osmosis etc. Flashcards
osmolarity
Is the concentration of osmotically active particles in a solution
osmolarity=GxC
g-number of particles in a solution
c-concentration
Osmosis
Flow of water across a semipermeable membrane from a solution of low solute concentration (where the water conc. is high) to a solution of high solute concentration (where the water conc. is low)
osmotic pressure
increases when the solute concentration increases.
oncotic pressure
Colloid osmotic pressure, (Oncotic pressure) is the osmotic pressure created by plasma proteins [=28mmHg]
hypotonic 200
.45 saline
hypertonic 360
3% saline
isotonic 280
0.9 saline
hypernatremia
increased water loss
excessive sweating
central or nephrogenic diabetes insipidus
hyponatremia
large water ingestion
siadh
ion channel ungated
determined by size, shape, distribution of charge etc.
Voltage-gated channels
are opened or closed by changes in membrane potential.
e.g. the activation gate of the Na+ channel in nerve is opened by depolarization; when open the nerve membrane is permeable to Na+ (e.g. during the upstroke of AP). Inactivation gate of Na+ channel in nerve is closed by depolarization; when closed, the nerve membrane is impermeable to Na+ (e.g. during the repolarization phase of AP)
Ligand-gated channels
are opened or closed by hormones, second messenger, or neurotransmitter
e.g. Nicotinic receptor for Acetylcholine at motor end plate is an ion channel that opens when Ach binds to it. When open, it is permeable to Na+ and K+ ,causing the motor end plate to depolarize.
Chloride channel are ligand-gated. These channels open when GABA binds to its receptor. When open , it allows inward movement of chloride ions in the cells (simple diffusion)
Other examples : Glutamate and 5-HT (Serotonin) receptors
Receptor binding GABA
Binding of GABA causes the chloride channels to open
Receptor binding GABA and benzodiazepine
Binding of GABA is enhanced by benzodiazepine, resulting in a greater entry of chloride ion which HYPERPOLARIZES (makes the cell less responsive) the cell making it more difficult to depolarize and therefore, reduces neural excitability
Receptor Empty (no agonist)
Empty receptor is inactive ,and the coupled chloride channels is closed
agonist
drug has an affinity for a receptor and stimulates it
antagonist
drug has an affinity for a receptor but displays little or no intrinsic activity
competitive antagonist blocker
competes with agonist for receptor sites, occupies the receptor site- NO ACTIVITY
non competitive antagonist
binds to the site other than receptor site and changes the shape of receptor-NO ACTIVITY
resting membrane potential
Membrane electrical potential difference (membrane potential) is generated by diffusion of K+ ions through ‘leaky’ K+ channels
resting membrane potential -70 to -90mv
resting membrane potential
-90 At rest, K+ slowly leaks out from cell Resting membrane potential (-90 mV)
depolarization
Makes the cell membrane potential less negative due to movement of positively charged sodium ions (Na+) into the cell increasing excitability
repolarization
Change after depolarization, that returns the membrane potential back to resting potential. Repolarization results from the movement of positively charged potassium ions (K+) out of the cells.
hyperpolarization
Makes the membrane potential more negative due to movement of negatively charged chloride ions (Cl-) into the cell.
DECREASE excitability
inward current
is the flow of positive charge into the cell. inward current depolarizes the membrane potential
outward current
is the flow of positive charge out of the cell. outward current hyper polarizes the membrane potential.
