General Physiology Flashcards
1
Q
What are transcription and translation
A
Transcription - sequence of DNA producing a specific mRNA
Translation - mRNA determining the final amino acid sequence via tRNA in a ribosome
2
Q
Which enzyme unzips dna during transcription, where?
What are the strands called, which is used to create the mRNA?
A
DNA polymerase
Nucleus
Sense and anti-sense
Antisense
3
Q
Nucleotide types and category
A
Guanine - purine
Cytosine - pyramidine
Adenine - purine
Thymine - pyramidine
Uracil - pyramidine
4
Q
What are transcription factors?
Function
A
Proteins that bind to specific DNA sequences
Either promote or repress RNA polymerase
5
Q
Where does translation occur
What does tRNA bind to specifically
Which way does the sequence get read
A
Ribosome
Codons
5’ to 3’
6
Q
What are the special codons that mark key points in translation
A
Start AUG
Stop UAA, UAG, UGA
7
Q
Where and how is the amino acid carried on tRNA
What loads it on
A
At the 3’ end covalently bonded
Aminoacyl tRNA synthetases
8
Q
How many codon combinations are there?
How many amino acids are there
A
4^3 = 64
20
9
Q
Where does the amino acid chain go after translation
What for
A
To the Golgi
Further processing and refinement then packaging into granules
10
Q
What are the levels of structures of proteins with link types
A
Primary - polypeptides chain - peptide bonds
Secondary - specific geometric shape eg beta sheet or alpha helix - hydrogen bonds
Tertiary - unique folded 3d structure - van de valls, hydrogen bonds, etc.
quaternary - combination of more than one polypeptide chain creating fibrous or globular proteins
11
Q
Structure of haemoglobin
How is it effected in SSD
A
2 alpha and 2 beta polypeptide chains with an inorganic haem group.
SSD - abnormal beta chain, lock together and thus precipitate forming sickle shaped RBCs
12
Q
Types of genetic mutation
A
Substitution - one base for another
Insertion
Deletion
13
Q
How can cells influence gene expression in other cells
A
Release of molecules that trigger intracellular signalling in the target cell via extracellular or intracellular receptors
14
Q
How does oestrogen effect target cells
A
Crosses cell membrane
Bonds to receptor
Enters nucleus
Binds to DNA
Alters transcription
OR
Binds to g-protein coupled receptor
15
Q
How does thyroid hormone effect target cells
A
Enters via transporter proteins
Enters nucleus
Binds to thyroid hormone receptor - unbound this causes transcription repression but bound causes activation
16
Q
Thickness of cell memebrane
Main functions
A
7.5 nm
Separation of internal from external
Maintenance of concentration gradients
Control of movement in and out
Maintenance of cell shape
Cell adhesion
Cell signalling
17
Q
What is the correlation of the structure of phospolipids in cell membranes
What holds the bilayer together
A
Hydrophilic head
Hydrophobic tail
Thus forms bilayer
Hydrophilic head out thus low permeability to ions and polarised molecules.
Van der waals, hydrogen bonds, non-covalent interactions
18
Q
Types of protein position on cell membranes
A
Integral, peripheral, surface
19
Q
Functions of cell memebrane proteins
A
Structure
Pumps
Carriers
Ion channels
Receptors
Enzymes
20
Q
Types of transport across cell membranes and description
A
Diffusion - net movement of particles down concentration gradient. Simple or facilitated (through carrier protein) tending to equilibrate the gradient
Osmosis - movement of solvent molecules across a semi-permeable membrane from an area of low solute concentration to high solute concentration tending to equilibrate the concentration
Active transport - movement of particles against their concentration gradient requiring energy (primary from atp, secondary from electrochemical gradient)
Endocytosis - cell absorbs molecules by engulfing them
Exocytosis - cells direction excretory vessels out of the cell membrane.
21
Q
What is a cell receptor, what does it react too?
A
Molecules that receive specific chemical signals from environment via ligands (peptides, neurotransmitters, hormones, drugs, toxins).
22
Q
Types of cell receptors
A
Peripheral membrane proteins - eg elastin
Transmembrane proteins - eg G protein or ligand gated ion channel
Intracellular receptors - eg hormone receptors
23
Q
How many transmembrane domains do G protein coupled receptors have?
