Case 14 flashcards
1
Q
What are thehistology and electrophoresis characteristics of beta thalassaemia trait?
A
Asymptomatic hypochromic microcytic anaemia with high RCC, target cells on blood smear, and elevated HbA2.
2
Q
What is the most common form of beta thalassaemia trait?
A
Beta thalassaemia trait.
3
Q
What are the symptoms of beta thalassaemia trait?
A
Mild anaemia, target cells on blood smear, and elevated HbA2.
4
Q
How is beta thalassaemia trait diagnosed?
A
By Hb electrophoresis/HPLC showing elevated HbA2.
5
Q
What is the treatment for beta thalassaemia trait?
A
It does not require treatment.
6
Q
What is thalassaemia intermedia?
A
It is a moderate severity form of thalassaemia that is less transfusion dependent.
7
Q
What are the complications of thalassaemia intermedia?
A
Bone deformities and iron overload.
8
Q
What is sickle cell trait?
A
It is the heterozygote form of sickle cell anaemia with normal life expectancy.
9
Q
What causes sickle cell disease?
A
Homozygosity for the HbSS mutation in the β globin gene.
10
Q
What happens to deoxygenated HbS?
A
It polymerises and forms insoluble aggregates that distort RBC shape.
11
Q
Describe what is a sickle cell disease?
A
Transfusion dependent anaemia, painful crises, and infarctive episodes.
12
Q
How is sickle cell anaemia diagnosed?
A
By FBC and PB smear showing sickle cells and Hb electrophoresis/HPLC.
13
Q
What are the complications of sickle cell anaemia?
A
Painful episodes, infections, neurological complications, pulmonary problems, gallstones, leg ulcers, glomerular injury, aplastic crises, and splenic sequestration.
14
Q
What is the treatment for sickle cell anaemia?
A
Immunisation, prophylactic antibiotics, folate supplementation, urgent treatment of infections, and transfusion as needed.
15
Q
What does RBC metabolism require energy for?
A
Cationic balance, RBC shape, membrane integrity, maintaining functional Hb, and 2,3 DPG formation.
16
Q
What is the main source of energy for RBC metabolism?
A
Anaerobic glycolysis.
17
Q
What is the role of the Rapoport Luebering shunt?
A
To form 2,3 DPG/BPG from glucose 6 phosphate.
18
Q
What is the most common hereditary RBC enzymopathy?
A
Glucose 6 Phosphate Dehydrogenase deficiency (G6PD deficiency).
19
Q
What is the inheritance pattern of G6PD deficiency?
A
X-linked recessive.
20
Q
What is the clinical manifestation of G6PD deficiency?
A
Oxidative injury to RBC membrane and contents resulting in haemolysis.
21
Q
What is the significance of G6PD deficiency?
A
It results in decreased NADPH synthesis and inability to maintain GSH.
22
Q
What causes acute haemolytic episodes in G6PD deficiency?
A
Infection, fava bean exposure, and oxidant drugs.
23
Q
How is G6PD deficiency diagnosed?
A
By measuring enzyme activity (not during acute haemolytic episode).
24
Q
How is G6PD deficiency treated?
A
By avoiding oxidant drugs and promptly managing infections.
25
What are the protein defects that result in hereditary spherocytosis?
Defects affecting vertical interactions between the membrane skeleton and lipid bilayer.
26
What is the most common non-immune haemolytic anaemia in Caucasians?
Hereditary spherocytosis.
27
What causes the spherical shape of RBCs in hereditary spherocytosis?
Reduced deformability due to defective interaction with membrane.
28
What is the treatment for hereditary spherocytosis?
Folate supplementation and splenectomy if severe.
29
What are the reasons for splenomegaly in some anaemias?
Congestion, infiltration, and hypertrophy/increased work.
30
What can cause splenomegaly due to congestion?
Portal hypertension due to any cause.
31
What can cause splenomegaly due to infiltration?
Haematological malignancy, such as myeloproliferative disorders and acute leukaemia.
32
What can cause splenomegaly due to hypertrophy/increased work?
Haemolysis.
33
What is the main function of mitochondria in erythroid cells?
To be used in the formation of haem.
34
What happens to apo transferrin after the formation of haem?
It is released.
35
Is there a known mechanism for iron excretion?
Apart from the sloughing of epithelial cells, there is no known mechanism for iron excretion.
36
Where does most of the circulating iron come from?
Most circulating iron is derived from iron already within the system.
37
How is iron mainly recovered from senescent red blood cells?
Old and damaged RBCs are phagocytosed by macrophages, mainly in the spleen, and are lysed, the haem catabolized (haemoxygenase) and the iron released.
38
What happens to some of the iron in macrophages after the phagocytosis of RBCs?
Some of the iron remains in the macrophage as ferritin.
39
How is most of the iron released after the phagocytosis of RBCs?
Most of the iron is released via ferroportin into circulation, where it is immediately oxidised by caeruloplasmin and picked up by transferrin.
40
How much iron is turned over by RBCs every day?
1% of RBCs turn over every day (= 25mg iron).
41
What is ferritin?
Ferritin is the storage form of iron. It is an iron (Fe3+) complexed with apoferritin.
42
How are ferritin levels regulated?
Ferritin levels are regulated by iron. When body levels of iron are low, ferritin levels are proportionally low.
43
What instances can increases ferritin levels?
Ferritin levels increase with inflammation and in liver disease, released from damaged hepatocytes.
44
What is haemosiderin?
Haemosiderin is a water-insoluble form of iron, poorly understood. It is a complex of ferritin, denatured ferritin, and other material.
45
Where is haemosiderin commonly found?
Haemosiderin is most commonly found in macrophages in tissues.
46
What is the main function of hepcidin?
Hepcidin is the regulator of iron status. It prevents the uptake of iron via the GIT and also prevents the release of iron from storage.
47
What stimulates the secretion of hepcidin?
Hepcidin is secreted in response to increased iron stores and inflammation (IL-6).
48
What suppresses hepcidin secretion?
Hypoxia and increased RBC production (erythropoiesis) suppress hepcidin secretion.
49
What happens when hepcidin binds to ferroportin?
It causes internalization and proteosomal degradation of the transporters, preventing the release of iron into the circulation.
50
Where is iron lost when hepcidin inhibits ferroportin?
Iron is lost into the stool during epithelial cell shedding, resulting in decreased uptake in the GIT.
51
Where is iron stored when hepcidin inhibits ferroportin?
Iron is stored in macrophages and hepatocytes.
52
What are the stimuli for hepcidin synthesis?
Iron overload and inflammation (IL-6) stimulate hepcidin synthesis.
53
What inhibits hepcidin synthesis?
Hypoxia, iron deficiency, and erythropoiesis inhibit hepcidin synthesis.
54
What are the consequences of decreased hepcidin?
Increased uptake of iron (GIT) and increased release from RES, leading to increased iron availability and chronically to iron overload (haemochromatosis).
55
What are the consequences of increased hepcidin?
Decreased uptake from GIT, decreased iron release, decreased iron availability, and chronically leads to decreased availability for erythropoiesis (anaemia of chronic disease).
