Red Cells Flashcards
1
Q
RBC lifecycle
A
EPO released by kidneys when it senses low oxygen tension
Stimulates RBC production in bone marrow
120 life span
Must pass through the sinusoids of MPS (mononuclear phagocyte system) where it is trapped and phagocytosed if deformed from ageing
RBC broken into haem (bilirubin/iron) and Globin (amino acids)
2
Q
What does RBC breakdown into
A
Haem - bilirubin and iron
Globin - amino acids
3
Q
How is an erythrocyte made and order of development
A
Pluripotent stem cell stimulated by specific IL to “pick” the erythroblasts lineage. This happens after EPO binds to stem cells to stimulate the process
BFU-E then CFU-E
Pro erythroblasts, erythroblasts, reticulocyte, erythrocytes
4
Q
Order of expansion from haemopoietic stem cells to erythrocytes
A
Haemopoietic stem cells
Proerythroblasts
Basophilic erythroblasts
Polychromatic erythroblasts
Reticulocytes - 7-10 days to get here
Erythrocytes
5
Q
What do the erythroblasts do in the bone marrow
A
Proliferate
Iron uptake from macrophages
Hb production
Removal of organelles via macrophages
6
Q
What is an erythroid island
A
Erythroblasts surround a macrophage in the bone marrow
7
Q
Where is haem and Globin produced
A
Globin produced on polyribosomes
Haem produced in mitochondria
8
Q
What is the MPS
A
Mononuclear phagocyte system also known as the reticuloendothelial system where monocyte derived cells phagocytose bacteria, present antigens and make cytokines and find old RBC
9
Q
What happens to RBC as they age
A
Membrane lipids and proteins are damaged and lost
Enzymes decrease
CD47 decrease
CD55/59 decrease
Increased phosphatidylserine
Increase rigidity and surface changes
10
Q
What is CD47
A
An adhesion molecule which stops phagocytosis of cells
Decreases as RBC age
11
Q
What is CD55/59
A
Decay acceleration factor which degrades activated complement proteins
12
Q
Where are RBC phagocytosed
A
Splenic cords, marrow and liver sinusoids through the MPS
13
Q
How does the splenic cords remove old RBC
A
old RBC are rigid with cell surface changes so they cannot pass through the endothelial cells in the splenic sinuses and are macrophages by RBC
14
Q
Hb triangle
A
Hb
MCH RBC
15
Q
Ht triangle
A
Ht
MCV RBC
16
Q
MCH triangle
A
MHC
MCHC MVC
17
Q
What are the 3 most important RBC indices
A
- Hb
- MCV
- MHC
Then RBC for disorders
18
Q
Define anisocytosis
A
Abnormal cell size
19
Q
Define ansiochromia
A
Variation in colour between cells
20
Q
Poikilocytosis
A
Variation in cell shape
21
Q
Polychromasia
A
More blue colour
22
Q
Conditions relating to hypochromic microcytic
A
Iron deficiency
Thalassaemia
HbE
Anaemia of chronic disease
Lead poisoning
23
Q
Conditions for normochromic normocytic
A
Renal disease
Anaemia of chronic disease and lead poisoning (tendency for microcytic)
Blood loss
BM failure
Haemoglobinopathies
24
Q
Conditions for macrocytic anaemia
A
Megaloblastic: B12/folate deficiency
Non-Megaloblastic: liver disease, drugs, alcohol, reticulocytosis, aplastic anaemia
25
Most common cause of anaemia
Iron deficiency
26
Causes of iron deficiency
Chronic blood loss (period, GI bleeding from tumour or ulcerations)
Increased demand in pregnancy/children/recovering from blood loss
Dietary deficiency
Malabsorption disorders
27
Iron cycle
Most goes to the bone marrow to make erythrocytes, this is recycled using transferrin
Iron lost chronic blood loss/urine/poo/hair/skin/nails
28
How to diagnosis iron deficiency anaemia
Blood film - microcytic hypochromic, pencil and targeting so poikilocytosis also o along with increased central pallor
Check ferritin levels - should be increased
29
False ferritin elevation seen when
In inflammation - recent or current
Cancers maybe
Acute liver injury
30
Anaemia of chronic disease appears like what on blood film
Normochromic with a tendency to be microcytic
31
What happens widely in anaemia of chronic disease
1. Hepcidin is up-regulated in the liver so iron sequestered in macrophage so less for RBC production
