SESSION 3 Flashcards
What are the fundamental differences in composition between intracellular and extracellular fluids?
Intracellular
- high potassium
- low sodium
- low chloride
- low calcium
Extracellular
- low potassium
- high sodium
- high chloride
- high calcium
What is the approximate total aqueous volume obtained within an average 70kg medical student?
42 litres- 60% of the body weight
What proportion of this fluid is intracellular and extracellular?
1/3- 14l extracellular
2/3- 28l intracellular
In what compartments does the extracellular fluid distribute?
What is the volume of fluid in each compartment?
11l to interstitial water
3l to circulating blood volume
What are the most important membrane transport mechanisms involved in the control of intracellular Na+, K+ and Ca2+ concentrations?
- Sodium and potassium ATPase
- sodium and calcium exchanger
- Calcium ATPase- PMCA
- SERCA
- Mitochondrial calcium uniport
What would the immediate consequence be of a sudden increase/ decrease in the extracellular sodium concentration for a cell?
Sodium concentration affects osmosis
Increased sodium extracellularly:
- cell crenation due to osmosis
Decrease sodium extracellularly:
- cell lysis due to osmosis- water moves into the cell
What are the consequences of an increase in the permeability of blood capillaries to plasma proteins?
Plasma moves out of the capillaries into the interstitial space, as well as the protein.
Osmolality of interstitial space increases die to the movement of proteins, therefore water also moves out causing swelling - oedema
How might cells use membrane transport systems to maintain a constant cell volume?
Using sodium pumps, as water follows sodium by osmosis
NaKATPase
NaKCl (co- transporter)
In what ways can membrane transport processes contribute to the regulation of intracellular pH?
Concentration of H+ ions controls the pH
Acid extruders:
- Na+/ H+ exchanger
- sodium bicarbonate co- transporter
Base extruders:
- Cl-/ HCO3 exchanger
Define membrane permeability
Selectively permeable cell membrane is one that allows certain molecules or ions to pass through by means of active or passive transport
What are the important roles of transport processes?
- maintenance of ionic composition
- maintenance of intracellular pH
- Regulation of cell volume
- concentration of metabolic fuels
- expulsion of metabolic waste products and building blocks
- generation of ion gradients necessary for the electrical excitability of nerve/ muscle cells
Define passive diffusion
Passive transport is a movement of biochemical and other atomic/ molecular substances across cell membranes without need of energy input
Passive transport is dependent on permeability and concentration gradient
Passive transport increases linearly with increasing concentration gradient
Define facilitated diffusion
Facilitated diffusion is the process of spontaneous passive transport of molecules or ions across a cell membrane via specific transmembrane integral proteins
Models for facilitated transport:
- protein pores- channels
- ping- pong proteins - carriers
- flip- flop proteins
ligand- gated ion channels- open/ close in response to ligand binding to a receptor site
voltage- gated ion channels - open/ close in response to the voltage potential difference across the membrane
Gap junction (connexin)- closed when cellular calcium conc rises above 10uM
Define active transport
Active transport allows the transport of ion of molecules against an unfavourable concentration and/ or concentration gradient
Energy directly or indirectly for ATP hydrolysis
Explain the transport equation
/\G= RT log (c2/c1)
R= gas constant
T= temperature
C1 and C2= concentration inside and outside
Active –>+ /\G
Passive –> -/\G
Define uniport
Uniport- only one molecule is transported at a time
E.g. Protein pump in mitochondria - Ca2+ Mg2+ ATPase
High affinity
Low capacity
What are the two types of co- transport molecules
Symport- transports two different substances in the same direction
Antiport- transports two different substances in the opposite direction
Relate membrane transport information to clinically useful examples
Fluoxetine
Outward flow of K+ down its concentration gradient leads to uptake of serotonin in the presynaptic cleft and by platelet with Na+ ion -> symport
Fluoxetine increases serotonin action making blood sticky
- transporters in cystic fibrosis
Relate membrane transport information to clinically useful examples
Diarrhoea
CFTR
Explain the importance of controlling the concentration of calcium within the cell
Intracellular Ca2+ -> 0.0001mM
Extracellular Ca2+ -> 1mM
10,000 fold difference in concentration across the plasma membrane
High intracellular calcium concentration is toxic to cells
Cells signal by small changes in intracellular concentrations
Outline the major physiological role of sodium potassium ATPase
- antiport
- 3Na+ expelled and 2K+ enter
- sodium pump creates Na+ and K+ gradient- necessary for electrical excitability
Drives secondary active transport:
- ion homeostasis
- intracellular Ca2+ concentration
- control of intracellular pH
- regulation of cell volume
- Absorption of Na+ in epithelia
- Nutrient uptake in the small intestine, e.g. Glucose
Outline the major physiological role of plasma membrane Ca2+ ATPase (PMCA)