56
What is the gold standard for investigating iron status?
The gold standard is bone marrow.
57
Which stain is used to identify iron in the bone marrow?
Prussian Blue staining is used to identify iron in the bone marrow.
58
What is the formula for calculating MCH?
MCH = Hb / RBC
59
What is the formula for calculating MCHC?
MCHC = Hb / Hct
60
What does RDW indicate?
RDW is an indicator of the distribution of individual RBC sizes in a sample
61
How is the RBC uniquely adapted for its function?
The RBC is anucleate and specialized for facilitating gaseous exchange and transporting O2, CO2, and NO
62
What is the size of a normocytic RBC compared to a lymphocyte nucleus?
The whole normocytic RBC is smaller than the nucleus of a lymphocyte
63
What are some acquired causes of anemia?
Acquired causes of anemia can include iron deficiency, blood loss with replacement of plasma volume, and red cell defects
64
What are some primary or inherited red cell defects that can lead to anemia?
Membrane or cytoskeleton defects, abnormalities of red cell metabolism, and abnormal hemoglobin synthesis can lead to anemia
65
What is the role of the Embden-Meyerhoff pathway in red cells?
The Embden-Meyerhoff pathway is an anaerobic glycolytic pathway that provides energy for maintenance of red cell volume, shape, and flexibility
66
What is the key enzyme involved in the Embden-Meyerhoff pathway?
The key enzyme is pyruvate kinase
67
What is the role of the hexose monophosphate shunt in red cells?
The hexose monophosphate shunt produces NADPH and reduces glutathione to protect RBC against oxidative stress
68
What is the key enzyme involved in the hexose monophosphate shunt?
The key enzyme is G6PD
69
What is the function of hemoglobin in RBCs?
Hemoglobin is a specialized iron-containing protein integral for O2 transport in RBCs
70
What are some requirements for effective hemoglobin synthesis?
Effective hemoglobin synthesis requires iron, folate, and Vitamin B12
71
How many O2 molecules can each heme group in hemoglobin bind?
Each heme group can bind a single O2 molecule, totaling four O2 molecules per hemoglobin molecule
72
What causes ineffective hemoglobin production?
Mutations in relevant genes can cause reduced or absent globin chain synthesis, leading to ineffective hemoglobin production
73
What are thalassemias and sickle cell anemia examples of?
Thalassemias are quantitative abnormalities of globin chain synthesis, while sickle cell anemia is a qualitative abnormality of hemoglobin
74
What is the major regulator of the O2 affinity of hemoglobin?
2,3-DPG (2,3-diphosphoglycerate) is the major regulator of the O2 affinity of hemoglobin
75
What is the P50 in the context of the dissociation curve of hemoglobin?
P50 is the partial pressure at which hemoglobin is 50% saturated with O2 (26.6mmHg for normal blood)
76
What can cause a left shift or right shift of the dissociation curve of hemoglobin?
Certain conditions and hemoglobins can cause a left shift (increased O2 affinity) or right shift (decreased O2 affinity) of the dissociation curve
77
What does anaemia indicate?
Anemia indicates low hemoglobin and insufficient RBC mass to adequately deliver O2 to peripheral tissues
78
What must be considered during FBC to determine anaemia?
During FBC, WBC, Hb, and platelets must be considered instead of RBCs themselves
79
Is anaemia itself a disease?
No, anaemia is a feature of an underlying disease and must be treated by identifying and addressing the underlying cause
80
What are the factors that increase polymerization of HbS molecules?
Deoxygenation, higher HbS concentration, acidosis
81
What are the factors that decrease polymerization of HbS molecules?
Decrease in 2,3 BPG, increase in HbF and HbA2; alpha thal, hydration
82
What are the causes of sickle cell disease/anaemia/trait?
RBC membrane damage, haemolysis - intra and extra vascular, veno-occlusion, hypercoagulable state
83
What are the different sub-phenotypes of sickle cell disease?
Vaso-occlusive, haemolysis and vasculopathy, high HbF, pain
84
What are the clinical investigations for sickle cell disease?
FBC: normocytic anaemia, peripheral smear: sickle cells, nucleated RBCs, target cells, Howell-Jolly bodies, HbS on electrophoresis, low HbA2
85
What are the treatment options for sickle cell disease?
Prevention of complications (education, routine health management, nutrition, antibiotics & vaccinations), blood transfusions, disease modifying therapies, symptomatic treatment (pain, antibiotics, transfusions, rehydration), curative (stem cell transplantation, gene therapies)
86
What is the life expectancy for individuals with sickle cell disease in different regions?
UK median survival is 67 years, Tanzania median survival is 33 years, Sub-Saharan Africa U5MR for children with SCD is 50 - 90%
87
What are the components of counselling for sickle cell disease?
Information of the condition, psycho-social support, recurrence risk, familial implications, genetic testing, carrier screening, prenatal testing
88
What is thalassemia?
Thalassemias are hereditary abnormalities of haemoglobin production characterized by a quantitative deficiency of alpha or beta globin gene
89
What are the common geographical regions where thalassemia is prevalent?
Mediterranean, SE Asia, Africa in malaria areas
90
What are the pathogenic mechanisms of thalassemia?
Oxidative injury, membrane damage, abnormal hydration, reduced deformability
91
What are the genetics of alpha thalassemia?
Each chromosome 16 has 2 alpha genes, involving 1-4 of the genes, autosomal recessive, phenotype dependent on mutations
92
What are the clinical features of thalassemia?
Anaemia, complications of haemolysis (jaundice, hepatosplenomegaly), complications of extramedullary haematopoiesis (skeletal changes, growth deficiency), complications of iron overload (endocrine, cardiovascular), leg ulcer, thrombosis
93
What are the treatment options for thalassemia?
Manage anaemia (transfusion, dietary care, supplements), assessment of iron stores and chelation therapy, splenectomy, monitor/ manage complications, stem cell transplant or gene therapy (mainly beta thalassemia)
94
What is the genotype and phenotype of alpha thalassaemia for Africa (equator)?
Genotype: alpha-/alphaalpha, Phenotype: silent carrier, normal
95
What is the genotype and phenotype of alpha thalassaemia for SE Asia?
Genotype: alpha-/alpha-, Phenotype: thalassemia (asymptomatic, mild microcytic anaemia)
96
What is the genotype and phenotype of alpha thalassaemia for the Mediterranean trait?
Genotype: alpha-/alpha-, Phenotype: HbH (mild to moderate microcytic anaemia)
97
What is the genotype and phenotype of alpha thalassaemia when there are no alpha globin genes?
Genotype: --/--, Phenotype: Hb Barts (Hydrops fetalis)
98
What are the blood tests used to investigate iron deficiency?
Serum iron, serum transferrin, % saturation transferrin, serum soluble transferrin receptors, serum ferritin, serum hepcidin
99
What is the normal range for serum iron?
9 - 30 umol/L
100
How is serum iron affected by diet?
It is affected by diet
101
What happens to serum iron in iron deficiency?
It is decreased
102
What happens to serum iron in iron overload?
It is increased
103
What is the transferrin concentration in iron deficiency?
