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Compiled By  BFF,  FYBPHARM,   BCP.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normoblasts  are approximately the size of mature RBCs and stain almost the same since most ribosomes have been lost as mo...
Basophilic erythroblast s  are large cells (12-15 um) with a large nucleus beginning to condense. The cytoplasm, full of f...
 
 
 
 
 
 
 
 
 
 
C 49 H 58 O 5 N 4 Fe Heme o C 34 H 36 O 4 N 4 S 2 Fe Heme c C 34 H 32 O 4 N 4 Fe Heme b C 49 H 56 O 6 N 4 Fe Heme a Chemic...
<ul><li>The enzymatic process that produces heme is properly called  porphyrin  synthesis, as all the intermediates are  t...
<ul><li>The pathway is initiated by the synthesis of  D- Aminolevulinic  acid  (dALA or δALA) from the  amino acid   glyci...
<ul><li>This mechanism is of therapeutic importance: infusion of  heme arginate  of  hematin  can abort attacks of  porphy...
 
<ul><li>Degradation of Heme </li></ul><ul><li>In the first step, heme is converted to  biliverdin  by the enzyme  heme   o...
<ul><li>  HOXG  </li></ul><ul><li>Heme  -------------->  biliverdin +  Fe  3+   </li></ul><ul><li>H +  + NADPH  NADP+  </l...
<ul><li>In the second reaction, biliverdin is converted to bilirubin  (reduced-reversible)  by  biliverdin   reductase  (B...
<ul><li>Bilirubin is transported into the liver bound to a protein ( serum albumin ), where it is conjugated with  glucuro...
<ul><li>This form of bilirubin is excreted from the liver in  bile . The  intestinal bacteria  deconjugate bilirubin diglu...
<ul><li>The haem is turned into unconjugated bilirubin in the  macrophages  of the spleen and bone marrow. It is then boun...
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
<ul><li>Granulopoiesis  - Formation Of Granular Leukocytes (WBCs) </li></ul><ul><li>-- This process occurs in bone marrow ...
<ul><li>Myelocytes  have a begun nuclear </li></ul><ul><li>changes, possessing a round nucleus or </li></ul><ul><li>one th...
<ul><li>Stab Cells or Band Metamyelocytes  are unique to the neutrophil lineage. These cells, approximately the size of ma...
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  <ul><li>INHIBITION OF EXCESSIVE CLOTTING  </li></ul><ul><li>It would be dangerous if blood clotting were to continue to ...
2.Fibrin fibers inhibit the activity of thrombin.  Thrombin acts to convert fibrinogen to fibrin, yet fibrin fibers have a...
CLOT REMOVAL   The clot itself stimulates the secretion of   tissue plasminogen activator  (TPA)  from the surrounding vas...
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COMPILED BY  BFF F.Y.B.PHARM,BCP. OCT,2007. Ref:- Tortora,RossNwilson,Internet.
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Compiled By BFF,F.Y.B.PHARM,BCP.
October, 2007

