Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Phase 2a > Haematology > Flashcards

Haematology Flashcards

1
Q

When do you get anaemic?

A

When there is a decrease of haemoglobin in the blood before the reference for age/sex of an individual

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What 2 things may anaemia be due to?

A
  • low red cell mass (RCM)

- increase plasma volume

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

RBC lifespan?

A

120 days

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What can reduce a RBC’s lifespan?

A
  • reduced production from marrow

- increased loss of RBC (by spleen, liver, marrow, blood loss)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How do you test to see if the bone marrow production is the cause for anaemia?

A

Look at reticulocyte count (count of immature RBC in bone)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What will the reticulocyte count be if the production of RBC is the issue?

A

Low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What will the reticulocyte count be if the removal of RBC is the issue?

A

High

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How are various types of anaemia classified?

A

By mean corpuscular volume (MCV)

- average vol of RBCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Name the 3 major types of anaemia

A
  1. Hypochroic microcytic
  2. Normochromic normocytic
  3. Macrocytic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What will a reduction in plasma volume lead to?

A

A falsely high haemoglobin (seen in dehydration)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

List the consequences of anaemia

A
  • reduced O2 transport

- tissue hypoxia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the compensatory changes for anaemia?

A
  • increased tissue perfusion
  • increased O2 transfer to tissues
  • increased RBC production
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

List the pathological consequences for anaemia?

A
  • myocardial fatty change
  • fatty change in liver
  • aggravates angina
  • skin & nail atrophic changes
  • CNS cell death
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

List the non-specific symptoms (clinical features) of anaemia

A
  • fatigue / headaches / faintness
  • dyspnea
  • breathlessness
  • anorexia
  • palpitations
  • intermittent claudication
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What clinical signs may anaemics show?

A
  • pallor
  • tachycardia
  • systolic flow murmur
  • cardiac failure
  • may be absent in severe anaemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the main causes of microcytic anaemia?

A
  • iron deficiency anaemia (most common cause world-wide)
  • anaemia of chronic disease
  • thalassemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Is microcytic anaemia high or low MCV?

A

Low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the average daily intake of iron?

A

15-20mg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What % of iron is normally absorbed and where?

A

10% - in the duodenum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How are iron ions absorbed?

A
  • actively transported into duodenal intestinal epithelial cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What transports iron ions into duodenal cells?

A

Intestinal haem transporter (HCP1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Where is HCP1 highly expressed?

A

In the duodenum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are some iron ions incorporated into?

A

Ferritin (acts as an intracellular store for iron)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What happens to absorbed iron that doesn’t bind to ferritin?

A
  • released into blood
  • binds to transferrin
  • circulates body
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Describe the function of transferrin

A

Transports iron in blood plasma to bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What happens to iron that is transported to bone marrow?

A

Incorporated int new erythrocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the majority of iron incorporated into?

A

Haemoglobin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Where is the rest of the absorbed iron stored?

A
  • reticuloendothelial cells
  • hepatocytes
  • skeletal muscle cells (as ferritin or haemosiderin)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What is the advantage of storing iron as ferritin?

A
  • more easily mobilised than haemosiderin

- for Hb formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Where is ferritin found?

A
  • plasma

- most cells: liver, spleen, bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Where is haemosiderin found?

A

Found in macrophages: in bone marrow, liver, spleen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

When does iron deficiency anaemia develop?

A

When there is an inadequate iron for Hb synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What causes iron deficiency anaemia to develop?

A
  • blood loss
  • poor diet
  • inc. demands (growth/pregnancy)
  • malabsorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Examples of blood loss events leading to iron deficient anaemia

A
  • menorrhagia (severe menstruation)
  • GI bleeding
  • hookworm - leads to GI blood loss (leading cause of iron deficiency worldwide)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Examples of malabsorption

A
  • poor intake (underdeveloped countries)

- coeliac disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What are the risk factors for iron deficient anaemia?

A
  • undeveloped countries
  • high vegetable diet
  • premature infants
  • introduction of mixed feeding delay
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Pathophysiology of microcytic anaemia

A
  • less iron available for haem synthesis
  • crucial for haem production
  • reduction ins iron = decrease in Hb
  • smaller RBC
    = microcytic anaemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What are the clinical presentations of microcytic anaemia?

A
  • brittle nails & hair
  • spoon shaped nails
  • atrophy of papillae of tongue
  • angular stomatitis (ulceration of corners of the mouth)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Differential diagnoses of microcytic anaemia

A
  • thalassaemia
  • sideroblastic anaemia
  • anaemia of chronic disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

How would you diagnose microcytic anaemia?

A
  • blood count & film
  • serum ferritin
  • serum iron
  • serum soluble transferrin receptors
  • low reticulocyte count
  • investigate cause of blood loss
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What will a blood count & film for microcytic anaemia?

A
  • RBC are microcytic & hypochromic

- poikilocytosis & anisocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What is poikilocytosis?

A

Variation in RBC shape

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What is anisocytosis?

A

Variation in RBC size

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

How will serum ferritin indicate microcytic anaemia?

