Anaemia Flashcards
(136 cards)
1
Q
How does anaemia present?
A
Fatigue Presyncope Dyspnoea Angina Palpitations Intermittent claudication
2
Q
Koilonychia indicates which kind of anaemia?
A
Iron def
3
Q
Jaundice indicates which kind of anaemia?
A
Haemolytic
4
Q
How is anaemia investigated?
A
FBC and blood film Reticulocyte count MCV Bone marrow assessment Iron stores B12 and folate
5
Q
Give examples of causes of iron deficiency?
A
Menorrhagia Occult blood loss Increased demand Dietary Decreased absorption
6
Q
What is responsible for reducing ferric iron to ferrous iron from the duodenum?
A
Duodenal cytochrome B
7
Q
What transports ferrous iron into duodenal enterocytes?
A
DMT1 (or natural resistance associated macrophage protein)
8
Q
What transports ferrous iron out of the enterocyte?
A
Ferroportin 1
Hephaestin
9
Q
Which factors may increase iron absorption?
A
Ascorbic acid
Alcohol
10
Q
Which factors may decreased iron absorption?
A
Tannins
Calcium
Phytates
11
Q
What is the major negative regulator of iron uptake?
A
Hepcidin
12
Q
Where is hepcidin produced?
A
Liver
13
Q
What is the action of hepcidin?
A
Binds to a degrades ferroportin
14
Q
What causes a fall in hepcidin levels?
A
Anaemia
15
Q
Why is furosemide less effective in renal impairment?
A
Reduced GFR causes large proteins in the urine
These bind to furosemide and it is therefore not active
16
Q
What is the specific transporter for haem iron?
A
Haem carrier protein 1
17
Q
Where is iron stored?
A
Hb
Hepatocytes
Skeletal muscle
Reticuloendothelial cells
18
Q
What is iron mostly stored as?
A
Ferritin
19
Q
What is 1/3 of iron stored as?
A
Haemosiderin
20
Q
What is ferritin?
A
Water soluble iron and protein complex
21
Q
What is haemosiderin?
A
Insoluble iron and protein complex
22
Q
How do you assess iron status?
A
%ferritin saturation
Apotransferrin : Holotransferrin
23
Q
What is transferrin?
A
Protein with 2 binding sites for iron
24
Q
How does iron deficiency anaemia present?
A
Brittle nails Koilonychia Atrophy of tongue papillae Brittle hair Angular stomatitis
25
How is iron deficiency investigated?
Serum ferritin
Serum transferrin receptors
Serum iron
26
How is iron deficiency anaemia managed?
Ferrous fumarate
27
What are the main side effects of ferrous fumarate?
Nausea, diarrhoea or constipation
28
Why does anaemia occur in chronic disease?
Decreased release of iron to bone marrow
29
How is anaemia of chronic disease investigated?
Hepcidin levels (tends to be overactive)
30
How is anaemia of chronic disease treated?
Recombinant erythropoietin and management of chronic disease
31
What is a sideroblastic anaemia?
Disorders characterised by excess iron; hypochromic cells and sideroblast rings
32
What causes disordered haem synthesis in sideroblastic anaemia?
Accumulation of iron in mitochondria
33
How may sideroblastic anaemia be acquired?
Myeloproliferative disorders
Isoniazid
Alcohol misuse
Lead toxicity
34
In which conditions may normocytic anaemia be seen?
Chronic disease
Endocrine dysfunction
Haemolytic anaemia
35
What causes the cells to be larger in megaloblastic anaemia?
Failure in DNA synthesis leading to impaired proliferation
36
Big cells with twisted nuclei are know as what?
Metamyelocytes
37
Give three examples of causes of megaloblastic change?
Vit B12 def
Folic acid def
Myelodysplasia
38
How do B12 and folate work to facilitate DNA synthesis?
Methylate promotor genes to cause switching on and off of appropriate genes
39
What is vit b12 otherwise known as?
Cobalamin
40
Give examples of vit b12 sources
Meat
Fish
Eggs
Milk
41
Approx how much B12 is stored in the liver of a healthy adult?
2-3mg
42
How much B12 is used per day in a normal healthy adult?
1-2micrograms
43
Give examples of causes of B12 deficiency
Vegan diet
PA
Gastrectomy
IF def
44
What is the role of the folate cycle?
Coverts uridine to thymidine
| Promotes nucleotide synthesis
45
What is the role of the methionine cycle?
