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Haematology Flashcards

1
Q

Where are RBC, platelets and most of the WBC produced?

A

Bone marrow

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2
Q

Who has more extensive bone marrow ?

A

Infants

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3
Q

In adulthood bone marrow is limited to predominantly where?

A 
Pelvis
Sternim
Skull
Ribs
Vertebrae
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4
Q

What controls haematopoeisis?

A

Hormones and cytokines

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5
Q

How do hormones and cytokines control haemopoiesis?

A

Alter gene expression, altering how a stem cell divides

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6
Q

For a haemopoetic stem cell to become an erythrocytes what must it first differentiate into

A

Myeloid progenitor

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7
Q

What system removes faulty cells (rbc)

A

Reticuloendothelial system (RES)

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8
Q

What is the main organ that disposed of faulty blood cells

A

Spleen

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9
Q

What does the mean cell volume help us differentiate between?

A

Microcytic, normocytic and macrocytic disorders.

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10
Q

How long is a red cells life?

A

120 days

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11
Q

In what state do rbc carry haemoglobin (the iron)

A

Ferrous state

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12
Q

Why do red cells need to generate atp

A

To maintain membrane and osmotic equilibrium

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13
Q

What shape are RBC

A

Biconcave

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14
Q

Why are RBC biconcave

A

It allows them to passage through microcirculation

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15
Q

A change in rbc shape often results in what?

A

Lysis

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16
Q

What are some RBC shape changes ?

A

Spherocytes, speculated, sickle

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17
Q

Haemaglobin is what structure?

A

Tetramer of 2 pairs of globin chains

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18
Q

What states can haemaglobin be in?

A

T and R

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19
Q

Where are the globin genes located?

A

Chromosome 11 and 16

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20
Q

What is important about globin gene expresion and age?

A

Different expression at different ages

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21
Q

When do we switch rom foetal to adult haemaglobin?

A

3-6months

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22
Q

What is the purpose of globin in relation to haem?

A

Protect haem from oxidation keeping it ferous.

Promotes variation in affinity

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23
Q

When RBC are broken down what is the fate of globin, haem and the iron?

A

Globin broken down into aminos and reformed
Iron retained from haem
Wate haem into billivurdin

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24
Q

What colour is billivurdin?