A

Serum ferritin will be low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

How will serum iron indicate microcytic anaemia?

A
  • Will be low

- total iron-binding capacity (TIBC) rises

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

When is iron deficiency present?

A

When transferrin saturation falls below 19%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

How will serum soluble transferrin receptors indicate microcytic anaemia?

A

No. of transferrin receptors will INCREASE in iron deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

How would you treat microcytic anaemia?

A
  • oral iron (ferrous sulphate / ferrous gluconate)

- parenteral iron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What are the side effects of ferrous sulphate?

A
  • nausea
  • abdominal discomfort
  • diarrhoea / constipation / black stools
    (FERROUS GLUCONATE IF SIDE EFFECTS ARE BAD)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Examples of parenteral iron

A
  • IV iron

- deep intramuscular iron in extreme cases (severe malabsorption)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Describe anaemia of chronic disease

A
  • if body is sick = bone marrow becomes sick

- anaemia is secondary to chronic disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Describe the appearance of RBCs in anaemia of chronic disease

A
  • often normocytic

- can be microcytic (in rheumatoid arthritis / Crohn’s)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Name which chronic infections can lead to anaemia

A
  • TB
  • Crohn’s
  • Rheumatoid arthritis
  • SLE
  • Malignant disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Pathophysiology of anaemia in chronic disease

A
  • decreased iron release from bone marrow
  • inadequate erythropoietin response
  • decreased RBC survival
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

List the clinical presentations of anaemia in chronic disease

A
  • fatigue / headaches / faintness
  • dyspnea / breathlessness
  • anorexia
  • palpitations
  • intermittent claudication
  • angina (if coronary disease)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

How would you diagnose anaemia in chronic disease?

A
  • low serum iron / TIBC
  • normal/raised serum ferritin due to inflammatory process
  • normal serum soluble transferrin receptor level
  • RBCs are normocytic/microcytic AND hypochromic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

How would you treat anaemia in chronic disease?

A
  • treat underlying chronic cause

- erythropoietin = raises Hb level

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

When is erythropoietin used to treat anaemia?

A
  • renal disease

- inflammatory disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

List the side effects of using erythropoietin to treat anaemia

A
  • flu like symptoms
  • hypertension
  • mild rise in platelet count
  • thromboembolism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Describe normocytic anaemia

A

Normal MCV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

List the main causes of normocytic anaemia

A
  • acute blood loss
  • anaemia of chronic disease
  • endocrine disorders
  • renal failure
  • pregnancy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Suggest endocrine disorders that may lead to normocytic anaemia

A
  • hypopituitarism
  • hypothyroidism
  • hypoadrenalinism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

What would indicate a diagnosis normocytic anaemia?

A
  • normal B12 & folate
  • raised reticulocytes
  • decreased Hb
  • RBC’s are normocytic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

How would you treat normocytic anaemia?

A
  • treat underlying cause
  • improve diet (vitamins)
  • erythropoietin injections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Describe macrocytic anaemia

A

High MCV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

What can macrocytic anaemia be divided into?

A
  1. Megaloblastic

2. Non-megaloblastic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Describe megaloblastic anaemia

A
  • presence of erythroblasts
  • delayed DNA synthesis = delayed nuclear maturation
  • megaloblasts w/ large MCV & no nuclei
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Describe non-megaloblastic anaemia

A

Erythroblasts are normal - normoblastic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

What are the main causes of megaloblastic anaemia?

A
  • vitamin B12 deficiency

- folate deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

What are the main causes of non-megaloblastic anaemia?

A
  • alcohol
  • liver disease
  • hypothyroidism
  • haemolysis
  • bone marrow failure / infiltration
  • myeloma
  • antimetabolite therapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

What deficiency does pernicious anaemia cause?

A

Vitamin B12 deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What does B12 deficiency cause?

A
  • impairs DNA synthesis
  • delayed nuclear maturation
    = larger RBC
    = reduced RBC production in bone marrow
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Why does low B12 affect DNA synthesis?

A
  • B12 is essential for thymidine

- thus important for DNA synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

What are the causes of B12 deficiency?

A
  • dietary (vegans)
  • malabsorption (lack of intrinsic factor / terminal ileum removal)
  • pernicious anaemia (most common cause)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

Describe pernicious anaemia

A
  • autoimmune disorder
  • parietal cells attacked
  • results in atrophic gastritis
  • loss of intrinsic factor production
    = B12 malabsorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

List the risk factors for pernicious anaemia

A
  • elderly (over 60)
  • female
  • fair haired / blue eyes
  • blood group A
  • thyroid / Addison’s disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

What % of patients are intrinsic factor antibodies found in?

A

50% - SPECIFIC FOR DIAGNOSIS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

What and how does autoimmune gastritis affect?

A
  • the fundus

- with plasma cell & lymphoid infiltration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

What are parietal and chief cells replaced by?

A

Mucin-secreting cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

What happens to the acid production in pernicious anaemia?

A

Reduced HCl production - Achlorhydria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

What are the clinical presentations of pernicious anaemia?

