MMSC407 Exam 3
lipid absorption
dietary cholesterol and triglycerides -triglyceride absorption is efficient -cholesterol absorption is less efficient
metabolic (nonrespiratory) acidosis
excessive loss of HCO3- -production of other acids, such as keto acidosis or lactic acidosis -reduced excretion of H+ which consumes HCO3-
ketone formation of fatty acids
starvation or impaired carbohydrate metabolism -excessive production of acetyl-CoA
3.0 (fill in blank)
strong acids have a pK of < ____ -very low pH -raising the pH above the pK will cause the acid to dissociate, releasing free H+
9.0 (fill in blank)
strong bases have a pK of > _____ -lowering pH below the pK will cause the base to dissociate, releasing free OH-
triglycerides (TG) reference range
60-150 mg/dL
normal arterial pH range
7.35-7.45
estimated oxygen saturation (O2Sat)
calculated from pH, pO@ and hemoglobin
dissociation constant (ionization constant K value)
describes relative strength of acids and bases -specifically Henderson-Hasselbach equation
pK
-negative log of ionization constant -pH in which protonated and unprotonated forms are present in EQUAL concentrations -pK = pH at which the acid is half dissociated
saturated fatty acids
-no double bonds -flexible and rotate freely
*triglycerides (TG) risk classification*
-normal: <150 mg/dL -*borderline high*: 150-199 mg/dL -high: 200-499 mg/dL -*very high*: > 500 mg/dL
VLDL risk classification
-normal: <30 mg/dL -high: >30 mg/dL
*statin drugs* (fill in blank)
*______ reduce production of cholesterol due to inhibiting HMG-CoA reductase*
*total cholesterol (TC) risk classification*
-*desirable*: <200 mg/dL -borderline high: 200-239 mg/dL -high: >240 mg/dL
HDL risk classification
-*low*: <40 mg/dL -high: >60 mg/dL (want MORE HDL protein due to their function, HIGHER IS BETTER)
LDL risk classification
-*optimal*: <130 mg/dL -*borderline high*: 130-159 mg/dL -high: 160-189 mg/dL -very high: >190 mg/dL
shift to right (oxygen-hemoglobin dissociation curve)
-*think of RIGHT arm facing down with fingers relaxed* -pH is decreasing -freely letting go of oxygen -pCO2, 2,3-DPG and temperature are increasing
Lp(a) elevation
-Lp(a) are variants of LDL with extra apo (a): extra apo (a) can contribute to CHD and CVD -increased risk of CHD and CVD -higher levels are found in these patient population -competes with plasminogen for fibrin binding sites, increasing plaque formation = doesn't allow plasminogen to break down = fibrin will continue to build = plaque will form -no definitive treatment
production and excretion of ammonia
-NH3 (ammonia) is generated from glutamine and AAs -NH3 gas in urine will diffuse across the tubular cells -NH3 gas and H+ associate to form NH4+ (ammonium ion) -acid pH of urine favors NH4+ production
regulation of excretion of acids and bases
-Na+-H+ exchange -production and excretion of ammonia -reabsorption of HCO3-
hemoglobin-oxygen dissociation
-O2 must be released from hemoglobin at tissues -oxygen dissociated from adult (A1) hemoglobin in characteristic fashion (S-shaped curve)
normal oxygen-hemoglobin dissociation curve
-S shape is due to oxygen loading: first oxygen to load takes the longest and most effort; loads much faster by the 4th hemoglobin -structurally change the shape of hemoglobin -at 50%, the pO2 should be ~26
hypoalphalipoproteinemia
-a (ssociated with several defects, often genetic, most are linked to increased risk of premature CHD -isolated decrease in circulating HDL (concentration <40 mg/dL), without presence of hypertriglyceridemia -alpha denotes region in which HDL migrates on agarose electrophoresis
oxyhemoglobin saturation (SO2)
-all oxygenated hemoglobin divided by the total hemoglobin capacity and expressed as a percentage -measured by a pulse oximeter
proper collection and handling of blood gas specimens
-anaerobic conditions -acceptable collection time into syringe can produce bubbles (relate to oxygen that might be in sample) can encourage micro clot formation can generate hemolysis -mixed immediately with dry anticoagulant: lyophilized heparin to prevent formation of clots -specimen should be rolled and turned in directions when mixing to allow heparin to fully incorporate into specimen
7 conditions necessary for adequate tissue oxygenation
-available atmospheric oxygen -adequate ventilation -gas exchange between lungs and arterial blood -loading of O2 onto hemoglobin -adequate hemoglobin -adequate transport -release of O2 to tissue
controls of measurement of pH and pCO2
-blood based: contain human erythrocytes -sealed vials with gas mixtures: known O2 and CO2 content
sources of error for pO2 electrodes
-buildup of protein material on surface membrane: prevents oxygen from cross membrane -bacterial contamination within measuring chamber: consumes oxygen and causes decrease in oxygen that's measured -exposure to room air: gives falsely decreased amount of oxygen -delay in measurement of drawn sample: loss of oxygen
classification of lipids
-cholesterol -fatty acids -acylglycerols: triglycerides and phospholipids
6 groups of lipids (only need to know first 4)
-cholesterol -fatty acids: saturated and unsaturated -acylglycerols: triglycerides and phospholipids (glycerol backbone with phosphorus and nitrogen components) -prostaglandins: big components of platelets -sphingolipids -terpenes
density from least to greatest (lipoproteins)
-chylomicron -VLDL -LDL -Lp(a) -HDL
classification of lipoproteins
-chylomicrons -VLDL -LDL -Lipoprotein a -HDL
major coronary heart disease (CHD) risk factors