A

Green

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25
What is haem broken down into (fully)
First billivurdin Then billirubin Then stercobillin in faeces or urobillnogen in urine
26
What organ controls erythropoeises?
Kidney
27
What does the kidney do if reduced pO2 is detected in the interstitial peritubular of the kidney?
EPO is produced
28
What does EPO stimulate?
Maturation and release of RBC from marrow
29
How is the release of EPO regulated?
A raise in pO2 reduced EPO production
30
Why is kidney damage associated with anaemia?
Reduced EPO production
31
What 2 metabolic pathways do RBC use to generate ATP?
Glycolysis (glucose to Lactate) | Pentode phosphate pathway
32
What are some key roles of iron?
Transport and store oxygen Integral part of many enzymes Collagen formation Neurotransmitter production
33
What mechanism do we have to excrete iron?
We dont!
34
How do we excrete iron from the body?
Bleeding Loss of skin and hair Can't actively excrete
35
What is the consequence of low or high iron?
Anaemia if low | Dangerous deposition if high
36
Iron in the body is in what 2 forms?
Available or stored
37
What examples of available iron in the body are there?
Haemoglobin Myoglobin Tissue iron (enzyme) Transported iron (serum iron)
38
What are some examples of stored iron in the body
Ferritin Haemosiderin Macrophage iron
39
When does the iron status (required) increase in life?
Pregnancy | Children
40
Where does 80% of active iron come from?
Recycling | Not from gut absorption
41
What is an iron macrophage?
One that eats an old senescent red blood ell mostly splenic macrophages and kupfer cells of the liver
42
Where is 85% of stored iron located?
As ferritin in hepatocytes
43
How much iron enters and leaves the body in a day?
1-2g
44
What is the best source of iron intake?
Haem sources
45
How much iron do we need in our diet in a day?
10-15mg
46
Why is haem intake of iron better than non haem?
Haem enters as fe2+ ferrous | Non haem enters as Fe3+ feriric
47
What has to happen to ferric iron before it can enter the body?
It has to be reduced
48
What does fe2+ bind to to enter cells (where)
Divalent metal transporter 1 in apical cells of duodenum and upper jejunum
49
How does iron get transported out of the apical cells of duodenum
Ferroportin
50
What is required for iron to enter a cell, such as a RBC?
Iron transferrin complex | Binds to transferrin receptor
51
What is essential in enhancing absorbtion of non haem iron? | What suggestion does this lead to when talking iron supplements
Ascorbic acid | Take with OJ not with cuppa (antacid)
52
How do we regulate how much iron we absorb?
Hepcidin
53
What does hepcidin do?
Binds to ferroportin and stops iron absorbtion
54
Where is hepcidin transported from?
LIver and kidneys
55
What leads to Hepcidin synthesis ? What leads to decreased hepcidin?
Iron overload increases synthesis | High EPO activity decreases it
56
What's the most common nutritional disorder
Iron defficency
57
Is iron defficency a diagnosis?
No its a symptom
58
What are the 3 root causes of iron defficeny
``` Poor intake Physiological loss (period) Pathological loss ```
59
What are some symptoms of iron defficent anaemia
Tiredness, reduced ex tolerance. Pale (reduced o2 carrying)
60
What are some signs of iron defficent anaemia
Tachycardia, increased RR, pallor
61
In iron defficent anaemia what is the HB content? What do the cells look like?
Hypochromic, low HB , look pale
62
What size are rbc in iron defficent anaemia?
Microcytic (small mcv)
63
What changes other than microcytic and hypochromic are there in iron defficent anaemia?
Change in shape Low serum ferritin Low reticulocyte haemoglobin content
64
What do reduced ferritin level indicate?
Iron defficent anaemia?
65
Can you rule out iron defficent anaemia with normal ferritin? Why
No | Ferritin raised with inflammation, liver disease, alcoholism
66
What marker is used to test for functional iron defficent anaemia? When can this not be used?
CHR | Thalassaemia
67
How would you treat iron defficent anaemia?
Diet, oral iron, IM injection, IV iron. | Transfusion if cardiac comprimise likely
68
Why is excess iron dangerous?
Causes damage to lipid membranes and proteins | Deposited in tissues
69
What ca reduced iron produce that are dangerous?
Reactive hydroxyl and lipid radicals
70
What disease is associated with excess iron ?
Haemochromatosis
