Hemostasis (Tim)

So, clotting is regulated by _______ formation

PAC

So, when a vessel ruptures, both pathways are activated, with ____ being very rapid in onset and begins the formation of the clot, while the _____ pathway will enhance this activity and clot formation

extrinsic, intrinsic

Thrombin, in addition to triggering clot formation, activates _____, which accelerates ______ function, which is an example of positive feedback

factor 5, factor 10

The fibrin mesh is loosely held together by _____ bonds until _____ comes in (from platelets) and forms the tightly-bound _______ in order to stabilize the clot

h bonds, factor XIII (fibrin stabilizing factor), covalent bonds

In response to a rupture, the blood vessels form a complex called the _________. The prothrombin activator complex is formed by ___, ____ and ____. PAC stimulates the conversion of ___ to _____. Thrombin converts _____ to _______ and the fibrin monomers polymerize to form an insoluble mesh.

prothrombin activator complex, factor X, factor V, calcium. Prothrombin (factor 2), thrombin (factor 2a), fibrinogen, fibrin

Intrinsic pathway is called so because everything needed to trigger clotting is present in the _____. All that is needed is exposure to _____. It all starts with ____, also called the _____, that is converted to _____ when exposed to ______ Factor 12 then activates factor ____, which then activates factor _____, which activates factor _____. Factor 8 then activates factor _____, which will form part of the ____. Factor __ and ____ come in to ____ factor 10's effect and form the PAC. PAC then converts ___ to ____, which converts ____ to ___ and activates the rest of the common pathway

blood, collagen, factor 12, hageman factor, active factor 12, collagen, factor 11, factor 9, factor 8, 10, PAC, 5, ca, enhance, prothrombin, thrombin, fibrinogen, fibrin

A hard clot is formed when connective mesh is formed. ____ forms the mesh and it is an insoluble protein made by proteolytic production from ______. 50 or more factors act to determine if fibrin is formed. Some are ____ and some are _____. The balance of the pros and cons determines if clotting occurs, and in a healthy state, the _____ predominate. With damage, the procoagulants are stimulated and ________ the anticoagulants.

Fibrin, fibrinogen, procoagulants, anticoagulants, anticoagulants, override

All these factors undergo ____, whereas one factor 12 can activate many factor 11s, and so on

amplification

Factor ____ actually does the conversion of ___ to ____, and factor __ and __ just enhance its activity in the PAC

10, prothrombin, thrombin, 5, ca

Vitamin K shortage is not very common and will lower factors __, __, __ and ___ and will result in ___ bleeding time. Liver disease like hepatitis, cirrhosis, etc, _____ bleeding time because many factors and plasma proteins are lowered bc they are produced by the liver.

2, 7, 9, 10

The fibrinolytic phase of hemostasis is phase ____, which is when we dissolve the clot. ______ also called fibrinolysin is the enzyme that breaks down clots. Plasminogen, also called ______, is converted to plasmin (fibrinolysin) by _________. Plasmin will then digest ______, fibrinogen, factors _________ and ______. So, plasmin digests the clot and triggers for the clot

4, PLasmin, profibrinolysin, fibrin threads, 5,7,8, prothrombin

Albumin is a smallish protein and is easily the most ____ of the plasma proteins. It functions in ____ regulation and is a really good ____ binder and binds things such as ffa, drugs, NTs, bilirubin, etc. Bilirubin, from hemoglobin catabolism is an ______ and it along with _____ and ____ are the primary blood antioxidants

abundant, osmotic,non-specific, anti-oxidant, uric acid, ascorbate

Platelets contain ___ and ____ that allows them to change their shape and plug holes. They contain ______ for making thromboxane. They also have _________ to help with clot formation. Lastly, they have _______ which stimulates endothelial and smooth muscle repair.

actin and myosin, prostaglandin synthase, fibrin-stablizing factor, platelet derived growth factor

