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Anemia

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Page 1: Anemia
Page 2: Anemia

Approach to Approach to Patients withPatients with

AnemiaAnemiaProf. Dr / Nabil LymonProf. Dr / Nabil Lymon

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Blood Cells Blood Cells and and

Hemoglobin Hemoglobin structurestructure

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DefinitionsDefinitions::- - AnemiaAnemia ::is defined as the lowering of hemoglobin is defined as the lowering of hemoglobin

concentration below the established normal concentration below the established normal levels: levels:

In male < 13.5 gm/dl & In female < 11.5 gm / dl.In male < 13.5 gm/dl & In female < 11.5 gm / dl.- Anemia is a clinical sign not a diagnostic entity.- Anemia is a clinical sign not a diagnostic entity.

-- Hematocrit (Hct):Hematocrit (Hct): is the proportion, by volume, of the blood occupied is the proportion, by volume, of the blood occupied

by red blood cells. The hematocrit (Hct) is by red blood cells. The hematocrit (Hct) is expressed as a percentage, normal levels are :expressed as a percentage, normal levels are :

0.4 - 0.54 in Adult male & 0.37 - 0.47 in Adult female0.4 - 0.54 in Adult male & 0.37 - 0.47 in Adult femaleFor example, a hematocrit of 25% means that there For example, a hematocrit of 25% means that there

are 25 milliliters of red blood cells in 100 are 25 milliliters of red blood cells in 100 milliliters of blood.milliliters of blood.

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DefinitionsDefinitions::Red Cell IndicesRed Cell Indices

Are measurements that indicate the size and Are measurements that indicate the size and hemoglobin content of red cells:hemoglobin content of red cells:

M.C.V (Mean Corpuscular Volume)M.C.V (Mean Corpuscular Volume)

M.C.H (Mean Corpuscular Hemoglobin)M.C.H (Mean Corpuscular Hemoglobin)

M.C.H.C M.C.H.C (Mean Corpuscular Hemoglobin (Mean Corpuscular Hemoglobin Concentration)Concentration)

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M.C.V M.C.V (Mean Corpuscular Volume):(Mean Corpuscular Volume):

Referred to the average volume of red cells , normally = 76 - Referred to the average volume of red cells , normally = 76 - 96 fl96 fl

It can be calculated from an independently-measured red It can be calculated from an independently-measured red blood cell count and hematocrit:blood cell count and hematocrit:

MCVMCV    (femtoliters) = 10 x HCT(percent) ÷ RBC (femtoliters) = 10 x HCT(percent) ÷ RBC (millions/(millions/µµL)L)

MICROCYTOSIS & MACROCYTOSISMICROCYTOSIS & MACROCYTOSIS  ::  By definition, microcytosis is taken to mean the presence of By definition, microcytosis is taken to mean the presence of

RBCs with a MCV less than normal, while macrocytosis RBCs with a MCV less than normal, while macrocytosis means the presence of RBCs with an MCV greater than means the presence of RBCs with an MCV greater than normal.normal.

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M.C.H M.C.H (Mean Corpuscular (Mean Corpuscular Hemoglobin):Hemoglobin):

or "mean cell hemoglobin" (MCH), is a measure of the or "mean cell hemoglobin" (MCH), is a measure of the mass of hemoglobin contained by a red blood cell. mass of hemoglobin contained by a red blood cell. It is diminished in microcytic anemias, and It is diminished in microcytic anemias, and increased in macrocytic anemias. It is calculated by increased in macrocytic anemias. It is calculated by dividing the total mass of hemoglobin by the RBC dividing the total mass of hemoglobin by the RBC count :-count :-

MCH=Hb/RBCMCH=Hb/RBCA normal value in humans is 27 to 32 picograms/cellA normal value in humans is 27 to 32 picograms/cell

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M.C.H.C M.C.H.C

(Mean Corpuscular Hemoglobin (Mean Corpuscular Hemoglobin Concentration):Concentration):

is a measure of the concentration of hemoglobin in a given is a measure of the concentration of hemoglobin in a given volume of packed red blood cell. volume of packed red blood cell.

It is diminished It is diminished ("hypochromic")("hypochromic") in microcytic anemias, and normal in microcytic anemias, and normal ("normochromic")("normochromic") in macrocytic anemias (due to larger cell size, in macrocytic anemias (due to larger cell size, though the hemoglobin amount or MCH is high, the though the hemoglobin amount or MCH is high, the concentration remains normal).concentration remains normal).

It is calculated by dividing the hemoglobin by the hematocrit: It is calculated by dividing the hemoglobin by the hematocrit:

M.C.H.C = Hb M.C.H.C = Hb / Hct/ Hct

A normal value is 30 to 36 g/dl.A normal value is 30 to 36 g/dl.

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Signs &Symptoms of Signs &Symptoms of AnemiaAnemia

- Cardiovascular :- Cardiovascular :EExertional Dyspnea xertional Dyspnea PPalpitations alpitations

OOrthopnearthopnea

TTachycardia achycardia AAngina ngina CClaudicationslaudications

CCardiomegally ardiomegally BBounding peripheral Pulsesounding peripheral Pulses

MMurmurs urmurs VVascular bruits ascular bruits PPedal edal edemaedema

- Neurological :- Neurological :HHeadache eadache TTinnitus innitus

DDizzinessizziness

FFaintness aintness FFatigue atigue CCold old Sensitivity Sensitivity LLoss of Concentrationoss of Concentration

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Signs &Symptoms of Signs &Symptoms of AnemiaAnemia

- Skin :- Skin :PPallor of skin , mucous membranes, nail beds and palms.allor of skin , mucous membranes, nail beds and palms.

- Gastrointestinal :- Gastrointestinal :AAnorexia norexia NNausea ausea

CConstipationonstipation

DDiarrheaiarrhea

- Respiratory :- Respiratory :IIncreased Respiratory Ratesncreased Respiratory Rates

- Genitourinary :- Genitourinary :MMenstrual irregularity enstrual irregularity AAmenorrhea menorrhea MMenorrhagiaenorrhagia

LLoss of libido or potencyoss of libido or potency

- Fundus Examination :- Fundus Examination :RRetinal Exudates Rarely etinal Exudates Rarely PPapilloedemaapilloedema

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Is the patient Anemic or Is the patient Anemic or not ?not ?

Anemic means single or Anemic means single or total decrease in :total decrease in :

- Hb- Hb - Hct - Hct

- RBCs - RBCs count in millionscount in millions ButBut……??

What Type of Anemia..?What Type of Anemia..?