71
What does haemochromatosis damage?
End organs
72
What secondary diseases can haemochromatosis lead to
Liver cirrhosis Diabetes Cardiomyopathy Arthropathy
73
Haemochromatosis is due to a mutation in what?
HFE gene
74
What's anaemia?
Inability to deliver enough oxygen to tissue due to decreased RBC or decreased haem
75
The spleen is where?
Left upper quadrant
76
The process of making red blood cells is known as what?
Eryhtropoesis
77
If erythropoeisis is reduced or not effective what is it known as?
Dyserythropoiesis
78
Why does chemo induce anemia?
The bone marrow can become empty meaning it cant respond to EPO
79
What does a marrow infiltrate do to cause anemia
Decreases the number of haematopoetic cells
80
What happens in anaemia of chronic disease?
The iron stored in bone marrow isn't released, this reduces red blood cell lifespan and the marrow has a lack of response to EPO
81
In anaemia of chronic disease what size RBC are seen?
It can be microcytic, normocytic or macrocytic
82
What clinical clue can be seen in anaemia of chronic disease?
Raised CRP and ferritin
83
What is myelodysplastic syndrome?
Production of abnormal clones of marrow cells
84
In myelodysplastic syndrome what kind of anaemia develops? And why
Red cells are defective and large- macrocytic
85
How is diagnosis of myelodyslplastic syndrome made?
Microscopy of blood and bone marrow cells | Often genetic change at chromosomes in marrow cells
86
What develops in a high proportion of myelodysplastic syndrome cases?
Acute Leukaemia | Pancytopenia
87
What is the treatment of myelodysplastic syndrome?
Chronic transfusion | Occcasionaly chemo followed by stem cell transplant
88
A defficency in what building blocks of dna synthesis leads to anaemia?
Vit b12 | Folate
89
What is seen in terms of red cells in b12 and folate defficencies and why?
Large red cel precursors with inappropriately large nuclei and chromatin This is because nuclear maturation and cell division lags behind cytoplasmic development
90
What anemia do you get with b12 or folate deficency
Macrocytic
91
What happens to b12 in the stomach
Combined with intrinsic factor produced by patietal cells
92
B12 bound to intrinsic factor in the ileum does what?
B12 is absorbed and the intrinsic factor destroyed
93
In portal blood what is b12 bound too?
Transcoblamin
94
A deficency is vit b12 can be the result of what? | 4
Poor diet eg vegan Intrinsic factor- pernicious anaemia IF-B12 complex- disease of ileum eg crohns Transcobalmin deficent
95
Where does folate absorbtion occur
Duodenum and jejunum
96
What is dietary folate converted to
MethylTHF
97
When are we physiologically more likely to develop folate deficency
Pregnancy
98
A defficency in folate can occur due to what 4 things?
Folate defficent due to diet or increased use (haemolytic anemia, skin disease etc) Duodenum/jejunum absobrtion issue MethylTHF issue- some drugs inhibit this eg methotrexate Urinary loss- liver and heart disease
99
What's a pancytopenia
Low rbc, low platelets, low wbc
100
The peripheral blood fill in folate or b12 defficency shows what?
Macrocytic red cells with hypersegmented neutrophils
101
What is b12 defficency associated with that folate isn't/
Focal demyelination
102
What is thalassaemia ?
Reduced rate of synthesis of normal alpha or beta globin genes
103
What is sick cell disease
Synthesis of abnormal haemoglobin
104
What mutation causes sickle
Point mutation Valine for glutamic acid Position 6 beta gene
105
What is a sickle cell crisis?
A vaso-occlusive episode that leads to organ damage.
106
What is the life cycle of a sickle cell like?
It's a reversibly sickled erythrocytes but repeated cycles of deoxigantion cause irreversible sickle
107
What do irreversibly sickled cells do?
They have increased adherence to endothelium | They can cause thrombosis.
108
What kind of RBC are seen in thalassaemia?
Hypochromic | Microcytic
109
Why are thalassaemia cells hypochromic?
Decreased haem
110
How does the body try and compensate with the anaemia induced by thalassaemia?
Extramedullary haemopoeisis -results in splenomegally | Stimulation of EPO
111
What's a major cause of death in thalassaemia patients? Why does it happen?
Iron overload- excessive dietary absorbtion as ineffective haematopoeisis is occurring
112
What are some heriditeray conditions associated with red cell membranes
Hereditary spherocytosis | Hereditary eliptocytosis