Produces methyl donors
| S-adenosyl-methionine
46
What does B12 bind to when it is ingested?
R protein
47
What cleaves B12 from R protein?
Pancreatic enzymes
48
What causes pancreatic enzymes to be secreted to cleave b12?
pH increase on ingestion of food
49
Which cells secrete intrinsic factor?
Gastric parietal
50
What carries b12 to the cubulin receptors in the ileum?
IF
51
Which transports carries B12 out of ileal cells to bone marrow?
Glycoprotein transcobalamin II (TCII)
52
What is "active B12"?
B12 bound to TCII
53
What is "active B12" otherwise known as?
Holotranscobalamin
54
What is pernicious anaemia?
Autoimmune condition involving destruction of the gastric parietal cells
55
Which type of anaemia is pernicious anaemia?
Macrocytic
56
How does pernicious anaemia affect b12 levels?
No IF secreted so cannot be transported to cubulin receptors to be absorbed
57
How does pernicious anaemia present?
```
Insidious onset
Jaundice
Glossitis
Angular stomatitis
Peripheral polyneuropathy
Progressive weakness and ataxia
Psychiatric features
```
58
What does a blood film show in macrocytic megaloblastic anaemia?
Megaloblasts and hypersegmented neutrophils
59
What would endoscopy reveal in pernicious anaemia?
Achlorhydria
60
Which antibodies are present in pernicious anaemia?
Anti-IF
| Anti-gastric parietal cell
61
How is life-threatening PA treated?
Red cell transfusion
62
How is non-life-threatening PA treated?
Vit B12 injections (Hydroxocobalamin)
63
How quickly does B12 therapy show clinical improvement in PA?
48 hours
64
What is dietary folic acid converted to?
Monoglutamate
65
Where is folic acid absorbed?
Jejunum and duodenum
66
Give examples of sources of folate?
Leafy green veg
| Fortified cereals
67
How long may body stores of folic acid last?
4 months
68
Which mechanisms may cause folate deficiency?
Inadequate intake
Malabsorption
Excess utilisation
Iatrogenic
69
Give examples of drugs which cause folate deficiency?
Phenytoin
Methotrexate
Trimethoprim
70
In which scenarios may there be excess utilisation of folate?
Haemolysis
Pregnancy
Malignancy
71
How is folic acid deficiency managed?
5mg per day for 4 months
72
In which physiological scenarios may macrocytic non-megaloblastic anaemia occur?
Pregnancy
| Newborn
73
Give examples of pathological causes of macrocytic non-megaloblastic anaemia?
Alcoholism
Liver disease
Hypothyroidism
Marrow failure
74
What do investigations show in aplastic anaemia?
FBC - pancytopenia
| Bone marrow aspirate - hypocellular
75
Which rare condition is an inherited form of aplastic anaemia?
Fanconi's anaemia
76
Give examples of causes of acquired aplastic anaemia
Chemicals
Antibiotics
Insecticide
Infection
77
How does aplastic anaemia present?
Anaemic features
Bleeding (epistaxis, gums, ecchymoses)
Recurrent infection
78
How is aplastic anaemia treated?
Treat the cause
| Stem cell infusion
79
What is a spurious macrocytosis?
False macrocytosis
80
Give causes of spurious macrocytosis
Reticulocytosis
| Cold agglutinins
81
What does blood film show with Reticulocytosis?
Polychromasia
| and retics, obvs
82
Where are red cells normally broken down?
Macrophages of spleen, liver and bone marrow
83
What is erythroid hyperplasia?
Increasing the cells in the bone marrow which are dedicated to erythropoiesis
Marrow can extend into cortical bone
84
Through which mechanisms is haemolysis compensated for?
Erythroid hyperplasia
| Early retic release
85
Where does extravascular haemolysis mostly take place?
Spleen
86
When Hb is freed in circulation what does it bind to?
Haptoglobin
87
Free Hb in the kidneys is broken down to....
Haemosiderin
88
Describe the normal cell membrane of a red cell
Lipid bilayer crossed by integral proteins
| Underlying protein spars and ankyrin to keep it together
89
How is hereditary spherocytosis inherited?
AD
90
Where is the defect most commonly found with hereditary spherocytosis?
Ankyrin
91
How does hereditary spherocytosis present?
Anaemic features
Splenomegaly
Leg ulcers
92
What does the blood film show on hereditary spherocytosis?
