LAB-INDICATORS-ACTION PLAN
Platelets must be counted in the blood if normal, we proceed to the tests that follow
3. TEST IN BLEEDING DISORDERS
3.1 BLEEDING TIME
This tests platelet and vessel wall interaction plus plug
formation.
This may be increased in thrombocytopenia, altered
Platelet function, Von Will brands disease factor V deficiency
and hypofibrinogenaemia .
It should not exceed 3-5 minutes.
3.2 PROTHROMBIN TIME
This test measures the efficiency of the extrinsic pathway.
Tissue source thromboplastin and calcium are added to citrated
plasma and the clotting time noted.
3.3 PARTIAL PROTHROMBIN TIME
This is a screening test for assessing the intrinsic pathway.
The range of normal varies and has to be compared with normal
control.
THROMBIN TIME (TT)
3.4 Tests Fibrinogen activity
The clotting time of patients’ plasma following addition of
standard controls are run.
Failure of clotting is evidence of low finbrinogen.
Excessive fibrinolysis can also prolong the thrombin time.
4 BLOOD COMPONENTS IN CLINICAL USE
4.1 PLATELET RICH PLASMA (PRP)
This is prepared by slow centrifugation of fresh whole blood.
Platelet concentrate is prepared by centrifuging PRP at 1500 rpm
for 20 minutes.
It can be stored and the platelet activity is preserved for seven days.
Platelets transfusions are indicated in cases of
* Thrombocytopenia
* Altered platelet functions
In general, platelets should not be given unless:
* There is micro vascular bleeding
* Patient of low count is for surgery
* Platelet count falls to below 10,000
After each unit, platelet count should rise by 5000/cmm at 1
hour.
4.2 Leukocyte concentrate
This is indicated in patients with granulocytopenia (<500/mm)
patient with infection (blood culture positive) with no response
to antibiotics.
Daily transfusions are required till counts exceed 1000/cmm.
4.3 Fresh Frozen Plasma (FFP)
This is normal plasma containing Citrate and is used in liver
disease and DIC.
This is indicated in a number of cases of coagulopathies with
proven deficiency of clotting factors.
This may be met with in:
* Liver dysfunction
* Congenital disorders
* Transfusion related deficiency
In cases of investigation documented factor deficienies.
Alternatives used are albumin, hetastarch.
4.4 Cryoprecipitate
If frozen plasma is brought to a temperature of 4oC white
Cryoprecipitate will seperate out.
This is rich in factor VIII and can be stored at -40oC.
The concentrate contains factor VII, fibrinogen, vWF.
This is indicated in Hemophilia, Von Wilhbrand's disease
Hypofibrinogenemia.
It may also help to treat uremia bleeding and DIC.
4.5 Packed RBC
A stable asymptomatic patient should not receive transfusion only
because haematocrit is below 30%.
Each unit of packed cell raises haematocrit by 2-3%
4.6 Washed RBC
Are indicated in patients who cannot tolerate plasma, leucocytes
and platelet debris.
These are patients with fever or renal failure
4.7 Deglycerised RBC
Deglycerised RBCs of rare blood groups can be stored for 3 years
at -65oC.
When they are required they are thawed, washed and transfused.
Any questions be sent to drmmkapur@gmail.com
Thursday, May 27, 2010
Saturday, May 22, 2010
BLEEDING IN OTHER DISORDERS
2.4.2 RENAL FAILURE
Uraemia causes reversible bleeding disorder related to platelet
dysfunction.
There is as a result reduced platlet aggregation and adhesion.
There is also a reduction in platlets factor II and prolonged bleeding time.
The intravenous adminstration of desmopressin 0.3 ug/kg helps to
stop bleeding.
Cryoprecptitate also help to control the bleeding disorders.
Conjugated estrogens also of use in uremia bleeding disorders.
A vast number of etiologic agents have been identified here and
must be kept in mind when a patient presents with a bleeding
tendency.
**Acquired Disorders
Vitamin K deficiency
The causes of vitamin K deficiency are many.
Dietary intake may be poor, or the intake may be adequate but malabsorbed.
Vitamin K is a fat soluble vitamin, so any factor that causes decreased fat emulsification by bile salts can lead to malabsorption (e.g. biliary obstruction, decreased bile salt formation cholestasis, biliary fistula).
Antibiotic causes include oral antibiotics that can kill vitamin K producing bacteria in the gut, or cephalosporin antibiotics containing the N methylthiotetrazole side chain (e.g. cefoperazone, cefotaxime, cefamandole, moxalactam).
Other etiologies include parenteral alimentation without vitamin K supplementation, renal insufficiency, and hepatic dysfunction.
Vitamin K is a necessary cofactor in the y-carboxylation of glutamate residues of factors II, VII, IX and X as well as protein C and protein S. As these factors are referred to as the vatimin K-dependent factors. Without vitamin K, these coagulants cannot bind calcium properly and thus are not active.
Treatment
Vitamin K may be given orally or parenterally to correct coagulopathy form deficiency or to reverse the effects of warfarin.
Anticoagulant Drugs
Drugs that affect hemostasis are abundant and their numbers increase each year. More detailed information on hemoactive durgs can be found later in this chapter.
I Thrombocytopenia
Thrombocytopenia is generally defined as a platelet count less than 100,000/mm3 .
Bleeding is more common after surgery or injury in cases with counts from 50,000 to 100,000 mm3
Spontaneous bleeding usually does occurs with count below 20,000 and is common with count below 10,000.
The etiology of thromboeytopenia may be
- Decreased production of platelets
- Increased use, consumption or sequestration of platelets;
- Dilution
Decreased production may occur with various oncologic disorders or after chemotherapy. Consumption of platelets may occur in sepsis, disseminated intravascular coagulation (DIC), or thrombotic thrombocytopenic purpura, and sequestration can occur in the spleen.
Dilutional thrombocytopenia is possible after massive transfusion.
Many drugs can cause thrombocytopenia through an immune mechanism, antibodies are formed to platelet glycoproteins. These drugs are quinidine, sulfa drugs histamine antagonists oral hypoglycemies, gold salts, rifarnpin, and heparin.
The most common of these is heparin.
Chronic alcohol consumption may lead to alcohol induced thrombocytopenia.
Clinical
Clinical manifestations of thrombocytopenia include cutaneous petechiae or purpura, cucosal bleeding, easy bruising, and excessive bleeding after surgery or injury.
Treatment
Management involves correcting or reversing the underlying cause if found. Transfusion of platelet concentrates is indicated for active bleeding associated with thrombocytopenia, and to keep platelet counts above 10,000 to 20,000/ mm3.