113
What are target cells?
Red cells that have abnormal haemaglobin
114
What are some acquired causes of red cell membrane disruption/
Mechanical damage- heart valves, vasculitis, DIC Heat damage Osmotic change in drowning
115
What are some well known deficiencies in metabolism that can result in red cell metabolism issues?
Glucose 6 phosphate dehydrogenase deficency G6PD | Pyruvate kinase defficency
116
If there is no issue with the bone marrow- erythropoesis or haemaglobin synthesis, no issue with the red blood cells structure or metabolism and no issue with the RES, then why could someone have anaemia? What kind of anaemia would it be?
Loss of blood- gastric ulcer, gastric cancer, excessive menstruation, bladder cancer Microcytic due to excess iron loss
117
What is haemolytic anaemia
Increased red cell destruction causing anaemia
118
What are some key lab features of excessive red cell removed by the RES
``` Increased reticulocytes (marrow trying to compensate) Raised billirubin (haem breakdown) Raised LDH (enzyme red cells are rich in) ```
119
Myelofibrosis causes anaemia how? Hint multifactorial
There is decreased Erythropoeisis as marrow fibrotic | The spleen grows to compensate but also breaks down more red cells (RES)
120
Thalassamia causes anaemia multifactorally, how so?
Ineffective haemoglobin synthesis Poor structure Increased removal
121
If there is an appropriate reticulocytes response but no evidence of haemolysis what should you look for?
Evidence of bleeding
122
When working out what kind of anaemia it is. If the reticulcytes are low/normal levels. What would you look at next?
MCV
123
What do myeloproliferative disorders involve?
Dysregulation at the multipotent haematopoetic stem cell
124
What is polycythaemia Vera (PV)
Neoplasm where too many red cells are produced
125
What is the diagnostic criteria for polycythaemia Vera?
High haematocrit
126
What is erythrocytosis?
Increase in conc of RBC
127
If a patient doesn't have a primary reason to have increased red cell mass (PV) what is a secondary cause likely driven by?
EPO production
128
What is physiologically appropriate EPO production ?
When there is central hypoxia- chronic lung disease, altitude training When there is renal hypoxia- renal artery disease
129
What are examples of pathological production of EPO
Hepatocellular carcinoa, renal cancer, meningionma, uterine leimyomas
130
If EPO production isn't pathological or a physiological response, what could it be?
Injected. Will cause polycythaemia
131
What is used to manage PV
Aspirin
132
What does the spleen consist of?
Red pulp and white pulp
133
What is red pulp? Spleen
Sinuses lined by endothelial macrophages and cords
134
What is white pulp?
Structure similar to lymphoid follicles
135
Where does blood enter the spleen from?
Via the splenic artery
136
What cells pass through what parts of the spleen?
White cells and plasma through white pulp | Red cells through red pulp
137
What are 4 functions of the adult spleen?
Sequestering and phagocytosis Blood pooling Extramedullary haemopoiesis Immunological function
138
What pools in the spleen and why?
Platelets and red cells for rapid mobilisation during bleeding
139
When does extramedullary haemopoiesis occur?
During haematological stress or if marrow fails
140
What proliferates in extramedullary haemopoiesis?
Pluripotent stem cells
141
What is the immunological function of the spleen?/ what does it have
25% of T cells and 15% of B cells in spleen
142
Where should you begin to palpate for the spleen? What are you feeling for? When does the spleen edge move towards you?
Right iliac fossa Feel for splenic notch Spleen edge moves towards you on inspiration
143
Why would the spleen grow in splenomegally?
``` Back pressure Over working red or white pulp Extramedullary haemopoiesis Cancer infiltrate Other infiltrate (eg sarcoidosis) ```
144
What kind of back pressure would cause splenomegally?
Portal hypertension in liver disease
145
Why would you get splenomegally with chronic lymphocytic leukaemia?
Expanded white pulp, infiltrated
146
What can cause a massive splenomegally?
Chronic myeloid leukaemia Myelofibrosis Chronic malaria Schistosomiasis
147
What size splenomegally would liver cirrhosis with portal hypertension cause?
Moderate
148
What size splenomegally would endocarditis cause?
Mild
149
What can occur in hypersplenism?
