Anemia 2011 Student Dental f Copy

8/7/2019 Anemia 2011 Student Dental f Copy

1/64

And hold fast, all together, by the rope which God (stretches out foryou), and be not divided among yourselves; and remember with

gratitude God's favour on you; for ye were enemies and He joined

your hearts in love, so that by His Grace, ye became brethren; and

ye were on the brink of the pit of Fire, and He saved you from it.

Thus doth God make His Signs clear to you: That ye may be

guided. [003:103]

Todays Quranic verse


2/64

No one can make you feel inferior

without your consent


3/64

Proerythroblast

(Pronormoblast)

Basophilic

Normoblast

Polychromatophilic

Normoblast

Orthochromatophilic

Normoblast

Reticulocyte

Erythrocyte

Early Intermediate Late

Steps in Erythropoisis


4/64

C.B.C

Haemoglobin - 152.5, 14 2.5 - g/dl

PCV - 0.47 0.07, 0.42 0.05 - l/l (%)

Haematocrit, effective RBC volume better

RBC count - 5.5 1, 4.8 1 x1012/l

MCHC - Hb/PCV - 30-36 - g/dl

Hb synthesis within RBC

MCH - Hb/RBC - 29.5 2.5 pg/l

Average Hb in RBC

MCV - PCV/RBC 85 8 fl

RDW (Red Cell Distribution Width )-13 1.5


5/64

Red Blood Cell Disorders

Anemias

AnemiaofBloodLoss: (Acutevs. Chronic) Anemiaof Erythropoiesis

Hemolytic Anemia: (Congenital/Acquired)

Polycythemia


6/64

Anemias

Hb (g/dL)

Male Female

13-17 12-15

(152) (13.5 1.5)

An (without) -emia (blood):

Reduction below normalinhemoglobinorred bloodcellnumber(forage & sex).


7/64

Anemias

REDISTRIBUTION2,3 DPG

C.O. PLASMA

Anemia

HYPOXIA

COMPENSATORY

MECHANISMS

C.O.PATHOPHYSIOLOGY

OF ANEMAIS


8/64

Anemias TIREDNESSLASSITUDE

EASYFATIGUABILITY

MUSCLEWEAKNESS

CLINICAL FEATURES

GISCNS

CRS GUSPALLOR


9/64

Anemias

Etiological Morphological

ClassificationClassification


10/64

AnemiasETIOLOGIC

Classification

BLOOD LOSS(Haemorrhagic)

IMPAIREDRED CELL

FORMATION(Erythropoiesis)(Dyshaemopoietic)

INCREASED

RED CELLDESTRUCTION(Haemolytic)

I

II III


11/64

Anemias

ETIOLOGICClassification

BLOODLOSS

IMPAIREDRED CELL

FORMATION

HEMOLYTICANEMIAS

I

II III

CHRONICACUTE

DEFICIENCYNON

DEFICIENCY

RBCABNORMALITIES

RBC ENVIRONMENTABNORMALITIES


12/64

DEFICIENCY ANEMIAS

ANEMIAS DUE TO DEFICIENCY OF SUBSTANCESESSENTIAL FOR ERYTHROPOIESIS

IRON

DEFICIENCYANEMAIS

MICROCYTIC HYPOCHROMIC

ANEMIAS

FOLIC ACID/VITAMIN B12

DEFICIENCYMEGALOBLASTIC ANEMAIS


13/64

NONDEFICIENCY ANEMIAS

ANEMIAS NOT DUE TO DEFICIENCY OF SUBSTANCESESSENTIAL FOR ERYTHROPOIESIS

APLASTIC

ANEMIA

ACD

ANEMIA OF

CHRONIC

DISORDERS

ANEMIA

OF

BONE MARROW

INFILTRATION

(myelophthisic)

OTHERS

LEUKEMIAS,LYMPHOMAS

MYELOMA,MYELOFIBROSIS

INFECTION COLLAGENDISEASES

RENALFAILURE, LIVERFAILURE

MALIGNANCY


14/64


15/64

Anemias

MORPHOLOGICClassification

IIMICROCYTIC

HYPOCHROMIC

III

MACROCYTICANEMIAS

I

NORMOCYTICNORMOCHROMIC

Iron DeficiencyThalassemias

ACD

Megaloblastic


16/64


17/64

Iron Deficiency Anemia

A world-wideproblem

3% oftoddlers age 1-2 years

2-5% ofwomenofchild bearingage

Ironmetabolism

Iron stores

Laboratoryfindings ofirondeficiency

Causes ofirondeficiency

Treatment


18/64

MajorIron Compartments

Metabolic

Hemoglobin 1800-2500 mg

Myoglobin 300-500 mg

Storage

Iron storage 0-1000 mg

Transit

Serumiron 3 mg

Total 3000-4000 mg


19/64

Causes ofIron Deficiency

Increasediron

requirements

Bloodloss

Gastrointestinaltract

Genitourinarytract

Blooddonation Worminfestation

Pregnancyandlactation

Inadequateiron supply Insufficientdietaryiron (malnutrition)

