Physiology, Blood Plasma


Article Author:
Joscilin Mathew


Article Editor:
Matthew Varacallo


Editors In Chief:
Stephen Leslie
Karim Hamawy


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
1/20/2019 8:17:57 AM

Introduction

Plasma, also known as blood plasma, appears light-yellowish or straw-colored. It serves as the liquid base for whole blood. Whole blood minus erythrocytes(RBCs), leukocytes(WBCs) and thrombocytes(platelets) make up the plasma. Serum, sometimes mistakenly considered synonymous with plasma, consists of plasma without fibrinogen. Plasma contains 91% to 92% of water and 8% to 9% of solids. It mainly comprises:

  1. Coagulants, mainly fibrinogen, aid in blood clotting,
  2. Plasma proteins, such as albumin and globulin, that help maintain the colloidal osmotic pressure at about 25 mmHg,
  3. Electrolytes like sodium, potassium, bicarbonate, chloride, and calcium help maintain blood pH.
  4. Immunoglobulins help fight infection and various other small amounts of enzymes, hormones, and vitamins.

Issues of Concern

Extraction of Plasma

It can be separated from whole blood by the process of centrifugation, i.e., spinning whole blood with an anticoagulant in a centrifuge. Plasma is lighter, so it forms the upper yellowish layer, while the denser blood cells fall to the bottom. Plasma forms 55% and red blood cells form 45% of the total blood. The plasma collected is frozen within 24 hours to preserve the functionality of the various clotting factors and immunoglobulins; it is thawed before use and has a shelf life of 1 year. Interestingly, while O- is the preferred universal donor for blood, the plasma of AB blood groups are the most preferred because their plasma does not contain antibodies, making it acceptable for everyone without fear of adverse reaction. 

Plasma, like whole blood, is initially tested, to ensure the safety of recipients. As per the FDA regulations, the collected plasma undergoes a battery of tests to identify transmittable diseases, mainly hepatitis A, B, and C along with syphilis and HIV. The process of fractionation separates individual plasma proteins.[1]

Cellular

The specific gravity of plasma is 1.022 to 1.026 as compared the specific gravity for blood which is 1.052 to 1.061.

Development

The origin of plasma, which constitutes 55% of total blood, is interesting because no organ produces it. Instead, it is formed from water and salts absorbed through the digestive tract. Plasma proteins, on the other hand, have distinct organs that produce them based on an individual's stage of development. In Embryo

In the embryonic stage, the mesenchymal cells are responsible for the plasma cell production. The first protein to be synthesized is albumin, followed by globulin and the other plasma proteins.

In Adults

The reticuloendothelial cells of the liver are in charge of plasma protein synthesis in adults. The bone marrow, degenerating blood cells, and general body tissue cells along with the spleen also contribute to the formation of plasma proteins. Gamma globulins originate from B lymphocytes, which in turn form immunoglobulins.

Function

As plasma forms the liquid base of blood, the functions carried out by plasma and blood overlap. The multitude of functions include:

  • Coagulation: Fibrinogen plays a major role in blood clotting along with other procoagulants like thrombin and factor X.
  • Defense: Immunoglobulins and antibodies in plasma play an important role in the body’s defense against bacteria, virus, fungi, and parasites.
  • Maintenance of Osmotic Pressure: The colloidal osmotic pressure is maintained at around 25 mmHg by the plasma proteins like albumin.
  • Nutrition: Transportation of nutrients like glucose, amino acids, lipids and vitamins absorbed from the digestive tract to different parts of the body as a source of fuel for growth and development.
  • Respiration: Transportation of respiratory gases, i.e., carrying oxygen to the various organs and carrying carbon dioxide back to the lungs for excretion.
  • Excretion: The blood removes nitrogenous waste products produced after cellular metabolism and transports them to the kidney, lungs, and skin for excretion.
  • Hormones: Hormones are released into the blood and transported to its target organs.
  • Regulation of Acid-Base Balance: Plasma proteins contribute to acid-base balance through their buffering action.
  • Regulation of Body Temperature: This is maintained through a balance between heat loss and heat gain in the body.
  • Role in Erythrocyte Sedimentation Rate (ESR): Fibrinogen, an acute phase reactant, increases during acute inflammatory conditions and contributes to the increase in ESR, which is used as a diagnostic and prognostic tool.

Related Testing

Water constitutes about two-thirds of the human body. In an adult man weighing 70 kg, the body water content is about 42L. This water content is divided into two major compartments:

  • Intracellular fluid (ICF): It forms about 28 L (about 40% of total body weight)
  • Extracellular fluid (ECF): It forms about 14 L (about 20% of total body weight) of which 15% is interstitial fluid and 5% is plasma.

