Red Blood Cell Pathology Case 1 44 yr old, male. c/o: Fatigue, weakness, dyspnea on exertion and palpitation.

itation. Mild diarrhea Noted intermittent numbness & tingling of lower extremities, loss of balance during walking. History of resection of the distal ileum Physical examination: tachycardia (110bpm) and systolic flow murmur. His skin is of lemon-yellow color; beefy red tongue with loss of papillae. Neurological examination: decreased sensation to a light touch and vibration in the lower extremities. Liver, spleen and peripheral lymph nodes are not enlarged.

Lab (hematological tests): Hb: 60g/l Mean corpuscular volume: 106m3 Erythrocytes: 1.5x1012/l RES: 26mm/h Reticulocytes: 0.3% Differential count (%) neutrophils: 46 band forms: 1

metamyelocytes: 0 lymphocytes: 48 monocytes: 3 eosinophils: 0 basophils: 0 platelet count: 100x109/l

White cell count : 4.1x109/l Blood film indicates: anisocytosis, poikilocytosis, anisochromia, macrocytes and hypersegmented neutrophils. Mean diameter of erythrocyte = 8.5m Serum iron: 38mol/L Serum bilirubin: 39mol/L

1. What is the most likely form of anemia in this patient? erythrocytes, reticulocytes % = B12-deficiency anemia 2. What is the pathogenesis of this disease? - Impaired red cell production > hyporegeneration, reticulocytes (0.3%) - Deficiency of vit B12 resulted from lack of vit b12 absorption at terminal ileum due to absent of intrinsic factor(IF) 3. What are the pathophysiological mechanisms of the mans symptoms of tachycardia, paresthesia and impaired prioception? Tachycardia < incr rate of breathing;dyspnea < hypoxia (hemolytic) Paresthesia < disorder of sensation < damaged peripheral nerves Impaired porprioception : B12 deficiency > d/o of metabolism of fatty acids & oils > methyl malonic acid > demyelination > damage of post columnar spinal cord > nervous syndrome > loss of balance. Additional : Biochemical features: Poorly differentiated, larger cells,macrocytic Stuck within the meshwork of spleen Hemolysis of RBC (hence RBC proliferation ) - mph Bilirubin Iron level JAUNDICE

Case 2 A 44 year old patient is admitted to the clinic with the following complaints:weakness, dysnea, heart palpitation on exertion , numbness and tingling in his lower limbs ,diarrhea signs . From history : 5 years ago he had a resection of the terminal part of the ileum. Now he is suffering from disbacterriosis .On peripheral lymph nodes are not enlarged , tendon reflexes are weakened .Blood examination :Hb 60g/L, Er -1.5x 1012/L, Thro-100x109/ L, Ret 0.3%, Leu-4.1x109/L, RES -26mm/h, Leuk, dif .count :bas -0.eos-2,neutr:metamyel-0,band -1,segm-46,lymph-48,monoc-3. In the thin blood smear:anisocytosis,poikilocytosis,anisochromia and single giant polysegmented neutrophils ,MD of erythrocytes is about 8.5 mcm.Serum iron -38 mol/L serum, bilirubin -39mol/L

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What type of red blood pathology does the patient have? B12 deficiency anaemia Give an explanation of your conclusion? Base on clinical diagnosis the patients have jaundice , thrombocytopenia ,leucopenia , megaloblastic anemia Describe the pathogenesis of this disease and its clinical features. (a) mechanism is b12+internal cascade factor leads to coagulates with internal factor (b) then transport to intestinal to ileum. (c) leads to adhesion of section of ileum.. (d) then lead to block of transport of b12 into bone so occur B12 deficiency anemia