If an invasive procedure or surgery is necessary in a thrombocytopenic patient, transfusion is most beneficial in providing hemostasis when given just before or during the procedure.
Multiple platelet transfusions often lead to formation of alloantibodies, thus decreasing the efficacy of repeated administration. Platelet transfusion is not indicated for empiric or prophylactic treatment during massive transfusion or resuscitation, unless there is clinical evidence of microvascular bleeding, or a prolonged bleeding time.**
Any questions be sent to drmmkapur@gmail.com
Uraemia causes reversible bleeding disorder related to platelet
dysfunction.
There is as a result reduced platlet aggregation and adhesion.
There is also a reduction in platlets factor II and prolonged bleeding time.
The intravenous adminstration of desmopressin 0.3 ug/kg helps to
stop bleeding.
Cryoprecptitate also help to control the bleeding disorders.
Conjugated estrogens also of use in uremia bleeding disorders.
A vast number of etiologic agents have been identified here and
must be kept in mind when a patient presents with a bleeding
tendency.
**Acquired Disorders
Vitamin K deficiency
The causes of vitamin K deficiency are many.
Dietary intake may be poor, or the intake may be adequate but malabsorbed.
Vitamin K is a fat soluble vitamin, so any factor that causes decreased fat emulsification by bile salts can lead to malabsorption (e.g. biliary obstruction, decreased bile salt formation cholestasis, biliary fistula).
Antibiotic causes include oral antibiotics that can kill vitamin K producing bacteria in the gut, or cephalosporin antibiotics containing the N methylthiotetrazole side chain (e.g. cefoperazone, cefotaxime, cefamandole, moxalactam).
Other etiologies include parenteral alimentation without vitamin K supplementation, renal insufficiency, and hepatic dysfunction.
Vitamin K is a necessary cofactor in the y-carboxylation of glutamate residues of factors II, VII, IX and X as well as protein C and protein S. As these factors are referred to as the vatimin K-dependent factors. Without vitamin K, these coagulants cannot bind calcium properly and thus are not active.
Treatment
Vitamin K may be given orally or parenterally to correct coagulopathy form deficiency or to reverse the effects of warfarin.
Anticoagulant Drugs
Drugs that affect hemostasis are abundant and their numbers increase each year. More detailed information on hemoactive durgs can be found later in this chapter.
I Thrombocytopenia
Thrombocytopenia is generally defined as a platelet count less than 100,000/mm3 .
Bleeding is more common after surgery or injury in cases with counts from 50,000 to 100,000 mm3
Spontaneous bleeding usually does occurs with count below 20,000 and is common with count below 10,000.
The etiology of thromboeytopenia may be
- Decreased production of platelets
- Increased use, consumption or sequestration of platelets;
- Dilution
Decreased production may occur with various oncologic disorders or after chemotherapy. Consumption of platelets may occur in sepsis, disseminated intravascular coagulation (DIC), or thrombotic thrombocytopenic purpura, and sequestration can occur in the spleen.
Dilutional thrombocytopenia is possible after massive transfusion.
Many drugs can cause thrombocytopenia through an immune mechanism, antibodies are formed to platelet glycoproteins. These drugs are quinidine, sulfa drugs histamine antagonists oral hypoglycemies, gold salts, rifarnpin, and heparin.
The most common of these is heparin.
Chronic alcohol consumption may lead to alcohol induced thrombocytopenia.
Clinical
Clinical manifestations of thrombocytopenia include cutaneous petechiae or purpura, cucosal bleeding, easy bruising, and excessive bleeding after surgery or injury.
Treatment
Management involves correcting or reversing the underlying cause if found. Transfusion of platelet concentrates is indicated for active bleeding associated with thrombocytopenia, and to keep platelet counts above 10,000 to 20,000/ mm3.
If an invasive procedure or surgery is necessary in a thrombocytopenic patient, transfusion is most beneficial in providing hemostasis when given just before or during the procedure.
Multiple platelet transfusions often lead to formation of alloantibodies, thus decreasing the efficacy of repeated administration. Platelet transfusion is not indicated for empiric or prophylactic treatment during massive transfusion or resuscitation, unless there is clinical evidence of microvascular bleeding, or a prolonged bleeding time.**
Any questions be sent to drmmkapur@gmail.com
Monday, May 17, 2010
DIC BY ANOTHER NAME
Consumptive Coagulopathy (PATH PHYSIOLOGY)
EVENTS LEADING TO THE EVENTS
**In certain conditions, bleeding is caused by a decrease is platelets and / or coagulation factors resulting from their USE UP in the blood vessels, a condition known as consumptive coagulopathy. Also called DIC
Rapid fibrin deposition occurs, decreasing the fibrinogen level, and also platelets due to trapping causing thromboeytopenia.
There is recent data showing that the receptor on the liver hapatocytes are responsible for
Depleting platelets and other factors.
Hypofibrinogenemia concurrent with thrombocytopenia in a bleeding patient is good evidence for a consumptive coagulopathy.
Fibrinolysis is induced, resulting in increased fibrin degradation products in the blood.
There are many etiologies of consumptive coagulopathy, with the principle example being the syndrome of DIC. The distinction between DIC and the other etiologic conditions listed below is ill defined, and one or more of the processes may be overlapping.
1. Sepsis. These conditions are a common cause of postoperabive thrombocytopenia. The mechanism is unclear, may is part be due to endotoxin-induced aggregation and destruction of platelets in the microvasculature or by direct activation of the coagulation cascade.
Also APC is deficient and so formation of microthrombi is not inhibited.
2. Shock, Trauma, Burns, and Pancreatitis.
These conditions cause release of thromboplastic substance that increase thrombin formation and consumption of coagulation factors. They also can lead to thrombocytopenia. In addition, inadequate tissue perfusion incites the inflammatory response, which leads to coagulopathy.
3. Traumatic Brain Injury. Injured brain tissue releases its rich stores of thromboplastin, which leads to hypercoagulability by accelerating fibrin formation and microvascular thrombosis. Coagulation sustrates are consumed and further clotting is impaired.
4. Obstetric Emergencies. Placental abruption, amniotic fluid embolism, dead fetus, eclampsia, septic abortion, and hydatidiform mole all can cause release of thromboplastic substances that increase thrombin formation and consumption of coagulation factors.
5. Disseminated Intravascular Coagulation. DIC is an acquired coagulation disorder that involves diffuse activation of the coagulation system, with fibrin deposition in the microvasculature, platelet aggregation, and thrombosis.