2. Inhibits EPO release in kidneys so less stimulation in BM
3. Inhibits erythroid production
4. Augments hemophagocytosis
32
Is normal RBC breakdown extravascular or intravascular
Extravascular
33
Where does normal RBC breakdown happen
Phagocytosis of old/damaged RBC in the splenic cords/marrow/liver sinusoids. This is the mononuclear phagocyte system. If the RBC cannot pass through the narrow endothelium it is phagocytosed
34
What does RBC breakdown into
Globin - amino acids
Iron - binds to transferrin
Protoporphyrin - bilirubin then liver into faeces/urine
35
Extravascular haemolysis
Destruction via macrophages in organs
Due to RBC abnormality
36
Intravascular haemolysis
Lysis of cells in blood vessels
Accompanied by extravascular haemolysis
37
What happens to Hb in intravascular haemolysis - oxidation route
Excess is oxidised to Fe3+ where the Globin chain is recycled
Methaem and albumin make methaemalbuminaemia
38
Intravascular haemolysis - haptoglobin route
Hb binds with haptoglobin and is cleared by macrophages in the liver
39
Intravascular haemolysis- kidney route
Filtered by glomeruli
Reabsorbed by renal tubules until saturated = haemoglobinuria
Iron from breakdown is absorbed by renal tubules and stored as Haemosiderin = haemosiderinuria
40
What does increased haemolysis lead too
Haemolytic anaemia
41
Hereditary causes of haemolytic anaemia
Membrane abnormalities
Some Haemoglobinopathies
Enzymopathies
42
Acquired causes of haemolytic anaemia
Antibodies directed at self RBC
Infections like malaria
Secondary to severe renal/liver disease
Mechanical/chemical/physical agents
Microangiopathic (TTP/HUS/DIC)
PNH - cells missing CD55/59
43
What does chronic haemolysis present as
Jaundice - as more RBC breakdown = more bilirubin
RBC production increases as there is never enough (6-8 times increase)
Erythroid hyperplasia
But mild haemolysis may be asymptomatic
44
Clinical features of haemolytic anaemia
Pallor
Jaundice = icteric sclera (yellow eyes), increase risk of gallstones
Splenomegaly (cell trapping)
45
Chronic hereditary haemolytic anaemia effect
Aplastic crisis
Infection with parvovirus B19, Hb will rapidly decline as erythropoiesis stops but haemolysis continues
46
Lab features in haemolytic anaemia
Increased unconjugated bilirubin, LDH, urinary urobilinogen
Haptoglobins are absent as Hb binds and then is cleared
Haemoglobinuria, Haemosiderin, methaemalbuminaemia
Reticulocytosis
Low folate levels
Erythroid hyperplasia (myeloid:erythroid ratio decreases)
Poikilocytosis
47
What are RBC membranes made of (%)
52% protein for protection and structure
40% lipids for elasticity and strength
8% carbs for protection
48
Name two RBC surface proteins
CD55 and CD59
49
What does CD55 do
Degrades complement
50
What does CD59 do
Inhibits lysis
MAC inhibitory protein
51
What do RBC membrane lipids do
Confers elasticity and cholesterol confers tensile strength
Phospholipids redistribute when membrane is disrupted
52
What do integral proteins do on RBC membrane
Transport and osmotic tension
Adhesion and receptors
53
List skeletal proteins in inner RBC membrane
Ankyrin, protein 4.1/4.2, actin, alpha and beta spectrum form a horizontal scaffold
54
What do skeletal proteins do
Interact with integral proteins for lateral structure and to maintain biconcave shape
55
What happens during RBC deformation (skeletal proteins)
Spectrin helices and bonds open and close during RBC deformation
Abnormalities cause poikilocytosis which decreases lifespan and deformability
56
What is the RBC membrane permeable too
water, HCO3-, Cl-
GLUT1 transports glucose
Ca2+ ATPase pumps out Ca2+
Na and K pumps
57
List RBC membrane disorders
Hereditary spherocytosis/eliptocytosis/stomatocytosis/ovalocytosis
58
What is HS
Hereditary spherocytosis
Mutated gene caused by deficiency of skeletal proteins like ankyrin/spectrin/protein 4.2, band 3
59
What happens to the RBC in HS
Loss of skeletal proteins
Loss of membrane as underlying connection is broken
Less SA:V ratio
Decreased deformability so cells get trapped in the spleen
