MEH Flashcards
What leads to pituitary dwarfism?
How is this condition characterised?
How is it treated?
Growth hormone deficiency in childhood - complete or partial
Height below 3rd percentile, growth rate slower than expected for age, delayed or no sexual development during teen years.
Responds to growth hormone therapy
What condition does growth hormone excess lead to in childhood and adulthood?
Childhood - GIGANTISM - often caused by a pituitary adenoma which is therefore secreting too much GH
Adulthood - ACROMEGALY - literally means large extremities e.g. Hands, feet, lower jaw
What is Chronic Granulomatous Disease?
- Genetic defect in NADPH oxidase (used to create superoxide in phagocytes to be used in oxidative burst)
- Leads to enhanced susceptibility to bacterial infections e.g. Pneumonia, abscesses, impetigo, cellulitis.
Build up of which toxic compound leads to oxidative stress in paracetamol overdose? What does this lead to?
What is the treatment for this? What does it do?
NAPQI –> depletes glutathione levels
Acetylcysteine - replenishes depleted glutathione
Why are RBCs particularly susceptible to oxidative damage?
In which disease is this going to be a particular issue?
Why is pyruvate kinase deficiency a problem for RBCs?
They have no nuclei so can’t transcribe new proteins if they become damaged
Particular problem in glucose-6-phosphate dehydrogenase deficiency - no NADH from pentose phosphate pathway so can’t regenerate reduced glutathione (GSH) from oxidised glutathione (GSSG)
Pyruvate kinase deficiency - RBCs have no mitochondria so rely on glycolysis for energy. Pyruvate kinase is responsible for the final step in glycolysis which allows for the net production of 2 ATP molecules. Without the step there would be no overall gain in ATP.
What is hereditary spherocytosis?
What complications can arise from it?
- Mainly autosomal dominant
- Gene mutation most commonly affects ankyrin, but also spectrin, protein 4.2 and band 3 - these connect plasma membrane to cytoskeleton in RBCs
- When these proteins are malformed or absent RBCs are spherical in shape
- -> not as flexible so for passing through/leaving capillaries so can lead to infarct
- -> smaller surface area for nutrient exchange
Complications:
- Infarcts in spleen as spleen tries to remove –> splenectomy may be needed
- Splenomegaly - spleen takes up spherocytes and macrophages of the RES invade to destroy
- Increased bilirubin due to haemolysis of spherocytes –> jaundice, gallstones
- Folate deficiency due to increased bone marrow requirement
- Aplastic anaemia - More EPO has been released and bone marrow has been left empty
- High MCV and reticulocyte count
What is hereditary haemochromatosis? Which gene and protein are affected? What happens as result? Which organs are most susceptible to damage? How do you treat?
- Autosomal recessive disorder
- Mutation in chromosome 6 in gene coding for HFE protein
- HFE normally binds to transferrin receptors (transferrin binds to iron in blood to transport it to cells) on cells such as macrophages so that transferrin-iron complexes can’t bind and iron can’t be absorbed.
- Mutated HFE can’t bind so too much iron is absorbed into cells.
Most susceptible organs: liver (cirrhosis), adrenal glands, heart (failure), joints (arthritis), pancreas (diabetes)
Treatment: venesection
What is transfusion-associated haemosiderosis?
How would you treat?
If not making enough RBCs, on chemo, have thalassaemia, sickle cell etc will be given blood transfusions.
Can get gradual accumulation and overload of iron.
Iron chelating agents, but mainly venesection.
Which syndrome can be caused by long-standing iron deficiency anaemia?
What does it involve?
Plummer-Vinson Syndrome
Changes to epithelia e.g. Oesophagus
What is sickle cell anaemia?
- Caused by a mutation on chromosome 11
- Leads to a mutation of glutamate to valine in B globin subunits of haemoglobin
- Valine is hydrophobic so joins with valines from other haemoglobins to avoid contact with water
Leads to clumps of deoxygenated Hb within red cells –> shape is distorted (sickle shaped)
Sickled cells are:
- more prone to lyse –> SICKLE CELL ANAEMIA
- more rigid - block capillaries –> SICKLE CELL CRISIS
What is thalassaemia?
Group of genetic disorders where there is an imbalance between the number of a and B globin chains
What is B-thalassaemia?
What are the major and minor forms?
When do symptoms appear? What are they?
- Mutation on chromosome 11
- Decreased/absent B globin chain production –> relative excess of alpha globin
- Alpha globin unable to form stable tetramers
Major: Individual is homozygous for B-thalassaemia
Minor: heterozygous - fewer symptoms
SYMPTOMS:
Appear after birth - HbF (foetal) is made up of alpha and gamma globins so child is unaffected until HbF changes to HbA
- Anaemia - can’t make proper Hb so can’t transport iron bound to O2
- Leads to SOB, tiredness/fatigue
- Palpitations
- Pale skin
What is a-thalassaemia?
On what does the severity depend?
When is onset?
What are symptoms?
