Session 5 Flashcards
(212 cards)
1
Q
Where are RBCs, platelets and most WBCs produced in the body?
A
Bone marrow
2
Q
Describe the arrangement of bone marrow in the skeleton of infants and adults
A
Extensive throughout the skeleton in infants
Active marrow more centrally located and less extensive in adults
3
Q
Give three examples of more centrally located areas of marrow in adults
A
Pelvis Sternum Skull Ribs Vertebrae
4
Q
Name two methods of testing bone marrow
A
Trephine biopsy
Bone marrow aspirate
5
Q
How is a trephine biopsy carried out?
A
Bone marrow is removed from the posterior left iliac crest
Marrow fixed and stained to see if there is enough of all cell lines/architecture
6
Q
In a trephine biopsy bone marrow is removed from..
A
The posterior left iliac crest
7
Q
How does a bone marrow aspirate vary from a trephine biopsy? (2)
A
Gives more detailed views of specific blood cells
More liquid bone marrow is taken
8
Q
The development of different blood cells from haemocytoblasts is controlled by…
A
Hormones/cytokines
Different concentrations of growth factors favours different development of haemocytoblast
9
Q
Control and removal of senescent blood cells is via the ___________________ system
A
Reticuloendothelial system
10
Q
What is the reticuloendothelial system?
A
A network in tissues/blood containing phagocytic cells
11
Q
Name 4 phagocytes found in the reticuloendothelial system
A
Monocytes
Macrophages
Microglial cells
Kupffer cells
12
Q
What are the main organs of the reticuloendothelial system?
A
Spleen
Liver
13
Q
What happens to damaged/old blood cells (particularly RBCs) in the RES?
A
Blood passes through the spleen and RE cells dispose of senescent blood cells
14
Q
What is the typical haemoglobin count for…
I) adult males
II) adult females
A
130-180 g/L
115-165 g/L
15
Q
What is the typical mean cell volume?
A
80-100 fL
16
Q
What is the typical platelet count?
A
150-400 x10^9/L
17
Q
What is the diameter of a RBC?
A
8 micrometers
18
Q
Changes in the components of the ________ _____________ of RBCs will change their shape
A
Cell membrane
19
Q
Describe the structure of haemoglobin
A
Tetramer of 2 pairs of globin chains (2x alpha, 2x beta) each with its own haem group
20
Q
Haemoglobin exists in which 2 configurations…
A
Deoxyhaemoglobin (T state)
Oxyhaemoglobin (R state)
21
Q
Which gene codes for the synthesis of haemoglobin? Where are they found
A
Globin gene clusters
Chromosome 11 and 16
22
Q
Are the individual globin chains synthesised independently or together?
A
Independently and the combined
23
Q
At what age does the switch from foetal to adult haemoglobin take place?
A
3-6 months
24
Q
What shape is the oxygen dissociation curve?
A
Sigmoid
25
Name three things that shift the oxygen dissociation curve to the right
2,3-BPG
H+ ions
Carbon dioxide
26
Haemoglobin is broken down into...
Globin
| Haem
27
What happens to the iron/amino acids and globin produced in the catabolism of haemoglobin?
It's recycled
28
What happens to the haem produced in Hb catabolism?
Excreted
29
Give an example of a condition in which there is excess of red blood cell destruction
Haemolytic anaemia
30
Excess of red blood cell destruction (e.g. Haemolytic anaemia) causes an excess of
An excess of bilirubin formation
Leading to jaundice
31
Excess ________________ formation leads to jaundice
Bilirubin
32
Bilirubin is the breakdown product of...
Heme
33
What two things happen to bilirubin in the liver
Sent to the kidneys - excreted as urobilinogen in the urine
Transported in the biles to the intestines where it will be excreted in the faeces as stercobilin
34
In which form is bilirubin excreted in the urine?
Urobilinogen
35
In which form is bilirubin excreted in the faeces?
Stercobilin
36
Which cells in the kidney detect reduced oxygen levels?