-cigarette smoking -hypertension (blood pressure >/equal to 140/90 mmHg or on anti-hypertensive medication) -low HDL cholesterol (<40 mg/dL) -family history of premature CHD male, first degree relative <55 years female, first degree relative <65 years -age (men > 45 years, women > 55 years)
chylomicrons
-contain apo B-48 -largest and least dense (big but light weight) float to top of a stored plasma specimen reflect in optical techniques: creates interference with excess scatter and causes falsely elevated levels -produced by intestine: primary function is to deliver dietary lipids to hepatic and peripheral cells -break into chylomicron remnants in plasma
delayed transport/testing of blood gas specimens
-decrease in pH: related to a decrease in glucose and increase in lactic acid -increase in pCO2: CO2 is a byproduct of glycolysis by leukocytes, platelets and reticulocytes
common factors influencing the amount of O2 that moves through alveoli into blood and then to tissue
-destruction of alveoli -pulmonary edema: excess amount of fluid in the lungs which doesn't allow O2 to move from lungs to blood -airway blockage -inadequate blood supply -diffusion of CO2 and O2
improvement and standardization of lipid and lipoprotein assays
-developed by NCEP (national cholesterol education program) -assay measurements will be the SAME, it doesn't matter where it was tested (could be tested in NY and will have same results if tested in DE) -allows comparison of results between laboratories and methods: provides guidance for continuity and consistency -reduces misclassification of patient risk factors, specifically for CHD
therapeutic life-style changes for CHD
-diet: saturated fat <7% calories and cholesterol <200 mg/day; increased soluble fiber (10-25 g/day) to enhance lowering LDL -weight management -increased physical activity (increases HDL)
exogenous pathway (dumbed down)
-dietary lipids (triglycerides and cholesterol) are being consumed -production of chylomicron -enters the circulation -LPL takes some free fatty acids (if there's excess) out to the adipose tissue -convert into chylomicron remnant with apo E component -some can be picked up from an HDL: called an empty HDL because at the moment it's not attached to anything else -chylomicron remnant with apo E on surface ends up going to the liver -liver breaks it down into free fatty acids and cholesterols
unsaturated fatty acids
-double bonds between carbons -monounsaturated: one double bond -polyunsaturated: many double bonds -the more double bonds in a chain, the less flexible and rotational capacity the fatty acid will have -fixed bends in the chains at the double bond location
calibration of measurement of pH and pCO2
-electrode sample chamber must be maintained at constant temperature (37C) -if the temperature increases, the voltage will increase: affects pH and pCO2 results -if the temperature decreases, the solubility of the gas will increase: gas will stay within the sample itself and won't be released -pH electrode is calibrated with 2 buffer solutions -gas mixtures are used to calibrate for pCO2 & pO2 -most instruments are self-calibrating calibrated to occur at specified intervals (takes place every 30-60 minutes) programmed to indicate a calibration error if electronic signal from electrode is inconsistent with programmed expected value
*Lp(a)*
-enhances LDL entry into the arterial wall -facilitates the oxidation of the LDL -enhances LDL uptake by macrophages to produce foam cells: spleen and liver have a lot of them but are present in vascular system too -contributes to thrombogenesis (creation of clot forming) by binding to fibrin, platelets and endothelial cells: PLTs are early clot formers and coagulation cascade helps create the fibrin to stabilize the clot -competitively inhibits the binding of tissue plasminogen activator (tpa) to its receptor: Lp(a) binds in receptor site of tpa, which doesn't allow tpa activation to convert plasminogen to plasma = DECREASES plasmin formation and thrombolysis -net result: atherogenic (plaque forms in lumen and interior of lumen shrinks, causes possible blockage)
exogenous pathway vs. endogenous pathway
-exogenous: dietary lipids enter small intestine --> chylomicrons form --> enter capillaries or vascular system --> go into muscles for metabolism --> excess goes into adipose tissue for storage --> chylomicrons start to break down and form remnants --> LDL receptor on liver for chylomicron --> liver breaks it up --> forms cholesterol and bile acids (bile acids are used to help with the breakdown of the exogenous products) -endogenous: liver creates VLDL and pushes it out into circulation --> goes to muscles for metabolism --> excess goes into adipose tissue for storage --> intermediary DL (IDL) can go back to the liver or can covert into an LDL, which can then either go back to the liver again or can go out to the peripheral tissues
pre-analytical considerations for blood gas sample collection
-experienced, knowledgeable personnel -proper patient ID -correct labeling of specimen and accurate info provided
other considerations of blood gas specimens
-exposure to room air: increase in pO2 and decrease in pCO2 -altitude: decrease in pO2 and pCO2 with rising altitude -patient position: supine position will have lower pCO2 -pregnancy, just prior to delivery: lower pCO2
potential sources of error in FO2Hgb
-faulty instrument calibration -light absorbing (interfering) substances
glycerol measurement (triglyceride analysis)