Pancytenia or thrombocytopenia due to pooling of blood
150
What's the risk in splenomegally
Rupture as not protected by rib cage
151
Asides from rupture leading to haematoma what is another complication of splenomegally?
Infarction
152
What is hyposplenism?
Lack of functioning splenic tissue
153
What are some causes of hyposplenism?
Splenectomy Sickle cell isease Coeliac
154
What do blood films demonstrate in hyposplenism?
Howell jolly bodies
155
What are Howell jolly bodies?
Dna remenants
156
A hypospleic patient is at risk of what? From what in particualr? What examples?
Sepsis Encapsulated orgnanisms Pneumococcus, haemophilus influenza, meningococcus
157
What is cytopenia
Reduction in the number of blood cells, can take many forms
158
What is a low red cell count known as?
Anaemia
159
What is a low white blood count known as?
Leucopenia
160
What is a low neutrophil count known as?
Neutropenia
161
What is a low platelet count known as?
Thrombocytopenia
162
What is a low RBC, WBC and platelet count known as?
Pancytopenia
163
If it is a cytosine or a philia, what is it?
An increase in the number of blood cells
164
What is a high red cell count known as
Erythrocytosis
165
What is a high white blood cell count known as
Leucocytosis
166
What is a high neutrophil count known as
Neutrophilia
167
What is a high lymphocyte count know as
Lymphocytosis
168
What is a high platelet count known as ?
Thrmbocytosis
169
What's the commonest white cell
Neutrophil
170
How many segments does a neutrophil have?
3-5
171
How long do neutrophils lasts?
1-4 days
172
Who is the first responder phagocyte
Neutrophil
173
What hormone controls neutrophil maturation?
G-CSF
174
What effect does G-CSF have?
Increase production of neutrophils Decrease time to release mature cells from bone marrow Enhances chemotaxis Enhances phagocytosis
175
If we need more neutrophils in a patient with neutropenia what can we do?
Administer recombinant GCSF
176
What are some causes of neutrophilia?
``` Infection Acute inflammation Tissue damage Cancer Smoking Myeloproliferative disease Acute haemorrhage ```
177
What range is the neutrophil count in a neutropenic? When does it become severe neutropenia?
1.5x10^9 | Severe if less than 0.5
178
What are the 3 causes (generally) of increased removal/use of neutrophils to induce neutropenia?
Immune destruction Sepsis Splenic pooling
179
What can reduce the production of neutrophils inducing neutropenia
``` B12/folate defficent Aplastic anaemia (empty marrow) Infiltration of marrow Radiation Drugs (chemo, antibiotics, anti epileptics...) Viral infection (common) Congenital cause ```
180
What are some consequences of neutropenia
Life threatening bacterial infection Life threatening fungal infection Mucousal ulceration
181
What do monocytes respond to?
Inflammation and antigenic stimuli
182
What to monocytes differentiate into? | What do there lysosomes contain?
Macrophages | Lysozyme, complement, interleukins, arachnoid acid, CSF
183
When do we see monocytosis?
Chronic infection Chronic inflammatory condition Carcinoma Myeloproliferative disorders/leukaemias
184
How long are eosinophils in circulation? What is there lifespan
3-8 hours in circulation | 8-12 day lifespan
185
What are eosinophils responsible for dealing with specifically?
Parasites
186
What do eosinophils mediate?
Allergic response | Hypersensitivity reactions
187
Eosinohils migrate where?
To epithelial surfaces
188
What do eosinophils granules contain?
Arginine, phospholipid, enzymes
189
When is eosinophilia seen?
Allergic diseases like asthma, eczema Drug hypersensitivity Parasitic infection Hodgkin lymphoma Certain leukaemias
190
When are basophils active?
Allergic reactions and inflammatory conditions
191
What do basophils granules contain?
Histamine, heparin, hyaluronic acid
192
When is basophilia seen?
Immediate hypersensitivity Ulcerative colitis RA
193
What do basophils look like?
Blackberrys
194
Where do lymphocytes originate?
Bone marrow
195
What lymphocyte is part of the humoral immune?
B cell
196
What lympcyte produces antibodies
B
197
What lympcyte would a cd4 be?
T helper
198
What cell is the lymphocyte of cellular immunity?
T cell
199
What lymphocyte is know for cell mediated cytotoxicity
NKC
200
When is a reactive lymphocytosis seen?
Viral infections Bacterial infection Stress- eg MI Post splenectomy
201
When is a lymphoproliferative lymphocytosis seen?