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Blood

  1. 1. Compiled By BFF, FYBPHARM, BCP.
  2. 36. Normoblasts are approximately the size of mature RBCs and stain almost the same since most ribosomes have been lost as more hemoglobin accumulates. The retain a small highly condensed (pycnotic) nucleus Polychromatophilic erythrocytes or reticulocytes are formed when a normoblast loses its nucleus. However, these cells still retain some ribosomes and combined with the hemoglobin, some polychromatic staining (pink-blue cytoplasm) is observed
  3. 37. Basophilic erythroblast s are large cells (12-15 um) with a large nucleus beginning to condense. The cytoplasm, full of free ribosomes, stains intensely basophilic Polychromatophilic erythroblasts are formed as the nucleus becomes more condensed (a soccer ball-like morphology) and hemoglobin begins to accumulate in the cytoplasm. The combined staining of the basophilic ribosomes and acidophilic hemoglobin give these cells a grayish cytoplasm
  4. 48. C 49 H 58 O 5 N 4 Fe Heme o C 34 H 36 O 4 N 4 S 2 Fe Heme c C 34 H 32 O 4 N 4 Fe Heme b C 49 H 56 O 6 N 4 Fe Heme a Chemical formula Heme
  5. 49. <ul><li>The enzymatic process that produces heme is properly called porphyrin synthesis, as all the intermediates are tetrapyrroles that are chemically classified are porphyrins. The process is highly conserved across biology. In humans, this pathway serves almost exclusively to form heme. In other species, it also produces similar substances such as cobalamin ( vitamin B12 ). </li></ul>
  6. 50. <ul><li>The pathway is initiated by the synthesis of D- Aminolevulinic acid (dALA or δALA) from the amino acid glycine and succinyl - CoA from the citric acid cycle (Krebs cycle). The rate-limiting enzyme responsible for this reaction, ALA synthase , is strictly regulated by intracellular iron levels and heme concentration. A low-iron level, e.g., in iron deficiency , leads to decreased porphyrin synthesis, which prevents accumulation of the toxic intermediates. </li></ul>
  7. 51. <ul><li>This mechanism is of therapeutic importance: infusion of heme arginate of hematin can abort attacks of porphyria in patients with an inborn error of metabolism of this process, by reducing transcription of ALA synthase. </li></ul><ul><li>The organs mainly involved in heme synthesis are the liver and the bone marrow , although every cell requires heme to function properly. Heme is seen as an intermediate molecule in catabolism of haemoglobin in the process of bilirubin metabolism . </li></ul>
  8. 53. <ul><li>Degradation of Heme </li></ul><ul><li>In the first step, heme is converted to biliverdin by the enzyme heme oxygenase (HOXG). NADPH is used as the reducing agent, molecular oxygen enters the reaction, carbon monoxide is produced and the iron is released from the molecule as the ferric ion (Fe3+). </li></ul>
  9. 54. <ul><li> HOXG </li></ul><ul><li>Heme --------------> biliverdin + Fe 3+ </li></ul><ul><li>H + + NADPH NADP+ </li></ul><ul><li>O2 CO </li></ul>
  10. 55. <ul><li>In the second reaction, biliverdin is converted to bilirubin (reduced-reversible) by biliverdin reductase (BVR): </li></ul><ul><li>BVR </li></ul><ul><li>Biliverdin -----------> Bilirubin </li></ul><ul><li>H+ + NADPH NADP+ </li></ul>
  11. 56. <ul><li>Bilirubin is transported into the liver bound to a protein ( serum albumin ), where it is conjugated with glucuronic acid to become more water soluble. The reaction is catalyzed by the enzyme UDP-glucuronide transferase (UDPGUTF). </li></ul><ul><li>UDPGUTF </li></ul><ul><li>+ 2UDP-glucuronate -------> </li></ul>Bilirubin- Diglucu ronide Bilirubin
  12. 57. <ul><li>This form of bilirubin is excreted from the liver in bile . The intestinal bacteria deconjugate bilirubin diglucuronide and convert bilirubin to urobilinogens . Some urobilinogen is absorbed by intestinal cells and transported into the kidneys and excreted with urine. The remainder travels down the digestive tract and is excreted as coprobilinogen, which is responsible for the color of Feces </li></ul>
  13. 58. <ul><li>The haem is turned into unconjugated bilirubin in the macrophages of the spleen and bone marrow. It is then bound to albumin and sent to the liver . </li></ul><ul><li>In the liver it is conjugated with glucuronic acid , making it water soluble. Much of it goes into the bile and thus out into the small intestine. Some of the conjugated bilirubin remains in the large intestine and is metabolised by colonic bacteria to stercobilinogen and then oxidised to stercobilin . </li></ul><ul><li>Some is reabsorbed, and excreted in the urine as urobilinogen and the oxidised form, urobilin . If the liver’s function is impaired, or biliary drainage blocked, some of the conjugated bilirubin appears in the urine, turning it dark amber . </li></ul>
  14. 74. <ul><li>Granulopoiesis - Formation Of Granular Leukocytes (WBCs) </li></ul><ul><li>-- This process occurs in bone marrow along side Erythropoiesis </li></ul><ul><li>--Two steps Simultaneously </li></ul><ul><li>Nuclei condense to adult form (bi-lobed, multi-lobed, etc) </li></ul><ul><li>The cell begins to synthesize and collect its specific granule population. </li></ul>
  15. 75. <ul><li>Myelocytes have a begun nuclear </li></ul><ul><li>changes, possessing a round nucleus or </li></ul><ul><li>one that is flatten on one side. The </li></ul><ul><li>cytoplasm shows a minimum of specific </li></ul><ul><li>granules (eosinophilic or basophilic or </li></ul><ul><li>azurophilic) </li></ul><ul><li>Metamyelocytes have begun nuclear indentation (horseshoe shaped to mature morphology) and an increase in specific granules </li></ul>
  16. 76. <ul><li>Stab Cells or Band Metamyelocytes are unique to the neutrophil lineage. These cells, approximately the size of mature PMNs have a deep horseshoe or ring-like morphology to their nuclei </li></ul><ul><li>Megakaryocytes are extremely large cells in the bone marrow from which platelets are derived. They are fragile so many are lost in smear preparations, however, when found are easily identified by the large size and multilobed nuclei </li></ul>
  17. 93.   <ul><li>INHIBITION OF EXCESSIVE CLOTTING </li></ul><ul><li>It would be dangerous if blood clotting were to continue to expand beyond the boundaries of the injury. Excessive clotting is inhibited because: </li></ul><ul><li>Clotting factors are rapidly inactivated . There are enzymes in the blood that function to inactivate clotting factors. As clotting factors are taken away from the site of injury by the blood stream, they become inactivated by these enzymes. This ensures that clotting will only occur at the site of injury and not progress steadily down the vessel.             </li></ul>
  18. 94. 2.Fibrin fibers inhibit the activity of thrombin. Thrombin acts to convert fibrinogen to fibrin, yet fibrin fibers have an inhibitory effect on the activity of thrombin. As the clot grows this inhibition intensifies. This constitutes a negative feedback loop, where the product of thrombin activity (fibrin) feeds back to shut off thrombin                           
  19. 95. CLOT REMOVAL The clot itself stimulates the secretion of tissue plasminogen activator (TPA) from the surrounding vascular epithelium. TPA is an enzyme that catalyzes the conversion of plasminogen to plasmin .
  20. 125. COMPILED BY BFF F.Y.B.PHARM,BCP. OCT,2007. Ref:- Tortora,RossNwilson,Internet.

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