-free glycerol in serum can interfere with the reaction -elevate TG result by 10-20 mg/dL -procedure uses a blank to measure the free glycerol in sample before lipase is added -corrects the TG result
interferences in cholesterol assays
-free hemoglobin: causes hemolysis and allows for falsely increased results -bilirubin: interferes with enzymes and won't create the next byproduct of the 3 step assay, which causes a falsely decreased results -ascorbic acid: also interferes with enzymes and won't create the next byproduct of the 3 step assay, which causes falsely decreased results; typically due to patient consuming too much
pH measurement
-glass membrane sensitive to H+ -internal Ag-AgCl electrode for measurement of free hydrogen -the potential that develops at the glass membrane surface is related to the cH+ in sample -compared against a reference electrode -electrode must be free from protein build up because it can block interaction with free hydrogen on surface of membrane and cause a in decrease H+ activity
pO2 (Clarke) electrodes
-glass permeable or polypropylene membrane on the electrode -oxygen selectively crosses the membrane and are drawn to the anode -amount of current flow in circuit related to amount of O2 being reduced at cathode -measurement the movement of electrons
lipids function
-hormones: structural component -digestion -energy -structural elements
shape of oxygen dissociation curve and affinity of hemoglobin for O2 is affected by
-hydrogen ion activity -pCO2 and CO levels -body temperature -2,3-DPG
lowering LDL
-important -every 1% decrease in LDL equals to a 2% decrease in the developing arteriosclerosis
bicarbonate-carbonic acid system
-low buffering capacity -H2CO3 dissociates into CO2 and H2O, allowing CO2 to be eliminated (via exhalation) and H+ as water -changes in CO2 modify ventilation (respiration) rate -HCO3- concentration can be kidneys
hsCRP reference values
-low risk: <1 mg/dL -moderate risk: 1-3 mg/dL -high risk: >3 mg/dL
apolipoprotein A-1 analysis
-major protein of HDL -measured by separation and analysis of HDL cholesterol
apolipoprotein B analysis
-major protein of LDL and VLDL -measured by immunoassays: use AgAb complexes and substrates, color change will evolve and be measured
cleavage of cholesteryl esters in cholesterol assays
-most circulating cholesterol is in the form of cholesteryl esters -draw serum specimen from patient and taking cholesteryl ester and converting it over to cholesterol
diagnosis and treatment of lipid disorders (dyslipidemias)
-not a lot you can do for treatment options -adult management of lipoprotein disorders: cholesterol screening: measures TC and gives useful info lipid panel for diagnosis: need to know why TC is so high assessment of CHD risk lifestyle changes: diet and physical activity adult treatment guidelines: evaluating patient against weight, hypertensive medication, etc. influence of increased TGs/low HDL pharmacologic agents: should medicine be prescribed to lower cholesterol?
Na+-H+ exchange
-occurs by the action of the sodium hydrogen exchanger (NHE) -in the cells of proximal tubules of nephrons, H+ ions are exchanged in the urine with sodium ions -the exchange is *enhanced in acidosis* and *inhibited in alkalosis*: enhanced in acid condition because want to get rid of free hydrogen and inhibited in alkalotic condition because want to pick up more free hydrogen -potassium ions compete with hydrogen ions in the NHE: increased potassium will decrease in hydrogen ions in urine which increases urine pH and plasma becomes more acidic -hydrogen ions excreted by the NHE will react with HPO4^2- to form H2PO4-: process is dependent on amount of phosphate filtered by glomeruli and pH of urine acidemia (a lot of free of hydrogen) increases phosphate excretion --> provides additional buffer for H+
fatty acid catabolism
-occurs in cellular mitochondria -produces energy due to beta-oxidation (but not a lot) -reduces chain by 2 carbons at a time
*emulsification* (lipid absorption)
-occurs prior to absorption in the small intestine -occurs by pancreatic lipase: released and enters the small intestine to convert triglycerides into monoglycerides -*triglycerides* are converted to monoglycerides, glycerol and fatty acids -*cholesteryl esters* are transformed to free cholesterol: makes cholesterol soluble
correction for temperature
-pH, PCO2, & PO2 are all measured at 37C -if patient's body temperature differs from 37C, blood gas instrument can "correct" values -results at 37C should be reported for reference -gives measurements based on current temperature then translates them to the results at 37C
cholesterol synthesis
-performed by all cells especially liver and intestine -multiple stages -second stage contains enzyme *HMG-CoA reductase*: enzyme is targeted for cholesterol therapy and lowers overall cholesterol production -HMG-CoA inhibits action of statin drug family, which is medicine used for cholesterol
triglycerides
-predominant form of glycerol ester in plasma in human circulation -structure: 3 fatty acid molecules attached to 1 molecule of glycerol by ester bonds saturated fatty aids = solid at room temperature unsaturated fatty acids = liquid at room temperature -digestion: occurs in small intestine and get hydrolyzed to glycerol, monoglycerides and fatty acids -absorption: reassemble as triglycerides and form chylomicrons with cholesterol and apo B-48 to form a micelle
measurement of pH and pCO2
-principle: increase in concentration or ion activity = increase in force exerted by these ions (relates to current) -ion force measurement requires: 2 electrodes (ion of interest and reference electrode) and voltmeter (measures potential difference between 2 electrodes)