Plasma can be measured by the use of marker substances like radioactive iodine (131 I) and Evans blue (T-1824). Evans blue is the commonly used marker substance aka tracer as it binds strongly with albumin. The concept behind using a tracer is to use one that is well distributed in the compartment of interest. A known amount of tracer is introduced into the compartment, and its volume of distribution is measured.

Volume = Amount of tracer/Concentration of tracer

Compartment volumes are measured based on the volume of distribution of tracer. In the case of measuring plasma volume, the albumin-bound tracer, i.e., Evans blue, is used. As albumin tends to continuously leak out of the circulation, the tracer concentration is measured at serial intervals and is plotted on a logarithmic curve. This curve is then extrapolated to identify a “zero time” that allows the estimation of a virtual volume of distribution. The volume of distribution measured is the volume of plasma. 

Clinical Significance

The numerous clinical uses of plasma can be best explained when considering the various forms and components of blood plasma: [2]

  1. Whole Plasma: Fresh frozen plasma is indicated in the treatment of massive bleeds resulting in shock, in disseminated intravascular coagulation, burns, and liver disease. The coagulants found in plasma aid in decreasing bleeding time and improving stabilization of the patient. Fresh frozen plasma also plays an important role as an immediate and effective antidote for warfarin reversal. The first-line treatment of thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) is plasma exchange with 40 mL of plasma per kg body weight. In neonates, plasma plays a role in exchange transfusion of plasma of neonates with severe hemolysis or hyperbilirubinemia. Plasma is also utilized in the filling the oxygenator in extracorporeal membrane oxygenation in neonates.
  2. Clotting factors: Clotting factors and von Willebrand factor (vWF) found in plasma play an essential role in blood clotting and are activated by damage to the endothelium resulting in exposure of collagen found beneath the endothelium of the blood vessel. People with blood clotting deficiencies such as hemophilia and von Willebrand disease can suffer massive internal bleeds with a minor injury. Such patients benefit greatly from plasma protein derivatives such as factor VIII concentrate and factor IX concentrate.
  3. Immunoglobulins: Immunoglobulins protect the body against invading bacteria and viruses and play a key role in the body’s defense. Certain immunological disorders like congenital or acquired primary immune deficiency, where the body can’t produce antibodies or other conditions such as the adverse effects seen in cancer treatments, resulting in harm to the bodies antibodies, benefit greatly from immunoglobulin infusions. Immunoglobulins also play a major role in passive immunization. Antidotes to diseases such as chickenpox, rabies, hepatitis, and tetanus are the initial treatment after suspected exposure, to limit disease progression. Such specific immunoglobulins are derived when patients who have been previously affected by a disease, for example, chickenpox donates plasma. This plasma contains high amounts of circulating antibodies against chickenpox that can be collected and stored after fractionation for use as post-exposure vaccines for varicella.
  4. Albumin: Albumin is the main protein that controls oncotic pressure and serves as the transporter of multiple endogenous as well as exogenous substances (e.g., drugs) throughout the body. Infusion of albumin is used in the treatment of burns and hemorrhagic shock. Studies have also shown marked improvement in the prognosis of cirrhotic patients.[3] In patients with liver cirrhosis, albumin infusions have decreased mortality in patients with spontaneous bacterial peritonitis and improved outcomes in large volume paracentesis.[4][5] Albumin is also useful in the management of hepatorenal syndrome.
  5. Alpha-1 antitrypsin: -Alpha-1 antitrypsin is produced in the liver and plays an important role in the lungs by increasing proteases which counteract the effect of elastases produced by the neutrophils in response to inflammation such as smoking. Alpha-1 antitrypsin deficiency is an inherited disorder that could result in emphysema and cirrhosis in early adulthood. Recent advances in treatment have shown success in decreasing the mortality and frequency of exacerbations when human plasma-derived alpha-1 antitrypsin is given intravenously once a week.[6][7]
  6. Plasma as a laboratory test: Plasm testing can diagnosis and confirm diseases like diabetes based on serum glucose levels or von Willebrand disease. Monitoring of international normalized ratio(INR) in patients on anticoagulants requires serial measurements of plasma prothrombin levels.[8]
  7. Plasmapheresis: Plasmapheresis is an effective temporary treatment in many autoimmune diseases. In therapeutic plasmapheresis, the patient’s venous blood is withdrawn, blood cells are separated, and a replacement colloid solution along with blood cells are infused in its place.[9] In most cases, a 4% to 5% human serum albumin solution in saline is the preferred replacement solution. The following are common conditions where plasmapheresis is utilized:
  • Myasthenia gravis
  • Chronic inflammatory demyelinating polyneuropathy
  • Hyperviscosity in monoclonal gammopathies
  • Thrombotic thrombocytopenic purpura
  • Guillain-Barre syndrome
  • Lambert-Eaton syndrome
  • Multiple sclerosis

Platelet-rich Plasma (PRP)

PRP is defined as autologous blood with a concentration of platelets above baseline reference values. Traditionally, PRP injections have been used over the last three decades in maxillofacial and plastic surgery.  More recently, its use throughout orthopaedics and sports medicine has been well-established and heavily controversial[10].

