Histology of Platelets and Capillaries Flashcards
Megakaryocyte/Erythrocyte Progenitor (MEP)
Megakaryocyte/Erythrocyte progenitor (MEP) cell makes magakaryoblast which matures into megakaryocyte
Thrombopoietin: stimulates megakaryocyte maturation from the liver and kidney
Megakaryocyte/Erythrocyte Progenitor (MEP) cell makes proerythroblast, basophilic erythroblast, polychromatophilic erythroblast, orthochromatophilic erythroblast, reticulocyte, and then RBC
Megakaryoblast
Basophilic cytoplasm; no specific granules;
Endomitosis: chromosomal replication without nuclear or cytoplasmic division.
16N most common form.
Non-Platelet Forming Megakaryocyte
Increasing amount of cytoplasm;
Decreased basophilia;
Appearance of many azurophilic granules;
Cytoplasm divided by demarcation membranes
Platelet Forming Megakaryocyte
Next to bone marrow sinusoids; Extend proplatelets into lumen Shed 4,000-8,000 platelets/mega Nucleus is multi-lobed - 16 or 32N Platelet demarcation channels = invaginations of plasma membranes, which extend cytoplasm in sinusoid to make proplatelets and platelets
Platelet Peripheral Zone
Peripheral zone (hyalomere): consists of plasma membrane and glycocalyx (glycoproteins for coagulation factors can adhere and other platelets can adhere to each other, GAGS, and fibrinogen can be converted to fibrin for secondary clot)
Platelet Structural Zone
Structural zone (hyalomere): supports cell membrane; helps maintain disk-shape; : consists of microtubules, actin, and myosin to support cell membrane and disc shape of platelet; actin and myosin helps in contraction (high concentration) to adhere to BV walls and extend filopodia to attach and when clot to contact
Platelet Membrane System
Membrane systems: composed of membranes/channels canaliculi, and have granules in the cell which fuse with membranes of canalicular system for granule release for granules get to outside; come from demarcation channels from megakaryocyte = open to outside
Dense tubular: store calcium ions for clotting; are not open to outside
Organelle zone: mitochondria, glycogen, granules, etc.
Membrane Systems:
- open canalicular system – from platelet demarcation channels; facilitates release of granule contents
- dense tubular system – storage of Ca++ ions; not connected to surface
Platelet Organelle Zone (Granulomere)
Organelle zone (central): mitochondria, glycogen, lysosomes, granules
Alpha granules: largest and most numerous; fibrinogen convert to fibrin; growth factors stimulate regeneration of damaged areas
Delta granules: D for delta, denser, and ADP; ADP help more platelets to aggregate with each other; serotonin is a vasoconstrictor to close off injured vessels
Lambda: dissolve the clot with lysosomes
Glycogen granules are used for energy
The open canalicular system facilitates release of granule contents to the platelet’s exterior
Hemostasis and vWF
Von Willibrand factor: released by damaged endothelial cells so platelets attach; reactive surface for adhesion and cleaving of fibrinogen to fibrin for permanent clot
Platelet needs to adhere to injured blood vessel
Lining of endothelial on basement membrane (lamina) and under that is collagen fibers and laminin glycoproteins and larger vessels have smooth muscle
When break in vessel/endothelial the collagen (IV) in subendothelial space will be exposed and glycoclayx will help bind; platelet extend pseduopods to walls and endothelial cells release von Willibrand factor that attach to glycoprotein to help platlet adhere
Adhesion, Aggregation, and Degranulation of Platelets
Adhesion – to subendothelial collagen
Aggregation – to other platelets via glycocalyx proteins
Degranulation – exocytosis of granules:
Serotonin - vasoconstriction
ADP – attracts more platelets, stims degranulation
Thromboxane A2 – from plasma membrane; promotes aggregation, degranulation, vasoconstriction
Thromboxanes are released from the plasma membrane via the arachidonic acid pathway.
The enzyme cyclooxygenase (COX) converts arachidonic acid to thromboxane.
Inhibition of Clot Formation
Thomboxin from plasma membrane comes from phospholipids and they are made into arachidonic acid and acted on cyclooxygenase to convert to thromboxin
Non steroidal will inhibits the COX and prevent formation of thromboxane and no clot formation – baby aspirin to prevent clots
Coagulation
Glycocalyx - a surface for the conversion of soluble fibrinogen into fibrin
Fibrinogen binds to integrins; bridges platelets
Thrombin cleaves fibrinogen into fibrin
Fibrin is cross-linked to make 2ndary hemostatic plug via factor XIII
Plasminogen incorporated into fibrin meshwork
Fibrinolysis
Plasminogen is a zymogen produced by the hepatocytes of liver. Zymogens are enzymes that are produced in an inactive form
t-PA is released only by damaged endothelial cells. Once the damage is repaired, t-PA release stops and the repaired cells release plasminogen activator inhibitors.
Endothelial cells release t-PA = converts plasminogen to plasmin to dissolve the clot
Also hydrolytic granules (lambda)
t-PA used therapeutically = coronary arteries clot – t-PA will dissolve the clot to prevent MI
Capillary Structure
3-7 um diameter
Single layer of endothelium + basement membrane
Pericyte – mesenchymal stem cells around capillaries and venules
Smaller than RBC, but that’s ok because the RBC plasma membrane is flexible
Pericytes can occur adjacent to the basal lamina. The pericyte itself is enveloped by its own basal lamina that is continuous with the BL of the endothelium. Pericytes are undifferentiated stem cells that can give rise to endothelial or smooth muscle cells during development or wound healing.
Capillary Permeability
Depends on tight junctions between endothelial cells
Increased by histamine during inflammation
Simple diffusion: oxygen, carbon dioxide
Active transport: glucose, amino acids, electrolytes
Pinocytosis: non-specific ingestion of water, small molecules, soluble proteins
Histamine can loosen tight junctions
Gases can diffuse easily, but other things need active transportation like glucose
Water and small molecules that solubilize in water
