Clinical Conditions + Other Flashcards
(105 cards)
1
Q
What is anaemia of chronic disease?
A
Anaemia of chronic disease is a condition characterised by a functional lack of iron and is commonly associated with chronic inflammatory conditions, chronic infections and malignancy
2
Q
What is myelofibrosis?
A
Myelofibrosis is characterised by replacement of the hematopoietic tissue by connective tissue leading to impairment of the generation of all blood cells (pancytopenia)
3
Q
What is homocystinuria?
A
- Homocystinuria is an autosomal recessive disorder, commonly due to a defect in cystathionine β-synthase, leading to an inability in breaking down methionine
- Excess homocystine (oxidised form of homocysteine) is excreted in urine
4
Q
Why is hyperparathyroidism?
A
Hyperparathyroidism is a rare hormone disorder due to the excessive production of parathyroid hormone by the parathyroid glands
5
Q
What is a phaeochromocytoma?
A
- A phaeochromocytoma is a chromaffin cell tumour which secretes catecholamines (mainly adrenaline)
- It may precipitate life-threatening hypertension
6
Q
What are hyperlipoproteinaemias?
A
- Hyperlipoproteinaemias are conditions causing a raised plasma level of 1/more lipoprotein classes as a result of over-production or under-removal
- This occurs due to defects in enzymes, receptors or apolipoproteins
7
Q
What is a metabolic syndrome?
A
A metabolic syndrome is a cluster of the most dangerous risk factors associated with CVD – diabetes and raised fasting plasma glucose, abdominal obesity, high cholesterol and BP
8
Q
What is hypopituitarism?
A
Hypopituitarism is a state of insufficient pituitary hormone production, commonly due to a pituitary adenoma and rarely due to radiation therapy, inflammatory disease or head injury
9
Q
What are myeloproliferative neoplasms?
A
- Myeloproliferative neoplasms are a group of diseases of the bone marrow in which excess cells are produced
- They arise from genetic mutations in the precursors of the myeloid lineage, specifically the gene coding for JAK2
10
Q
What is iron deficiency anaemia?
A
Iron deficiency anaemia is the type of anaemia which develops if the supply of iron is inadequate for the requirements of haemoglobin synthesis
11
Q
What is microcytic anaemia?
A
- Microcytic anemia is a form of anaemia wherein there is a presence of small, hypochromic red blood cells in a peripheral blood smear
- It is usually characterised by a low MCV
12
Q
What are malabsorption conditions?
A
- Malapsorption conditions are caused by the failure to digest and/or absorb ingest nutrients e.g. Coeliac disease and Crohn’s disease
- Under-nutrition may result from eating disorders like anorexia and bulimia nervosa or from reduced availability of food such as in developing countries
13
Q
What is aplastic anaemia?
A
Aplastic anaemia refers to an inability of haematopoietic stem cells to generate mature blood cells
14
Q
What is hyperthyroidism?
A
Hyperthyroidism is an endocrine disorder wherein the thyroid gland is overactive and produces an excess amount of T3/T4
15
Q
What is Secondary Lactase Deficiency?
A
- Secondary lactase deficiency is a condition occurring due to injury to small intestine
- It occurs in both infants and adults and is generally reversible
16
Q
What is pyruvate kinase deficiency?
A
Pyruvate kinase deficiency is an inherited disorder due to the lack of the enzyme pyruvate kinase, which is used by red blood cells to form ATP in the final step of glycolysis
17
Q
What is Congenital lactase deficiency?
A
- Congenital lactase deficiency is an extremely rare condition caused by an autosomal recessive defect in lactase gene
- The infant cannot digest breast milk
18
Q
What is essential thrombocythaemia?
A
Essential thrombocythaemia is a condition characterised by the overproduction of platelets by megakaryocytes
19
Q
What is haemolytic anaemia?
A
Haemolytic anemia is a form of anaemia due to hemolysis either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular, spleen)
20
Q
What is pernicious anaemia?
A
- Pernicious anaemia is a a deficiency in intrinsic factor which results in anaemia from a lack of B12 absorption
- The B12-intrinsic factor complex needs to form to be internalised by receptors in the ileum
21
Q
What is glucose-6-phosphate dehydrogenase deficiency?
