Blood Part 1 PDF

BLOOD 1 Dr Nageeb ‫الموضوع‬ ‫الصفحه‬ RBCS 2 Hemoglobin 4 Erythropoiesis 8 Anemia Classification 14 Hemolytic anemia 15 Nutritional anemia 18 Polycythemia 23 Blood...

BLOOD 1 Dr Nageeb ‫الموضوع‬ ‫الصفحه‬ RBCS 2 Hemoglobin 4 Erythropoiesis 8 Anemia Classification 14 Hemolytic anemia 15 Nutritional anemia 18 Polycythemia 23 Blood groups 24 Blood transfusion 28 Make it Easy 1 BLOOD 1 Dr Nageeb Blood Blood is A connective tissue with fluid matrix inside the CardioVascular system  plays an important role in homeostasis. Blood is composed of: A. Clear yellowish fluid called plasma (55% of blood volume). B. Cellular elements (45% of blood volume): RBCs & WBCs & Platelets. Red Blood Corpuscles (Erythrocytes)  Shape & size of RBCs: Shape: Biconcave, non-nucleated discs ( ‫) بيحبوها لإلمسكيو‬ Volume: 90 cubic micron 3 Diameter 7.5 microns Thickness 2.5 microns thickness in edges & 1  in center (So, the center appears paler than periphery due to the biconcavity). Structure of RBCs A. Red cell membrane: 1) Antigenic property of RBCs. e.g. antigens of blood grouping. 2) Binding of cytoskeleton (Spectrin & actin) ‫البروتين المسؤول عن ليونه‬ 3) Channels & Carrier for ions e.g. Na+, K+, Cl-. B. Contents of RBCs: 1) Hemoglobin (Hb)  give red Eosinophilia color and carry O2 ‫الهٌموجلوبٌن ٌصبغ الخلٌه باالحمر‬ 2) enzymes: as - Carbonic anhydrase enzyme  catalyze Co2 transport - glucose-6-phosphate dehydrogenase & Pyruvate Kinase 3) Ions  K+ & Na+ & Mg++ & Cl- & HCO3- & phosphate. 4) doesn’t contain normal cellular organelles ( ‫لإلمسكيو‬ ‫) بيحبوها‬ Make it Easy 2 BLOOD 1 Dr Nageeb functions of RBCs: 1) Related to Red cell membrane: A) Biconcavity and spectrin protein ( ‫) بيحبوها لإلمسكيو‬ - increase surface area which facilitate Gas exchange - deformation in narrow capillaries (flexible & plastic) - Give the RBCs its shape so in case of hydration the cell swell without rupture. ‫حت يسمح‬ ‫كبي ى‬ ‫تتمي بأن يكون مساحه سطح الخليه ر‬ ‫ بالتال يجب ان ر ن‬.. ‫األكسجي للخاليا‬ ‫رن‬ ‫ وظيفتها توصيل‬rbcs ‫بما إن ال‬ ‫ي‬ ‫الشعيات الدمويه‬ ‫الت تجعلها تمر من خالل‬ ‫ى‬ ‫ن‬ ‫ وكذلك يجب ان ر‬.. ‫بتبادل الغازات مع األنسجه بشكل أفضل‬ ‫ر‬ ‫تتمي بالمطاطيه ي‬ ‫ن‬ ‫الصغيه جداا ى‬ ‫ وده هيعطيها القابليه انها تتنفخ‬Biconcave ‫الطبيع‬ ‫ي‬ ‫ وكذلك الحظ ان الخليه يف‬.. ‫حت تصل لجميع الخاليا‬ ‫ر‬ ‫ر‬ ‫ن‬ ‫ تقدر تستوعب مياه اكي بدون ما تنفجر‬.. ‫يعت المياه دخلت للخليه‬ ‫ ي‬hydration ‫أكي فلو حصل‬ ‫بشكل ر‬ B) the ion channels Maintain - the normal ionic composition , osmotic pressure - Cl— shift phenomenon. C) It responsible for blood groups D) It keeps Hb inside RBCs  to prevent the bad effects of escape of HB in the plasma ‫رن‬ ‫ هيقفل انابيب الكليه وده هيسبب فشل كلوي‬, ‫الهيموجلوبي لو خرج للدم‬ ‫رن‬ ‫ إلن‬.. ‫الهيموجلوبي بداخلها‬ ‫ هو حبس‬RBCS ‫هدف ال‬ ‫ن‬ ‫ وكمان ر ن‬renal failure 😊 ‫قلت‬‫ يا ر ي‬.. ‫قلت‬ ‫كبيي ممكن يتسبب يف فشل ر ي‬ ‫هيود لزوجه الدم ويرفع الضغط بشكل ر‬ 2) Functions related to contents: A) Carry O2: - 1 molecule of Hb  carries  4 (02 molecule) each gram of Hb  carries  1.33 ml of oxygen. B) Carry Co2 - in form of carbamine Hb facilitated by carbonic anhydrase enzyme , Co2  HCO3. C) Buffer Acid and base: by Hemoglobin ‫ن‬ ‫رن‬ ‫الطبيع‬ ‫ي‬ ‫ الجسم يف المستوي‬PH ‫بالتال يحافظ عىل ال‬ ‫ي‬ ‫الهيموجلوبي له القدره عىل التعادل مع االحماض والقواعد‬ D) Blood viscosity and Blood pressure controlled