Clinical Conditions

Question 1

Describe achondroplasia

Answer 1

One of the most common forms of short limb dwarfism. Autosomal dominant point mutation in fibroblast growth factor receptor-3 gene, causing gain of function of gene, leading to reduced endochondral ossification, decreased cartilage matrix product. and inhibited proliferation of chondrocytes in growth plate cartilage.

Question 2

What is Paget’s disease?

Answer 2

Bone enlargement and distortion, with resultant increase in fracture risk. Disorder of bone turnover. Skull, spine, femur= most common. Bones thicker and more porous as brittle bone deposited. Altered balance between levels of activity of cells in bone remodelling.
May be severe pain
When the skull is affected, it slowly enlarges, as do the jaws – the maxilla more frequently than the mandible that necessitates adjustments to dentures. The teeth may become displaced and become fused with bone, complicating extractions. Oral surgery may become complicated by severe haemorrhage.

Question 3

Describe cretinism

Answer 3

Permanent intellectual and neurological damage in infant with thyroid hormone deficiency

Question 4

Describe acromegaly

Answer 4

Enlarged extremeties as excess GH in an adult when epipyhses have fused so bones can’t grow in length, but only in width- periosteal growth.

Question 5

What is osteoporosis?

Answer 5

Reduced bone density with bone matrix loss, loss of structural density and demineralisation, with increased fracture risk, espc. in spine, hip and wrist.

Question 6

What is the most common cause of pathological fractures?

Answer 6

Osteoporosis

Question 7

Name the two different types of Osteoporosis

Answer 7

Primary- age-related( type 1 and type 2, 1= mainly post-menopausal women, 2= low-turnover) and Secondary- related to another condition or drugs.

Question 8

Describe osteogenesis imperfecta

Answer 8

Genetic disorder affecting synthesis of type 1 collagen in bone ossification. Bones brittle and prone to fractures. Possible confusion with multiple fractures caused by deliberate injury= legal importance.
Symptoms include: blue sclera, hearing loss, fragile bones-multiple fractures, hypermobile joints.

Question 9

What is Vitamin D essential for and what conditions may result if deficient?

Answer 9

Normal bone ossificiation. Rickets may result if deficiency in children when bones still growing, or osteomalacia in adults when epiphyses have fused so bones become pliable in remodelling. Osteoid formed- pliable + poorly mineralised matrix, so bones prone to fractures and unable to support body weight so bend.

Question 10

What is hypoglycaemia and what are its clinical symptoms?

Answer 10

Plasma glucose < or equal to 3mmol/L. Sweating, anxiety, hunger, tremor, palpitations, dizziness, confusion, visual trouble, seizures, coma, tiredness, tingling around lips, slurred speech, staggering walk. Often confused with symptoms of alcohol intoxication.

Question 11

Causes of fasting hypoglycaemia

Answer 11

Main cause= insulin or sulphonylurea (OHD) treatment in known diabetic. In a non-diabetic, may result from EXPLAIN: EXogenous drugs, Pituitary insufficiency, Liver failure + rare inherited enzyme defects, Addison’s disease, Islet cell tumours and immune hypoglycaemia and Non-pancreatic neoplasms e.g. fibrosarcomas.

Question 12

What are the symptoms of Multiple Sclerosis?

Answer 12

Visual disturbances, muscle weakness, loss of feeling

Question 13

What is Multiple Sclerosis?

Answer 13

AI myelin sheath destruction, resulting in an increased membrane capacitance, and leakage of K+ ions, causing hyperpolarisation and conduction failure.

Question 14

Why do patient with MS suffer multiple remissions in symptoms?

Answer 14

This occurs as the myelin starts to grow back, as the myelin is insufficient for saltatory conduction, and interferes with ion channel redistribution, so nerve conduction via passive conduction is prevented, as would occur in an unmyelinated nerve.

Question 15

Which enzyme is defective in phenylketonuria?

Answer 15

Phenylalanine hydroxylase- responsible for conversion of phenyalanine to tyrosine.

Question 16

Name 2 hormones synthesised from tyrosine.

Answer 16

Adrenaline, Tri-iodothyronine(T3), Thyroxine(T4), Noradrenaline

Question 17

Name the 6 Ps for an acute arterial occlusion

Answer 17

Pallor, Perishingly cold, Pain, Paraesthesia, Pulselessness, Paralysis

Question 18

Describe the classic triad of symptoms of diabetes mellitus and why each one occurs.

