Hematology: Red Blood Cells and Anaemia

Rbc mostly
Remainining ferritin and haemosiderin

liver and spleen

Presence of RNA

Elevated

'TAILS'
Thalassaemia
Anaemia of chronic disease
IDA
Lead poisoning
Sideroblastic

the size of nucleus of small lymphocytes

Low HCT, Hb
Low MCV, MCH, MCHC
Increase TIBC****
Increase SFTR
High platelet
Low ferritin (<15 is virtually specific but can be high/normal due to it being the acute phase reactant)
Low TSAT
Low reticulocytes

Diet
-tea
-vegetarian

malabsorption
-Achlorhydria
- Coeliac disease
- H. pylori gastritis

Increase loss
-Menorrhagia
-Worms
-Colon cancer

Signs
• Koilonychia,
• Angular stomatitis
• Glossitis
• Pharyngeal webs
Symptoms
• Reduced effort tolerance
• Impaired cognitive
• PICA

Gold standard for iron assessment but invasive so it is rarely done

Diurnal variation (lower in the morning)
Less in inflammation
High in liver disease

So how do we measure the iron?
Must be measured with TIBC/ TSAT

Available transferrin that is left unbound (Represents the "empty seats on a train")
Rise-IDA
High/normal-inflammation

measure of iron in storage (transferrin that is iron bound)
Formula:serumiron/TIBCX100%

when the cells lack iron, the number of receptors is increased

Hence increase in IDA and erythroid hyperplasia
Not influenced by infection/ inflammation

Low iron level

Primary iron storage protein
Ferittin synthesis decreases when iron levels are low

transports iron in blood

Protein found in cell membranes that binds to the iron-transferrin complex and allows it to be taken up by cells.

Electrogenic pump to transport Fe (2+) through the duodenal enterocyte
Upregulated in IDA

an iron transporter that helps regulate intestinal iron absorption and the release of iron from the enterocyte into the general circulation

Copper-carrying feroxidase in blood that oxidise FE2+ to Fe3+
-Fe2+ from macrophage converted to Fe3+ by ceruloplasmin before loaded to transferrin

decreases /destroy ferroportin
Inhibit iron absorption , iron release from macrophages and iron across placenta (promotes cellular storage and lower plasma concentration of iron)
Increase in high iron and inflammation (chronic disease)
Suppressed in IDA, high epo and hypoxia

Regulates hepcidin expression by cleaving HJV

1. Fe3+ ->Fe2+ by Ferrireductase (DCYTB/STEAP3)
2. Fe2+ pass through enterocytes through Heme carrier protein 1/ DMT1
3. Fe2+ stored as Mucosal Ferritin / exported through ferroportin
4. Fe2+ -> Fe3+ by haephaestin
5. Fe3+ pass through ferroportin to the blood vessel and circulate by transferrin
6. Fe3+ to erythronium precursors (bone marrow)/ liver where hepcidin is present for negative feedback

aniso, poik, hypochromic microcytes
Pencil cells

IDA hence parenteral iron must be given together

GI problem
CKD
Late pregnancy

Nausea, constipation, epigastric pain

'ABCD'
Acute blood loss
Bone marrow failure
Anemia of chronic disease (CKD, cancer, acquired)
Destruction

-Small organic molecule functioning as a cofactor/coenzyme/prosthetic group
-Iron surrounded by porphyrin which consists of 4 pyrrole interconnected via methine bridges

Proteins that has haem prosthetic group

Transport O2-myoglobin/haemoglobin
Transport electron-mitochondrial cytochromes
Activate O2-cytochrome oxidase/cytochrome p450
Activate hydrogen peroxidase- peroxidase
Decompose hydrogen peroxidase-catalase

Bone marrow (80%)
Liver parenchyma cells (20%)-depend on metabolic requirements

1. Iron+ protoporphyrin = haem
2. Haem exits mitochondria
3. Haem combines with globin synthesised in ribosomes= Haemoglobin
4. Negative feedback by ALA synthase

- defects in heme synthesis
-usually inherited but can be acquired (hepatitis C, high iron in liver, AIDS/HIV)

Sloughing off intestinal mucosal cells
Mestruation

Produced by uptake of aggregated ferritin molecules into lysosomes
-Store iron leaked out of tissue/ protect body from loose toxic iron in the blood

Haematochromatosis(iron overload)

Decreased.
Blood volume increased
RBC same
Hence lower RBC%/HCT

Unchanged.
Same proportion of plasma and RBC loss
No change in RBC%/HCT

Decreased.
Blood loss-> Low BP
Compensatory mechanism will cause less Hydrostatic P in capillaries
Fluid shift-> plasma from interstitial fluid enter capillary
Plasma increase-> Less HCT

Increased.
Plasma loss due to sweating
Same amount of RBC
HCT increase

Increase .
Low O2-> High epo->Hb

Decreased.
Less epo from kidney, Less HB

Time taken for vessel constriction and platelet plug formation

Time taken for generation of thrombin

Bleeding time-increase
Clotting time -no change

bleeding time -no change (platelet synthesised by bone marrow)
Clotting time-increase (Clotting factor produced in liver)

1. Rouleaux formation-> High ESR
2. Protein plasma high-> High ESR (Less rbc repellation)
3. RBC high-> low ESR(more RBC repel each other)
4. Size and shape (Sickle cell anaemia , hard to stack)-> Low ESR