by RBCs & plasma proteins Make it Easy 3 BLOOD 1 Dr Nageeb ( Hemoglobin ) Definition: It is the principal constitute (33%) of RBCs. It is a red pigment which gives the blood its red colour Normal levels of Hb: (gram% or gram/100 ml of blood or gram/dl) ‫األسباب زف الجدول ز ز‬ MCQ ‫بتنل‬ ‫ي‬ Adult Male 13 – 18 gm/dl. Due to  androgens (testosterone) in male. Adult Female 12 – 16 gm/dl. Due to  androgens in female & loss blood in menses. Child 3 – 12 y 11 – 14 gm/dl. Due to  androgens & gradual destruction of RBCs. Newborn Infant 20 gm/dl. Due to relative intrauterine hypoxia   erythropoietin Infant after 1 w 15.5 gm/dl. Due to gradual destruction of RBCs. Structure of Hb: (1) Globin: 2 pairs of polypeptide chains (2 α and 2 β) (2) 4 Haem: Pathways : 1) ( 2 succinyl — CoA + 2 glycine )  pyrrole ring 2) 4 pyrrole ring joined together  protoporphyrin 3) protoporphyrin joined with Fe2  Haem it is made of 4 subunits each of them is formed from  one Haem and one polypeptide 4) 4 Haem Joined with 4 Polypeptide chain  Hemoglobin Functions of Hb: 1). Strong buffer system 2). Carriage of O2 & CO2 Make it Easy 4 BLOOD 1 Dr Nageeb Reactions of Hb 1) Oxy hemoglobin ( Carry O2 )‫إمسكيو‬  O2 bind with iron in Ferrous (Fe++) state. So, it is called oxygenation not oxidation.   affinity of Hb to O2 by : a)  pH. ( H+) b) Temperature. c) CO2 d) 2,3-DPG (di phospho glycerate) ‫ن ن‬ ‫رن‬ ‫االكسجي‬ ‫الهيموجلوبي ىييك‬ ‫رن‬ ‫ وفائدتها انها ي‬.. ‫اإلكسجي يف الجسم‬ ‫تخىل‬ ‫ر‬ ‫ ن يف حاالت نقص‬rbcs ‫ تتكون داخل‬2,3-DPG ‫ماده ال‬ ‫رن‬ 😊.. ‫باالكسجي بتاعه من أجل الجسم‬ ‫بيضح‬ ‫رن‬ ‫الهيموجلوبي‬ , ‫للخاليا علشان يلحقها‬ ‫ي‬ 2) Carbamin Hb. ( Carry O2 & CO2 )  CO2 is attached to the globin part of Hb  It is the only reaction with globin part of Hb.  Binding of Hb to CO2   affinity of Hb to O2. Make it Easy 5 BLOOD 1 Dr Nageeb 3) Met Hb. (oxidized Hb) ) Not carry O2 ( ‫أكسده‬  Strong oxidation by drugs or oxidizing agents  iron is oxidized into ferric (Fe+++) state.  Oxidized Hb  dusky coloration of skin like cyanosis.  Normally, Met Hb not exceed 0.5% Due to activity of NADH-MetHb-reductase enzyme.  Met Hb increased in cases of a) strong oxidation b) deficiency of the NADH-MetHb-reductase enzyme.. ‫ لو زاد بكمٌه كبٌره ٌصبح لون الدم ازرق قاتم‬.. ‫الحظ ان الحدٌد فً التكافؤ الثالثً ال ٌمكنه حمل االكسجٌن‬ ‫ وهو ازرقاق الشفاٌف واالطراف وهً عالمه خطٌره تدل على نقص تشبع‬..cyanosis ‫بالزرقه‬ ُ ‫وٌصاب االنسان‬ ‫الدم باالكسجٌن‬ 4) Carboxy Hb. ) Not carry O2 (  Carbon mono oxide (CO) is a toxic gas produced by incomplete burning of carbon.  CO is attached to Fe++ in high affinity (210 times as O2). ‫رن‬  The Part of Hb attached to CO not carry O2. ‫إكسجي‬ ‫ال يحمل‬  Remaining part of Hb which carry O2 not give its O2 to the tissue. ‫األكسجي‬ ‫رن‬ ‫يعط‬ ‫ي‬ ‫ال‬ Make it Easy 6  BLOOD 1 Dr Nageeb Types of Hb According to the composition of the globin poly peptide chains: 1) Adult Hb. (HbA) 2) HbA2. 