very low density lipoproteins (VLDL)
-produced by liver: major carriers of endogenous (liver created) triglycerides (made WITHIN THE LIVER, not consuming through diet) to peripheral tissues -contain apolipoproteins: apo B-100 -increased production: excess carbohydrates, saturated fatty acids and trans fatty acids (usually because of consumption)
transport of blood gas specimens
-room temperature -analyze in less than 30 minutes to minimize changes in O2 and CO2 levels -if expected to be delayed to lab, specimen should go on ice to prevent increase in O2 and decrease in CO2
shift to left (oxygen-hemoglobin dissociation curve)
-same shape of the curve, but everything is happening a little bit sooner and lower at the mmHg scale -*think of LEFT arm in air with hand in fist* -pH is increasing and becoming more alkaline -holding onto oxygen very tightly -pCO2, 2,3-DPG and temperature are decreasing
specimen collection and patient preparation for lipids
-serum is most common and best -fasting 12 hours is best: diet has smaller effect on cholesterol than it does on triglycerides -sample should be clear and yellow colored -sample SHOULD NOT be milky (chylomicrons are floating at the top forming a white band) or cloudy (lipemic)
cholesterol received via uptake of extracellular lipoproteins by cell surface receptors
-single cell in body -LDL receptors bind to the LDL -apo B-100 and cholesterol ester within the LDL will grab a hold of the LDL receptor -body pulls it into the cell -brings it in and breaks the receptor free from the LDL structure -recycles the receptors -rest of structure (cholesterol ester and apolipoprotein) can be sent to the lysosome to be broken down into amino acids -lysosome has to decide what to do with it: has cholesterol and can be stored there and be available for cell membrane to serve as steroid hormones or bile acids can store it as cholesterol ester if body decides it needs to make cholesteryl ester, HMG CoA reductase will be used can activate ACAT (acetyl CoA cholesterol transferase): transfer enzyme that takes the cholesterol and puts it into storage as cholesteryl esters -cells have the ability to produce additional LDL receptors: low supply of cholesterol inside cell = produce more; sufficient amount of cholesterol = produce less
high density lipoproteins (HDL)
-smallest and most dense -synthesized by liver and intestine -can exist either as disk-shaped or spherical particles (flat and frisbee shaped): depends on apo A-1 presence and what HDL is carrying -capable of removing excess cholesterol from peripheral cells: reverse cholesterol transport (takes it out of the peripheral cells and mobilizing it)
lipids
-soluble in organic solutions -nearly insoluble in water (think of oil mixing with water) -contain non polar carbon-hydrogen bonds: produce fatty acids and/or alcohols when hydrolyzed -some also have polar groups: affinity for water and organic solutions (ex. phospholipids and cholesterol) -6 groups
basic pathways in LDL regulation
-start at liver -liver produces VLDL -within the VLDL, you will see apo B, apo C and apo E in the structure -apo C will stimulate lipase breakdown of VLDL -multiple things can happen: can covert into a VLDL remnant and could go directly back to liver OR it can convert into an LDL which can be carried out to other sites (coronary arteries) or can go back to liver to get cleared
low density lipoproteins (LDL)
-structurally similar to VLDLs -contain apo B-100 and cholesterol -forms as a result of lipolysis of VLDL (breaks down VLDL) -readily taken up by cells via LDL receptors in liver and peripheral cells -significantly smaller than VLDLs: can pass into extracellular spaces and are collected by macrophages (macrophages are found throughout the body in the circulation system and they grab VLDLs to maintain balance) -plaque formation when in excess: interior of lumen in the arteries becomes smaller
lipid and lipoprotein population distributions
-total and LDL cholesterol and triglyceride levels increase with age in both men and women -on average, women have higher HDL cholesterol levels but lower cholesterol and triglyceride levels then men -after menopause, no difference in total cholesterol -total and LDL cholesterol and triglycerides are much lower in young children than adults because they are smaller in size and are more active -lower rates of LDL cholesterol and heart disease in Asians
Friedewald calculation
-total cholesterol (TC) = LDL + HDL + VLDL -LDL (approx.) = TC - (HDL + VLDL) -VLDL (approx.) = TG/5 --> *EXCEPT WHEN TG >400 mg/dL or for non-fasting samples*
general lipoprotein structure
-transport mechanisms for lipids -typically, spherical with a non polar core and an amphipathic surface: presence of cholesterol and phospholipids in the actual surface component of the protein -contain a specific protein on surface that provide characteristics (ex. apo B-48) -cholesteryl esters: non polar core and are kept inside the lipoprotein -phospholipids and cholesterol line the surface of the cell to give amphipathic properties -apolipoprotein gives individual lipoprotein its characteristics
Lp(a) analysis
-variant of LDL -measured by immunoassays
lipoprotein (a) (Lp(a))
