Fluids and Functions of Blood

Fluids of the Body

• Cells are serviced by blood and interstitial fluid
• Blood is composed of plasma and blood cells, circulates, and transports various substances
• Interstitial fluid is found around cells, formed from blood filtration, and becomes lymph after entering lymphatic vessels
• Nutrients and oxygen diffuse from blood to interstitial fluid and then to cells
• Wastes move in the reverse direction

Functions of Blood

• Transportation: Blood carries oxygen, carbon dioxide, metabolic wastes, nutrients, heat, hormones, and medications
• Regulation: Blood helps regulate pH through buffers, body temperature by absorbing and carrying heat, and intracellular fluid composition
• Protection from Disease: Provides immunity and carries out inflmmation

Physical Characteristics of Blood

• It is thicker (more viscous) than water, and flows more slowly as a result
• Determined by the amount of blood cells, mainly RBCs
• Blood 'thinners' such as aspirin reduce clotting
• The blood temperature is 38°C
• The pH is around 7.4 (range 7.35-7.45)
• It constitutes 8% of total body weight
• Blood volume: 5 to 6 litres in average male or 4 to 5 litres in average female

Blood Composition

• Blood composition is 55% plasma and 45% formed elements (cells)
• The formed elements of cells contain 99% RBCs, less than 1% WBCs, and platelets (thrombocytes)
• Haematocrit is the percentage of total blood volume occupied by red blood cells
• Haematocrit values are 47% ± 5% for males and 42% ± 5% for females.

Blood Plasma

• It is over 90% water
• Proteins form 7% of plasma
• Albumin maintains blood osmotic pressure and helps transport lipid-soluble substances and some drugs
• Globulins are divided into alpha, beta, and gamma groups
  • Gamma globulins (immunoglobulins) are antibodies
• Fibrinogen takes part in blood clotting
• Only 2% of plasma are made up of electrolytes, nutrients, hormones, gases, and waste products

Blood Cells

• Red blood cells are referred to as erythrocytes
• White blood cells are referred to as leukocytes
• Granular leukocytes have small granules in the cytoplasm
  • Eosinophils have granules that stain orange-red
  • Basophils have granules that stain dark blue
  • Neutrophils have granules that remain in between, a pale lilac color
• Agranular leukocytes have no granules
  • Lymphocytes are T cells, B cells, and natural killer cells
  • Monocytes are phagocytic cells that transform into macrophages
• Platelets are called thrombocytes
  • Represent cell fragments, and originate through fragmentation of megakaryocytes in bone marrow

RBC structure and function

• Oxygen-carrying protein haemoglobin is what gives blood its red colour
• 1/3 of erythrocyte's weight is haemoglobin
• Biconcave disks increase surface area/volume ratio
• Shape provides flexibility for narrow passages like capillaries
• Lacking nucleus/organelles prevents cell division
• This limits energy production through anaerobic processes
• The normal RBC count for males is 5.4 x 1012/L
• The normal RBC count for females is 4.8 x 1012/L
• New RBCs enter circulation at a rate of 2 million/second
• Blood cells are often described by their appearance
  • Normocytic: Normal size (7-8μm)
  • Normochromic: Normal red colour
• Changes to RBCs in diseases such as anaemia can be described as
  • Macrocytic: larger sized RBCs
  • Microcytic: smaller-sized RBCs
  • Hypochromic: decreased red-coloured cells
  • Hyperchromic: deeper hue of red.