Prothrombin is an ___ globulin made by the _______. _____ is necessary for prothrombin synthesis. If not present, we will still have a prothrombin form, but it will not produce a functional thrombin. Other factors that need vitamin K include:

alpha 2, liver, vitamin K factor 2 (prothrombin), factor 8, factor 9, factor 10

Beta 1 lipoproteins are present at a concentration similar to HDLs and these are known as the LDLs, aka the ____ cholesterol. These are huge in size, with MW of 20 million. 80-90% of the LDL is made of lipid, and the rest is apoprotein, typically _____. Function is to transport ____ and for ffa donation to ______ particularly ______. These also leak cholesterol as they make their way back to the liver, hence why they are called bad cholesterol

bad, b100, lipids, tissues, adipocytes,

Hemophilia is a genetic disorder mainly affecting males that prolongs ______ time and minor wounds may become life threatening. Type A hemophilia is the most ____ and resulting in low _____. treated by administering pure ____ which is expensive. Type B is about 15% of cases and is due to low factor ___. Type C is rare and caused by low factor ____.

bleeding, common, factor 8, factor 8, 9, 11

Lastly plasma proteins also function in blood clotting. Plasma are used to produce ____ as well as ____ clot formation.

blood clots, regulate

The secondary phase of hemostasis is necessary when the damage is more extensive. This is when stages 3 and 4 come in. Stage 3 is the coagulation phase which actually forms a ____ rather than just a platelet plug. This is produced by _____ crosslinking and a clot lasts for days. the 4th phase is the fibrinolytic phase which is the process of ____ the clot allowing _____ through the vessel after the damage is repaired.

clot, fibrin, dissolving, reperfusion

First stimuli of vasoconstriction is the nerve reflex. Pain receptors on the vessel wall are stimulated by _____ to the vessel and they conduct action potentials along ____ pathways to the CNS and then ___ axons will stimulate the vascular smooth muscle to contract

damage, afferent, efferent

PLatelets contain 2 forms of secretory vesicles. ______ contain the Adp and serotonin (5-ht) that are released when platelet is stimulated. the other secretory vesicle is ______ that contain platelet derived growth factor (pdgf) and platelet factor 4

dense bodies, alpha granules

With this loose plug, if the damage is minor, the plug will ___ as tissue repairs and ___ is hidden. If the damage is more severe, we will see fibroblasts invade, connective tissue form in the clot and see the formation of a ____ clot

dissolve, collagen, hard

Fibrinogen is a very large glycoprotein which is present at a concentration of 300% and it is the precursor to ____, which forms the mesh that holds clots together. Function is to form ___ in blood clot. Plasminogen is an intermediate sized protein present at low concentration, and it is the precursor to _____ aka ____ which dissolves the _____. Function is to ____ blood clots

fibrin, mesh, fibrinolysin, plasmin, blood clot, dissolve

Another anticoagulant mechanism is the _____ that coats the surface of the endothelium. This mucopolysaccharide, which is a ________, provides a _____/slick surface which tends to ___ platelets and clotting factor adhesion.

glycocalyx, proteoglycan (protein + gag), oily, repel

Everyday, healthy individuals have multiple ruptures of blood vessels and even these small ruptures can be very damaging in _____, where hemostasis is NOT timely. Hemostasis is critical to maintaining health by preventing ____ of blood when blood vessel is damaged.

hemophiliacs, exit

Alpha 1 lipoproteins are known as the ______ and are present at about 350-450 mg%. 40-70% of the structure is ___ and the rest is _____. They function to scavenge _______ and donate ____ to vldl and chylomicrons in order to _____ them. Alpha 1 lipoproteins are the good cholesterol

high density lipoproteins, lipid, apoprotein, cholesterol, apoprotein, activate

What causes PAC activation? Either the ___ of ____ pathway. Both of these will end up triggering the ____ pathway because they both end in the formation of PAC.

intrinsic, extrinsic, common

Transferring is an intermediate-sized glycoprotein present at about 40%mg and its function is to transport ___ in BLOOD. Ceruloplasmin is similar in size and concentration to transferring and function is transport ______ in the blood.

