Exam 6 Flashcards
Lipids are
Fatty acids linked to the backbone of glycerol and phospholipids by an ester bond, albumin bound
Lipid composition
Hydrocarbon chains of various lengths and carboxylic acid chain
Lipid classifications
Saturated or unsaturated, monounsaturated or polyunsaturated, cis or trans configuration
triglycerides
Contains 3 fatty acid molecules attached to 1 molecule of glycerol by ester bonds
Triglycerides containing saturated fatty acids
Solid at room temp
triglycerides containing unsaturated fatty acids
Form oils at room temp
Triglycerides from plants
Rich in polyunsaturated fatty acids
Triglycerides from animals
Mostly saturated fatty acids
Phospholipids
2 esterized fatty acids and a hydrophilic phospholipid head group attached by ester bonds, amphipathic
Most common phospholipid
Phosphatidylcholine
Cholesterol
Unsaturated steroid alcohol with 4 rings and C-H side chain, amphipathic liquid found on surface of lipid layers with phospholipids
Cholesterol converted to
Primary bile in liver, various hormones, 7-dehydrocholestrol in skin from the sunlight
Cholesterol as fuel
Cannot be used as fuel since it cannot be catabolized by most cells
Esterified form of cholesterol
Cholesteryl ester in which the OH group is conjugated by an ester bond to a fatty acid
Lipoproteins structure
Consist of lipids and proteins with amphipathic cholesterol and phospholipid on surface, hydrophobic, neutral triglyceride and cholesteryl ester in core
Chylomicron
Largest in size, lowest in density due to high lipid to protein ratio, highest amount of triacyclglycerols, cause turbidity of postprandial plasma, on top of stored plasma forming creamy layer, deliver dietary lipids to hepatic and peripheral cells
VLDL
very low density lipoprotein, 2nd highest in triacyclglycerols, major carriers of endogenous triglycerides and transport triglycerides from liver to peripheral tissues, cause most turbidity in plasma, no creamy layer
IDL
intermediate density lipoprotein
LDL
low density lipoprotein, highest in cholesteryl esters, can infiltrate extracellular space, oxidized and taken up by macrophages
HDL
high density lipoprotein due to high protein to lipid ratio
Apolipoproteins
Located on surface of lipoproteins, serve as ligands for cell receptors and as activators/inhibitors of different enzymes that regulate lipoprotein particles
Apolipoprotein A-1
Major protein on HDL
Apolipoprotein B
Principle protein on LDL, VLDL and chylomicrons
Apo B-100
Found on LDL and VLDL, a ligand for the LDL receptor and linked to lipoprotein (a)
Apo B-48
found in chylomicrons, produced by posttranscriptional editing of the apo B-100 mRNA
Apo C-I, C-II, and C-III
On chylomicrons, VLDL and HDL
Apo E
on many types of lipoproteins, functions as ligand for LDL receptor and chylomicron remnant receptor, exists in 3 forms: E2, E3, and E4
Increased production of VLDL
by liver, caused by excessive intake of carbs, saturated fatty acids, and trans fatty acids
Lipoprotein (a)
LDL-like particles with 1 molecule of apo (a) linked to apo B-100, heterogenous in size and density with plasma concentration widely distributed
elevated concentration of lipoprotein (a)
Increased risk for premature coronary heart disease and stroke due to inhibitory effect on plasminogen, a protein that enhance clot lysis
Spherical HDL
more lipid, cholesterol esters and triglycerides
Discoidal HDL
contains apo A-I to form a ring around central lipid bilayer of phospholipid and cholesterol, represents newly secreted HDL and the active form in removing cholesterol from peripheral cells
Lipoprotein metabolism
Absorption pathway, exogenous pathway, or endogenous and other pathways
Lipid absorption
Digestion of dietary lipids and absorption through passive transport via specific transporters, pass into portal circulation for short chain fatty acids but packaged into chylomicrons, re-esterified from monoglycerides and diglycerides
Triglyceride digestion
Monoglycerides and diglycerides
Cholesterol ester digestion
free cholesterol
Phospholipid digestion
lysophopholipids and bile acids
Exogenous pathway
- Chylomicrons interact with proteoglycans on surface of capillaries
- Binding of LPL to hydrolyze triglycerides on chylomicrons to produce fatty acids and glycerol
- Products (free fatty acids and glycerol) taken up as energy source
- Re-esterified into triglycerides for storage in intracellular lipid drops in fat
- Adipose cells release fatty acids from triglycerides by hormone sensitive lipase, regulated by epinephrine/cortisol/insulin
- Chylomicrons converted to chylomicron remnant after transferring lipid and apolipoproteins onto HDL
