Session 4- Introduction to anaemia & Vitamin B12 and folate metabolism Flashcards

1
Q

define anaemia

A

a haemoglobin concentration lower than the normal range which varies

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2
Q

clinical signs of anaemia

A

glossitis, spoon shaped nails, angular chelitis

-Pallor
• Tachycardia
• Systolic flow murmur
• Tachypnoea
• Hypotension
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3
Q

symtoms of anaemia

A
Shortness of breath
• Palpitations
• Headaches
• Claudication
• Angina
• Weakness & Lethargy
• Confusion
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4
Q

key clinical point of anaemia

A

Anaemia in itself is not a diagnosis but a
manifestation of an underlying disease state and it
is important to establish the cause of the anaemia

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5
Q

specific signs associated with the cause of anaemia

A

Koilonychia

Glossitis

Angular stomatitis

Abnormal facial bone
development
Rare in recent times as
preventable with early diagnosis

Thalassaemia

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6
Q

koilonychia

A

(Spoon shaped nails)

Iron deficiency

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7
Q

glossitis

A

(inflammation & depapillation of tongue)

Vitamin B12 deficiency

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8
Q

angular stomatitis

A

(Inflammation of corners of the mouth)

Iron deficiency

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9
Q

why might anaemia develoop- bone marrow

A
Reduced or dysfunctional
erythropoiesis
Abnormal Haem synthesis
Abnormal globin chain
synthesis
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10
Q

why might anaemia develop- peripheral red blood cells

A

abnormal structure
mechanical damage
abnormal metabolism

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11
Q

removal- spleen

why might anaemia develop

A

increased removal by reticuloendothelial system

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12
Q

what is the role of erythropeitin in the hormonal control of erythropoiesis

A

when there is low blood oxygen pericytes in kidney sense hypoxia and produce erythropoietin

EPO travels in bloodstream and binds to receptors on erythblasts in bone marrow and stimulates red cell production

increased number of red cells in blood

high blood oxygen

negative feedback on pericytes

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13
Q

why might anaemia develop in reduced or dysfuntional erythpoiesis

A

Anaemia can result from marrow being
unable to respond to EPO

myelofibrosis

anaemia of chronic disease

myelodysplastic syndroms

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14
Q

myelofibrosis

A

If marrow is infiltrated by cancer cells
or fibrous tissue (myelofibrosis) the
number of normal haemopoietic cells is
reduced

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15
Q

anaemia of chronic disease

A

In Anaemia of chronic disease e.g. in
rheumatoid arthritis, iron is not made
available to marrow for rbc production

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16
Q

myelodysplastic syndrome

A
In rare forms of blood cancer called
myelodysplastic syndromes
abnormal clones of marrow stem cells
limit the capacity to make both red and
white blood cells
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17
Q

why might anaemia develop- defects in haemoglobin synthesis

A

Defects in the haem synthetic
pathway can lead to
Sideroblastic anaemia

Insufficient iron in diet can lead
to iron deficiency anaemia (not
enough iron to make Haem)
Anaemia of chronic disease can
result in a functional iron
deficiency (sufficient iron in body
but not made available for
erythropoiesis

mutations in the genes encoding the globin chain proteins
• α Thalassaemia
• β Thalassaemia
• Sickle cell disease

18
Q

why might anaemia develop- defects in red cell metabolism

A

G6DPH deficiency

pyruvate kinase deficiency

19
Q

why might anaemia devlop- excessive bleeding

A

Chronic bleeding

• Heavy menstrual bleeding
• Repeated nosebleeds
• Haemorrhoids
Occult gastrointestinal bleeding
(blood lost in stool)
   • Ulcers (stomach or
small intestine)
    • Diverticulosis
    • Polyps in large intestine
    • Intestinal cancer
• Kidney or bladder tumours (blood
lost in urine)
20
Q

autoimmune haemolytic anaemia

A

autoantibodies bind to the red cell membrane
proteins causing them to be recognised by
macrophages in the spleen and destroyed

21
Q

2 key features can help to work out the cause of an anaemia

A
  • The rbc size – macrocytic, microcytic, normocytic (big, small, normal)
  • The presence or absence of reticulocytosis (has the marrow responded normally?)
22
Q

reticulocytes

A

• Immature red blood cells (i.e. those which have just
been released from the marrow into blood)
• No nucleus & eliminate remaining mitochondria
• Typically compose ~1% of all red blood cells and take
~ 1 day to mature into erythrocytes

23
Q

macrocytic anaemia

FAT RBC

A

foetus- increased folate demand in late pregnancy

alcohol- toxicity towards bone marrow + secondary likely B12/Folate deficiency

hypoThyrodism- low thyroid hormones affect hormones involved in haemopoiesis

reticulocytes- secondary to blood loss, many reticulocytes are produced

B12/Folate- deficiency/pernicious- thymine deficiency- uracil used - constant DNA repaire - nucleus never matures, glossitis

Cirrhosis/ chronic liver disease- not fully confirmed yet, maybe excess cholesterol deposition