The severity ranges from subelinical or low grade to serve and life threatening.
Clinically DIC is manifested by generalized bleeding, and end-organ failure results form the diffuse microvascular thrombosis.
The more severe form can lead to multiple organ system failure and death. Mortality is increased in septic or severely injured patients with DIC.
A variety of clinical conditions are associated with DIC. In addition to all of the process listed 1 to 4 DIC may be associated with massive transfusion, hemolysis liver discase, and malignancy (including leukemis).
The pathophysiologic process in DIC is limited through inflammatory mechanisms and cytokines, especially interleukin-6.
The systemic formation of fibrin results form three mechanisms.
-First TF activated factor VII, and the TF factor VIIa complex mediates formation of thrombin, with subsequent conversion of fibrinogen to fibrin and activation of platelets.
-Second, the natural anticoagulant mechanisms operating via antithrombin III (ATIII), protein C and TF pathway inhibitor all are impaired in DIC. This leads to a shift in the hemostatic balance toward thrombosis.
-Finally, fibrin clearance is decreased because of a relative excess of PAI-I(plasmin activator inhibiter), which inhibits plasmin formation and fibrinolysis.
Diagnosis of DIC is made by the combination of clinical finding and certain supportive laboatory tests. There is no specific test that confirms or rules out the diagnosis. Clinically one suspects DIC in paitents with a generalized coagulopathy, bleeding and the presence of an inciting factor or disease associated with DIC.
The patient usually has a low or decreasing platelet count and prolonged PF/PTT. FSPs may be present in the plasma and coagulation inhibitors such as ATIII may be deficient.
Fibrinogen levels may be low in severe DIC, but, because fibrinogen is an acute phase reactant, its production is increased as part of the stress response, and levels may be normal.
The D-dimer assay is the most sensitive test for DIC, being abnormal in up to 94% of patients with a diagnosis of DIC.
In many patients with coagulopathy who are suspected of having DIC, hypothermia needs to be considered as the primary etiology of the bleeding disorder, especially if sepsis is not present.
Treatment of DIC
Treatment is of the underlying disease process is essential.
Symptomatic treatment can be tried but is futile if the underlying disease is not treated at the same time.
Several specific strategies have been investigated as therapy of DIC.
Anticoagulation has been used as an attempt to halt the underlying hypercoagulation in DIC.
Currently there have been no controlled studies showing any benefit of.**
Any questions be sent to drmmkapur@gmail.com
EVENTS LEADING TO THE EVENTS
**In certain conditions, bleeding is caused by a decrease is platelets and / or coagulation factors resulting from their USE UP in the blood vessels, a condition known as consumptive coagulopathy. Also called DIC
Rapid fibrin deposition occurs, decreasing the fibrinogen level, and also platelets due to trapping causing thromboeytopenia.
There is recent data showing that the receptor on the liver hapatocytes are responsible for
Depleting platelets and other factors.
Hypofibrinogenemia concurrent with thrombocytopenia in a bleeding patient is good evidence for a consumptive coagulopathy.
Fibrinolysis is induced, resulting in increased fibrin degradation products in the blood.
There are many etiologies of consumptive coagulopathy, with the principle example being the syndrome of DIC. The distinction between DIC and the other etiologic conditions listed below is ill defined, and one or more of the processes may be overlapping.
1. Sepsis. These conditions are a common cause of postoperabive thrombocytopenia. The mechanism is unclear, may is part be due to endotoxin-induced aggregation and destruction of platelets in the microvasculature or by direct activation of the coagulation cascade.
Also APC is deficient and so formation of microthrombi is not inhibited.
2. Shock, Trauma, Burns, and Pancreatitis.
These conditions cause release of thromboplastic substance that increase thrombin formation and consumption of coagulation factors. They also can lead to thrombocytopenia. In addition, inadequate tissue perfusion incites the inflammatory response, which leads to coagulopathy.
3. Traumatic Brain Injury. Injured brain tissue releases its rich stores of thromboplastin, which leads to hypercoagulability by accelerating fibrin formation and microvascular thrombosis. Coagulation sustrates are consumed and further clotting is impaired.
4. Obstetric Emergencies. Placental abruption, amniotic fluid embolism, dead fetus, eclampsia, septic abortion, and hydatidiform mole all can cause release of thromboplastic substances that increase thrombin formation and consumption of coagulation factors.
5. Disseminated Intravascular Coagulation. DIC is an acquired coagulation disorder that involves diffuse activation of the coagulation system, with fibrin deposition in the microvasculature, platelet aggregation, and thrombosis.
The severity ranges from subelinical or low grade to serve and life threatening.
Clinically DIC is manifested by generalized bleeding, and end-organ failure results form the diffuse microvascular thrombosis.
The more severe form can lead to multiple organ system failure and death. Mortality is increased in septic or severely injured patients with DIC.
A variety of clinical conditions are associated with DIC. In addition to all of the process listed 1 to 4 DIC may be associated with massive transfusion, hemolysis liver discase, and malignancy (including leukemis).
The pathophysiologic process in DIC is limited through inflammatory mechanisms and cytokines, especially interleukin-6.
The systemic formation of fibrin results form three mechanisms.
-First TF activated factor VII, and the TF factor VIIa complex mediates formation of thrombin, with subsequent conversion of fibrinogen to fibrin and activation of platelets.
-Second, the natural anticoagulant mechanisms operating via antithrombin III (ATIII), protein C and TF pathway inhibitor all are impaired in DIC. This leads to a shift in the hemostatic balance toward thrombosis.
-Finally, fibrin clearance is decreased because of a relative excess of PAI-I(plasmin activator inhibiter), which inhibits plasmin formation and fibrinolysis.
Diagnosis of DIC is made by the combination of clinical finding and certain supportive laboatory tests. There is no specific test that confirms or rules out the diagnosis. Clinically one suspects DIC in paitents with a generalized coagulopathy, bleeding and the presence of an inciting factor or disease associated with DIC.
The patient usually has a low or decreasing platelet count and prolonged PF/PTT. FSPs may be present in the plasma and coagulation inhibitors such as ATIII may be deficient.
Fibrinogen levels may be low in severe DIC, but, because fibrinogen is an acute phase reactant, its production is increased as part of the stress response, and levels may be normal.
The D-dimer assay is the most sensitive test for DIC, being abnormal in up to 94% of patients with a diagnosis of DIC.
In many patients with coagulopathy who are suspected of having DIC, hypothermia needs to be considered as the primary etiology of the bleeding disorder, especially if sepsis is not present.
