Constituents of the blood Flashcards
Erythrocytes
Red blood cells
Erythrocyte function
Gas transport - carry oxygen from lungs to tissue + carbon dioxide from tissues to lungs, where it’s breathed out
Erythrocyte histological appearance
Rounded, bright pink-stained cells. Paler in centre than periphery. Oxygen carrying haemoglobin binds to acidic eosin dye –> acidophilia (bright pink colour)
Acidophilia
Bright pink colour
Erythrocyte diameter and shape
6.5-8.5 micrometres.
Biconcave disk.
Erythrocyte form/function
Biconcave disk gives high SA:volume ratio - rapid diffusion for gas exchange
Structure of erythrocytes
No nucleus - lost in formation.
Cell membrane surrounding electron-dense cytoplasm (containing haemoglobin)
No organelles - lost in differentiation
Erythrocyte cytoskeleton
Filamentous skeleton of protein spectrin anchored to cell by band 3 protein, ankyrin, band 4 protein.
Short actin piecies (15 actin monomers long) linking spectrin to band 4 proteins.
Maintains shape.
Metabolic activity of erythrocytes
Derive energy from anaerobic metabolism of glucose, and from ATP generation by hexose monophosphate shunt.
Life-span of erythrocytes
100-120 days in circulation
Production of erythrocytes (site)
Red bone marrow
Reticulocyte
Young erythrocytes in bone marrow still containing ribosomes - produces web-like reticular appearance. Lose ribosomes ~ 1 day in circulation.
Factors in erythrocyte ageing
Diminishing efficiency of ion pumping
Less deformable –> can’t negotiate microcirculation
Disposable of erythrocytes
Spleen (most active), liver and bone marrow. Aged and defective
Breakdown product of erythrocyte breakdown
Bilirubin - returned to circulation. Gives plasma its yellow colour.
Iron
Element to which oxygen binds to on haemoglobin molecule
Iron loss
Urine, faeces, sweat, cells, menstrual blood
Iron replenishment
Ingestion of iron-containing foods
Iron deficiency
Disruption of body’s iron balance - inadequate haemoglobin production
Anemia
Hemochromatosis
Excess of iron in body. Abnormal iron deposits + damage in organs: liver, heart, pituitary gland, pancreas, joints
Homeostasis of iron
Intestinal epithelium. Active absorption of iron from food. Fraction absorbed is increased or decreased in negative feedback.
Storage of iron
Bound up in protein ferritin, in liver.
Proportions of iron in body
50% in haemoglobin, 25% in heme-containing proteins (cytochromes), 25% in liver
Recycling of iron
Iron from erythrocyte breakdown is transferred to plasma, then bound to iron-transport plasma protein: transferrin.
Transferrin
iron-transfer plasma protein, delivers almost all of iron to bone marrow.
Folic acid - where it’s found and its function in synthesis
Vitamin in leafy plants, yeast, the liver.
Synthesis of thymine –> needed for DNA formation and cell division.
Consequences of lack of folic acid
Impairment of cell division
Extreme effects on rapidly proliferating cells (e.g erythrocytes) - fewer erythrocytes produced.
What else is required for production of normal erythrocyte numbers?
Vitamin B12.
Vitamin B12 - what is it, where is it found
cobalt-containing molecule (cobalamin).
found in animal products
Vitamin B12 and erythrocytes
Required for action of folic acid.
Absorption of vitamin B12
from GI tract by intrinsic factor (protein secreted by stomach)
Intrinsic factor
Protein secreted by stomach. Absorbs vitamin B12
Lack of intrinsic factor consequences
vitamin B12 deficiency, erythrocyte deficiency: pernicious anemia
Erythropoiesis
Normal erythrocyte production
Direct control of erythropoiesis
Erythropoietin
Erythropoietin secretion
Small group of hormone-secreting connective tissue cells in the kidney
Erythropoietin function
Acts on bone marrow to stimulate proliferation of erythrocyte progenitor cells and differentiation into mature erythrocytes
Flow chart of erythropoietin production
Decreased O2 delivery to kidneys
Increased erythropoietin secretion by kidneys
Increased plasma erythropoietin
Increased production of erythrocytes by bone marrow
Increased blood Hb concentration
Increased blood O2 carrying capacity
Restoration of O2 delivery
Which other hormone stimulates production of erythropoietin?
Testosterone - higher hematocrit in males.