A
- G6PDH deficiency is an X- linked recessive inborn error of metabolism wherein the G6PDH enzyme in the pentose phosphate pathway is deficient
- It presents with RBC defects as NADPH cannot be produced by the pentose phosphate in the erythrocytes to reduce glutathione and protect against oxidative damage
22
Q
What is chronic granulomatous disease?
A
Chronic granulomatous disease is a condition caused by a genetic defect in NADPH oxidase complex leading to an enhanced susceptibility to bacterial infections e.g. pneumonia, cellulitis, impetigo
23
Q
What is galactosaemia?
A
Galactosaemia is a clinical condition wherein one cannot use galactose obtained from the diet because of a lack of the kinase or transferase enzyme
24
Q
What is megaloblastic anaemia?
A
Megaloblastic anaemia is a form of anaemia arising due to deficiencies in Vitamin B12 and folate as RBC precursor cells are unable to synthesise DNA and therefore divide
25
What is refeeding syndrome?
- **Refeeding syndrome** is a condition which can occur when nutritional support given to severely malnourished patients
- Ammonia toxicity significant factor (urea cycle down regulated)
26
What is hyperaldosteronism?
- **Hyperaldosteronism** is a physiological state/condition wherein there is an excessive production of aldosterone
- It can be primary due to a defect in adrenal cortex or secondary due to the over-activation of RAAS
27
What is Type II Diabetes?
- **Type II Diabetes** is a long-term metabolic disorder that is characterised by high blood sugar, insulin resistance, and relative lack of insulin
- 90% of patients are overweight/obese, over 40 years old and often asymptomatic (diagnosis made at routine health checks)
28
What is goitre?
- **Goitre** is the enlargement of the thyroid gland due to its overstimulation
- It may accompany either hypo- or hyperthyroidism
29
What is hypothyroidism?
**Hypothyroidism** is an endocrine disorder wherein the thyroid gland is underactive and produces an insufficient amount of T3/T4
30
What is normocytic anaemia?
**Normocytic anemia** is a form of anaemia with a normal MCV but a decreased haematocrit and haemoglobin
31
What is hereditary spherocytosis?
- **Hereditary spherocytosis** is a familial hemolytic disorder associated with a variety of mutations that lead to defects in RBC membrane proteins
- The morphologic hallmark is the microspherocytes which are sphere-shaped erythrocytes rather than biconcave shaped
32
What is diabetes mellitus?
- **Diabetes mellitus** is a group of metabolic disorders in which there are high blood sugar levels over a prolonged period
- Over time, damage of small and large blood vessels causes premature death from cardiovascular diseases
33
What is Graves' disease?
- **Graves' disease** is an autoimmune disease resulting in hyperthyroidism caused by the production of thyroid stimulating immunoglobulin (TSI)
- TSI continuously stimulates thyroid hormone secretion outside normal negative feedback control
34
What is Cushing's Syndrome?
- **Cushing’s Syndrome** is a clinical condition arising due to chronic excessive exposure to cortisol
- It leads to the re-distribution of fat especially in abdomen, supraclavicular fat pads, dorso-cervical fat pad, (buffalo hump), & on face (moon face)
35
What is Hashimoto's disease?
- **Hashimoto's disease** is an autoimmune disease resulting in destruction of thyroid follicles, leading to hypothyroidism
- Is is 5x more common in women and goitre may be present
36
What is hypercholesterolaemia?
- **Hypercholesterolaemia** is a condition where there is a high level of cholesterol in blood
- It presents with cholesterol depositions in various areas of body
37
What is obesity?
- **Obesity** is a chronic condition characterised by excess body fat and is most often defined on the basis of Body Mass Index (BMI)
- The body weight in most adults represents the balance between energy intake and energy expenditure but other factors also contribute to weight gain *e.g. genes, drug therapy, endocrine disorders*
38
What is macrocytic anaemia?
- **Macrocytic anaemia** is a form of anaemia in which the red blood cells are larger than their normal volume
- It is usually characterised by a high MCV
39
What is phenylketonuria?
- **PKU** is the common inborn error of amino acid metabolism due to an autosomal recessive deficiency in phenylalanine hydroxylase
- Phenylalanine accumulates in the tissue, plasma & urine, hence presenting with phenylketones in urine (musty smell)
40
What is polycythaemia vera?
- **Polycythaemia vera** is a specific form of polycythaemia which arises from a myeloproliferative neoplasm in the bone marrow resulting in overproduction of erythrocytes
- In most cases, it is driven by oncogenic mutations that constitutively activate the JAK-STAT signalling pathway
41
What is hereditary hemochromatosis?