Treatment of DIC
Treatment is of the underlying disease process is essential.
Symptomatic treatment can be tried but is futile if the underlying disease is not treated at the same time.
Several specific strategies have been investigated as therapy of DIC.
Anticoagulation has been used as an attempt to halt the underlying hypercoagulation in DIC.
Currently there have been no controlled studies showing any benefit of.**
Any questions be sent to drmmkapur@gmail.com
Friday, May 14, 2010
COAGULATION SYSTEM BREAKDOWN
SYSTEM OVERLOAD
2.4.1 Disseminated Intravascular Coagulation (DIC).
This syndrome is a systemic Thrombo-hemorrhagic disorder.
It occurs in small vessels (micro vascular) or sometimes in large vessels, and can leads to organ failure and death.
It is met with as a mild or severe form in the following conditions:
* Hemolytic
* Gram positive or gram negative sepsis
* Viremia
* Crush injury
* Burns
* Leukemia
* Malignancy with Metastasis
2.4.2 Clinical features
In DIC there is evidence of coagulation activation, fibrinolytic
activation, inhibiter consumption resulting in biochemical
evidence of some end organ damage.
In low grade DIC, there are minimal symptoms and laboratory
evidence while in severe DIC there is life threatening bleeding
disorders.
The simultaneous activation of coagulation and fibrinolytic
systems results in presence of both thrombin, and plasmin in
circulation.
Thrombin alters fibrinogen and fibrin monomers are released.
These cause fibrin clots resulting in microvascular thrombosis.
Platelets are entrapped in Thrombus leading to their depletion in
the blood.
Plasmin in circulation further acts on the degraded products in circulation, resulting in depressed levels of fibrinogen and increased levels of fibrinogen degradation products.
Plasmin also degrades factor V, VIII, IX and XI and
activates complement system all these derangements lead to D
**Fibrinolysis (and Regulation of Thrombosis)
-The fobrinolytic system aims to break down fibrin and dissolve thrombus, allowing healing of the wound. If provides a to limit the thrombotic mechanism.
-The main means for fibrinolysis is the breakdown of fibrin into soluble fragments by the proteolytic enzyme plasmin.
-Plasmin binds fibrin, and splits it at multiple sites, resulting in fibrin split products (FSPs)
The process Steps.
-Plasminogen is the precursor to plasmin. It is converted to plasmin by tissue plasminogen activator (tPA), which is released form endothelial cells near the site of injury.
-Although this reaction is inefficient in the general circulation, in the presence of a fibrin clot it is rapid.
-Thus fibrin is both the target and controler of its own destruction. Urokinase, so named because of its high concentration in the urine, is a plasminogen activator that is not fibrin specific.
-That, it converts plasminogen to plasmin in the circulation and not just on the clot.
-It is also the main activator of fibrinolysis in the extravaseular space.
-Urokinase is formed form the singlechain urokinase plasminogen activator precursor.
-Alpha2 antiplasmin (alpha2-AP) is the main inhihitor of plasmin, but also can bind plasminogen.
-Plasmin is inhibited by alpha2-AP when in the circulation, but its degradation is prevented when bound to the fibrin clot.
-This ensures localized, and not systemic, fibrinolysis.
-Fibrinolysis is kept in check by several inhibitors of plasminogen activation.
-These include plasminogen activator inhibitor type I (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI).**
Lab. Diagnosis
- No test confirm fibriolysis, but the process can be assed by laboratory tests
- One can measure levels of fibrinogen.
- FSPs,
- Plasminogen
- Plasminogen activator and
- Plasimin inhibitors
- The thrombin time (TT) is prolonged in fibrinolysis, and is useful in monitoring the fibrinolytic state during fibrinolytic therapy.
- Bleeding complications from such therapy are more common when the fibrinogen level is less than 100mg/dL and when FSPs are greater the 100U/dL,
Treatment
- Fresh frozen plasma (FFP) can be used to correct fibrinogen levels and reduce coagulopathy in such situations**.
Any questions be sent to drmmkapur@gmail.com
2.4.1 Disseminated Intravascular Coagulation (DIC).
This syndrome is a systemic Thrombo-hemorrhagic disorder.
It occurs in small vessels (micro vascular) or sometimes in large vessels, and can leads to organ failure and death.
It is met with as a mild or severe form in the following conditions:
* Hemolytic
* Gram positive or gram negative sepsis
* Viremia
* Crush injury
* Burns
* Leukemia
* Malignancy with Metastasis
2.4.2 Clinical features
In DIC there is evidence of coagulation activation, fibrinolytic
activation, inhibiter consumption resulting in biochemical
evidence of some end organ damage.
In low grade DIC, there are minimal symptoms and laboratory
evidence while in severe DIC there is life threatening bleeding
disorders.
The simultaneous activation of coagulation and fibrinolytic
systems results in presence of both thrombin, and plasmin in
circulation.
Thrombin alters fibrinogen and fibrin monomers are released.
These cause fibrin clots resulting in microvascular thrombosis.
Platelets are entrapped in Thrombus leading to their depletion in
the blood.
Plasmin in circulation further acts on the degraded products in circulation, resulting in depressed levels of fibrinogen and increased levels of fibrinogen degradation products.
Plasmin also degrades factor V, VIII, IX and XI and
activates complement system all these derangements lead to D
**Fibrinolysis (and Regulation of Thrombosis)
-The fobrinolytic system aims to break down fibrin and dissolve thrombus, allowing healing of the wound. If provides a to limit the thrombotic mechanism.
-The main means for fibrinolysis is the breakdown of fibrin into soluble fragments by the proteolytic enzyme plasmin.
-Plasmin binds fibrin, and splits it at multiple sites, resulting in fibrin split products (FSPs)
The process Steps.
-Plasminogen is the precursor to plasmin. It is converted to plasmin by tissue plasminogen activator (tPA), which is released form endothelial cells near the site of injury.
-Although this reaction is inefficient in the general circulation, in the presence of a fibrin clot it is rapid.
-Thus fibrin is both the target and controler of its own destruction. Urokinase, so named because of its high concentration in the urine, is a plasminogen activator that is not fibrin specific.
-That, it converts plasminogen to plasmin in the circulation and not just on the clot.
-It is also the main activator of fibrinolysis in the extravaseular space.
-Urokinase is formed form the singlechain urokinase plasminogen activator precursor.
-Alpha2 antiplasmin (alpha2-AP) is the main inhihitor of plasmin, but also can bind plasminogen.
-Plasmin is inhibited by alpha2-AP when in the circulation, but its degradation is prevented when bound to the fibrin clot.