iron, copper

This thrombomodulin mechanism will ____ the extent to which the clots forms and prevent clotting from starting in areas outside the damaged part. So, to limit the size of the clot, we must keep active thrombin from getting too far from wound site. _____ will bind what escapes, but there are other things that limit thrombin circulation

limit, thrombomodulin

Thrombocytopenia is a disease whose name means _____ and will prolong ______. Treatment consists of whole blood or platelet ______. _____ can also help, because spleen removes platelets from the blood.

low platelets, bleeding time, transfusion, spleenectomy

Heparin, a very negative polysaccharide, is present at ____ levels in human blood. Synthesized and released by ______, and is most abundant in the ____ because lung clots here would be very dangerous. Heparin greatly increases ______ ability to bind ______. Heparin also binds to _____. In high pharmaceutical doses, heparin produces a nearly instant loss of thrombin

low, mast cells, lung capillaries, anti-thrombin 3's, thrombin, ca,

Platelets are derived from _____ in the bone ______. They contain no ____ so they constantly need to be replaced (constant turnover; lifespan-9-13 days). Their cell membranes are rich in ____ and platelets also contain many other structural metabolites.

megakaryocytes, marrow, nuclei, phospholipids

The next stimuli is the myogenic spasm. Damaged smooth muscle will ___ contract, even in absence of ___ stimuli or innervation. These smooth muscle cells can also stimulate neighboring smooth muscle cells to contract via ______. The 3rd stimulus that occurs to facilitate vasoconstriction is the humoral release. The release of paracrines from damaged cells and platelets arriving at the scene stimulate ___ of smooth muscle. These paracrines have a short ____ and only have local effects. These paracrine agent are _____, ____ and ______

naturally, external, gap junctions, contraction, half life, serotonin (5ht), thromboxane A, ADP

PLasma proteins also function in ____ regulation, where the physical presence of proteins, mainly _____, tends to suck water into the vasculature (tissue oncotic pressure), thereby maintaining blood volume. There is little to no protein in _____. Blood flows due to hydrostatic pressure provided by the ____. Plasma tends to ooze into the isf through capillary pores (capillary hydrostatic pressure) and the osmolarity of proteins counters this effect

osmotic, albumin, isf, heart,

Extrinsic pathway is when we need material from ___ the blood to trigger the activation of the PAC. Extrinsic pathway starts during tissue trauma and damaged cells release _______, or commonly known as ______. This has proteolytic activity, and it will combine with ___ and ____, and it is the ____ that will trigger the conversion of ______ to active ____. Then, ___ and ___ come in, enhance factor 10's activity to create the PAC to convert prothrombin to thrombin, and then fibrinogen to fibrin.

outside, thromboplastin, tissue factor, factor 7, ca, factor 7, factor 10, factor 10, factor 5, ca,

First phase of hemostasis is the vasoconstriction phase. The problem is that a rupture in a blood vessel will result in blood exiting the vasculature and entering the interstitium. This happens because blood flows forward while also pushing ____, keeping vessel inflated from ______ produced by contraction of the heart that moves blood all over the body. There are several stimuli for vasoconstriction.

outward, hydrostatic

Gamma-globulins are made by _____ derived from b-lymphocytes. These are glycoproteins which range in concentration from 700,1500mg%, depending on health, etc. These vary the most in concentration because they depend on health of person. Function of gamma-globulins is to be _____ and they recognize _____ of the foreign protein, dna/rna or polysaccharide, which is the ______

plasma cells, antibodies, epitope, antigen

Phospholipids in the platelets gives rise to ______ while the glycolipids in cell membrane cause platelets to ____ the endothelium and keep them free circulating.