60
HS signs
Jaundice
Splenomegaly
Can be asymptomatic or severe anaemia
61
HS blood film
Spherocytosis
High bilirubin
Low haptoglobin or none
Reticulocytosis
Polychromatic cells
Poikilocytosis
Anisocytosis
62
DAT for HS
Negative for IgG on RBC
63
What is an EMA and when is it used
Eosin 5 maleimide assay
Fluorescent dye binds to skeletal proteins in RBC so low fluorescence in HS as they are deficient in these proteins
64
What is an SDS-PAGE and why is it not good
Genetic test for HS
identifies primary gene defect
BUT difficult as many proteins can be affected and expensive
65
What is a historical test for HS
Increased RBC osmotic fragility
Measures haemolysis in increasing conc of saline
Doesn’t confirm
66
Complications of HS
Haemolytic crisis
Megaloblastic crisis from folate deficiency
Gallstones
Aplastic crisis in parvovirus B19
67
Treatment for mild HS
None needed
68
Treated for severe HS
Splenectomy
69
How does a splenectomy help HS
Cells survive longer
Less bilirubin and so lower risk of gallstones
70
What are you at the risk of post splenectomy
Sepsis and strep pneumoniae infections so need vaccinations and prophylaxis
71
Blood film after a splenectomy
Howell jolly bodies
Spherocytea
Target
Thrombocytosis
Pappenheimer bodies
Acanthrocytes
72
What is G6PD deficiency
genetic decrease in G6PD leading to early death of RBC in spleen
73
Genetical pattern of G6PD
X linked recessive
7.5% Africa as malaria resistance
74
Class 1 and 2 G6PD
Severe
All RBC have less G6PD so chronic haemolysis
75
Class 3 G6PD
Mild - African type
Young RBC have normal G6PD but it loses function
Oxidative stress = acrid haemolysis
76
What type of haemolysis is seen in G6PD deficiency
Extravascular mainly by macrophages
Some intravascular
77
How does G6PD deficiency cause Heinz bodies
Hb gets oxidised by radicals which damages RBC membrane and Hb is oxidised
The denatured Hb precipitates and sticks to inner membrane
78
Blood film G6PD
If in haemolytic crisis - blister cells, bite cells, Heinz bodies, spherocytosis, fragments, poikilocytosis, reticulocytosis
79
What makes G6PD WORSE
Oxidative stress from drugs, infections, fava beans
80
Other lab finding of G6PD
Haemoglobinuria and retics
81
How to treat or avoid G6PD crisis
Vaccination
Antibodies
Avoid fava beans and some drugs
Transfusion, dialysis, splenectomy if severe
82
G6PD blood film in a haemolytic crisis
Normal
FBC normal too
83
G6PD should be done when
After a crisis when reticulocytosis count and Hb are normal
120 days after as reticulocytes have increases G6PD
84
Core four in G6PD crisis
Increased reticulocytes/LDH/bilirubin
Low or absent haptoglobin
85
G6PD effect on neonates
Neonatal Hyperbilirubinaemia
2-3 days after birth = jaundice
86
What is kernicterus
Bilirubin in Brain
Possible in neonatal Hyperbilirubinaemia
87
4 types of AIHA
Warm
Cold
Paroxysmal cold haemoglobinuria
Mixed - rare
88
What does a DAT do
Positive in AIHA
Detects IgG and Cd3 on RBC surface
89
What type of haemolysis is happening in AIHA
Extravascular by macrophages
And/or intravascular complement mediated haemolysis
90
What causes warm AIHA
IgG that reacts at 37
Idiopathic, secondary to autoimmune disorders/neoplasms/viral infections/immunodeficiency
91
Treatment of warm AIHA
Splenectomy is chronic and refractive
Treat underlying (immunotherapy)
92
Presentation of warm AIHA
fever
Jaundice
Hepatosplenomegaly
Mainly extravascular with spherocytea and polychromasia
93
Cold AHIA cause by what antibody
IgM autoantibodies reacting at 4 degrees
94
Pathogenic cold AHIA
High IgM autoantibody titres, reactive above 30C causing cold agglutin disease
95
Non pathological cold AIHA
low titres of IgM autoantibodies, polyclonal antibodies, non reactive above 30C
96
What causes acute cold agglutinin disease
Secondary to infection
EBV, mycoplasma pneumoniae
Self limiting, polyclonal with some anaemia
97
What causes chronic cold agglutinin disease
Idiopathic
Secondary to LPD
98
How to diagnosis CAD
