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Home , Carbaminohemoglobin, Stercobilin

LECTURE 7

BLOOD PHYSIOLOGY (ll) Erythropoiesis (Males)

• ‘Red : important • Black : in male / female slides • Pink : in girls slides only • Blue : in male slides only • Green : notes, Extra Objectives

• Describe essential elements needed for RBC formation. • Describe the process of Vit B12 absorption and its malabsorption. • Recognize haemaglobin structure and its functions. • Discuss iron metabolism (absorption, storage and transport) Describe the fate of old RBC. • Describe the fate of old RBC. • Describe anemia and its causes. • Recognize causes of polycythemia. HAEMOGLOBIN

2) Carriage of 3) Carriage of Function CO2 O2 of • Hb bind CO2 = • Hb reversibly bind Heamoglobin carboxy- O2 to form hemaglobin oxy- affect by 1) Buffer 1. pH 2.Temperatre 3.H+ Any protein act as a buffer Hb molecules consist 4 chains each formed of

Protoporphyrin Poly-peptide ring + iron (F2+) chain HAEMOGLOBIN Types of Hb

Normal HB F → Fetal Life Abnormal موجود في البيبي سحب higher affinity to االكسجن بكمة اكبر عشان ياخذه من األم ولما يكبر البيبي يتحول لـ Hb A Hemoglobino- Hb A Hb A2 Hb F pathies • 2α & 2beta • 2 α & 2 delta • 2α & 2γ chains Abnormality in the chains chains • adult Hb • Hb of polypeptide chain • 2% • 98% intrauterine life e.g thalassemias and

• tetrameric protein α2β2 sickle cell (HbS). • alpha 141 aa residues • beta 146 aa residues Hemoglobin

Polypeptide chain () Amino acids Iron formation of globin in formation of haemoglobin haemoglobin Iron

Synthesis: 1. In Mitochondria 2. Attach to transferrin 3. Combine with α and β protein chains Essential elements for RBC formation & Maturation Deficiency Elements Function Lead To Examples formation of Anemia Vit B12 and Amino acids globin in (Hemoglobino Folic acid haemoglobin pathies) Other: Vit B6, Riboflavin, nicotinic formation of Anemia acid, biotin, Vit C, Iron Vit E haemoglobin (Micro-cytic hypochromic) Essential elements Copper, Cobalt, Vitamins Synthesis of Anemia zinc, manganese nucleoprotein (Macro-cytic Hormones Essential elements megaloblastic) Androgens, Thyroid, cortisol & Hemo-globin anemia means deficiency Hormones Hemo:iron Globin:protein of hemoglobin growth hormones RBC Life Cycle

RBCs live only 120 days • In macrophages of or spleen: Cells wear out from bending to fit through capillaries – Globin portion is broken down into amino acids and recycled Repair is not possible due to lack of organelles Worn out cells are removed by macrophages in spleen and liver – portion is split into iron Breakdown products are recycled (Fe+3) and (green pigment)

Biliverdin Stercobilin → Heme Feces (Green) (Yellow) → Urine

Fe + Red bone Heme Transferrin Liver Marrow

Globin Amino Acids Recycled Anemia and Polycythemia Normal: 5 million :Polycythemia َع َرض وليس مرض ANEMIA POLYCYTHEMIA 15 million • Decrease number of RBC • Increase number of • Decrease Hb RBC • For the same age and sex. Types Primary Secondary to Symptoms Types (Polycythemia Rubra Vera - PRV) hypoxia • Tired • Macrocytic • Fatigue anemia high altitude uncontrolled RBC (physiological), • short of breath • Microcytic • heart failure. production. chronic respiratory hypochromic or cardiac disease سبب حقيقي anemia سبب غير حقيقي يعوض الجسم عن نقص Oxygen (Type of Adaption) Anemia Causes of Anemia

RBC Haemolytic Loss Decrease production excessive destruction acute Chronic Nutritional Bone marrow causes failure Abnormal Incompatible Erythroblastosis cells or Hb blood fetalis . transfusion • Iron destruction by Accident microcytic → Microcytic • cancer لما يُنقل للشخص RBC return hypochromic •Spherocytosis) دم غير مناسب hypochromic anaemia. • radiation to normal anaema •sickle cells • Drugs→ • Vit B12 & Folic acid 3-6weeks) (ulcer,worms) Aplastic → megaloblastic Spherocytosis → مشكلة بـ .anaemia anaemia (Macrocytic) cell membrane تتكسر الـ RBCs بسرعة خساره كميات قليلة حاد <- Acute من الدم في وقت →sickle cells خساره دم كثير في Example: wrong diet, vegetarian طويل مثل الدورة تغير في شفرة وحدة فحدثت وقت قصير الشهرية، البواسير و طفرة، وراثي. )األنيميا قرحة المعدة. المنجلية( & Folic acid

Dietary source: meat, milk, liver, Type of Anemia fat, green vegetables. Macro-cytic (megaloblastic) Oval shape RBC

Importantance Deficiency ? • reduced RBC Nuclear •fvfsz Lead to count & Hb • DNA synthesis division • Final maturation Failure of of RBC. Maturation Lead to • Abnormally large oval shape RBC • استنا ًدا على أهمية الفيتامين نستنتج نقصه ايش يأثر فيه • Short life span Malabsorption of Vit. B12 Pernicious anemia is a type of megaloblastic anemia in which the body isn't able to absorb vitamin B12 due to a lack of intrinsic factor in stomach secretions.