- **Hereditary hemochromatosis** is an autosomal recessive disease characterised by excessive absorption of dietary iron
- Iron accumulates in tissues and organs disrupting normal function *e.g. liver, adrenal glands, heart, joints, and pancreas*
42
What is Addison's disease?
- **Addison’s disease** is a clinical condition due to chronic adrenal insufficiency, commonly due to the destructive atrophy from autoimmune response
- Affects more women than men and the exact reason for autoimmunity is unknown
43
What is hyperpituitarism?
**Hyperpituitarism** is a state of excess pituitary hormone production mainly due to a functional hypersecreting pituitary adenoma
44
What is marasmus?
- **Marasmus** is a type of protein-energy malnutrition most commonly seen in children \< 5
- Patient is emaciated, muscle wasting, loss of body fat, thin & dry hair, diarrhoea (no oedema)
45
What is Addisonian Crisis?
- **Addisonian Crisis** is a life threatening emergency due to adrenal insufficiency
- It is often precipitated by severe stress, salt depravation, infection, trauma or abrupt steroid drug withdrawal
46
What is anaemia?
- **Anaemia** is defined as a haemoglobin concentration lower than the normal range
- It is not a diagnosis but a manifestation of an underlying disease state
47
What is Type I Diabetes?
- **Type I Diabetes** is the absolute lack of insulin secondary to autoimmune destruction of β cells
- The aetiology not fully understood but the patient is usually young (\< 30 years)
48
What is Primary Lactase Deficiency?
- **Primary lactase deficiency** is a condition occurring due to the absence of lactase persistence allele
- It only occurs in adults and has its highest prevalence in Northwest Europe
49
What is kwashiorkor?
- **Kwashiorkor** occurs typically in a young child displaced from breastfeeding and fed with a high carbohydrate, very low protein diet
- Patient is apathetic, lethargic, anorexic, anaemic, has generalised oedema and low serum albumin
50
What is hereditary haemochromatosis?
Autosomal recessive
Mutation in HFE gene
HFE protein _usually_ interacts with tranferrin receptor- reducing its affinity for iron-bound tranferrin
Mutated HFE can't bind to transferrin-
TOO MUCH Iron enters cells
Iron accumulates in end organs- damageing
Treated with venesection
51
What are the symptoms of hereditary haemochromatosis?
Liver cirrhosis
Diabetes mellitus
Hypogonadism
Cardiomyopathy
Arthropathy
Increased skin pigmentation
52
What is haemosiderosis?
form of iron overload disorder-haemosiderin (insoluble form of iron transport\_
53
Define thalassaemia.
= reduced rate of synthesis of normal alpha or beta globin chains
54
Why does are red cells defective if there is an excess of a globin chain?
Insoluble aggregates form
Aggregates are oxidised
Damage red cell membrane
55
Why is thalassaemia a form of haemolytic anaemia?
Defective haemoglobin production, RBCs=destroyed
* Erythrocytes in bone marrow
* Mature red cells in spleen
56
On which chromosome are the alpha and beta globin genes located?
* Beta= Chromosome 11
* Alpha= Chromosome 16
57
What are the 4 types of α-thalassaemia?
1. **Silent carrier state**
1. Single α-globin gene deletion
1. Asymptomatic
2. **α-thalassaemia trait**
1. Deletion of 2 α-globin genes
1. Minimal/ No anaemia
3. **Hemoglobin H (HbH) disease**
1. Deletion of 3 α-globin gene
1. Moderately severe anaemia
1. Microcytic, hypochromic, target cells, Heinz bodies
4. **Hydrops fetalis**
1. Deletion of 4 α-globin gene
1. Usually intrauterine death
58
What are the 2 β-Thalassaemia types?
1. **β-Thalassaemia Major**
1. ****βo/(βo/βo)/(β+/β+)
1. Severe- transfusion dependent anaemia- symptoms show 6-9 months after birth
2. **β-Thalassaemia Minor/ β-Thalassaemia Trait**
1. ****=asymptomatic/mild anaemia
2. *Heterozygous*
3. βo/β or β+/β
* βo=total absence of globin production
* β+=reduction of globin production
59
Give 2 causes of microcytic anaemias.