A
  • fatigue/headache
  • pallor
  • dyspnea
  • anorexia
  • palpitations/tachycardia
  • yellow skin
  • red sore tongue
  • angular stomatitis
  • neurological features
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

Why might patients with pernicious anaemia appear yellow?

A
  • due to pallor & mild jaundice

due to excessive breakdown of Hb - as body tries to get rid of defective RBC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

When might neurological features present in pernicious anaemia?

A

When B12 levels are very low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

What type of neurological features may present in pernicious anaemia?

A
  • symmetrical parenthesis (burning/prickling pain) in toes / fingers
  • early loss of vibration/proprioception
  • progressive weakness / ataxia
  • paraplegia
  • dementia / hallucinations / delusions / psychiatric problems
  • optic atrophy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

What are the differential diagnoses of pernicious anaemia?

A
  • differentiate from other cause of megaloblastic anaemia
  • differentiate from other causes of B12 deficiency
  • terminal ileum disease
  • bacterial overgrowth in small bowel
  • gastrectomy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

What would suggest a diagnosis of pernicious anaemia?

A
  • RBCs are macrocytic
  • raised serum bilirubin
  • low serum B12
  • low Hb
  • low reticulocyte
  • intrinsic factor antibodies (not present in all patients)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

What would a peripheral blood film of pernicious anaemia show?

A
  • oval macrocytes
    WITH
  • hypersegmented neutrophil polymorphs
  • 6< lobes in nucleus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

Why might serum bilirubin be raised in pernicious anaemia?

A
  • ineffective erythropoiesis

- increased RBC breakdown

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

How would you treat anaemia if it is not pernicious?

A

Treat underlying cause

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

How would you treat low B12 due to malabsorption?

A

Injections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

How would you treat low B12 due to dietary causes?

A

Oral B12

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

How can you replenish B12 levels?

A

Intra muscular hydroxocobalamin (injectable form of B12)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

What type of anaemia is folate deficiency?

A

Megaloblastic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

What is folate found in?

A
  • spinach
  • broccoli
  • nuts
  • yeast
  • liver
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

How long can you live with low stores of folate for?

A

4 months

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

When might folate deficiency develop rapidly?

A
  • patients w poor intake + excess utilisation

E.G patients in ICU

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

Where is folate absorbed?

A

Duodenum / proximal jejunum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

What does folate deficiency impair?

A
  • DNA synthesis (same as B12)

- fetal development (results in neural tube defects)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

List the causes of folate deficiency

A
  • poor intake
  • increase demand
  • malabsorption (Crohn’s coeliac’s)
  • antifolate drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

When might there be an increased demand for folate?

A
  • pregnancy

- increased cell turnover (haemolysis, malignancies, inflammatory disease, renal dialysis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

Examples of antifolate drugs

A
  • methotrexate

- trimethoprim

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

Clinical presentations of folate deficiency

A
  • patients may be asymptomatic
  • symptoms similar to anaemia
  • glossitis
  • no neuropathy (WILL HELP TO DISTINGUISH BETWEEN B12)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

How would you diagnose folate deficiency?

A
  • macrocytic RBC in blood film
  • oval macrocytes in peripheral film
  • low serum & RBC folate
  • GI investigation
  • raised serum bilirubin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

How would you treat folate deficiency?

A
  • treat underlying cause

- folic acid tablets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

How long would you prescribe folic acid tablets for?

A

Daily for 4 months

- ALWAYS WITH B12 (unless patient has normal B12)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

Describe haemolytic anaemia

A
  • RBCs can be normocytic
  • if many young RBCs due to excessive destruction of old RBCs
  • if so, then RBCs are macrocytic
  • premature breakdown of RBCs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

Name the 2 sites where premature RBC breakdown in haemolytic anaemic occurs?

A
  1. Circulation - intravascular

2. Reticuloendothelial system & bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

Describe what happens when RBC are prematurely broken down in the circulation

A
  • Hb is liberated
  • binds to haptoglobulin
  • these become saturated
  • excess free Hb filtered in glomerulus
  • enters urine
  • Hb broken down in renal tubular cells
  • deposited in the cells as haemosiderin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

Why does decreased RBC survival not always lead to anaemia?

A

There is a compensatory increase in RBC production in bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

How many times can bone marrow increase its RBC output by?

A

6-8 times

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

How does bone marrow increase RBC output?

A
  • increases proportion of cells that produce RBC

- expands volume of active marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

What are the consequences of haemolysis?

A
  • bone marrow increases output

- premature release of reticulocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

What are reticulocytes? What is their appearance?

A

Immature RBC

  • larger than mature cells
  • macrocytic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

How and what do reticulocytes stain?

A
  • stain with light blue tinge

- on peripheral blood film

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

What are the main causes of haemolytic anaemia?

