4B: Anatomy, Physiology, and Path of the S. Intestine (Part 2) Flashcards
What is emulsification?
First step of digestion in the SI.
Fat globule is broken up and coated by lecithin and bile acids.
What is fat hydrolysis?
Emulsification droplets are acted upon by pancreatic lipase, which hydrolyzes the first and third fatty acids from triglycerides, usually leaving the middle fatty acid.
What is a good Emulsifying agents?
Bile acids
How are micelles formed?
Several types of lipids form micelles coated with bile acids
What do pancreatic lipase and colipase do?
Chew up fat droplets and the reason why we do emulsification.
Intestinal cells absorb lipids from micelles, resynthesize triglycerides & package triglycerides, cholesterols, and phospholipids into what?
Into protein-coated chylomicrons
What packages chylomicrons into secretory vesicles?
The Golgi complex
Chylomicrons are released from basal cell membranes by what?
exocytosis and enter the lacteal (lymphatic capillary) of the villus
Once the chylomicrons (CM) enter the lymphatic circulation where are they transported?
Upward through the thoracic duct and emptied into the venous circulation at the junction of the jugular & subclavian veins.
When does Lipemia usually occur?
Within an hour after eating a fatty meal
Why does plasma usually become clear within a few hours?
Because Chylomicrons have a short half-life (<60 min)
How are Chylomicrons are removed from the blood?
As they pass through the capillaries of adipose tissue and the liver
Capillaries of adipose tissue and liver both contain large quantities of what?
Lipoprotein lipase
Lipoprotein lipase is especially active where?
In the capillary endothelium, where it hydrolyzes the TGs of chylomicrons into fatty acids & glycerol, which diffuse into adipocytes (storage) & hepatocytes (re-packaged into lipoproteins & exported to blood)
What are the 5 classes of lipoproteins?
1) Chylomicrons
2) Very low density lipoproteins (VLDL)
3) Intermediate density lipoproteins (IDL)
4) Low density lipoproteins (LDL)
5) High density lipoproteins (HDL)
Chylomicrons are synthesized by_____________, while VLDL, IDL, LDL, & HDL are synthesized by____________________
Enterocytes
Liver hepatocytes
The naming of lipoproteins is based on what?
The results of ultracentrifugation by which the lipoproteins are separated according to their density
VLDL contains what?
high TGs/moderate cholesterol & phospholipids
IDL contains what ?
moderate TGs, cholesterol & phospholipids
LDL’s contain what?
low TGs/ high cholesterol & phospholipids
HDL’s contain what?
low TGs, cholesterol & phospholipids
Which lipoproteins are the the only one routinely monitored and used to screen of atherosclerosisis, MI & stoke risk, heat disease, etc.
LDL-C & HDL-C
What is the role of LDLs?
(bad cholesterol) is to transport cholesterol and other lipids from the liver to the peripheral tissues, making them available (via receptor) mediated endocytosis) for membrane or steroid hormone synthesis.
What is the function of HDLs?
(good cholesterol) is to transport excess cholesterol from peripheral tissues to the liver, where it is broken down and becomes part of the bile
What are the most effective drugs currently in use for treating elevated LDL-C ?
1) Atovastatin (Lipitor)
2) Fluvastatin (Lescol)
3) Lovastatin (Altoprev, Mevacor)
4) Pravastatin (Pravachol)
5) Simvastatin (Zocor)
6) Rosuvastatin (Crestor)
7) Pitavastatin (Livalo)
What is Myopathy?
General term for any muscle disease
Myalgia?
Refers to muscle pain or weakness without increased creatine kinase , whereas myositis includes elevated CK.
What is Rhabdomyolysis?
Is defined as muscle symptoms, very high CK (<10 times the upper limit of normal), and increased serum creatine often with dark urine and myoglobinuria
What are all statins associated with?
Myopathy
Approx. 1 in 10 patients taking a statin report complaints of?
muscle complaints
What are risk factors for stain myopathy ?
1) Elderly
2) Small size
3) high statin dose
4) liver or renal disease
5) diabetes
6) uncontrolled hypothyroidism
7) interacting medications
Niacin was the first what?
lipid-lowering agent that was associated with a reduction in total mortality, with some of the earliest studies occurring in the mid 1970s.
What are the 3 basic preparations?
1) immediate (refular) release (IR) crystalline niacin
2) Sustained/extended release (SR + ER)
3) No-flush (inositol hexaniacinate; niacin-amide)
Drug names of immediate (refular) release (IR) crystalline niacin ?
1) Niacor (prescription)
2) Generic (OTC)
Drug names of Sustained/extended release (SR + ER)
1) Niaspan (prescription) (ER)
2) Slo-Niacin (OTC) (SR)
Drug names of No-flush (inositol hexaniacinate; niacin-amide)?
Niacinamide or no flush niacin
What active ingredient is taken out with no-flush ?
They contain NO nicotine acid, which is the active ingredient.
Are No-flush drugs useful?
No they are WORTHLESS and do NOT affect lipid levels
Niacin reduces the production of what?
