Lap midicine Flashcards
General Features Of Hemolytic Anemias 8
1- Increased rate of red cell destruction, 2- Erythroid hyperplasia within the bone marrow → Reticulocytosis 3- Hemolytic jaundice: heme→ bilirubin → indirect or unconjugated
hyperbilirubinemia produces jaundice if >2.5 mg/dL
4- Pigment stones in gall bladder (? ↑ bilirubin in bile + long-standing hemolysis) → calcium bilirubinate gallstones
5- Generalized hemosiderosis or in severe cases, 2ndry hemochromatosis
due to excess iron accumulation 6- Extramedullary hematopoiesis in the spleen and liver of infants 7- Enlarged liver and spleen (splenomegaly) due to hyperplasia of the
mononuclear phagocyte system and extramedullary hematopoiesis.
8- Decreased serum haptoglobin (intravascular hemolysis → binding Hb →
hemoglobin-haptoglobin complex in the blood →Removed by macrophages →Markedly reduced haptoglobin levels Increased serum lactate dehydrogenase (LDH) from hemolyzed RBCs
The master iron regulatory hormone
Hepcidine
The master iron regulatory hormone
Hepcidine
Give me example Function of Hepicidine
Less transferrin iron less decrease Hepcidin so in the liver it is allowed to circulation ferroportine 1 to bind transferin
Hereditary spherocytosis
Defenation and etiology ,pathogensis
Autosomal dominant trait 25%Autosomal recessive
It is defect in the red cell membrane protine spectrin
Becomes spherocyte ➡️Less deformable destroyed by spleen by mQ= Extravascular hemolysis .
Lap finding of spherocytosis :
Decrease Hb ,Normal MCH with increase MCHC
Normocytic normochromic
Blood film :Spheroidal in shape with absence of the central zone of pallor pallor
General findings ⬆️Reticulcytic count ⬆️serum indirect bilirubin⬆️urine urobilinogen ,Serum haptoglubin normal
Special test increase osomatic fragility
Clinical finding of Sperocytosis treatment
Anemia ,
Jundence , increase pigment stone ,Splenomegaly ,In long standing cases systemic hemosidrosis
Treatment:Splenoctomy
Sickle cell Disease Defenation and etiology
Hereditary presence of abnormal Hb
Replacement glutamic acid by valine at the sixth position
Type of sickle cell disease
Homozygous state SS both gene is abnormal
Heterozygous is sickle cell trait AS
Phathogensis of sickle cell
First mechanism : The sickle cell is removed by phagocytosis
Second mechanism :Upon deoxygenating Hbs crystallization rigid crescentic bout like shape
Reoxygenation unsickling
Micro vascular occlusion ➡️pain crises
Clinical of Sickle cell anemia
Homozygone after six months
🩸splenomegaly in children 👦 but in Adult autosplenmegaly
Sudden vasocclusive or pain crises
Increase susceptialy of infection
The acute chest syndrome to death
Lap finding of sickle cell
1- General : normocytic ,normochromic decrease Hb Ht
2-General finding of Hemolysis :Marked reticulocytosis ,uncontrolled hyperbilirubinemia
3- Sickle cell disease =Irreversible ,Sickle cell trait =Normal
4- sickling test : sodium metabisufiter
Thalassemia Defenation and etiology
Caused by mutation decrease rate of synthesis of a or B globin chains
Four gene الفاً قلوبين 16
Tow gene بيتا قلوبين 11
الفاً thalassemia
Clinical disease
Four a-globin gene 🧬 on chromosome 16p
1- Silent -carrier state 75%
2- aThalassemia 50% production as mild Anemia Two of a is deleted microcytic hypochromic
3-Three of the four a-globin gene are deleted 25%a chaine
4- Hydrops fetalis Hb Bart Y4 ➡️No a chain fatal condition Lethal in utero
B - thalassemia Clinical disease state
Autosomal recessive
1- B-Thalassemia minor ➡️Asymptomatic Milde hypochromic microcytic anemia
2- B-Thalassemia intermedia ➡️sever hypochromic microcytic anemia
3- B-thalassemia Cooley’s insoluble aggregate
Regular blood transfusion required
Clinical in B thalassemia
1- sever hemolytic Anemia (Hypochromic microcytic )
2-Chipmunk Rodent face
3-Splnomegaly ;hepatomegaly
4- congestive heart failure
5-Erythroid hyperplasia ➡️crewcut skull X-ray crewcut skull x-ray
Lap finding B thalassemia :
1- Increase microcytic hypochromic
2-Increased reticulocyte count
3-Marked uncjugated
4-Increase serum iron
Treatment of B thalsemia
Supportive treatment for effective erythropoiesis: - Regular blood transfusions:
- minimize anemia - suppress ineffective erythropoiesis
- Iron-chelating agents:
- as Desferrioxamine (DFO) and deferiprone (DFP) - It is Chelating agents acts by binding free iron in the bloodstream and enhancing its elimination in the urine - reduce excess iron → show a significant decline in serum iron - demonstrated great efficacy for cleaning cardiac iron
- Stem cell or bone marrow transplants:
- are the only cure for thalassaemia,, but they are not done very often because of the significant risks involved
Prognosis:
- If Untreated : die during the 1st or 2nd decade
Glucose 6 phosphate dehygence deficiency
X linked recessive disorder
Decrease synthesis and half life enzyme
Pathogensis OF G6PD
G6PD ⬇️ synthesis NADPH ⬇️synthesis of glutathione GSH neutralizes H2O2 oxidant Hb Heinz bodies
1-damage Membrane RBCmembrane intravacscular hemolysis
2- removed RBCs by splenic Extravascular hemolysis
In second baronet half life of G6PD markedly reduced enzyme highest in young RBCs old RBCs are more susceptible to destruction
Lap finding
1-Noromocytic , normochromic
2-peripheral Blood finding
$-Heinz bodies
$Bite cell
3-Hemoglobinuria
Erythroblastosis RH
Etiology &pathogensis
Rh (-) maternal , fetus Rh(+)
IgG gross placenta to the blood fetus hemolysis
This not to first pregnant
Clinical feature of Rh
Treatment
Presentation
Severely affected fetus hydrops fetalis
Heart failure, generalized edema jaundice
T: Exchange blood
P: D immunoglobulin in last month
Test 1 : ESR Erythrocyte sedimentation Rate
- To detect any inflammation - To monitor the progress of inflammatory disease - to evaluate the response to treatment
Dose not spesfic diagnosis
1- What dose ESR Measure
ESR test measure the rate sediment ▶️ترسب
When is in inflation RBCs increase mainly fibrinogen ▶️Rouleaux formation
How to perform Erythrocytes sedmination Rate :
Take 0.4 mL of sodium 🧂 solution +1.6 mL of blood in EDTA After one hour
Men<13
Women<20
Increase , Decreased ESR
High : Arthritis , vasculitis ,appendicitis,Heart valve infection ,SLE ,Rheumatic Arthritis Anemia ,Lymphoma physiology pregnancy
🔽polycythemia Vera
RDW
Is quantitative measure the degree of anisocytosis
Normal 11.5% 14.5 %
2-Test , Retoculcytes normal range
Corrected above 3%
Are newly released RBCs supravital staighn
Men (0,5-1,5%)
Above Hemolytic Anemia , spherocytosis and G6PD
Low iron defiance and Aplastic Anemia Renal failure
Extramedullallry hematopoiesis
Defenation
Definition: RBC, white blood cell (WBC), and platelet production that
occurs outside the confines of the bone marrow
Common sites: for EMH are the liver and spleen. Pathogenesis: 1- Intrinsic bone marrow disease (e.g., myelofbrosis)
2- Accelerated erythropoiesis (e.g., severe hemolysis in sickle cell disease)
The process expands the bone marrow cavity.
Radiograph of the skull shows a “hair-on-end” appearance, due to expansion of the bone marrow within the skull bones.
3- EMH produces hepatosplenomegaly N.B.: In the fetus, hematopoiesis (blood cell formation) begins in the yolk sac and subsequently moves to the liver and finally the bone marrow by the fifth to sixth months of gestation.
MCV ,MCHC ,MCH
Mean Corpuscular Volume (MCV)
= Average volume of RBCs = (Normal: 80-100 fl) or cubic micron µm3
MCV = HCT% x 10 / RBC count → Average volume of a single RBC - Used to classify anemia into: - Microcytic (MCV < 80): e.g. - Iron deficiency anemia,
- Thalassemia, - Anemia of chronic disease
- Macrocytic (MCV > 100): e.g. Folate deficiency or Vit. B12 deficiency - Normocytic (MCV 80 – 100): e.g. - Hemolytic anemias,
- Aplatic anemia, - Anemia of chronic disease - Bone marrow metastasis 1
- Chronic renal
Measure the average concentration of hemoglobin in packed RBCs - It gives the Ratio of the weight (amount) of hemoglobin to the
volume of red blood cells
MCHC = Hb (g/dl) x 100 / HCT (%) = g / dl
- Normal = 30-35 g/dl
- Used to classify anemia into: - Normal MCHC: → Normochromic anemia e.g. ……..…… - Decreased MCHC: → Hypochromic anemia e.g. ……..……
- Increased MCHC: → e.g. Hereditary spherocytosis
Lab Med: RBCs Disorders:
Lab Med: RBCs Disorders: 1
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Prof. Magdy ElShamy
Prof. Magdy ElShamy
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Mean Corpuscular Hemoglobin
(MCH)
MCH Is a measure of the average weight (amount) of hemoglobin
per a single red blood cell.