It is increased
104
What is the transferrin concentration in iron overload?
It is decreased
105
What is the % saturation of transferrin in iron deficiency?
It is decreased
106
What is the % saturation of transferrin in iron overload?
It is increased
107
What is the normal amount of transferrin that can bind to iron?
Up to 60 umol/L
108
What is the normal range for % saturation of transferrin?
20 - 45%
109
What is the serum ferritin concentration in iron deficiency?
It is decreased
110
What is the serum ferritin concentration in iron overload?
It is increased
111
What happens to serum ferritin concentration in inflammation?
It is increased
112
What happens to soluble transferrin receptors in iron deficiency?
They are increased
113
What happens to soluble transferrin receptors in iron overload?
They are decreased
114
What happens to soluble transferrin receptors in inflammation?
They remain unchanged
115
What are the diagnostic indicators for simple iron deficiency anemia?
Low serum iron, microcytic hypochromic anemia, low ferritin, low % saturation of transferrin, high soluble transferrin receptors
116
What are the common causes of iron deficiency anemia?
Blood loss, frequent pregnancies, malabsorption
117
What is the cause of anemia of chronic disease?
Inadequate erythropoietin production, inhibition of erythroid proliferation, and sequestration of iron into the RES
118
What causes the sequestration of iron in anemia of chronic disease?
Stimulation of hepcidin secretion by IL-6
119
What are the biochemical results of anemia of chronic disease?
Low plasma iron, normal or increased ferritin, normal or low transferrin, and normal % saturation of transferrin
120
What is the challenge in diagnosing anemia of chronic disease?
Identifying patients with concomitant iron deficiency
121
What is a good indicator of inflammation?
C-Reactive Protein (CRP) level
122
What is the recommended assessment for functional vs real iron deficiency with and without acute phase response?
Combined measurements of CHr, sTfR, and Ferritin with calculation of a sTfR/log Ferritin ratio
123
What can cause cardiac arrhythmias if cold blood is rapidly infused?
Infusing cold blood rapidly can cause cardiac arrhythmias.
124
How are platelets stored and why can they be transfused quickly?
Platelets are stored at room temperature and can be transfused quickly because of this.
125
How are plasma products prepared before transfusion and why?
Plasma products are frozen and thawed to body temperature before use, allowing for quick transfusion.
126
What vital signs should be recorded before starting a blood transfusion?
The vital signs of the patient should be recorded before beginning the transfusion.
127
How long should the patient be monitored after starting a transfusion?
The patient should be carefully monitored for the first 30 minutes of the transfusion.
128
What should be watched for during the first 30 minutes of a transfusion?
Any adverse symptoms suggestive of a transfusion reaction should be watched for.
129
What are dietary sources of Folic acid?
Leafy vegetables, legumes, and egg yolks are dietary sources of Folic acid.
130
What is the biological role of folate?
The biological role of folate is to carry 1-carbon (methyl) fragments for DNA/RNA synthesis and methylation reactions.
131
Which cells are affected first by folate deficiency?
Rapidly dividing cells, such as blood cell precursors in the bone marrow, are affected first by folate deficiency.
132
What are the manifestations of folate deficiency?
Manifestations include macrocytic anemia with megaloblastic marrow, malabsorption in intestinal mucosal cells, and neural tube malformation in growing fetuses.
133
Who is at risk of folate deficiency?
People with intestinal disease, malabsorption syndromes, and folate-poor diets are at risk of folate deficiency.
134
What is the role of folate in the production of nuclear bases?
Folate is needed for the synthesis of nuclear bases for DNA/RNA, but its deficiency can cause megaloblastic anemia and cell division to stop.
135
What happens when B12 deficiency occurs?
In B12 deficiency, available folate gets trapped as 5-methyl-THF, leading to megaloblastic anemia and potential neurological damage.
136
Why does B12 deficiency cause megaloblastic anemia?
B12 deficiency causes megaloblastic anemia because folate becomes trapped as methyl-THF, resulting in the inability to make nuclear bases for cell division.
137
What happens when SAM levels are low?
When SAM levels are low, MTHFR is disinhibited and available folate is diverted to MTHF, leading to megaloblastic anemia if folate levels are already low.
138
What is the priority in B12 deficiency?
Cycle 2, which prevents neurological degeneration, is prioritized in B12 deficiency.
139
What occurs in B12 deficiency even with adequate folate levels?
In B12 deficiency, folate essentially becomes trapped as methyl-THF, causing 'functional' folate deficiency and megaloblastic anemia.
140
What is the result of B12 deficiency when SAM production decreases?
When SAM production decreases due to B12 deficiency, methionine cannot be regenerated, leading to neurological disease.
141
What is targeted in the treatment of certain diseases?
Folate pathways in bacteria, protozoa, and humans are targeted in the treatment of certain diseases.
142
What are some examples of organisms that synthesize their own folate?
Plants, bacteria, and parasitic organisms like malaria and toxoplasmosis synthesize their own folate.
143
What is the role of methionine in the CNS?
Methionine is an essential methyl donor in the CNS for the synthesis of neurotransmitters and phospholipids used to make myelin.
144
What happens in B12 deficiency even with adequate folate levels?
In B12 deficiency, folate becomes trapped as methyl-THF, causing 'functional' folate deficiency and potentially leading to megaloblastic anemia.
145
What is the effect of low methionine synthase activity?
Low methionine synthase activity can lead to reduced SAM production, impacting essential methylation reactions in the CNS.
146
What are the earliest symptoms of dorsal column involvement?
The earliest symptoms are paresthesia, observed in the form of tingling, burning, and sensory loss of the distal extremities.
147
How does loss of proprioception usually present?
Loss of proprioception usually presents as a difficulty in maintaining balance in the absence of visual cues.
148
What are the symptoms of lateral corticospinal tract dysfunction?
The symptoms include muscle weakness, hyperreflexia, and spasticity.
149
What are the other signs of upper motor neuron damage?
Other signs include Babinski sign, spasticity, and possible progression to paraplegia or quadriplegia.
150
What causes gait abnormalities in the form of sensory ataxia?
Spinocerebellar tract degeneration causes gait abnormalities in the form of sensory ataxia.
151
What are the late signs in diagnosing B12 deficiency?
Measuring B12 in plasma, checking for megaloblastic anemia, and increased LDH 1 isoenzymes.
152
What are the early biochemical manifestations of B12 deficiency?
Elevated total homocysteine and elevated urinary and plasma methyl-malonic acid.
153
What is the recommended method when measuring Red Cell Folate and B12 levels?
Always measure Red Cell Folate AND B12 together.
154
What are some possible causes for B12 deficiency?
Possible causes include diet, gastric mucosal integrity, Pernicious Anemia, distal Ileum investigation, and celiac disease screening.
155
What is the Schilling test used for in B12 deficiency diagnosis?
The Schilling test is used to determine the cause of B12 deficiency by assessing absorption and factors like PA or bacterial overgrowth.
156
What are the indicators of intravascular hemolysis?
Unconjugated bilirubin elevation, increased urobilinogen on urine dipstick, elevated LDH 1 and AST in plasma, decreased haptoglobin levels, visible schistocytes, and potential hemoglobinuria.
