Protien Catabolism & Nitrogenous Waste Excreation Flashcards
Functions of EPO?
Anti apoptosis function
Produce more RBC 
_____________ recycles HCO3
Kidneys
How can kidney disease lead to lysed RBCs?
Decreased EPO—> anemia and decreased bicarb ——> acidosis ——> causes membrane damage of RBCs and ruptures the cells
What is the most abundant serum protein?
Albumin
What is A:G ratio?
Albumin : total globulin
NPNs…
Non-protein
-cholesterol
-glucose
-urea nitrogen
-uric acid
-creatinine
-iron
Albumin range
3.4-5.0 g/dl
Total globulin range
2.2- 4.0 g/dl
Transferrin
250 mg/dl
Haptoglobin range
30- 205 mg/ dl
Ceruloplasmin range
25-45 mg/dl
Ferritin range
15- 300 ug/ dl
Hemopexin range
50- 100 mg/dl
Cholesterol range
140-250 mg/dl
Glucose range
70- 110 mg/dl
Urea nitrogen
6-23 mg/dl
Uric acid range
4.1- 8.5 mg/dl
Creatinine range
0.7- 1.4 mg/dl
Iron range
50-150 ug/dl
What can be a source of oxidative stress when not bound?
Haptoglobin when not bound to alpha globin chain
Free haptoglobin ______ can tell if if alpha is defective
G
_____________ becomes toxic when not bound
Transferrin
-can bind to free heme
-delivered to liver to be recycled
Haptoglobin
Hemopexin
Source of NPNs
Amino acids
Urea is synthesized in the ___________ from NH3 (Bacterial metabolism and got it and AA deamination) 
Liver
More protein ———-> more _____________ in GI.
Ammoniagesin
Why is determination important metabolic process?
Allows product (protein?) to be used for energy or to be converted into carbs or fat
urea in circulation is reported as ….
Blood urea nitrogen (BUN) 
BUN is increased with….
High protein diets and tissue breakdown
BUN is decreased with…
Protein synthesis, chronic and progressive renal insufficiency (No reabsorption), low protein intake and severe liver disease
Urea filtered in the kidney (______% reabsorbed in collecting duct, ____% excreted in urine)
40-50
50-60
Because BUN increased or decreased while GFR is normal, BUN is a _____________ Indicator of renal function.*****
Nonspecific **
(Compared to other markers) 
C.f. Urea production > Urea excretion: Urea remains in system —-> Degraded to ______ by intestinal bacteria and process by liver and cleared.
NH4
What is the most abundant NPN?
BUN
What are the three types of acute renal failure?
-Prerenal (Hypovolemia or poor perfusion) Before kidneys
-Renal (Rapid deterioration, e.g. Acute tubular necrosis) at kidneys
-post Renal (Obstructions, When osmolarity becomes the same in blood and tubule Filtration stops) After kidneys 
Pre-renal acute failure is usually due to altered ____________ function. 
Cardiovascular
(given ACE or angiotensin)
In normal serum, what is the year BUN/urea: Creatinine ratio? ***
10:1 - 20:1*
If both BUN and creatinine is elevated, ratio will still be normal bit could indicate…
Renal disease
- Both can be out of range but have normal ratios
What is the most common cause of increased BUN in middle aged men? 
G.I. bleeding
What can cause an abnormal urea to creatine ratio?
Increase amino acid breakdown as in muscle wasting, high protein diet or G.I. bleeding
Serum BUN serum creatinine ratio greater than 20:1 Is observed in patients with…
• pre-renal azotemia*** (Accumulation of nitrogenous products in blood)
• Gastrointestinal bleeding
• Excessive protein intake
-Post-renal azotemia
BUN is absolute for determining renal function. true or false?
False! 
What is used to determine urea BUN ratio? 
-Berthelot reaction
-enzymatic glutamate dehydrogenase (340nm)
-Conductance
-protentiometric
-diacetyl monoxime
-O-phthalaldehyde 
-absorption maximum measured at 560 nm
-Performed directly on blood, serum or urine
Berthelot Reaction (rarely used)
(Urea methodology) 
Why is Berthelot Reaction rarely used? What’s the disadvantage?