How do they exert their action
How are they deactivated
A
7
Conformational change on ligand binding allows GDP to be exchanged for GTP of the Galpha subunit
Subunit disassociate to Galpha-GTP and beta-gamma.
Subunits act on effector organs or on ion channels to effect response
GTPase exchanges the GTP back to GDP and all subunits re-associate on the receptor
24
Q
Examples of ligands for tyrosine kinase receptors
A
Insulin
Erythropoietin
25
How do tyrosine kinase receptors work
Ligand binds to extracellular N terminal, beta unit spans membrane, effect exerted by intracellular c-terminal
At the c-terminal kinase enzymes cause phosphorylation. Phosphorylation of tyrosine leads to activations of signal transduction pathways in the cell
26
How does insulin work via its receptor (very simply)
Binds to tyrosine kinase receptor
Cascade triggers release of vesicle with GLUT transporters to membrane allowing glucose into cell
27
What are ionotropic receptors
How do they work
Ligand gated ion channels open and close in response to ligand binding
28
Examples of ligand gated ion channels
Nicotinic ACh receptor
NMDA receptor
GABA receptor
29
What is the term when a ligand binding site is away from the active site
Allosteric
30
What does NMDA and GABA stand for
N-Methyl-D-Aspartic acid
Gamma-AminoButyric Acid
31
Structure of a nicotinic AcH receptor
Function
5 membrane spanning sub units (each made of 4 helical domains) with ion channel centrally, ACH binding sites on the 2 alpha subunits, other units beta gamma and epsilon
Conformational change on both domains bound ACH - Na + Ca flow in and K out down concentration gradients
32
Structure of an NMDA receptor
4 membrane spanning sub units (each made of 3 full and 1 partial helical domaine) with central ion channel
Glycine binding sites on N2 subunits
Glutamate binding sites on N1 subunits
Transmits sodium and calcium ions.
33
Structure of a GABA receptor
5 membrane spanning subunits (each with 4 helical domains) around a central channel binding site for benzodiazepines between alpha and beta subunits
Transmits chloride ions
34
Another name for G protein coupled receptor (broader type)
Metabotropic - a receptor that uses signal transduction through the membrane
35
Definition of full agonist
Induces a receptors maximal response
36
Definition of partial agonist
Induces a receptors submaximal response
37
Definition of inverse agonist
A drug that induces the opposite effect to the intrinsic agonist
38
Definition of Competitive antagonist
A drug that competes with the intrinsic agonist for the receptor and thus blocks its activity
39
Definition of non-competitive antagonist
A drug that binds at a different site to the intrinsic agonist and prevents receptor activation
40
Definition strong and weak acid
Acid - proton donor
Strong - fully dissociates in solution
Weak - partially dissociates in solution
41
Definition strong and weak base
Base - proton acceptor
Strong - fully dissociates
Weak - does not fully dissociate
42
What is an acid base buffer
Action
A weak acid and it’s conjugate base (the anionic product of an acid)
Limits the effect of a proton load in any physiological solution
43
Definition of pH including constituent units
Negative log base 10 of hydrogen ion concentration in nmol/l
44
What is physiological ph and h+ concentration
7.4
40nmol/l
45
What is a neutral pH?
Effect of temperature?
pH 7 and hydrogen and hydroxyl concentrations equal. True at 25oC, at 37oC neutral pH is 6.8
46
pH of:
Gastric juices
Urine
Arterial blood
Venous blood
CSF
pancreatic fluid
Gastric juices 1-3
Urine 5-6
Arterial blood 7.38-7.42
Venous blood 7.37
CSF 7.32
pancreatic fluid 7.8-8
47
Definitions of acidosis and acidaemia
Acidosis - excess of acid moieties within physiological system
Acidaemia - pH <7.4
48
What processes are most impacted by deranged pH in the body
Oxidative phosphorylation
Enzyme function
Carrying power of Hb (Bohr effect)
Chemical reactions
Ionic flux
49
What is the H+ ion concentration at pH
7.4
7.7
7.1
6.8
7.4 - 40nmol/l
7.7 - 20nmol/l
7.1 - 80nmol/l
6.8 - 160nmol/l
50
What is the main source of body acid production
CO2 from glucose metabolism
51
What process produces non-volatile acids in the body
Amino acid metabolism
52
What systems are involved in hydrogen ion control, over what timeframes
Buffer - seconds
Resp - minutes
Renal - hours
Hepatic - hours
53
Definition of pK
Neg log base10 of the dissociation constant for a chemical reaction
Also happens to be pH at which a buffer is most efficient and at which the system is at 50% ionisation
54
Blood based buffers and their pK
Bicarbonate 6.1
Histidine on haemoglobin 7.8
Amino/carboxyl in plasma proteins 7.4
55
Interstitial buffers and their pK
Bicarbonate 6.1
56
Intercellular buffers and their pK
Proteins - 7.4
Phosphates 6.8
57
What is the Henderson-hasselbach equation?