3) Fetal Hb. (HbF) Globin part is formed of: Globin part is formed of: Globin part is formed of: a) 2 alpha  chains (141 amino acids). a) 2 alpha  chains (141 amino acids). a) 2 alpha  chains (141 amino acids). b) 2 beta  chains (146 amino acids). b) 2 delta  chains (146 amino acids). b) 2 gamma  chains (146 amino acids). Which differ from  chains in the terminal 10 a.a. Which differ from  chains in 37 a.a. Amount: Amount: Amount: 97.5% of Hb in Adults 1 - 2% of Hb in adults. It is present in the Fetus. ( ‫) بيحبوها لإلمسكيو‬ ( ‫) بيحبوها لإلمسكيو‬ ( ‫) بيحبوها لإلمسكيو‬ Then, it is replaced by adult Hb after birth. Character: It has high affinity for O2 & less affinity to 2,3- DPG. ( ‫) بيحبوها لإلمسكيو‬ This facilitate movement of O2 from maternal circulation to fetus. ‫اول ما ٌلمح االكسجٌن جاي من عند‬ ‫امه ٌخطفه علطول وٌمسك فٌه بإٌده وسنانه‬ 4) Glycosylated Hb (Hemoglobin A1c) ‫تحليل السكر التراكمي‬ 5) HbS ‫ هيموجلوبين األنيميا المنجليه‬sickle cells Glucose is attached to terminal valin amino acid in -chain. It is abnormal type of Hb Amount: 3 - 7% of Hb. due to congenital abnormality of  chain. Importance: Glycosylated Hb increases in cases of Valin amino acid present instead of Glutamic acid at position 6 in  uncontrolled diabetes mellitus. (during the last 3 - 4 months). chain. ) ‫ ٌكفٌكم شر الفالٌن ( مش الجاٌٌن‬.. ‫ٌا راٌحٌن‬ Hb. S  sickle cell hemolytic anemia Make it Easy | Dr Nageeb 7 BLOOD 1 Dr Nageeb Formation of RBCs (Erythropoiesis) (A) Sites of formation: 1- In the foetus:  Yolk sac: in the first few weeks of pregnancy.  Liver & spleen: from 6 wks to 6 months.  Bone marrow: from the 6th month. 2- In infancy & childhood:  From red bone marrow of all bones. 3- In adult life:  The red bone marrow restricted to the central skeleton as : (flat bones as skull, vertebrae, ribs, sternum, pelvic bones) also proximal ends of long bones as humerus, femur & tibia.  The yellow bone marrow can change to active red marrow to produce RBCs as in case of severe anemia (extramedullary hemopiosis). (B) Factors affecting erythropoiesis: [I]- Oxygen supply to tissue: (hypoxia): Erythropoietin Hormone [II] - Dietary factors: a-Proteins b- Metal ions 1- Iron 2-Copper 3-Cobalt c- Vitamins: (Erythrocytic Maturation factors) 1- Vitamin B12 2- Folic acid 3- Vit. C 4- Vit B complex [III]- Hormonal factors: a) Androgens b) Thyroid c) Pituitary d) hormones e) Glucocorticoids f) Haemopoietic growth factors [IV]- State of liver, bone marrow and kidney: a) Liver: b) Bone marrow c) Kidney Make it Easy | Dr Nageeb 8 BLOOD 1 Dr Nageeb Oxygen supply to tissue: (hypoxia):  As the main function of RBCs is O2 supply to tissue, so  hypoxia (in anemia, high altitude, heart , lung diseases) is the main stimulus for RBCs.  Hypoxia stimulate the secretion of Erythropoitin Hormone secretion from the kidney (85%) and the remaining from the liver. hypoxia stimulates the kidney to release Renal Erythropoietic Factor (REF), which act on the plasma alpha globulin released from the liver in hypoxia to form erythropoitin hormone (glycoprotein-MW = 34000) which stimulates the red bone marrow to form new RBCs. Erythropoitin formation is stimulated by  alkalosis  high altitude  catecholamines  prostaglandins  androgens  cobalt. Regulation :  If hypoxia is corrected there is negative feed back inhibition of erythropoitin secretion.  