This depends on the RBCs This depends on the RBCs indicesindices

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Red Cell IndicesRed Cell IndicesAccording to MCV & MCHAccording to MCV & MCH

NormalNormal

Normocytic Normochro

mic Anemia

Decreased Decreased

Microcytic

Hypochromic Anemia

IncreasedIncreased

Macrocytic

Anemia

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Normocytic Normochromic Normocytic Normochromic AnemiaAnemiaIt may be due to :It may be due to : - Acute Blood Loss - Acute Blood Loss - Aplastic Anemia - Aplastic Anemia - Hemolytic Anemia ( Except - Hemolytic Anemia ( Except Thalasemia)Thalasemia) - A.O.C.D (Anemia Of Chronic - A.O.C.D (Anemia Of Chronic Diseases)Diseases)

NormalNormal

A.O.C.DA.O.C.D e.g.: e.g.: TB, SLE, Malignancy, TB, SLE, Malignancy,

Rh. ArthritisRh. Arthritis

Note:Note:

- Evidence of the - Evidence of the causecause

- Anemia May be - Anemia May be Micro- cytic Micro- cytic HypochromicHypochromic

Low or AbsentLow or Absent

B.M.FB.M.F ““Aplastic Aplastic

AnemiaAnemia””

BM biopsy or BM BM biopsy or BM aspiration aspiration show :show :

Acellular or Hypo- Acellular or Hypo- cellular BMcellular BM

HighHigh - Acute Blood - Acute Blood

LossLoss

( search for ( search for evidence of evidence of the cause)the cause)

- Hemolytic - Hemolytic AnemiaAnemia

Which of Which Which of Which …….?.? Do Reticulocytic Do Reticulocytic CountCount

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Hemolytic AnemiaHemolytic Anemia - low Hb &/or Hct & /or RBCs count - low Hb &/or Hct & /or RBCs count - Normal RBCs indices - Normal RBCs indices - Reticulocytosis - Reticulocytosis

Do Indirect Serum BillirubinDo Indirect Serum Billirubin

Unconjugated Hyper-Unconjugated Hyper-billirubinemia billirubinemia ““ jaundicejaundice””

Other Evidences of Hemolysis e.g.:-Other Evidences of Hemolysis e.g.:-

- Hemoglobinuria - Hemoglobinemia - Hemoglobinuria - Hemoglobinemia (increased free Hb)(increased free Hb)- Decreased Haptoglobin.- Decreased Haptoglobin.

What is the Further What is the Further StepStep?..………?..……… Coombs TestCoombs Test

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Coombs TestCoombs Test PositivePositive

Immune Immune

Hemolytic Hemolytic Anemia:Anemia:

-- Iso immuneIso immune

- Auto immune- Auto immune

NegativeNegative

Non-immune Non-immune

Hemolytic Hemolytic Anemia:Anemia:

May be due to :May be due to :

- Membrane Defect- Membrane Defect e.g. e.g. Spherocytosis (lab Spherocytosis (lab show increased O.F.) & show increased O.F.) & P.N.HP.N.H

- Enzyme Defect- Enzyme Defect

e.g. G6PD (lab : Enz. assay)e.g. G6PD (lab : Enz. assay)

- Hb Defect- Hb Defect (Hemoglobinopathy) (Hemoglobinopathy)

e.g. Sickle Cell Anemia (lab: e.g. Sickle Cell Anemia (lab: Hb Hb Electrophoresis).Electrophoresis).

- Others- Others : Malaria (lab: Bl. : Malaria (lab: Bl. Film)Film)

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Red Cell IndicesRed Cell IndicesAccording to MCV & MCHAccording to MCV & MCH

Decreased Decreased

Microcytic

Hypochromic Anemia

IncreasedIncreased

Macrocytic

Anemia

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Microcytic Hypochromic Microcytic Hypochromic AnemiaAnemia- The Commonest Cause is:- The Commonest Cause is:

Iron Deficiency AnemiaIron Deficiency Anemia-Other Causes: - Thalasemias-Other Causes: - Thalasemias - Sedroplastic Anemia - Sedroplastic Anemia - Lead Poisoning - Lead Poisoning - A.O.C.D - A.O.C.D

- - Serum Iron Serum Iron

- Serum Ferritin- Serum Ferritin- T.I.B.C - T.I.B.C (Total Iron Binding (Total Iron Binding

Capacity)Capacity)

- Transferrin Saturation- Transferrin Saturation

Which of Which Which of Which …….?.? Do Iron StudiesDo Iron Studies::

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According to Iron According to Iron StudiesStudies

Iron Iron DeficiencDeficiency Anemiay Anemia

ThalasseThalassemiamia

SideroplaSideroplasticstic

AnemiaAnemia

A.C.O.DA.C.O.D

Serum Fe

Serum Ferritin

NormalNormalN orN or

T.I.B.CNormalNormalTransferrin Saturation

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Iron Deficiency AnemiaIron Deficiency Anemia

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Iron Deficiency AnemiaIron Deficiency Anemia

IronIron

StudiesStudiesNotes:Notes:- Search For The - Search For The Cause:Cause:

e.g.:e.g.:

Chronic Blood LossChronic Blood Loss

AnkylostomaAnkylostoma

Cancer ColonCancer Colon

Nutritional causesNutritional causes

- Severe Aniso-cytosis - Severe Aniso-cytosis and Poikilo-cytosis:and Poikilo-cytosis:

Increased R.D.W(N ≤ Increased R.D.W(N ≤ 13%)13%)

Serum Fe

Serum Ferritin

T.I.B.C

Transferrin Saturation

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Anisocytosis with Anisocytosis with hypochromia and hypochromia and microcytes (IDA)microcytes (IDA)

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Spoon Nails:Spoon Nails: If nails look scooped out, like a If nails look scooped out, like a spoon, it could be a sign of iron-spoon, it could be a sign of iron-

deficiency anemiadeficiency anemia..