Full blood count reference ranges

• Haemoglobin for males should be 13.5-17.5 g/dL, and for females 12.0-16 g/dL
• Haematocrit for males should be 38-50%, and for females 34-44%
• The red blood cell count should be 4.3-5.9 x 1012/L for males, and 3.5-5.5 x 1012/L for females
• Mcan Corpuscular Volume (MCV) should be 80-100 fL
• Mean Corpuscular Haemoglobin (MCH) should be 27-32 pg
• Mean Corpuscular Haemoglobin Concentration(MCHC) should be 320-360 g/L
• Platelet count should be 150-400 x 109/L
• White Cell Count (WCC) should be 4.0-11.0 x 109/L
• Neutrophils should be 2.0-7.0 x 109/L
• Lymphocytes should be 1.0-3.0 x 109/L
• Monocytes should be 0.2-1.0 x 109/L
• Eosinophils should be 0.002-0.5 x 109/L
• Basophils should be 0.0-0.1 x 109/L

Platelet Physiology

• They are disc-shaped with no nucleus and a size of 2-4 mm
• The normal count of platelets is 150-400 x 109/L
• Platelets play a role in haemostasis, which is stopping bleeding (haemorrhage) of damaged blood vessels
• Involves these three steps
  • Vascular spasm, reflex constriction of the damaged blood vessel
  • Platelet plug formation occurs when platelets are activated in contact with damaged tissue. This process releases chemical mediators that speed up their adhesion, causing them to stick together
  • Blood clotting (coagulation), which is the formation of fibrin threads in a meshwork

Platelet Plug Formation

• Platelets don't typically stick together
• Damage to the endothelium exposes collagen that allows platelets to adhere
• A glycoprotein von Willebrand factor stabilises adhesion and activates platelets
• Chemical signals (ADP, serotonin, and thromboxane A2) are released by activated platelets
• Attracts more platelets, promotes further aggregation and vasoconstriction
• Platelet plugs block blood loss in small vessels, but are less effective in larger vessels

Blood Clotting

• Substances like Ca2+, clotting proteins produced in the liver (clotting factors I-XIII), and substances released by platelets work as clotting stimulants
• It is a cascade of reactions in which each clotting factor activates the next in a fixed sequence
• This results in the formation of fibrin meshwork
• The clotting cascade can be activated by
  • Extrinsic pathway: occurs in tissue trauma in the presence of tissue factor, also known as thromboplastin
  • Intrinsic pathway: occurs when platelets come in contact with damaged endothelium or foreign material Platelet activation is a crucial event

Clotting Continued

• Both the extrinsic and intrinsic pathways yield prothrombin activator, converging on the final common pathway, where prothrombin (factor II) is converted into thrombin
• Thrombin cuts fibrinogen (factor I) into smaller strands of fibrin
• Fibrin strands polymerize (bind together) to form a fibrin meshwork, which traps blood cells forming a blood clot
• The protein, fibrin stabilizing factor (XIII), helps reinforce the blood clot
• Blood clotting in the absence of bleeding is known as thrombosis, which can occur in both arteries and veins

Haematopoiesis

• Is the process of making RBCs
• In adults, it occurs in the red bone marrow of flat bones, ends of long bones and in lymphoid organs
• It depends on stem cells, which are the same for all formed elements
• About 100 billion RBCs are produced per day
• RBCs live for about 120 days
• Most blood cells types need to be continually replaced

Control of Red Blood Cell (RBC) production

• Requires iron, vitamin B12, and folic acid
• Depends of amount of oxygen
• Tissue hypoxia influences erythrocyte production
• At high altitude, air has less oxygen
• In anemic states (low haemoglobin in blood)
• In circulatory problems – reduced delivery of blood
• The kidneys respond to hypoxia by release of hormone erythropoietin (EPO), speeds up the production of new RBCs

RBC Oxygen Carrying Capacity

• Haemoglobin = globin + haeme
• can be denoted at Hb
• Globin is a protein with 4 polypeptide chains: normally 2 alpha and 2 beta.
• Haeme, a coloured molecule, is attached to each polypeptide chain
• Each haeme contains an iron ion (Fe2+) that can combine reversibly with 1 oxygen molecule
• Once oxygen is bound to haemoglobin it becomes oxyhaemoglobin
• 1 RBC carries 25 x 10° Hb
• Each haemoglobin molecule can carry 4 oxygen molecules
• Most of the O2 carried in the blood is in the form of oxyhaemoglobin
• Most haemoglobin is saturated with oxygen
• Haemoglobin transports 23% of total CO2 waste from tissue cells
• CO2 combines reversibly with amino acids on globin