Answer 18

Polyuria, polydipsia and weight loss. Polyuria: high glucose conc in b.stream, not all of this glucose can be reabsorbed at kidney nephron so remains in nephron as renal threshold exceeded, placing an extra osmotic load on nephron so water moves in and is excreted as copious urine. Polydipsia then ensues as more water is excreted and due to osmotic effects of glucose on body’s thirst centres. Glucose is unable to be used by the body’s cells for energy as can’t be uptaken from blood so increased protein and fat metabolism in tissues, resulting in weight loss.

Question 19

Explain why a diabetic may experience damaged vision (retinopathy).

Answer 19

High glucose concentration. Excess glucose undergoes metabolism via aldose reductase to produce sorbitol. This reaction consumes NADPH required to maintain free SH groups on adjacent Cyst residues of proteins in lens of eye so proteins become cross-linked, causing cataracts.

Question 20

Why might a diabetic be more susceptible to UTIs?

Answer 20

Excess glucose attracting bacteria in kidneys.

Question 21

Describe differences between type 1 and 2 diabetes mellitus.

Answer 21

Type 1

• AI destruction of almost all beta cells of islets of Langerhans in pancreas,so no endogenous insulin prod-lack of insulin.
• Typically young people, <30yrs.
• Always requires insulin injections from start.
• Diabetic ketoacidosis.
• Urgent treatment required at diagnosis to prevent life-threatening diabetic ketoacidosis.

Question 22

Why do patients with type 2 diabetes feel TATT?

Answer 22

Cells unable to utilise glucose from blood as insulin lack/insulin resistance and so there is reduced ATP resulting from glucose metabolism/reduced aerobic respiration.

Question 23

Describe why excess ketones are formed in an untreated type 1 diabetic?

Answer 23

Ketones are able to cross the blood-brain barrier and so can be utilised by the brain in addition to glucose. FA cannot on the otherhand be used by the brain as they are unable to cross the blood brain barrier. The lack of insulin in type 1 diabetic means inability of brain to utilise glucose for efficient functioning so reverts to ketones produced as low insulin:anto-insulin and high rate of beta-oxidation of FA, meaning ketone prod. from FA.

Question 24

Give 2 examples of oral hypoglycaemic drugs used in diabetics.

Answer 24

Sulphonylureas and metformin.

Question 25

How can malignant hyperthermia be treated?

Answer 25

Administer a muscle relaxant e.g. dantrolene- inhibitor of ryanodine-sensitive non-classical ligand-gated Ca2+ channel, so inhibited Ca2+ release from SR. Supportive therapy includes cooling, O2, blood pH correction and electrolyte imbalances and treatment of cardiac abnormalities.

Question 26

Describe malignant hyperthermia

Answer 26

Excessive muscle rigidity and severe hyperthermia with rapid onset after administration of certain muscle relaxants and anaesthetics such as succinylcholine. This is a genetic disease resulting from excessive/prolonged Ca2+ release from SR, most commonly as result of mutations in Ca2+ release channels within SR. Prolonged increase in sarcoplasmic Ca2+ conc results, with subsequent muscle rigidity from Ca2+ dependent ATP consumption, and hyperthermia as increased met. to replenish ATP. Cardiac abnormalities result from hyperkalaemia as ATP-dependent maintenance of ion gradients across PM fails.

Question 27

Describe the genetics of cystic fibrosis

Answer 27

Most common mutation=3bp deletion in the CFTR gene, on chromosome 7, causing a deletion of codon for phenylalanine(F) at position 508=delta-F508 mutation, so deletion of 1 aa from protein CFTR, so protein isn’t targeted to the membrane, so is absent from epithelial cells.

Question 28

Describe the movement of ions across a lung epithelial cell in terms of the CFTR protein, Na+-K+-2Cl- cotransporter, Na+-K+-ATPase and K+channel, in order to maintain electro-neutrality.

Answer 28

Using the Na+ gradient, K+ and Cl- ions are moved into the cell via the Na+-K+-2Cl- cotransporter. Cl- in cell can then pass across the cell from the interstitium facing the blood, and through the CFTR, and so into the lumen of the alveoli. Na+-K+-ATPase pums Na+ back out of the cell, and as Cl- is an osmotically active ion, H2O follows Cl- out into the lumen, across the mucous membrane, keeping it moist. K+ channel allows some K+ efflux to balance all ions so that the electrical potential remains the same.