-very structurally similar to an LDL -LDL-like particles: appear in different sizes and densities; apo (a) linked to apo B-100 -plasma levels of Lp(a) vary widely among individuals in population but remain constant within an INDIVIDUAL person -elevated levels can indicate risk of coronary heart disease and stroke (excess levels can cause plaque formation) -lipoprotein levels vary throughout the population so its hard to come up with reference ranges due to many forms and sizes
lipid absorption process
-villa increase surface area in small intestine -pancreatic lipase converts triglyceride into glycerol and free fatty acid -take broken down pieces and add cholesterol and bile salt -micelle is developed and gets absorbed via intestinal villa -micelles get converted to a chylomicron: packaged with triglycerides, phospholipids and apolipoprotein B-48 --> secreted into lymphatic system --> enter circulation --> delivered to the liver and tissues
total cholesterol (TC) reference range
140-200 mg/dL
HCO3- reference range
22-26 mmol/L
cholesterol assay
3 step enzymatic procedure -cholesteryl ester + H2O --> cholesterol + fatty acid -cholesterol + O2 --> cholestenone (ketone) + H2O2 -H2O2 + phenol + 4-aminoantipyrine --> quinonimine dye (color) + 2H2O -directly proportional: more color created = higher amount of cholesterol that's present in the patient sample
pCO2 reference range
35-45 mmHg
HDL reference range
40-75 mg/dL
LDL reference range
50-130 mg/dL
fractional oxyhemoglobin equation
FO2Hgb = cO2Hgb / c(total)HHgb -numerator = oxygenated hemoglobin -denominator = includes all hemoglobin varieties (includes oxyhemoglobin plus deoxyhemoglobin, methemoglobin, carboxyhemoglobin, sulfhemoglobin and dyshemoglobins)
Henderson-Hasselbalch (fill in blank)
HCO3- can be measured based on the ______ equation
decreased blood pH (kidneys)
HCO3- is reclaimed from glomerular filtrate to prevent excessive acid gain in blood from loss of HCO3- in urine -occurs in the cells of the proximal tubules -if there's too much free oxygen in the blood, the body will save some of the bicarb and reabsorb it to balance out the free H+ -*acidosis = reabsorb bicarb*
oxyhemoglobin (O2Hb)
O2 reversibly bound to hemoglobin -hemoglobin that has oxygen on board -when it gets to site of tissue, hemoglobin can release the oxygen
20:1 (fill in blank)
_______ ratio of HCO3- to H2CO3 in Henderson Hasselbach equation -cHCO3- reflects kidney function -pCO2 reflects lung function
acid
a substance that can yield a hydrogen ion (H) or hydronium ion when dissolved in water
base
a substance that can yield hydroxyl ions (OH-)
fractional (or percent) oxyhemoglobin (FO2Hgb)
actual percent of oxyhemoglobin can be determined using co-oximeter designed to measure various hemoglobin species -dependent on the number of wavelengths incorporated into instrument (spectrophotometric measurement) -most co-oximeters have 4 wavelengths and measure the 4 most common hemoglobin species: O2Hgb, HHgb, COHgb & MetHgb each species of Hgb has a characteristic absorbance curve (relates to the wavelength in which they can be optimally measured at)
amperometric
amount of current flow indicates oxygen present (pO2) -*think OXYGEN*
LDL cholesterol analysis
beta-quantification -ultracentrifugation to remove chylomicrons and VLDL -chemical precipitation to separate HDL -measure cholesterol -LDL = TC - HDL
H+ (fill in blank)
body controls and excretes _____to maintain pH homeostasis -lungs and kidneys work together to control and maintain the range
physiologic compensation
body's attempt to restore acid-base balance -alters the mechanism NOT primarily affected by the pathologic response
lipids, lipoproteins and apolipoproteins measurement
can be affected by: -comorbidities -medications (not just the ones that relate to cholesterol) -anticoagulant (plasma specimens): requires correction on cholesterol value and have to be careful of the anticoagulant that's present -specimen storage
solubility coefficient (fill in blank)
carbonic acid concentration can be calculated using _______ of CO2 in plasma at 37C (conversion of 0.0307)
potentiometric
change in voltage indicates analyte activity (pCO2, pH) -*think pCO2 and pH*
HDL cholesterol analysis
chemical precipitation -pretreatment of sample: take patient specimen --> add chemical to it --> removes everything that IS NOT HDL -removes non-HDL lipoproteins (LDL, VLDL, Lp (a) and chylomicrons) by polyanions high degree of positively charges AAs within their structures --> form complexes and becomes insoluble --> gets centrifuged out --> HDL remains in solution and is quantified as cholesterol
buffer
combination of weak acid or weak base and its salt -system resists changes in pH: constantly making adjustments where it needs to be to avoid big swings in the pH -depends on the pK of the buffering system & pH of the environment
transcutaneous (fill in blank)
continuous measurements for pO2 are possible using _______ electrodes placed directly on skin -used on neonates and infants because they can't constantly have blood drawn -affected by skin thickness and tissue perfusion at the site
hyperlipoproteinemia
creating high levels of lipoprotein
respiratory acidosis
decrease in alveolar ventilation (hypoventilation) -causes decreased elimination of CO2 by lungs -decreases HCO3-
dyslipidemia
diseases of abnormal lipid concentrations -usually no identifiable genetic mutation: runs in families (so there's a genetic component but it's not identifiable) and many different environmental and eugenic factors -secondary to common disorders -arteriosclerosis: single leading cause of death and disability in US, lipids and TGs are not maintained within healthy ranges which contributes to morbidity and mortality