Case 3 A 25 year old patient was admitted to the clinic with the following complaints: weakness, fever accompanied by chill, pain in the lumbar region, dyspnea, tachycardia in rest, dark color urine. On examination: enlargement and tenderness of the spleen were noticed, peripheral lymph nodes were not enlarged. Blood picture: Hb 53 g/L, Er 2.0 x 10 /l, Thro 180 x 10 /l, Ret 26%, RES 30 mm/h. Leuk. diff. count: bas 0, eos 4, neutr: metamyel 4,band 14, segm 58, lymph 17, monoc 3. In the thin blood smear: anisocytosis, poikilocytosis, polychromatic erythtrocytes and single oxyphil normocytes. Serum iron 40micromol/l, serum bilirubin 60micromol/l, decreased osmotic resistance of erythtrocytes, Coombs test is positive. Questions: 1. What blood dieses does patient have? Aacquired hemolytic anemia (in Coombs Test can find anti-erythrocyte antigen) 2. Explain the pathogenesis of disease & mechanism of its symptoms. Mech of cytotoxic reaction (hypersensitivity type II) 1st stage - Cooperation of (APC with ag + Thcell + Bcell) - Proliferation & differentiation of B cell & transformation into plasmatic cell (B cell plasma cell) - Secretion of specific Ab (Ig M + Ig G) 2ND stage - Aactivation of cells: neutrophils, eosinophil, monocyte & NK - Secretion of mediators from neutrophils eg PG, Leukotrienes. 3rd stage - cell covered with Ab - Opsonin C3b bind to Fc receptor of Ig & enhance phagocytosis lysis of Ab covered cell Mech of symptoms a) pain in lumbar region - Hb flow from blood into membrane of kidney (infiltrated) - immune neuropathy (synt Ab, fixated into membrane, activate compliment syst, increase phagocytosis damage filtrate membrane) b) enlargement & tenderness of spleen - synthesis of Ab & destroyed RBC in spleen c) Dark color of urine - increase ureobilirubin d) Fever

- development of APR bcoz destroyed erythrocyte 3. Name possible causes of describe pathology - drug that play role as hapten Additional 1.Classification on pathogenesis. - Acquired hemolytic anemia increased destruction of RBC - in Coomb test can find anti-erythrocytic antigen 2.Estimate regeneration of RBCs. - Hyperegeneration - increase young cell polychromatic erythrocyte & oxyphil normocyte, increase Ret 26% 3.Type of erythtropoiesis(normoblastic/megaloblastic) - normoblastic 4.Calculate CI - 0.8 (normochromic) 5.Size of erythtrocytes - normal 6.Causes and mechanism of number of RBCs - drug act as haptens by binding to RBC membrane - autoantibody directed against RBC antigen(cytotoxic reaction) -Ig G opsonization (phagocytosis decrease number of RBC) 7.Explain mechanism of clinical symptoms - dark color of urine increase of bilinogen - hemolytic hypoxia - fever develop of APR becoz destroyed of erythrocyte

Case 5 A 39 year old patient is admitted to the clinic with the following complaints weakness, easy tiredness,dyspnea,heart palpation on exertion.From history Since youth he has a marked fatigue and weakness. His father and brother suffer from anemia, but mother and sister are healthy. He has a gallstone disease. Blood picture; Hb-64 g/l, Er-2.4x10 l, Thro-240x10 l, Ret-24%, Leu-13x10 l, RES-17 mm/h, Leu diff count: bas-0, eos-2, neutr: metamyel-4 band-11, segm-59, lymph-20, monoc-4. in the thin blood smear : anisocytosis (microcytosis),poikilocytosis and single ortochromic normocytes. Serum iron-36 mmol/l serum bilirubin-48mmol/l. Osmotic resistance of erytrocytes is decreased. Question 1.What kind of red call sysytem pathology does the patien have Hemolytic anemia-spherocytosis 2.Give explanation to your conclusion Because osmotic resistance of erythrocyte is decreased 3.Describe the pathogenesis of the disease Pathogenesis -membranopathy-microcytosis - decrease of membrane contact of protein.. eg: spectrin and ankyrin - decrease osmotic resistance Shape of erytrocytes- spheroid Cause -disturbance of electrolyte channel -result in decrease number of level in na iron in ctoplasmic of erythrocyes -Increase osmotic pressure in cytoplasma -increase absorption water into erythrocyte -lysis osmotic of erythrocyte -cause membranopathy and decrease osmotic resistance Main symptoms -hypoxia -gall bladder disease

4. What are the mechanism of reticulocytosis and gall baldder formation in this patient? Mechanism of reticulocytosis -It is caused by a molecular defect in one or more of the proteins of the red blood cell cytoskeleton (usually ankyrin, sometimes spectrin). - Because the cell skeleton has a defect, the blood cell contracts to its most surface-tension efficient and least flexible configuration, a sphere, rather than the more flexible donut-shape. - The sphere-shaped red blood cells are known as spherocytes. Formation of gall stone -The detritus of the broken down blood cell bilirubin accumulates in the gall bladder and causes gall stones