In severe haemorrhage, the level of erythropoitin increases to activate the yellow bone marrow and liver and spleen (extramedullary sites) to form RBCs. Make it Easy | Dr Nageeb 9 BLOOD 1 Dr Nageeb Dietary factors a-Proteins:  high biological value as animal proteins (contain essential A.A) to form globin part of Hb. b- Metal ions 1- Iron 2-Copper carried by plasma protein (ceruloplasmin) to catalyse the oxidation of ferrous into ferric state to be carried as transferrin 3-Cobalt stimulate erythropoitin release from the kidney, so increase cobalt may lead to polycythemia c- Vitamins: (Erythrocytic Maturation factors) 1- Vitamin B12: (Extrinsic factor) (Antipernicious anemia) 2- Folic acid 3- Vit. C required for reduction of ferric to ferrous and help maturation of red blood cells 4- Vit B complex needed for normal erythropoiesis Iron Importance: - for synthesis of haem part of Hb. - for synthesis of myoglobin and enzymes as cytochrome oxidase, peroxidase & catalase. Sources: meat, liver, green vegetables & molasses (it must be added to infant diet as the mother milk is not sufficient in iron). Requirement: - adult male require 10 mg/day. - adult female require 15 mg/d. - pregnant require 20 mg/d. - infant require 10 mg/d Make it Easy | Dr Nageeb 11 BLOOD 1 Dr Nageeb Loss: - In faeces, sweat, exfoliated skin (about 1mg/day) - very little amount in urine and in lactating milk. - Women loss in menstruation: 0.5 mg/d (3.5 mg/period) Factors affecting iron absorption: 1- Body need of iron: increase need as in pregnancy lead to increase absorption directly from intestinal to plasma. 2- pH of stomach: acidic pH → change of ferric to ferrous with increase absorption.(so, patient with gastrectomy demonstrate impaired iron absorption with iron deficiency anemia). 3-Contents of food: - Oxalates, phytate & phosphate →  absorption. - Ascrobate, lactate & succinate →  absorption. 4-Hypoxia and anemia → increase iron absorption. Vitamin B12: (Extrinsic factor) (Antipernicious anemia) Importance: It is very important for maturation of RBCs, biosynthesis of purine, pyramidines, nucleic acids and DNA synthesis and cell division. Absorption: - Vit B12 present in diet as protein bound complex. - It is fred by HCl & proteolytic enzymes. - Then it combines with glycoprotein secreted from parietal cells of gastric glands called the intrinsic factor to prevent its digestion by enzymes till it reaches the terminal ileum. - In the terminal ileum, absorption of B12 occurs by pinocytosis into intestine then to blood. - In the blood vit. B12 carried by transcobalamin to bone marrow. Storage: in liver. Requirement: - 1-2 g/day - storage in liver is very high = 1-5 mg. So  intake or absorption of vit.B12 is not manifested till 5 years. Deficiency: Due to malabsorption → megaloblastic pernicious anemia. Make it Easy | Dr Nageeb 11 BLOOD 1 Dr Nageeb Folic acid - It is water soluble vitamin. - It is present in green vegetables, some fruits, liver and meat. - It is absorbed easily from all small intestine - changed into active folinic acid which is essential for DNA formation and cell maturation. - Its deficiency leads to megaloblastic anaemia. Hormonal factors: - Androgens  stimulate erythropoitin production from the kidney and its effect on bone marrow causing increase RBCs (so in male RBCs count more than in female). - Thyroid hormone  stimulates the bone marrow cells and general metabolism & increase O2 consumption and decrease O2 supply hypoxia which stimulates erythropoiesis.  