- Mutation on chromosome 16 leads to decreased/absent a-globin chain production –> relative excess of B globin
- The B globin chains form tetramers with high affinity for oxygen making them poor O2 transporters
- Severity depends on how many of the 4 relevant genes are affected: 1 - silent carrier 2 - mild 3 - severe/fatal 4 - dead!
Onset is before birth - foetal Hb (HbF) contains a-globins so will be affected
Symptoms: Tiredness/fatigue, palpitations, SOB
What leads to pernicious anaemia?
Intrinsic factor deficiency
IF binds to B12 in small intestine and the complex can then be absorbed in the ileum.
Without IF this is not possible, meaning RBC count is low as B12 is needed for DNA synthesis - can’t make more RBCs
How does G6PDH deficiency relate to anaemia?
What might be a sign of this?
What needs to happen before you prescribe any patient with a haemolytic drug?
When patients with G6PDH deficiency are in states of oxidative stress (such as infection or on certain medications) their red blood cells are more vulnerable to damage by reactive oxygen species.
They will then be removed by the RES –> HAEMOLYTIC ANAEMIA
Patient may become jaundiced due to damaged RBCs being phagocytosed in the spleen and their Hb being metabolised to bilirubin.
Ask lab to screen for G6PDH deficiency before giving haemolytic drugs.
How is pyruvate kinase deficiency related to anaemia?
Pyruvate kinase catalyses final step in glycolysis - without it there is not net ATP production
Na+/K+ATPase therefore stops working –> K+ lost to plasma and water follows –> cells shrink and die –> HAEMOLYTIC ANAEMIA
What abnormality will typically be seen on a blood film of someone with hyposplenism?
What are these?
Howell-Jolly bodies
Remnants of basophilic nuclei (clusters of DNA) in circulating red blood cells.
These cells would normally be removed by the spleen, so shows low splenic function.
What is neutropenic sepsis?
Patients who have received chemotherapy (which kills neutrophils) are at risk of developing sepsis - immune response depleted
What are Heinz Bodies?
When would you see them?
Oxidative damage leads to haemoglobin and other proteins becoming cross-linked by disulphide bonds, forming insoluble aggregates called Heinz bodies.
Would likely be seen in G6PDH deficiency.
What is the difference between Osteoporosis and Osteomalacia?
Osteoporosis - decreased bone density
Osteomalacia - Not enough mineral in bone due to vitamin D deficiency (not absorbing enough calcium) –> RICKETS
What causes cretinism? What are its features?
Hypothyroidism - discovered in infancy and correctable if treated within first few weeks
Dwarfed stature, mental deficiency, poor bone development, slow pulse, muscle weakness, GI disturbances
What causes myxedema? What are its features?
Hypothyroidism
Thick, puffy skin, muscle weakness, slow speech, mental deterioration, intolerance to cold
What is Hashimoto’s Disease? How do you treat it?
What T3, T4 and TSH levels would be seen?
Autoimmune destruction of thyroid follicles (contain the thyroglobulin used to make T3 and T4) –> hypothyroidism
Treatment: Oral thyroxine (T4)
Low T3 and T4
High TSH - T3 and T4 not exerting negative feedback. Thyroid not able to respond appropriately to the resulting high TSH
What causes Grave’s disease?
What are its features?
How do you treat it?
Autoimmune disease - Thyroid Stimulating Immunoglobulin (TSI) stimulates TSH receptors on follicle cells –> increased T3 and T4 –> decreased TSH due to negative feedback, but doesn’t affect T3 and T4 secretion.
Increase in BMR, excessive sweating, tachycardia, weight loss, muscle weakness, bulging eyes (sometimes)
Treat with Carbimazole (blocks formation of T3 and T4)
What are the cause, symptoms and treatment of growth hormone deficiency?
CAUSE: generally unknown, but can be due to genetic mutation or autoimmune inflammation
SYMPTOMS: Subtle - decreased tolerance to exercise, decreased muscle strength, increased body fat, reduced sense of ‘well-being’
TREATMENT: GH manufactured by recombinant DNA technology
What are the symptoms of gonadotropin (LH and FSH) deficiency?
Lack of libido, infertility, oligomenorrhea or amenorrhea
What are the possible causes of ADH deficiency? What does it lead to?
CAUSES: Hypothalamic tumour or one which has extended into the hypothalamus. Also cranial radiotherapy, pituitary surgery or infections such as meningitis
RESULT: Excess excretion of dilute urine –> dehydration, thirst, hypernatraemia = DIABETES INSIPIDUS
Which hormones regulate prolactin release?
What causes hyperprolactinaemia?
What are its symptoms?
How would you treat it?
Hormones: Prolactin releasing hormone (stimulates) and dopamine (PIH) (inhibits)
Causes: Pituitary adenoma that secretes prolactin = prolactinoma
Can also be due to pregnancy, stress, exercise, antipsychotics and antidepressants
Symptoms: Galactorrhea (unexplained milk production, gynecomastia (hard breast tissue), hypogonadism, amenorrhea, erectile dysfunction
Treatment: Dopamine receptor agonists - inhibits prolactin secretion
Sometimes trans-sphenoidal surgery if necessary