pH = pK + log10[A-]/[HA]
58
How is the Henderson-hasselbach equation derived
H+A <=> HA
k1 [H][A] = k2 [HA] With k being rate constant
[H] = K [HA]/[A] with K being k2/k1
Log10 then -log10 both sides
Log10[H] = log10K + log10[HA]/[A]
-Log10[H] = -log10K - log10[HA]/[A]
Substitute pH and pK
PH = pK + log10[A]/[HA]
59
Why is the bicarbonate buffer system so effective
Easily regulated components
CO2 by lungs and HCO3 by kidneys
60
What is the Henderson hasselbach equation for the bicarbonate buffer system
PH = 6.1 + Log [HCO3-] / pCO2 x 0.225
0.225 is the solubility coefficient for CO2
61
How much CO2 is dissolved in typical arterial blood
5.3 kPa x 0.23 = 1.2 mmol/L
62
What is the most powerful buffer and provides 75% of all intracellular buffering
Histidine residues on haemoglobin
63
What is the relationship between buffer systems termed
What is it
Isohydric principle
When in a compartment all buffer pairs are in equilibrium with the same H+ concentration. Only those buffers with a pK within 1 pH unit of that in the solution participate effectively in the buffering of the pH
64
What is the respiratory response to excess hydrogen ions
Increased CO2
Detected by chemoreceptors in the medulla and carotid bodies
Increased alveolar ventilation
Increased H+ directly on the respiratory centre in the medulla
65
What is control effectiveness
The ability of a physiological homeostatic mechanism to deal with change in the parameter it controls.
66
What is the control effectiveness of the respiratory system to hydrogen ion concentration
Example numbers
50-75%
Will deal with 5-7.5nmol of a 10nmol change in H+
67
How do kidneys affect acid base balance
H+ secretion
HCO3- filtered
HCO3- generated
68
How is H+ secreted in the kidneys
Secreted by epithelial cells in the collecting system by primary and secondary active transport
Also by interaction between hydrogen ions and bicarbonate within the collecting system.
69
How does secondary active transport result in H+ excretion in the kidneys
Where does it occur
Proximal collecting duct
Small but significant electrochemical gradient against diffusion.
Primary active transport transports Na from the renal tubule into the cells, with hydrogen ions transported the other way by countercurrent transport.
70
How does primary active transport result in H+ excretion in the kidneys
Where does it occur
Distally in collecting duct
Large electrochemical gradient to work against
Hydrogen transporting ATPase on tubule membrane expel hydrogen into the tubule against its concentration gradient. The bicarbonate is moved back into the extracellular fluid in exchange for chlorine which moves right through with the hydrogen into the renal tubule
71
What happens to secreted H+ in the tubules? What is the net effect
Combines with a buffer (bicarbonate, phosphate, ammonia)
Net effect is increased bicarbonate in the blood
72
What enzyme is activated int he renal tubules in response to decreasing pH
What does it do
Glutaminase
Increased activity producing more ammonia for secretion acting as a urinary buffer.
73
What is the livers role in acid base management?
Carbon dioxide produce
Metabolism of organic acid anions
Plasma proteins production
Metabolism of ammonium
Ureagenesis - regulates urea produce in the face of the need to either conserve or consume bicarbonate
74
What is the distinction between type A and B hyperlactaemia
Type A impaired normal oxygen delivery, type B from other cause (e.g. leukaemia, renal failure, drugs)
75
Causes of hyperlacataemia
Increased cellular production
Reduced uptake or use of oxygen (causing anaerobic metabolism)
Reduced lactate clearance
Adrenergic stimulation causing increased glycolysis
76
What is the significance of the lactate:pyruvate ratio? What is it normally?