Interstitial peritubular cells of the kidney
37
Reduced oxygen levels detected by the kidney result in an increased production of...
Erythropoietin
38
Which hormone causes an increased rate of erythropoiesis?
Erythropoietin
39
Erythropoietin stimulates the release of...
Red cells from the bone marrow
40
By which two pathways does metabolism take place in red blood cells?
What does each pathway supply the red cells with?
Glycolysis
ATP generated
Pentose phosphate pathway
NADPH generated
41
Which molecule is metabolised in the pentose phosphate pathway?
Glucose-6-phosphate
42
Apart from transporting/storing oxygen what is another function of iron in the body?
Integral part of many enzymes
43
How is iron excreted?
We have NO mechanism for excreting iron
44
How much iron is lost each day from the body? From where in the body?
How are these losses made up?
Small amounts - 1-2 mg/day
Skin/Gut Cells
In the diet
45
Iron is available in the body in which 2 main forms?
Available (Functional) Form
Stored Form
46
Give 4 examples of function forms of iron?
Haemoglobin
Myoglobin
Tissue iron
Transported serum iron
47
Give two examples of stored forms of iron
Ferritin
| Haemosiderin
48
Describe the solubility of ferritin and haemosiderin
Ferritin - soluble
Haemosiderin - insoluble
49
When in life might you see higher iron requirements?
During pregnancy
50
Where does most active iron come from?
From recycling in the body in the breakdown of RBCs
51
In which form is iron predominantly stored in the liver?
Ferritin
52
Apart from as ferritin, iron in the liver is stored as...
Haemosiderin mainly in Kupffer cells
53
Haemosiderin in the liver is predominantly stored in...
Kupffer cells
54
Haem iron is mainly found in which foods?
Non-haem iron is mainly found in which foods?
Meats
Beans/pulses
55
Which is a better source of iron in humans - haem or non-haem iron?
Haem iron
56
Why is haem iron a better source of iron than non-haem?
Haem iron is already present in the ferrous form. Whereas non-haem iron is present in the ferric form and requires reduction by acid in the stomach.
57
The iron in haem iron is present in which form?
Ferrous form
58
The iron in non-haem iron is present in which form?
Ferric form
59
How much iron do we require from the diet each day?
10-15 mg/day
60
What happens to iron in the ferrous form that we receive from the diet?
Binds to transferrin
61
What converts iron from the ferric form into the ferrous form when it is taken in, in the diet?
Stomach acid - reduces ferric iron to ferrous iron
62
In which part of the intestine is ferrous iron taken up?
By which cells?
Apical surface of the duodenum/upper jejunum
Enterocytes
63
How is ferrous iron taken up at the apical surface of enterocytes in the duodenum/upper jejunum?
Transferrin-iron complex binds to transferrin receptors on the enterocytes
64
Ferrous iron is converted to which form inside the enterocytes?
Ferric iron
65
What two things can happen with the ferric iron in enterocytes?
Stored as ferritin
| Travels in the blood in its ferrous form bound to transferrin
66
How is ferrous iron transported out of the enterocytes if it is to travel in the blood bound to transferrin?
By ferroportin
67
What is the action of ferroportin in enterocytes?
Exports ferrous iron out of the enterocyte
68
What two things can happen to the ferrous iron exported from enterocytes?
Can be stored in the liver
Used in Hb
69
How do fetal enterocytes differ from adult enterocytes?
Fetal enterocytes have receptors for milk iron (lactoferrin)
70
Which type of cells contain the highest number of transferrin receptors?
Erythroid cells (cells that develop into RBCs)
71
Absorption of non-haem iron is better in which sorts of conditions?
Acidic conditions
72
Orange juice contains which acid?
Ascorbic acid
73
How does precipitation/chelation of iron affect its absorption?
Which foods cause the precipitation/chelation of iron?
