Adv chemistry exam 1

identify structures in the liver

identify structures in the liver

Cholesterol

Phospholipid

Triglyceride

Free fatty acid

saturated fatty acid

(saturated with hydrogens)

unsaturated fatty acid

unsaturated: doesn’t have all the hydrogens it could possibly have; has a at least 1 double bond

Polyunsaturated fatty acid

Omega-3 fatty acid

has double bond between 3rd and 4th carbon from far end away from the COO-/COOH

Of glutathione

Identify markers of MI on timeline chart

Recognize functions of Kupffer cell and acenstery/derivation

-Macrophages (monocytes that have migrated from blood vessels to tissue) that line the sinusoid (blood vessel in liver)
-Act as scavenger, removing big particulates (complexes of coagulation factors and inhibitors, antibodies and antigens) from circulation, detoxifier, and antimicrobial

Identify markers of protein nutrition

Prealbumin
-AKA transthyretin (thyroxine-binding prealbumin)
-Transports vitamin A and thyroid hormones
-Sensitive index of protein nutrition
Prothrombin (factor II)
PLT count

synthetic function of the liver

Markers of liver function (synthesis)
-Total protein
-Albumin
-Transports insoluble compounds
-FAs
-Bilirubin
-Calcium
-Lipophilic medications
-Keeps water in vasculature
-Decrease albumin = edema
-Moderately informative of protein nutrition
-3-week half life

synthetic function of the liver (shorter 1/2 life)

factor VII (clotting factor)
-half-life of 4 hours
-Basis of INR, depends on adequate activity and levels of factor 7. No protein = low factor 7 activity
prealbumin
-Half life of 2-3 days

Markers of hepatobiliary function (will rise when blockage/disease exists)

Total and conjugated bilirubin
ALP activity
gamma-GT
-Participates in glutathione detoxification

Markers of liver cell injury (will rise when cell injury/death present)

AST
ALT

Recognize metabolic function of liver in regard to blood glucose

-Liver doesn’t metabolize glucose (saves it for brain since fatty acids and lipoproteins can’t cross blood-brain barrier)
-Liver utilizes fatty acids

glycogenesis

Conversion of glucose to glycogen (storage form)
Instigated by insulin

Glycogenolysis

Break down of glycogen (storage form) to glucose
Instigated by glucagon

Lipolysis

Breakdown of cholesterol and triglycerides to form free fatty acids
Instigated by glucagon and epinephrine
Forms 3 fatty acids and 1 glycerol
Transported via blood stream with cholesterol as lipoprotein
Other cells take up FAs, liver uses glycerol

Fatty acid synthesis

Synthesis of fatty acids from acetyl CoA

Gluconeogenesis

Formation of glucose-6-phosphate from noncarbohydrate sources
Instigated by glucagon

Anaerobic glycolysis

Metabolism of a glucose molecule to pyruvate or lactate for production of energy

function of glutathione and importance in RBC and hepatocyte

RBCs use glucose to run salt pumps
-Keeps glutathione in reduced state? (intact glucose-6-phosphate pathway)
Important antioxidant
Can be depleted in G6PD deficiency, acetaminophen overdose
Detoxifies both xenobiotic and endogenous compounds
Facilitates excretion of toxins from cells, body
Directly neutralizes compounds
Scavenges oxidants (superoxide anion, hydroxyl radical, nitric oxide, carbon radicals)
Recycles vitamin C and E

Differentiate markers of hepatobiliary disease with those sensitive to liver cell injury

AST/ALT = liver cell injury
-Leak out of damaged cells
ALP, gamma-GT: hepatobiliary function
-Induced by biliary stasis or obstruction/hepatobiliary disease

Which aminotransferase is used most often to monitor toxic effects of medications?

