WEEK 8 Flashcards
Explain the divisions of the fluid compartments of the body.
The body is 60% aqueous fluid - most of the fluid is intracellular (2/3rds) - the remainder is extracellular (1/3rd) The extracellular fluid is separated into interstitial fluid (80%, tissues that bathe the tissues) and plasma (20%, the fluid part of the blood). The exchange between these fluids occurs in the capillaries. The only difference between these two fluids is the presence of plasma proteins which are too large to pass through the capillaries into the interstitial fluid. The intracellular and extracellular fluid are separated by the cell membrane.
What are the concentrations of the major components of intracellular and extracellular fluid?
EXTRACELLULAR FLUID (mM) Na+ 140 K+ 5 Cl- 110 HCO3- 27 Ca2+ 2 Mg2+ 1 Anions- 8 pH 7.4 potential + (mV) IINTRACELLULAR FLUID (mM) Na+ 10 K+ 140 Cl- 5 HCO3- 10 Ca2+
The membrane is a barrier but diffusion of polar and non-polar substances can occur. What are the 2 types of diffusion?
PASSIVE DIFFUSION of fat soluble non-polar substances through the lipid bilayer FACILITATED DIFFUSION of hydrophilic substances through integral membrane protein pores or carriers
What is the difference between integral and membrane proteins?
Membrane proteins confer distinctive functions by acting as transport systems, enzymes, receptors etc. PERIPHERAL proteins are weakly bound and can be removed by mild treatment (changing the pH) INTEGRAL proteins are embedded in the bilayer and can only be removed by disrupting the bilayer.
What is the importance of the amphipathic properties of membrane lipids?
Membrane lipids are amphipathic: small molecules with hydrophobic and hydrophilic regions. Hydrophilic groups are charged (polar) and are readily soluble in aqueous environment. Hydrophobic groups are uncharged (non-polar) and are poorly soluble in an aqueous environment.
What are the key roles played by membrane transport processes?
- Regulate cell volume and maintain intracellular pH and ionic composition within a narrow range 2. Concentrate essential nutrients from extracellular space and excrete metabolic waste products.
Use flux equation to explain diffusion into an enclosed compartment.
F = P (Co-Ci) note P = permeability constant. The rate of diffusion is measured as T90%, which is the time taken for concentration of the extracellular space to increase to 90% of the capillary concentration (in the case of movement from the capillary to extracellular space) Efflux is from inside to outside, influx is from outside to inside. Flux is the number of molecules crossing a unit area of membrane in a unit time i.e. moles/cm2/sec
What 3 things/processes occur in the first week of embryonic development?
fertilisation, cleavage, and transport to the nucleus
Describe the process of fertilisation. What does it result in? (HINT: there’s 3 things)
Occurs in the ampulla of the uterine tube within 12 hours of ovulation (no more than 24 hours, however sperm can live for unto 48 hours in the female genital tract). Fertilisation results in: - completion of meiosis in the oocyte - restoration of the diploid number of chromosomes - determination of sex and initiation of cleavage of the zygote within the zona pellucida.
Describe the process of cleavage. When does it occur? What is it? What does it do? Where does it occur? What does it form?
Occurs within 36 hours of fertilisation, initially cells are totipotent up to the blastocyst stage. Cleavage is a series of mitotic divisions that gives an increase in the numbers of cells (blastomeres). As the cytoplasm is shared, cells become smaller with each division giving a high surface area to volume ratio that enhances the uptake of nutrients, O2 and removal of waste products. Cleavage occurs as the zygote passes along the fallopian tube to the uterus. 16 cells form the morula = a solid ball of cells arranged in inner and outer layers.
What is going on/happens 3-4 days AFTER fertilisation?
The morula consists of approximately 100 cells as it enters the uterus and the zona pelludica dissapears. The outer cells divide to become trophoectoderm Fluid begins to accumulate in the centre of the morula which now becomes know as the BLASTOCYST. Cavities develop between the cells and they fill with fluid. The outer wall of the blastocyst or trophoblast will form the embryonic part of the placenta and secretes early pregnancy factor (EPF) - an immunosuppressant protein to prevent mother recognising embryo as foreign and rejecting it. The inner cell mass consists of blastomeres and forms at one pole of the blastocyst; these cells will give rise to the embryo proper.
What occurs on days 5.5-6?
BINDING TO UTERUS WALL - Binding at the uterus epithelium occurs (embryonic pole attaches) - Down regulation of anti-adhesion molecule MUCN1 - Allows binding via selectins (embryo) to glyco-components on epithelial cells (uterus) - Similar mechanism to white blood cell adhesion to blood vessel walls. - Integrins, laminin and fibronectin involved in initial penetration.
What are the main events which happen during days 6-7?
Implantation begins Trophoblast becomes the “invasive” syncytiotrophoblast and cytotrophoblast (cap the embryoblast which will become the embryo) Syncytiotrophoblast multinucleate syncitium invasion via metalloproteases Immunosuppression of host/graft and graft/host reactions
What occurs on (i) Day 8 and (ii) Day 9 or embryology?
(i) Trophoblast divides and part becomes “invasive” syncytiotrophoblast and cytotrophoblast Two layers form in the embryo – epiblast (inner) and hypoblast The amniotic cavity begins to form as a space within the epiblast. (ii) The flattened cells spread out from the hypoblast to line the inner surface of the cytotrophoblast forming the primitive yolk sac
What happens during days 11-12?
Spaces form in the extra embryonic mesoderm, fusion of these spaces forms the chorionic cavity The blastocyst burrows completely into the endometrium Syncytiotrophoblast (SCT) cells erode through the walls of large maternal capillaries which bleed into the spaces H primitive placental circulation (breakthrough bleeding may occur) The embryonic disk is now bilayered
Why is week 2 known as the week of 2s?