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Plummer Vinson SyndromePlummer Vinson SyndromeLeft : Spoon shaped finger nailsLeft : Spoon shaped finger nails

Right Right : : Showing angular cheilitis, and Showing angular cheilitis, and

dry skindry skin

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Plummer Vinson Plummer Vinson SyndromeSyndrome

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Iron Deficiency AnemiaIron Deficiency Anemia

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ThalassemiaThalassemia

IronIron

StudiesStudiesNotes:Notes:- Hb Electrophoresis - Hb Electrophoresis will show:will show:

Persistence of Persistence of Hb[f]Hb[f]

- Specific Clinical - Specific Clinical Features of Features of Thalasemia:Thalasemia:

Huge SpleenHuge Spleen

Mongoloid FacesMongoloid Faces

HemosedrosisHemosedrosis

Serum Fe

Serum Ferritin

T.I.B.C

Transferrin Saturation

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Thalassemia minorThalassemia minor is an inherited form of hemolytic anemia that is an inherited form of hemolytic anemia that is less severe than thalassemia major. This is less severe than thalassemia major. This blood smear from an individual with blood smear from an individual with thalassemia shows small (microcytic), pale thalassemia shows small (microcytic), pale (hypochromic), variously-shaped (hypochromic), variously-shaped (poikilocytosis) red blood cells. These small (poikilocytosis) red blood cells. These small red blood cells (RBCs) are able to carry less red blood cells (RBCs) are able to carry less oxygen than normal RBCsoxygen than normal RBCs

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Thalassemia,Thalassemia, being a genetic disease, runs in being a genetic disease, runs in a family. Most are silent carriers or suffer a family. Most are silent carriers or suffer mild anemia. Severe cases such as the mild anemia. Severe cases such as the Hemoglobin H disease with enlarged spleen, Hemoglobin H disease with enlarged spleen, small body and malnourished look shows more small body and malnourished look shows more prominent symptoms. prominent symptoms. [Pic below: Enlargement [Pic below: Enlargement of spleen, small body]of spleen, small body]

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Sideroplastic AnemiaSideroplastic Anemia

IronIron

StudiesStudiesNotes:Notes:Sedroplastic Anemia Sedroplastic Anemia is due to:is due to:

- B6 Deficiency- B6 Deficiency

- Drugs e.g.: INH- Drugs e.g.: INH

- Inherited - Inherited

Blood film show:Blood film show:

RBCs contain Iron RBCs contain Iron GranulesGranules

Treated by: Treated by:

B6 supplyB6 supply

Serum Fe

Serum Ferritin

NormNormalal

T.I.B.CNormNormalal

Transferrin Saturation

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Many rounded sideroblasts are present Many rounded sideroblasts are present in this field. This is the hallmark in this field. This is the hallmark feature of feature of sideroblastic anemiasideroblastic anemia

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Lead PoisoningLead Poisoning

Notes:Notes:- - History is Suggestive.History is Suggestive.

- Elevated Serum Lead level.- Elevated Serum Lead level.

- Purely Motor Neuropathy (foot and - Purely Motor Neuropathy (foot and wrist drop)wrist drop)

- Blood Film show:- Blood Film show:

Basophilic Stippling of Basophilic Stippling of RBCs RBCs

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Basophilic Stippling of Basophilic Stippling of RBCsRBCsBasophilic stippling appears as round, dark-Basophilic stippling appears as round, dark-blue granules in red blood cells on smears blue granules in red blood cells on smears stained with supra vital stains such as brilliant stained with supra vital stains such as brilliant cresyl blue. cresyl blue. They may be observed in They may be observed in lead poisoninglead poisoning, , exposure to some drugs, severe burns, exposure to some drugs, severe burns, anemiaanemia, , or septicemia. The granules are precipitated or septicemia. The granules are precipitated ribosomes and mitochondriaribosomes and mitochondria

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Red Cell IndicesRed Cell IndicesAccording to MCV & MCHAccording to MCV & MCH

IncreasedIncreased

Macrocytic

Anemia

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Macrocytic AnemiaMacrocytic Anemia- In Which :- In Which : - low Hb &/or Hct & /or RBCs count - low Hb &/or Hct & /or RBCs count - Increased RBCs indices - Increased RBCs indices- Causes :- Causes :# Folic Acid Deficiency # B12 Deficiency# Folic Acid Deficiency # B12 Deficiency

- Search For The Cause:- Search For The Cause:# Pregnancy # Mal-absorption # Pregnancy # Mal-absorption SyndromeSyndrome# Chronic Gastritis # Atrophic Gastritis# Chronic Gastritis # Atrophic Gastritis# Cancer Stomach # Iliac Resection# Cancer Stomach # Iliac Resection# Drugs: Methotrexate / Metformin / Epanutin# Drugs: Methotrexate / Metformin / Epanutin

- To be sure do the following tests:- To be sure do the following tests:Serum Folic Acid / Serum B12 / Serum Folic Acid / Serum B12 / Schilling test / FIGLU testSchilling test / FIGLU test

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Schilling Schilling TestTestThe Schilling test is The Schilling test is performed to evaluate performed to evaluate vitamin B12 absorption. vitamin B12 absorption. B12 helps in the B12 helps in the formation of red blood formation of red blood cells, the maintenance of cells, the maintenance of the central nervous the central nervous system, and is important system, and is important for metabolism. for metabolism. Normally, ingested Normally, ingested vitamin B12 combines vitamin B12 combines with intrinsic factor, with intrinsic factor, which is produced by which is produced by cells in the stomach. cells in the stomach. Intrinsic factor is Intrinsic factor is necessary for vitamin necessary for vitamin B12 to be absorbed in the B12 to be absorbed in the small intestine. Certain small intestine. Certain diseases, such as diseases, such as pernicious anemia, can pernicious anemia, can result when absorption of result when absorption of vitamin B12 is vitamin B12 is inadequateinadequate

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FIGLU testFIGLU test a test of vitamin b12 deficiency, a test of vitamin b12 deficiency, folic acid deficiency, liver disease, folic acid deficiency, liver disease, or genetic deficiency of glutamate or genetic deficiency of glutamate formimino-transferase, based on formimino-transferase, based on urinary excretion of urinary excretion of formimino-formimino-glutamic acid (glutamic acid (figlufiglu)),, an an intermediate metabolite in intermediate metabolite in histidine catabolism in the histidine catabolism in the conversion of histidine to glutamic conversion of histidine to glutamic acid, with the formimino group acid, with the formimino group being transferred to being transferred to tetrahydrofolic acidtetrahydrofolic acid . .

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11( -( -commentarycommentary)) A healthy 52-year-old man presents to the A healthy 52-year-old man presents to the

doctordoctor’’s office complaining of increasing s office complaining of increasing fatigue for the past 4-5 months. He exercise fatigue for the past 4-5 months. He exercise every day but lately he has noticed becoming every day but lately he has noticed becoming short of breath while jogging. short of breath while jogging.

He denies orthopnea. Paroxysmal nocturnal He denies orthopnea. Paroxysmal nocturnal (PND), or swelling in his ankles. The patient (PND), or swelling in his ankles. The patient reports occasional joint pain for which he reports occasional joint pain for which he uses over the counter ibuprofen.uses over the counter ibuprofen.