Inhibit its absorption
Tea, chapatis, antacids
74
Name three factors that affect the regulation of iron absorption
Dietary factors
Body iron stores
Erythropoiesis
75
Dietary iron levels are sensed by...
The villi of enterocytes
76
Name three control mechanisms that affect the regulation of iron absorption
Regulation of transports
Expression of receptors
Chemicals
77
What is hepcidin?
Negative regulator of iron absorption
78
Where is hepcidin secreted?
Liver
79
Where is hepcidin excreted?
Kidneys
80
When is synthesis of hepcidin...
I) increased
II) decreased
In iron overload
When there is high erythropoietic activity
81
How does hepcidin work to reduce iron absorption?
Stops the action of ferroportin ---> less iron absorption from the gut/less iron release from macrophages
82
Hepcidin leads to a build-up of non-functional iron in... (2)
Enterocytes/Macrophages
83
Is iron deficiency a symptom or a diagnosis?
Symptom
84
Iron deficiency results from either... (2)
Insufficient intake/poor absorption
Increased use
85
What is pallor?
An unhealthy pale appearance
86
Name 5 symptoms of anaemia
```
Tiredness
Pallor
Reduced exercise tolerance
Angina
Palpitations
```
87
What causes the pallor/reduced exercise tolerance seen in anaemia?
The reduced oxygen carrying capability of RBCs
88
Name two cardiac symptoms of anaemia
Angina
| Palpitations
89
Name 5 signs on examination you may see with an anaemic patient
Pallor
Tachycardia
Increased respiratory rate
Epithelial changes - glossy tongue, spooning of nails
90
Give two examples of epithelial changes you may see in someone with anaemia
Glossy tongue
| Spooning of nails
91
Name three blood film features seen in iron deficiency
Hypochromic RBCs
Microcytic RBCs
Anisopoikilocytosis
92
What are hypochromic RBCs? How do they appear under a microscope?
RBCs with a low Hb count
They appear pale
93
What are microcytic RBCs? What causes microcytic RBCs to be produced in iron deficiency?
Small RBCs
RBCs divide until they have a sufficient iron concentration
94
What is anisopoikilocytosis of RBCs?
Change in size and shape of RBCs
95
What is the most commonly used measure of iron status?
Ferritin
96
What do reduced levels of ferritin in an individual indicate?
Iron deficiency
97
Why might normal/increased levels of ferritin not exclude iron deficiency?
Ferritin is an acute phase protein and is seen in increased levels in inflammation/malignancy
98
What other test can be used to test for iron deficiency other than ferritin?
CHR
99
What does CHR test for? What is the problem with this test?
Tests for functional iron deficiency (amount getting to erythroid cells)
Levels stay low with thalassaemia
100
Name 5 treatments for iron deficiency
```
Dietary advice
Oral iron supplements
Intramuscular iron injections
IV iron
Blood transfusion
```
101
IV iron is usually avoided as a treatment for iron deficiency in the case of...
Anaphylactic shock
102
When is transfusion given as a treatment for iron deficiency?
In severe anaemia with imminent cardiac compromise
103
What increase in Hb levels should you expect to see when iron deficiency is treated?
20 g/L in 3 weeks
104
Name two consequences of iron excess
Fe2+ can produce highly reactive hydroxyl and lipid radicals --->>> damage to membranes, nucleic acids and proteins
Excess iron deposited in tissues - haemochromatosis
105
What is haemochromatosis?
Disorder of iron excess resulting in end organ damage due to iron deposition
106
Name 6 consequences of haemochromatosis
```
Liver cirrhosis
Diabetes mellitus
Hypogonadism
Cardiomyopathy
Arthropathy
Skin pigmentation
```
107
What are two types of haemochromatosis?
Hereditary haemochromatosis
| Transfusion associated haemosiderosis
108
In which way is hereditary haemochromatosis inherited?
Autosomal recessive
109
Which mutation leads to hereditary haemochromatosis?
Mutation of HFE gene on chromosome 6 (p arm)
110
What is the normal function of the HFE protein?