-This ensures localized, and not systemic, fibrinolysis.
-Fibrinolysis is kept in check by several inhibitors of plasminogen activation.
-These include plasminogen activator inhibitor type I (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI).**
Lab. Diagnosis
- No test confirm fibriolysis, but the process can be assed by laboratory tests
- One can measure levels of fibrinogen.
- FSPs,
- Plasminogen
- Plasminogen activator and
- Plasimin inhibitors
- The thrombin time (TT) is prolonged in fibrinolysis, and is useful in monitoring the fibrinolytic state during fibrinolytic therapy.
- Bleeding complications from such therapy are more common when the fibrinogen level is less than 100mg/dL and when FSPs are greater the 100U/dL,
Treatment
- Fresh frozen plasma (FFP) can be used to correct fibrinogen levels and reduce coagulopathy in such situations**.
Any questions be sent to drmmkapur@gmail.com
Saturday, May 8, 2010
THE CASCADE EVENTS
**Hemostasis(BASIC SCIENCES)
THE STEPS AND SEQUENCE
Hemostasis is a process of linked physiologic events aimed at limiting of bleeding. It can be divided into two broad stages.
Primary and secondary hemostasis.
-Primary hemostasis involves the initial clot formation by adherence of platelets to the damaged blood vessel wall.
-Secondary hemostasis includes initiation of the coagulation cascade thrombin generation, and fibrin deposition.
Steps
-The main partners of primary hemostasis are platelets and endothelial cells. Platelets are 1.5 to 3.5µm discoid blood cells without nucleus or DNA that are formed from bone marrow megakaryocytes.
-Their key structure are their secretory granules, contractile cytoskeleton, and outer proteoglycan coat, which contains membrane receptors.
-The intracellular granules are of two types, alpha granules and dense granules (or dense bodies).
-Alphgranules contain platelet thrombospoundin, fibrinogen, fibronectin, platelet factor 4, von Willebrand’s facto (vWf), platelet derived growth factor (PDGF), factors V, X and VIII, and many other.
-Proteins dense granules contain ATP, ADP, GTP, GDP, other phosphates, calcium and serotonin.
-After platelet activation, these contents are released the presence of platelet specific proteins in the serum is the start of platelet activation.
-The endothelium is recognized as a metabolically active tissue that plays a role in coagulation and inflammation.
-The normal endothelium functions to maintain a nonthrombogenic surface in normal blood vessels, and keep a balanced steady state between the continuous process of coagulation and fibrinolysis. --Although the normal endothelium is nonthrombogenic, it secretes a subendothelial matrix gets exposed to the plasma (with break of endothelium), acts as highly thrombogenic.
-Another function of the endothelium (and megakaryocytes) is production of vWf. Stores of vWf are released into the subendothelium when the endothelium is damaged.
This initiates platelet, adhesion, leading to degranulation and further adhesion. Primary hemostasis is further enhanced by the initial vasoeonstriction of the damaged vessels.
Secondary Hemostasis:
Coagulation Cascade
Steps
-Following the initiation of the primary hemostatic process the coagulation cascade is activated which ends with the formation of a stable fibrin clot. Inactive forms of factors in the blood are converted to their active forms and this leads to a cascade effect with progressively larger amounts of coagulation factors produced.
-Fibrin monomers are generated as the final product of this cascade and are physically cross-linked to form the final stable clot.
-Normal state coagulation involves the interaction of many factors and is limited to the vessel wall injured.
This occurs through a series of inhibitory and regulatory substances, with their feedback loops.
The diluting effect of the blood flowing through the affected area is also a factor.
Till now coagulation has been understood to involve two “pathways” intrinsic and extrinsic.
-The intrinsic pathway did not require interaction with the injured vessel wall and resulted in the activation of factor XII as the initiating event for coagulation.
-Activated factor XII then activated factor XI, which in turn activated factor IX. A complex of activated factor VIII (factor VIIIa) and activated factor IX (Factor IXa) with calcium and phospholipid then activated factor X.
-Activated factor X (Factor Xa) then converted prothrombin to thrombin, which in turn converted fibrinogen to fibrin.
-Factor XIIIa converted the fibrin monomers into a cross-linked fibrin clot in the presence of calcium.
In the extrinsic pathway, coagulation is initiated when circulating factor VII interacts with subendothelial tissue factor (TF) in the presence of calcium. Subendothelial TF is exposed to the circulation as a result of endothelial injury.
-The activated factor VII (factor VIIa) TF complex activated factor X. Factor Xa then converts prothrombin to thrombin, and the reaction proceeds as described previously to generate a stable fibrin clot.
It is now felt that the
-The intrinsic pathway play a minor role. Inadequate levels of some of its key components will render standard coagulation tests abnormal but do not result in a clinically significant bleeding disorder.
-However the importance of the TF pathway as the predominant mechanism for in vivo coagulation is supported by recent research.
-The distribution of TF in the subendothelial layer, the epidermis, and myoepithelial cells.
-Thus the intact cells constitutes a “hemostatic barrier”.
-Injury puts TF into contact with factor VII, thus initiating coagulation.
-This concept of a single coagulation pathway (TF pathway) fits with current data and observed clinical syndromes and should replace the older concept of twin pathways**
Any questions be sent to drmmkapur@gmail.com
THE STEPS AND SEQUENCE
Hemostasis is a process of linked physiologic events aimed at limiting of bleeding. It can be divided into two broad stages.
Primary and secondary hemostasis.
-Primary hemostasis involves the initial clot formation by adherence of platelets to the damaged blood vessel wall.
-Secondary hemostasis includes initiation of the coagulation cascade thrombin generation, and fibrin deposition.
Steps
-The main partners of primary hemostasis are platelets and endothelial cells. Platelets are 1.5 to 3.5µm discoid blood cells without nucleus or DNA that are formed from bone marrow megakaryocytes.
-Their key structure are their secretory granules, contractile cytoskeleton, and outer proteoglycan coat, which contains membrane receptors.
-The intracellular granules are of two types, alpha granules and dense granules (or dense bodies).
-Alphgranules contain platelet thrombospoundin, fibrinogen, fibronectin, platelet factor 4, von Willebrand’s facto (vWf), platelet derived growth factor (PDGF), factors V, X and VIII, and many other.
-Proteins dense granules contain ATP, ADP, GTP, GDP, other phosphates, calcium and serotonin.
-After platelet activation, these contents are released the presence of platelet specific proteins in the serum is the start of platelet activation.
-The endothelium is recognized as a metabolically active tissue that plays a role in coagulation and inflammation.
