Where is cholesterol in the intetstine from?
How is cholesterol in the intestine solubilised?
in mixed micelles
Where are bile acids reabsorbed?
terminal ileum
What effect does cholesterol have on HMG-CoA-reductase?
it inhibits the enzyme
fates of cholesterol in the liver
How are triglycerides moved from small intestine to plasma?
via chylomicrons
How is LDL taken up by cells?
processed by lysosomes
How common is homozygous and heterozygous familial hypercholesterolaemia?
homozygous: 1 in 10^6
heterozygous: 1 in 500
What is PCSK9? What happens in gain and loss of function mutations?
a chaperone protein
its role is to bind to the LDL receptor and promote its degradation
gain of function mutations -> high LDL (because more LDL R is degraded and LDL not taken up by liver)
loss of function mutations -> low LDL
What medications are used to lower cholesterol? What effects do they have on HDL, LDL and TG?
statins - good reduction in LDL, slight reduction of TG, slight elevation of HDL
fibrates - very good at lowering TG, slight reduction/increase in LDL/HDL
resins - bind bile acids
Pharmacological approaches to obesity
orlistat - inhibits pancreatic lipase -> not hydrolysed, not absorbed, excreted via stool
surgical approaches to obesity (and indication)
bariatric surgery
if BMI >40
Different types of bariatric surgery
Why can people with sarcioud have high Ca?
1-a-hydroxylase can be expressed lungs; uncontrolled; activation of vitamin D -> high CA
25-hydroxylase is found where?
Liver
Where is 1-alpha-hydroxylase found?
KIDNEYS
can be ectopiicallly expressed in sarcoid
When do you prescribe cholecalciferol and calcitriol?
calcitriol is dangerous because it is active Vit D3; only prescribed in renal failure; easy to overdose;
cholecalciferol - OTC, has to be activated;
Compare osteoporosis vs osteomalacia
Osteoporosis: reduced bone density with normal biochemistry
Osteomalacia: bone demineralisation; Blood: low Ca, low phos, high ALP/PTH?
How do you calculate corrected calcium?
CC = measured calcium + 0.02x(40-albumin)
T-score vs Z-score
T-score SD of 20yo
Z-score is SD from age-matched
Causes of osteoporosis
Mx of osteoporisis
lifestyle: weight bearing exercise, stop smoking, reduce etoh
Drugs
- vit D / Ca
- bisphosphonates (e.g. alendronate) -> decreased bone resorption -> very strong bone, not biodegradable; unnatural phosphate; osteoblasts Can use it, casts struggle with breakdown. do not have it with calcium, taken 1x/w on empty sttomach with water and nothing else. gut irritant.
alternative is 1/year IV zonlendronate
- teriparatide (PTH) derivative - anabolc;
- Strontium: anabolic + anti-respoptive
- oestrogens/HRT
- SERMs e.g, raloxifene (
Tamoxifen actions
Tamoxifen agonist in bone, antagonist in breast
raloxifene similar; good for bone and prevent Br ca but worsen Sx of menopause.
Which antibiotic groups belong to beta lactams?
Penicllins
Cephalosporins
Carbopenems
Monobactams