- Chylomicrons remnant taken via specific remnant receptors on liver cells
- Release fatty acids, cholesterol and AA by lysosomal enzymes
- Cholesterol and bile acids excreted into the bile with half cholesterol and almost all of the bile acids reabsorbed by the intestine
Lipid and lipoprotein levels in women
increased HDL, decreased total cholesterol and triglyceride
Lipid and lipoprotein levels in children
Decreased total cholesterol, LDL and triglycerides, no change in gender, HDL comparable to adults
Lipid and lipoprotein levels by age
Increase total cholesterol, LDL and triglyceride with age
Lipid and lipoprotein levels increasing risk of heart diseases
Increased serum cholesterol level, influenced by diet
Diseases related to lipid metabolism
Arteriosclerosis, hyperlipoproteinemia, hypertriglyceridemia, combined hyperlipoproteinemia, lipoprotein (a) elevation, hypolipoproteinemia, hypoalphalipoproteinemia
Dyslipidemias
Caused by abnormal synthesis, transport or catabolism of lipoproteins
Hypoalphalipoproteinemia
Decreased HDL due to genetic defects, associated with increased risk of CHD
Hypertriglyceridemia
caused by genetic or acquired diseases, such as hormonal diseases and DM, mainly derived from an imbalance between synthesis and clearance of VLDL, potentially treatable risk factor for VDH
Hypercholesterolemia
Autosomal dominant with total cholesterol as high as 1000 mg/dL, leads to heart attacks in teenagers, heterozygotes with total cholesterol 300-600, heart attack 20-50s, xanthomas, elevated LDL cholesterol, increased synthesis of cholesterol cells for cell membrane and hormone production due to decreased uptake of cholesterol by cells
Combined hyperlipoproteinemia
increased serum total cholesterol and triglycerides with increased risk for CHD, 4 forms
Lipoprotein (a) elevation
Increase the risk of CHD and CVD, especially in conjunction with elevated LDL, homologous to coag factor, plasminogen so may compete with plasminogen for fibrin binding sites to increase plaque formation
Cholesterol measurement
Hexane extraction after hydrolysis with alcoholic KOH followed by reaction with Liebermann-Burchard color reagent, enzymatic method commonly used nowadays with adequate accuracy but no pretreatment
Triglyceride measurement
Enzymatic reactions widely on automatic chemistry analyzers, endogenous free glycerol contributing 10-20 mg/dL, overestimation of triglyceride can be corrected by calibration blanking, accuracy less important compared to cholesterol due to large physiologic variation
High-density lipoprotein measurement
Measured as risk factor and in treatment decisions, homogenous methods automate HDL measurement, reference method developed at CDC
Low-density lipoprotein measurement
Primary basis for treatment decisions in the NCEP guidelines, beta-quantification: combine ultracentrifugation, apply Friedwals calculation
Renal functions
Urine formation, regulation of fluid and electrolyte balance, regulation of acid-base balance, excretion of waste products of protein metabolism, hormonal function
Glomerular function
Filter blood, allowing water, glucose, amino acids, urea, creatinine and other molecules to pass freely but retain albumin, other plasma proteins, cells and protein bound substances, filter function caused by steep pressure difference across capillary walls, measurement of the volume of blood filtered/min important for evaluating renal function
Tubular function
Receive and contain filtrate with both waste products and essential molecules, reabsorb compounds like NA+, Cl, glucose, amino acids, vitamins, proteins, ions, reabsorption is active and saturable, secrete products of renal tubular cell metabolism, like H+ and drugs
Function of Henle’s loop
Provide countercurrent multiplier system, maintain hyperosmolality in interstitial space by pumping Cl and Na into it by ascending loop, which facilitates the reabsorption of water
Function of distal tubule
Maintain electrolyte balance and acid-base homeostasis, under control of aldosterone, releasing in response to decreased blood flow in the afferent renal arteriole and regulated mainly by renin-angiotensin, reabsorption of Na and secretion of K and H that is associated with HCO3 and ammonia secretion
Function of collecting duct
Reabsorption of Na controlled by aldosterone, reabsorption of water, controlled by ADH, released when increased blood osmolality or decreased intravascular volume, responsible for producing concentrated urine
Elimination of urea
Majority of non-protein nitrogenous compound that is filtered by glomerulus and partially reabsorbed, depending on GFR, the plasma renal flow and urine flow rate
Elimination of creatinine