How will hereditary haemochromatosis affect this?
Competes with transferrin for binding to the transferrin receptor
Mutated HFE protein ---> Can't bind/compete ---> Too much iron enters cells
111
What is the treatment hereditary haemochromatosis?
Venesection
112
What is venesection?
Removal of blood by IV
113
A normal bag of blood contains ~400ml. How much iron will be present in this?
200mg of iron
114
What happens in transfusion associated haemosiderosis?
Blood transfusion results in a gradual accumulation of iron and iron overload
115
In what conditions may transfusion associated haemosiderosis be seen?
In transfusion dependent anaemias
116
What is the treatment for transfusion associated haemochromatosis? (2)
Limiting transfusion
Iron chelating agents
117
What is anaemia?
Inability of RBCs to deliver enough oxygen to the tissues
118
Anaemia can be as a result of not enough... (2)
RBCs
| Hb in RBCs
119
What is the function of the RES?
Recycles and removes dead/damaged blood cells
120
What is the main organ of the RES?
Spleen
121
Name two important cells of the RES
Macrophages
| Kupffer cells
122
Name two causes of loss of red cells that can result in anaemia
Reduced erythropoiesis
| Dyserythropoiesis
123
What are three causes of reduced erythropoiesis?
Chronic kidney disease
Empty bone marrow due to chemotherapy/toxic insult
Bone marrow infiltrated by cancer cells/fibrous tissue
124
How does chronic kidney disease result in reduced erythropoiesis?
What is the treatment for someone with chronic kidney disease causing anaemia?
Stops making erythropoietin ---> anaemia
Give erythropoietin
125
Name two things that can cause 'empty bone marrow' and as a result reduced erythropoiesis and anaemia
Chemotherapy
| Toxic insult - e.g. Parvovirus
126
Why can 'empty' bone marrow result in reduced erythropoiesis?
Bone marrow is unable to respond to erythropoietin
127
Name two diseases that can result in dyserythropoiesis
Anaemia of Chronic Disease
| Myelodysplastic Syndromes
128
In what sort of conditions is anaemia of chronic disease seen? (2)
Inflammatory conditions
| Chronic Infections
129
Name three features of anaemia of chronic disease
Iron stored in macrophages is not released for use in bone marrow
Circulating red cells have a reduced lifespan
Bone marrow shows a lack of response to erythropoietin
130
Is Anaemia of Chronic Disease due to iron deficiency?
No
131
The anaemia seen in Anaemia of Chronic Disease is of which type?
Can be microcytic, normocytic or macrocytic
132
What is the treatment for Anaemia of Chronic Disease?
No specific treatment - treat the underlying cause
133
How will CRP and ferritin levels be affected in Anaemia of Chronic Disease?
Often raised
134
In which people is myelodysplastic syndrome seen?
Elderly
135
What happens in myelodysplastic syndrome?
Production of abnormal clones of marrow stem cells
136
How is diagnosis of myelodysplastic syndrome made?
Microscopy of blood/bone marrow cells - RBCs will be defective and large (macrocytic)
137
What type of anaemia will be seen in myelodysplastic syndromes?
Macrocytic anaemia that gets progressively worse
138
Why is progressive anaemia seen in myelodysplastic syndromes?
Cells are prematurely destroyed by the RES
139
What is the treatment for anaemia as a result of myelodysplastic syndromes? (2)
Chronic transfusions of red cells
| Stem cell transplant
140
Define megaloblastic anaemia
Anaemia due to deficiency in building blockers for DNA synthesis as a result of vitamin B12 and/or folate deficiency
141
What is B12 and folate essential for?
Nuclear divisions and nuclear maturation (DNA synthesis)
142
A deficiency in B12/Folate will result in...
Nuclear maturation/cell divisions that lag behind cytoplasmic development
143
How will the RBCs in megaloblastic anaemia appear?
Large (macrocytic) with large nuclei and open chromatin
144
Vitamin B12 is synthesised by...