24
Q

megaloblastoc anaemia

A
• Interference with DNA
synthesis during erythropoiesis
causes development of nucleus
to be retarded in relation to
maturation of cytoplasm
• Cell division delayed and
erythroblasts continue to grow
to form megaloblasts which
give rise to larger red cells
25
macronormoblastic erythropoiesis
``` • Normal relationship between development of nucleus and cytoplasm is retained but erythroblasts are larger than normal and give rise to larger red cells ```
26
stress erythropoiesis
``` Conditions associated with a high reticulocyte count (reticulocytes are larger than normal red cells) • High level of erythropoietin leads to an expanded and accelerated erythropoiesis ```
27
microcytic anaemia TAILS
These anaemias present with a reduced RBC size that are often pale (hypochromic) Thalassaemia: Reduced/absent synthesis of a globin chain in haemoglobin → abnormal facial bone development as the bone marrow tries to ramp up haemopoiesis Anaemia of chronic disease: Reduced iron availability (covered in a few slides) Iron deficiency: insufficient iron available to meet haem synthesis requirements Lead poisoning: inhibits haem synthesis enzymes Sideroblastic anaemia: genetic defect in haem synthesis
28
normocytic anaemia
These anaemias present with normal sized RBCs Acute blood loss: blood volume has been lost, but no effect on RBC structure/size Bone marrow failure (aplastic): either inherited or acquired, the bone marrow stem cells can no longer produce sufficient RBCs to meet the demands of the body. Chronic disease: Reduced iron availability Destruction (haemolytic): abnormal excess breakdown of RBCs
29
what causes folate deficiency
``` • Dietary deficiency (Poor diet) • Increased requirements • Pregnancy • Increased erythropoiesis e.g. haemolytic anaemia • Severe skin disease (e.g. psoriasis, exfoliative dermatitis) • Disease of the duodenum and jejunum (e.g. coeliac disease, Crohn’s disease) • Drugs which inhibit dihydrofolate reductase (e.g. Methotrexate) • Alcoholism (poor diet and damage to intestinal cells) • Urinary loss of folate in liver disease and heart failure ```
30
symtoms of folate deficiency
``` Those related to anaemia • Reduced sense of taste • Diarrhoea • Numbness and tingling in feet and hands • Muscle weakness • Depression ```
31
vitamin B12 absorption
``` • B12 released from food proteins by proteolysis in stomach where it then binds to haptocorrin • Haptocorrin B12 complex digested by pancreatic proteases in small intestine releasing B12 which then binds intrinsic factor (produced by gastric parietal cells). • Intrinsic factor–B12 complex binds to cubam receptor which mediates uptake of complex by receptormediated endocytosis into enterocytes • After lysosomal release in enterocytes, B12 exits via basolateral membrane through MDR1 • Binds to transcobalamin in blood and transported around bloodstream ```
32
causes of B12 deficiency
``` -Dietary deficiency (Vegan diet lacking B12 supplementation) • Lack of intrinsic factor (Pernicious anaemia) • Diseases of the ileum (Crohn’s disease, ileal resection, tropical sprue) • Lack of transcobalamin (congenital defect) • Chemical inactivation of B12 e.g. frequent use of anaesthetic gas nitrous oxide • Parasitic infestation (rare tapeworm found in fish can trap B12) • Some drugs can chelate intrinsic factor (e.g. hypercholesterolaemia drug Cholestyramine) ```
33
symptoms of b12 deficiency
``` Those related to anaemia • Glossitis & mouth ulcers • Diarrhoea • Paraesthesia • Disturbed vision • Irritability ```
34
symotoms of subacute combined degeneration of the cord
degeneration of posterior and lateral columns of the spinal cord ``` • Gradual onset weakness, numbness & tingling in arms, legs & trunk which progressively worsens. • Changes in mental state ```
35
how can folate/ b12 defiency affect the nervous system
``` • Folate deficiency in pregnancy can cause neural tube defects • Vitamin B12 deficiency associated with focal demyelination ```
36
why do b12 and folate deficiency cause a megaloblastic anaemia
• Vitamin B12 and folate are both necessary for nuclear division and maturation. • When B12 and folate are deficient, nuclear maturation and cell divisions lag behind cytoplasm development. • Leads to large red cell precursors with inappropriately large nuclei and open chromatin. The mature red cells are also large leading to a macrocytic anaemia
37
anisopikilocytosis
variance in size and shape
38
treatment of vitamin b12 deficiency
For Pernicious anaemia: Hydroxycobalamine intramuscular (NOT oral) for life For other causes of B12 deficiency: oral cyanocobalamine
39
what is Hb1AC
glycated haemoglobin which is when Hb is linked to a sugar
40
what is haemoglobinaemia
excess haemoglobin in the blood. If the normal reticuloendothelial pathway for removal of red blood cells is overwhelmed or haemolysis is very severe (e.g. due to incompatible blood transfusion), a direct breakdown of red blood cells rusults in release of haemoglobin into the circulation
41
coombs test
autoantibody test for autoimmune haemoltyic anaemia
42
what is pernicious anaemia
autoantibodies interfering with the production or function of intrinsic factor Intrinsic factor is essential for the absorption of vitamin B12 in the ileum. Without intrinsic factor, vitamin B12 deficiency will occur and production of red blood cells will be impaired causing anaemia. "Pernicious” means “deadly”. Pernicious anemia was often fatal in the past before vitamin B12 treatments were available.