A
  1. RBC membrane defect
  2. Enzyme defect
  3. Haemoglobinopathies
  4. Autoimmune haemolytic anaemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

Name an example of RBC membrane defect that leads to haemolytic anaemia

A

Hereditary spherocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
117
Q

Name an example of enzyme defect that leads to haemolytic anaemia

A

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
118
Q

Name 3 examples of haemoglobinopathies that lead to haemolytic anaemia

A
  1. B thalassaemia
  2. A thalassaemia
  3. Sickle cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
119
Q

List the features of haemolytic anaemia

A
  • high serum unconjugated bilirubin
  • high urinary urobilinogen
  • high faecal stercobilinogen
  • splenomegaly
  • bone marrow expansion
  • reticulocytosis
120
Q

What is hereditary spherocytosis? (HS)

A
  • defect of structural membrane proteins in RBC

- deficiency in spectrin (structural protein)

121
Q

What is the abnormal cell membrane functionally associated with?

A
  • increased Na+ permeability

- requires inc. rate of active transport of Na+ OUT of cells

122
Q

What happens to the RBC due to increased outward Na+ transport?

A
  • decreased SA:V ratio

- cells become SPHEROCYTIC (spheres)

123
Q

Describe properties of spherocytes

A
  • more rigid
  • less deformable than normal RBC
  • unable to pass through splenic microcirculation
124
Q

Why do spherocytes become trapped in the spleen?

A
  • more rigid & less deformable

- can’t pass through splenic microcirculation

125
Q

What happens due to spherocytes becoming trapped in the spleen?

A
  • shorted lifespan

- destroyed via extravascular haemolysis

126
Q

Epidemiology of HS

A
  • autosomal dominant
  • most common cause of inherited haemolytic anaemia
  • can spontaneously occur 25% (even if neither parent is affected)
127
Q

List the clinical presentations of HS

A
  • jaundice at birth (may be delayed onset)
  • haemolytic anaemia
  • splenomegaly
  • ulcers on the leg
  • chronic haemolysis = gall stones
128
Q

What might interrupt the course of HS?

A
  • aplastic anaemia

- megaloblastic anaemia

129
Q

What is aplastic anaemia? When might it occur?

A
  • sudden stop in RBC production

- after infection (erythrovirus etc.)

130
Q

What is megaloblastic anaemia caused by ?

A
  • folate depletion

- because of hyperactivity of bone marrow

131
Q

How would you diagnose HS?

A
  • blood film
  • blood count
  • haemolysis
  • direct antiglobulin test (Coombs’)
132
Q

What would a blood film show in confirmed HS?

A
  • spherocytes

- reticulocytes

133
Q

What would a blood count show in confirmed HS?

A
  • low Hb (anaemia)

- increased reticulocytes

134
Q

What would suggest haemolysis is occurring for HS diagnosis?

A
  • increased serum bilirubin

- increased urinary urobilinogen

135
Q

How would the Coombs’ test confirm HS?

A
  • would be negative

- ruling out autoimmune haemolytic anaemia

136
Q

How would you treat HS?

A

SPLENECTOMY

  • relieves symptoms
  • after childhood (due to infection risk post-op)
  • immunisations & life long penicillin prophylaxis after op
137
Q

Epidemiology of G6PD deficiency

A
  • heterogenous X-linked - more males affected
  • present with haemolytic anaemia
  • heterozygous females can also have clinical problems
138
Q

Which parts of the world is G6PD deficiency more common?

A
  • Africa
  • Mediterranean
  • Middle East
  • SE Asia
139
Q

How many different structural types of G6PD are there?

A

Over 400

140
Q

Which type of mutation are most G6PD types?

A
  • single amino acid substitutions (MIS-SENSE POINT MUTATIONS)
141
Q

How / what is G6PD essential for?

A
  • provides NADPH
  • NADPH is used with glutathione
  • which protects RBC from oxidative damage from compounds (e.g hydrogen peroxide)
142
Q

How does G6PD deficiency affect RBC?

A
  • reduces lifespan

- because they can’t be protected against oxidative damage

143
Q

Where is the gene for G6PD localised?

A
  • chromosome Xq28

- near factor VIII gene

144
Q

Why might patients with G6PD deficiency experience an oxidative crisis?

A

Because of reduced glutathione production

145
Q

What is reduced glutathione production precipitated by?

A

ACUTE DRUG INDUCED HAEMOLYSIS (dose related):

  • aspirin
  • antimalarials
  • antibacterials
  • dapsone
  • quinidine
146
Q

What are the clinical presentations of G6PD deficiency?

A

In attacks:

  • rapid anaemia
  • jaundice

General:

  • chronic haemolytic anaemia
  • neonatal jaundice
  • haemoglobinuria
147
Q

What are the clinical features of G6PD deficiency due to?

A
  • rapid intravascular haemolysis
148
Q

How would you diagnose G6PD deficiency?

A
  • blood count (normal between attacks)
  • blood film during attacks
  • G6PD enzyme levels (LOW)
149
Q

What will a blood film of G6PD show during an attack?

A
  • irregularly contracted cells
  • bite cells (have indentation in the membrane)
  • reticulocytosis (inc. reticulocytes)
150
Q

Why might there be falsely high G6PD enzyme levels after an attack?

A
  • oldest RBCs w/ least G6PD activity are destroyed selectively
151
Q

How would you treat G6PD deficiency?

