BioChem Lab Quiz 8

What is atherosclerosis?

sticky plaque buildup in the arteries

A patient who presents with coronary artery disease is most likely to have what features from their life style?

sedentary, overweight, male

What does atheroscleorosis in patients with coronary artery disease (CAD) cause?

decrease in nitric oxide → pro-inflammatory surface and endothelial damage

Plaque deposition leads to what effects on the arteries?

hardening and narrowing

What other factor can lead to narrowing of the arteries?

stress

What will lead to plaque deposition on arteries?

endothelial damage

Narrowing of the blood vessels will lead to what?

hypertension and ischemia (low O2)

What does hypertension increase?

increase resistance → cardiac work + shear stress

Shear stress increase from CAD has what affect?

rougher endothelium, decrease nitric oxide, weaker heart wall

A weak heart wall causes what?

dissecting aneurysm → rupture → hemorrhage and death

Increased cardiac work causes what?

left ventricle hypertrophy + increased O2 demand

The O2 demand from LVH and decreased supply from ischemia leads to?

angina pectoris (chest pain)

arrhythmia (solely from ischemia)

The rough endothelium caused by shear stress causes what?

thrombosis + tissue hypoxia

Tissue hypoxia leads to what?

myocardial infarction (permanent damage) → heart failure, death, chest pain

In the slides, the patient with CAD presented with the following:

insulin resistance, hyperinsulenemia, hyperglycemia, dyslipidemia

glucotoxicity, AGEs, lipotoxicty, ROS, inflammation

With all of the symptoms that the patient presents with for CAD, what does it all lead to?

endothelial damage

How does LDL normally act?

crosses healthy endothelium

Oxidative stress leads to what regarding LDL?

LDL oxidation

AGEs lead to what regarding LDLs?

LDL glycation

If LDL goes through glycation and oxidation it becomes trapped and becomes what?

more dense

What attempts to destroy LDL and in turn becomes trapped as well?

foam macrophages

The lipid core that forms in the endothelium is known as what?

plaque and calcification cover that

Unstable plaque leads to rupture causing what?

platelet adhesion → thrombosis → acute occlusion

Warning signs of heart attack:

pressure in center of chest

pain in shoulders, neck, arms

chest discomfort with fainting, sweating or nausea

Stable angina is what?

predicatable

Prinzmetal angina is what?

unpredictable, coronary thrombosis → ischemia

Silent ischemia has what?

no detectable symptoms

What are examples of acute coronary syndromes?

unstable angina

non ST-segment elevation MI

St-segmi elevation MI

Non ST-segment elevation MI shows with what?

persistent coronary occulusion → infarction of the myocardium closest to the endocardium

ST-segment elevation MI shows with what?

coronary occlusion → transmural MI extending from endocardium to pericardium

ST Segment Depression usually means what?

ischemia; can be infaction

ST Segment Elevation usually means what?

infarction

Angina Pectorina is mainly caused by?

ischemia

Management of CAD:

lifestyle changes, diet, activity, stress managment, BP control

Risk factors of cholecystitis:

female, fat, fair(caucasian), fourties, fertile(pregnant), fatty food diet

What does estrogen do to cholesterol levels?

increase

S/S of cholecystitis:

right upper quadrant of abdomen pain

scapular pain

N/V, bloating

fever

murphy’s sign

After eating what does a patient with cholecystitis right upper quadrant of abdomen pain? Why?

spicy or greasy food; release of CCK

Gallbladder pathologies:

cholelethiasis - gallbladder stones

acute cholecystitis - stone gets stuck in cystic duct

chronic cholecystitis - inflammation caused over long period of time

choledocolithiasis: stone stuck in bile duct pushing bile away from gallbladder

cholangitis

What does cholangitis present with?

charcot triad: fever, juandice, RUQ pain

What are most of ALLLL gallstones made of?

cholesterol

Pigmented gallstones are usually made of what?

calcium, bilirrubin, phosphate

Does menopause increase or decrease risk of cholesytitis?

decrease

What causes cholesterol secretion?

estrogen bind to ESR1 → SREBP-2 causing increase in HMG-CoA

What causes bile and phospholipid secretion?