Question 29

List the complications of CF

Answer 29

Respiratory infection, infertility, malabsorption, steatorrhoea, pancreatitis

Question 30

Is CF caused by a frame shift mutation and explain you answer?

Answer 30

No, CF results from a 3bp deletion which doesn’t cause a change in the reading frame.

Question 31

6 main features of diabetic ketoacidosis

Answer 31

prostration, hyperventilation, vomiting, nausea, dehydration, abdominal pain.

Question 32

Why do patients with diabetic ketoacidosis deteriorate so quickly?

Answer 32

Ketones= acidic, they lower blood pH, resulting in electrolyte imbalances and an inability for enzymes to function properly. Patients vomit due to the effect of ketoacidosis on the gut, and so they are unable to overcome their thirst. Respiratory rate increases to exhale more CO2 as carbonic acid=acidic.

Question 33

Describe botulism

Answer 33

Botulinum toxin produced by bacterium clostridium (gram +ve bacilli, anaerobic and spore-forming). Toxin can block ACh release at synapses and NMJ so no binding to motor end plate required to stimualte muscle contraction. Paralysis of face and limbs, may kill if cardiac and respiratory centres of brain shut down.

Question 34

Describe how organophosphate poisoning e.g. from herbicides, insecticides and nerve gases, can cause muscle disorder.

Answer 34

Results in irreversible inhibition of the acetylcholinesterase enzyme. so ACh remains in motor end-plate receptors, and muscle stays contracted.

Question 35

Describe muscular dystrophy

Answer 35

genetic faults cause absence or reduced synthesis of specific proteins which anchor actin filament to sarcolemma so in absence, muscle fibres may tear themselves apart when contracting. Progressive disease with gradual muscle weakening.

Question 36

Describe Duchenne Muscular dystrophy

Answer 36

X-linked recessive condition in which complete absence of protein dystrophin, which attaches actin filaments to sarcolemma, allowing sarcolemma to move with actin filaments during contraction. Without the protein, the fibres pull and tear, resulting in a damaged sarcolemma. CK in released into serum so blood test can be done. Also, excess Ca2+ enters cell, causing necrosis. Swelling (pseudohypertrophy) occurs before fat and CT replace muscle fibres.

Question 37

Give some symptoms of Myasthenia Gravis

Answer 37

Ptosis, double vision, sudden falling and fatigueability.

Question 38

Give some signs and symptoms of Duchenne muscular dystrophy

Answer 38

Gower’s sign: use of hands on knees to generate strength, early onset, contractures- fibrosis of skeltetal muscle, muscle weakness.

Question 39

How can DMD be treated?

Answer 39

Steroid therapy(prednisolone-stimualtes muscle growth). Physiotherapy provides relief. Gene therapy?

Question 40

Describe the CT disorder of Marfan’s syndrome.

What other condition may be mistaken for this syndrome in children?

Answer 40

Autosomal dominant, abnormal expression of fibrillin gene causes undeveloped elastic fibres. Large arteries rutpute as high BP due to bulging of arteries creating a smaller lumen. Sypmtoms: abnormally tall, frequent joint dislocation, may be at risk of catastrophic aortic rupture.
Homocystinuria.

Question 41

Describe Ethlers-Danlos syndrome

Answer 41

Deficieny in type III collagen (reticular fibres), so rupturing in tissues with high reticullin content. May have unstable joints and bruise easily.

Question 42

What is the crisis point for Myasthenia Gravis?

Answer 42

When respiratory muscle is affected

Question 43

Why would a patient with CF have salty sweat?

Answer 43

Cl- is not reabsorbed from the lumen into the sweat glands due to faulty CFTR, so Na+ also remains with the Cl- in the lumen in order to maintain electro-neutrality.

Question 44

Why do sickle-cell disease sufferers experience anaemia?

Answer 44

Sickle cells have a shorter lifespan than normal rbc, as undergo frequent changes in shape depending on pO2, so their cell membrane is abnormal, and there is increased premature breakdown by the spleen, so less haemoglobin in the blood stream than normal due to rapid breakdown of sickle cells.

Question 45

What is the typical rbc life span, and what is the life span of a sickle cell?

Answer 45

120 days

30 days=sickle cell

Question 46

why are significant vascular changes associated with diabetes?

Answer 46

because of the hyperglycaemia, glycosylation of proteins occurs, which damages the integrity of the vessel wall, leading to hardening and thickening.

Question 47

only form of hyperthyroidism to give exophthalmos?

Answer 47

grave’s disease