The use of PRP injections in the setting of acute or acute-on-chronic musculoskeletal pathology continues to remain debated.  One of the more heavily debated areas regarding PRP use is in the management of moderate knee osteoarthritis. Knee osteoarthritis afflicts a significant portion of the adult population and has an exorbitantly high impact on the healthcare system, financial resources, and overall disability both in the United States and worldwide[11][12][13].  A recent Level I study investigating nearly 200 patients randomized between 3 groups (sham control, hyaluronic acid injections, and leukocyte-poor PRP injections) demonstrated superior patient-reported pain and functional outcome scores at 12-month follow-up in patients managed with PRP injections as opposed to the sham control injection group (normal saline only) and those managed with hyaluronic acid injections[14].  


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Physiology, Blood Plasma - Questions

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What is the approximate plasma volume in a 70 kg male?



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Removal of which component would identify a specimen as serum rather than plasma?



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Serum or plasma must be separated from cells within 2 hours of collection. Which of the following is an exception to this rule?



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Where are plasma proteins synthesized in adults?



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Which of the following plasma proteins contribute most to colloidal pressure?



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Which of the following constituents of plasma plays a major role in blood clotting?



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Physiology, Blood Plasma - References

References

Burnouf T, Modern plasma fractionation. Transfusion medicine reviews. 2007 Apr     [PubMed]
Heim MU,Meyer B,Hellstern P, Recommendations for the use of therapeutic plasma. Current vascular pharmacology. 2009 Apr     [PubMed]
Garcia-Martinez R,Noiret L,Sen S,Mookerjee R,Jalan R, Albumin infusion improves renal blood flow autoregulation in patients with acute decompensation of cirrhosis and acute kidney injury. Liver international : official journal of the International Association for the Study of the Liver. 2015 Feb     [PubMed]
Garcia-Martinez R,Caraceni P,Bernardi M,Gines P,Arroyo V,Jalan R, Albumin: pathophysiologic basis of its role in the treatment of cirrhosis and its complications. Hepatology (Baltimore, Md.). 2013 Nov     [PubMed]
Salerno F,Navickis RJ,Wilkes MM, Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis: a meta-analysis of randomized trials. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2013 Feb     [PubMed]
Traclet J,Delaval P,Terrioux P,Mornex JF, Augmentation therapy of alpha-1 antitrypsin deficiency associated emphysema. Revue des maladies respiratoires. 2015 Apr     [PubMed]
Wewers MD,Crystal RG, Alpha-1 antitrypsin augmentation therapy. COPD. 2013 Mar     [PubMed]
Gosselin R,Hawes E,Moll S,Adcock D, Performance of various laboratory assays in the measurement of dabigatran in patients receiving therapeutic doses: a prospective study based on peak and trough plasma levels. American journal of clinical pathology. 2014 Feb     [PubMed]
McLeod BC, Plasma and plasma derivatives in therapeutic plasmapheresis. Transfusion. 2012 May     [PubMed]
Huang Y,Liu X,Xu X,Liu J, Intra-articular injections of platelet-rich plasma, hyaluronic acid or corticosteroids for knee osteoarthritis : A prospective randomized controlled study. Der Orthopade. 2019 Jan 8;     [PubMed]
Varacallo M,Chakravarty R,Denehy K,Star A, Joint perception and patient perceived satisfaction after total hip and knee arthroplasty in the American population. Journal of orthopaedics. 2018 Jun;     [PubMed]
Varacallo MA,Herzog L,Toossi N,Johanson NA, Ten-Year Trends and Independent Risk Factors for Unplanned Readmission Following Elective Total Joint Arthroplasty at a Large Urban Academic Hospital. The Journal of arthroplasty. 2017 Jun;     [PubMed]
Varacallo M,Johanson NA, Total Knee Arthroplasty 2018 Jan;     [PubMed]
Hall MP,Band PA,Meislin RJ,Jazrawi LM,Cardone DA, Platelet-rich plasma: current concepts and application in sports medicine. The Journal of the American Academy of Orthopaedic Surgeons. 2009 Oct;     [PubMed]

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