A
  • stop any drugs causing it
  • blood transfusion

(splenectomy is not usually helpful)

152
Q

Describe structure of normal Hb (HbA)

A
  • haem
  • 2 alpha chains
  • 2 beta chains
153
Q

Describe structure of foetal Hb (HbF)

A
  • haem
  • 2 alpha chains
  • 2 gamma chains
154
Q

Describe structure of Hb delta (HbA2)

A
  • haem
  • 2 alpha chains
  • 2 delta chains
155
Q

What is the percentage of HbA in an adult?

A

97%

156
Q

What is the percentage of HbF in an adult?

A

1%

157
Q

What is the percentage of HbA2 in an adult?

A

2%

158
Q

What is the balanced production of alpha & beta chains?

A

1:1

159
Q

Describe the thalassaemias

A
  • genetic disease
  • unbalanced Hb synthesis
  • under production (no production) of one globin chain
160
Q

What does an imbalance of globin chains in RBC precursors result in?

A
  • cell damage
  • death of precursors in bone marrow
  • INEFFECTIVE ERYTHROPOIESIS
  • in mature cells = haemolysis
161
Q

What is beta thalassaemia?

A
  • reduced beta chain synthesis

- excess alpha chains

162
Q

What happens to with the excess alpha chains produced in B thalassaemia?

A
  • combine with delta/gamma chains

- results in increased HbA2, HbF

163
Q

What mutation causes B thalassaemia?

A
  • point mutations
164
Q

What do mutations in B thalassaemia lead to?

A

Defects in:

  • transcription
  • RNA splicing
  • modification
  • translation (via fram shifts / nonsense codons)
165
Q

What do frame shifts/ nonsense codons in B thalassaemia lead to?

A
  • production of highly UNSTABLE b-globin

- can’t be utilised

166
Q

Pathophysiology of heterozygous B-thalassemia

A
  • asymptomatic microcytosis

- with or without mild anaemia

167
Q

List the clinical presentations of B-thalassaemia minor (carrier)

A
  • asymptomatic

- hypochromic & microcytic RBCs ( low MCV)

168
Q

What does a Hb electrophoresis of B-thalassaemia show?

A
  • raised HbA2

- raised HbF

169
Q

How can B-thalassaemia be distinguished from iron deficiency?

A
  • serum ferritin & iron stores are normal
170
Q

Clinical presentations of B-thalassaemia intermedia

A
  • splenomegaly
  • bone deformities
  • recurrent leg ulcers
  • gallstones
  • infections
171
Q

Clinical presentations of B-thalassaemia major

A
  • severe anaemia at age 3-6 months
  • extra medullary haematopoiesis
  • life long transfusion dependent
  • hypertrophy of ineffective bone marrow
  • normal serum ferritin
172
Q

What does extra medullary haematopoiesis result in?

A
  • hepatosplenomegaly (due to haemolysis)

- bone expansion

173
Q

What would a skull X-ray of B-thalassaemia major show?

A
  • “hair on end” due to increased marrow activity
174
Q

What would blood results of B-thalassaemia major show?

A
  • v low MCV - microcytic
175
Q

What would blood film of B-thalassaemia major show?

A

Large and small irregular hypochromic RBCs

176
Q

What would be the diagnostic indicators B-thalassaemia major?

A
  • hypochromic, microcytic anaemia
  • raised reticulocyte count
  • nucleated RBC in peripheral circulation
177
Q

What would haemoglobin electrophoresis of B-thalassaemia major show?

A
  • increased HbF

- absent/fewer HbA (normal)

178
Q

How would you treat B-thalassaemia major?

A
  • regular life-long transfusions
  • iron-chelating agents
  • large doses of ascorbic acid
  • splenectomy
  • bone marrow transplant
  • long term folic acid
179
Q

How frequent would transfusions have to be in B-thalassaemia major?

A

Every 2-4 weeks

180
Q

Transfusions help to keep the Hb level above what? (B-Thalassaemia)

A

90g/L

181
Q

How do transfusions help B-thalassaemia major?

A
  • suppress ineffective extramedullary haematopoiesis

- allows normal growth

182
Q

Examples of iron-chelating agents

A
  • oral deferiprone

- subcutaneous desderrioxamine

183
Q

How do iron chelating agents help B-thalassaemia major?

A
  • prevent iron overload

esp. during infusions

184
Q

What are the side effects of iron-chelating agents?

A
  • pain
  • deafness
  • cataracts
  • retinal damage
185
Q

How does ascorbic acid help B-thalassaemia major?

A

Increases urinary excretion of iron

186
Q

What are the complication of transfusions for B-thalassaemia major?

A
  • progressive increase in body iron load
  • liver cirrhosis & fibrosis
  • diabetes
  • hypothyroidism
  • hypocalcaemia
  • premature death
187
Q

Where is iron deposited as a result of transfusions?

A
  • liver
  • spleen
  • endocrine glands
  • heart
188
Q

What is alpha thalassaemia?

A
  • gene for alpha globin chains is duplicated on both chromosomes 16
  • deletion might be of one or both alpha chain genes on chromosome 16
189
Q

What type of mutation causes alpha thalassaemia?

A

Gene deletions

190
Q

What is 4 gene deletion in A-thalassaemia?