Impairedironabsorption

Gastric surgery

Intestinalmalabsorption

Celiacdisease

Iron deficiency is a symptom, not a disease


20/64

Esophageal webs and strictures

Koilonychia

Systemic Manifestations ofIron

Deficiency

Behavioralandneuropsychiatric

manifestations

Pica (pagophagia)

Angularstomatitis

Glossitis


21/64

Lab Findings

Hb lowMCV low

Serum iron lowTIBC high

Ferritin lowBM iron absent

Peripheral smear: Microcytic hypochromic


22/64

Hypochromic Microcytic RBC

Smear

Microcytic / Hypochromic RBCs,Anisocytosis, Poikilocytosis


23/64

Macrocytic Anaemias

Defition:- Anaemias with MCV >95 fl

Classification:-

A. Megalo-blasticB. Non-megalo-blastic


24/64

Megaloblastic anemia

Vitamin B12/Folicaciddeficiency

Secondmostcommontypeofanemia.

Multi SystemdiseaseAllorgans withincreasedcelldivision.

Macrocyticanemia, pancytopenia.

Pernicious anaemia

autoimmune, Gastricatrophy, VitB12 def.


25/64

Enteric Processing & Absorption

of Cobalamin

Peptic

digestionH+

Cbl + R-binder

R-Cbl

Pancreatic

enzymes

OH-IF + Cb

Cbl-IF

Food-Cbl

IF receptor Cbl + TC

Cbl-TC complex

Stomach

Duodenum

Distal ileum

R-Cbl

Cbl-IF


26/64

Vitamin B12 Deficiency

Mechanisms Malnutrition

Intragastricevents Inadequatedissociationofcobalaminfromfoodprotein

Totalorpartialgastrectomy Absentintrinsicfactorsecretion

Proximal smallintestine Impairedtransferofcobalaminfrom R proteintointrinsicfactor

Usurpationofluminalcobalamin

Bacterialovergrowth Diphylobothrium latum (fishtapeworm)

Distal smallintestine Diseaseoftheterminalileum


27/64

Megaloblastic Anemia-Pathogenesis

Decreased VitB12 / Folate

Decreased DNA Synthesis

Delayed maturation of erythroblasts (Nucleus)

Increased cell size (macrocytes)

Normal Hb content(Normochromia)

Decreased RBC number & Decreased WBC number (pancytopenia)

Anemia & Pancytopenia.


28/64

Pernicious Anemia

Mostcommoncauseofvitamin B12 deficiency

Occurs inallages andethnic backgrounds

Autoimmunedestructionofgastricmucosachronic Atrophicgastritis IF

Associated withotherautoimmunediseases

Screenforthyroiddiseaseevery 1-2 years

Pernicious anemiais a systemicdisease

Gastrointestinaltractinvolvement

Neurologicinvolvement (sub-acutecombineddegenerationofspinalcord)

Anti-intrinsicfactorantibodies (~60% positive) Specific butnot sensitive

Anti-parietalcellantibodies (~90% positive) Sensitive butnot specific

Schillingtest


29/64

Macrocytes & Macropoly & Megaloblast


30/64

Folate Deficiency

Minimumdailyfolaterequirementis 50 g

Usualdietaryfolate 50-500 g

Absorptionin smallintestine

Causes offolatedeficiency

Dietary (90%)

Alcoholabuse

Pregnancy

Malabsorption

Drug-induced

Treatment - oralfolicacid supplementation


31/64


32/64

Anemia of Chronic Disease

Associatedconditions Prevalence Infection 20-95%

Viral, bacterial, TB, parasitic, fungal

Autoimmunedisease 8-17% RA, SLE, sarcoidosis, IBD, vasculitis

Cancer 30-77%

Chronic solidorganrejection 8-70%

Characteristics

WBC andplateletcounts arenormal Anemiaofvariable severity (mild-severe)

