case 10: ischemic stroke Flashcards
1
Q
What Is a CT Scanner?
A
- Computerized axial tomography scan (CT scan, CAT scan),
uses computer-processed combinations of many X-ray images
taken from different angles to produce cross-sectional images
2
Q
Provisional Diagnosis
A
- A provisional diagnosis – acute ischemic stroke secondary
to occlusion of the M1 segment of middle cerebral artery
(MCA) - Treatment – intravenous injection of tissue plasminogen
activator (tPA) at 2 h after symptom onset
3
Q
What is a Stroke?
A
- Stroke is a sudden impairment in brain function, sudden
paralysis or sensation - The term “brain attack” – is increasingly being used as an
indication of medical emergency - The term “stroke” does not imply the causes. There are
many causes
4
Q
What causes a stroke?
A
- A stroke occurs when a blood vessels that carries O2 and
nutrients to the brain is either blocked by a clot (ischemic
stroke) or bursts (hemorrhagic stroke)
5
Q
Adult Human Brain – Facts
A
- ~2% body weight
– ~1,350 g (male); ~1,200 g (female) - Receives 15-20% of cardiac output
- Consume 20% resting O2
- Preferred energy substrate – glucose
– When do neurons use ketone bodies? during starvation
6
Q
Cerebral Blood Flow (CBF) – Facts
A
- CBF – 750 ml/minute
- Normal CBF – ~50-65 ml/100 g/min
– ~1/3 in white matter; ~2/3 in gray matter - CBF at 20-30 ml/100g/min -> loss of electrical activity
(“ischemic penumbra”) - CBF at <10 ml/100g/min -> neuronal death
- 8” of interruption in blood flow -> unconsciousness
7
Q
Stroke Facts
A
- Stroke is the fourth leading cause of death in the U.S.
– 795,000 people in the U.S. suffer strokes each year
– 133,000 deaths in the U.S. each year
– One person suffers a stroke every 40 seconds in the U.S. - A leading cause of adult disability
– Women suffer greater disability after stroke then men - Up to 80% of all strokes are preventable through risk factor
management - Stroke kills more than twice as many American women every
year as breast cancer - African Americans is nearly double that of Caucasians for
incidence of stroke
8
Q
Stroke Symptoms
A
- sudden and severe headache
- trouble seeing in one or both eyes
- sudden dizziness
- trouble walking
- sudden confusion
- trouble speaking
- sudden numbness or weakness of face, arm or leg
9
Q
Stroke Strikes FAST
A
- F – Face, ask the person to smile
– If not symmetry -> weakness on one side - A – Arm, ask the person to raise both arms
- S – Speech, ask the person to speak a simple sentence
- T – Time (with a stroke, time lost is brain loss)
– If you observe any of these signs, call emergency immediately
10
Q
Risk Factors of Stroke
A
- Risk factors of stroke – SHAME
– Smoking; Hypertension; Atrial fibrillation; Male; Elderly - Risk factors in young age – 5C
– Cancer; Cardiogenic emboli; CNS infection (HIV conditions);
Congenital arterial lesion; Cocaine - Other risk factors
– Things you cannot change - Race (African Am, native Am, and Alaskan natives)
- Family history, history of stroke or TIA
– Things you can change - Hypertension; DM; high cholesterol; diet (salt, antioxidants)
- Physical inactivity and being overweight
- Birth control pills and hormone replacement therapy; alcohol
11
Q
Transport of Lipoproteins in Blood
A
- What are lipoproteins?
– Transport of absorbed lipids in the blood –
lipids (hydrophobic) must bind to amphipathic
proteins (apo-lipoproteins) → lipoproteins →
water-soluble
– Lipoproteins – hydrophobic lipids (triglycerides,
TG) in core; hydrophilic lipids (phospholipids,
PL) on surface, interacting with blood plasma - Six lipoprotein forms based on densities:
– Chylomicrons (CM) – lowest in density (largest size)
– Very low density lipoproteins (VLDL)
– Intermediate density lipoproteins (IDL) – as
intermediates
– Low density lipoproteins (LDL)
– High density lipoproteins (HDL)
– Albumin-free fatty acids (FFA) – highest in
density
12
Q
Chylomicrons – Formation
A
- Pancreatic lipase digests triacylglycerols (triglycerides, neutral fat) ->
fatty acids & monoacylglycerol -> absorbed by enterocytes (intestinal mucosal cells) (enter freely because cell membrane has lipid bilayer) - Formation of chylomicron (CM) in enterocytes:
– In enterocytes (cytosol), fatty acids + monoacylglycerols -> triacylglycerols
– Absorbed triacylglycerols + apolipoprotein -> (nascent) CM
– CM – 98% lipids, mostly triacylglycerols (~85%)
the more FA the more glycerol enters into enterocyte
CM transported out via exocytosis into central lacteal (because of larger pores)
13
Q
Chylomicrons – Transport
A
- Transport of nascent chylomicron (CM)
– Exocytosis -> central lacteal -> lymphatic vessels -> thoracic duct -> vena
cava (into venous blood) -> entering blood circulation (not by portal circulation)
– Refract light, cloudy appearance in plasma
– CM deliver ~80% to adipose t., muscle & peripheral t.; ~20% to liver - Modifications of nascent CM particles:
– The nascent CM is rapidly modified into CM by combining apoE + apoC-II
from circulating HDL -> mature CM
– The apoC-II is important for the metabolism of lipids in the CM
14
Q
CM – Lipoprotein Lipase
A
- Lipoprotein lipase (LPL) – produced
mainly by adipocytes -> move to
endothelium
– Resides on the capillary walls