Types of leukocytes and their proportions
Neutrophils 40-75% Eosinophils 5% Basophils 0.5% Lymphocytes 20-50% Monocytes 1-5%
Increased proportions
If increased activity is required, number and proportion rises accordingly
Granulocytes/Myeloid cells
Neutrophils, eosinophils and basophils have prominent granules in their cytoplasm.
Originate from bone marrow.
Polymorphonuclear leukocytes/Polymorphs
Neutrophils - multilobed nucleus
Lymphocytes and monocytes classification as leukocytes
Both are constituents of blood and originate from bone marrow.
Lymphocytes and monocytes location
Lymph nodes and spleen
Lymphocytes and monocytes transformation
Monocytes -> macrophages
Basophils -> mast cells
In tissues
Neutrophils circulation
circulate in resting state, w/ activation they leave blood and enter tissues
Neutrophils functions
Phagocytic. Ingest and destroy invading microorganisms in tissues. Early stages of acute inflammatory response to tissue injury. Major constituent of pus.
Neutrophil nucleus
2-5 lobes, joined by fine strands of nuclear material.
Lobulation develops w/ cell maturity.
Diameter of neutrophils
12-14 micrometres
Chromatin in neutrophils
Highly condensed - low degree of protein synthesis
Neutrophils in females
In 3% of females, nuclei exhibit small, condensed nuclear appendage - quiescent X chromosome (Barr body)
Granules
Membrane-bound vesicles
Primary granules in neutrophils - contents, appearance, formation
Similar to lysosomes
First to appear in formation, number falls in development
Large and electron dense
Contain acid hydrolases, antibacterial and digestive substances (myeloperoxidase)
Detection of myeloperoxidase
Peroxidase stain
Secondary granules in neutrophils - diameter, contents
Specific to neutrophils
0.2-0.8 micrometres
2x numerous as primary
substances involved in mobilisation of inflammatory mediators and complement activation
Tertiary granules contents and function
Contain enzymes secreted into extracellular environment
Insert glycoproteins into cell membrane - promotes cellular adhesion, phagocytic process
How do leukocytes leave vessels?
Stick to endothelium lining capillaries and pass into tissues by traversing vessel wall
Mediation of adhesion of leukocytes to endothelium
Mediated by complementary cell adhesion molecules expressed on leukocyte and endothelium surface
Movement of leukocytes during disease states
Cytokines activate leukocytes and endothelium - high expression of adhesion molecules, firm sticking. Further cell signals make leukocytes motile - migrate into tissues.
Contents of neutrophils
Few organelles apart from granules. Few RER and free ribosomes, remnants of Golgi complex is involved in granule packaging. Few mitochondria (50% energy needs). Antioxidants to destroy toxic peroxides
Activated neutrophils
Need to be able to function in devascularised tissue (low O2 and glucose)
Abundant glycogen for anaerobic metabolism (glycolitic pathway or hexose monophosphate shunt)
Hexose monophosphate shunt
Mainly to generate microbicidal oxidants, and anaerobic metabolism
Phagocytosis
Cells ingest extracellular particles for destruction
Chemotaxins
Chemicals - degradation products of complement, products leaking from dead cells, bacterially derived polysaccharides in extracellular space
Neutrophil motility
Derived from assembly and disassembly of cellular actin filaments
Death of neutrophils
Die soon after phagocytosis, as the high energy dependent process uses up glycogen reserve. Lysosomal enzymes are released into extracellular space -> liquefaction of adjacent tissue
Pus
Collection of dead neutrophils, tissue fluid and abnormal material
Neutrophil membrane receptors
for Fc portion of antibodies, complement factors bound to foreign particles, bacterial polysaccharides
1st step of phagocytosis
Neutrophil binds to abnormal particle via receptors. Pushes out pseudopodia to surround particle - driven by assembly and disassembly of actin filaments
2nd step of phagocytosis
Pseudopodia fuse to completely enclose abnormal particle - forms an endocytotic vesicle. Special proteins allow final sealing of membrane.
Phagosome
Enclosed particle in endocytotic vesicle
3rd step of phagocytosis
Phagosome fuses w/ primary granules - discharge lysosomal enzymes. Bacterium - killing is enhanced by hydrogen peroxide and superoxide is generated by reduction of oxygen by respiratory burst oxidase (RBO)
RBO
respiratory burst oxidase - membrane enzyme which generates superoxide when reducing oxygen. During killing of a bacterium by hydrogen peroxide
Foreign particle destruction
Formation of residual body containing degraded material
