3.8 - Plasma Flashcards
What are the four main fluid compartments in the body?
- intracellular (55% of the fluid) - inside cells
- there are three extracellular fluids:
- interstitial fluid (36%) - found between cells and vital for carrying oxygen and nutrients to cells and transporting away waste products - drains into lymphatic vessels from tissues where it is called lymph
- plasma (7%) - liquid component of blood - very similar to interstitial fluid but more protein
- transcellular fluid (2%) - group of remaining fluids like ocular fluids in eye and cerebrospinal fluid
What is plasma?
- the liquid component of blood
- comprises around 55% of blood volume
- if we treated blood with anticoagulant and centrifuged it we would see:
- plasma - 55% of blood volume (top)
- buffy coat - <1% of blood volume - separates plasma and red cells in the tube - consists of leucocytes and platelets
- red cells - 45% of whole blood
What is serum?
- plasma minus the clotting factors
- blood is taken into a tube without an anticoagulant, allowed to clot and then centrifuged
- generated by letting blood clot for several minutes, depleting the plasma of coagulation factors and trapping cells and platelets within the clot
- plasma is quicker to prepare, but serum is a cleaner sample (few cells) but takes longer
Serum separator tubes (SST) have: - a silica coating which induces clotting
- a layer of gel forming a physical barrier between cells and serum
What are the functions of plasma?
- clotting - contains clotting factors and VWF
- immune defence - contains antibodies and complement proteins
- osmotic pressure maintenance - proteins like albumin help to maintain colloidal osmotic pressure
- metabolism - nutrients like glucose, amino acids and vitamins are transported in plasma
- endocrine - many hormones are soluble in plasma and following release into blood, travel to their target organs
- excretion - cell metabolism waste products like urea are transported via plasma to kidneys for removal
Plasma proteins
- proteins make up around 7% of plasma
- we can assay them by electrophoresis
- resulting pattern reflects the size and abundance of two major types of plasma protein - serum albumin (55% of plasma proteins) and globulins (35% - alpha1, alpha2, beta1, beta2 and gamma globulins)
Serum albumin
- produced by the liver
- several key functions including:
- transport of lipids, hormones and ions
- maintaining osmotic pressure of plasma
- fatty acids released by lipolysis from the breakdown of triglycerides in adipose are transported by albumin for use by tissues in beta oxidation
Alpha-1 globulins
- alpha-1 antitrypsin (A1AT) is produced by the liver and enters the circulation
- A1AT plays an important role in inhibiting proteases (in order to protect tissues from other enzymes, notably the neutrophil elastase, released by neutrophils during inflammation)
- defective/deficient A1AT can compromise the lung where degradation of lung tissue leads to a loss of elasticity and respiratory problems
Alpha-2 globulins
- haptoglobin binds to haemoglobin released from erythrocytes and the resulting haptoglobin-haemoglobin complex is removed by the spleen
- measuring haptoglobin levels can be informative in the diagnosis of haemolytic anaemia in combination with other parameters
- alpha2-macroglobulin is a broadly active protease inhibitor which can inactivate fibrinolysis (breakdown in fibrin in blood clotting)
Beta globulins
- examples include C3 and C4 complement proteins
- transferrin - generated by liver, key role in transportation of dietary iron that is released from ferritin stores
Gamma globulins
Main examples:
- immunoglobulins (antibodies)
- C-reactive protein (acute-phase protein)
Diagnostic uses - increases in relative amounts of the gamma fraction of globulins can indicate infection or myeloma
What are the sodium and potassium ion levels in the plasma vs RBCs?
- Na+ is the most plentiful cation in the plasma - 30x lower in RBCs
- K+ levels are 30x lower outside RBCs
- the positive charge from intracellular potassium is mainly balanced by extracellular Cl-
- the internally high concentration of K+ inside the cell is also neutralised by a variety of anions e.g. proteins, nucleic acids, phosphorylated proteins
How are calcium levels like in cells?
- Ca2+ found at intracellular levels several thousand times lower than outside the cell
- increase in intracellular Ca2+ is associated with signalling (opened Ca2+ channels allows influx from exterior / release of intracellular stores)
What is intracellular Mg2+ important for?
Important cofactor of many enzymes
How is the balance of electrolyte gradients maintained?
- by the active transport of ions by protein pumps like Na+K+ATPase (ATP hydrolysis needed for energy for transportation)
- for every 3 Na+ out of cell, 2 K+ enter the cell
- more than 1/3 of ATP consumed during rest is used to power the pump
- maintaining concentration gradient is key to functioning of electrically excitable cells e.g. muscle fibres, neurones, and maintenance of cell volume
- ATP levels depleted = cells have a tendency to become more spherical due to inward movement of sodium ions and water
What can we use plasma for? - Biomarkers
- plasma and serum provide an easy to obtain clinical specimen that can be subjected to laboratory tests for diagnostic purposes
- the study of plasma proteome and links with disease, medications and lifestyle is useful to inform treatment decisions
- elevated levels of some key molecules provide handy biomarkers of disease
What can we use plasma for? - Passive immunotherapy
- plasma contains antibodies
- immunoglobulins found in the gamma globulin fraction can be used to transfer immunity from one individual to another
- intravenous immunoglobulin G (IVIG) - allows introduction of relatively large amounts of IgG, protects against most of the common pathogens donors are exposed to
- hyperimmune globin - donors are screened for high levels/titres of IgG against a particular pathogen, the IgG fraction is isolated from the plasma of these donors and concentrated
- provides passive immunity to a specific pathogen - often given following high-risk exposure to a pathogen
- vaccinations provide active immunity but require days/weeks to elicit a response
How could convalescent plasma be used to treat COVID-19 patients?
- patients infected with SARS-CoV-2 develop antibodies against the virus
- after the patient has recovered (convalesced), plasma is donated to obtain antibody-rich plasma
- the plasma is tested for strength (affinity) and number of antibodies
- if these levels are fine, the plasma is given to a patient infected with COVID-19
- efficacy remains debatable