action potential
Is a property of excitable cells (nerve & muscle) that consists of a rapid depolarization, or upstroke, followed by repolarization of the membrane potential. Action potential have stereotypical size and shape, are propagating and are all-or-none
threshold
Is the membrane potential at which the action potential is inevitable. At threshold potential, net inward current becomes larger that net outward current. The resulting depolarization becomes self-sustaining and gives rise to upstroke of action potential. If net inward current is less than net outward current, no action potential will occur (i.e. all- or- none response)
during the upstroke of an action potential
Na permeability increases
Due to opening of Na+ channels
Inward movement of Na+
During the downstroke of an action potential
Na permeability decreases due to inactivation of Na+ channels K permeability increases due to opening of K+ channels Outward movement of K+
After hyperpolarization of membrane following an action potential:
There is increased K+ conductance
due to delayed closure of K+ channels
Resting membrane potential
is the measured potential difference across the cell membrane in mV (-70 to - 90mV)
At rest , the nerve membrane is far more permeable to K+ than to Na+
Leaky K+ channels are responsible for resting membrane potential.
The Na+/K+ pump maintains resting membrane potential ( 3Na+ out and 2K+ in)
Action Potential “Nerve Impulse”
is a property of excitable cells (nerve, muscles) that consist of a rapid depolarization (interior becomes less negative) or upstroke , followed by repolarization of membrane potential.
Lidocaine (depolarization)
Inward Na+ movement
Lidocaine block these voltage sensitive Na+ channels and abolish action potential
Downstroke of the Action potential (repolarization)
Outward K+ movement Inward current (flow of Na+ into the cell) depolarizes the membrane potential , while outward flow of K+ hyperpolarize the membrane potential. Both ions flow by simple diffusion.
Properties of AP
Constant size and shape Propagation/ spread ( 60 m/sec ) Myelinated vs. non-myelinated fibers All-or-none Law (no percentage) Threshold is the membrane potential at which the AP is inevitable
Refractory periods
Absolute refractory period
is a period during which another action potential cannot be elicited, no matter how large the stimulus.
Due to closure of inactivation gates of Na+
refractory periods
Relative refractory period
is a period during which an action potential can be elicited only if a larger than usual stimulus is provided
refractory period
Refractory period protects the cell from over-excitation. It allows a recovery period between the action potentials.
local anesthetics mechanism of action
procaine, cocaine, lidocaine, bupivacaine
Local anesthetics are weak bases present in un-ionized form (LA) and ionized form (LAH+)
Un-ionized form (LA) penetrates the cell membrane.
The pH is slightly acidic inside the cells more ionized form (LAH+) produces.
Ionized form (LAH+) blocks the Na+ channels (from inside)
Inhibit conduction of pain impulses from periphery to CNS (afferent fibers)
Uses: minor surgical procedures, spinal anesthesia
local anesthetics
slow the rate of depolarization of the nerve action potential such that the threshold potential is not reached. As a result, an action potential cannot be propagated in the presence of local anesthetic and conduction blockade results.
Inhaled Anesthetics
Isoflurane, Desflurane, Sevoflurane
Enhance the effect of GABA
Increase entry of Cl-
Hyperpolarization of cell (makes the cell less responsive) - more difficult to depolarize and therefore, decreased neural excitability
hypokalemia
Hypokalemia increase the diffusion gradient leads to hyperpolarization leading to muscle weakness
hyperkalemia
decrease the diffusion gradient leading to depolarization. AP does not occur because inactivation gates of Na+ channels are closed by depolarization. Without AP , there is no contraction leading to muscle weakness.
K+ rich cardioplegic
(heart paralysis) solution causes rapid membrane depolarization. But No repolarization can occur due to high extracellular K+ . Na+ channels are locked in the inactive state. The heart muscle is essentially in a permanent absolute refractory period. “pharmacological arrest”.
succinylcholine
causes continuous depolarization leading to resistance to depolarization leading to flaccid paralysis
what do local anesthetics block?
Local anesthetics interrupt nerve conduction by blocking Na+ channels.
Inotropic receptors
ligand gated channels
cAMP Mechanism
hormone (first messenger) binds to a receptor on cell membrane. activates g protein (middle man) g (stimulatory) protein stimulates adenylate cyclase, g (inhibitory) inhibits the adenylate cyclase. activated adenylate cyclase converts atp to cAMP (second messenger). ( increased camp inhibits adenylate cyclase and decreases camp levels). camp activates protein kinase-a which phosphorylates proteins and creates cellular action.