= Hb (g/dl) x 10 / RBC count = picogram (pg) / cell Normal value : 27 - 32 pg / cell picogram (pg) / cell
- Used to classify anemia into:
- Decreased MCH: → associated with microcytic anemia
- Increased MCH: → associated with macrocytic anemia
N.B.: MCHC is more commonly used than MCH to classify anemia
Acute leukemia De , pathogensis ¿
Defenation: Acute leukemias are characterized by clonal proliferation of myeloid or lymphoid precursors (Blast cells) with reduced
capacity to differentiate into more mature cellular elements.
Pathogenesis: Block in stem cell di fferentiation at an early stage leading to a monoclonal proliferation of neoplastic leukocytes behind the block (blasts) 2- Blasts accumulating in the B. marrow → suppress the growth of normal hematopoietic cells → eventually this suppression produces bone marrow failure → which accounts for the major clinical manifestations.
3- Leukemic Blast cells ➡️entire peripheral blood 🩸
General characteristics of Aplastic
Bone Marrow:
- has increased immature leukemic cells (Blasts); - the diagnostic criteria is > 20% blasts in the bone marrow
- Peripheral Blood:
- has decreased mature forms and - increased immature forms called Blasts
- Infiltration of various organs: is a common feature
Clinical features of Acute leukemia
Symptoms & signs at presentation are either due to depression of depression of
normal
normal bone marrow function or organ infiltration These include: Abrupt onset of - Anemia → pallor, dyspnea, fatigue - Neutropenia → fever, recurrent infections e.g. sore throat, pneumonia - Thrombocytopenia → bleeding as
(petechiae, ecchymoses, epistaxis, gum bleeding)
- Generalized Lymphadenopathy, splenomegaly & hepatomegaly
(due to dissemination of the leukemic cells). are more marked in ALL than in AML - Tissue infiltrations
e.g. testis & meninges: more in ALL, (→ headache, vomiting)
skin, gum and bone: more in AML
(Bone pain & tenderness due to marrow expansion & infiltration)
Acute lymphoblastic leukemia clinical feature
Anemia
Anemia (…….….) (…….….),
, Fever
Fever (………….),
(………….), bleeding
bleeding (…….…….), (…….…….),
Generalized Generalized Lymphadenopathy
Lymphadenopathy.
. Moderate
Moderate Hepatosplenomegaly
Hepatosplenomegaly
Tissue infiltration e.g. testicular, meningeal (→ headache, vomiting) (→ headache, vomiting)
Bone pain and tenderness:
Bone pain and tenderness: due to bone marrow expansion by the leukemic cells
due to bone marrow expansion by the leukemic cells
Acute Myeloblastic Leukemia
Anemia (…….….), Fever (………….), bleeding (…….…….),
Moderate Hepatosplenomegaly.
No significant lymphadenopathy
Tissue infiltration e.g. skin, gums, bone (bone pain & tenderness)
Laboratory Findings of Acute Leukemias
Peripheral blood: CBC:
1- Anemia: : is almost always present, usually Normochromic Normocytic 2- Thrombocytopenia: Platelet count → is usually below 100,000 /μL 3- Total leucocytic count: usually raised,
but ranges from less than 10,000 cells/µL up to 100,000 cells/µL or more 4- Blood film: (differential count): usually show
- characteristic leukemic blast cells (Lymphoblasts, OR myeloblasts)
- Neutropenia is also a common finding in the peripheral blood
N.B: The peripheral blood sometimes: TLC is normal or ↓ & contains No blasts (aleukemic leukemia); in such cases the diagnosis can be established only by bone marrow examination
II- Bone marrow aspirate: (Diagnostic) usually shows
- increased cellularity with
Lab Med: WBCs Disorders: Lab Med: WBCs Disorders: - high percentage of abnormal lymphoid or myeloid blast cells (>20%)
Chronic Myloid leukemia
De, pathogensis
Definition: - CML is a clonal myeloproliferative disorder where Neutrophils (mature) and their precursors (immature myeloid cells) increase in the peripheral blood & the bone marrow. Pathogenesis: - Translocation between chromosome 9 and chromosome 22 results in an
abnormal chromosome 22 which is called Philadelphia chromosome (Ph) Leading to malignant proliferation of hematopoietic stem cells.