A
  • deletion of both genes on both chromosomes
191
Q

Describe 4 gene deletion

A
  • no alpha chain synthesis

- only Hb barts (4 gamma chains) present

192
Q

Why is Hb Barts bad?

A
  • they cannot carry O2

- incompatible with life

193
Q

Clinical presentations of 4 gene deletion

A
  • infants are stillborn / die soon after birth
  • pale
  • oedematous
  • v large livers & spleens (HYDROPS FETALIS)
194
Q

Describe 3 gene deletion

A
  • severe reduction in A chain synthesis
  • results in HbH disease
  • HbH has 4 beta chains
195
Q

Clinical presentations of 3 gene deletion

A
  • moderate anaemia
  • splenomegaly
  • patient not usually transfusion dependent
196
Q

Describe 2 gene deletion

A

(A-thalassaemia carrier)

  • microcytosis
  • with or without mild anaemia
197
Q

Describe 1 gene deletion

A

Usually a normal blood picture

198
Q

What is sickle cell anaemia?

A
  • production of abnormal beta globin chains

- autosomal recessive

199
Q

What are the probabilities for sickle cell anaemia?

A
  • 25% chance of disease
  • 50% carrier
  • 25% disease free
200
Q

What type of mutation causes sickle cell haemoglobin? (HbS)

A

SINGLE BASE MUTATION

- of adenine to thymine

201
Q

What does HbS mutation cause?

A
  • produces substitution of valine for glutamic acid

- at 6th codon of beta globin chain

202
Q

At what stage does the sickle cell manifest, and why?

A
  • at 6 months of age

- HbF synthesis is normal - so only manifests until HbF decreases to adult levels

203
Q

Pathophysiology of sickle cell anaemia

A
  • HbS is insoluble & polymerises when deoxygenated
  • cell flexibility decreases
  • become rigid = sickle
204
Q

Is sickling of cells reversible?

A

Only INITIALLY

205
Q

What happens with repeated sickling?

A
  • cells lose membrane flexibility
  • become irreversibly sickled
  • irreversible cells are dehydrated & dense
    (don’t return to normal even when oxygenated)
206
Q

What does sickling result in?

A
  • shortened RBC survival = leads to haemolysis
  • impaired passage of cells through microcirculation
  • leads to obstruction of small vessels & tissue infarct = pain
207
Q

What is sickling precipitated by?

A
  • infection
  • dehydration
  • cold
  • acidosis
  • hypoxia
208
Q

Why do patients still feel well despite being anaemic? (sickle cell)

A

HbS releases O2 into tissues more readily than normal RBCs

209
Q

What are the clinical presentations of heterozygous sickle cell?

A
  • symptom free except in hypoxia

- protection against falciparum malaria

210
Q

What are the clinical presentations of homozygous sickle cell?

A
  • vaso-occlusive crises
  • acute chest syndrome
  • pulmonary hypertension
  • anaemia
211
Q

Describe vaso-occlusive crises

A
  • acute pain in hands & feet
  • pain in long bones
  • possible CNS infarcts in children = stroke, seiners, cognitive defects
212
Q

What causes acute pain in the hands, feet & long bones in sickle cell anaemia?

A
  • Vaso-occlusion of small vessels

- avascular necrosis of bone marrow in children

213
Q

What is acute chest syndrome?

A

Vaso-occlusive crises of pulmonary vasculature

214
Q

Name the most common cause of deaths in adults with sickle cell?

A
  • pulmonary hypertension

- chronic lung disease

215
Q

Causes of acute chest syndrome

A
  • infection (chlamydia, strep. pneumonia etc)
  • fat embolism from necrotic bone marrow
  • pulmonary infarction due to sickle cells (cells get trapped in pulmonary vasculature)
216
Q

What is the definition of pulmonary hypertension?

A

Mean pulmonary artery pressure greater than 25mmHg by right heart catheterisation

217
Q

What percentage of sickle cell patients suffer from PT?

A

10%

218
Q

What causes pulmonary hypertension in sickle cell?

A
  • damage from repeated chest crises
  • repeated thromboembolism
  • intravascular haemolysis
219
Q

What does PT increase the risk of?

A
  • hypoxaemia

- worsening sickle cell crises

220
Q

How does chronic haemolysis affect Hb levels?

A

Stabilises Hb levels

221
Q

What can cause an acute fall in Hb level?

A
  1. Splenic sequestration

2. Bone marrow aplasia

222
Q

What is splenic sequestration?

A

When sickle cells get trapped in the spleen due to their shape

223
Q

What does splenic sequestration lead to?

A
  • acute, painful spleen enlargement
  • acute fall in Hb
  • fibrotic, non-functioning spleen
224
Q

When does bone marrow aplasia occur?

A
  • most commonly after infection (erythrovirus B19)
225
Q

How does bone marrow aplasia affect the body?

A
  • rapid fall in Hb levels
  • no reticulocytes in peripheral blood
  • failure of erythropoiesis in marrow = APLASTIC CRISIS
226
Q

What can sickle cell affect in the long term?