-The normal endothelium functions to maintain a nonthrombogenic surface in normal blood vessels, and keep a balanced steady state between the continuous process of coagulation and fibrinolysis. --Although the normal endothelium is nonthrombogenic, it secretes a subendothelial matrix gets exposed to the plasma (with break of endothelium), acts as highly thrombogenic.
-Another function of the endothelium (and megakaryocytes) is production of vWf. Stores of vWf are released into the subendothelium when the endothelium is damaged.
This initiates platelet, adhesion, leading to degranulation and further adhesion. Primary hemostasis is further enhanced by the initial vasoeonstriction of the damaged vessels.
Secondary Hemostasis:
Coagulation Cascade
Steps
-Following the initiation of the primary hemostatic process the coagulation cascade is activated which ends with the formation of a stable fibrin clot. Inactive forms of factors in the blood are converted to their active forms and this leads to a cascade effect with progressively larger amounts of coagulation factors produced.
-Fibrin monomers are generated as the final product of this cascade and are physically cross-linked to form the final stable clot.
-Normal state coagulation involves the interaction of many factors and is limited to the vessel wall injured.
This occurs through a series of inhibitory and regulatory substances, with their feedback loops.
The diluting effect of the blood flowing through the affected area is also a factor.
Till now coagulation has been understood to involve two “pathways” intrinsic and extrinsic.
-The intrinsic pathway did not require interaction with the injured vessel wall and resulted in the activation of factor XII as the initiating event for coagulation.
-Activated factor XII then activated factor XI, which in turn activated factor IX. A complex of activated factor VIII (factor VIIIa) and activated factor IX (Factor IXa) with calcium and phospholipid then activated factor X.
-Activated factor X (Factor Xa) then converted prothrombin to thrombin, which in turn converted fibrinogen to fibrin.
-Factor XIIIa converted the fibrin monomers into a cross-linked fibrin clot in the presence of calcium.
In the extrinsic pathway, coagulation is initiated when circulating factor VII interacts with subendothelial tissue factor (TF) in the presence of calcium. Subendothelial TF is exposed to the circulation as a result of endothelial injury.
-The activated factor VII (factor VIIa) TF complex activated factor X. Factor Xa then converts prothrombin to thrombin, and the reaction proceeds as described previously to generate a stable fibrin clot.
It is now felt that the
-The intrinsic pathway play a minor role. Inadequate levels of some of its key components will render standard coagulation tests abnormal but do not result in a clinically significant bleeding disorder.
-However the importance of the TF pathway as the predominant mechanism for in vivo coagulation is supported by recent research.
-The distribution of TF in the subendothelial layer, the epidermis, and myoepithelial cells.
-Thus the intact cells constitutes a “hemostatic barrier”.
-Injury puts TF into contact with factor VII, thus initiating coagulation.
-This concept of a single coagulation pathway (TF pathway) fits with current data and observed clinical syndromes and should replace the older concept of twin pathways**
Any questions be sent to drmmkapur@gmail.com
THE CASCADE
FLOW CHART OF CAGULATION EVENTS
HOMEOSTASIS 3
THE FACTORS AND THE PATH
As stated earlier the process of coagulation may be initiated by intrinsic cause
or by extrinsic causes
The factors involved and there interactions are shown in Fig. 2.1.
The factors are Named and the deficiency management is tabulated in Table 2.1 below.
Intrinsic Path
(Present in Blood)
XII--------------
? HMWK *
XIIa
XI--------------
XIa
IX------------- Extrinsic Path
ca2+ (Outside the blood vessel)
Present in Tissue Protein
IXa------ -------
ca2+ ca2+
Phospholipid VIII Tissue Thromboplastin
X-----------------------
Phospholipid ca2+
V
Xa
Prothrombin---------------
Thrombin
Fibrinogen---------------------> Fibrin
ca2+ XI
Firm clot
* High Molecular weight Kininogen
Fig. 2.1 COAGULATION CASCADE AND FACTORS REQUIRED
BMJ 1997 314 1026
Factors that take part in these mechanisms are named and listed
in Table 2.1.
TABLE 2.1
NOMENCLATURE OF COAGULATION FACTORS
_______________________________________________________________________
FACTOR SYNONYM TREATMENT DEFECIENCY STATES
_______________________________________________________________________
I Fibrinogen FFP,cryoprecipitate platelet
II Prothrombin FFP, Platlets
III Thromboplastin (tissue
factors)
IV Calcium ion
V Proacclerin,labile factor FFP,minimal in platelets
vWF Von Willebrand's factor FFP,cryoprecipitate,full
concentrate
VII Serum prothrombin conversion FFP, Platelets
accelerator, stable factor
VIII Antihemophilic Factor A FFP,cryoprecipitate,factor
VIII concentrate(plasma
derived or recombinant)
*IX Christmas factor FFP,prothrombin complex
concentrate,factor IX
concentrate,platelets
*X Suart-Power factor FFP,Platelets
XI Plasma thromboplastin FFP,minimal in platelets
antecedent
XII Hageman factor FFP, platelets
XIII Fibrin Stabilizing factor
Low Platelets counts Platelets
_______________________________________________________________________
* Vitamin K-dependent factors
FFP Fresh frozen plasma, platelet packs
The mechanism involved in the intrinsic process of coagulation
are initiated by inactive factor XII coming in contact with
factor VII to form a complex which activates factor X.
Then onwards the process follows a common pathway ending with the
production of fibrin.
Any questions be sent to drmmkapur@gmail.com
HOMEOSTASIS 3
THE FACTORS AND THE PATH
As stated earlier the process of coagulation may be initiated by intrinsic cause
or by extrinsic causes
The factors involved and there interactions are shown in Fig. 2.1.
The factors are Named and the deficiency management is tabulated in Table 2.1 below.
Intrinsic Path
(Present in Blood)
XII--------------
? HMWK *
XIIa
XI--------------
XIa
IX------------- Extrinsic Path
ca2+ (Outside the blood vessel)
Present in Tissue Protein
IXa------ -------
ca2+ ca2+
Phospholipid VIII Tissue Thromboplastin
X-----------------------
Phospholipid ca2+
V
Xa
Prothrombin---------------
Thrombin
Fibrinogen---------------------> Fibrin
ca2+ XI
Firm clot
* High Molecular weight Kininogen
Fig. 2.1 COAGULATION CASCADE AND FACTORS REQUIRED
BMJ 1997 314 1026
Factors that take part in these mechanisms are named and listed
in Table 2.1.