157
What are the common causes of intravascular hemolysis?
Causes include autoimmune factors, mechanical stress on red cells, infectious agents like malaria, inherited red cell fragility disorders, and osmotic factors.
158
What are the common causes of extravascular hemolysis?
Hypersplenism, large hematomas, and acute pancreatitis are common causes of extravascular hemolysis.
159
What are the clinical signs and consequences of hemolysis?
Clinical signs include pallor, mild jaundice, red urine in cases of intravascular hemolysis, and the potential for Acute Renal Failure.
160
What is ex vivo hemolysis and what causes it?
Ex vivo hemolysis is red cell lysis during blood draw, often caused by poor phlebotomy technique.
161
How is intravascular hemolysis differentiated from ex vivo hemolysis?
Intravascular hemolysis causes specific indicators like increased bilirubin, urobilinogen, LDH 1, decreased haptoglobin, schistocytes, and potential hemoglobinuria.
162
What are some extremities that can be affected by certain conditions?
Fingers, noses, and ears
163
What are some conditions associated with extremities?
Acrocyanosis, Raynaud’s phenomenon, Livido reticularis, severe pain on eating/drinking cold things, cutaneous necrosis/ulcers
164
What antibodies are classically associated with syphilis?
Donath-Landsteiner antibodies
165
In what conditions can Donath-Landsteiner antibodies arise?
Other conditions like chickenpox
166
How do Donath-Landsteiner antibodies behave under different temperatures?
They bind to the P-group antigen at cold temperatures but do not dissociate at higher temperatures
167
What is the primary immunoglobulin class of the antibodies?
IgG
168
What is the consequence of Donath-Landsteiner antibodies fixing complement in the circulation?
They cause intravascular haemolysis
169
What are some clinical presentations of paroxysmal cold hemoglobinuria?
Dark urine, back or leg pain, abdominal cramping, weakness, malaise, nausea, vomiting, fever or chills, subsequent pallor and/or jaundice in severe cases
170
What investigations are helpful in diagnosing autoimmune hemolytic anemia?
Clinical history and examination, full blood count, smear, haemolytic screen, Coombs test/Direct Antiglobulin Test
171
What are some findings in a full blood count of autoimmune hemolytic anemia?
Decreased Hb, increased red cell distribution width, increased numbers of nucleated RBCs
172
What are some findings in a smear of autoimmune hemolytic anemia?
Spherocytes, fragments
173
What are some markers in the haemolytic screen for autoimmune hemolytic anemia?
Increased lactate dehydrogenase, increased bilirubin, decreased haptoglobin, increased reticulocyte count
174
What does the Coombs test/Direct Antiglobulin Test detect in autoimmune hemolytic anemia?
IgG antibodies and bound complement
175
What type of cold agglutinin disease is generally C3d positive?
Cold agglutinin disease
176
What type of warm autoimmune hemolytic anemia is generally IgG positive?
Warm AIHA
177
What condition is generally positive for both IgG antibodies and bound complement?
Paroxysmal cold hemoglobinuria
178
What are some possible secondary causes of AIHA?
Infections (EBV, atypical bacteria, syphilis), autoimmune conditions (SLE), malignancies (B-cell clonal disorders)
179
What is the treatment for most cold agglutinin diseases and paroxysmal cold hemoglobinuria?
Supportive treatment until underlying condition resolves, nutrients supplementation (e.g. folate, iron), warm temperature maintenance
180
What specific treatments can be used for warm AIHA?
Corticosteroid therapy, Rituximab, complement inhibition, immunosuppression, splenectomy in severe/refractory cases
181
What are the characteristics of malaria?
Endemic in many parts of sub-Saharan Africa, South and South-East Asia, Central and South America, affecting about 3.4 billion people
182
What were the estimated malaria cases and deaths in 2018?
228 million cases worldwide, 405,000 deaths worldwide
183
Which regions have the highest risk of malaria?
Africa and South/South-East Asia
184
What is the process of haematopoiesis in the yolk sac?
Haematopoiesis in the yolk sac involves the generation of microglia and production of erythro-myeloid progenitors (EMPs) and lympho-myeloid progenitors (LMPs).
185
What is the role of the pro-definitive wave in haematopoiesis?
The pro-definitive wave generates erythro-myeloid progenitors (EMPs) and lympho-myeloid progenitors (LMPs) in the yolk sac or embryo.
186
What is the function of the definitive wave in haematopoiesis?
The definitive wave generates pre-HSCs, which mature into HSCs capable of self-renewal.
187
Where do the pro-definitive and definitive wave progenitors travel to?
The pro-definitive and definitive wave progenitors travel to the liver.
188
What types of cells are produced in the liver during haematopoiesis?
Erythrocytes, megakaryocytes, granulocytes, T and B cells, and monocyte-derived macrophages are produced in the liver.
189
What is the source of tissue-resident macrophages at birth?
EMP-derived macrophages colonize the embryo and constitute the majority of tissue-resident macrophages at birth.
190
Where does primitive haematopoiesis take place?
Primitive haematopoiesis takes place in the blood islands along the wall of the yolk sac.
191
What are the characteristics of progenitors in the yolk sac?
Progenitors in the yolk sac cannot fulfil the functions of adult-type HSC when transplanted to older individuals.
192
What types of cells are produced during primitive haematopoiesis?
Large, nucleated erythrocytes are produced during primitive haematopoiesis.
193
Where does definitive intraembryonic haematopoiesis begin?
Definitive intraembryonic haematopoiesis begins in small clusters of cells in the splanchnopleuric mesoderm associated with the ventral wall of the dorsal aorta and AGM region.
194
What are hemogenic endothelial cells and where are they located?
Hemogenic endothelial cells are found within the ventral half of the paired dorsal aortae, which are clusters of hematopoietic stem cells.
195
What is the shift in haematopoiesis from the liver to the bone marrow controlled by?
The shift in haematopoiesis from the liver to the bone marrow is controlled by cortisol secreted by the foetal adrenal cortex.
196
Which organs serve as minor sites of blood cell production?
The spleen, kidney, thymus, and lymph nodes serve as minor sites of blood cell production.
197
Which cell type is retained in the brain during haematopoiesis?
Microglia, of primitive macrophage origin, are retained in the brain as a stable and self-renewing population.
198
Which cells replace those produced during the primitive wave for WBCs?
Monocyte-derived macrophages gradually replace those produced during the primitive wave for WBCs.
199
What is the role of EMPs in haematopoiesis?
EMPs generate granulocytes, a cell type not produced during primitive haematopoiesis.
200
Where do angioblasts initially form small cell clusters?
Angioblasts initially form small cell clusters (blood islands) within the embryonic and extraembryonic mesoderm.
201
What are the causes of secondary iron overload?
Another disorder or treatment such as thalassaemia or blood transfusions.
202
What are the biochemical features of iron overload?
Increased serum iron, low transferrin, high % transferrin saturation, increased ferritin, and low hepcidin.
203
How does chronic iron overload differ from acute iron overdose?
In chronic overload, transferrin and ferritin have had time to respond.