Low erythropoietinlevel

Low reticulocytecount


33/64

Anemia of Chronic Disease

PathogenesisCytokines

(IL-1, TNF, IL-4)

Disturbedironmetabolism

Diversionofironfromcirculationtothe RE system

Decreased RBC

precursors

InadequateEpo

response

Normch/normocy, Hypoch/microcy, serum iron, /N TIBC, /N S.Ferritin, Storage iron


34/64

Aplastic Anemia

Suppression of multipotentmyeloid stem cells Anemia, thrombocytopenia, neutropenia Etiology: idiopathic (65%), irradiation, myelotoxic drugs, chemicals,

viruses Idiosyncratic reaction: chloramphenicol, sulfonamides

BM: hypocellular with fat replacement

No splenomegaly, if + diagnosis, notAA

No reticulocytosis Treatment: stop drug, BMT(< 40 y/o) for idiopathic,

immunosuppression for older patients, w/o donors


35/64

Aplasticanemia


36/64

HEMOLYTICANEMIA


37/64

Hemolytic Anemia with Extravascular

HemolysisHereditary

Hemoglobinopathies (sicklecellanemia, thalassemia)

Enzymopathies (G6PD deficiency)

Membranedefects (hereditary spherocytosis)

Acquired Immunemediated

Autoimmunehemolyticanemia Nonimmunemediated

Spurcellhemolyticanemia

Extravascular (reticuloendothelial system)


38/64

Sickle Cell Anemia

Mostprevalenthemoglobinopathy caused by mutations ofthe -globin chain sickle Hb (HbS)

8% of American blacks (1:600)

30% of African blacks (protective effectof HbS vs. malaria)

Autosomal recessive

Single AA substitution in the globin chain (val for glu)

Normal adult: 96% HbA, 3% HbA2, 1% HbF

On deoxygenation: HbS polymerize (gelation/crystallization)

Change in physical state cause RBC distortion sickle/crescents

Reversible sickling irreversible sickling despite adequate O2

RBC hemolysis (anemia), capillary stasis (ischemia/thrombosis)


39/64

TargetcellSicklecells

Anisocytosis/poikilocytosis


40/64

Hemolytic Anemia: Sickle Cell Anemia

Clinical: anemia + complications: acutechest syndrome, strokes, acutepaincrisis, priapism, legulcers (vaso-

occlusion),

Susceptibletoinfection: S. pneumoniae, Staphylococcal, Salmonella(osteomyelitis)

Diagnosis:

-Peripheral smear, Lab iron studies & Electrophoresis

Treatment:

Hydroxyurea Increases HbF = retards sickling byinhibitingpolymerformation

RBC transfusions

RBC exchanges duringacutecrises


41/64


42/64

Hereditary Spherocytosis

Abnormal RBC skeletal/membrane proteins (ie. Ankyrin)

RBCs with reduced membrane stability lose membranefragments, assume a sphere

Clinical: anemia, splenomegaly, jaundice

Lab: osmotic fragility

Upon exposure to hypotonic saltsolution, spheroidal shapelimits volume of expansion.

RBCs shortened lifespan

Treatment: splenectomy to alleviate anemia, continue to havespherocytes


43/64

Hereditary Spherocytosis


44/64

Glucose-6-Phosphate Dehydrogenase

Deficien

cy

G-6-PD essentialformaintainingglutathioneinactiveform Detoxifies freeradicals andperoxides

Sex-linkeddisorder Effects > 200 millionpeople

Hemolyticanemiaoccurs inthepresenceofstress (infectionordrugs- antimalarial, sulphonamide, nitrofurantoinetc)

Africanform - mildhemolysis

Mediterraneanform - more severe

Peripheral smearshows Heinz bodies & bitecells

Unique sensitivitytofava beans


45/64

Immunohemolytic Anemias

Caused by antibodies reacting againstnormal or altered RBCmembranes- Autoimmune, drug-induced- Antigen thatstimulates antibody or complement-mediateddestruction ofRBCs

Classification:1. Warm antibody: idiopathic, B-cell Neoplasms (CLL/SLL), SLE,

drugs (aldomet, PCN, Quinidine)2. Cold antibody: M. pneumoniae. Infectious mono.