familial hyperlipoproteinemia (FH)
elevated levels of serum TC or TG -can be due to elevated apo B-100 overproduction -increased risk for CHD -genetic forms: familial combined hyperlipoproteinemia; elevated cholesterol AND elevated triglycerides
hypertriglyceridemia
elevated triglyceride levels -imbalance of production and clearance of VLDL in circulation deficiency in lipoprotein lipases (LPL) or it's cofactor apolipoprotein C: causes decrease of VLDL production deficiency prevents clearing of chylomicrons and triglycerides remain high: chylomicrons are not properly cleared from circulation -*patients are NOT LIKELY to have atherosclerotic diseases: DO NOT see plaque formation because chylomicrons are TOO BIG to enter into vessels* -HDL is often decreased -due to either genetic abnormalities or endocrine abnormalities -treatment by dietary modifications
*catabolism* of cholesterol
end of REVERSE cholesterol TRANSPORT pathway -last step of the pathway -most cholesterol returns to the liver: converts to bile acids and is absorbed in the small intestine -some cholesterol is excreted into the bile directly: can be made soluble by bile acids
apo B-100 (fill in blank)
endogenous pathway is mediated by _____ containing proteins -apo B-100, apo C and apo E are in the liver forming the VLDLs --> converting that into the IDLs --> could potentially come LDLs -present on VLDLs, IDLs and LDLs -can be converted into a cholesterol ester or could move back to the liver
acidemia
excess acid or H concentration -pH level below reference range (< 7.35) -leads to acidosis
akalemia
excess base or decrease H concentration -pH level above reference range (> 7.45) -leads to alkalosis
reverse cholesterol transport pathway
excess cholesterol is actively pumped out of peripheral cells -HDL takes cholesterol pumped out of the cells to the liver in the form of cholesteryl esters (cholesteryl esters are used for transport) -HDL will change form from disk-shaped to spherical when cholesteryl esters are generated spherical shaped HDL can pick up additional cholesterol -liver can selectively remove the cholesteryl esters from the HDL and return HDL to circulation
coronary heart disease (CHD)
excess lipids (esterified cholesterol) deposit on the artery walls and, over time, develops into plaque -peripheral vascular disease (PVD), coronary artery disease (CAD) and cerebral vascular disease (CVD) are referred to as CHD -can also deposit in the liver, kidneys, and skin (xanthomas)
regulation of acid base balance in kidneys
excretes acids or bases to maintain pH range -when excretion of HCO3- doesn't work properly or is exceeded: kidney failure, chronic nephritis, infection, loss chloride, diuretics
chylomicrons (fill in blank)
exogenous pathway is mediated mainly by ________
lipoprotein metabolism major pathways
exogenous pathway, endogenous pathway, intracellular cholesterol transport pathway, reverse cholesterol transport pathway -all are dependent on apo B containing lipoproteins -energy contribution: movement of fatty acids to peripheral cells -when there's a carb depletion, stored fatty acids can be taken and used for energy
Tangier disease
extreme form of hypoalphalipoproteinemia -HDL as low as 1-2 mg/dL = very concerning -orange tonsils -splenomegaly: deposition of cholesteryl esters into macrophages -peripheral neuropathy: low HDL and excess cholesterol impacts the nervous system causing numbness in hands and feet -limited treatment options
metabolic (nonrespiratory) alkalosis
gain in HCO3- -increases pH -excess addition of base -decrease excretion of base
familial hypercholesterolemia (FH)
genetic abnormality predisposing people to elevated cholesterol levels -caused by defects in LDL receptor pathway cholesterol production is normal: making what they need cholesterol cannot enter the cells when transported: cells generated cholesterol intracellularly -causes early death from myocardial infarction (MI) -treatment seeks to reduce cholesterol production and stimulate generation of LDL receptors (allows them to grab any cholesterol in the cell for use)
acylglycerols (glycerol esters)
glycerol + fatty acid chain -monoglyceride, diglyercide and triglyceride
carboxyhemoglobin (COHb)
hemoglobin bound to CO -carbon monoxide has an affinity 200-400x stronger to hemoglobin than oxygen -when exposed to CO, its life threatening due to CO holding onto hemoglobin and not letting go
deoxyhemoglobin (HHb)
hemoglobin not bound to O2 but capable of forming a bond when O2 is available -can pick up hydrogen and other things (ex. sulfur) -has something OTHER THAN oxygen on board
methemoglobin (MetHb)
hemoglobin unable to bind O2 because iron (Fe3+) is in an oxidized rather than reduced state -not able to bind due to iron being in center of the heme ring -oxidized state = ferric iron, reduced state = ferrous iron
hypercholesterolemia
high cholesterol -lipid abnormality most closely linked to CHD
LDL (fill in blank)
high levels of ___ are central to promoting plaque formation -deposited in macrophages: a lot of fat in the macrophages can make it appear as a foam cell -promotes inflammatory response: body sees plaque as foreign and sends WBCS to activate complement -generates plaque -increases pressure in the vascular spaces
C-reactive protein (fill in blank)
high-sensitivity __________ (hsCRP) is used for advanced testing for risk of CHD -specific form of CRP -acute phase reactant: reacts early and rapidly, making it a good marker for inflammation -correlated with future CHD risk -interrelationship of inflammation, atherothrombosis, diabetes and hypertension -predictor of MI, stroke, PVD and sudden cardiac death