TABLE 2.1
NOMENCLATURE OF COAGULATION FACTORS
_______________________________________________________________________
FACTOR SYNONYM TREATMENT DEFECIENCY STATES
_______________________________________________________________________
I Fibrinogen FFP,cryoprecipitate platelet
II Prothrombin FFP, Platlets
III Thromboplastin (tissue
factors)
IV Calcium ion
V Proacclerin,labile factor FFP,minimal in platelets
vWF Von Willebrand's factor FFP,cryoprecipitate,full
concentrate
VII Serum prothrombin conversion FFP, Platelets
accelerator, stable factor
VIII Antihemophilic Factor A FFP,cryoprecipitate,factor
VIII concentrate(plasma
derived or recombinant)
*IX Christmas factor FFP,prothrombin complex
concentrate,factor IX
concentrate,platelets
*X Suart-Power factor FFP,Platelets
XI Plasma thromboplastin FFP,minimal in platelets
antecedent
XII Hageman factor FFP, platelets
XIII Fibrin Stabilizing factor
Low Platelets counts Platelets
_______________________________________________________________________
* Vitamin K-dependent factors
FFP Fresh frozen plasma, platelet packs
The mechanism involved in the intrinsic process of coagulation
are initiated by inactive factor XII coming in contact with
factor VII to form a complex which activates factor X.
Then onwards the process follows a common pathway ending with the
production of fibrin.
Any questions be sent to drmmkapur@gmail.com
Friday, May 7, 2010
BLOOD A LIVING TISSUE
HEMOSTASIS 2
**Red Blood Cell Life and death
The red blood cell does not possess the structures required for DNA synthesis nor, for transcription and translation of proteins.
Cellular life depends on the cell’s ability to generate ATP through the utilization of glucose. Without the pathway for ATP generation, the cell would not be able to maintain its membrane integrity, and ionic gradients.
The ability to maintain hemoglobin in its reduced form for the transport and delivery of oxygen would also be limited.
Glucose is the primary fuel of the erythrocyte. It enters the cell through diffusion from the plasma, and through glycolysis ultimately is converted to lactate and pyruvate.
This process uses 2 moles of ATP and produces 4 moles of ATP, for a net gain of 2 ATP molecules.
The rate limiting step is controlled by the activity of phosphofructokinase, which converts fructose 6-phosphate to fructose 1,6 phosphate. This enzyme is inhibited by high concentrations of ATP, which signal the “fed” state.
Conversely, high concentrations of AMP signal an “energy starved” state favouring continued glycolysis.
The energy generated by glycolysis is utilized by the Na+ -K+ ATPase pump to regulate cell membrance potentials.
Maintenance of the appropriate redox potential is essential for the red blood cell to complete its function of oxygen delivery.
The red cell ultimately dies as its enzyme systema burn out.
The inability to continue glycolysis to maintain membrane gradients leads to changes in membrane permability and ultimately to cell destruction.
More than 90% of red cells with altered membrane are destroyed by the macrophages of the reticuloendothelial system (spleen, liver and marrow).
As the cells are destroyed, the hemoglobin molecule is further degraded. The iron is largely conserved, redistributed to the marrow, and incorporated into new hemoglobin**
1. Coagulation
1.1 Intrinsic
In all injuries, there is injury to blood vessels with the
resulting exposure of blood to tissue factors and collagen in the
injured wall of the blood vessels factors V and VIII are
available in the endothelium.
There follows as a result platelet aggregation and adherence with formation of a plug at the injury
site.
Hemostasis(control of bleeding) is achieved within the body by four events occurring in
sequence:
* Vessel wall smooth muscle constriction at the site of injury
Vasoconstriction limits the blood loss. This occurs in
response to release of Thromboxane A and Serotonin from the
platelets. Endothalin is also responsible and is released
from the endothelial cells.
* Platelet function. The platelets adhere to one another and
also to the vessel wall at the site of injury to form a plug
* Coagulation wherein prothrombin is converted to thrombin and
their product in turn converts fibrinogen to fibrin
improves the platelet plug
* Fibrinolysis. This process causes the lysis of the fibrin
to restore the patency of the blood vessel.
Any questions be sent to drmmkapur@gmail.com
**Red Blood Cell Life and death
The red blood cell does not possess the structures required for DNA synthesis nor, for transcription and translation of proteins.
Cellular life depends on the cell’s ability to generate ATP through the utilization of glucose. Without the pathway for ATP generation, the cell would not be able to maintain its membrane integrity, and ionic gradients.
The ability to maintain hemoglobin in its reduced form for the transport and delivery of oxygen would also be limited.
Glucose is the primary fuel of the erythrocyte. It enters the cell through diffusion from the plasma, and through glycolysis ultimately is converted to lactate and pyruvate.
This process uses 2 moles of ATP and produces 4 moles of ATP, for a net gain of 2 ATP molecules.
The rate limiting step is controlled by the activity of phosphofructokinase, which converts fructose 6-phosphate to fructose 1,6 phosphate. This enzyme is inhibited by high concentrations of ATP, which signal the “fed” state.
Conversely, high concentrations of AMP signal an “energy starved” state favouring continued glycolysis.
The energy generated by glycolysis is utilized by the Na+ -K+ ATPase pump to regulate cell membrance potentials.
Maintenance of the appropriate redox potential is essential for the red blood cell to complete its function of oxygen delivery.
The red cell ultimately dies as its enzyme systema burn out.
The inability to continue glycolysis to maintain membrane gradients leads to changes in membrane permability and ultimately to cell destruction.
More than 90% of red cells with altered membrane are destroyed by the macrophages of the reticuloendothelial system (spleen, liver and marrow).
As the cells are destroyed, the hemoglobin molecule is further degraded. The iron is largely conserved, redistributed to the marrow, and incorporated into new hemoglobin**
1. Coagulation
1.1 Intrinsic
In all injuries, there is injury to blood vessels with the
resulting exposure of blood to tissue factors and collagen in the
injured wall of the blood vessels factors V and VIII are
available in the endothelium.
There follows as a result platelet aggregation and adherence with formation of a plug at the injury
site.
Hemostasis(control of bleeding) is achieved within the body by four events occurring in
sequence:
* Vessel wall smooth muscle constriction at the site of injury
Vasoconstriction limits the blood loss. This occurs in
response to release of Thromboxane A and Serotonin from the
platelets. Endothalin is also responsible and is released
from the endothelial cells.
* Platelet function. The platelets adhere to one another and
also to the vessel wall at the site of injury to form a plug
* Coagulation wherein prothrombin is converted to thrombin and
their product in turn converts fibrinogen to fibrin
improves the platelet plug
* Fibrinolysis. This process causes the lysis of the fibrin
to restore the patency of the blood vessel.