platelet factor 3, avoid

As platelets clump together they form a ___ in the wound site. This is all that is needed to repair minor wounds that occur normally. These platelet plugs are not affected by _____ such as ___ and _______

plug, anti-coagulants, heparin, dicumarol

Thanks to these three stimuli, vasoconstriction occurs and this ____ velocity of blood flow through the wound site. This reduction in velocity decreases ____ and also makes damaged area less ______, which will facilitate phase 2 of hemostasis. Picture it like trying to build a dam in a torrential river vs a smooth one

reduces, blood loss, turbulent

ONce activated by coming in contact with the collagen, the platelet releases _____, ___ and ____. Specifically, the ____ promotes more platelets to clump at the site and activate

serotonin (5-ht), thromboxane A, adp, adp

Some anticoagulant mechanisms include the ____ of the endothelium thats provides no place for platelets to adhere and spontaneously activate. It also covers the _____ present in the tunica media. Roughening of this endothelium, like in _____, can trigger _____ formation (clumped platelets). These can break lose and occlude ____ downstream

smooth surface, collagen, atherosclerosis, thrombus, smaller vessels

Functions of plasma proteins include transport, where certain plasma proteins can _______(transferrins) and ____ (albumin) reversibly bind many chemicals and thereby transport them throughout the body like fatty acids, lipids, etc. Plasma proteins can also function as antibodies, such as the gamma globulins, and can recognize and bind to _____ aka the antigen as part of the immune response

specifically, nonspecifically, foreign material

Prothrombin is a small glycoprotein that is the precursor to _____ and thrombin is important in triggering ________ formation. Thrombin converts _____ to ____. Function of prothrombin is to trigger _______

thrombin, fibrin mesh, fibrinogen, fibrin, clot formation

Another anticoagulant mechanism is ______ protein found in the endothelium. It binds to ______, getting rid of any thrombin that escaped the clotting site. In addition, once the thrombomodulin binds to thrombin, the complex activates _______, which inactivates factor ___ and ____, which will prevent clotting.

thrombomodulin, thrombin, protein c, factor 5, factor 8

Anti-thrombotics like aspirin and NSAIDs prevent platelet aggregation (platelet plug) by inhibiting _____ synthesis by inhibiting _______. Anti-coagulants like ____ stimulate anti-thrombin 3. ________ inhibits vitamin K, as it is an inactive analog and so decreases ______. Thrombolytics ____ clots. Examples of these are ___ and _____ which break up clots that form. Used to treat stroke patients where clots and lodged in vessels

thromboxane a2,. cyclooxygenase, heparin, warfarin (coumadin), clotting factors, dissolve, streptokinase, urokinase

Plasminogen is trapped as the clot forms. INjured endothelium and neighboring tissue release ________. This is what converts plasminogen to plasmin. TPA is like a ticking time-bomb, which takes ___ to activate and begin converting ___ to ____. The clot then dissolves and if wound persists, new clot forms and process being again

tissue plasminogen activator (TPA), 1-2 days, plasminogen, plasmin

Most of the thrombin does not escape the clot because it is ____ in the fibrin mesh. ________% of thrombin remains trapped in clot. Anti-thrombin 3, an alpha globulin binds to ___ and inactivates it. _____ is handled this way (most of what escapes).

trapped, 85-90, thrombin, 10-15

Now that we have made the blood less turbulent, it is time for the next phase of hemostasis; platelet aggregation. Platelets do not usually clump in blood in a healthy state. The key to them clumping is the _____, which is the _______ of blood cells and contains the ____ that produces vasoconstriction. In addition to smooth muscle, it contains _____ and contact with collagen stimulates ______. Normally, platelets do not contact collagen (due to the inner later of vessel, endothelium), but when there is a laceration/hole in the vessel, we will see the platelets contact the collagen of tunica media and initiate platelet formation.

tunica media, middle layer, smooth muscle, collagen, platelets,

4 phases of hemostasis when vessel is damaged. The ____ and ______ are the only two necessary during ____ hemostasis when there is a minor wound. First is the vascular phase and this is where there is _____ proximal to the wound and this ________ blood flow to the damaged vessel by increasing _____. This occurs for minutes to hours. The second phase is the platelet phase, where platelets aggregate at the wound site, physically _____ the opening of the vessel and blocking blood loss

vascular phase, platelet, primary, vasoconstriction, decreases, resistance, blocking