more intense if threshold is exceeded
What is the difference between absolute refractory and relative refractory period?
Absolute: no stimulus, no matter how strong with excite the nerve
Relative: stronger than normal stimulus can cause excitation
Therefore the intensity required to elicit another spike is increased
What are the 3 types of presynaptic vessels?
Small and clear: Ach, glycine, GABA or glutamate
small with dense core: catecholamines
large with dense core: neuropeptides
What receptors does Ach act on?
Muscarinic: can be blocked by atropine selectively
Nicotinic: found at NMJ and CNS/autonomic ganglia
Therefore atropine does not cause problems at NMJ when administered a
What controls/inhibits the firing of motorneurons?
Inhibited by nerve terminal which release glycine
Inhibited by nerve terminals which release GABA
Is subject to supraspinal control
Negative feedback control by means of Renshaw cells
Where are nerve growth factors produced and where do they bind?
Produced my muscles they innervate or come from astrocytes
Bind to receptors at nerve ending, internalised then transported retrograde to neuronal cell body, increases production of proteins (assists with neuronal development, growth and survival)
Does not increase growth of myelinated motor neurons
Which subunits make up nerve growth factor?
Beta subunits: have all nerve growth promoting activity, structure similar to insulin
Alpha: has trypsin like activity
Gamma: serine proteases
In the skin where complete nerve degeneration has occurred, does the triple response to stroking occur?
No -because the flare of the triple response (red, wheal and flare) is mediated by an axon reflex
Which neurons are cholingeric (as opposed to noradrenergic)?
All preganglionic neurons
Parasympathetic postganglionic neurons
Sympathetic post ganglionic neurones that innervate sweat glands
Sympathetic neurons that act on blood vessels in skeletal muscles and produce vasodilation when stimulated
What type of ganglion is the adrenal medulla?
Sympathetic ganglion
Which hormone is released by parasympathetic vs sympathetic ans?
Ach: parasympathetics
NA: sympathetics
Describe the key facts about the ANS
Axons of postganglionic parasympathetic neurons are typically short
Adrenal medulla is functionally a sympathetic ganglion
Transmission at parasympathetic ganglia and sympathetic ganglia are pharmacologically the same
Salivary glands receive both sympathetic and parasympathetic supply
Most Blood vessels have a sympathetic nerve supply
Which nerves cause micturition?
A nervous reflex triggered by intravesical pressure
Postganglionic parasympathetic nerve fibre stimulation
What are the actions of noradrenaline?
Relaxes accommodation and dilates pupils
Increases HR and raises BP
Dilates blood vessels in muscles but constricts blood vessels in the skin
Stimulates sweat glands
Elevates plasma glucose and mobilises FFA
Why does atropine abolish salivary secretion?
Parasympathetic innervation is probably most important for salivary secretion
Why does destruction of the conus medullaris paralyse defecation?
Spinal cord mediated defecation is intergrated in conus medullaris
Which nerve supplies skin of the external auditory canal and preganglionic cholinergic axons to cardiac ganglia?
Vagus
What are the characteristics of sympathetic vasodilator fibres?
Liberate Ach preganglionic endings
Cannot sustain vasodilation for more than 30 seconds
What are the characteristics of alpha-adrenergic receptors at sympathetic postganglionic nerve endings?
Blocked by phenoxybenzamine
Present at presynaptic location on nerve endings
Blocked by phentolamine
What does the amino acid glycine do?
Probably mediator for direct inhibition on the spinal cord
Causes hyperpolarisation when directly applied to membranes
With arginine and methionine is responsible for synthesis of creatinine
Has an inhibitory function in spinal cord but NOT antagonised by atropine
Which 2 different nerve fibre systems are responsible for pain
Nociception
Unmyelinated C fibres
Associated with signficant levels of substance P in the substantia gelatinosa
Travels via ascending pathways in dorsal column (lateral spinothalamic tract)
When conscious, which type of stimuli to the bowel will cause pain?
Visceral distension
Visceral ischaemia
Not surgical diathermy
Not cutting with a sharp instrument
What is the main energy supply of the brain?
Glucose
Little glycogen is stored in neurons
Metabolic rate is much higher than the body average
Neuronal uptake of glucose is insulin dependent
What is the post central gyrus responsible for?
Motor control
Projections of afferents are not innate and may be changed by experience
What are some key differences between cerebellar tremors and parkinsonian tremors?
At rest: cerebellar is hypotonia, Parkinsonism is hypertonia
During movement: cerebellar tremor is worse, parkinsons is better
Parkinsonian tremor is present during sleep
What are the 4 key features of a cerebellar disorder?
Dymetria
Dysdiadochokinesia
Intention tremor
Hypotonia
What occurs below a hemisection of the spinal cord?
Ipsilateral paralysis
Contralateral pain and temperature loss
Ipsilateral touch and pressure (as these fibres decussate in the medulla)
What is the likely sequelae within the 1st week of a complete transection of the lower cervical spinal cord?
Bradycardia
Negative nitrogen balance
Hypothermia
What occurs following transection of cord in spinal shock?
Profoundly depresses spinal tendon reflexes (resting membrane potential rises 6mV)
Patient becomes poikilothermic
Lasts 1-2 weeks
Associated with disappearance of vasomotor responses
Which tissues demonstrate denervation hypersensitivity?
Skeletal and smooth muscle
Iris becomes hypersensitive to adrenaline
Smooth muscle does not atrophy but skeletal muscle does after denervation
Skeletal muscle still shows sporadic contraction
Exocrine glands (exception of sweat glands) also shows denervation hypersensitivity