So, increase thyroid hormone lead to polycythemia and its decrease leads to anemia - Pituitary hormones  [Growth h., Gonadal h., Thyroid-stimulating h. & Adrenocorticotrophic hormones] stimulate bone marrow. - Glucocorticoids:  stimulate the general metabolism and stimulate bone marrow - Haemopoietic growth factors:  secreted by lymphocytes, monocytes, endothelial cells and fibroblasts  stimulate stem cells in bone marrow to produce mature RBCs. Make it Easy | Dr Nageeb 12 BLOOD 1 Dr Nageeb State of liver, bone marrow and kidney: - Liver: 1) -It is site for storage of iron, vit B12, folic acid & copper. 2) -It shares in formation of erythropoietin hormone. 3) -It is responsible for formation of globin part of hemoglobin. 4) -It is responsible for synthesis of RBCs in the fetal life. 5) -It is responsible for destruction of old RBCs. - Bone marrow: is site of erythropoiesis  any disease (atomic irradiation, deep x-ray, drugs) aplastic anaemia - Kidney: is the site of formation of erythropiotin protein  its failure lead to decrease erythropoitin and retention of toxic substances as urea lead to depression of bone marrow. Make it Easy | Dr Nageeb 13  BLOOD 1 Dr Nageeb anaemia the decrease in red cell count or hemoglobin content leading to decrease O2 supply to tissues with symptoms of hypoxia.  Classifications of anemia: A. Etiological: (according to the causes) B. Morphological: (according to the Size And Hb content ) Increase blood loss Increase blood destruction Decrease blood Microcytic Macrocytic Normocytic (Hemorrhagic) (Hemolytic) formation ( MCV) ( MCV) (normal MCV) 1. Acute: 1. Intra-corpuscular defects: 1. Nutritional: Hypochromic Hyperchromic Normochromic trauma. 1)  Iron. ( MCH) ( MCH) (normal MCH) 1) Cell membrane defect 2)  Vit. B12 (congenital spherocytosis). 2. Chronic: 3)  Folic acid. (Megaloblastic) peptic ulcer 2) Enzyme defect 4)  Protein. 1. Iron deficiency. 1. Vit. B12 1. Hemolytic. piles. (G-6-P-D deficiency). 5)  Vit. C deficiency. 2. Chronic Epistaxis 2. Acute 3) Hemoglobinopathies: blood loss. 2. Aplastic: 2. Folic acid hemorrhagic. a) Thalassemia. 3. Disorders deficiency. Bone marrow b) Sickle cell anemia. of globin. 3. Aplastic. failure as in:  Irradiation. 4. Disorders 2. Extra-corpuscular defects: 4. Erythropoietin  Infection. of porphyrin. 1) Infection as malaria.  Toxins.  Renal failure. 2) Incompatible blood  Tumor.  Liver failure. transfusion.  Autoimmune 3) Physical agents as heat.  Congenital 4) Chemical poisons as lead. 5) Snake venom & fava bean. Make it Easy | Dr Nageeb 14 BLOOD 1 Dr Nageeb Hemolytic anaemia Excessive destruction of RBCs due to: a-Defect in membrane (1) Congenital [hereditary]spherocytosis: (2) Enzyme defect: b-Defect in hemoglobin (3) Thalassemia (Mediterranean Sea Anaemia): (4) Sickle cell anaemia: General features of hemolytic anaemia 1) Blood Picture :  Normocytic ( Normal MCV ) normochromic ( Normal MCH ) anaemia  (decrease RBCs count, Hb content, Ht. Value) 2) RBCs have  abnormal shape (poikilocytosis)  abnormal size (anisocytosis)  increase reticulocytes. 3)Bone marrow  hyperplasia (compensatory increase in bone marrow activity). 4) Jaundice  (yellow discoloration of skin and mucous membranes due to increase indirect bilirubin). 5) Splenomegaly and good response to spleenectomy. 6) Dark urine after few minutes due to increased urobilinogen. 