- removes Ca2+ from the cell
- regulator of calcium concentration in the extracellular space
- pump powered by hydrolysis of ATP
- effective at binding to calcium when its conc is very low
Outline the major physiological role of sarcoplasm in reticulum Ca2+ (SERCA)
- resides in the SR
- the rate at which SERCA moves Ca2+ across the SR membrane can be controlled by the regulatory protein phospholaben (PLB/PLN)
- usually inhibited by PLB
Outline the major physiological role of: sodium calcium exchanger (NCX)
- role in expelling intracellular Ca2+ during cell recovery
- exchanges 3 Na+ for 1Ca2+. –> increase positive charge
- electrogenic- current flows in the direction of the Na+ gradient
- possible role in cell toxify during ischaemia/ reperfusion
- ATP depleted- sodium pump inhibited
- NCX reverses Na+ pumped out and Ca2+ in
Outline the major physiological role of: anion exchanger (chloride bicarbonate exchanger)
- principal regulators of pH
- exchange HCO3- for Cl-
- vital role in acid- base movements in the stomach, pancreas, intestine, kidney, reproductive organs and the central nervous system
Summary of the control of resting calcium
Primary active transport
- PMCA expels Ca2+ out of the cell
High affinity, low capacity (removes residual Ca2+)
- SERCA accumulates Ca2+ into the SR
High affinity, low capacity (removes residual Ca2+)
Secondary active transport
- Na+ Ca2+ exchange (NCX)
Low affinity, high capacity (removes most Ca2+)
Facilitated transport
- mitochondrial Ca2+ uniport
- operate at high Ca2+ to buffer potentially damaging Ca2+
Describe how ion transport contributes to cellular pH regulation
Acidification can be opposed by expelling H+ ion or inward movement of bicarbonate ions
Acid extruders:
- Na+/ H+ exchanger (NHE)
- Na+ dependent Cl-/HCO3- exchanger
Alkalisation is opposed by expelling bicarbonate via the anion exchanger
Base extruders:
- Cl-/ HCO3- exchanger (Anion exchanger)
Explain the role of Na+/ H+ exchanger (NHE)
- exchanges extracellular Na+ for intracellular H+
- electroneutral charge
- regulate pH
- regulates cell volume- proton movement results in osmosis
- activated by growth factors
- inhibited by amiloride - a potassium sparing diuretic
How ion transport contributed to cell volume regulation
EXAM
- transport of osmolality ‘active ions’ e.g. Na+, K+ and Cl- out of the cell
- water follows
Mechanisms to resist cell swelling- extrude ions
Mechanisms to resist cell shrinking- influx ions
(See diagrams for further revision )
Explain how ion transport contributes to renal bicarbonate reabsorption
- if filtration occurred on its own
- then Na+ and HCO3- ions would leave the body
- H2O would follow
- the patient would rapidly dehydrate
The kidney reabsorbs all the bicarbonate filtered into the proximal tubule- to retain base for pH buffering capacity
Explain how ion transport contributes to renal Na+ ion handling
Almost all Na+ that appears in the glomerular filtrate is reabsorption from the kidney nephron
Driving force for the reabsorption i the low Na+ concentration maintained by Na+K+ATPase activity in the tubular cells
Define osmosis
The passive movement of water across the plasma membrane
Water is small and non- hydrophobic
Define osmotic gradient
water will diffuse passively across lipid bilayer up the concentration gradient of a solute
Define aquaporins
Water channels that facilitate the movement of water
Explain diuretic drug actions to control water balance and fluid loss
Fluid loss is required to treat oedema or hypertension
Block of one or more of the Na+ reabsorption mechanisms with diuretic drugs
Increase Na+ excretion to produce hyperosmotic urine- excretion of water
How does the uptake of glucose from the blood into adipose, brain, liver and skeletal muscle cells differ that in intestinal and kidney epithelial cells?
Glucose concentration gradient favours uptake.
Glucose enters by facilitated transport down the glucose concentration gradient via glucose transporters.
A family of glucose transport proteins (GLUT-1-7) exists with different kinetic properties to suit the needs of individual tissues.
In some cells, these transporters are not permanently within the plasma membrane, but need insulin to stimulate their translocation from the cytoplasm when specific glucose uptake is required, such as in the adipose, brain, liver and skeletal muscle cell
How does insulin stimulate the rate of uptake of glucose into adipose tissue and skeletal muscle?
Recruits GLUT-4 glucose transporters from internal vesicular membranes to the plasma membrane to increase the transport capacity of the membrane.
What prevents the efflux of glucose from cells in tissues such as adipose and skeletal muscle when the circulating glucose concentration falls to resting levels in the post- adsorptive period after a meal?
Glucose is rapidly converted to glucose-6-phosphate on entering the cell
By the actions of hexokinase in the liver
and glucokinase in other cells
Thus, the intracellular glucose concentration never rises high enough to reverse the concentration gradient.
Apart from glucose, what other metabolites use the sodium gradient for their uptake into cells against the concentration gradient?
Amino acids- there is a family of known transporters for different groups of related amino acids.