Chronic lymphocytic leukaemia T or NK leukaemia Lymphoma
202
What are 3 reasons that cause pancytopenia through increased removal
Splenic pooling hypersplenism Haemophagocytosis Immune destruction
203
What can be underlying causes for a pancytopenia due to reduced production?
``` B12/ folate defficent Marrow fibrosis/infiltrate Radiation Drugs Virus- EBV, viral Hepatitis, HIV, CMV ```
204
What is aplastic anaemia
Pancytopenia with a hypocellular bone marrow in the abscence of abnormal filtrate or fibrosis
205
What can haematological malignancies cause?
Pancytopenia
206
What are symptoms of pancytopenia?
Symptoms of anaemia- fatigue, dizzy chest pain etc + Symptoms of thrombocytopenia- bleeding, brushing etc + symptoms of neutropenia- infection, ulcers etc + Symptoms of underlying cause
207
What are some sources of haematopoetic stem cells
Bone marrow aspitarate Leucopheresis- stem cells mobilised into blood by GCSF Umbilical cord stem cells
208
When does haemopoeises begin in the embryonic liver?
Week 5-8 of gestation
209
What factors alter the lineage pathway a differentiating progenitor cell takes?
Transcription factors, hormones, interactions with non haemopoetic cell types
210
How many major lineages arise from the haemopoietic stem cell?
5
211
What kind of nuclei do platelets have?
They have no nucleui
212
What is megakaryocyte formation driven by?
Thrombopoietin TPO
213
What kind of cell is a megakaryocyte?
Polyploid- several copies of each chromosome
214
What are the granulocytes?
Basophils, neutrophils, eosinophils
215
What do granulocytes arise from?
Myeloblast cells
216
What can monocytes differentiate into?
Macrophages or dendritic cells
217
The development of B lymphocytes commences where?
Fatal liver and bone marrow
218
What happens to the immunoglobulin genes of B lymphocytes in development
Genes rearracnce to produce antibodies with wide array of variation
219
Where to T lymphocytes arise from and then mature
Arise from fetal liver mature in thymus
220
What commits progenitor cells to erythroid lineage?
Transcription factors GATA1, FOG1, PU1
221
Once the progenitor cell has been committed to erythroid lineage what drives it ?
EPO from kidneys
222
How does EPO work?
Inhibits apoptosis of colony forming units of ertyhroid cell line.
223
What do reticulocytes do once in the bloodstream
Extrude ruminants of organelles- mitochondria and ribosomes
224
What is a diagnostic estimate of EPO level?
Reticulocytes count
225
Why are red blood cells particularly succeptibe to oxidative damage
Lack nuclei, cant replace damaged proteins
226
What cells make up the RES system
Kupffer (liver) Microglia (CNS) Re pulp macrophage (Spleen) Langerhans (skin and mucosa)
227
What does the shape of RBC allow them to have as a properties
Optimal laminar flow
228
What proteins of the erythrocytes lipid bilayer are particulary important
Spectrin, ankyrin, band 3, protein 4.2
229
What conditions are associated with gene mutations in spectrum, ankyrin, band 3 or protein 4.2
Alter rbc cell membrane eg hereditary spherocytosis
230
How much of the RBC cell volume is haemoglobin?
95%
231
What does 2,3 BPG do to oxygen afffinity in rbc
Decreases it
232
A fall in ph or increase in co2 does what to rbc affinity
Decrease (Bohr)
233
Ferric iron is reduced to ferrous iron by what
Duodenal cytochrome b reductase
234
Iron within enterocytes can either be what
Stored as ferritin | Transported via ferroportin
235
Hepcidin binds directly to what? It also inhibits transcription of what
Ferroportin | DMT1 gene
236
What does the normal haemoglobin range vary on?
Age, sex, ethnicity
237
How does the body adjust to a slow anaemia
Increase stroke volume, increase conc of 23bpg
238
How is an initial iron defficency overcome
Mobilisation of iron from stores
239
In anaemia of chronic disease what happens to macrophage activity
It's increased
240
In anaemia of chronic disease what is happening to hepcidin?
Cytokines IL-6 increases production resulting in less iron absorbtion
241
What's folate converted into? What's its purpose
Tetrahydrofolate | It's a one carbon carrier, needed for synthesis of base thymidine
242
Folate defficency in pregnancy can result in what
Neural tube defect
243
Vit b12 can only be obtained from what
Animal origin food
244
Where is half the dietary b12 taken up
Liver
245
If b12 stores are high how long before its depleted
3-6 years