High titres antibodies in blood tube but needs to be warmed to 37 for a blood film and analysis
99
What should people with chronic CAD do
Avoid cold temps
Supportive therapy
Monoclonal Ab therapy (anti CD20)
100
Presentation of chronic CAD
Monoclonal antibodies in middle aged and elderly
Variable anaemia and cyanosis
101
What is paroxysmal cold haemoglobinuria
Acute intravascular haemolysis after cold exposure
102
What triggers paroxysmal cold haemoglobinuria
Viruses and syphilus
Self limiting tho
103
What do the antibodies do in paroxysmal cold haemoglobinuria
IgG antibody binds to P blood group antigens
Binds to RBC in cold but in warm lysis of RBC happen
104
3 methods of drug induced immune haemolytic anaemia
1 Hapten mediated (antibody against drug membrane complex in penicillin)
2 complement mediated (Ab against drug-protein complex)
3 True AIHA (unclear drug does)
105
What is microangiopathic haemolytic anaemia
Endothelial injury from shear stress causes micro thrombi formation
Fibrin damages RBC in small vessels
Two types : TTP and HUS
106
What is microangiopathic haemolytic anaemia associated with
Gram nega septicaemia
DIC
malignant hypertension
Pre eclampsia
Some drugs
107
Lab findings with microangiopathic haemolytic anaemia
Schistocytes
Severe - jaundice, reticulocytosis
108
What is TTP Pentad
MAHA
thrombocytopenia
Neurological effects
Maybe fever and renal dysfunction
109
HUS triad
MAHA
renal failure
Thrombocytopenia
110
TTP and HUS is more common in who
TTP - women 30-40y
HUS - children 6m-4y
111
TTP stands for
Thrombotic thrombocytopenic purpura
112
HUS stand for
Haemolytic uraemic syndrome
113
What happens in TTP
Autoantibody go ADAMTS13
Enzyme that cleaves vWF causing accumulation of lots of large vWF multimedia leading to thrombosis
114
What happens to EPO in anaemia of renal disease
Low EPO also triggers neocytolysis
Less RBC made
So you get normocytic normochromic anaemia with Hb 50-80g/L
115
What happens to RBC in anaemia of renal disease
RBC survival decreases to 70-90 days
Waste products build up in kidneys further impacts lifespan
116
Anaemia of renal disease blood film
Burr cells
117
What does lead poisoning interfere with
Porphyrin production and incorporation of iron
118
How to treat lead poisoning
Remove lead by chelating using EDTA
119
Leading poisoning symptoms in children and adults
Peripheral neuropathy
Vomiting
Abdomen cramps
120
Leasing poisoning effects on infants
CNS effects
Impaired mental
121
Lead poisoning blood film more
Normocytic to microcytic
Reticulocytosis
Basophilic stippling
122
What is basophilic stippling
Undegraded ribosomes aggregates
123
What happens to DNA synthesis in Megaloblastic anaemia
DNA synthesis and cell division is inhibited
Cells will die or grow without diving making them bigger but less are there
124
Less common causes of Megaloblastic anaemia
MDS
myelosuppressive drugs
Congenital
125
Most common cause of Megaloblastic anaemiA
B12 and folic acid deficiency
126
Causes of B12 deficiency
Nutritional - vegetarian
Need intrinsic factors as hard to absorb
127
Causes of folate deficiency
Nutritional
Malabsorption
128
Main sources of B12
Animal and diary produxts
129
Body stores for B12
2-4 years
130
Where is B12 absorbed
Distal ileum
131
Where is folate absorbed
Duodenum/jejunum
132
Body stores for folate
3-4 months
133
Where is folate found
Greens
Nuts
Eggs
Liver
Cereal
134
Is folate destroyed in cooking
Yes
135
Megaloblastic clincial features
Loss of epithelial cells as all cell division is effected so GI and skin problems
Jaundice
Neurological
136
Blood film Megaloblastic anaemia
Low reticulocytes
Pancytopenia if severe
Oval cells
NRBC
Poikilocytosis -ani
Hypersegmented neutrophils
Howell jolly bodies
Basophilic stippling
Leftover spindle
137
What happens to LDH and bilirubin in Megaloblastic anaemia
Increase LDH and bilirubin from ineffective erythropoiesis
138
Non Megaloblastic causes
Liver disease
Alcohol
Hypothyroidism
Reticulocytosis
Aplastic anaemia
Normal in neonates
Drugs