He denies bowel changes, melena or bright He denies bowel changes, melena or bright red blood per rectum, but reports vague left red blood per rectum, but reports vague left side abdominal pain for a few months off and side abdominal pain for a few months off and on, not related to food intake. The patient on, not related to food intake. The patient denies fever, chills, nausea or vomiting. denies fever, chills, nausea or vomiting.

He has lost a few pounds intentionally with He has lost a few pounds intentionally with diet and exercise.diet and exercise.

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ContCont.. On examination, his weight is 90kg and he is On examination, his weight is 90kg and he is

aferbrile. There is slight pallor of conjunctiva, aferbrile. There is slight pallor of conjunctiva, skin and palms.skin and palms.

No lymphadenopathy is noted chest is clear to No lymphadenopathy is noted chest is clear to auscultation bilaterally.auscultation bilaterally.

Cardiovascular system: regular rate and Cardiovascular system: regular rate and rhythm, with no rub or gallop.rhythm, with no rub or gallop.

There is a II/IV systolic ejection murmur.There is a II/IV systolic ejection murmur. His abdomen is soft, nontender and without His abdomen is soft, nontender and without

hepato-splenomegaly. hepato-splenomegaly. Bowel sounds are present. He has no Bowel sounds are present. He has no

extremity edema, cyanosis or clubbing. extremity edema, cyanosis or clubbing. His peripheral pulses are palpable and His peripheral pulses are palpable and

symmetric. A hemoglobin level is 9.2g/dl, symmetric. A hemoglobin level is 9.2g/dl, MCV 75µMCV 75µ33

Discuss the most likely diagnosisDiscuss the most likely diagnosis

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What is the differential diagnosis What is the differential diagnosis

such case?such case?

Investigations of insulin Investigations of insulin

malabsorptionmalabsorption

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Comprehension Comprehension QuestionsQuestions

1- A 25year-old man with a history of a 1- A 25year-old man with a history of a

duodenal ulcer is noted to have a duodenal ulcer is noted to have a

hemoglobin level of 10g/dl. Which of the hemoglobin level of 10g/dl. Which of the

following is most likely to be seen on following is most likely to be seen on

laboratory investigation?laboratory investigation?

a- Reticulocyte count of 4%.a- Reticulocyte count of 4%.

b- Elevated total iron-binding capacity (TIBC).b- Elevated total iron-binding capacity (TIBC).

c- Normal serum ferritin.c- Normal serum ferritin.

d- MCV of 105 fL.d- MCV of 105 fL.

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2- A 22-years-old Woman is pregnant and 14 weeks 2- A 22-years-old Woman is pregnant and 14 weeks

gestation. Her hemoglobin level is 9g/dl. She asks why gestation. Her hemoglobin level is 9g/dl. She asks why

she could have iron deficiency when she is no longer she could have iron deficiency when she is no longer

menstruating. Which of the following is the best menstruating. Which of the following is the best

explanation:explanation:

a- Occult gastrointestinal blood loss.a- Occult gastrointestinal blood loss.

b- Expanded blood volume and transport to the fetusb- Expanded blood volume and transport to the fetus

c- Hemolysisc- Hemolysis

d- Iron losses as a result of relative alkalosis of pregnancyd- Iron losses as a result of relative alkalosis of pregnancy

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3- A 35-year-old man has undertaken a self 3- A 35-year-old man has undertaken a self imposed diet for 3 months previously, he imposed diet for 3 months previously, he has been healthy, but now complains of has been healthy, but now complains of fatigue. His hemoglobin level is 10g/dL and fatigue. His hemoglobin level is 10g/dL and his MCV is 105fL. Which of the following is his MCV is 105fL. Which of the following is the most likely etiology of his anemia?the most likely etiology of his anemia?

a- Iron deficiencya- Iron deficiency

b- Folate deficiencyb- Folate deficiency

c- Vitamin B12 deficiencyc- Vitamin B12 deficiency

d- Thalassemiad- Thalassemia

e- Sideroblastic anemiae- Sideroblastic anemia

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Match the following laboratory Match the following laboratory parameters (a to e ) to the clinical parameters (a to e ) to the clinical

picture (4 to 6)picture (4 to 6)

4- A 20 year-old woman with heavy menses.4- A 20 year-old woman with heavy menses.

5- A 34 year-old man of Mediterranean descent with 5- A 34 year-old man of Mediterranean descent with a family history of anemia.a family history of anemia.

6- A 50 year-old man with severe rheumatoid 6- A 50 year-old man with severe rheumatoid arthritis. arthritis.

MCVMCVFerritinFerritinTIBCTIBCRDWRDW

a- Elevated a- Elevated DecreasedDecreasedElevatedElevatedDecreasedDecreased

b- b- DecreasedDecreased

DecreasedDecreasedElevated Elevated IncreasedIncreased

c- Normalc- NormalElevated Elevated Normal Normal NormalNormal

d- d- DecreasedDecreased

IncreasedIncreasedNormalNormalNormalNormal

e- Elevatede- ElevatedIncreasedIncreasedDecreasedDecreasedIncreasedIncreased

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ConclusionsConclusions Anemia is a clinical finding, not a Anemia is a clinical finding, not a

diagnosis and requires some diagnosis and requires some investigation to determine the underlying investigation to determine the underlying etiology.etiology.

Iron deficiency anemia in men or Iron deficiency anemia in men or postmenopausal women is primarily a postmenopausal women is primarily a result of gastrointestinal blood losses; result of gastrointestinal blood losses; therefore, finding iron deficiency anemia therefore, finding iron deficiency anemia in this patient population warrants a in this patient population warrants a through GI workup.through GI workup.

Iron deficiency anemia in women of Iron deficiency anemia in women of reproductive age is most often caused by reproductive age is most often caused by menstrual blood loss.menstrual blood loss.

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ContCont.. The fecal occult blood testing (FOBT) The fecal occult blood testing (FOBT)

is negative in about 50% of patients is negative in about 50% of patients with GI cancer. Therefore, a negative with GI cancer. Therefore, a negative FOBT in the presence of iron FOBT in the presence of iron deficiency anemia should not deficiency anemia should not discourage you from pursuing a discourage you from pursuing a through GI workup.through GI workup.

The mean corpuscular volume, RDW The mean corpuscular volume, RDW and the reticulocyte index are and the reticulocyte index are important parameters in the important parameters in the evaluation of anemia.evaluation of anemia.

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PolycythaemiaPolycythaemia

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Polycythaemia refers to an increase in red Polycythaemia refers to an increase in red

cell count, haematocrit and usually cell count, haematocrit and usually haemoglobin.haemoglobin.