Spherocytes (obvs)
93
How is hereditary spherocytosis managed?
Splenectomy
Immunisations
Prophylactic penicillin
94
How is hereditary elliptocytosis inherited?
AR
95
What is hereditary elliptocytosis?
Milder form of HS
| Weakness of horizontal membrane proteins
96
Warm autoimmune haemolytic anaemia is associated with which antibody?
IgG
97
Cold autoimmune haemolytic anaemia is associated with which antibody?
IgM
98
Give causes of warm autoimmune haemolytic anaemia
SLE
CLL and other malignancy
Penicillins
Idiopathic
99
Give causes of cold autoimmune haemolytic anaemia?
Infection
Lymphoma
Idiopathic
100
How does warm autoimmune haemolytic anaemia present?
Anaemia symptoms which relapse and remit
Splenomegaly
Infection
101
What do investigations show in warm autoimmune haemolytic anaemia?
Spherocytes on blood film
Anaemia on FBC
Raised bilirubin
Coomb's test positive
102
How is warm autoimmune haemolytic anaemia managed?
Prednisolone 1mg/kg
| Splenectomy if this is unsuccessful
103
Describe the pathogenesis in cold autoimmune haemolytic anaemia
At low temp, IgM causes agglutination of red cells in peripheries which haemolyse when they return to central circulation
104
What is paroxysmal cold haemoglobinuria associated with?
Childhood infection
105
Which antibody is associated with paroxysmal cold haemoglobinuria?
IgG
106
How is paroxysmal cold haemoglobinuria treated?
Red cell transfusions
107
What is the mechanism of haemolytic disease of the newborn?
Alloimmune
108
How is paroxysmal nocturnal haemoglobinuria inherited?
X-linked
109
Where is the mutation in paroxysmal nocturnal haemoglobinuria?
PIG-A
110
Roughly what does paroxysmal nocturnal haemoglobinuria do to red cells?
Makes them more susceptible to complement
111
What are the clinical features of paroxysmal nocturnal haemoglobinuria?
VT in abnormal sites
Haemoglobinuria
Urine voided in night/first thing is dark in colour
112
What does paroxysmal nocturnal haemoglobinuria show on investigation?
Increased plasma Hb
Haemosiderinuria
Low haptoglobin
Hypoplastic bone marrow on aspirate
113
How is paroxysmal nocturnal haemoglobinuria managed?
Blood transfusions
| Eculizumab
114
What is Zieve's syndrome?
Haemolysis due to changes in liver metabolism
115
What does blood film show in Zieve's syndrome?
Polychromatic macrocytes
| Reticulocytosis
116
Approx how much iron is lost per day in the faeces?
0.5-1mg
117
Approx. how much iron is used per day in pregnancy?
1-2mg
118
What does hereditary haemochromatosis cause?
Increased iron absorption
119
By approx. how much should Hbh rise per week on treatment of iron def?
10mg
120
Which reaction shows a ring of iron granules around the mitochondria in sideroblastic anaemia?
Perl's
121
What acute situation would cause normocytic anaemia?
Blood loss
122
What does peripheral blood film show in macrocytic anaemia?
Hyper-segmented polymorphs
123
Which system (other than the haematological system) does B12 def affect?
Neurological and psychiatric
124
What does Schillings test determine?
How well B12 is absorbed
125
What would indicate that B12 is absorbed out of the GI tract in Schillings test?
B12 in urine
126
How is folic acid found in the serum?
As methyl THF monoglutamate
127
Approx how long do stores last before folic acid deficiency presents?
4 months
128
How long after treatment for folic acid def can reticulocytosis be seen on blood film?
2-3 days
129
What may occur in the first few weeks of treatment of folic acid def?
Iron def
130
How long may polyneuropathies from B12 def take to heal?
6-12m
| Spinal cord damage is irreversible
131
What is aplastic anaemia?
Pancytopenia with hypocellular bone marrow and no other abnormality
132
What results in aplastic anaemia?
Reduction in number of stem cells combined with a flaw in the remaining ones or an immune process against them
133
What does a positive Schumm's test indicate?
Intravascular haemolysis
134
How is hereditary elliptocytosis inherited?
AD
135
What causes hereditary elliptocytosis??
Defects of 4.1 or spectrin/actin/4.1 complex in the membrane
136
What are stomatocytes?
Red cells with a slit-like, pale central area