ALT
More liver specific

End result of severe urea cycle defects

Build-up of ammonia

Function of UDP-glycosyl transferases

Transport (derivative of glucose) glucuronic acid
Catalyze covalent addition of sugars to lipophilic molecules
Eliminates exogenous chemicals and by-products of endogenous metabolism
Controls levels and distribution of endogenous signaling molecules
Liver attaches polar and charged glucose (glucuronates) to facilitate excretion through bile

Gibert

Defect in bilirubin uridine diphosphate glucuronosyltransferase (bilirubin UGT)
Mild
Unconjugated hyperbilirubinemia is induced by stress/illness

Crigler-Najjar syndrome

Rare
Autosomal recessive disorder
Loss of UGT1A1
Severe unconjugated hyperbilirubinemia and kernicterus

Identify the type of large complexes cleared from blood by the liver

Haptoglobin
-scavenges free heme from blood
Removes coagulation-inhibitor complexes, hemopexin-heme, haptoglobin-globin complexes

Identify conditions or disorders other than MI/ACS which result in elevations in plasma Troponins

Renal failure
Trauma
CHF
Aortic valve disease
Pulmonary embolism
Renal insufficiency
Pneumonia
Septic shock

Chylomicrons

Transports dietary triglycerides

Chylomicron remnant

Remnant of chylomicron after delivery of triglyceride to adipose tissue
Taken up by liver

VLDL

Transports endogenous triglyceride to adipose

IDL

Intermediate density lipoprotein
Remnant of VLDL after delivery of triglycerides
Taken up by liver

LDL

Transports cholesterol
Size is clinically significant
Receptor-mediated uptake in liver and adipose (LDL-R)

HDL

Important in reverse cholesterol transport

Lipoprotein lipase

“Digests” triglycerides transported to adipose
enzyme

LCAT

Enzyme
Transports cholesterol out of blood and tissues via cholesterol esterification
Uses phosphatidylcholine

ACAT

Enzyme
Uses acyl-CoA
Catalyzes formation of cholesteryl esters from cholesterol

Apo B-100

Atherogenic
Structural protein for VLDL and LDL
Ligand for binding to LDL receptor
Mainly on VLDL, IDL, LDL

Apo A-IV

Mainly on HDL, chylomicrons
Activator of LPL and LCAT

Apo C-II

Mainly on chylomicrons, VLDL
Essential cofactor for LPL

Apo a

Structural protein for Lp(a)
Inhibitor fo plasminogen activation
Increases risk for heart disease and stroke
Similar to LDL
-Has aspoB and aspo(a) attached to surface
-Contains oxidized phospholipids

Clinical significance of increased circulating Lp(a)

Increased risk of heart disease and stroke
Genetic predisposition

Small dense LDL

Associated with raised triglycerides and decreased HDL-c levels
Adiposity and diabetes
Genetic predisposition

Oxidized LDL

atherosclerosis

mutated LDL-R

Coronary artery disease

Table 6 from AACE, match LDL goals to risk category

Familial hypercholerolemia

Changes in LDLR gene
Results in increased LDL
Caused by mutations in APOB, LDLRAP1, or PCSK9 gene
LDLR is unable to remove cholesterol from blood

Abetalipoproteinemia

Very low LDL and VLDL
Cause by genetic variants in MTTP gene; autosomal recessive
-Makes microsomal triglyceride transfer protein
-Produces beta-lipoproteins (carry dietary fats and cholesterol)

Friedewald formula

LDLC = (Total Cholesterol) − (HDLC) − (TGs/5)
TGs/5 = VLDL

Identify conditions that invalidate the use and calculation of the Friedewald formula

Triglycerides >400,

Frederickson phenotypes I

Type I: impaired chylomicrons

Frederickson phenotypes IIa

Type IIa: Receptor defects in CSK9 protein

Frederickson phenotypes IIb

Type IIb: Impaired clearance of VLDL

Recognize technique to routine measurement of HDL

Precipitation
-Add precipitant
-All non-HDLs precipitate
-Centrifuge sample
-Measure HDL in supernatant
colorimetry

Recognize two systems that utilize receptor mediated endocytosis as a vehicle to deliver their goods to the inside of target cells

LDL
Cholesterol

PCSK9

Dismantles LDLR

Evolocumab (Repatha)