arrows (fill in blank)
if *both pCO2 and HCO3-* are abnormal, then you need to refer to your _____ -need to see *WHICH SIDE OF pH 7.40 THE VALUE RESIDES*
metabolic (fill in blank)
if *only HCO3-* is abnormal, then it is _____
respiratory (fill in blank)
if *only pCO2* is abnormal, then it is ______
acidotic (fill in blank)
if pH is within 7.35 - 7. 39 range, patient is in the ______ state
alkalotic (fill in blank)
if pH is within 7.41 - 7.45 range, patient is in the ______ state
respiratory alkalosis
increase in alveolar ventilation (hyperventilation) -causes excessive elimination of CO2 by lungs -increases HCO3-
type V hyperlipoproteinemia
increase in chylomicrons and VLDL -likely caused by increased production of VLDL or decreased removal of VLDL -lipoprotein lipase activity is often normal, as is apo-C lipoprotein -modestly increased risk of CHD -considered a familial hyperlipoproteinemia
nonvolatile (fill in blank)
kidneys excrete _____ acids -decreases pH -after plasma filters through the glomerulus, it becomes more acidic due to the acids, which causes the pH to lower
alkalosis
kidneys will conserve acids and excrete more bases -conserves more hydrogen
acidosis
kidneys will excrete more acids and conserve bases -allows for more free hydrogen and will reabsorb bicarb
fatty acids
linear chains of carbon-hydrogen bonds terminating in carboxyl group -general structure is RCOOH (R is the alkyl chain and gives the fatty acids their properties) -vary in length -most are synthesized in the body
micelles (fill in blank)
lipid absorption generates amphipathic ________ -unesterified (free) cholesterol -fatty acids -monoglcyerides -phospholipids -bile acids -come into contact with intestinal villa and are absorbed (resemble triglycerides)
plasma
liquid portion of the blood -pK 6.1 -pH 7.4 -bicarbonate-carbonic acid system: buffering system in body that helps maintain pH
hypoventilation
lungs don't remove CO2 -not picking it up from the blood, not crossing over into the alveolar spaces of the lungs and not exhaling -low and slow breathing -increase in H+ --> decrease in pH (*acidosis*)
hyperventilation
lungs remove CO2 too fast -start panting and breathing faster -decrease in H+ --> increase in pH (*alkalosis*)
quickly, several days (fill in blank)
lungs respond ____; kidneys may take _____ to respond to acid base imbalance
intracellular cholesterol transport pathway
maintains cellular balance of cholesterol (too much cholesterol is toxic to the cells and will do more harm than good) -cholesterol uptake of extracellular lipoprotein by cell-surface receptors (LDL receptors): used for cell membrane maintenance --> converted and stored in lipids reserves within cells --> removed by the reverse cholesterol transport pathway
blood gas analyzers
measure pH, pCO2 and pO2 with electrodes -2 methods: amperometric and potentiometric -HCO3- is calculated using Henderson Hasselbach equation and not measured directly -cathode: negative electrode, site to which cations tend to travel and site at which reduction occurs -anode: positive electrode, site to which anions tend to travel and site at which oxidation occurs -electrochemical cell: formed when 2 opposite electrodes are immersed in a liquid that will conduct current
lipoprotein analysis methods
measurement based on physical properties -density: relates to lipid and protein content, ultracentrifugation is used to separate -size and charge: electrophoretic separation -size, charge and apolipoprotein content: chemical precipitation (add chemicals into sample and see insoluble samples form and settle to bottom), most common for HDL
bicarbonate buffering system and the Henderson Hasselbach equation
measurement of components of bicarb buffering system provides information on other buffers and systems that regulates product, retention and excretion of acids and bases
hemoglobin (fill in blank)
most O2 arterial blood is transported to tissue by ______ -blood hemoglobin exists in 1 of 4 conditions: O2Hb, HHb, COHb, MetHb
triglyceride analysis
multiple enzyme steps -TG + H2O --> glycerol + fatty acid -glcyerol + ATP --> glycerophosphate + ADP -glycerophosphate + O2 --> dihydroxyacetone (ketone) + H2O2 -H2O2 + phenol + 4-aminoantipyrine --> quinonimine dye (color) + 2H2O -color change looks similar to cholesterol assay
increased blood pH (kidneys)
occurs when kidneys excrete HCO3- -body excretes the bicarb to decrease the pH -*alkalosis = excrete bicarb*
opposite (fill in blank)
pCO2 2,3-DPG and temperature are all ____ to pH
Henderson Hasselbach equation
pH = pK + log [cHCO3- / (0.0307 x pCO2)} -c = concentration -0.0307 = constant used in equation -pCO2 relates to the amount of H2CO3
temperature (fill in blank)
pH and blood gas measurements are extremely sensitive to ______ -blood gas analyzer should be in an environment where there's not going to be a lot of extremes
compensated
pH is *normal* and *both* pCO2 and HCO3- are abnormal
partially compensated
pH is abnormal and *both* pCO2 and HCO3- are abnormal
uncompensated
pH is abnormal and *either* pCO2 or HCO3- are abnormal
*esterification* of cholesterol
part of INTRACELLULAR cholesterol transport and REVERSE cholesterol transport pathways -forms cholesteryl ester within the cells: stored in intracellular lipid drops within the (circulation) plasma: binds to high density lipoproteins (HDL)
atherosclerosis