Normally 10:1
If >10:1 indicates tissue hypoxia
77
What is the anion gap?
What is the formula?
Normal values
The difference between the sun of measured cations and anions
(Na+K)-(Cl+bicarb)
3-11
78
Sources of error in anion gap calculations
Blood sample not processed immediately - contained leukocytes continue metabolism increases bicarb concentration
Haemolysis alters k concentrat
79
Causes of high anion gap acidosis
Electroneutrality maintained by extra unmeasured anions - bicarb levels drop binding with the H+ leaving the unmeasured anion around.
M - methanol
U - uraemia
D - DKA
P - paraldehyde
I - Isonicotinc acid
L - Lactic acid
E - ethanol
S - salicylates
80
Causes of Normal anion gap acidosis
Hyperchloraemic acidosis, fall in bicarb compensated by rise in cl-
Diarrhoea
Proximal renal tubular acidosis
Renal failure
Distal renal tubular acidosis
Ammonium chloride
Acetazolamide
TPN
Alcohol (!)
81
What causes a low anion gap acidosis?
Low albumin (constitutes 80% of unmeasured anions)
Increase in cations eg paraproteins or lithium
82
What is the distinction between standard and actual bicarbonate on an ABG
Standard - bicarb corrected to normal temp and CO2 level - reflects true metabolic picture
Actual - calculated by Henderson hasslbach from rest of ABG
Ie standard controls for respiratory component
83
What is the base excess?
The amount of acid that must be added to the sample of blood in vitro to restore the sample to pH 7.4
WHILE THE CO2 IS HELD AT 5.33kPa
84
What issues may effect an ABGs gas and acid base interpretation, why?
Air bubbles (esp froth as lrg surface area) - time dependant change in O2 as bubbles with have a PaO2 of 21kpa
Time delay - ongoing metabolism in cells (worse in leucocytosis)
Heparin in syringe - dilution
Catheter dilution - withdrawing blood from a line still contaminated with a drip
Halothane - messes with pO2 electrode
Temp - when blood is cooled CO2 becomes more soluble so PaCO2 falls and pH rises as HB accepts more hydrogen ions when cooled.
Syringe type - old plastic can interfere - modern plastic used or glass
85
What are the two scientific methods of blood gas interpretation?
Brief description
Alpha stat - ionisation of imidazole on histidine (haemoglobin) remains constant at different temps - ie. Intracellular pH is maintained at different temps so no need to alter patient parameters to maintain pH in the face of change of temp
pH stat - correct blood gases for temp, physiological parameters should be altered to maintain pH in the face of changing temps.
86
What method is used to correct ABGs for temperature
Rosenthal correction
87
What can commonly cause metabolic alkalosis
Diuretics
Ingestion of alkali
Loss of chloride
Excess aldosterone
88
How might pyloric stenosis cause a metabolic alkalosis
Loss of chloride and hydrogen ions from vomiting
Dehydrated kidneys respond by conserving sodium at expense of hydrogen thus also paradoxical renal hydrogen loss.
89
What diuretic produces a metabolic acidosis rather than alkalosis? Why?
Acetazolamide
Inhibits carbonic anhydride preventing the regeneration of bicarb in the kidney
90
What effect do salicylates have on acid base
Stimulate resp centre producing resp alkalosis
Uncouple oxadative phosphorylation producing metabolic acidosis
91
What is the strong ion difference in acid base theory?
Normal value
Sum of +ve ions minus major -ve charge ions. (Strong ions which dissociate fully in solution)
40-42mEq/L
92
Why does the Stewart hypothesis suggest alkalosis occurs in vomiting
Loss of chloride increasing the SID
NOT H+ loss as water provides an inexhaustible supply of H+
93
What is the effect on acid base of administrating large volumes of normal saline
Hyperchloraemic acidosis
Reduction in SID and increased water dissociation
94
What are the three principles of Stewart’s theory of acid base
Dissociation - strong ions separate fully, others only partially dissociate (eg weak acids
Electroneutrality - aqueous solutions will always have equal +ve to -ve ions
Mass conservation
95
What acid base disturbance results from albumin loss according to Stuart? How does the body react
Alkalosis - albumin is a weak acid
Decreasing the strong ion gap
96
How would the Stewart approach to acid base suggest sodium bicarb raises ph
Increases plasma sodium thus increasing SID and reducing plasma water dissociation and a fall in fee H+
97
What changes ph in Stewart equation of acid base?