- In more than 95% of patients, the leukemic cells are Philadelphia positive (Ph +ve) = t(9;22) BCR-ABL fusion gene is the most sensitive and specifc test for chronic
myelogenous leukemia
Clinical features, Chronic Myeloid Leukemia (CML
Clinical Features: - Age: mostly Adults between 25 - 45 yrs, = Middle age, sometimes older
Can occur in childhood and adolescence.
- Onset is usually gradual, may be discovered accidentally during routine laboratory investigation.
- C/P: Easy fatigability, weakness (signs & symptoms of anemia),
Low grade fever, and weight loss
- Marked splenomegaly (in ↑ 90% of cases),
- Lymph node and liver are moderately enlarged due to infiltration by leukemic cells.
Chronic Myloid leukemia lab finding
Peripheral blood: (CBC): 1- Anemia, usually Normocytic Normochromic 2- Total leukocyte count is elevated, often ↑ 100,000 cells/μL. -The cells are mainly neutrophils, bands, metamyelocytes & myelocytes
Myeloblasts are less than 5% - Increased Basophils (common) and may be increase eosinophils, 3- Platelet count: usually Increased (Thrombocytosis) II- Bone marrow aspirate: - The bone marrow is markedly hypercellular due to hyperplasia of granulocytic (mainly) & megakaryocytic precursors. III- Neutrophil Alkaline Phosphatase (NAP) score:
The NAP score is markedly low or zero in CML Neutrophils
Normal Neutrophils contain this enzyme in their granules.
IV- Cytogenetic Analysis:
Ph chromosome is present in peripheral blood & bone marrow cells
Prognosis of CML
course of CML is of slow progression
- After a variable period The main cause of death in CML is transformation into acute leukemia (Acute Blast Transformation or Blast Crisis) marked by:
1- increasing number of blast cells in the peripheral blood (> 10%) and bone marrow (> 20%)
2- Increasing anemia, splenomegaly, thrombocytopenia
Course of CML:
CML may be Biphasic or Triphasic: - CML chronic phase (< 5% blasts) → Accelerated Phase (blasts 5% - <20%
in PB or BM) → Acute Blast Transformation (blasts ≥ 20%)
- CML chronic phase (< 5% blasts) → Acute Blast Transformation
(blasts ≥ 20% In PB or BM)
Chronic Chronic Lymphocytic Leukemia
De
CLL is a clonal lymphoproliferative disease characterized by uncontrolled proliferation and accumulation of Mature looking lymphocytes in the
blood, bone marrow, lymph nodes and spleen
- Most CLL (95%) are due to B lymphocyte clonal proliferation
Clinical features
Usually old age (over 50 y), with slow onset (over years)
- Early, often Asymptomatic & discovered accidentally (How??
(Persistent Absolute Lymphocytosis)
- With BM infiltration → Easy fatigability, weakness (signs & symptoms of anemia), weight
loss,
-First, Generalized lymph node enlargement (Lymphadenopathy), a
common clinical sign, and later Spleen, & liver enlargement
- May be bleeding tendency (due to thrombocytopenia) - Recurrent bacterial & viral infections (due to hypo gammaglobulinemia)
Laboratory finding of CLL
Immunophenotyping: - Lymphocytes are monoclonal (derived from one clone of cells). - They are B cells in most cases with co-expression of CD 19 and CD 5.
IV- Serum immunoglobulins
are decreased (Hypogammaglobulinemia)
Computed Tomography (CT) Scan:
- For cervical, chest, and pelvi-abdominal regions
- To evaluate the extent of lymph node enlargement and presence of splenomegaly
Peripheral blood: (CBC) 1- Hb may be Normal. Anemia (Normocytic Normochromic) may occur 2- Total leukocytic count:
is increased with Persistent Absolute Lymphocytosis
3- Blood film shows small mature-appearing lymphocytes +
characteristic smudge cells (due to cell rupture)
4- Thrombocytopenia occurs in advanced cases (due to BM infiltration)
N.B.: - In some cases there is production of autoantibodies leading to autoimmune hemolytic anemia and/or autoimmune thrombocytopenia
II- Bone marrow aspirate: - Bone marrow is heavily infiltrated with normal-appearing neoplastic lymphocytes (>30%)
Prognosis of CLL
The course and prognosis: are extremely variable
- Many patients live up to10 years after diagnosis and die of
unrelated causes;
- The median survival is 4 to 6 years.
Treatment :is indicated in advanced and/or symptomatic disease: e.g.
- Doubling of lymphocyte count in 6 months - B.M. failure = ……………, ……………, ………………….. - Autoimmune hemolytic anemia - Systemic manifestations: fever, night sweats, weight loss - Massive lymphadenopathy or splenomegaly