A
  1. Growth & development
  2. Bones
  3. Infection in bones, lungs, kidneys
  4. Heart
  5. Brain
  6. Liver
  7. Renal
  8. Eye
  9. Pregnancy
227
Q

How can sickle cell affect growth and development?

A
  • young children are short - regain height in adulthood
  • below normal weight
  • delayed sexual maturation
228
Q

How can sickle cell affect bones?

A
  • avascular necrosis of hips & shoulders
  • compression of vertebrae
  • shortening of bones in hands / feet
  • osteomyelitis (due to staph. aureus / pneumonia, salmonella)
229
Q

What are bones, lungs & kidneys most susceptible to in sickle cell?

A

Vaso-occlusive crisis

230
Q

How can sickle cell affect the heart?

A
  • cariomegaly
  • arrhythmias
  • iron overload cardiomyopathy
  • MI
231
Q

How can sickle cell affect the brain?

A
  • TIA
  • fits
  • cerebral infarction
  • coma
  • occurs in 25% of patients
232
Q

How can sickle cell affect the liver?

A
  • chronic hepatomegaly

- liver dysfunction (due to trapping of sickle cells)

233
Q

How can sickle cell affect the kidneys?

A

Chronic tubulointerstitial nephritis

234
Q

How can sickle cell affect the eyes?

A
  • retinopathy
  • vitreous haemorrhage
  • retinal detachments
235
Q

How can sickle cell affect pregnancy?

A

Impaired placental blood flow - results in spontaneous abortion

236
Q

How would you diagnose sickle cell?

A
  • blood count
  • blood film
  • sickle solubility test
  • Hb electrophoresis
237
Q

What will a blood count of sickle cell show?

A
  • level of Hb in the range of 60-80 g/L

- raised reticulocyte count

238
Q

What will blood films of sickle cell show?

A

Sickled erythrocytes

239
Q

How will a sickle solubility test confirm sickle cell?

A

Test will be positive

240
Q

What will Hb electrophoresis of sickle cell show?

A
  • 80-95% HbS
  • absent HbA
  • diagnose at birth (cord blood) - aids prompt pneumococcal prophylaxis
241
Q

How and what would you treat to treat sickle cell?

A
  • treat precipitating factors ASAP
  • folic acid to ALL
  • acute painful attacks
  • anaemia
242
Q

List some precipitating factors of sickle cell?

A
  • infection
  • cold
  • dehydration
243
Q

How would you treat acute painful attacks?

A
  • IV fluids
  • analgesic (morphine, codeine, paracetamol, NSAIDS)
  • O2 & antibiotics
244
Q

How would you treat anaemia in sickle cell?

A
  • blood transfusions
  • oral hydroxycarbamide
  • stem cell transplant
245
Q

What is blood transfusion given for?

A
  • acute chest syndrome
  • acute anaemia due to splenic sequestration
  • aplastic crisis
  • stroke
  • heart failure
246
Q

What does oral hydroxycarbamide do?

A

Increases HbF conc

247
Q

Describe the epidemiology of aplastic anaemia due to bone marrow failure?

A
  • rare stem cell disorder
  • pancocytopenia
  • hypocellularity (aplasia) of bone marrow
248
Q

What is pancocytopenia?

A

Reduction in all major cell lines; RBC, RBC, platelets

249
Q

What is hypocellularity of the bone marrow?

A

Marrow stops making cells

250
Q

Is aplastic anaemia due to bone marrow failure acquired or inherited?

A
  • mainly acquired

- may be inherited

251
Q

What are the main causes of aplastic anaemia due to bone marrow failure?

A
  • idiopathic acquired
  • benze, toluene, glue sniffing
  • chemotherapeutic drugs
  • antibiotics (chloramphenicol, carbamazepine, azathioprine)
  • infections (EBV, HIV, TB)
252
Q

Describe the pathophysiology of bone marrow failure?

A
  • reduction in no. of pluripotent stem cells
  • fault in remaining stem cells / immune reaction against them
  • unable to repopulate bone marrow
253
Q

List the clinical presentations of bone marrow failure

A

BC OF RBC, WBC, PLATELET DEFICIENCY;

  • anaemia
  • increased susceptibility to infection
  • bleeding
  • bleeding gums/bruising with minimal trauma
  • blood blisters in mouth
254
Q

List the differential diagnoses of bone marrow failure

A

(Differentiated from other causes of pancocytopenia)

  • drugs
  • Hodgkin’s AND non-Hodgkin’s lymphoma
  • myeloma
  • SLE
255
Q

How do you diagnose bone marrow failure?

A
  • blood count

- bone marrow examination

256
Q

What will a blood count test show for bone marrow failure?

A

Pancocytopenia with low reticulocyte count

257
Q

What will a bone marrow examination show to diagnose bone marrow failure?

A
  • hypocellular marrow

- increased fat spaces

258
Q

How would you treat bone marrow failure?

A
  • treat cause
  • red cell transfusion & platelets
  • bone marrow transplant
  • immunosuppressive therapy (in those over 40 & below 40 with severe disease, transfusion dependent)
259
Q

Criteria for bone marrow donor

A
  • from HLA identical sibling

- donor treatment of choice under 40

260
Q

Why should bone / platelet transfusion be used cautiously?