Case 6. A 34-year-old patient is admitted to the clinic with the following complaints : easy tiredness, gastrointestinal disturbances, diarrhea. From history : six months ago she had resection of the proximal part of the jeunum. On examination : the skin is pale, the sclera are yellow. Tendon reflexes are normal, no disturbances in sensation or movement are revealed. Secretion of the acid by the stomach glands is normal. Blood picture : Hb - 60 g/1, Er - 1.5 x 101z/1, Thro - 120 x 109 /1, Ret - 0.2%, Leu - 4.1 x 109/I, RES - 24 mm/h. Leuk. dif. count (%) : bas- 0, eos - 3, neutr: metamyel - 0, band - 2, segm - 40, lymph - 51, monoc - 4. In the thin blood smear : anisocytosis (many macrocytes), poikilocytosis, and single giant polysegmented neutrophils. Serum iron is 37 pmol/l, bilirubin - 42 mol/1. 1. Calculate the color index . Hb=(60g/l x 3)/150 = 1.2 x 10.12/l Hyperchromic-macrocytic 2. What is the diagnosis? - Jaundice-Intravascular hemolysis - Mainly macrocytes Right shift >96Fe 3. Give a full explanation of your conclusion and describe the pathogenesis of this disease and the mechanisms of its clinical features. Jaundice-pale skin,yellow sclera Pathogenesis: Autoimmune hemolytic system 4. What does the term" noneffective erythropoiesis" mean? Estimate this value in this case. -formation of noneffective erythrocytes due to folic acid insufficiency (proximal jejunum removal-for absorption of folic acid) Folic acid deficiency causes: decrease in DNA synthesis,decrease in proliferation of Hb,but metabolism of fat is normal=no neurologic pathology(myelin sheath of CNS) Type of erythropoesis= normoblastic 1.Disturbance in differentiation of erythrocytes 2.erythrocyte increase in size 3.vessel too small for erythrocyte to pass Estimated reticulocyte 0.2% = 2 in peripheral blood 1-2 day to form erythrocytes

Case 7. A 24 year old patient is admitted to the clinic with the following complaint: fatigue,easy tiredness,weakness,dizziness,heart palpation,dyspnea in rest. On examination: The skin is pale, the face is puffy, there is multiple hemmorhage all over the body. Th lien and liver are not enlarged. Blood pictures: Hb-50 g/l, Er-1.5x10 /l, Thro-25x10 /l, Ret -0%, Leu-1.3x10 /l, RES- 34mm/h. Leuk diff count(%) : bas-0, eos-0, neutr :metamyel-0, band-1, segm-16, lymph-80, monoc-3. In thin blood smear : anicocytosis,poikilocytosis and toxic inclusions inside the neutrophils. Serum iron is 40 mmol/l, bilirubin -19 mmol/l. In the bone marrow aspirate there are no signs of neoplastic lymphoid infiltration but the signs of increased noneffective erythropoiesis are found. 1. Calculate colour of index C.I=1 therefore normochromic anemia 2. What is your diagnosis in this case? Explain your conclusion -Aplastic anemia -Decrease number of all cells

-Pancytopenia: Ret 0% aregenerative anemia thrombocytopenia neutropenia relative lymphocytosis (no sign of neoplastic lymphoid infiltration) - serum iron 40 mmol/l demand of iron decrease - increase non effective erythpoesis 3. What is the mechanism of hemorrhagic syndrome in this patient? Throbocytopenia damage of primary hemeostasis 4. List the possible causes of this blood disease and its prognosis Possible causes -autoimmune disoder -viral infection -exposure to substance such as benzene, radiation or certain drugs such as chloramphenicol and phenylbutazone Prognosis - can be cured with few modern therapy 5. Describe modern patterns of its treatment -Treating aplastic anemia involves suppression of the immune system, an effect achieved by daily medicine intake -Bone marrow transplant -Medical therapy of aplastic anemia often includes a short course of anti-thymocyte globulin globulin) and several months of treatment with cyclosporin to modulate the immune system. (ATG or anti-lymphocyte