Not H+, there is an inexhaustible supply from breakdown of water
Independent variables
CO2
Strong ions
Weak acids
98
How does SID differ from anion gap?
Bicarb is not a strong ion
Sid = (na k ca mg) - (cl lactate)
99
According to Stewart how does sid influence ph
What is normal range of sid
Sid has a strong effect on electrochemical gradient of water hence on h concentration.
Low sid causes dissociation of H and low pH
40-44 mol/L
100
What are the main weak acids in Stewart’s theory of acid base
What term represents them?
Albumin
Phosphate
Atot = (AH+A-)
101
How would the Stewart approach consider renal input into acid base balance
Loss of chlorine ions increases SID thus causes acidosis,
No effect of H or bicarb loss as will be replenished from water
102
How does the liver impact on acid base balance via the kidneys
Production of ammonium which is excreted with Cl increasing anion gap
Production of glutamine in response to acidaemia used by the kidneys to produce ammonium
103
How would varied GI losses impact on SID
Stomach losses - high Cl loss - increased SI D
Pancreatic or large intestine losses - loss of high SID fluid with low Cl thus decreased SID
104
How is hartmans neutral according to Stewart acid base
Sid slightly smaller than Plasma thus slightly acidotic
However, contains no ATOT (albumin) thus tends back to neutral
105
How does hypovolaemia cause alkalosis by Stewart acid base
Proportionally greater na retention than Cl thus increased SID
106
What is the strong ion gap of Stewart’s acid base?
SIG = SID - HCO3- - albumin
Should be 0 ie net negative of bicarb and albumin counter positive sid
The gap is unknown elements eg ketones
107
Bonds in forming protein tertiary structure
Hydrogen
Ionic
Hydrophobic
Disulphide bridges
108
What is the general function of enzymes
Protein catalysts - increase rate of chemical reaction without being changed themselves. Lower activations energies associated with the uncatalysed reation
109
What model replaced lock and key for enzyme substrate binding
Induced fit - enzyme active site changes shape.
110
What is the term for other molecules needed to assist an enzyme in its function? Broad categories and examples?
Cofactors
Metal ions eg - mg for hexokinase, zn for carbonic anhydrase
Coenzymes
Organic molecules eg - coenzyme A in acyl group reactions or coenzyme B12 in alkyl group reaction.
111
What can effect rate of an enzyme reaction?
Concentration of substrate
Intrinsic ability of enzyme
Temperature
pH
112
What is the relationship between enzyme reaction speed and temp
Generally increases until reaches a certain point where enzyme denatures and rapidly falls.
113
What is the michaelis mention equation in relation to enzyme kinetics?
E+S reversible ES unidirectional E+P
With rate constants k1 and k1- over the reversible stage and k2 over the unidirectional
V0 (initial max velocity) = Vmax[S] (max velocityxsubstrate ) / Km+[S] (rate constant + substrate)
The rate constant being k-1+k2 /k1
114
What plot type is used to evaluate enzyme kinetics
What are the axis
What are the values of x intercept, y intercept
Lineweaver burke
X is 1/[s], intercept gives -1/km
Y is 1/v0, intercept is 1/vmax
115
What is the effect on the enzyme substrate relationship of an increasing Km, how can it be read on a graph of substrate vs V0
Increasing Km means lower affinity of substrate to enzyme (higher concentration of substrate required for same reaction velocity)
It is the substrate concentration when velocity is half v max
116
What are the characteristics of a competitive enzyme inhibitor?
Effect on enzyme graphs
Reversible binds the enzyme usually at active site stopping substrate from binding
If binds away from active site causes shape change that stops substrate from binding
Both methods are overcome by increasing substrate concentration
Causes a right shift on a substrate velocity graph - Km increases but vmax is unaffected (just takes longer to get there
On a lineweaver burke steepens the line (crosses x axis closer to 0 larger Km) but crosses y axis in same place vmax same
117
Characteristics of non competitive inhibitor
Graph effects
Binds away from active site often permanent (covalently)
Substrate binding ineffective but still occurs
Net effect is decrease in the amount of functional enzyme
Thus lowers vmax but Km the same
On a substrate vs velocity reaches a lower v max (shifted down) but same Km
On a lineweaver Burke same end point on x axis but steeper line crossing the y axis higher (lower vmax)
118
What enzymes do not exhibit michalas menton kinetics? How do they appear to act?