Destruction of RBCs

• RBCs don't have a nucleus so they have limited repair ability
• RBC structure changes enough to be captured and engulfed in spleen, liver, & bone marrow, after 120 days
• After macrophages engulf the RBC, the cell undergoes hemolysis
• haemoglobin is broken into haeme and globin
• Globin is recycled into amino acids
• Iron is recycled for future RBCs
• Haem converted to bilirubin

ABO Blood Groups

• Blood type determined by the presence or absence of specific antigens (A and/or B) on their surface
• Genes coding antigens are on chromosome 9 and inherited from both parents
• ABO gene encodes an enzyme with glycosyltransferase activity, adds sugar molecules to red blood cells
• A allele adds N-acetyl galactosamine.
• B allele adds galactose.
• O allele does not modify the glycoprotein to add sugar.
• Resulting in production of antibody

Inheritance Patterns

• A and B alleles exhibit codominance, meaning that both alleles are expressed when present together. An individual with an AB genotype has both A & B antigens on their RBCs, expressing both alleles equally
• While A and B alleles are codominant, the O allele is recessive to both A & B alleles, and does not express antigens on RBCs
• AO genotype expresses the A antigen as the A allele is dominant over the O allele.

Agglutination and Haemolysis

• If your blood type is type A, you will have surface antigens for A and anti-B antibodies
• If your blood type is type B, you will have surface antigens for B and anti-A antibodies
• If your blood type is type AB, you will have surface antigens for both A and B with neither anti-A nor anti-B antibodies
• If you have type O you won't have A or B surface antigens, you will have both anti-A and anti-B antibodies
• You will create antibodies against antigens that you DO NOT have

ABO Typing

• All donated blood undergoes ABO blood typing
• Mixing incompatible blood can cause agglutination when the recipient's antibodies attack the donor's blood cells
• RBC antigens are called agglutinogens

Rhesus Factor

• Another important antigen on the surface of RBCs
• Blood cells containing antigen are Rh+
• Blood cells lacking antigen are Rh-
• Anti-Rh antibodies (known as anti-D) are only produced after exposure to the antigen
• problematic for a Rh+ male & Rh- mother to have children
• If bub is Rh+ & mum is Rh-, the mum may produce anti-D antibodies
• In subsequent pregnancy, mums anti-D may attack RBCs of bub, causing haemolytic disease of newborn

Frequency of Blood Types in Australia

• O+ 40%
• A+ 31%
• B+ 8%
• AB+ 2%

Blood types

• The body will create antibodies against ALL antigens that the blood type does NOT have
• Donor's blood may not be recognized

HDN

• Haemolytic disease of the newborn (HDN) is a condition where the pregnant woman's blood is incompatible with the fetus
• Rh- Mums receive the Anti-D during pregnancy and within 72 hours of giving birth
• Normally at ~28 and ~34 weeks gestation (as an antenatal prophylaxis)
• This neutralises the Rh+ antigen, and stops sensitisation
• The injection given slowly by deep intramuscular injection, intravenous can be adminstered
• Doses can also be given earlier in the pregnancy

Events

Can sensitise body to generate anti-D antibodies

• History can sensitise her body to generate anti-D antibodies: Ectopic Pregnancy Termination of Pregnancy Miscarriage Ultrasound Abdominal trauma Antepartum haemorrhage External cephalic version

Women

• Who are Rh+ do NOT receive the Rh(D) Immunoglobulin
• All of Australia’s anti-D plasma comes from a tiny pool of around 200 donors
• Special care and attention is provided to the mother and foetus, under the supervision of a obstetrician
• Early are made early-on regarding the concentration of the antibodies
• The foetus is managed to the best of the local health care’s requirements

Physiological

• Anemia
• Jaundice (Hyperbilirubinemia)
• Enlarged Spleen and Liver
• Erythroblastosis
• Hydrops fetalis