Microorganisms
145
B12 can be stored in the body for how long?
Years
146
How is vitamin B12 acquired in the diet?
By eating foods of animal origin
147
How is vitamin B12 absorbed and transported to the bone marrow?
Combined with intrinsic factor (glycoprotein)
IF-B12 complex bind to cells in the ileum
B12 absorbed, IF destroyed
B12 binds to transcobalamin in the portal blood
148
Which cells of the body produce intrinsic factor?
Parietal cells of the stomach
149
Where is vitamin B12 absorbed in the gut?
Ileum (bound to IF - IF destroyed, B12 absorbed)
150
Which plasma protein does B12 bind to in the portal blood?
Transcobalamin
151
Name 4 causes of B12 deficiency
Dietary deficiency
Pernicious anaemia
Disease of the terminal ileum
Congenital deficiency of transcobalamin
152
What is pernicious anaemia?
Where autoimmune disease affects parietal cells of the stomach causing a lack of intrinsic factor ---> B12 deficiency ---> anaemia
153
Apart from an autoimmune disease, in which other cases may pernicious anaemia be seen?
In case of gastrectomy
154
Name a disease of the terminal ileum that can cause B12 deficiency
Crohn's disease
155
In which foods is folate present?
Most foods - particularly yeast, liver and leafy greens
156
Folate is particularly present in which foods? (3)
Liver
Leafy greens
Yeast
157
Where does absorption of folate in the gut take place?
In the duodenum and jejunum
158
What happens to dietary folate that is consumed?
It is all converted to methylTHF ---> circulates in the plasma
159
Folate is essential for...
DNA synthesis
160
What is dietary folate converted to in the body?
MethylTHF
161
Name 5 causes of folate deficiency
```
Dietary deficiency
Increased use
Proximal small bowel disease
MethylTHF drugs
Alcoholism
```
162
When may increased use of folate be seen (possibly resulting in a deficiency)?
During pregnancy
163
Give an example of a proximal small bowel disease
Crohn's disease
164
How will the blood film in vitamin B12/folate deficiency appear?
Macrocytic red cells
| Hyper-segmented neutrophils
165
How do RBCs appear in B12/folate deficiency?
How do neutrophils appear in B12/folate deficiency?
Macrocytic
Hyper-segmented
166
As B12/Folate deficiency progresses what may be seen?
Pancytopenia
167
What is vitamin B12 deficiency associated with (other than anaemia)?
Neurological disease
Depression
Dementia
168
In sickle cell disease, which gene is mutated?
The gene coding for the B-globin chain
169
What mutation is seen in sickle cell disease? In which position?
Valine ---> Glutamate
6th amino acid
170
What happens to HbS in RBCs?
It polymerises, causing an inflexible sickled shape
171
What happens if someone is a HbS carrier and has sickle cell trait?
They will have mild, asymptomatic anaemia and be protected against malaria
172
How does HbS give up its oxygen compared to HbA?
HbS gives it up readily
173
What clinical problems can result from sickle cell disease? (3)
Blocking of small blood vessels
Pain
Problems affecting chest/spleen
174
Beta-thalassaemia is most common in which part of the world?
South Asia
| Mediterranean
175
Alpha-thalassaemia is most common in which part of the world?
Far East
176
How will red blood cells appear in someone with thalassaemia? Why?
Hypochromic (Pale)
Microcytic
Due to low intracellular levels of Hb
177
There is increased destruction of red cells in the _________ due to their incorrect globin chain make-up
Spleen/Bone Marrow
178
Name three compensatory mechanisms/consequences of thalassaemia
Extramedullary haemopoiesis
Stimulation of erythropoietin
Iron overload
179
What is extramedullary haemopoiesis? What can it result in?
Where there is an attempt to produce more blood cells out of the bone marrow into the bone cortex
Impaired growth/skeletal abnormalities
180
Why might iron overload be seen in someone with thalassaemia?