A

To avoid sensitisation

261
Q

What is the immunosuppressive therapy given for bone marrow failure?

A
  • antithymocyte globulin (ATG)

- ciclosporin

262
Q

What is polycythaemia?

A

Any increase in RBC

263
Q

What can polycythaemia also be referred as?

A

Erythrocytosis - increase in RBC mass

264
Q

What is polycythaemia defined as?

A
  • increase in Hb
  • increase in packed cell volume (PCV) - known as haematocrit
  • increased RBC count
    (ALL dependent on plasma volume & RBC mass)
265
Q

Which is a more reliable indicatory of polycythaemia - Hb or PCV?

A

PCV

- Hb may be disproportionally low in iron deficiency

266
Q

What can polycythaemia be divided into?

A
  1. Absolute

2. Relative

267
Q

What is absolute polycythaemia due to?

A

Increase in RBC mass

268
Q

What can absolute polycythaemia be divided into?

A
  1. Primary

2. Secondary

269
Q

What can primary absolute polycythaemia be due to?

A
  • polycythaemia vera (PV)
  • mutations in erythropoietin receptor
  • high O2 affinity Hb
270
Q

What can secondary absolute polycythaemia be due to?

A
  • hypoxia

- inappropriately high erythropoietin secretion

271
Q

When might someone be hypoxic?

A
  • high altitude
  • chronic lung disease
  • cyanotic congenital heart disease
  • heavy smoking
272
Q

When might someone have inappropriately high erythropoietin secretion?

A
  • renal carcinoma

- hepatocellular carcinoma

273
Q

What is relative polycythaemia due to?

A

Decreased plasma volume

- normal RBC mass

274
Q

What is relative polycythaemia split into?

A
  1. Apparent polycythaemia

2. Dehydration

275
Q

What is apparent relative polycythaemia?

A
  • chronic form of polycythaemia
276
Q

What is apparent relative polycythaemia associated with?

A
  • obesity
  • hypertension
  • high alcohol / tobacco intake
277
Q

What is dehydration relative polycythaemia?

A

Acute

- due to dehydration (alcohol / diuretics)

278
Q

Epidemiology of polycythaemia vera

A
  • 95% of patients have acquired mutations of gene JAK2
279
Q

What is gene JAK2?

A
  • Janus kinase 2
  • cytoplasmic tyrosine kinase
  • transducer signals - triggered by haemopoietic growth factors (erythropoietin)
280
Q

What type of mutation leads to polycythaemia vera? (PV)

A

Point mutation

  • substitutes phenylalanine with valine
  • at position 617
281
Q

Pathophysiology of PV

A
  • clonal stem cell disorder

- results in malignant proliferation of clone derived from one pluripotent marrow stem cell

282
Q

Why are erythroid progenitor offspring unusual?

A

Don’t need erythropoietin to avoid apoptosis

283
Q

What does PV result in?

A
  • excess proliferation of RBCs, WBCs & platelets

- causes raised haematocrit

284
Q

What does raised haematocrit result in?

A
  • hyper viscosity

- thrombosis

285
Q

List the clinical presentations of PV

A
  • may be asymptomatic
  • over 60
  • severe itching when patient is hot
  • erythromelalgia
  • gout
  • HT
  • angina
  • intermittent claudication
  • plethoric complexion
  • hepatosplenomegaly
  • risk of thrombosis / haemorrhage
286
Q

List the vague symptoms of PV due to hyper viscosity

A
  • tiredness
  • dizziness
  • headaches
  • itching
  • tinitus
  • visual disturbance
287
Q

What is erythromelalgia?

A

Burning sensation in fingers / toes

288
Q

What is plethoric complexion?

A

Congested / swollen with blood in facial skin

289
Q

What is hepatosplenomegaly in PV due to?

A

Extramedullary haemopoiesis

- distinguishes PV from secondary causes

290
Q

How do you detect asymptomatic PV?

A

With FBC

291
Q

How do you diagnose PV?

A
  • blood count - raised WBC count / platelets
  • raised HB
  • presence of JAK2 mutation
  • bone marrow biopsy
  • low serum erythropoietin
292
Q

What will a bone marrow biopsy of PV show?

A

Prominent erythroid, granulocytic & megakaryocytic proliferation

293
Q

How do you treat PV?

A

NO CURE - treat to maintain blood count

  • venesection
  • chemo
  • low dose aspirin (along with others)
  • radioactive phosphorus
  • allopurinol
294
Q

What is the purpose of venesection?

A
  • to treat PV
  • lowers PCV & platelets count
  • roves 400-500mL of blood weekly - relieves symptoms
295
Q

Which chemotherapy agents would you give for PV?

A
  • hydroxycarbamide

- low dose busulfan

296
Q

Under what conditions would you administer radioactive phosphorus for PV patients?

A
  • over 70

- due to increased risk of acute leukaemia

297
Q

What does allopurinol do?

A
  • blocks uric acid production

- reduces gout

Phase 2a (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions