Lipid Metabolism, Dyslipidemia

Tg made of

3 FFA + Glycerol

Chylomicron special apolipoprotein

Apo48

VLDL, IDL, IDL special apolipoprotein

ApoB-100

HDL special apolipoprotein

ApoA-1

ApoA-1 function

Activate LCAT → Change FFA into cholesterol → Added to immature HDL → Mature HDL

Rank the lipoproteins by most Tg to lowest Tg

Chylomicron (most Tg) → VLDL → IDL → LDL → HDL (IDL, LDL, HDL is very small Tg content)

ApoB-100 function

Bind to LDL receptor to deliver cholesterol

ApoC-II function

Activate LPL → Extraction of Tg from VLDL to use as energy

ApoE function

Allows for liver uptake

Exogenous lipid metabolism

Tg broken down by pancreatic lipase in small intestine → Bile acid emulsify into micelle → Reassembled into chylomicron → Enter lymph → Systemic → ApoC-II activate LPL → FFA go to target → Chylo remnant go back to liver → Enter by ApoE → Break down into cholesterol → Made to bile acid

What are the targets of lipoproteins

Skeletal, smooth muscle and adipose tissue

Endogenous lipid metabolism

Liver pack CE and Tg into VLDL → Systemic → ApoC-11 activate LPL → VLDL remnant = IDL → Either go back to liver or become LDL

HDL pathway

Liver + small intestine make nascent HDL → Get CE → Becomes mature HDL

What is familial hypercholesterolemia

Auto dom mutation of LDLr or PCSK9 → Impaired LDL clearance → HIGH LDL

Clinical finding of familial hypercholesterolemia

Tandon xanthoma, early onset of ASCVD (<55 in men, <65 in women)

What is Familial Combined Hyperlipidemia

ApoB-100 overproduction → High VLDL, IDL and LDL

Complication of Familial Combined Hyperlipidemia

Premature ASCVD, insulin resistance, hypertension, NO XANTHOMA

What is Familial Hypertriglyceridemia

Auto recessive mutation of LPL or Apo-C-II → HIGH chylo and VLDL + LOW LDL

Clinical findings of Familial Hypertriglyceridemia

Acute pancreatitis, eruptive xanthoma, hepatosplenomegaly

What is Familial Dysbetalipoproteinemia

Autosomal recessive mutation of ApoE → Liver cannot clear chylomicron → IDL and chylomicron remnant high

Clinical finding of Familial Dysbetalipoproteinemia

Palmar and tuberoeruptive xanthoma, premature ASCVD

Complication of dyslipidemia

Pancreatitis, MASLD, signs = xanthoma, xanthelasma, corneal arcus, lipaemia retinalis

Pathogenesis of atherosclerosis

Endothelial injury → LDL trap in intima → Oxidization of LDL → Inflammation → MC attraction to site → PLT adhesion and GF release → MC engulf LDL → Foam cell formation → SMC migration and proliferation from PLT factors → ECM deposition and fibrous plaque formation

Describe what is being seen

Purple pink layer → Fibrosis

White area → Necrosis

Dark purple → Calcium deposit

What cell is this

Foam cell

What happens if there is fracture of plaque fibrous cap

Exposed tissue factor → Red thrombus (fibrin rich)

What happens if there is superficial erosion of plaque

Expose collagen → White thrombus → Activate coagulation