Example?
Allosteric enzymes - their kinetics influenced by other molecules
Sigmoid curve indicating binding of Allosteric molecule.
Can also exhibit changes to vmax much like non competitive inhibition and Km like competitive
Haemoglobin (binding of oxygen)
119
What characteristic makes Allosteric enzymes important?
Allows an end product in a series of reactions to effect earlier enzymes providing a negative feedback system.
120
What are pro enzymes?
Common use
Inactive enzymes or zymogens
Proteolytic enzymes left inactive until in the desired location
121
Percentage of body water by compartments
Whole body 60% weight is water
66% in ICF
34% in ECF
APPROX:
Intravascular - 9% of water
Interstitial - 21% of water
Transcellular - 2% of water
Bone and connective tissue - 2% of water
122
What are the constituents of intravascular fluid? Percentages
Plasma (55%) blood cells
123
What does plasma consist of? Percentages?
Water 90%
Proteins 7%
Ions
124
Rough volume of intravascular space in adult
70-75ml/kg - appprox 5L in adult
2 litres of which are RBC
125
Roughly how much interstitial fluid is there in an average sized adult 70kg
Contents
Function
10L
Water and ions (no proteins)
Transport medium
Lymphatics
126
How does the ionic composition of icf and plasma compare? Implication?
Same composition and same osmolality
Fluid administered into intravascular space freely exchanges with ICF
127
What is transcelluar fluid
Examples
Secreted fluid separate from plasma
Eg GI fluid, csf, urine, aqueous humour, bile
128
What determines waters distribution across a semipermeable membrane?
The concentrations of the respective solutions
Water will move from a low solute concentration to a high solute concentration to equalise the concentrations
129
What is osmotic pressure?
The hydrostatic pressure required to prevent the movement of water across a semipermeable membrane (the minimum pressure that needs to be applied to a solution to prevent the inflow of its pure solvent across a semipermeable membrane)
130
What are
Osmoles
Osmolality
Osmolarity
Osmoles - osmotic ally active particles
Osmolality - number of Osmoles per kg of water
Osmolarity - number of Osmoles per litre of water (depends on temperature)
131
What is plasma osmolality typically
How can it be calculated
280-305 mosmol/kg
Plasma osmolality = urea + K + (2xNa)
132
What is the principle determinate of water distribution between ECF and ICF
ECF solute concentration - very little change in ICF concentration but ECF changes radically at times. Mainly this is dependant on ECF Na concentration
133
What controls fluid distribution within the ECF
Relative volumes of compartments as ions can move freely between blood and ISF
The size of compartment is determined by number of solute particles rather than osmolality.
Fluid is also pushed out of vessels by hydrostatic pressure and kept in by oncotic pressure (osmotic effect of proteins)
134
How is water intake regulated in the awake patient
Sensor - osmoreceptors in hypothalamus respond to changes in ECF toxicity (reflecting Na concentration)
Controllers - mechanisms in hypothalamus
Effectors - thirst (resulting in conscious intake of more water), ADH release from pituitary causing water reabsorption in collecting ducts
135
What is Ficks Law
Rate of diffusion across a membrane of unit area is proportional to concentration gradient
136
What is grahams law
Rate of diffusion is inversely proportional to square route of molecular weight
137
Width of capillary wall
Width of interstitial space
Rough time frame to equilibriate in ideal conditions by diffusion.
10 micro meters
1.2 micro meters
0.05s
138
What is ion trapping
Relevance to clinical anaesthesia
Unionised weak acid travels through cell membrane by diffusion then dissociates
Relevant in obstetrics where local anaesthetics pass to baby then dissociate in lower foetal blood pH
139
What is osmosis
Diffusion of solvent across a membrane that is impermiable to its solute from a region of low to high solute concentration so to equalise the solute concentrations.
140
What conditions are required for 1 mol of a substance to produced 1 atmosphere of osmotic pressure
Dissolved in 22.4L at 0degrees Celsius across a semipermeable membrane
141
Hoffs formula for calculating osmotic pressure
P = RT Sum(c1-c2)
Osmotic pressure = universal gas constant x temp (K) x sum of differences in ion concentrations across membrane
142
Universal gas constant with units
8.31 joules/kelvin/mole
143
What is the osmolarity of proteins in the blood
What is the specific term
Oncotic pressure exerted?
