AnaemiaDR. AAMIR FAROOQM. PHIL. PATHOLOGYdr.aamirfarooq@hotmail.com

TerminologyMCV: Average volume of individual cell

MCV=MCHC: Its average conc. of Hb in individual erythrocyte

MCHC

MCH: It tells us about total Hb.

MCH=

AnaemiaAbsolute fall in haematocrit, erythrocyte count and Hb concentrationClinical signs depends upon amount of blood lostPale mucus membranesIncrease in heart rateLow oxygen carrying capacityExercise intoleranceLab Finding: Decrease in Hb, RBCs count and PCV.

Classification

Morphological CharacteristicsEtiologyBone Marrow Response

Morphological CharacteristicsDecreased (Microcytic)

Normal (Normocytic)

Increased (Macrocytic)

MCV

Decreased (Hypochromic)

Normal (Normochromic)

Increased (Hyperchromic)

MCHC

ClassificationAnaemia MCV MCHC

Normocytic, Normochromic Normal Normal

Normocytic, Hypochromic Normal Decreased

Macrocytic, Normochromic Increased Normal

Macrocytic, Hypochromic Increased Decreased

Microcytic, Normochromic Decreased Normal

Microcytic, Hypochromic Decreased Decreased

Classification

MCV, MCHC and AnaemiaMCV increases….. Immature cells in circulation…..bone marrow compensation…… regenerative anaemia.MCV decreases…… hyper mature cellsMCV Normal……. May be regenerative or non-regenerativeMCHC increases….. Excessive intravascular haemolysisMCHC decreases…… excessive loss of blood/ iron deficiency in diet.MCHC Normal……..haemorrhages…..iron available…..Hb formation

Etiological ClassificationHaemorrhagic

Haemolytic

Bone marrow depression

Haemorrhagic AnaemiaLoss of blood due to: accident Fracture surgery internal haemorrhagesBlood sucking parasites

AcuteChronic

AcuteInitiallyAll parameter normal……… hypoxia………. Epinephrine release…….. Spleenic contraction……..hyperviscoucity due to old RBCs…… PCV increase up to 80%2-3 hours post-haemorrhagesInterstitial fluid absorption……. PCV decreases….. hypoproteinemia….. Thrombocytosis to stop haemorrhages.48 hours post-haemorrhagesPlasma protein at normal level

Cont.…72 hoursPolychromatic/ reticulocytes….. Remain in circulation for 2-3 weeksThen patient recover to normal condition

Reticulocytes remain in circulation for 2-3 weeks…… iron deficiency or persistent haemorrhages in body.

ChronicBlood parasites, ulcers or haemorrhages.All parameters reduced before appearing of clinical signsPersistent thrombocytosis and regenerative response is lessHypoproteinemia and hypovolemia may or may not developDeficiency of iron…..regenerative response is lessInternal and external haemorrhages…………. Regenerative response more and less respectively

Haemolytic Anaemia

Break down (lysis) of Erythrocytes.1. Intravascular2. Extravascular

Clinical FindingsEvidence of haemorrhages are absentPlasma protein is normal or slightly increasedMCH and MCHC increasedAcute cases----------- neutrophilocytosisChronic cases--------- monocytosisincreased bilirubin------------- Icterus may be presentMorphological abnormalities in erythrocytes e.g. Heinz bodies, erythrocytes containing parasites etc.

Anaplasma

Babasia

Heinz Bodies

NormalErythrocytes

Extravascular HaemolysisLysis of RBCs outside the blood vesselsLab findings:oHaemoglobinemia and haemoglobinuria absentoBilirubin highoBone marrow response presentoNeutrophilic leucocytosis (acute), monocytic leucocytosis (chronic)

EtiologyAntibodies and C3b mediated haemolysisImmune mediated haemolytic anaemia (IMHA)Anaemia by some infectious agent or drugsDeformities of ErythrocytesReduced glycolysis and low ATP productionSplenomegaly/increased macrophages activity

Antibodies and C3b mediated haemolysisAg exposed

on RBCsLymphoid system

recognition

Formation of Ag-Ig complex

Complement system activation

Macrophages recognize it

IMHAMechanism not exactly knownRBCs recognized as AgIgs produced against RBCs.May be caused by bacteria, virus or medication.

Anaemia by some infectious agent or drugsInfectionMycobacterium hemolyticum

Hidden Receptor Exposed / Cell Membrane Changed

Deformities of ErythrocytesChanges in Cell Membrane

Internal Viscosity is High..... Spherocytes

Enter in spleen

Phagocytosis

Low production of ATPSuch cells predisposed to phagocytosisReduction is accelerated in pyruvate kinase and phosphofructokinase deficiency

SplenomegalySpleen enlargedMacrophage activity increased

Intravascular HaemolysisBreak down of erythrocytes inside the blood vesselLab Findings:oRegenerative response 2-3 post-haemolysisoHaemoglobinuria and haemoglobinemiaoIncreased bilirubinoAbnormal erythrocytes e.g. eccentrocytes, spherocytes or blood parasite etc.