Inhibits PCSK9
LDLR not broken down; cholesterol/LDL taken into cells and plasma levels lowered
Monoclonal antibody against PCSK9

Statins

Competitive inhibitors of HMGCoA reductase
Starves cells of cholesterol; increases expression of LDLR

Vitamin C

Keeps iron in reduced state
Increases iron absorption

Deficiency
-Low iron
-scurvy
Excess
-Iron overload

ethanol

Increases iron absorption

Hemolytic anemia

Increases absorption

Phytate (vegetable) intake

Decreases absorption

Elevated inflammatory cytokines

Decreases absorption

Elevated inflammatory cytokines

Decreases absorption

Anemia of chronic inflammation

Decreases absorption

Anemia of chronic disease

Decreases absorption

Hereditary hemochromatosis

Increased absorption

Transferrin

Transports iron
Chelates iron to be rendered soluble
Prevent formation of reactive oxygen species

Ferritin

Increases with hereditary hemochromatosis
Stores iron inside cells

Transferrin receptor 1

Transfers iron from circulation (transferrin) into cells

Transferrin receptor

Senses iron status
On hepatocytes

Dcytb

Duodenal ferric reductase
Reduces iron from 3+ to 2+ for absorption

DMT-1

Divalent metal transporter-1
Absorbs Fe2+

Hepcidin

Liver hormone
Regulates iron absorption and mobilization
Increased hepcidin = decreased iron

Hephaestin

Transmembrane copper-dependent ferroxidase
Effective iron transport from intestinal cells to circulation
Dependent on hepcidin levels

Ceruloplasmin

With hephaestin: oxidizes and binds ferric iron to transferrin

Ferroportin

Transports iron across the membrane from cell to circulation
Bound by hepcidin (which decreases iron absorption)

Hemojuvelin

Controls levels of hepcidin

HFE

Controls levels of hepcidin
Mutation causes hereditary hemochromatosis

Identify function of lactoferrin in neutrophils

Keeps tight hold on iron to prevent parasites/bacteria from getting ahold of it

Calculate transferrin saturation given appropriate variables

Serum iron/TIBC x 100
Example:
Serum iron = 100 micrograms/L
TIBC = 300 micrograms/L
100/300 * 100 = 33% transferrin saturation

interpret transferrin saturation

70-100% saturation = iron overload (hemochromatosis)
10% saturation = iron deficiency
35% = normal

Both should agree, differences in methodology
TIBC
-Radiated iron is added to a sample
-The more radiated iron is attached to transferrin, the more open spaces there are on transferrin
-Excess iron is removed
-Iron is dissociated from transferrin
-Measurement of iron is indication of transferrin levels
-More iron after dissociation = more transferrin
Immunochemical
-Anti-transferrin antibody attaches to transferrin

Iron panel

TIBC
Ferritin
Transferrin
Hemoglobin

ACD

TIBC is low
Stores are high

IDA

TIBC is high
Stores are low

Iron overload

TIBC low or normal
Iron high
Ferritin high

Hemachromatosis

TIBC high
Ferritin high
Serum iron high

Ceruloplasmin

In plasma
Catalyze oxidation and binding of ferric iron to transferrin

Hephaestin

Basolateral membrane of RBCs
Catalyze oxidation and binding of ferric iron to transferrin

Identify what is meant by a negative acute phase reactant

Quantity goes down in inflammation
Example: ferritin, transferrin

Identify the earliest and most sensitive marker of iron deficiency

Ferritin
-Storage form of iron
-Use all storage when absorption of iron is low
-Low ferritin = early sign of iron deficiency

Identify the earliest and most sensitive marker of iron overload

Ferritin increased

Hepcidin

Regulates ferroportin
High hepcidin turns off ferroportin
Keeps iron inside of cells
Potentiates excretion of iron; soughs enterocytes into feces

hepcidin in ACD/ACI? Hereditary Hemochromatosis?

Is positive acute phase reactant
-Increases in inflammation
-Keeps iron inside of cells to keep it away from parasites/bacteria
Increases in ACD
Decreases in hemochromatosis