2 layers develop in the trophoblast: - syncytiotrophoblast - cytotrophoblast 2 layers in the inner cell mass: - epiblast (= ectoderm) - hypoblast ( = endoderm) 2 cavities form: - amniotic - chorionic
What site is the most common for ectopic implantation? Why can this occur?
Ampulla There may be a number of causes including mucosal adhesions due to pelvic inflammatory disease (can be caused by chlamydia) 95-97% of ectopic pregnancies are in the ampulla/isthmus of the fallopian tube
What does rupture of the fallopian tube during ectopic pregnancy result in? What are the symptoms of this often confused with?
Rupture of the tube causes blood loss that may be life threatening to mother and fatal for the embryo, the symptoms can be confused with appendicitis leading to misdiagnosis.
Apart from the ampulla of the fallopian tube, where is another place that an ectopic pregnancy can occur?
Very occasionally pregnancies develop on the mesentery and the baby may survive if surgical intervention occurs as mesentery has a good blood supply for early embryo development.
When is the embryo most vulnerable to environmental insult? What do the environmental causes include?
Embryonic period. Most organs and organ systems are formed during the 3rd week, critical period for normal development of organs systems. Drugs chemicals: nicotine/alcohol, chemotherapy/thalidomide/retinoic acid Infectious agents e.g. rubella Ionising radiation
Where are the (i) dorsal-ventral (ii) left-right axes determined in the embryo?
(i) in the oocyte (ii) determined cilia movement in the node
What is the function of (i) channel proteins (ii) carrier proteins?
(i) have watery spaces through the molecule allowing free movement of water and some molecules and ions that move along their concentration gradient. (ii) bind to molecules or ions and move them through the protein to cross the bilayer Channel proteins and carrier proteins are usually selective for a particular molecule
What is the role played by the permeability constant in determining transmembrane diffusion? What does P depend on?
The permeability constant (P) incorporates the factors inherent in both the molecule and the membrane that determines the probability of the molecule crossing the membrane P = ωRT k/a (NOTE: dont need to know this) P depends on: - the size of the molecule and viscosity of solution being diffused through (ω) - The thickness of the membrane (a) - And the molecule resistance (k) eg: lipids are ‘slippery’ and will move more easily than a charged particle which will offer some resistance
Explain the anomalous permeability characteristic permeability properties of water.
Water is one of the small molecules that have anomalous behaviour when comparing permeability across the lipid bilayer to k. Its permeability far exceeds the expected value from the trend of most of the other molecules. This shows that water must be moving by a different mechanism than simple diffusion through the lipid bilayer. ….AQUAPORINS
What is the structure and membrane organisation of the Aquaporin water channel?
Aquaporin is an integral membrane protein found in biological membranes allowing movement of water by offering an alternative route for the movement of water across the membrane without the molecule having to interact with the lipid. The basic aquaporin unit comprise 6 trans-membrane α-helices NPA : asparagine - proline - alanine (amino acid motif) Aquaporins form tetramers in the membrane – each monomer acts as a water channel.
How does ADH regulates of the transepithelial movement of water?
Anti diuretic hormone (ADH), also called vasopressin, is a 9 amino acid long polypeptide. It increases water reabsorption in the kidneys by up-regulating AQP-2 in the epithelial cells of the late distal tubules, collecting tubules and collecting ducts (requires urine output) Increased AQP-2 channels allows increased water up-take. Whilst AQP-3 channels remain constant.
What are the 2 types of active transport? Describe them.
- PRIMARY ACTIVE TRANSPORT:
- molecules are pumped against an EC gradient at the expense of energy (ATP) = direct use of energy - SECONDARY ACTIVE TRANSPORT:
- Transport is driven by the energy stored in the
EC gradient of another molecule (usually Na+) that was already pumped into the cell using active transport = indirect use of energy
What are 3 examples of primary active transport? Describe them.
1. Sodium potassium pump transports sodium ions out and potassium ions into cells. Establishes a negative voltage inside the cell important for nerve function and signal transmission.
- When 2 x K+ are bound to the external K+ sites and 3 x Na+ to the internal sites ATPase is activated. One ATP is cleaved to ADP + 1 x high energy phosphate bond. Phosphorylation causes a chemical and conformational change to the carrier protein causing the 3 x Na+ to be extruded across the membrane and the 2 x K+ to be introduced into the cell.
- it is responsible for secondary active transport.
2. Ca2+ ATPase transporter: Present on the cell membrane and the sarcoplasmic reticulum in muscle fibers. Maintains a low cytosolic Ca2+ concentration
3. H+ ATPase transporter: Found in parietal cells of gastric glands (HCl secretion) and intercalated cells of renal tubules (controls blood pH). Concentrates H+ ions up to 1 million-fold
What are the 4 ways that molecules can move across cell membranes?
- Diffusion across the membrane (non-polar molecules)
- Diffusion through membrane pores
- Protein carrier facilitated diffusion
- Active transport (primary with specific ATPases and secondary with specific transporters)
Describe secondary active transport (co1 transport) with Na+ symporter.
[Na+] across the membrane is high outside / low inside the cell
Na+ high creates electrochemical energy due to pressure to diffuse through the membrane.
Na+ and a second molecule bind to the symporter and both are transported into the cell using Na+ electrochemical energy eg. glucose, amino acids and 2 x HCO3-
What is the function of (i) symporters (ii) antiporters?
(i) transport substance in the same direction as a ‘driver’ ion e.g. Na+. It involves the use of an EC gradient
(ii) transport substance in the opposite direction as a ‘driver’ ion like Na+
What is endoderm? How is it formed?
The yolk sac becomes the gut tube
Amnion enwraps the embryo almost completely cuttng off gut from yolk sac