There are two main types of There are two main types of polycythaemia, the classification polycythaemia, the classification depending on the results of measurement depending on the results of measurement of red cell mass and plasma volume:of red cell mass and plasma volume: Relative (pseudo) polycuthaemia: due to Relative (pseudo) polycuthaemia: due to

decrease in plasma volume.decrease in plasma volume. True polycythaemia: the red cell mass in True polycythaemia: the red cell mass in

increased.increased.(True polycythaemia may either a primary or secondary).(True polycythaemia may either a primary or secondary).

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Primary true Primary true polycythaemiapolycythaemia

In the meloproliferative disorder polythaemia In the meloproliferative disorder polythaemia rubra vera (PRV), there is uncontrolled rubra vera (PRV), there is uncontrolled production of red cells by the marrow, even production of red cells by the marrow, even though erythropoietin is switched off.though erythropoietin is switched off.

Clinical features: Clinical features: hypertension, splenomegaly, hypertension, splenomegaly, arterial and venous thrombosis, pruitus, arterial and venous thrombosis, pruitus, plethoric features, peptic ulceration, gout.plethoric features, peptic ulceration, gout.

Laboratory featuresLaboratory features: there is high red cell : there is high red cell count, haemoglobin, haematovril, whole blood count, haemoglobin, haematovril, whole blood viscosity and uric acid. The white cell count, viscosity and uric acid. The white cell count, platelete count and neutrophil alkaline platelete count and neutrophil alkaline phosphates are also increase and the latter three phosphates are also increase and the latter three parameters help to distinguish PRV from parameters help to distinguish PRV from secondary polycythaemia. secondary polycythaemia.

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Secondary true Secondary true polycythaemiapolycythaemia

This condition is associated This condition is associated

with increased levels of with increased levels of

erythropoietin, which is erythropoietin, which is

produced by other the kidney produced by other the kidney

or an ectopic tumor.or an ectopic tumor.

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Cause of secondary Cause of secondary polycythaemiapolycythaemia

Increased renal erythrpoietin production due to hypoxia

Inappropriate erythropoietin production

• Physiological Adaptation to altitude in neonates

• From the kidney(eg pyonephrosis, renal cysts, renal artery stenosis after renal transplantation)

• Congential cyanotic heart disease (eg Fallot’s tertragoly, Eisenmenger’s complex)

• From a tumor (ectopic erythropoietin secreted in an uncontrolled fashion)(eg carcinoma of the kideny, giant uterine fibroids, hepatoma, cerberallar haemangioma)

• Respiratory related Smoking COPD

•High- affinity haemoglobins (eg haemoglobin M)

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Relative polycythaemiaRelative polycythaemia A reduction in circulating plasma volume can be to A reduction in circulating plasma volume can be to

pyrexia, diarrhoea, vomiting and diuretic therapy.pyrexia, diarrhoea, vomiting and diuretic therapy.

Gaisbok’s polycythaemiaGaisbok’s polycythaemia Refers to a from of stress polycythaemia; this has Refers to a from of stress polycythaemia; this has

been noticed in middle-aged men who have been noticed in middle-aged men who have stressful occupations, a chronically reduced stressful occupations, a chronically reduced plasma volume of uncertain cause.plasma volume of uncertain cause.

Treatment of polycythaemiaTreatment of polycythaemia Treatment is indicated for polycythaemia as high Treatment is indicated for polycythaemia as high

blood viscosity leads to an increased incidence of blood viscosity leads to an increased incidence of thrombosis, hypertension, stroke and athermanous thrombosis, hypertension, stroke and athermanous vascular disease.vascular disease.

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Venesction to a great haematocril: the packed Venesction to a great haematocril: the packed cell volume is more closely related to the cell volume is more closely related to the blood viscosity than is the haemoglobin (as blood viscosity than is the haemoglobin (as repeated vensection may result in iron-repeated vensection may result in iron-deficient red cells with a low haemoglobin deficient red cells with a low haemoglobin content). Venesection may be traditional or content). Venesection may be traditional or isovolamic (with saline replaement). The isovolamic (with saline replaement). The latter is used in patients with cardiovascualr latter is used in patients with cardiovascualr risk factors (eg angina or hypertension), in risk factors (eg angina or hypertension), in those who are taking drugs that may impair those who are taking drugs that may impair physiological response to vensection (ACE physiological response to vensection (ACE inhibitors, beta blockers), or in patients with inhibitors, beta blockers), or in patients with relative polycythaemia. relative polycythaemia.

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Cytotoxic agent (particularly Cytotoxic agent (particularly hydroxyurea): this presuppose hydroxyurea): this presuppose erythropoiesis ad cause a erythropoiesis ad cause a macrocytosis which is not related to macrocytosis which is not related to vitamin B12 or folate deficiency. vitamin B12 or folate deficiency. Unlike other cytotoxic agents (eg Unlike other cytotoxic agents (eg busslfan) it is unlikely to be busslfan) it is unlikely to be leukaemogenic.leukaemogenic.

Aspirin and anticoagulants: if the Aspirin and anticoagulants: if the patient presents with thrombosis. patient presents with thrombosis.

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Multiple Multiple myelomamyeloma

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MyelomaMyeloma In myeloma there is a clonal proliferation of

plasma cells and the clinical manifestations of disease "= are -Mated to substances secreted by the plasma cells as much as to the effects of marrow infil tration. Clonality (all diseased cells originating from one parent plasma cell) may be confirmed by:  the presence of a paraprotein (monoclonal) band on

serum electrophoresis, or by Immunopheno typing the increased numbers of

plasma cells in the bone marrow, and finding,. that they all express either kappa or lambda light chains rather than a mixture of the two.

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Paraprotein sub-typesParaprotein sub-typesThe normal immunoglobulin

concentrations in serum parallel the relative frequency of the three main sub-classes of myeloma paraprotein. Hence, IgG is the most common form of myeloma, followed by IgA, with IgM being the least common type.

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Plasma hyperviscosity syndrome may Plasma hyperviscosity syndrome may be found be found This: consists of confusion, capillary bleeding, This: consists of confusion, capillary bleeding, oedema and renal impairment. The incidence of oedema and renal impairment. The incidence of hyperviscosity syndrome relates to the size of hyperviscosity syndrome relates to the size of the immunoglobulin molecule as well as its the immunoglobulin molecule as well as its concentration. As IgM is the largest molecule concentration. As IgM is the largest molecule (750, 000 daltons) this syndrome is seen (750, 000 daltons) this syndrome is seen relalatively frequently in IgM myeloma, less relalatively frequently in IgM myeloma, less frequently in IgA myeloma and rarely in IgG frequently in IgA myeloma and rarely in IgG myeloma:. Transfusion should be avoided in myeloma:. Transfusion should be avoided in patients with plasma hyperviscosity syndrome, patients with plasma hyperviscosity syndrome, as it willas it will,, cause a big increase in whole blood cause a big increase in whole blood viscosity.viscosity.