* Iron deficiency
* β=Thalassaemia minor
60
What are the consequences of Thalassaemia? (4)
* Extramedullary haemopoiesis
* Splenomegaly
* Hepatomegaly
* Expansion of haemopoiesis into bone
* Impairs growth, skeletal abnormalities
* Reduced Oxygen delivery- increased EPO
* Iron overload
* Excessive absorption--\> ineffective haematopoiesis
* Repeated blood transfusions treating anaemia
* Reduced life expectancy
61
How is thalassaemia treated?
* RBC transfusion
* Iron chelation- bind iron
* Folic acid - depleted in body
* Immunisation
* Holistic care
* Stem cell transplantation
* Preconception counselling- for couples at risk
62
What causes sickle cell disease?
Inheritance of sickle beta-globin chain
Point mutation- substitution
Valine--\> Glutamic acid
HbSS= homozygous sickle cell anaemia
HbS + another abnormal Hb= sickle cell anaemia
HbS= Carrrier state= mild asymptomatic anaemia- protection against malaria
63
What happens to the red blood cells in someone who has sickle cell anaemia in a low oxygen state?
Deoxygenated HbS forms polymers
Irreversibly sickled red cells are less deformable - cause occlusion of small blood vessels
64
What are the 3 crisis types that can be caused by sickle cell disease?
1. **Vaso-occlusive**
1. Painful bone crisis
2. Pooling in organs- chest/spleen
2. **Aplastic**
1. No RBCs produced
2. *(often triggered by parovirus infection in kids)*
3. **Haemolytic**
65
How are sickle cell disease crises treated?
* Folic acid
* Penicillin and vaccinations if hyposplenic
* Red cell exchange
66
What are the consequences of having sickle cell anaemia? (3)
* Reduced life expectancy- stroke, acute chest syndrome, multi-organ failure
* Acute and chronic pain
* Stroke, cognitive problems, kidney failure
67
The bone marrow can compensate for a decrease in lifespan of red blood cells by increasing its capacity how many times?
6x
(Anaemia is this is exceeded)
68
What are the symptoms and consequences of haemolytic anaemias?
* Jaundice
* Pigment gallstones
* Splenomegaly
* Cardiac arrest
* Lack of oxygen delivery to tissues
* Hyperkalaemia due to release of intracellular contents
69
Name 4 causes of inherited haemolytic anaemias and 4 causes of acquired haemolytic anaemias.
Mechanical damage: Heart valves, vasculitis, DIC
Osmotic changes eg Drowning
70
What are the 3 key lab features of haemolytic anaemias?
1. Increased reticulocytes
2. Raised bilirubin
3. Raised LDH (Lactate dehydrogenase- high in RBCs)
71
Name each of these abnormal red blood cell types:
72
What are the 2 broad classes of autoimmune haemolytic anaemias?
Warm: IgG= maximally active at 37 degrees C
COld: IgG= maximally active at 4 degrees C
73
Name to causes of autoimmune haemolytic anaemias.
1. Infections- chest infections in children
2. Cancers- of lymphoid system (eg Beta cell lymphoma)
74
What are the causes of macrocytic anaemia?
FATRBC
* **F**etus (pregnancy)
* **A**lcohol
* **T**hyroid disease(ie hypothyroidism)
* **R**eticulocytosis
* **B**12 and folate deficiency
* **C**irrhosis and chronic liver disease
75
What are the 2 main causes for the overproduction of blood cells?
1. Myeloproliferative disorders
2. Physiological reaction
76
What are myeloproliferative disorders?
Myeloproliferative neoplasms (MPN)
(Dysregulation st multipotent haematopoietic stem cell)
77
Name 4 myeloproliferative disorders.
1. **Essential thrombocythaemia**:
1. too many platelets
2. **Polycythaemia Vera**:
1. too many RBCs
3. **Myelofibrosis**:
1. hardening of bone marrow
4. **Chronic myeloid leukaemia**
1. ****too many immature white blood cells
78
What are the clinical features of myeloproliferative disorders?
1. Hypercellular marrow/marroe fibrosis
2. Cytogenetic abnormalities
3. Thrombotic/haemorrhagic _diatheses_ *(=tendency to suffer from)*
4. Extramedullary haemopoiesis
5. Potential to transform to acute leukaemia
79
What does the mutant copy of the JAK2 (Janus kinase 2 gene) result in? (Chromosome 9)
Increased proliferation and survival of haematopoietic precursors--\> cause myeloproliferative disorder
Cytoplasmic tyrosine kinase on chromosome 9
80
What is the cause of Polycythaemia Vera in the majority of patients?