246
What is functional folate defficent
Lack of b12 traps folate in stable methyl state
247
What is G6PDH the rate limiting enzyme in?
Pentose phosphate pathway
248
Myeloproliferative neoplasms are cursed by what
Mutation in the gene coding for tyrosine kinase Janus kinase
249
In post cases what is PV driven by?
Oncogenes mutations that activate jack-stat pathway
250
What does white pulp do
Synthesised antibodies and removes antibody coated bacteria and blood cells
251
Howel jolly bodies are an indicator of what
Reduced splenic function
252
What colour do basophils stain
Dark blue
253
What colour do eosinophils stain
Red
254
What colour do neutrophils stain
Pink
255
Eisoniphils nuclues are..
Bilobed
256
When do basophils release histamine and heparin
Following binding of IGE to surface receptor
257
How is increased EPO stimulated?
Reduced pO2 in the intersitital peritubular of the kidney
258
Iron is either available or stored, what are some forms of available iron? And what are some forms of stored iron? Are the stored irons soluble or insoluble?
Available: haemoglobin, myoglobin, tissue iron (enzymes), transported serum iron Stored: ferritin (soluble) haemosiderin and macrophage iron (insoluble)
259
Stored iron is mostly ferritin or haemosiderin, what is it mostly stored as?
Ferritin (95%) haemosiderin (5%)
260
Where Is iron absorbtion occuring? What channel is needed for Fe2+ to be absorbed? What converts Fe3+ to Fe2+ for absorbtion?
Duodenum and jejunum DMT1 Enzyme DcytB, ferrireductase, citric acid can form complexes to increase absorbtion of Fe3+
261
How is haem converted to Fe2+ in the enterocyte? | What is the fate of Fe2+ within the enterocyte?
Haem oxidase converts him to fe2+ form Fe2+ stored as ferritin in fe3+ state Exported from cell via ferroportin
262
What 3 effects does hepcidin have to decrease iron absorbtion?
Degrades ferroportin Inhibits transcription of DMT1 Inhibits release of stored iron from macrophages
263
Once Fe2+ is bound to transferrin in the blood where does it go? What competes with it? What inherited disorder results in iron overload due to changes with this syste?
Can bind to transferrin receptors eg on red blood cells HFE competes with these receptors Hereditary haemochromatosis is an error in the gene for HFE
264
How is hepcidin release controlled?
High EPO reduces its expression | High iron increases its expression
265
What are 2 tests for iron defficency
Ferritin- also an acute phase protein | CHR- reticulocyte haemoglobin content (would also be low in thalassaemia
266
A 32 year old man presents worried about the fact his dad died of heart attack at a young age You do labs to look for what
Total cholesterol Serum Traicyglycerol Serum lipoprotein profile and check blood glucose for diabetes
267
What is hyperlipoproteinaemias?
Any condition where after 12 hour fast the plasma cholesterol and/or plasma triglyceride is raised
268
A man who's dad died early of a heart attack and has labs indicating high serum holesterol and increased LDL is likely to have what hyperlipoproteinaemia?
Familial hypercholeseramia
269
What are the 2 pathways in which tissues obtain the cholesterol they need?
1. Direct synthesis via HMG coa | 2. Cells can obtain via receptor mediated endocyots of LDL
270
What's a well known statin? | And a well known bile sewquestant?
Atorvastatin | Cholestyramine
271
Why are serum iron levels not reliable indicators of iron defficency?
Diurnal variation in levels
272
What vitamin defficency would cause a sideroblsatic anaemia
B6
273
What ferritin level indicates iron defficency? | What excludes it?
Low serum ferritin indicates it | High or normal doesnt exclude it
274
Where are blister cells commonly seen on blood film
G6PDH defficency
275
How does anaemia of chronic disease result in anaemia with a high ferritin and a high CRP
Chronic inflammation causes high levels of IL 6 which stimulates hepcidin which causes ferroportin to go back into cell and also for macrophage stores not to be released. The RBC doesnt get the iron and therfore has short lifespan leading to anaemia. But body iron levels are high
276
How does myelodysplastic syndrome lead to anaemia or pancytopenia
Abnormal clones of marrow stem cells are produced. These produce macrocytic cells that get prematurely destroyed inducing anaemia

ESA 2 (10 decks)

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