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Cryoglobulin: rarely, the paraprotein Cryoglobulin: rarely, the paraprotein

may be a cryoglobulin, so that the may be a cryoglobulin, so that the

protein precipitates from plasma in protein precipitates from plasma in

the cold. This may be a cause of the cold. This may be a cause of

vasculitis. Some myeloma vasculitis. Some myeloma

paraproteins precipitate within tissue paraproteins precipitate within tissue

to form amyloid.to form amyloid.

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Bence-Jones Bence-Jones proteinprotein Sometimes, the malignant plasma cells

are so defective that they cannot make a complete immunoglobulin molecule and are only able to make light chains. The latter are small enough to he filtered within the glomerulus and to appear in the urine as Bence-Jones proteinurias. They may obstruct the renal tubules and contribute to the renal failure which is often found in myeloma.

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Role Role of of cytokines cytokines in myelomain myeloma Osteoclast-activating factors Osteoclast-activating factors

stimulate the normal osteoclasts stimulate the normal osteoclasts to dissolve bone and lead to bone to dissolve bone and lead to bone pain, hypercalcaemia and pain, hypercalcaemia and pathological fractures in myeloma. pathological fractures in myeloma. In other myeloma cases, IL -6 may In other myeloma cases, IL -6 may be produced in excess by bone be produced in excess by bone marrow stromal cells infected with marrow stromal cells infected with human herpes virus (HHVB).human herpes virus (HHVB).

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Treatment of myeloma Inn younger patients, most centers are moving

away from single-agent melphalan therapy towards continuous low-dose combination chemotherapy such as VAD (Vincristine, Adriamycin and Dexamethasone) or ZDex (oral idarubicin and dexamethasone). Malignant cells are most sensitive to the action of chemotherapy when they are dividing; as plasma cells divide relatively infrequently, it is necessary to administer the chemotherapy over several days in order to maximise the chances of treatingg dividing cells.

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Thalidomide has a proven role in myeloma treatment although its mechanism of action remains uncertain. It is likely to inhibit cytokine release, but an anti-angiogenesis activity has not been ruled out.

Bisphosphonates, such as monthly intravenous pamidronate, have an important role in the prevention off pathological fractures and in the treatment of myeloma-associated hypercalcaemia.

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Monoclonal gammopathy of undetermined significance (MGUS)

A common clinical problem is the differentiation between myeloma and MGUS (benign monoclonal gammopathy) in patients found to have a paraprotein. Ten per cent of patients with MGUS develop myeloma at 5 years, and 50% at 15 years. It is probable that most patients would eventually develop myeloma but many die of other causes before this occurs.

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Differentiation of myeloma from Differentiation of myeloma from MGUSMGUS

MGUS Low level of paraprotein (< 20 g/I for an IgG paraprotein)Paraprotein level remains stable over a period of observation depressed(months or years)Other immunoglobulin levels are normalNo clinical evidence of myeloma(bone disease, renal disease)

MyelomaHigh level of paraprotein Level risesOther immunoglobulin levels are depressedClinical evidence of myeloma

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SummarySummary It is a malignancy of B-lymphocytes.It is a malignancy of B-lymphocytes. The malignant plasma cells and their The malignant plasma cells and their

lymphocytes precursor are present in lymphocytes precursor are present in the bone marrow. Sometimes they are the bone marrow. Sometimes they are detected in the peripheral blood and in detected in the peripheral blood and in soft tissue.soft tissue.

The tumor cells secrete factors which:The tumor cells secrete factors which: Activate osceoclasts which destroy the bone.Activate osceoclasts which destroy the bone. Suppress bone marrow function.Suppress bone marrow function. Decrease antibody formation. Decrease antibody formation.

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Laboratory findingsLaboratory findings CBC: Anemia (normocytic and normochromic)CBC: Anemia (normocytic and normochromic) ESR: IncreasedESR: Increased Renal function:Renal function:

Decreased Decreased Blood urea sr. creatinine increasedBlood urea sr. creatinine increased

Serum calcium: IncreasedSerum calcium: Increased Serum alkaline phosphatase: Normal.Serum alkaline phosphatase: Normal. Serum total proteins:Serum total proteins:

Elevated Elevated Protein electrophoresis + immunoelectrophoresis Protein electrophoresis + immunoelectrophoresis

monoclonal band. monoclonal band.

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Immunoglobulin level:Immunoglobulin level:

Increase of the type affected Increase of the type affected

B.MB.M

Infiltration with malignant plasma cells.Infiltration with malignant plasma cells.

Urine analysis:Urine analysis:

Bone jones proteins may be presents.Bone jones proteins may be presents.

B2- microglobulin: IncreasedB2- microglobulin: Increased

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DiagnosisDiagnosis

Two of the following criteria should be Two of the following criteria should be

present:present:

Bone marrow infiltration by more than 30% Bone marrow infiltration by more than 30%

of malignant plasma cells.of malignant plasma cells.

Osteolytic bone lesions.Osteolytic bone lesions.

Presence of monoclonal Ig in blood and/or Presence of monoclonal Ig in blood and/or

urine, as a whole molecule or as light chains.urine, as a whole molecule or as light chains.

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Commentary Commentary A healthy 52-year-old man presents to the doctor’s A healthy 52-year-old man presents to the doctor’s

office complaining of increasing fatigue for the past office complaining of increasing fatigue for the past 4-5 months. He exercises every day but lately he has 4-5 months. He exercises every day but lately he has noticed becoming short of breath while jogging, he noticed becoming short of breath while jogging, he denies orthopnea, paroxysmal nocturnal (PND), or denies orthopnea, paroxysmal nocturnal (PND), or swelling in his ankles. The patient reports swelling in his ankles. The patient reports occasional joint pain for which he uses over the occasional joint pain for which he uses over the counter (OTC) ibuprofen, he denies bowel changes, counter (OTC) ibuprofen, he denies bowel changes, melena or bright red blood per rectum, but reports melena or bright red blood per rectum, but reports vague left side abdominal pain for a few months off vague left side abdominal pain for a few months off and on, not related to food intake. and on, not related to food intake.