Goes to parietal cells of Secrets intrinsic terminal Ileum stomach. factor

Needed to absorb VB12 + intrinsic factor is VB12 absorbed in the terminal Ileum Causes of VB12 رخيص نخليه لين النهاية ثم deficiencies نمتصه في terminal lleum الموجودة في نهاية األمعاء الدقيقة

Inadequate Poor absorption Poor absorption = intake (low due to Intestinal decrease in intrinsic intake) disease factors Anemia Types Macro-cytic Micro-cytic VERY IMP. You compare for the anemia same AGE and the same SEX hypochromic anemia (female Hb count to normal female Hb count. NOT to a male) RBC are almost as large as the RBC's are smaller than normal lymphocyte Caused by the deficiency of Iron caused by the deficiency of vitB12 and Thalassemia. and Folic Acid

Hyper-segmented neurotrophil increased zone of central pallor

fewer RBCs microcytic hypochromic anemia smaller size less hemoglobin Hyper-segmented neurotrophil of each RBC in each RBC

↑ anisocytosis (variation in size) ↑ poikilocytosis (variation in shape) Hyper-segmented normal Central pollar Iron metabolism (Fe)

65% Haemo- globin 5% other Iron is needed for the synthesis of hems Total Iron • haemoglobin in the body = • oxsidase 15-30% 4-5g • peroxidase stored iron in the form of • catalase ferritin in the 1% bound to liver, spleen transferrin and bone (betaglobulin) marrow. in blood Transferrin: transport protein Iron absorption

Goes to Gives Ferric, F+3 stomach Ferrous, F+2

• oxidized form in stomach Ferric • reduced form • in food F+3 is reduced by • Better to absorb gastric acid, Vitamin C.

عشان كذا لما ناخذ حديد ( Iron( ينصحون نشرب معه عصير برتقال ( vitamin C) ألنه يساعد باالمتصاص

Rate of iron absorption depend on the amount of iron stored Transport and storage of iron

-Ferritin: intracellular iron-storage protein -Ferritin that is not combined with iron is called apoferritin. Haemosiderin (insoluble complex molecule, in liver, spleen, bone marrow) Forms of Storage Transport and storage of Ferritin iron (apoferritin + iron)

Form of Transferrin Transportation (apotransferrin + (in plasma) iron)

Daily loss of iron is 0.6 mg in male & 1.3mg/day in females. Destruction of RBC

RBC life span in circulation = 120 days

Old cell has a fragile cell membrane, cell will rupture as it passes in narrow capillaries (and spleen).

Released Hemoglobin is taken up by macrophages in liver, spleen & bone marrow

Iron (get away from the heme)→ Hb is broken into its ferritin (iron without heme) component

Globin Heam

()→ bilirubin→ secreted by Polypeptide → amino acids Iron → ferrtin the liver into . [excess destruction (protein pool = storage) of RBC ] Quiz 1) Which of the following nutrient deficiencies is most often associated with microcytic hypochromic anemia? A) Cobalamin B) Folic acid C) Iron D)

2) The protein responsible for iron transport in plasma is

A) α 1 -anti trypsin B) Ferritin C) Apo-transferrin D) Apo-ferritin key answers: 1) C 3) A 30 years old male is brought to the hospital with history of gastrectomy. His skin appears lemon-yellow.Investigations 2) C reveal hemoglobin 10 g/dl, odd shaped RBCs and Serum Vitamin B 12 is low. He is likely to be sufferingfrom: 3) D A) Hemolytic Anemia C) Pernicious Anemia D) Megaloblastic Anemia 4) A B) Aplastic Anemia 5) C 4) A 34-year-old man with schizophrenia has chronic fatigue for 6 months. He has a good appetite but has developed adislike for vegetables since last 1 year. Hisphysical and neurological examinations are normal. His hemoglobin level is 9.1 g/dl, leukocyte count is 10,000/mm andMean Corpuscular Volume is 122fl (normal 77-93 fl). Which of the following is the most likely diagnosis? A) Folic acid deficiency B) Aplastic anemia C) Sickle cell anemia D) Hemolytic anemia

5) The form of hemoglobin that has attached is called A) oxyhemoglobin B) deoxyhemoglobin C) D) carbaminohemoglobin Thank you

Boys team members Girls team members • اروى االمام • عمر الدوسري • ديما المزيد • زياد الدوسري • جود الخليفة • جود العتيبي • محمد الحمد • رغد المبارك • فيصل القفاري • ريناد المطوع • عبدهللا باسمح • ريما المطوع :Team leaders • جهاد العريني o عمر الشيناوي • طرفة آل كلثم o ايالف المسيحل • مي بابعير • نجود العلي • نورة المزروع