Case 8 A patient, aged 52 was admitted to hospital with d following complaints: malaise, easy tiredness, headache, disturbance in vision, pain on d heart region, spontaneous nose bleeding & pain in d lower limb. On examination: d skin had dark-red (cherry) color, hyperemia of conjuctiva, d spleen enlargement & arterial hypertension were found. In blood: Hb-216 g/l, Er-7.2 x 1012/l, Thro-640x109/l, Ret-0%, Leu-12.5x109/l, RES-1mm/h, hematocrit-0.65. Leuk. diff count: bas- 1, eos- 4, neut: metamyel-1, band-11, segm-58, lymp-20, monoc-5. In d thin blood smear: aisocytosis, polychromatic erythrocytes, single oxyphilic normocytes. 1. What type of blood disorder does the patient have? Erythrocytosis due to Hb,Er. & hematocrit number(RBC mass result from autonomous proliferation of myeloid stem cell) 2. Describe the pathogenesis of the disease and the mechanisms of its clinical features. splenomegaly extramedullary blood production in spleen nose bleeding blood vessel at mucous membrane of the nose burst Arterial hypertension increase blood volume in vessels or presence of thrombosis Headache,disturbances in vision(blurred),malaise,easy tiredness hyperviscousity of RBC The skin had a dark-red quote cherry colour dilatation of peripheral vessels (>blood count) 3. Explain the low RES in this condition. Because increase blood volume. Case 9 A 46-year-old woman came to the clinic with the following complaints: difficulty in the nose breathing accompanied by attacks of sneezing and profuse nose mucous secretion, eyelids itching, profuse tear secretion and gripes in the eyes. These attacks were usually observed at the start of summer over the last 2 years. From history: The patient has myoma and ulcerative colitis. On examination: pallor of the skin and fragility of nails were noticed. Blood picture: Hb 70 g/l, Er 3.5x10 /l, Thro 240x10 /l,Ret 1.2x10 /l, Leu 7.8x10 /l, RES 12mm/h. Leuk. diff. count(%): bas 0, eos 12, neutr: metamyel 0, band 1, segm 50, lymph 32, monoc 5. In the thin blood smear: anisocytosis,pokilocytosis,anisochromia. There are 3% of sideroblasts in the bone marrow aspirate. The iron binding capacity of the serum is increased.Bilirubin content in the serum is 14 micromol/l.

1.Calculate the color index - 0.6 (hypochromic) 2.What alterations do you reveal in the patients blood? - MCV decrease, increase level of iron 3.What is the diagnosis?

- sideroblastic anemia 4.What finding would confirm your diagnosis? - iron binding capacity of serum is increased -3% sideroblasts in the bone marrow aspirate

Case 10 A 24 y/o patient was admitted to the hosp 10 days ago after a car accident in a poor condition: his skin was pale, AP was 60/90 mm Hg, pulse was weak & thready. Blood analysis: Hb- 66 g/l, Er- 2.5 x 1012/l, Thro- 340 x 109/l, Ret- 60%, Leu-13 x 109/l, RES-12mm/h. Leuk diff count(%): bas-0, eos-2, neutr: metamyel-2, myel-0, band-10, segm-60, lymp-20, monoc-6. In thin blood smear; aisocytosis, poikilocytosis, erythrocytes with basophile granules, toxogenic granules & hypersegmentation of nuclei are absent, polychromatophilia is expresses; single oxyphil normocytes. Indirect bilirubin 18 mol/l, serum iron-10 mol/l. Question: 1. Calculate d color index 66 x 33 = 0.792 250 2. What form of anemia does this hemogram indicate? - acute post-haemorrhagic anemia 3. Explain your conclusion - classification on pathogenesis is anemia of blood loss - it is acute because the patient has sign of hypovolumic shock (AP= 60/20mmHg, pulse is weak) 4. Point out the change of erythrocyte amount, Hb level & color index which could take place: 1 hour after injury erythrocyte amount Hb level color index Additional Hemorrhage stage: 1) reflective (1 hour after injury) decrease blood loss compensative activate symphatetic nervous syst peripheral vasoconstriction pale of skin compensative reaction: - fluid from interstial space move into the vessles 2) hydremic stage (1 day after injury) - early normalization of plasma volume - then normalization of erythrocytes Activation of RAAS(renin-angiotensin-aldosterone system) increase reabsorption of water (because increase production ADH) blob vol up to normal but hematocrit decrease due to hemodilution 3) Aactive regenerative of RBC (after 10 days) activate erythropoietin receptor increase erythpoetin that move into bone marrow activate proliferation of RBC can find polichromatophilia, oxyphil & young cell (reticulocyte) in peripheral blood Normal Normal Normal 1 day after injury Normal Normal Normal