JAK2 mutation
81
What are the clinical features of Polycaemia Vera?
* Arterial thrombosis
* Venous thrombosis
* Haemorrhage into skin/GI tract- breaking cappillaries
* Splenic discomfort, splenomegaly
* Gout
* Pruritis (severe itching of the skin)
82
How is Polycythaemia Vera managed?
Venesection
Aspririn (reduce arterial thrombosis)
Manage CVS risk factors
83
What are the primary and secondary causes of polycythaemia?
* Primary: Polycythaemia vera
* Secondary: EPO production
* Physiologically appropriate
* Hypoxia
* CO poisoning
* Physiologically inappropriate
* Renal carcinoma
* Renal artery stenosis
84
What is essential thrombocythaemia?
Excess platelets in blood
85
What can cause essential thrombocythaemia?
* JAK2/CALR gene mutations
* Large and excess megakaryocytes in bone marrow
* Thrombotic events eg acute infection
86
How should thrombocythaemia be managed?
CVS risk factors- aggressively managed:
**Aspirin**
Use **hydroxycarbomide**- return platelet count to normal range
Treat cause if:
* Infection
* IBS
* Injury eg trauma
* Cancer
* Haemorrhage
* Cancer
* Post splenectomy
87
The following blood film shows tear drop shaped RBCs. What is this indicative of?
Heavily fibrotic marrow- little space
88
What might cause myelofibrosis?
* Polycythaemia Vera
* Essential thrombocythaemia
89
What are the clinical features of myelofibrosis?
Fatigue
Sweats
Weight loss
90
What are the consequences of massive splenomegaly?
1. Pain
2. Early saiety: can't eat full meal- stomach can't expand
-marrow failure- requires transfusions
* Can transform to leukaemia
* Early death
91
How might a patient with Chronic Myeloid Leukaemia present?
(disease of adults, very rare in children)
* Splenomegaly
* Hyperviscosity (sticky blood)
* Bone pain
92
What will the blood film of Chronic Myeloid Leukaemia show?
Excess of all myeloid series
93
How does the cancer drug Imantinib work?
Tyrosine kinase inhibitor
94
What are the 2 main causes of pancytopenia ?
* Reduced production
* Increased removal
95
What may cause the increased removal of cells causing pancytopenia? (rare)
**Immune destruction**
**Splenic pooling**- hypersplenism in massive splenomegaly
**Haemophagocytosis** (in bone marrow)
96
Identify some causes of reduced production of blood cells causing pancytopenia.
* B12/floate deficiency
* Drugs- chemotheraphy, antibiotics
* Viruses- EBV, viral hepatitis, HIV, CMV
* Marrow fibrosis
* Radiation
* Idiopathic aplastic anaemia
* Congenital bone marrow failure eg Fanconi's anaemia
* Bone marrow infiltration
97
What is aplastic anaemia?
Pancytopenia with hypocellular bone marrow in absence of an abnormal infiltrate and no increase in fibrosis (thought to be autoimmune)
98
What are the 3 causes of thrombocytopenia?
99
What are the symptoms/consequences of severe thrombocytopenia?
* Patients generally not symptomatic until platelet count \<30
* Easy bruising
* Petechiae, purpura
* Mucosal bleeding
* Severe bleeding after trauma
* Intracranial haemorrhage
100
How is thrombocytopenia due to increased platelet destruction (Autoimmune thrombocytopenic purpura) treated?
Immunosuppression:
* corticosteroids
* IV immunoglobulin
(platelet transfusions do not work- transfused platelets get destroyed too)
101
What are the 2 types of causes of disorders of platelet function?
Hereditary (rare)
Acquired (common)
102
Name a hereditary platelet disorder.
Bernard Soulier syndrome
103
Give some examples of acquired platelet function disorders.
* Aspirin
* NSAIDs
* Clopidogrel
* Uraemia
104
What is von Glerke's disease?
Glucose-6 phosphatase deficiency
(Converts Glucose-6 phosphate to glucose in liver)
106
What is McArdle disease?
Muscle glycogen phosphorylase deficiency
(Rate limiting enzyme in glycogen degradation)