EccentrocytesKeratocytes

Spherocytes Theleria

EtiologyAntibody and Complement mediated/ immune mediated hemolysisPhysical injury to RBCsOxidative injuryOsmotic lysisAlteration in cell membrane of RBCs

Antibody and Complement mediated/ immune mediated hemolysis

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Mechanical damage to Erythrocytes

Increased fibrinEtiology includes: DIC Damaged valves

Oxidative injury

Cont….Heinz bodies increased….. Denatured Hb….. Functional ability reducedCross linkages formed between cell membranes…..disfigure the cellMethemoglobin is formed…… oxygen carrying capacity reduced

Osmotic LysisHypotonic solution administrationHypophosphatemia…..osmosis increased Osmotic diuretics if uncontrolled e.g. diabetes mellitus

Alteration of Cell MembraneEtiology includes:oSnake venomsoCaster beans containing ricinoBlood parasites (babasiasis)

Bone Marrow ResponseSuch anaemia are:Non regenerativeCaused be abnormal bone marrowThey are of two types:I. Reduced erythropoiesisII. Defective erythropoiesis

Reduced ErythropoiesisFactors causing reduced erythropoiesis:1. Chronic disordersChronic inflammationNeoplasm

2. Cytotoxic bone marrow damageBracken fernCytotoxic cancerous drugsestrogen FurazolidonePhenylbutazoneRadiation

Cont.…..3. Deficiency of erythropoietin (EPO)

Chronic renal disease Hypoadrenocortisism Hypoandrogenism Hypopituitarism Hypothyroidism

4. Immune mediated Pure red cell aplasia (PRCA)

Cont.….5. Infections

Ehrlichia spp. Feline leukemia virus Feline panleukopenia virus Parvovirus Trichostrongyles

6. Mylopathies Lymphocytic leukemia Matastatic neoplasm Myloproliferative disease Osteopetrosis, osteosclerosis Myelofibrosis

Defective ErythropoiesisCauses of defective erythropoiesis are:1. Abnormal maturation

Erythremic mylosis Erythroleukemia Myelodysplastic syndrome Macrocytosis of Poodles

2. Abnormal nucleic acid synthesisVit. B12 deficiency, malabsorptionFolic acid deficiency

Cont….3. Disorders of heme synthesisChloramphenicol toxicityCopper deficiency Iron deficiencyLead poisoningMolybdenum poisoningPyridoxine deficiency

Factors required for normal ErythropoiesisPrecursor cells (Stem cells, myloid cells, erythroid cells)Nutrients (B12, folic acid)Stimulation (EPO, IL-3)Micro environment of bone marrowGrowth stimulating factors (G-CSF, GM-CSF)

Bone marrow failurePrimaryIf cause is within the bone marrow e.g. PRCA, aplastic anaemiaSecondary If cause is extra-marrow e.g. Decreased EPO or nutritional factorsBone marrow failure may be selective for erythroid cells (PRCA)

Bone marrow response anaemia1. Inadequacy of precursor cells or erythrpoietic stimulation is

inadequate2. Maturation abnormalities with hypercellular marrow e.g. MDS3. Suboptimal response of marrow following haemorrhages or

hemolysis

Non-regenerative anaemia On the basis of morphology divided into following subtypes:1. Normocytic, normochromic with normal to increased neutrophils2. Normocytic, normochromic with neutropenia3. Microcytic, hypochromic anaemia with variable neutrophils4. Macrocytic, normochromic anaemia

Normocytic, normochromic with normal to increased neutrophils

Normal to increased neutrophils and platelet count and M:E ratio increasedThis type of anaemia includes followings:

1. Decreased EPO which may be due to followings: Chronic renal damage Uremia/ increased BUN Increased BUN leads to inhibition of uptake of EPO by BM, GIT haemorrhages

caused by abnormal platelet function, inhibit erythropoiesis and haemolysis by uremic plasma

Cont.…..2. Anaemia of inflammatory disease (AID) Chronic inflammation/neoplasm…… production of IL-1 α and β, TNF- α,

cytokines and interferon-γ…… depress erythropoiesis Life span of erythrocyte is shortened

3. Endocrinopathies Hypothyroidism, hypoandroginism and hypopituitarism leads to

inhibition of release of EPO from kidneys4. FeLV5. PRCA

Normocytic, normochromic with neutropenia

1. Aplastic anaemia…… a-cellular or fatty bonemarrow Radiation therapy Chloramphenicol, phenylbutazone toxicity Increased activity of cytotoxic T-cells FeLV Plants toxicity (Bracken fern)

2. Myelophthistic anaemiaMyelofibrosisOsteosclerosisMetastatic cancer

Microcytic, hypochromic anaemia with variable neutrophils

Variable neutrophils and platelet countVariable M:E ratioIncludes followings:

1. Iron Deficiency Chronic external blood loss Young growers on complete milk diet have deficiency of iron

2. Pyridoxine deficiency…..cofactor of heme synthesis3. Copper deficiency……. Iron absorption impaired form GIT

Cont….4. Dyserythrpoiesis5. Microcytosis….. No anemia MCV decreased6. Microcytosis without anemia in porto-systemic shunt (PSS)7. Drugs and chemicals like chloramphenicol or lead toxicity

Macrocytic, normochromic anaemiaVariable neutrophils and platelet count. M:E ratio is usually low.Causes includes:

1. Ruminant grazing Co-deficient and Molybdenum rich pastures2. Vit. B12 and folic acid deficiency3. Macrocytosis of poodles4. Congenital dyseythropoisis5. FeLV infection

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