3.8 - Plasma Flashcards

1
Q

What are the four main fluid compartments in the body?

A
  • 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
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2
Q

What is plasma?

A
  • 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
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3
Q

What is serum?

A
  • 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
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4
Q

What are the functions of plasma?

A
  • 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
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5
Q

Plasma proteins

A
  • 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)
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6
Q

Serum albumin

A
  • 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
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7
Q

Alpha-1 globulins

A
  • 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
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8
Q

Alpha-2 globulins

A
  • 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)
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9
Q

Beta globulins

A
  • examples include C3 and C4 complement proteins
  • transferrin - generated by liver, key role in transportation of dietary iron that is released from ferritin stores
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10
Q

Gamma globulins

A

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

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11
Q

What are the sodium and potassium ion levels in the plasma vs RBCs?

A
  • 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
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12
Q

How are calcium levels like in cells?

A
  • 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)
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13
Q

What is intracellular Mg2+ important for?

A

Important cofactor of many enzymes

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14
Q

How is the balance of electrolyte gradients maintained?

A
  • 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
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15
Q

What can we use plasma for? - Biomarkers

A
  • 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
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16
Q

What can we use plasma for? - Passive immunotherapy

A
  • 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
17
Q

How could convalescent plasma be used to treat COVID-19 patients?

A
  1. patients infected with SARS-CoV-2 develop antibodies against the virus
  2. after the patient has recovered (convalesced), plasma is donated to obtain antibody-rich plasma
  3. the plasma is tested for strength (affinity) and number of antibodies
  4. if these levels are fine, the plasma is given to a patient infected with COVID-19
  • efficacy remains debatable