204
What are the common causes of elevated ferritin?
Chronic inflammation, chronic alcohol consumption, liver disease, renal failure, metabolic syndrome, or malignancy.
205
How can iron overload be excluded clinically?
By conducting initial tests such as FBC, liver and renal function, and inflammatory markers.
206
What serum ferritin values indicate further investigation?
Unexplained values > 1000 uG/L.
207
How can hereditary haemochromatosis be screened?
By considering HFE mutation and checking for elevated ferritin and transferrin saturation (>45%).
208
What is the most common form of primary iron overload?
Haemochromatosis type 1.
209
What mutation is associated with haemochromatosis type 1?
Mutation in HFE protein, specifically C28Y and H63D.
210
How can primary iron overload be definitively diagnosed?
By liver biopsy with hepatic iron index/MRI quantitation and genetic screening.
211
What are the features of primary African iron overload?
Increased iron absorption from diet, accumulation of iron in RES and hepatocytes, and increased risk of liver disease and infections.
212
What are the causes of secondary iron overload?
Conditions requiring repeat blood transfusions or ineffective erythropoiesis (thalassaemia).
213
How is acute iron toxicity caused?
By acute ingestion of iron salts and organ damage due to iron-mediated oxygen free radicals.
214
What are the biochemical markers of acute iron toxicity?
Increased serum iron, normal transferrin, 100% transferrin saturation, and normal ferritin.
215
What is the treatment for acute iron toxicity?
Resuscitation and chelation with desferrioxamine.
216
What is the percentage composition of HbA, HbA2, and HbF?
HbA = 97%, HbA2 = 2%, HbF = 1%.
217
What are the two types of haemoglobinopathies?
Qualitative (sickle cell anaemia) and quantitative (thalassaemia's).
218
What are the characteristics of sickle cell disease?
Incidence in African population, carrier frequency, pathogenesis, and heterozygote advantage.
219
What is the shape and lifespan of normal RBC?
Disc-shaped, soft, easily flows through small blood vessels, and a lifespan of 120 days.
220
What is the shape of sickle RBC?
Sickle shape, rigid, often gets stuck in small blood vessels.
221
Where does absorption of iron take place?
Absorption of iron takes place in the proximal duodenum.
222
What are the two forms in which iron is taken up in the diet?
Iron is taken up in the diet in its inorganic form (Fe3+) and as myoglobin and haemoglobin.
223
How is haem iron taken up?
Haem iron is taken up via a haem-specific transporter and the Fe released from the haem inside the cell.
224
What happens to Fe3+ iron before it is taken up by the divalent metal transporter (DMT1)?
Fe3+ iron is first reduced to its Fe2+ form before it is taken up by the DMT1.
225
Which substances help convert Fe3+ to Fe2+?
Gastric acid and reducing agents (especially vitamin C and the protein DCytb) help convert Fe3+ to Fe2+.
226
Where does iron go once inside the epithelial cell of the proximal duodenum?
Once inside the epithelial cell of the proximal duodenum, iron can either be stored as ferritin or transported out of the cell via Ferroportin.
227
How is iron transported out of the cell?
Iron is transported out of the cell via a basolateral transporter called Ferroportin.
228
What happens to iron inside the cell?
Once inside the cell, iron is stored as ferritin or transported out of the cell.
229
In what form is iron transported in circulation?
Iron is transported in its ferric (Fe3+) form in circulation.
230
What happens to iron once it is in circulation?
Once in circulation, iron is oxidized to its ferric (Fe3+) form via hephaestin or caeruloplasmin.
231
What does transferrin do with iron?
Transferrin solubilizes iron, and also dampens its reactivity.
232
How much of iron binding sites on transferrin does iron occupy in normal human beings?
In normal human beings, iron occupies approximately 30% of iron binding sites on transferrin in plasma.
233
How do cells take up iron?
Cells take up iron by expressing transferrin receptors on their surfaces.
234
What happens when transferrin receptors bind with transferrin?
Transferrin laden with two ferric irons binds transferrin receptors and is endocytosed.
235
Where does iron go once it is inside the endosome?
Once endocytosed, iron is reduced and then transported out of the endosome via DMT1 into the cytoplasm.
236
What are the two options for iron once it is in the cytoplasm?
Iron is either stored as ferritin (non-erythroid cells) or taken up into cells.
237
What does Rh positive refer to?
Presence of the D antigen
238
What does Rh negative refer to?
Absence of the D antigen
239
Can other Rh antigens be present on red cells regardless of the D status?
Yes
240
Which genes determine Rh expression?
RhD and RhCE
241
What antigens does RhCE confer?
C, c, E and e antigens
242
When are Rh antibodies formed in Rh-negative individuals?
Following an incompatible blood transfusion or transplacental passage of blood during pregnancy
243
Why is Rh antibody formation a concern in Rh-negative pregnant women?
Because it can harm the fetus
244
Can Rh-positive people receive Rh-negative blood?
Yes
245
Can Rh-negative women of childbearing age receive Rh-positive blood?
No
246
Which antibodies can occasionally cause transfusion reactions and HDFN?
Antibodies to C, c, E and e antigens
247
What is the cause of Haemolytic disease of the fetus and newborn (HDFN)?
Maternal IgG antibodies crossing the placenta and binding to fetal red cells with corresponding antigens
248
What are the most frequent cause of HDFN?
Anti ABO antibodies
249
Which type of antibodies are usually associated with the most severe cases of HDFN?
Anti Rh (specifically anti D) antibodies
250
Which antibodies can also be IgG and cross the placenta to affect the fetus?
Anti A and anti B antibodies
251
Which antibodies are most commonly seen in Group O pregnant women?
IgG anti A and B antibodies
252
What is the main aim of managing Rh HDN?
To prevent Rh D antibody formation in Rh-negative pregnant women
253
When can Anti D antibody be administered to Rh-negative women?
At 28 weeks, during any potentially sensitizing events (e.g., amniocentesis, abortion), and 72 hours after birth if the baby is Rh positive
254
What are the risks associated with blood product transfusions?
Incompatible blood transfusions and transmission of infection from donor to patient
255
What is the most frequent cause of incompatible blood transfusions?
Human error
256
What is the window period risk associated with transfusion of blood products?
Transmission of infection from a donor to a patient during a period where the infection is not yet detectable
257
How should a blood product be ordered?
Using a blood ordering request form and providing a blood sample in a crossmatch tube
258
In what type of sets are blood and products given?
Specialized IV sets containing filters
259
Can fluids or drugs be added to the blood product?
No
260
What should be compared before starting a blood transfusion?
The details on the product with the order form and patient folder at the bedside
261
What information should be checked before starting a blood transfusion?
Patient name & hospital number, unit serial number & blood type, expiration date
262
What must the patient do before receiving a transfusion?
Sign informed consent for the transfusion
263
How quickly should red cell units be transfused?
Very slowly over 1 - 2 hours
264
When can blood be transfused rapidly?
For rapid red cell transfusions
265
What are the possible causes of intrinsic hereditary haemolytic anaemia?
Abnormal RBC membrane, abnormal RBC metabolism, haemoglobin abnormalities
266
What are the possible causes of acquired haemolytic anaemia?