mainly on adipose tissue, cardiac &
skeletal muscles, lactating
mammary glands
– LPL is activated by apoC-II (from
HDL)
– LPL hydrolyzes the triacylglycerol to
yield monoacylglycerol, fatty acids
-> transport to adipocytes ->
promotes lipogenesis
– LPL (insulin-sensitive) – insulin -> increase LPL activities
pancreatic lipase is for digestion of lipid in lumen of small intestine. hormone sensitive lipase is to convert fat in adipose tissue into monoacylglycerol and FFA to circulate in blood, insulin decrease hormone sensitive lipase so less lipolysis occurring
LPL purpose is to synthesize neutral fat present in CM in blood
LPL anabolic
15
Q
CM – Metabolism
A
- After being degraded by
LPL:
– CM decrease in size and increase in density
-> apoC-II returned to the
HDL -> the remaining particle
is called a “CM remnant” - CM remnants in the blood -> the liver
– CM remnants deliver leftover lipids to liver
– Hepatocyte membranes
contain CM lipoprotein
receptors bind to
apoB-48/apoE complex
16
Q
VLDL – Production
A
- VLDL – produced by the liver
(hepatocytes) - 90% lipid, triacylglycerols (55-65%)
- The dietary intake of both fat and
carbohydrate, in excess of the needs of
the body, leads to the conversion into
triacylglycerols in liver - Function of VLDL – transport
endogenously synthesized triacylglycerols
from liver to peripheral tissues (mainly
muscle and adipose tissue)
– Cloudy appearance – somewhat visible in
plasma
17
Q
VLDL – Metabolism
A
- Modification of circulating VLDL – similar to
CM:
– VLDLs are released from the liver as nascent
VLDL
– Nascent VLDL acquires apoC (I, II, & III) and
apoE from circulating HDL.
– Degradation of triacylglycerol by lipoprotein
lipase (LPL) →VLDL decrease in size and
become more dense
– The apoC-II are transferred back to HDL.
– VLDL → IDL → LDL (no apoC-II) - ↑ Liver lipogenesis (from high lipid or carb
intake) → exceed liver production of VLDL →
non-alcoholic fatty liver
VLDL formed into liver and converted to neutral fat to adipose tissue then lipogenesis
18
Q
Metabolism of IDL
A
- Production of LDL from VLDL in plasma:
– After degradation of triacylglycerol by lipoprotein lipase, VLDL has
been converted in the plasma to an intermediate-sized particle
(IDL) then to LDL.
– IDL contain more proteins, thus less cholesterol than LDL. - The fate of IDL (a.k.a. VLDL remnants):
– 1. Direct uptake by liver – through receptors (apoB-100/apoE
complex) → endocytosis - In most animal species, the majority of IDL is removed from blood by
liver. - In primates, 60-70% IDL are converted to LDL
– 2. Conversion to LDL – contain only apoB-100 - Characteristics of IDL
– IDL are essentially absent from serum under normal
circumstances
19
Q
Metabolism of LDL
A
- ~80% Lipids – cholesterol > phospholipids > triacylglycerols > FFA
- The primary function of LDL is to provide cholesterol to peripheral
tissues (liver 75%, adrenals, gonads, blood vessels & adipose t.) - Hormones and LDL uptake
– Insulin and tri-iodothyronine (T3) increase the binding of LDL to liver
cells. Cholesterol then is eliminated via bile (bile salt, bile acid, bilirubin, cholesterol).
– Diabetes or hypothyroidism → hypercholesterolemia → ↑ risk of
atherosclerosis in primates
20
Q
Metabolism of HDL
A
- HDLs are synthesized de novo in the liver and small intestine, as
protein-rich particles
– These newly formed HDLs are nearly devoid of any cholesterol and
cholesteryl esters.
– The primary apoproteins of HDLs are apo-A-I, apo-C-I, apo-C-II and
apo-E. - 50% lipoproteins, another 50% lipid (phospholipids > cholesterol ~
triacylglycerols) - HDLs are converted into spherical lipoprotein particles through the
accumulation of cholesteryl esters - Functions of HDL
– As a reservoir of apolipoproteins (apoC-II, apo-E) for CM & VLDL
– Reverse cholesterol transport – carry cholesterol back to liver
– Cholesterol can be eliminated to feces through bile
21
Q
Summary – Lipoprotein Functions
A
- Chylomicrons deliver dietary triacylglycerols
from the intestine to adipose and muscle
– Chylomicron remnants deliver leftover lipids to
liver - VLDL from liver deliver endogenous
triacylglycerols to adipose tissue and muscle - LDL deliver cholesterol to many tissues
- HDL deliver excess cholesterol from other
tissues to liver, reservoir of apolipoproteins (apoC-II) - Liver is the main organ that can eliminate
cholesterol out of the body
22
Q
Structure of a Normal Artery
A
- 3 layers (tunica) – intima, media & adventitia
- Intima – endothelial cells, the underlying extracellular
matrix, and a smattering of smooth muscle cells - Media – smooth muscle cells (SMC)
23
Q
Atherosclerosis – Definition
A
- Sclerosis – abnormal hardening of body tissue
- Arteriosclerosis – the thickening, hardening and loss of elasticity of arterial wall (eg. calcification, atherosclerosis)
- Atheroma – the lipid deposits in intima of arteries, producing a yellow swelling on the endothelial surface
- Plaque (atheromatous plaque) is made up of fat,
macrophages, calcium, and other substances found in the blood - Atherosclerosis – a disease in which plaque builds up
inside your arteries
24
Q
Atherosclerosis Begins in Childhood
A
due to endothelial dysfunction