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The patient denies fever, chills, nausea or vomiting, The patient denies fever, chills, nausea or vomiting, he has lost a few pounds intentionally with diet and he has lost a few pounds intentionally with diet and exercise. On examination, his weight is 90kg and he exercise. On examination, his weight is 90kg and he is aferbrile. There is slight pallor of conjunctiva, skin is aferbrile. There is slight pallor of conjunctiva, skin and palms. No lymphadenopathy is noted chest, is and palms. No lymphadenopathy is noted chest, is clear to auscultation bilaterally, regular rate and clear to auscultation bilaterally, regular rate and rhythm of pluse with no rub or gallop, There is a rhythm of pluse with no rub or gallop, There is a grade II/IV systolic ejection murmur, his abdomen is grade II/IV systolic ejection murmur, his abdomen is soft, nontender and without hepato-splenomegaly, soft, nontender and without hepato-splenomegaly, bowel sounds are present. He has no extremity bowel sounds are present. He has no extremity edema, cyanosis or clubbing, his peripheral pulses edema, cyanosis or clubbing, his peripheral pulses are palpable and symmetric. A hemoglobin level is are palpable and symmetric. A hemoglobin level is 9.2g/dl, MCV 75µ9.2g/dl, MCV 75µ33, MCH 25 Pgm., MCH 25 Pgm. Discuss the most likely diagnosis.Discuss the most likely diagnosis. Differential diagnosis of this case.Differential diagnosis of this case.

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The typical features of acute hepatic failure The typical features of acute hepatic failure include, except:include, except: Onset within 8 weeks of the initial illness.Onset within 8 weeks of the initial illness. Hepatoplenomegaly and ascitis.Hepatoplenomegaly and ascitis. Encephalopathy and fetor hepaticus.Encephalopathy and fetor hepaticus. Nausea, vomiting and renal failure.Nausea, vomiting and renal failure. Cerebral oedema without papilloedema.Cerebral oedema without papilloedema.

The typical feature of primary biliary cirrhosis The typical feature of primary biliary cirrhosis include:include: Xanthomata of the palmar creases and eyelids.Xanthomata of the palmar creases and eyelids. Poor prognosis even in asymptomatic patients.Poor prognosis even in asymptomatic patients. Hepatomegaly without splenomegaly.Hepatomegaly without splenomegaly. Dilated bile ducts on ultrasonography.Dilated bile ducts on ultrasonography. Improved survival rate without immunosuppressant therapy.Improved survival rate without immunosuppressant therapy.

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The clinical features of acromegaly include, except:The clinical features of acromegaly include, except: Arthropathy and myopathy.Arthropathy and myopathy. Hypertension and impaired glucose tolerance.Hypertension and impaired glucose tolerance. Goiter and cardiomegaly.Goiter and cardiomegaly. Increased sweating and headache.Increased sweating and headache. Skin atrophy and decreased sebum secretion.Skin atrophy and decreased sebum secretion.

Causes of short stature in childhood include, except;Causes of short stature in childhood include, except; Klinefelter's syndrome.Klinefelter's syndrome. Turner's syndrome. Turner's syndrome. Emotional deprivation.Emotional deprivation. Cushing's syndrome.Cushing's syndrome. Primary hypothyroidism.Primary hypothyroidism.

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Which of the following studies is most Which of the following studies is most sensitive for detecting diabetic nephropathy:sensitive for detecting diabetic nephropathy: Serum creatinine levelSerum creatinine level Creatinine clearanceCreatinine clearance Urine albuminUrine albumin Glucose tolerance testGlucose tolerance test Ultrasonography Ultrasonography

Haematocrit value of 45% means that:Haematocrit value of 45% means that: 45% of the Hb in the plasma.45% of the Hb in the plasma. 45% of the total blood volume is made up of plasma.45% of the total blood volume is made up of plasma. 45% of the total blood volume is made up of blood cells.45% of the total blood volume is made up of blood cells. 45% of the Hb is in the red blood cell.45% of the Hb is in the red blood cell.

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An anaemic subject has R.B.Cs count An anaemic subject has R.B.Cs count 3.5millom/mm3, PCV42% & Hb 14gm%, by 3.5millom/mm3, PCV42% & Hb 14gm%, by using the blood indices this subject most using the blood indices this subject most probably has?probably has? Aplastic anaemia.Aplastic anaemia. Macrocyric hyperhormic anaemia.Macrocyric hyperhormic anaemia. Normocytic normochromic anaemia.Normocytic normochromic anaemia. Microcytic hypochromic anaemia.Microcytic hypochromic anaemia.

If a man's plasma agglutinates both A and B If a man's plasma agglutinates both A and B red cells, he is group:red cells, he is group: BB AA ABAB OO

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Clinical features suggesting severe aortic Clinical features suggesting severe aortic stenosis include, except:stenosis include, except: Early systolic ejection click.Early systolic ejection click. Pulsus bisferiens.Pulsus bisferiens. Heaving displaced apex beat.Heaving displaced apex beat. Syncope associated with angina.Syncope associated with angina.

Which of these is not a peripheral sign of Which of these is not a peripheral sign of infective endocarditis?infective endocarditis? Osler's nodes.Osler's nodes. Splinter haemorrhages.Splinter haemorrhages. Janeway lesions.Janeway lesions. Clubbing.Clubbing. Palmar erythema.Palmar erythema.

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Thrombin is required for activation of all the Thrombin is required for activation of all the following except:following except: PlasminogenPlasminogen FibrinogenFibrinogen Clot retractionClot retraction Factor IIIFactor III

All the following drugs for the treatment of All the following drugs for the treatment of peptic ulcer disease alter gastric acid pH peptic ulcer disease alter gastric acid pH except:except: Calcium carbonateCalcium carbonate CimmetidineCimmetidine OmeprazoleOmeprazole PirenzepinePirenzepine Sucralfate Sucralfate

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Characteristic feature of cholestatic Characteristic feature of cholestatic jaundice include, except:jaundice include, except: Dark green stool.Dark green stool. Dark brown urine.Dark brown urine. Conjugated hyperbilirubinaemia.Conjugated hyperbilirubinaemia. Serum alkaline phosphatase concentration increased Serum alkaline phosphatase concentration increased

>2.5 normal.>2.5 normal. Increased serum bile acid concentrations.Increased serum bile acid concentrations.

The typical clinical features of diabetic The typical clinical features of diabetic ketoacidosis include, except:ketoacidosis include, except: Abdominal pain and air hunger.Abdominal pain and air hunger. Rapid weak pulse and hypotension.Rapid weak pulse and hypotension. Dry skin and polyuria.Dry skin and polyuria. Vomiting and constipation.Vomiting and constipation. Coma with extensor plantar response.Coma with extensor plantar response.

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Cause of polyuria include, except:Cause of polyuria include, except: Chronic hyperglycaemia.Chronic hyperglycaemia. Chronic renal failure.Chronic renal failure. Hypercalcaemia.Hypercalcaemia. Hypothyroidism.Hypothyroidism. Lithium toxicity.Lithium toxicity.