7) Dark stool due to increased amount of stercobilinogen. Make it Easy | Dr Nageeb 15  BLOOD 1 Dr Nageeb Hemolytic anemias Congenital Enzyme defects Thalassemia Sickle cell anemia Spherocytosis (G-6-P-D deficiency) (Mediterranean sea anemia) Cause: Cause: Cause: Cause: It is Hereditary as The disease is Hereditary. The disease is Hereditary. The disease is Hereditary. Mendelian dominant a) If from the two parents a) If from the two parents non sex-linked. (homozygous)  (homozygous)  sickle cell thalassemia major (severe). anemia (Hbss). Due to: Due to: RBCs Cell membrane glucose 6-phosphate dehydrogenase b) If from the one parent b) If from the one parents (defect in Spectrin protein). (G-6-P-D) deficiency. (heterozygous)  (heterozygous)  sickle cell thalassemia minor. trait (HbAs). Effect: Effect: Defect in spectrin   Na+  G-6-P-D   ability of RBCs to Due to: permeability & osmosis of form reduced glutathione to protect Defect in hemoglobin synthesis Due to: H2O  more fragile RBCs. itself against oxidative agents  affecting the globin part: Formation of HbS.  met Hb & RBCs hemolysis. It is abnormal type of Hb due to There is also abnormal a) If the disease affect  chain: congenital abnormality of  glycolysis inside the cells Oxidative agents as: fava bean &  -thalassemia. chain. sulpha & chloramephnicol & (fatal & rare). Valin amino acid present The RBCs are small and antimalaria drugs. instead of Glutamic acid at spherical b) If the disease affect β chain: position 6 in  chain. (microspherocytes). Favism:  β-thalassemia. It is hereditary hemolytic disease (mild & common). Effect: caused by eating or smelling the HbS  sickle cell  hemolysis. pollens of fava beans   met Hb & RBCs hemolysis. Make it Easy | Dr Nageeb 16  BLOOD 1 Dr Nageeb Laboratory findings: Laboratory findings: Laboratory findings: Laboratory findings: 1. General features of 1. General features of hemolytic 1. General features of 1. General features of hemolytic anemia. anemia. hemolytic anemia. hemolytic anemia. 2. Fragile RBCs by both: 2. Attacks of hemolysis on exposure 2. RBCs show abnormal 2. HbS is insoluble at low O2 - by spleen. to oxidizing agent. morphology (Target cells). tension  RBCs sickle shaped - By Osmotic hemolysis And this is the most  more hemolysis. (osmotic fragility). 3. Decrease G-6-P-D in RBCs by diagnostic feature So, occur as crisis associated enzyme assay. to decrease oxygen tension. 3. Decrease RBCs spectrin 3. RBCs have: protein in cell - More mechanical fragility 3. Sickling test: for membrane. in spleen diagnosis of sickle cell anemia - But, less osmotic fragility. one drop of bl. from the patients + 2% Na metabisulphite (as a -  content of Fetal Hb. reducing agent) for 1-2 hours sickle cells on blood film. 4. Defect of globin chains. Make it Easy | Dr Nageeb 17  BLOOD 1 Dr Nageeb Nutritional anemias Iron deficiency anemia Vit.B12 deficiency anemia Folic acid deficiency (Pernicious anemia) Causes: Causes: Causes: 1)  Iron intake: due to malnutrition, as in 1) caused by decrease of intrinsic factor secretion 1) Increase demand as in - prolonged breast feeding in infants without Due to: pregnancy. iron intake. a) Atrophy of gastric mucosa. b) Autoimmune disease or Ulcer. 2) Decrease intake. 2)  Iron absorption: c) Gastrectomy. -  HCl (achlorohydria). 3) Malabsorption. -  Phosphate & Oxalates & Phytate in food. 2) Diseases affecting Lower ileum  - Dysentery or steatorrhea.  vit.B12 absorption. 3)  Iron utilization: 3) Diphyllobothrium Latum (D. latum)  Lead poison & renal failure.  vit.B12 absorption. 4)  Iron requirements: Pregnancy & babies. 