plaque buildup of fat and cholesterol on artery walls -reduces diameter of the lumen of the artery -inner space becomes smaller and puts greater pressure on the artery walls = will require more energy for blood to travel through -key component in cardiovascular diseases: myocardial infarctions; artery blockage leading to heart cerebrovascular disease: artery blockage leading to brain peripheral vascular disease: outside of the main trunk (arms and legs)
endogenous pathway
primary function of this pathway is to move the lipids (triglycerides) made in the liver to peripheral cells for energy metabolism -movement is mediated by apo B-100 containing proteins -packaged as VLDL and mostly triglyceride in structure -VLDL loses core lipids, causing dissociation and transfer of apolipoproteins and phospholipids to other lipoprotein particles loss of core lipids = whole structure dissociates takes apolipoproteins from the surface and allows them to be used by other lipoprotein particles -apo C activates lipoprotein lipase, which will hydrolyze the VLDL -during this loss of triglycerides from the core of the VLDL, VLDL is converted to VLDL remnants OR can be further transformed into LDL
reabsorption of HCO3-
purpose of reabsorption is to maintain pH in plasma -carbon dioxide in the tubular cell reacts with water to form carbonic acid, which dissociates into bicarbonate and hydrogen ions -when HCO3- exceeds 26 mmol/L, its excreted in the urine
acid base mnemonic (ROME)
respiratory opposite -alkalosis ↑ pH ↓ PaCO2 -acidosis ↓ pH ↑ PaCO2 metabolic = equal -alkalosis ↑ pH ↑ HCO3 -acidosis ↓ pH ↓ HCO3
HDL (fill in blank)
reverse cholesterol transport pathway is mostly mediated by ______ -plaque/foam cells are referred to as peripheral cells and are seen in macrophages that have too much fat or cholesterol -to much and body is trying to get rid of it = HDL picks it up and transports it back to the liver -LDL receptors, HDL receptors and remnant receptors are located on the liver surface: very efficient and will grab the structure in any shape it can -converts cholesterol into bile acids -gets sent back for the digestive processes
pCO2 measurement
severinghaus electrode is used -modified pH electrode -CO2 from the sample crosses semipermeable (Teflon or silicon, NOT glass) membrane into a bicarbonate buffer inside the electrode -carbonic acid is formed when CO2 enters and combines with bicarbonate buffer -carbonic acid dissociates & H+ ions are measured -also affected by protein build up: causes falsely decreased CO2
phospholipids
structure is similar to triglycerides, except with only 2 esterified fatty acids -1 fatty acid chain is often saturated and the other is unsaturated: fatty acid chains are hydrophobic -third position on glycerol backbone contains phospholipid head group: hydrophilic
disorders of lipoprotein metabolism
too much cholesterol or triglycerides are synthesized or too little is removed -cholesterol lowered by statin drugs (related to intracellular pathway) inhibit HMG-CoA reductase increases LDL receptors and pulls cholesterol in removes LDL from circulation -too little HDL is produced: HDL picks up the cholesterol and returns it back to the liver -faulty transportant mechanisms
bicarbonate (fill in blank)
total carbon dioxide content can be calculated by _____ + dissolved CO2 (carbonic acid) + associated CO2 with proteins
role of lipoproteins
transport lipids
exogenous pathway
transports dietary lipids from the intestine to the liver and peripheral cells -mediated by chylomicrons -after chylomicrons enter circulation, they interact with proteoglycans (combo of sugar and protein structure that's found throughout the body in various tissues) on surface of capillaries in various tissues -proteoglycans promote the binding of lipoprotein lipase (LPL) which will hydrolyze the triglycerides into free fatty acids and glycerol: stimulates the binding of LPL so it can split them into the glycerol backbone and the free fatty acid chains fatty acids combine with albumin and go to the muscle cells (skeletal or heart) to be used as energy OR excess fatty acids are re-esterified to triglycerides and stored in adipose tissue -LPL is activated by the apo C from the VLDL -during chylomicron breakdown, triglycerides and apo A-1 will attach to HDL and the remaining chylomicron remnants are picked up by the liver via interaction of apo E with LDL receptors -inside the liver, remnants break down further and release fatty acids, free cholesterol and amino acids -LDL particles are the major lipoproteins responsible for the delivery of exogenous cholesterol to the peripheral cells due to the efficient uptake of LDL by the LDL receptors
cholesterol
unsaturated steroid alcohol containing 4 rings -membrane component of all cells: very important part of the structure of all cells throughout the body -consumption of cholesterol is important but excess can be harmful to humans -synthesized almost exclusively by animals -not a source of fuel
regulation of acid-base balance in the lungs
ventilation affects pH of blood -O2 is inspired and diffuses from alveoli into blood to bind with hemoglobin, which then carries oxygen to peripheral tissues -CO2 diffuses into alveoli from blood and is eliminated via ventilation -result in minimal change in H+ conc. between venous and arterial circulations
gallstones (fill in blank)
when cholesterol in the bile excess the capacity to be made soluble, ______ form -too much cholesterol and not enough bile acid to break it down -reached in-saturation point and body takes bile solution and forms it into a solid phase