Any questions be sent to drmmkapur@gmail.com
Monday, May 3, 2010
BLOOD AND BLEEDING
HEMOSTASIS AND BLEEDING DISORDERS
In health blood in the Blood vessels stays in the
fluid state.
This is essential for delivery of oxygen and nutrients
**Blood composition and Formation
The Blood is made up of two components:
- The plasma and
- The cellular elements floating in it.
The plasma represents the fluid fraction and accounts for 55% of the total blood volume; plasma volume is estimated to be roughly 7% to 8% of the total body weight.
The plasma reaches the tissues and provides nutrients and soluble ions, and carries proteins (such as albumin, complement immunoglobulin, and enzymes) to the cells and tissues.
-The cellular component represents 45% of the blood volume and is divided into three major cell type erythrocytes, leukocytes, and megakaryocytes.
-Each of these cells can be traced back to a single pluripotent stem cell.
-Erythrocytes (Red Blood Cells) function is to carry oxygen to body tissues.
-Leukocytes (White Blood Cells) are a variety of more specialized cells, whose function involves host defense and immunity. The last major cell type is the megakaryocyte. -Platelets and endothelial cells are derived from this cell line and are essential for the mechanisms of hemostasis.
-The process of blood formation is called hematopoiesis. Hematopoiesis is an ongoing, lifelong process in the bone marrow in the adult.
-The production of blood cells starts in the yolk sac of the embryo and continues throughout the first trimester.
-Extramedullary hematopoiesis (outside the bone marrow) begins during the third gestational month in the fetal liver.
-The spleen, kidneys, thymus, and lymph nodes are responsible for a minor role in hematopoiesis during fetal development.
-After birth, the lymph nodes assume a primary function in the proliferation and differentiation of leukocytes and lymphocytes, while the bone marrow takes over as the major source of blood cell production.
-Similarly, the liver and spleen assume important role in the reticuloendothelial system for the destruction and turnover (apoptosis) of aged and dysfunctional cells.
Red Blood Cell
The normal red blood cell is a biconcave disk approximately to 7.5µ in diameter. It is the major component of the cellular compartment of the blood, with a circulating life of about 100 to 120 days.
The primary role of RBC is to deliver oxygen to the tissues for metabolism and carry dissolved carbon dioxide to the lungs for release into the air. The red cell depends on the hemoglobin molecule to for transport of these gases.
The number of erythrocytes in the blood ranges form 3.8 to 5.9 million cells per micro liter of blood, with a hemoglobin concentration ranging form 17 to 17g/dl and a hematocrit of 35% to 52%.
This normal range is broad for it cover men and women young and old, and with people living at altitude. Induced erythropeiesis, leading to the expansion of red cell mass, occurs in response to hypoxia, blood loss, and a variety of hormones and disease states.
The most potent stimulator of erythropoiesis is erythropoietin.
Erythropoietin is a hormone produced by the kidney in response to hypoxia. This hormone stimulates the pluripotent stem cells in the bone marrow to become mature.
The bone marrow is capable of increasing the production of red cells by 5 to 10 times normal under the influence of erythropoietin. However, because of the limiting factor of iron in diet the increase is only two to three times normal.
In patients with chronic renal failure or after a nephrectomy, the ability to generate a erythropoietin response is slower.**
Any questions be sent to drmmkapur@gmail.com
In health blood in the Blood vessels stays in the
fluid state.
This is essential for delivery of oxygen and nutrients
**Blood composition and Formation
The Blood is made up of two components:
- The plasma and
- The cellular elements floating in it.
The plasma represents the fluid fraction and accounts for 55% of the total blood volume; plasma volume is estimated to be roughly 7% to 8% of the total body weight.
The plasma reaches the tissues and provides nutrients and soluble ions, and carries proteins (such as albumin, complement immunoglobulin, and enzymes) to the cells and tissues.
-The cellular component represents 45% of the blood volume and is divided into three major cell type erythrocytes, leukocytes, and megakaryocytes.
-Each of these cells can be traced back to a single pluripotent stem cell.
-Erythrocytes (Red Blood Cells) function is to carry oxygen to body tissues.
-Leukocytes (White Blood Cells) are a variety of more specialized cells, whose function involves host defense and immunity. The last major cell type is the megakaryocyte. -Platelets and endothelial cells are derived from this cell line and are essential for the mechanisms of hemostasis.
-The process of blood formation is called hematopoiesis. Hematopoiesis is an ongoing, lifelong process in the bone marrow in the adult.
-The production of blood cells starts in the yolk sac of the embryo and continues throughout the first trimester.
-Extramedullary hematopoiesis (outside the bone marrow) begins during the third gestational month in the fetal liver.
-The spleen, kidneys, thymus, and lymph nodes are responsible for a minor role in hematopoiesis during fetal development.
-After birth, the lymph nodes assume a primary function in the proliferation and differentiation of leukocytes and lymphocytes, while the bone marrow takes over as the major source of blood cell production.
-Similarly, the liver and spleen assume important role in the reticuloendothelial system for the destruction and turnover (apoptosis) of aged and dysfunctional cells.
Red Blood Cell
The normal red blood cell is a biconcave disk approximately to 7.5µ in diameter. It is the major component of the cellular compartment of the blood, with a circulating life of about 100 to 120 days.
The primary role of RBC is to deliver oxygen to the tissues for metabolism and carry dissolved carbon dioxide to the lungs for release into the air. The red cell depends on the hemoglobin molecule to for transport of these gases.
The number of erythrocytes in the blood ranges form 3.8 to 5.9 million cells per micro liter of blood, with a hemoglobin concentration ranging form 17 to 17g/dl and a hematocrit of 35% to 52%.
This normal range is broad for it cover men and women young and old, and with people living at altitude. Induced erythropeiesis, leading to the expansion of red cell mass, occurs in response to hypoxia, blood loss, and a variety of hormones and disease states.
The most potent stimulator of erythropoiesis is erythropoietin.
Erythropoietin is a hormone produced by the kidney in response to hypoxia. This hormone stimulates the pluripotent stem cells in the bone marrow to become mature.
The bone marrow is capable of increasing the production of red cells by 5 to 10 times normal under the influence of erythropoietin. However, because of the limiting factor of iron in diet the increase is only two to three times normal.
In patients with chronic renal failure or after a nephrectomy, the ability to generate a erythropoietin response is slower.**
Any questions be sent to drmmkapur@gmail.com
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