essay 5 - lipid metabolism disorders - abnormal disgestion and absorpttion of lipids in gastrointestinal tract. lipoproteins - types, metabolism. disordered lipid transport in the blood. dyslipidemias, athersclerosis

abnormal digestion and absorption of lipids can occur due to?

• decreased bile salts (needed to emulsify fat)

• decreased pancreatic enzyme production, specifically lipase (digest fat)

• high dietary levels of calcium and magnesium salts as they impair fat absorption by forming insoluble soaps with fatty acids and bile salts, the soaps cannot be absorbed and trap bile salts and increase fat loss in stool

• diarrhoea syndromes that shorten intestinal transit time

• hypovitaminosis limits fat utilisation by depriving the body of fat-soluble vitamins

• protein starvation impairs lipoprotein formation and transport, leading to defective lipid absorption and fatty liver

what transports lipids in the blood and what are the types ?

• lipoproteins transport lipids in the blood

• Chylomicrons - transport dietary triglycerides and cholesterol from intestine to tissues

• VLDL (very low density lipoproteins) - carry triglycerides from liver to tissues

• IDL (intermediate density lipoproteins) - VLDL remnants, precursor to LDL

• LDL (low density lipoproteins) - cholesterol transport to tissues “bad cholesterol”

• HDL (high density lipoproteins) - reverse cholesterol transport back to the liver “good cholesterol”

what do disorders of lipid transport depend on and what do they lead to

• disorders of lipid transport occur when the balance between lipoprotein production, utilisation and clearance is disturbed.

• they lead to dyslipidaemias and atherosclerosis

genetic causes of disorders of lipid transport

• familial hypercholesterolemia → defective or absent LDL receptors prevent clearance of LDL particles, leading to markedly elevated plasma LDL

• apolipoprotein E defects → impaired clearance of remenant particles (IDL and chylomicron remanent)

secondary causes of disorders of lipid transport

• diabetes mellitus → insulin resistance increases heaptic VLDL production and reduces HDL

• hypothyroidism → reduced LDL receptor activity raises LDL cholestrol

• obesity, alcohol excess and diets high in saturated fats also contribute to abnormal lipid transport

what is dyslipidaemia

• the clinical manifestation of disordered lipid transport, defined by abnormal concentrations of lipoproteins in the blood

what are some some clinical manifestations of disordered lipid transport (dyslipidemia)

• hypercholesterolemia → elevated LDL cholesterol

• Hypertriglyceridemia → elevated VLDL and triglycerides

• mixed dyslipidaemia → combined elevation of LDL cholesterol and triglycerides; often associated with metabolic syndrome and type 2 diabetes

• low HDL cholesterol → independent risk factor for atherosclerosis and CAD; reduces reverse cholesterol transport and antioxidant activity. recommendations for maintaining a healthy level of HDL to quit smoking, weight loss, niacin and physical activity

what is atherosclerosis

• Atherosclerosis is a chronic, progressive disease of medium and large arteries in which fats accumulate in the intima, triggering inflammation and leading to the formation of fibrous plaques.

pathogenesis of atherosclerosis

1) Endothelial injury (the trigger)

Caused by:

• Hypertension

• Smoking

• Hyperlipidemia (↑ LDL)

• Diabetes

• Toxins

Injury makes the endothelium “sticky” and permeable.

2) LDL infiltration + oxidation

• LDL enters the subendothelial space

• It becomes oxidized (ox‑LDL)

• Ox‑LDL is pro‑inflammatory + toxic

3) Monocyte adhesion → macrophages → foam cells

• Monocytes stick to the injured endothelium

• Migrate into intima

• Differentiate into macrophages

• Macrophages engulf oxidized LDL → become foam cells

4) Fatty streak formation

• Foam cells accumulate

• This forms the earliest visible lesion of atherosclerosis

• Seen even in teenagers

5) Smooth muscle migration + proliferation

• Smooth muscle cells move from media → intima

• They proliferate

• They produce collagen + extracellular matrix

• This forms the fibrous cap

6) Mature plaque → complications

Over time:

• Plaques calcify

• Fibrous cap may rupture

• Rupture exposes thrombogenic material → thrombosis

• Can cause:

  • Myocardial infarction

  • Stroke

  • Peripheral arterial disease

⭐ Risk Factors for AtherosclerosisModifiable

• High LDL

• Low HDL

• Hypertension

• Diabetes

• Smoking

• Obesity

• Sedentary lifestyle

Non‑modifiable

• Age

• Male sex

• Family history (genetic predisposition)