Less Hb, hct
-Normocytic
-Higher FEP
-LEss reticulocytes
-Serum iron
-High ferritin (respond to IL-6)
-Low TIBC,saturation
-Normal STFR

Reticulocytosis
Alcohol
Hypothyroidism
Liver disease

B12
Folate
Drugs (methotrexate, hydroxyurea, 2-MP, cytarabine)
Myelodysplastic syndrome

Macroovalocytes
Hypersegmented neutrophils
Tear drop cells
Howell Jolly bodies

B12 (cobalamin)

Folate

High MCV >100
Pancytopenia
Symptoms of anaemia

Lack of b12 and folate cause defect in DNA synthesis

A) Ado form-in mitochondria , cofactor methylmalonyl COA mutase (Convert MMA to succinyl CoA)
B) Methylcobalamin-cytoplasm and plasma, cofactor methionine synthase (Homocysteine to methionine )

Food of animal origin

IIleum.

Duodenum-iron
Jejunum-Folate

B12 is bound to proteins in food --> Pepsin and HCL in Stomach releases the B12 from animal protein, then B12 binds to haptocorrin (secreted by pancreatic enzyme)-->In Small Intestine: B12 binds to intrinsic factor (which is secrete by parietal cells in stomach lining) --> "Intrinsic Factor -B12 Complex" binds to receptor proteins in ileum-> Transcobalamin II transport B12 in plasma

Nutrition
-Vegan
-Infant of cobalamin deficient mother

Malabsorption and gastric causes
-pernicious anaemia
-Congenital If deficiency
-Gastrectomy
-Achlorhydria

-FBC
-Increase homocysteine
-Increase MMA*** (characteristic, folate do not have increase in MMA)
-<100ng/ L serum cobalamin
-Can use holotranscobalamin

autoimmune disease that destroys stomach mucosa that produces intrinsic factor

Premature greying, blue eyes and vitiligo

Blood group A- higher risk

-Antibody towards Intrinsic Factor
-Antibody towards Parietal cell
-Serum gastrin

B12-2-3 mg last for 4 years
Folate-10-12 mg last for 4 months

B12-Transcobalamin
B9-albumin

pregnancy,
Malignant disease
Anticonvulsants
Nitrofurantoin,methotrexate, tetracycline

-Serum folate(use ELISA)-affected by diet and can increase in cobalamin deficiency, chronic disease
-red cell folate-less affected by diet but can increase in rbc transfusioneticulocytosis

Hydroxycobalamin (Intramuscular injection )
Folic acid /(oral)

macrophages (large phagocytic cells) in the liver and spleen

RBC phagocytized by RE cells
Broken down RBC produce bilirubin (conjugated and excreted by liver) and iron (return to bone marrow by transferrin )

Destruction of red blood cells within blood vessels
Free haemoglobin removed by haptoglobin or converted to methemalbumin. the proteins will be removed by liver , heme broken down to recover iron and produce bilirubin

Anaemia
Jaundice
Reticulocytosis
High MCV, RDW
Elevated bilirubin, LDH
Low haptoglobin
+Ve DAT

Polychromasia
Spherocytosis

Causes: Blood transfusion, infections (p.falciparum and clostridiA),mechanical heart valves, Paroxysmal Nocturnal Haemoglobinuria
Clinical manifestation:Fever,chills, low back pain and hemoglobinuria
Lab findings:Low haptoglobin, haemoglobinemia (pinked plasma), Haemoglobinuria (browned_, urine hemosiderin, methemalbuin

No. Jaundice is not typical as red cell breakdown is not in macrophage
While Spherocytes are made by removal of red cell membrane from red cells by macrophages in RE too

Iron. It is lost as hemosiderin

-Stop transfusion
-IVF
-Mannitol
-Iron supply and folate

Sudden fall in hemoglobin level with no evidence of bleeding or intravascular hemolysis (no hemoglobinemia or hemoglobinuria)

Infections
Drugs-Induced
Autoimmune
Haemoglobinopathies
Membrane structural defects
Malignancy assosciated DIC, TTP, Eclampsia

Reticulocytes

Penicilin
Methyldopa
Streptomycin

Sulfa and primaquine-GDPD

Heinz bodies, bite cells, blister cells

Generally acute extravascular hemolysis
*Warm-* IgG mediated--Coomb's Positive, no Anti-C binding.Spherocytes more prominent. Tansfusion when needed *Steroids and Splenectomy*

Cold- IgM to Complement, anti-complement + in Coomb's test, anti-IgG negative. Can get agglutination in the cold (extremely high MCV),. Occasional Transfusion*Chemotherapy (cyclophosphamide, chlorambucil) and plasmapheresis *

SLE, CLL, lymphomas
Penicillin

ABO mismatched transfusion
Rh incompatibility between mother and foetus

Folate supplies

autosomal dominant
Gallstones
Spherocytes
Negative COOMB test
Treatment: Splenectomy

- Microangiopathic hemolytic anemia (HUS, TTP, DIC)

pancytopenia with persistent hypocellular marrow
In the absence of dysplasia and marrow fibrosis
-Inherited cause: Franconia anemia, dyskeratosis congenital)