CLINICAL CONDITIONS Flashcards
What clinical conditions relate to connective tissue issues?
Scurvy
Marfan’s syndrome
Osteogenesis imperfecta
What is scurvy due to?
Vitamin C deficiency - essential in collagen production to hydroxylation proline + lysine to procollagen
Signs and symptoms of scurvy
Think pirates
- gum disease + tooth loss
- bruising
- hair loss
- bleeding from gums
- poor wound healing
- impaired bone development when young
What cause Marfan’s Syndrome?
Mutation of fibrillin 1 gene»_space; elastic tissue is abnormal
Autosomal dominant disorder
Signs + symptoms of Marfan’s syndrome
Abnormally tall
Arachnodactyly - ‘spider fingers’
Arm span is greater than height
Frequent joint dislocation
What are people with Marfan’s syndrome at risk of?
Aortic rupture
What is osteogenesis imperfecta due to?
Mutation in col1A or col2A gene
Mutated collagen fibres that don’t cross link/not enough produced
Autosomal dominant
Signs and symptoms of osteogenesis imperfecta
Weakened bone - ‘brittle bone disease’
Blue sclera
Spinal curvature
Hyper mobility
Poor teeth development
Shortened height + stature
What is an eptopic pregnancy?
When implantation occurs at site other than uterine body often in fallopian tubes
What is placenta praevia?
Implantation of zygote in lower uterine segment
Placenta blocks birth canal
Why is a C section required in placenta paraevia?
Placenta blocks birth canal
Risk of haemorrhage due to fragile vessels
What is sinus inversus?
Developmental disorder in which here is a complete mirror image of organs
What causes sinus inversus?
- Lack of left ward flow of signally molecules in trilamiar disc in gastrulation
- Signals cannot initiate signalling cascades that correspond for development of left sidedness
What clinical conditions are related to bone diseases?
Osteogenesis imperfecta
Rickets + osteomalacia
Osteoporosis
Achondroplasia
What is rickets due to?
Vitamin D deficiency - produces calcitriol
Poor calcium mobilisation + ineffective mineralisation
Weakened bone development
In children
Characteristic of rickets
Bowed legs
What is osteomalacia?
Rickets in adults
Vitamin D deficiency
What is hydroxyapatite made of?
Calcium
What is osteoporosis?
A degernative bone disease in which the bone matrix is broken down+ bone demineralises»_space; loss of structural density
Causes of osteoporosis
Mismatch of osteoblasts and osteoclast numbers
Results in greater rate of bone resorption than bone synthesis
Risk factors for osteoporosis
Menopause > age
Chronic kidney disease
Corticosteroids
Smoking
Inactivity
How is menopause a risk factor for osteoporosis?
Decreased oestrogen levels
Oestrogen is protective factor for osteoporosis
Outline primary type 1 osteoporosis
Post menopausal women
Due to increased osteoclast number
Loss of oestrogen after menopause
Outline primary type 2 osteoporosis
Occurs in ~70 year old men and women
Due to loss of osteoblast function
Loss of oestrogen and androgen
Outline secondary osteoporosis
Result of drug therapy - corticosteroids
Steroids use increases osteoclast action + affects calcium excretion
Bone remodelling affected
Modifiable risk factors of osteoporosis
Increase calcium intake
Exercise
Smoking cessation
What is achondroplasia?
What type of inheritance is it?
Dwarfism
Autosomal dominant mutation on the FGF3 receptor gene
Cause of achondroplasia
What does this cause?
- Inherited mutation on the FGF3 receptor gene
- FGF promotes collagen formation from cartilage»_space; affects endochondral ossification NOT intra-membranous
- long bones affected, not flat bones
- normal sized head + torso but smaller limbs due to inadequate long bone development
Characteristics of achondroplasia
Short stature
Normal sized head and torso
Long bones cannot lengthen properly
What clinical conditions relate to muscle dysfunction?
Duchene muscular dystrophy
Rhabdomyolysis
Myocardial infarction
Botulism + organophosphate poisoning
Malignant hypothermia
What is the cause of Duchene muscular dystrophy
Mutation of the dystrophin gene
What does the a mutation in dystrophin cause?
Duchene muscular dystrophy
- Excess Ca2+ enters muscle cells
- Ca2+ taken up by mitochondria
- Water taken with it
- Muscle cells burst > Rhabdomyolysis
- High levels of creatine kinase + myoglobin
What is botulism toxin and what does it do?
Toxin produced by clostridium botulinum
Blocks neurotransmitter release
Causes non-contractile state of skeletal muscle
Uses of botulism toxin
- clinically - to treat muscle spasm + urgency UI
- cosmetically - Botox - to treat wrinkles
What is organophosphate and what does it do?
A pesticide
Inhibits the normal function of ACh esterase
Muscarinic symptoms of organophosphate poisoning
SLUDGE
Salivation
Lacrimation
Urination
Defecation
GI cramping
Emesis
Nicotinic symptoms of organophosphate poisoning
Days of the week MTWTF
Muscle cramps
Tachycardia
Weakness
Twitching
Fasciculations - muscle twitch
What causes malignant hypothermia?
Mutation in RyR1 receptor
What type of inheritance is Marfan’s syndrome
Autosomal dominant
What type of inheritance is Duchene muscular dystrophy?
X linked recessive
What type of inheritance is achondroplasia?
Autosomal dominant
Outline collagen synthesis
1- preprocollagen undergoes vit C dependent hydroxylation of proline + lysine
2- precollagen formed - 3 PPC cross linked to form triple helix
3- C and N terminals of PC cleaved
4- tropocollagen formed
5- TP cross link formation
6- microfibrils, fibrils + collagen fibres made