Of VLDL which leads to a secondary reduction in LDL
Niacin (Nicotinic Acid, Vitamin B3) is also the most potent agent for ________________
raising HDL levels
What is the average effect of full dose niacin mono therapy ?
5-25% reduction in LDL-C
15-35% increase in HDL-C
20-50% reduction in triglycerides
The exact MOA of niacin is _______________
Still poorly understood
What is the percent increase in HDL when using Statins therapy/intervention?
6%-14%
What is the percent increase in HDL when using Fibrates therapy/intervention?
5% to 15%
What is the percent increase in HDL when using Physical activity therapy/intervention?
5-30%
What is the percent increase in HDL when using Weight reduction therapy/intervention?
5% to 20%
What is the percent increase in HDL when using smoking cessation intervention?
5%
Is the intolerance to niacin common?
Yes, intolerance is common.
Only 50-60% of patients may be able to take full doses
***Clinicians should warn patients to expect the flush and explain that is it s a harmless side effect
Why the intolerance?
tingling, flushing & sensation of warmth in the face and/ or upper body typically occurs after each dose when the drug is started or when the dose is increased.
What can help relieve the effect of niacin?
Taking ASA or other NSAIDs (e.g.- ibuprofen) 30-45 min prior to each niacin dose blunts this prostaglandin mediated effect
What are Bile Acid Binding Resins called?
Bile Acid Sequestrants
***The resins are the among the OLDEST of the HYPOLIPIDEMIC DRUGS
Why are resins considered the safest?
Since they are not absorbed from the intestine
What are some available resins include?
-Colestipol (Colestid)
–Cholestyramine (Questran, Questran Light)
-Colesevelam (Welchol)
What forms are resins available in?
Granular form (Colestid, Questran) which can be mixed with water or as tablets (Colestid, Welchol)
When Resins bind bile aids in the intestinal lumen what does it lead to?
1) Decreased emulsification of dietary fat
2) Prevention of bile acid reabsorption (via enterohepatic circulation)
What does prevention of bile acid reabsorption cause?
Causes the liver to increase its production of bile acids, using hepatic cholesterol to do so
What are statins referred to as?
When do they work best?
HMG-CoA reductase inhibitors (shut down endogenous production)
-Work best with life-style changes
True or False. Plasma LDL levels can be reduced by up to 30% with maximal doses?
True
Do Resins have a effect on HDLs and triglyceride levels in the blood?
Have little effect
What are the MOST common adverse effects related to the GI system ?
1) Constipation (in some cases, fecal impaction)
2) bloating/abdominal distention/pain
3) flatulence
4) nausea
5) vomiting
6) dyspepsia
When do symptoms (related to GI system) usually decrease?
With slow dose titration and tie
What may relieve constipation and bloating ?
Increased dietary fiber or a fiber supplement (e.g. -Metamucil)
Resins can bind to what other drugs/substances and interfere with their absorption?
1) Fat soluble vitamins (supplementation should be considered)
2) folate (supplementation should be considered)
3) thiazides
4) tetracyclines
5) warfarin
6) propanolol
7) penicillin
How can you avoid some of these drug-drug interactions?
To take the resin a few hours after taking medications on the list (e.g., folate, antibiotics, warfarin..etc)
All H20 absorption in the small intestine is ____________ and __________ to solute movement
- PASSIVE
- Secondary to solute movement
What are some examples of solutes?
Electrolytes such as Na+ or non-electrolytes such as glucose
What stimulates lots of water absorption?
Na+/glucose and Na+/amino acid mechanisms
How is K+ absorbed?
Passively when luminal [K+] rises because of absorption of water (solvent drag)
Where does calcium absorption occur?
In the duodenum & jejunum
Calcium absorption is regulated by what?
Primary regulated by VITAMIN D3 or 1, 25 dihydroxycholecalciferol (AKA “active vitamin D”)
What does calcium absorption stimulate?
The synthesis of Ca2+ binding proteins called CALBINDINS in ENTEROCYTES
How are Fat-soluble vitamins (A, D, E, K) absorbed?
Similar to fat absorption
What are the MOST wate-soluble vitamins absorbed by?
Simple diffusion
What does one of the water-soluble vitamins (vitamin B12; cobalamin; CBL) require?
Intrinsic factor (IF) for normal absorption
What do Ileal cells absorb across the brush border?
IF-Vitamin B 12 complexes
What does Atrophy of the gastric mucosa result in?
In a deficiency of IF and acid secretion that causes vitamin B12 deficiency
What do peristaltic contractions do? and where do they occur?
- They propel and mix food along the GI tract
- Occur in the esophagus, stomach & small intestine
How long does it take chyme to move through the entire SI via peristalsis?
Approx. 3-5 hours
What is segmentation?
A series of contractile and relate periods that mechanically digests food
What are BOTH peristalsis and segmentation controlled by?
Autonomic Nervous System.
How do sympathetic and parasympathetic nerves affect muscular activity?
Sympathetic= INHIBITS
Parasympathetic= EXCITES