Immune mechanisms, fragmentation syndromes, macrovascular haemolysis, toxins
267
What are the features of increased RBC production in haemolytic anaemia?
Reticulocytosis, nucleated red blood cells on blood film, bone marrow erythroid hyperplasia, haemoglobinuria/haemosiderinuria
268
What are the features of increased red cell breakdown in haemolytic anaemia?
Unconjugated hyperbilirubinaemia, increased urinary urobilinogen, decreased or absent serum haptoglobin
269
What are the possible damaged red cell characteristics in haemolytic anaemia?
Morphology, raised LDH
270
What is the significance of peripheral blood smear in investigating haemolytic anaemia?
RBC morphology is critical, polychromasia and nucleated red cells suggest a bone marrow response, spherocytes indicate loss of central area of pallor, burr cells are seen in renal failure
271
How can the precise diagnosis of haemolytic anaemia be determined?
Distinguishing between inherited and acquired causes, conducting tests such as G6PD screen, Hb electrophoresis/HPLC, Coombs test, flow cytometric immunophenotyping
272
What are the characteristics of warm autoimmune haemolytic anaemia?
Idiopathic or secondary to an underlying systemic condition, usually IgG autoantibodies, extravascular haemolysis, presence of polychromasia, spherocytosis, and nucleated red blood cells
273
What are the characteristics of alloimmune haemolytic anaemia?
Results from antibodies to RBC antigens produced by another individual, can occur in haemolytic transfusion reactions or haemolytic disease of the newborn
274
What are the characteristics of cold autoimmune haemolytic anaemia?
Less common than warm AIHA, spontaneous agglutination of RBCs, may be secondary to lymphoproliferative disorders or infections, can result in cold haemagglutinin disease with mild anaemia, jaundice, and acrocyanosis
275
What activates the system in response to pattern recognition receptors?
Pattern recognition receptors activate the system.
276
What is the role of cellular and humoral responses in malaria?
Both cellular and humoral responses are important in malaria.
277
Which forms are targeted by cytotoxic responses in malaria?
Cytotoxic responses target the hepatic and merozoite forms in malaria.
278
What do antibodies target in malaria?
Antibodies target the merozoites and erythrocyte stages in malaria.
279
What is the significance of malaria vaccines in the fight against malaria?
Malaria vaccines represent a key development in the fight against malaria.
280
Which malaria vaccine has been approved by WHO in 2021?
The RTS, S vaccine has been approved by WHO in 2021.
281
What is anaemia?
Anaemia is a condition associated with reduced red cell mass and haemoglobin levels.
282
How is anaemia diagnosed?
Anaemia can only be diagnosed with a lab test.
283
What causes autoimmune haemolytic anaemia (AIHA)?
AIHA is caused by immune-mediated destruction or lysis of red blood cells.
284
What are the mechanisms of haemolysis?
Mechanical, infections (such as malaria), venoms, and copper/zinc toxicity can cause haemolysis.
285
Where does haemolysis occur in autoimmune haemolytic anaemias?
Haemolysis can occur intravascularly or extravascularly.
286
Under what conditions does warm AIHA occur?
Warm AIHA occurs at body temperature.
287
Under what conditions does cold AIHA occur?
Cold AIHA occurs in extremities and below body temperature.
288
What is the role of the spleen in haemolysis?
The spleen is the major effector organ of extravascular haemolysis.
289
What are the clinical presentations of warm AIHA?
Warm AIHA presents with anaemia, pallor, tiredness/weakness, and potentially jaundice and splenomegaly.
290
What is cold agglutinin disease?
Cold agglutinin disease is characterized by antibodies targeting the I system antigens.
291
Which infections can lead to the development of cold agglutinin disease?
Epstein-Barr virus infection, Mycoplasma spp infections, and certain autoimmune diseases can lead to the development of cold agglutinin disease.
292
What does the I antigen bind weakly to?
The I antigen binds weakly to antibodies.
293
What is the most severe form of malaria?
P. falciparum
294
What causes all the clinical symptoms associated with malaria?
Rupture of infected erythrocytes, host cytokine response to infection, cytoadherence of infected erythrocytes to vascular epithelium
295
What is tropical splenomegaly syndrome?
Chronic untreated non-falciparum malaria in people who live in areas of high intensity transmission
296
What are the signs and symptoms of malaria?
Fever, headache, confusion, dizziness, weakness, nausea, vomiting, diarrhoea, loss of appetite, poor feeding in children, muscle/joint aches, cough in children, classical febrile paroxysms with chills, fevers, and sweats
297
Who are the risk groups for complicated malaria?
Pregnant and post-partum women, children under 5, splenectomised people, elderly under 65, immunocompromised including HIV+
298
What is the gold standard technique for laboratory confirmation of malaria?
Blood smear stained with Giemsa stain
299
What is the recommended treatment for uncomplicated malaria in adults?
Artemether-lumefantrine or quinine plus doxycycline
300
What is the recommended treatment for uncomplicated malaria in children under 5 and pregnant patients?
Artemether-lumefantrine or quinine plus clindamycin
301
What is the recommended treatment for complicated malaria in adults and children?
IV artesunate followed by oral artemether-lumefantrine or IV quinine followed by artemether-lumefantrine or quinine plus doxycycline/clindamycin
302
What is the most common non-falciparum malaria in South Africa?
P. ovale
303
What is the recommended treatment for non-falciparum malaria?
Artemether-lumefantrine for extra-hepatic phases, primaquine for hepatic stage and radical cure; treat mixed infections as P. falciparum and add a course of primaquine if P. vivax or P. ovale is identified
304
What is the laboratory diagnosis for malaria?
Blood smear (thick smear to make the diagnosis, thin smear to identify species), rapid diagnostic test detecting parasite antigen
305
What are the four basic functions of antibodies?
Opsonisation, Complement fixation, Antibody dependent cellular cytoxicity, Neutralisation
306
Which cells are responsible for phagocytosing parasites and infected red cells?
Dendritic cells and macrophages
307
What is the role of Th1 CD4+ T cells?
Activating the cell-mediated wing of the immune system and activating antigen presenting cells
308
How do T-cells kill infected cells?
By secreting perforin and granzyme
309
What is the function of antibodies in P. falciparum?
Disrupting all stages of the lifecycle, promoting the clearance of infected red blood cells
310
What are some factors that can inhibit dendritic cells?
Certain factors, especially haemozoin
311
What is the role of CD4+ T cells in immunity to malaria?
Critical to immunity, potentiating the activity of cytotoxic CD8+ T cells
312
What is the RTS,S vaccine targeting?
The sporozoite to prevent hepatocyte infection
313
How is herd immunity achieved against malaria?
Stimulating the production of antibodies in the host to block parasite proliferation in mosquitoes
314
What are the three distinct stages of Plasmodium falciparum in humans?
Pre-erythrocyte or hepatic stage, Erythroid asexual stage, Sexual stage
315
What is the efficacy of the RTS,S vaccine in preventing severe disease?
About 29%
316
What is the relationship between malaria immunity and individuals living in malaria-endemic areas?