estrogen bind to ESR1 →CYP7A1

Is ther a supersaturation of bile in order to make gallstones?

yes

Progression of cholesytitis:

increase pressure and inflammation/edema

→early necrosis

→advanced necrosis and

Gold standard diagnosis for cholesytitis is what?

abdominal ultrasound

What criteria are there with the abdominal ultrasound to diagnose cholecystitis?

large obstructing stone within GB neck

edema in gallbladder wall

positive sonographic murphy sign

Labratory testing for cholecystitis are?

neutrophilia

ALP/GGT/AST/ALT

Bilirubin levels

amylase/lipase

Tx for cholecystitis

surgical removal

IV antiobiotic

Avoid greasy and fatty spicy food

Ursodeoxycholic acid

What does Ursodeoxycholic acid do?

inhibit absorption of cholesterol

What is ICP?

intrahepatic cholstasis of pregnancy

What are some S/S of ICP?

pruritus, N/V, loss of appetite, jaundice

When does ICP occur?

end of 2nd trimester/placenta at 20 weeks when progesterone and estrogen levels increase

What does increasing estrogen and progesterone levels in ICP cause?

decrease in phosphoplipids, bilirubin and bile salts exiting cell (??? video hasn’t released yet)

Phospholipid pump is what?

MDR3

Bilirubin pump is what?

MRP2

Bile salt pump is what?

BSEP

Because of inhibition of pumps in ICP what ends up in bloodstream?

MRP3

What are the gene mutations of ICP?

ABCB4 → MDR3

ABDB11→ BSEP

What is the best way to dx ICP?

GGT and ALP level check

both increased

what do increased ALT, AST, and TBili tell you?

hepatocellular damage

What is the tx for IPC?

Ursodeoxycholic acid, vitamin k and delivering baby

What does Ursodeoxycholic acid do?

decrease absorption of fat soluble vitamins (vitamin K)

How long after delivery of baby will pruritis decrease? What about full resolution?

2-3 days; 2-3 weeks

What is epigastric pain a sign of?

pancreatic issue

What does the patient of hyperlipidemia present with

mild distress, hepatomegaly, few scattered xanthomas

Bile and lipase are used to break what down? What does it break that down into?

TAGs → FA + glycerol

What are FA and glycerol packed into in order to enter enterocyte?

michelles

What do FA and glycerol becomes once inside the enterocyte?

TAGs then protein gets added

What do TAGs become when protein gets added to it in the enterocyte?

chylomicrons which enter lacteals

Path of chylomicrons is what?

lacteals → thoracic duct → SC vein → circulation throughout body → liver

What is the lipoprotein lipase pathway?

lipoprotein contacts endothelial LPL

LPL leaves TAG → FFA + glycerol

What does FFA do? What about glycerol?

FFA: energy/storage

Glycerol: liver gluconeogenesis

Defective LPL causes what?

increase in TAGs in plasma

What does CM contain?

B48

Where does LPL go to?

muscles and adipocytes

Which is high density vs low density?

Low: VLDL; High: LDL

What does HDL do?

clean up cholesterol and take it to liver

What does LDL become?

steroidogenic cells and peripheral cells

VLDL, IDL, LDL have what?

B100; endogenous

What is familial combined hyperlipidemia caused by?

B100 in VLDL, LDL + TAG increase

Decrease clearance via LPL

Peancreatic lipase acting on retained TAGS do what?

increase free fatty acid causing toxicity

→ capillary injury → edema and necrosis → acute pancreatitis

What specific type of hyperlipidemia do we have in our patient?

Familial combined hyperlipidemia Type IIb

How to fix hyperlipidemia?

lifestyle, omega-3, fibrates, red yeast rice, fasting

Manifestation of hyperlipidemia?

xanthomos, fatty liver, pancreatitis if TAG > 500

early atherosclerosis, hepatomegaly

Hypertriglyceridemia is described by what?

biochemical traffic jam

Our goal during hyperlipidemia?

prevent pancreatitis and cardiovascular disease

Secondary/aquired of hyperlipidemia?

high carb diet, IR, obesity, diabetes, alcohol, estrogen therapy