4) Low storage of vit.B12 as in Liver disease. 5)  Iron loss: 5) Low intake of vit.B12 (rare). Chronic hemorrhage & ancylostoma. Make it Easy | Dr Nageeb 18  BLOOD 1 Dr Nageeb Laboratory findings: Laboratory findings: Laboratory findings: 1. Blood picture: 1. Blood picture: 1. Blood picture: Microcytic Hypochromic anemia: Macrocytic Hyperchromic anemia Macrocytic Hyperchromic -  RBCs count &  Hb content. (Megaloblastic): anemia -  MCV &  MCH &  MCHC. -  very RBCs count &  Hb content. (the same as in vit.B12 -  MCV &  MCH & normal MCHC deficiency). 2. Target cells may be present. 2. bone marrow  Hyperplasia & premature cells 2. No gastric signs. 3. Abnormal Shapes of RBCs (see before). 3. Abnormal shape of RBCs (see before). 3. No neurological signs. 4.  RBCs Survival: (short life span of RBCs). 4. Stomach: 4. Decreased plasma level of Achlorohydria ( HCl) or Atrophy. folic acid 5.  Serum iron concentration. (normal = 2-20 ngm/ml) (normal male = 75-175 g/dl ) 5. Nervous system: (normal female=50-150 g/dl ) Degeneration of spinal cord as vit B12 is required for metabolism of myelin sheath. 6.  Iron Stores in bone marrow (So, it is called pernicious). Diagnosis: ( HaemoSiderin). 1.  Folic acid in blood. Diagnosis of Vit B12 deficiency: 2. Figlu test. 7.  total Iron binding capacity. 1.  Vit B12 in blood. (normal = 240 – 450 g/dl). 2. Schilling test. Make it Easy | Dr Nageeb 19 BLOOD 1 Dr Nageeb Diagnosis of vit B12 deficiency: 1) VB12 in blood (normal 200-900 pico.gm/ml). 2) Schilling test: First : Large dose of non radioactive vit B12 is injected to meat body requirement of vit.B12.  Then radioactive B12 is given orally. ‫ وبعد كدا تدي حبوب فٌتامٌن مشعه علشان‬.. ‫هتدي كمٌه كبٌره من الفٌتامٌن علشان تعمل تشبع لكل احتٌاجات الجسم‬ ‫نعرف نحسب كمٌتها فً البول‬ Normally this radioactive B12 absorbed and not needed as body is saturated now , so it is excreted in urine (more than 15% of amount intaked). ‫الطبٌعً الحبوب المشعه ٌحصلها امتصاص وبعدٌن تنزل فً البول الن الجسم اصال مش محتاج الفٌتامٌن دلوقتً النه‬.. ‫حصله تشبع خالص‬ - If no excretion in urine the cause may be: ‫يبق معناها مدخلش الدم اصال ومحصلوش امتصاص وهنا نف احتمال من ر ن‬ ‫اتني‬ ‫ى‬ ‫ن‬ ‫نن‬ ‫ي‬ ‫لو ميلش يف البول ي‬ 1)Decreased intrinsic factor secretion by stomach (pernicious anaemia), so  if the intrinsic factor is given to this patient before the test ,this lead to vit B12 excreted in urine. intrinsic ‫ معناها حصله امتصاص وبالتالً المشكله كانت فال‬intrinsic factor ‫لو نزل فً البول بعد ما ادٌته‬ factors 2) Diseased lower ileum (known by if intrinsic factor is given no excretion in urine occur). ‫ وده معناها ان المشكله‬, intrinsic factor ‫كون انه منزلش البول معناها محصلوش امتصاص برضو رغم انك ادٌت‬ lower ileum ‫ ٌعنً فال‬.. ‫المرادي اكٌد فً مكان االمتصاص نفسه‬ Make it Easy | Dr Nageeb 21 BLOOD 1 Dr Nageeb Diagnosis of Folic acid deficiency Diagnosis: by Figlu test: The amino acid histidine is metabolished to Formimino-Glutamic acid (Figlu).  