All the following drugs are associated with All the following drugs are associated with an increased risk of osteoporosis in adults an increased risk of osteoporosis in adults except:except: CyclosporineCyclosporine DilantinDilantin HerparinHerparin PresnisonePresnisone Ranitidine Ranitidine

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Hypercyanotic spell of Tetralogy of fallot is Hypercyanotic spell of Tetralogy of fallot is treated with all of the following except:treated with all of the following except: Knee chest position.Knee chest position. Morphine.Morphine. Digoxin.Digoxin. Propranolol.Propranolol. Sodium bicarbonate.Sodium bicarbonate.

Which of the following symptoms lists of Which of the following symptoms lists of rheumatic fever are in the correct order of most rheumatic fever are in the correct order of most common least common?common least common? Erythema Marginatum, subcutaneous nodules, carditis, fever.Erythema Marginatum, subcutaneous nodules, carditis, fever. Arthritis, carditis, chorea, erythema Marginatum.Arthritis, carditis, chorea, erythema Marginatum. Chorea, Erythema Marginatum, subcutaneous nodules.Chorea, Erythema Marginatum, subcutaneous nodules. Arthritis, chorea, fever, Carditis,, subcutaneous nodulesArthritis, chorea, fever, Carditis,, subcutaneous nodules Fever, chorea, carditis, erythema MarginatumFever, chorea, carditis, erythema Marginatum

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All of the following are included in the All of the following are included in the revised Jones major criteria Except:revised Jones major criteria Except: New significant murmur indicative of carditis.New significant murmur indicative of carditis. Migrating polyarthitis.Migrating polyarthitis. Chorea.Chorea. Erythema multiforme.Erythema multiforme. Subcutaneous nodules.Subcutaneous nodules.

Laboratory finding in a case of thalassemia Laboratory finding in a case of thalassemia include all of the following except:include all of the following except: High serum ferritinHigh serum ferritin RecticulocytosisRecticulocytosis Decreased osmotic fragilityDecreased osmotic fragility Normocytic hypochromic anaemiaNormocytic hypochromic anaemia hyperbilirubinaemiahyperbilirubinaemia

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The following are essential for diagnosis of The following are essential for diagnosis of primary nephrotic syndrome except:primary nephrotic syndrome except: Severe edemaSevere edema Massive albuminuria Massive albuminuria Renal failureRenal failure HypoalbuminemiaHypoalbuminemia HypercholesterolaemiaHypercholesterolaemia

The following are features of acute The following are features of acute glomerulonephritis except:glomerulonephritis except: HaematuriaHaematuria Ascities & pleural effusionAscities & pleural effusion HypertensionHypertension ProteinuriaProteinuria Oliguria Oliguria

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In Tetralogy of Fallot, all are true except:In Tetralogy of Fallot, all are true except: Pulmonary congestion in chest X-rayPulmonary congestion in chest X-ray Central cyanosis and clubbingCentral cyanosis and clubbing Basal ejection systolic murmur and single 2Basal ejection systolic murmur and single 2ndnd heart sound. heart sound. Cyanotic spells due to infundibular pulmonary spasm and Cyanotic spells due to infundibular pulmonary spasm and

decrease blood flow.decrease blood flow. Heart failure rarely occurs.Heart failure rarely occurs.

Anaphylactoid purpura may be associated with Anaphylactoid purpura may be associated with all except:all except: Urticarial maculopapular rash distributed manily on Urticarial maculopapular rash distributed manily on

extensor surface of limbs.extensor surface of limbs. HepatosplenomeglayHepatosplenomeglay Microscopic haematuria and mild notenuriaMicroscopic haematuria and mild notenuria Abdominal pain with occult blood in stool.Abdominal pain with occult blood in stool. Joint painsJoint pains

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All of the following are normocytic All of the following are normocytic normochromic anemia except:normochromic anemia except: Sickle cell anemiaSickle cell anemia A plastic anemiaA plastic anemia Juvenile pernicious anemiaJuvenile pernicious anemia Immune hemolytic anemiaImmune hemolytic anemia

Treatment of thalassemia includes all the Treatment of thalassemia includes all the following except:following except: Repeated blood transfusion.Repeated blood transfusion. Iron therapyIron therapy SplenectomySplenectomy Bone marrow transplantionsBone marrow transplantions Gene therapy. Gene therapy.

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One of the following is a not a minor One of the following is a not a minor manifestation in the diagnosis of initial attack manifestation in the diagnosis of initial attack of rheumatic fever:of rheumatic fever: FeverFever ArthralgiaArthralgia High ESRHigh ESR Elevated or rising antistreptococcal antibody titer.Elevated or rising antistreptococcal antibody titer. Prolonged P-R interval on ECG.Prolonged P-R interval on ECG.

Causes of huge splenomegaly include all of the Causes of huge splenomegaly include all of the following except:following except: Bilharzial splenomeglyBilharzial splenomegly Chronic myeloid leukemiaChronic myeloid leukemia Chronic malariaChronic malaria Thalassemia majorThalassemia major E.B virus infectionE.B virus infection

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Which of the following is a cause of Which of the following is a cause of microcytic hypochromic anemia:microcytic hypochromic anemia: Iron deficiency anemiaIron deficiency anemia Thalssemia Thalssemia Lead poisoningLead poisoning Anemia of chronic infectionAnemia of chronic infection All of the aboveAll of the above

The following are essential for diagnosis of The following are essential for diagnosis of primary nephrotic syndrome except:primary nephrotic syndrome except: Severe edema.Severe edema. Massive albuminuriaMassive albuminuria Low C3Low C3 HypoalbuminemiaHypoalbuminemia Hypercholesterolemia.Hypercholesterolemia.

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Which of the following statements Which of the following statements concerning infectious mononucleosis concerning infectious mononucleosis is incorrect:is incorrect: Rash appears in 10-20% of cases, discrete Rash appears in 10-20% of cases, discrete

macular, petichial, morbilliform or macular, petichial, morbilliform or scarlentiform appearance.scarlentiform appearance.

Triad of membranous tonsillitis, Triad of membranous tonsillitis, lymphadenopathy and splenomegaly.lymphadenopathy and splenomegaly.

Causative organism is EnterovirusCausative organism is Enterovirus Incubation period: 5-15 days.Incubation period: 5-15 days. Prodromal period: fever, fatigue, headache, Prodromal period: fever, fatigue, headache,

myalgia, abdominal pain.myalgia, abdominal pain.

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Thank YouThank You