These individuals develop semi-immunity to malaria, experiencing less severe infection compared to those living outside these areas
317
How do mosquitoes and malaria parasites counteract control measures?
Mosquitoes become resistant to pesticides, parasites become resistant to anti-malarial drugs
318
What is the potential problem with CD4+ T cells and the red blood cell?
The red blood cell does not express high levels of MHC 1, making it 'invisible'
319
What is the best way to elicit a potent immune response in controlled malaria infection?
By irradiating mosquitoes and allowing them to bite the individual
320
What are the complications of severe malaria?
Overwhelming stimulation of pattern receptors, increased vascular permeability, disseminated coagulopathy, systemic organ dysfunction
321
What are some types of abuse that migrants may face?
Murder, rape, sexual violence, extortion, kidnapping, degrading body searches, torture, and muggings.
322
What are some risks associated with imprisonment and detention for migrants?
Risk of tuberculosis (TB) and reported cases of multi-drug resistant TB (MDR-TB) in detention centers.
323
What are some mental health issues that migrants may experience?
Stress, depression, and trauma.
324
How does mobility affect vulnerability to high-risk sexual behavior among migrants?
Mobility per se can make people vulnerable to high-risk sexual behavior, especially among migrant communities with high infection rates of HIV/AIDS.
325
Why is it challenging to reach and provide interventions for migrant populations?
Mobility makes people more difficult to reach through classic interventions, and there is a lack of harmonized treatment regimes and protocols between different countries.
326
What attitudes should health professionals have when working with migrant patients?
Courtesy, respect for human dignity, patience, empathy, and tolerance (as per the patient rights charter).
327
What are some practical examples of adapting consultations and care for migrant patients?
Using translators or visual aids if no translator is available, tailoring treatment plans, providing detailed referrals, and managing patient expectations.
328
What rights do refugees and asylum seekers have regarding healthcare?
Access to healthcare, choice of health services, confidentiality, informed consent, continuity of care, healthy and safe environment, participation in decision-making, treated by a named healthcare provider, refusal of treatment, a second opinion, and the right to complain about health services.
329
What are some key barriers for migrants in accessing healthcare?
Structural/health system-related barriers, contextual barriers (cultural and communication), and behavioral/patient-related barriers (poor health-seeking behaviors, socio-economic factors, lack of orientation/induction to the healthcare system).
330
What are the two populations of cells that exist within the blood islands?
Peripheral cells (endothelial cells) and core cells (haemocytoblasts)
331
What is the thymus responsible for?
Maturation of T lymphocytes into immunocompetent T cells
332
What role does thymosin play in the thymus?
Thymosin plays a role in the maturation process of T lymphocytes
333
What are the two areas that make up the structure of the thymus?
Outer area (cortex) and inner area (medulla)
334
Where does haematopoiesis begin in the embryo?
In the yolk sac of the embryo
335
What is the chief site of blood cell production in the human embryo?
Foetal liver
336
Which organs serve as minor sites of blood cell production?
Spleen, kidney, thymus, and lymph nodes
337
What is the primary site of haematopoiesis throughout life?
Bone marrow
338
What are the major blood components?
Erythrocytes, leukocytes, platelets, and plasma
339
What does FBC stand for?
Full blood count
340
What are the normal reference ranges for RBC count in men and women?
Men: 4.3-5.6 X10^12/L, Women: 3.9-4.9 X10^12/L
341
What is anaemia?
Reduced circulating haemoglobin per unit volume of blood compared to the reference range
342
How is haemoglobin measured in the FBC?
Converted to stable form (hemiglobincyanide) and measured using light transmittance
343
Why is anaemia important?
It is a common global healthcare problem with significant morbidity and can indicate underlying diseases/disorders
344
What is the formula for Hct (haematocrit)?
Hct = VolumeRBC/VolumeTOTAL
345
What is MCV (mean cell volume)?
MCV is the ratio of Hct to RBC count
346
What are the common causes of macrocytic anaemia?
Many causes
347
What is the characteristic feature of megaloblastic anaemia?
Oval macrocytes
348
What are the blood film findings associated with megaloblastic anaemia?
Nucleated RBCs, hypersegmented neutrophils
349
Which vitamin deficiencies can cause megaloblastic anaemia?
Vitamin B12 or folate deficiency
350
What is the shape of RBCs in sickle cell anaemia?
Sickle cell shape
351
What problems can be caused by abnormal RBCs in sickle cell anaemia?
Tissue hypoxia due to obstruction of small vessels
352
What are the characteristics of autoimmune haemolytic anaemia on a blood film?
Spherocytes, increased reticulocytes
353
Which condition is associated with spherocytes and Coombs test negative?
Hereditary spherocytosis
354
What is the most important condition associated with circulating fragments and anaemia?
Thrombotic thrombocytopenic purpura
355
Which patient populations have unique reasons for anaemia?
Premature neonates, pregnant women, chronic renal failure patients, HIV patients, patients with severe hepatosplenomegaly
356
What is the reticulocyte count percentage?
The percentage of all RBCs that are reticulocytes
357
How can the reticulocyte count be corrected for the degree of anaemia?
Multiply by the patient's hematocrit divided by a normal hematocrit
358
What is the reticulocyte production index?
A correction for reticulocyte lifespan
359
What is haemolytic anaemia?
A group of anaemias resulting from reduced RBC survival
360
What are the causes of haemolysis?
Intrinsic RBC defects, loss of structural integrity of RBCs, external factors
361
Where does extravascular haemolysis occur?
In the reticuloendothelial system, mainly spleen
362
What is the site of haemolysis in intravascular haemolysis?
In the blood vessels
363
How can haemolytic anaemias be classified?
Hereditary haemolytic
364
How can mutations in stem cells affect bone marrow activity?
Mutations in stem cells can lead to increased bone marrow activity, which may lead to leukemia, lymphoma, myeloproliferative neoplasms, and other cancers.
365
What are the potential outcomes if diseased stem cells can be repaired or replaced?
If diseased stem cells can be repaired or replaced, the underlying disease could potentially be cured.
366
What are the components of a whole unit of donated blood?
A whole unit of donated blood consists of plasma, a buffy coat containing white blood cells and platelets, and red blood cells.
367
What are the main proteins found in plasma?
Plasma contains proteins including clotting factors, immunoglobulins, fibrinogen, and albumin.
368
Why are platelets important in blood?
Platelets are important for clotting and prevention of bleeding.
369
What biomolecule is found in red blood cells and binds oxygen?
Red blood cells have hemoglobin, an iron-containing biomolecule that binds oxygen.
370
What are antigens and where are they found?
Antigens are proteins found on the surface of red blood cells.
371
How do individuals develop naturally occurring ABO antibodies?
By 3-6 months of age, the immune system will have been exposed to A and B-like antigens in exogenous sources, leading to the development of antibodies unless these antigens are present on the red cells.
372
What are the four blood groups discovered by Karl Landsteiner?
The four blood groups discovered by Karl Landsteiner are A, B, AB, and O.
373
What is the H antigen and its relation to the A and B antigens?
The H antigen is a precursor to A and B antigens. ABO genes code for enzymes that affect the outcome of the H antigen.
