Clinical Conditions - ESA 1

Question 1

What is Amyloidosis?

Answer 1

Misfolding of proteins that leads to insoluble aggregates

Question 2

What causes Sickle Cell anaemia?

Answer 2

Hydrophilic Glutamate -> Hydrophobic Valine, causes Hydrophobic pocket when cell is in T-state. Hb can then polymerise causing the cell to adopt sickle shape

Question 3

What causes Cystic Fibrosis?

Answer 3

Mutation of the CFTR gene, leads to impaired Cl-

Question 4

What causes α + β Thalassaemia? Which is more serious and why?

Answer 4

Decreased or absent α or β chains.

α-chains unable to form stable tetramers by themselves, after Foetal Hb goes they suffer growth problems

Question 5

What causes Haemophillia A?

Answer 5

Reduced or Absent Factor VIII production meaning blood doesnt clot as well

Question 6

What causes Scurvy and what does it lead to?

Answer 6

Vit. C deficiency, Causes reduced H-bonds and cross links in Collagen so its not as strong as usual

Question 7

What is an Ectopic Pregnancy?

Answer 7

Implantation of the embryo in the Fallopian tube

Question 8

What is Placenta Praevia?

Answer 8

Implantation of the embryo in the lower segment of the uterine wall blocking the cervix

Question 9

What is Ethlers-Danlos Disease?

Answer 9

Deficiency of type III collagen leading to loss of reticulin, presents as stretchy skin, unstable joints + easy bruising

Question 10

What is Vitiligo?

Answer 10

Autoimmune destruction of melanocytes leading to depigmentation

Question 11

What is Alopecia Areata/Universalis?

Answer 11

Autoimmune destruction of hair follicles

Question 12

What is Osteogenesis Imperfecta?

Answer 12

Disease resulting in type I collagen deformity/deficiency, most cases repeated fractures cause bowed long bones, blue sclera

Question 13

What is Rickets?

Answer 13

Deficiency of vitamin D in children, leads to bowed bones as they are still growing

Question 14

What is Osteomalacia?

Answer 14

Vitamin D deficiency in adults, leads to bone/back arch. Can be cause by damage to kidneys or liver. More common in people with dark skin as they don’t synthesis Vit. D so well

Question 15

What is Osteoporosis?

Answer 15

Type I - (Menopausal) due to oestrogen no longer mediating Osteoblasts
Type II - (Old age) due to loss of Osteoblast function

Question 16

What causes Acromegaly?

Answer 16

Too much GH leads to increase in bone width from intramembranous growth

Question 17

What is Cretinism caused by?

Answer 17

Neonatal Hypothyroidism leads to retardation + short stature. Corrected with thyroxine before 3 weeks

Question 18

What is Myasthenia Gravis?

Answer 18

Autoimmune destruction of the end plate ACh receptors. Causes droopy eyelids, fatigue, sudden collapse. Treated by immunosuppressants + AChesterase inhibitors

Question 19

What is Muscular Dystrophy?

Answer 19

Absence of dystrophin means the muscle fibres tear on contraction, this leads to calcium induced necrosis. Fat + connective tissue layer down (pseudohypertrophy), presents with Gowers sign (brace thighs with arms)

Question 20

What is Malignant Hyperthermia?

Answer 20

Reaction to Succinylcholine leads to release of Ca2+ from Sarcoplasmic reticulum -> spike in oxidative phosphorylation of skeletal muscle -> temperature spike overwhelms control mechanisms -> death.
Treated with Dantrolene which prevents Ca release

Question 21

What is Glucose-6-Phosphate Dehydrogenase deficiency?

Answer 21

Rate limiting enzyme in PPP, leads to reduction in NADPH -> Heinz bodies -> Haemolytic anaemia,
Primaquine (anti-malarial) produces ROS so makes symptoms worse

Question 22

What is Marasmus?

Answer 22

Total malnutrition, body breaks down fat + muscle so emaciated appearance. Diahorrea + anaemia. Treat with nutritional diet

Question 23

What is Kwashiorkor?

Answer 23

No protein intake, fatty liver as there is no LDL to remove fats from liver. Oedema due to low serum albumin. Don’t give to much protein as leads to ammonia build up (refeeding syndrome)

Question 24

What is Lactate Dehydrogenase Deficiency?

Answer 24

Lack of enzyme means no reconversion to pyruvate. Builds up -> lactic acidosis

Question 25

What is Cyanide poisoning?

Answer 25

It non competitively inhibits Cytochrome C oxidase, this stops oxidative phosphorylation causing death

Question 26

What is Phynylketonuria?

Answer 26

Lack of Phenylalanine Hydroxylase leads to build up of Phenylalanine as it can’t be converted to tyrosine. Converted to phenyl pyruvate instead, this interferes with brain metabolism (prevents pyruvate entering mitochondria). Phenyl ketones detected in blood as they overcome the renal threshold

Question 27

What is Homocystinuria?

Answer 27

Deficiency of cystathione B synthase, causes Homocysteine build up as it can’t be converted to Cysteine. Affects connective tissue, can be confused with Marfans.
Second pathway converts to methionine which can be found in the urine

Question 28

What is Hyperlipidaemia?

Answer 28

Deficiency of Lipoprotein lipase means chylomicrons aren’t broken down so cholesterol in the blood is high, can block pancreas and cause pancreatitis

Question 29

What is Hypercholesterolaemia?

Answer 29

Caused by diet -> increased LDL production. Statins block HMG CoA reductase to block cholesterol release from Acetyl CoA

Question 30

What happens in Paracetamol Overdose?

Answer 30

Overdose saturated primary pathway leading to secondary metabolism generating NAPQI, this is toxic to hepatocytes. Glutathione depleted trying to breakdown NAPQI -> no defence against ROS. Treat with B-acetyl cysteine or activated charcoal if

Question 31

What is Diabetic Ketoacidosis?

Answer 31

Lack of insulin activates HMG CoA lyase, Acetyl CoA -> Ketones, this leads to acidosis

Question 32

What is Addison’s Disease (Hypoadrenalism)?

Answer 32

Autoimmune destruction of adrenal cortex, secondary to reduced ACTH due to problems with ant. Pituitary.
Weakness, fatigue, decreased BP, abdominal pain

Question 33

What is an Addisonian Crisis?

Answer 33

Total lack of Cortisol leads to Nausea, vomiting, shock -> coma -> death

Question 34

What is Cushing’s Disease + Syndrome?

Answer 34

Disease - Pituitary adenoma produces ACTH -> increased Cortisol
Syndrome - Adrenal Adenoma produces Cortisol
Leads to moon face, big belly, purple striae

Question 35

What is Hypothyroidism (Hashimoto’s)?

Answer 35

Autoimmune disease produces antibodies that block TSH or destroys Follicular cells.
Cold intolerance, weight gain, lethargy, apathy, constipation, Goitre.
Treated with oral Thyroxine

Question 36

What us Hyperthyroidism (Grave’s)?

Answer 36

Autoimmune disease that produces antibodies that stimulate TSH receptors.
Weight loss, heat intolerance, hyperactivity,