1-2 mOsmol/L
Oncotic pressure
3.5kPa (26mmHg)
144
What is the ideal gas equation
PV=nRT
Pressure x volume = number of moles x universal gas constant x absolute temp
145
What is tonicity
The behaviour of cells when bathed in solution as a comparison of osmolarity of plasma and solution. (Ie a hypo, iso hypertonic solution)
146
What is the function of sodium potassium atpase in detail
What is the normal sodium concentration gradient
Moves 3 na out of the cell and 2 k in for 1 atp to adp.
15mmol/l to 145mmol/l
147
What ion does nakatpase need for normal function
What upregulates it?
What down regulates it?
Mg
Upregulated by insulin, thyroid hormone, aldosterone
Dow regulated by cardiac glycosides, dopamine
148
How does insulin impact on Glut?
Causes vesicles containing GLUT 4 to merge with cell membrane increasing number of glucose transporters
149
How is glucose taken up in the gut?
Secondary active transport -
NaKatpase at basal membrane creates sodium gradient out of cell
Na is taken up from gut along with glucose through sodium dependant glucose transporters
Facilitated diffusion
Glucose diffuses through GLUT 2 carrier proteins at basal membrane into blood.
150
Characteristic points of a membrane channel
When open allow access from both sides of membrane
Contain one or more binding site in a transmembrane sequence
Provide a rapid portal through the membrane which approaches the free rate of diffusion
Can be open or gated for control
151
What are aquaporins. How are they activated?
Where are the types found?
Water channels. Located in endosomes. Moved to luminal surface when vasopressin binds to V2 receptor
1-3 in the kidney (2 in the collecting duct)
4 - in the brain
5 - in the salivary, lacrimal and respiratory glands.
152
What sorts of gated channels are there?
Voltage - eg in nerves, open and close due to electrical signal
Chemical - open and close due to chemical signal, either directly - ligand gated channels where ligand receptor is part of channel or indirectly - ligand gated channel where ligand binds remotely causing an release in an intracellular messenger e.g. G protein coupled receptors
Mechanical - e.g stretch activated channels on sensory nerve terminals
153
What is transcytosis?
Endocytosis or exocytosis
Proteins that could not otherwise cross the membrane passed in or out via vesicle formation/fusion with membrane.
154
Types of Endocytosis and description
Key protein involved
Phagocytosis - cell pushes out to engulf external object
Pinocytosis - external object into internal invagination
receptor mediated Endocytosis - pinocytosis with receptors
Key protein is clathrin - stabilise vesicle structure
155
What are The flask shaped invaginations that are needed for Endocytosis called? What protein pinches them off?
Caveoli
Dynamin
156
What triggers exocytosis
Usually increased calcium concentration. Needs atp .
157
How many subunits does a nakatpase have
2
158
What is the Gibbs-Donnan effect
When ions on one side of a membrane can’t diffuse through it the distribution of diffusible ions is also effected (e.g. non diffusible anions hinder diffusion of diffusible cations)
Results in electrochemical gradient
High protein in blood and cells trap ions
159
What equation calculates equilibrium potential across membrane
Nernst equation
160
What is the resting potential
A diffusion potential due to distribution of K -90mV
Some movement of Na and Cl drop it to -70mV
161
What is the Nernst equation?
E = RT ln(c1/c2) +ZFv
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What is the most predictive measurement of morbidity in obesity
Waist circumference NOT BMI
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What pathways are involved in obesity
Hyperinsulinaemia - increased deposition of fat
Insulin resistance - t2dm
Suppressed leptin - reduced satiety
Insulin mediated reduction in dopamine clearance - increased food reward
164
What is the site of release, function of leptin
Released from adipose tissue
Signals adipose tissue mass and thus adequacy of energy supply to CNS
Overall reduces food intake and permits energy expenditure
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What is the CNS effect of insulin
Similar to leptin
Reduces feeding, causes satiety
Activates SNS
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Where in the brain senses leptin and insulin levels
Hypothalamus
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What are the end effects of leptin and insulin centrally
Increased saitity to decrease meal size
Increased SNS activity causing energy expenditure - glycogen breakdown, lipolysis