374
What are the most common Rh antigens?
The most common Rh antigens are D, C, c, E, and e.
375
What happens when IgG or IgM antibodies attach to specific RBC antigens?
When IgG or IgM antibodies attach to specific RBC antigens, they can cause agglutination and result in intra vascular or extra vascular hemolysis.
376
What is the main cause of raised potassium levels in the blood?
Red cell cytoplasm releasing potassium
377
Name three techniques to prevent raised potassium levels during blood collection.
Avoid using tiny needles, high vacuum, and drawing blood rapidly through long thin lines.
378
What is methaemoglobin and why can't it carry oxygen?
Methaemoglobin is oxidized ox Fe2+ to Fe3+ and cannot carry oxygen.
379
What is the purpose of MetHb reductase in red blood cells?
To protect RBCs from oxidation.
380
How does cyanide poisoning affect cytochrome oxidase and Met-Hb?
Cyanide binds to cytochrome oxidase and Met-Hb, causing methaemoglobin anaemia.
381
Name two drugs that can cause methaemoglobin anaemia.
Local anaesthetics and nitrites.
382
What are porphyrias?
Inherited defects of haem biosynthesis.
383
What are the two types of precursors that build up in porphyrias?
Porphyrinogens and PBG (porphobilinogen) and d-ALA (delta-aminolevulinic acid).
384
What are the symptoms of acute porphyric attacks?
Abdominal pain, sensory and motor neuropathy, autonomic neuropathy, CNS dysfunction, and hyponatremia.
385
What should be given during acute porphyric attacks to shut down fatty acid oxidation?
Dextrose.
386
What are the key diagnostic tests for acute intermittent porphyrias?
Measuring PBG (porphobilinogen) and d-ALA (delta-aminolevulinic acid) in urine.
387
What are the management steps for acute porphyric attacks?
Make a diagnosis, stop haem synthesis by giving extra glucose, and correct hyponatremia.
388
What is the process by which blood cells are formed in the body called?
Haematopoiesis
389
Name one type of anaemia that may require the removal of damaged cells.
Megaloblastic anaemia or Sickle cell anaemia
390
What is the term for an enlargement of the spleen?
Splenomegaly
391
Which blood test is the most commonly ordered and provides clues to underlying disease processes?
Full Blood Count (FBC)
392
What is the most immature precursor cell that gives rise to the production of blood cells called?
Haematopoietic stem cell
393
How many bone marrow stem cells become 500 billion cells per day?
1 in 10,000
394
What is the term for the production of red blood cells?
Erythropoiesis
395
How long do red blood cells survive in circulation?
Approximately 120 days
396
What is the main role of red blood cells?
Carrying oxygen in haemoglobin
397
What is the term for the production of platelets?
Thrombopoiesis
398
Where are megakaryocytes mainly found in the bone marrow?
Around blood vessels (perivascular)
399
What cytokine stimulates the production of megakaryocytes?
Thrombopoietin (TPO)
400
What are the three types of granulocytes?
Eosinophils, basophils, neutrophils
401
What is the term for the production of lymphocytes?
Lymphopoiesis
402
What are the three types of bone marrow failure syndromes mentioned?
Aplastic anaemia, myelodysplastic syndromes, and acute leukaemia
403
What can stem cells give rise to?
All blood cells in the body
404
What are the symptoms of anaemia?
Shortness of breath, weakness, palpitations, headaches, etc.
405
What are the signs of anaemia?
Pallor of mucous membranes, tachycardia, splenomegaly, etc.
406
What are the specific symptoms of iron deficiency anaemia?
Pica
407
What are the specific symptoms of vitamin B12 deficiency anaemia?
Loss of proprioception and vibration sense
408
What are the clinical features of anaemia?
Influenced by speed of onset, severity of anaemia, patient age, comorbidities, and factors affecting the O2 dissociation curve
409
What are the classifications of anaemia?
According to RBC size and mechanism for reduced Hb
410
What are some causes of microcytic anaemia?
Iron deficiency, mixed deficiency, thalassaemia
411
What are some causes of normocytic anaemia?
Anemia of chronic disorders, megaloblastic (Vit B12/folate def), blood loss
412
What are some causes of macrocytic anaemia?
Vitamin B12 and folate deficiency, myelodysplastic syndrome, hypothyroidism
413
What is the role of reticulocytes in anaemia?
Marker for effective erythropoiesis, increased in haemolytic anaemia
414
What are the characteristics of iron deficiency anaemia?
Microcytic, hypochromic, presence of pencil cells
415
What is the most common type of microcytic anaemia?
Iron deficiency anaemia
416
What are the maternal complications of thalassaemia?
Maternal complications are mostly fatal
417
What is the treatment for thalassaemia?
Treatment includes blood transfusion or chelation as needed, bone marrow transplants, and monitoring for complications
418
What is the genotype and phenotype of β/β0 thalassaemia?
Genotype: β/β0; Phenotype: Beta thalassaemia minor/trait, normal with sometimes mild anemia and microcytosis
419
What are the major species of malaria?
The major species of malaria are P. falciparum, P. malariae, P. vivax, P. ovale, and P. knowlesi
420
What is the most prevalent and severe form of malaria?
Plasmodium falciparum is the most prevalent form in Africa and is also the most severe form
421
How does malaria disease manifest?
Malaria disease manifests with symptoms like headache, muscle pain, and photophobia, followed by paroxysms of chills and high fevers
422
What are the severe complications of malaria?
Severe complications include cerebral malaria, placental malaria, and malaria-associated renal impairment and blackwater fever
423
What is the role of the innate immune system in malaria?
The innate immune system recognizes non-mammalian molecular patterns in malaria and stimulates an inflammatory response
424
What is the process of inflammation in malaria?
Inflammation in malaria involves activation of pathways that promote increased vessel permeability, pyrexia, pain, and swelling
425
What percentage of malaria cases in 2020 were accounted for by Africa?
96%
426
Which country in sub-Saharan Africa is an exception to malaria transmission?
Lesotho
427
Which areas in South Africa have high malaria risk?
North-eastern Kwa-Zulu Natal, low altitude areas of Mpumalanga and Limpopo
428
During which months does malaria transmission typically occur in South Africa?
September and May
429
What is the term for accidentally transported mosquitoes to non-endemic areas transmitting malaria?
Odyssean malaria
430
Which species of mosquito is the vector for malaria?
Female mosquito of the genus Anopheles
431
What is the most important species of malaria in Africa?
P. falciparum
432
What type of host are humans in the life cycle of malaria?
Intermediate host
433
During which stage of the life cycle do merozoites infect new red blood cells?
Schizont stage
434
Which species of malaria has the widest distribution in temperate and subtropical areas?
P. vivax
435
What is the incubation period of P. falciparum?
10-21 days
436
Which species of malaria can persist in hepatocytes as hypnozoites for months to years?
P. ovale
437
Which species of malaria generally causes the mildest disease?
P. malariae
438
What is the serious complication of P. malariae infection?
Nephrotic syndrome
439
Which monkey malaria parasite can infect humans?
P. knowlesi