Folic acid combine with Figlu to changed into formiminofolic compound and glutamic acid (execreted in urine) - Folic acid deficiency excretion of large amount of Figlu in urine. ‫ النه مش القٌه‬folic acid ‫ مع‬combination ‫ معناها انه محصلوش‬, ‫ نزل فالبول بحاله كدا‬Figlu ‫كون ان ال‬ Folic acid deficiency ‫ ٌعنً بالمخخخ كده اكٌد ناقصص‬, ‫فالجسم‬ Megaloblastic anaemia(Macrocytic hyperchromic) caused by   vit12 or  folic acid failure of cell division in bone marrow. The RBCs increase in size (megaloblasts) and decrease in number (anaemia). In treatment of megaloblastic anaemia the cause must be known as  if the case due to  vit.B12 and wrongly treated by folic acid  stimulate the metabolism of the myelin sheaths and increase the need of vit B12 which is already deficient leading to the nervous lesions becomes worse. 21 ‫ وعلشان ٌشتغل محتاج فٌتامٌن ب‬myelin sheath ‫الفولٌك اسٌد وظٌفته ٌحفز نمو االعصاب وال‬ myelin sheath ‫ الفولٌك اسٌد هٌحفز نمو االعصاب وال‬, 21 ‫لو انت ادٌت العٌان فولٌك اسٌد فقط بدون فٌتامٌن ب‬ ‫ بالتالً ده هٌزود المشكله‬, ‫ اللً هو اصال ناقص فالجسم‬, 21 ‫ولكن كده هٌضطر ٌستهلك كمٌه كبٌره من فٌتامٌن ب‬ ‫ علشان تبقً دكتور فخم‬.. ‫ بالتالً اتعلم كدا انك تدي االتنٌن سوا مع بعض‬, ‫اكترر‬ Make it Easy | Dr Nageeb 21 BLOOD 1 Dr Nageeb General Effects of anaemia 1) Anaemia decreases the blood viscosity decrease resistance to blood flow  cardiac output 2) Anaemia causes decrease O2 supply to tissue and metabolite accumulation leading to  vasodilatation of tissue vessels with increase venous return to the heart and increase cardiac output. 3) If the patient increases his activity, this may lead to heart failure due to  heart load. 4) heart failure may occur due to severe decrease in oxygen supply to cardiac muscle itself. venous return  ‫كميه الدم اللي هترجع من خالل االورده علشان تملي القلب‬ cardiac output.  ‫كميه الدم اللي القلب هيضخها في الشرايين‬ Destruction Of Rbcs - Life span of RBCs = 120 days. - Old RBCs destroyed in narrow capillaries of RES (spleen)  Hb released.  Globin: used in protein synthesis in liver.  Iron part of haem: stored as ferritin in liver. - Protoporphyrin part of haem: produce bile pigments (bilirubin). - Bilirubin is conjugated in liver. Then, excreted in bile. Finally, excreted in stool & urine. Make it Easy | Dr Nageeb 22 BLOOD 1 Dr Nageeb Polycythemia Definition: - Abnormal increase in RBCs number may reach 10 millions / mm3. Types: 1. Primary polycythemia (Polycythemia Vera): - The cause is unknown (may be tumor). - The bone marrow produces excessive amount of red blood cells (8-9 millions) 2. Secondary polycythemia: - Due to: Overstimulation of bone marrow by hypoxia. 1) Chronic mountain sickness. (Physiologic type). At high altitude for several weeks  hypoxia  release of renal erythropoietic factor   erythropoietin  stimulate RBCs formation from bone marrow. 2) Congenital Cyanotic Cardiac diseases  hypoxia. 3) Chronic lung diseases  hypoxia. 4) Cigarette smoking  hypoxia. 5) Kidney diseases associated with high erythropoietin secretion. Effects: -  RBCs   blood Volume & blood Viscosity. This leads to: 1)  Venous return   cardiac output   arterial blood pressure. 2)  Total peripheral resistance   arterial blood pressure. 3)  COP &  ABP  Hyperdynamic circulation & Heart failure. (Due to increased load on the heart). 4) Sluggish blood flow  Capillaries plugged with blood  Hemorrhage. 5) Sluggish blood flow  stagnant hypoxia  Cyanosis (bluish skin). 6) Sluggish blood flow  thrombosis (intravascular Clotting). Treatment: 1) Repeated Venosection to decrease blood Volume & Viscosity. 2) Chemotherapy to suppress the over activity of the bone marrow. 3) Treatment of the Cause of the secondary type. Make it Easy | Dr Nageeb 23