(ie calcium)
caffeine and amionphollin
phosphodiesterase of camp and increasing cAMP level.
IP3 (inositol triphosphate) Mechanism
Hormone binds to a receptor on the cell membrane which activates a g protein (middle man) to activate phospholipase C which liberates diacylglycerol (DAG) and IP3 (inositol triphosphate) from membrane lipids. ip3 makes calcium release from endoplasmic reticulum. calcium plus dag activate protein kinase c which phosphorylates proteins and causes specific physiological actions.
what action does IP3 cause
action of acetylcholine on muscarinic receptor
atropine and ipratroprium MOA
block the acetylcholine on the muscarinic receptor. causing bronchodilation
dobutamine
In cardiac muscle, beta agonist such as dobutamine acts through cAMP. increase cAMP results activation of protein kinases that enhances the entry of Ca++ into the myocardial cell increase force of contraction
milrinone-
phosphodiesterase inhibitors prevent hydrolysis of cAMP and prolong the action of protein kinase. (increasing the amount of calcium into the cell)
steroid hormone
diffuse across cell membrane and binds to a cytosolic receptor and then nuclear receptor. (this causes a change in the receptor which exposes a DNA-binding domain) transcription is initiated and new mRNA is formed. mRNA is translated in the cytoplasm and produces specific proteins that have physiological actions.
nitric oxide
diffuses across the cell membrane and works on cGMP causing bronchodilator.
terbutaline
beta2 receptor activates g protein which activates adenylyl cyclase. atp forms cAMP. activates protein kinase and causes BRONCHODILATION.
Thick filament
contains myosin
thin filament
Contain actin, tropomyosin and troponin Tropomyosin covers the active site Troponin is a complex of 3 proteins Troponin T ( binds with tropomyosin) Troponin I (binds with actin) Troponin C ( binds with calcium)
T tubules
Are continuous with the cell membrane
Invaginate the cells at the Z lines and carry AP into the cell interior
Sarcoplasmic reticulum (SR)
Are small diameter tubules in close proximity to the contractile elements
Are the site of storage and release of Ca++ for excitation-contraction coupling
Steps in excitation-contraction coupling“Conduction to contraction
action potential spreads from the cell membrane into the t tubules- L-type calcium (diphydrophyridine receptors) calcium enters the cell. causing a calcium spark/releast from the ryanodine receptors from the sarcoplasmic reticulum. intracellular calcium increases!
dantrolene
decrease calcium release from ryanodine receptors on sr.
calcium channel blockers
block L-type calcium channels dihydropyridine receptors.
how does actin and myosin binding work with calcium
Ca++ binds to troponin C, and tropomyosin is moved out of the way, removing the inhibition of the actin and myosin binding.
Actin and myosin bind, the thick and thin filaments slide past each other and the muscle contract. (power stroke). The magnitude of the tension that develops is proportional to the intracellular [Ca++]
Norepinephrine
acts on 1 receptors on heart and causes cAMP that in turn Ca++ influx through L-type Ca++ channels increase force of contraction. (Acetylcholine does the opposite)
Camp
Beta 1 Beta 2 Alpha receptors 2 Gluconate Hcg Calcitonin Tsh Pth Lh Fsh Adh v2 ACTH
Ip3
Alpha 1 receptors Adh v1 Trh Gnrh Ghrh Oxytocin Cholinergic Muscarinic receptors Angiotensin ii
Steroid hormone
Vitamin d Thyroid hormone Glucosteriods Esterogen Progesterone Aldosterone Testerone
Tyrosine kinase
Insulin
IGF-1
CGMP
Nitric oxide
Anp
Nicotine receptors and ach
Allow sodium in and potassium out permeability and cause the motor end plate to depolarize
Troponin c
Calcium