formed from creatine + ATP, filtered by the glomerulus but not reabsorbed, small amount secreted into urine, levels in blood are a function of muscle mass and GFR
Elimination of uric acid
Major metabolic product of purine, filtered by glomerulus, can be reabsorbed and secreted, secretion into urine may lead to urolithiasis and gout when urine pH is low
Endocrine function of kidney
Produce renin, a member in the renin-angiotensin-aldosterone feedback system, in response to decreased extracellular fluid volume, generate erythropoietin whose level is regulated by blood oxygen levels, produce 1,25-dihydroxy Vitamin D3
Acute glomerulonephritis
Related to recent infection by group A beta hemolytic strep where the circulating immune complexes leads to an inflammatory response in the glomerular basement membrane, causing its injury, acute kidney infections and drug-related exposures, rapid onset of hematuria and proteinuria with decreased GFR, anemia, elevated serum creatinine, hyaline and granular casts and blood cell casts
Chronic glomerulonephritis
Result from renal disease or idiopathic cause, not recognized for long period because of slight decrease of renal function, proteinuria and hematuria, leads to glomerular scarring, gradual develop of uremia and eventual loss of functional nephrons
Nephrotic syndrome
Caused by increased permeability of the glomerular basement membrane, evidenced by massive proteinuria, resulting in hypoalbuminemia, decreased plasma oncotic pressure, generalized edema, development of hyperlipidemia and lipiduria
Tubular diseases
Can be part of the progression of all renal diseases with GFR falls or is the only manifestation, show decreased excretion/reabsorption and compromised concentrating capacity, primary tubular disorder affects acid-base balance, causing renal tubular acidosis
Acute renal failure
Sudden decline in renal function, shown as GFR lass than 10 mL/min, oliguria and anuria, resulting in decreased secretions of electrolytes and water, leads to increased extracellular fluid, causing peripheral edema, hypertension, hyponatremia, hyperkalemia and CHF
Chronic renal failure
Gradual decline in renal function over time, stage 1 undetectable, stage 2 slight insufficiency, stage 3 abnormal high serum BUN and creatinine, development of anemia and systemic acidosis, stage 4 class symptoms of uremic syndrome
Renal function assessed by measuring creatinine
Standard method to measure GFR, creatinine produced at constant rate, colorimetric methods, direct relationship with muscle mass makes serum creatinine high in males and low in females
GFR equation
Urine creatinine concentration X urine volume excreted in 24 hours / serum creatinine concentration x 1440 minutes, modified by normalization factor 1.73/A
Estimated GFR
Recommended by National Kidney Foundation, calculated based on serum creatinine, age, body size, gender and race when creatinine is reported, designed to detect chronic kidney disease earlier since it doesn’t require a timed specimen
eGFR equation
GFR = (140-age) X weight / (72 X serum creatinine concentration), modified by 0.85 if female
Renal function by measuring urea
Used in past, 40% or urea is reabsorbed after being filtered at the glomerulus
renal function by systatin C
A small protein molecule produced by nucleated cells, filtered by glomerulus followed by reabsorption and catabolism by the proximal tubule, serum concentration not affected by gender, age, race and muscle mass, abnormal values appear earlier before a decrease in GFR or increase in serum creatinine
Urea
makes about half the NPN molecules in blood, synthesized in liver from CO2 and ammonia, main excretory product of protein metabolism, readily filtered from plasma by glomerulus and half is reabsorbed, plasma urea affected by renal function and perfusion, protein content and catabolism
Why is BUN used for measurement of blood urea
Assays for urea were based on nitrogen measurement
Decreased serum/plasma urea seen in
Decreased protein intake, severe liver diseases
Differentiation of prerenal, renal and postrenal diseases
High BUN:Creatinine seen in prerenal diseases that only increase urea, high ratio with elevated creatinine seen in postrenal, low ratio seen in low protein intake, acute tubular necrosis and severe liver disease
Normal BUN/Creatinine ration
10:1 to 20:1
Urea measurement
Reported in terms of nitrogen concentration
Enzymatic urea measurement
Hydrolysis of urea by urease and quantitation of NH4+
Electrode urea measurement
Measure the rate of increase in conductivity due to production of NH4+
Chemical urea measurement