They receive transfusions and may have excessive absorption of dietary iron as well
181
Name 4 treatments for thalassaemia
Transfusions
Iron chelation
Folic acid
Stem cell transplantation
182
When is onset of beta-thalassaemia? Why at this time?
6-9 months after birth
There is a switch from HbF to HbA
183
Is onset of a-thalassaemia before or after birth?
Before birth
184
What condition can result from abnormalities of the proteins making up the red cell membrane?
Anaemia
185
Name two inherited abnormalities of the structure of RBCs (as a result of their membrane proteins)
Hereditary spherocytosis
| Hereditary elliptocytosis
186
What happens to the shape of RBCs in hereditary elliptocytosis?
What happens to the shape of RBCs in hereditary spherocytosis?
Elliptical shaped
Sphere shaped
187
Name three things that cause structural abnormalities to RBCs (acquired abnormalities)
Mechanical damage to red cells
Burns
Drowning
188
Why do abnormalities in the structure of RBCs cause anaemia?
Leads to RBCs being removed by the RES at a higher rate than normal ---> Anaemia
189
Give an example of an enzyme that if deficient in RBCs can result in anaemia
Glucose-6-phosphate dehydrogenase
190
How can acute blood loss (trauma/haemorrhage) cause anaemia?
Hypovolaemic shock ---> Anaemia
191
Name two causes of chronic blood loss that can result in anaemia
Excessive menstruation
| Gastric ulceration
192
Anaemia due to blood loss can present as which type of anaemia? Why?
Microcytic
Iron deficient state in the body due to bleeding
193
Haemolytic anaemia is caused by...
What are two types of haemolytic anaemia?
The destruction of red blood cells
Intravascular
Extravascular
194
What is intravascular haemolytic anaemia?
What is extravascular haemolytic anaemia?
Occurs within blood vessels
Occurs outside blood vessels and in the RES by macrophages
195
What happens in autoimmune haemolytic anaemia?
Autoantibodies (IgG) bind to red cell membrane protein cause their destruction
196
What three things will be seen in someone with autoimmune haemolytic anaemia?
Increased reticulocytes
Raised bilirubin (jaundice)
Increased LDH
197
What are reticulocytes?
Immature RBCs
198
How is anaemia classified (3 ways)?
By mechanism
By size
By presence or absence of reticulocytosis
199
What value do microcytic RBCs take?
What value do macrocytic RBCs take?
< 80fl
> 100fl
200
Patients with overproduction of blood cells due to myeloproliferative disorders often have a mutation in a copy of which gene? On which chromosome?
JAK2 Gene
Chromosome 9
201
How are levels of blood cells affected in Polycythaemia Vera?
There are too many red cells
202
What is polycythaemia? What investigation can indicate polycythaemia?
A group of varied disorders with an increase in circulating red cells
Measurement of the haematocrit
203
How will the haematocrit is someone with Polycythaemia Vera be affected?
Will be persistently raised
204
What is haematocrit?
The ratio of the volume of RBCs against the total blood volume
205
How does Polycythaemia Vera affect the consistency of blood?
Thick, concentrated blood
206
What haematocrit value will indicate Polycythaemia Vera?
Raised
> 0.52 - MEN
> 0.48 - WOMEN
207
As well as a high haematocrit how else can Polycythaemia Vera be diagnosed?
By a raised cell mass (>25%)
208
What is relative polycythaemia?
Where there is normal red cell mass but lower plasma volume
209
What is absolute polycythaemia?
Where there is increased cell mass
210
Name 4 clinical features of polycythaemia
Arterial thrombosis
Venous thrombosis
Haemorrhage into skin/GI tract
Gout
211
Name two treatments for Polycythaemia Vera
Venesection
| Aspirin (75 mg)
212
Why is venesection carried out in the management of Polycythaemia Vera?
Why is aspirin carried out in the management of Polycythaemia Vera?
Maintains correct haematocrit
Thins blood