Lab:- + DAT detects anti-RBC antibodies- Microspherocytes on peripheral smear


46/64

Anti-Globulin (Coombs) Testing

Directantiglobulintesting

Indirectantiglobulintesting

Patients RBCs

Patients serum

Anti-C3d

Anti-IgG

+

RBCs

+

Anti-IgG

+


47/64

Hemolytic Anemia with Intravascular

Hemolysis

Mechanicaldamage (Microangiopathichemolyticanemia)

Chemicaldamage (Burns)

Infection (MalariaorBabesiosis)

Transfusionreaction (ABO incompatibility)


48/64


49/64

Thalassemia


50/64

4 -globin genes

on chromosomes No 16

( 2 oneach chromosome)

2 fromthe father

& 2 fromthemother

2 - globin genes

on chromosomes No 11

(1 oneach chromosome)

1 fromthe father

& 1 fromthemother

NORMAL INDIVIDUAL

Normal / globinchainratiois 1/1

Net result :-


51/64

Normal Hemoglobin(s)

2 2 A

2

F

Hb%

FA2

AAdult 1 1.6 - 3.2 97

Infant 7020 Negligible 3020


52/64

Thalassemia

Decreasedproductionofnormalglobinchains

E thalassemia - deficiencyofE gene(s)

F thalassemia - deficiencyofF gene(s)


53/64

Thalassemia

Imbalance of globin chain production

E- vs. F-thalassemia

anemia due to both decreased production and increased hemolysisin spleen

F- thalassemia has decreased/absentHgb A, increased Hgb F, andincreased Hgb A2

Treatment- hypertransfusion with chelation, splenectomy, bonemarrow transplantation

E thalassemiaEurope 4-12%MiddleEastand westernAsia - 12-55%

SoutheastAsia 6-75%

Africa 11-50%

SouthAmericaandthe Caribbean - 7%

HeterozygoteF thalassemiaItalian, Sicilian,and Greek10%

SoutheastAsian populations 5% in

inAfricanandAmerican blackpopulations1.5%


54/64

Father Mother

/

Normal


55/64

-/

--/

--/---/--

Silent carrier

- thal minor(-thal trait)

HbH disease

Hb. Barts

Hydrops fetalis

-Thalassemia(s)


56/64

Alpha Thalassemia: Clinical

Features Absenceof1-2 alphachains

Common

Asymptomatic

Does notrequiretherapy

Absenceof3 alphachains

(Hgb H disease)

Microcyticanemia (Hgb 7-10)

Splenomegaly

Absenceof4 alphachains

Hydrops fetalis (non-viable)

EE

EE

EE

EE

EE

EE

EE

EE

XXX

X X

X XX

EE

EEX XX X


57/64

-

thalassemia

minor

-thalassemia

major

- Thalassemia(s)


58/64


59/64

Beta Thalassemia: Clinical

Manifestations

Skeletal Osteoporosis dueto bonemarrow expansion (crew cut)

Pneumatizationofthe sinuses is delayed byexpandedhematopoiesis

Dilatedcardiomyopathy secondaryto severeanemia

Growthanddevelopmentdelayed

Hepatomegalyduetoextramedullaryhematopoiesis


60/64

Skeletal

Osteoporosis

Delayed pneumatization ofthe sinuses

Dilated cardiomyopathy

Growth and developmentdelayed

Hepatomegaly

Beta Thalassemia

Crew cut appearance


61/64

Thalassemia

Smear

Microcytic / Hypochromic RBCs,Anisocytosis, Poikilocytosis, targetcells


62/64

Hemolytic Anemia

RBC destruction

erythropoiesis:reticulocytosis

Iron accumulation:hemosiderosis

Etiology:

Intravascular: heat,

clostridia toxin, traumacomplement fixation

Extravascular (RES)

Intravascular:

hemoglobinemia,hemoglobinuria,

hemosiderinuria haptoglobin

Extravascular

No hemoglobinemia orhemoglobinuria

Normal haptoglobin

Microspherocytes


63/64

Causes of High Hct/polycythemia

Relative or spurious erythrocytosis Hemoconcentration secondary to dehydration

(diarrhea, diaphoresis, diuretics, deprivation of water, emesis,

ethanol, etc.)

Absolute erythrocytosis (True ): Tissuehypoxia Smoking (Co), Highaltitude, Pulmonarydisease,

Cardiac shunts, Highoxygen-affinity Hb.

HighEPO - Tumors eg. HCC. Androgentherapy

Primary - Polycythemiavera


64/64

Documents

Anemia 2011 Student Dental f Copy