Measure the yellow color from direct condensation with diacetyl monoxime in the presence of strong acid and oxidizing agent, or measure colored compounds formed between urea and O-phthalaldehyde and naphthyethylenediamine
Isotope-dilution mass spectrometry urea measurement
Definitive method for urea measurement
Specimen requirements and interfering substances
Avoid urease inhibitors such as Na+ F or Na+ citrate when collecting, fasting specimen is not required due to single protein diet has very small effect, refrigerate samples if not analyzed right away because urea is susceptible to bacteria decomposition, preserve urine samples with few crystals of thymol when analyzing urine urea, may need to modify method used to measure serum urea for urine measurement if urine specimens contain high concentration of urea and ammonia compared to serum sample
Creatinine
Derived from creatine phosphate, synthesized in liver before transported to other tissues, released into circulation as relatively constant rate, proportional to muscle mass, eliminated by glomerular filtration and a small amount secreted by proximal tubule, plasma levels reflect relative muscle mass and renal function, elevated plasma levels associated with decreased renal function
Elevated serum/plasma creatinine
Mainly caused by abnormal renal function, the clearance of creatinine : the volume of plasma from which creatinine is cleared /min reflects GFR that determines renal function, diet does not affect, most commonly used monitor of renal function
Jaffe reaction
previously considered reference method creatinine in protein-free filtrate adsorbed onto Fuller’s earth, then released with alkaline pictrate to yield colored Janovski complex
Creatininase-CK
generate NAD+ through a serious coupled reaction, not widely used due to large sample requirement
Myoglobin
Function to bind and transport oxygen from the plasma membrane to the mitochondria in muscle cells, released into blood stream in skeletal and cardiac muscle injury, mainly bound to plasma proteins so filtration through glomerulus is not as much as predicted from size, can induce acute renal failure if its release from muscle overloads the renal proximal tubules to cause myoglobinuria
Urinalysis physical features
Morning specimens preferred, especially for protein measurement, should be obtained by clean midstream catch into a clean and dry container with tight-fitting cover, be analyzed within 1 hour of collection at room temp or refrigerated for < 8 hours
Urine color
The darker the color, the more concentrated the specimen, yellow-amber due to urobilin, yellow-brown due to bile pigment, red-brown due to porphyrins or hemoglobin or RBCs, brown-black due to alkaptonuria and malignant melanoma
Urine odor
Pungent odor due to volatile aromatic acids, ammonia odor due to allowed to stand, noxious, fecal smell due to UTIs, fruity due to ketones, maple sugar due to maple sugar urine disease
urine turbidity
in alkaline due to suspended precipitates of amorphous phosphates and carbonates, in acidic due to amorphous urates, cloudiness due to gross bacteriuria, smoke due to hematuria, threadlike due to mucus
Urine volume
Normal: 750-2000 mL/24 hours
Polyuria due to diabetes, chronic renal disease and myxedema, oliguria or anuria due to nephritis, end stage renal disease, urinary tract obstruction and acute renal failure
UA requirements
10-12 mL aliquot from well-mixed sample
Specific gravity
The weight of 1 mL or urine (g) / the weight of 1 mL of water, usually measured by refractometer, indication of hydration and concentrating abilities
Low specific gravity
Due to diabetes insipidus, pyelonephritis and glomerulonephritis
High specific gravity
Due to diabetes mellitus, CHF, dehydration, adrenal insufficiency, liver disease and nephrosis
Urine pH
measurement on fresh urine because of alkalization on standing, normal: 4.5-8.0
Urine acidity
Due to phosphates and NH4+, excretion of nonvolatile metabolic acids, metabolic acidosis
Alkaline urine
Due to ingestion of alkaline food or medication, UTIs and bacterial contamination, Fanconi’s syndrome
Nitrite analysis
Assesses amount of urinary reduction of nitrate by the enzyme of gram-negative bacteria, positive results in some gram-negative bacterial infection although negative result doesn’t rule out due to not producing nitrate-reducing enzymes and urine may not have been retained in bladder long enough
Leukocyte esterase
Positive dipstick for esterases indicates possible WBC in specimen
Bilirubin/urobilinogen
Glucose, ketones and protein
Hemoglobin/blood analysis
positive dipstick results indicate renal trauma/injury, infection or obstruction from stones or cancer/tumors