Difficult to automate, lack of specificity, beers law narrow range
Beers law?
A =  epsilon b c ?
Berthelot Reaction test can be monitored at _____nm and Produces a bluish color from indophenol complex
560
-Method used quite frequently in clinical labs
-Conductivity increases with formation of
Urea ——Urease —->(NH,),COg —->2NH, +CO,
-Conductively measured at the same time
Conductance (Urea methodology)
-NH3 ISE Monitors urease reaction
-Urease covalently linked to electrode, converts urea to NH3
-Change in pH measured by electrode
-Very specific but not commonly use due to possibility of contamination***
UREA METHODOLOGY: POTENTIOMETRY
-Direct chemical analysis of urea (Instead of using urease)
-Commonly used
***Diacetyl Monopxime (urea methodology) 
Reference interval (BUN) for Diacetyl Monopxime?
8-26 mg/dl
(A lot of fluctuation in numbers, lab sets their own range) 
What is the disadvantage of Diacetyl Monopxime?
-Photosensitivity of product
-large dilution of sample required for beers law
-Corrosive reagents
Diacetyl Monopxime:
Yellow Diazine
-chromagen _____nm
-Fluorescence _____ nm 
550
415
no use of enzymes in this test
-Rarely used because of interference with other primary amines
O-phthalaldehyde*
A group of atoms and electrons forming part of an organic molecule that causes it to be colored
Chromophore
(At 510 nm with O-phthalaldehyde)
Why is O-phthaladehyde rarely used for urea? 
Interference with other primary amines 
What are the benefits of using dry slide urease-pH indicator?
-excellent accuracy
-Little interference from other biochemicals
- Commonly used and can use different dyes 
What specimen is used for urea testing?
Serum or heparinized plasma or diluted urine
When testing for urea, CANNOT use ___________ (Inhibits urease reaction) or ___________ (Causes artificial elevation)
Fluoride, NH4 heparin***
What is the storage requirements for urea?
serum and plasma is stable for one week at 4°C or six months at -20°C
Creatinine is proportional to…
Muscle mass
What lab marker is important in liver disease?
Creatinine
CK requires ______. It is important for diagnosis of many diseases (ex: CK1, CK2, CK3)
ATP
Creatinine is formed from __________ creatine and creatine ________.**
Muscle
Phosphate
Creatinine in serum is proportional to…
Muscle mass. Generally increased in males compared to females
Serum concentrations of creatinine depends on?
-rate of production
-Rate of removal
*** Does not change dramatically, very stable!
There is little effect on serum creatinine from diet, urine volume and exercise
-plasma creatinine is stable with less than 10% variation in a day because….
-concentration in muscle is constant
-Rate of spontaneous breakdown is constant
Measure _____________ Clearance to determine filtration GFR**
Creatinine
How is creatinine filtered in the kidneys?Is creatinine reabsorbed?
-Freely filtered
-Not REABSORBED (5 to 20% may be secreted, from tubular secretion, not filtration)
- Urinary excretion is directly proportional to muscle mass

About _____ mmol/creatinine excreted/kg of muscle mass
5
Exercise __________ Increases creatinine in serum and or urine
Slightly
Protein deficiency long-term ___________ Decreases creatinine in serum
Decreases
Tubular secretion ____________ as creatinine in serum increases in patients with renal insufficiency
Increases
Increased renal insufficiency = increased secretion of creatinine
Because rate of production and removal are constant, creatinine is used to assess….
GFR (Renal function) 
Creatinine clearance is a good estimate of GFR but still not…
The best method
(creatinine clearance more specific?) 
Creatinine clearance is more sensitive for determining renal function than Creatinine _________ levels Because based on rate of excretion.
Serum
Volume of plasma from which an amount of creatinine is removed in a specific amount of time (1 min) 
* creatinine clearance**
Formula for creatinine clearance (Urine and serum: 24 hour test) 
Creatinine clearance (mL/min) = (Ux*V/Px)
Ux: Urine concentration
Px:  Plasma concentration
V: Urine volume or flow rate
What is the reference intervals for creatinine clearance (Corrected for surface area) = 
90-120 mL/min
What is the average persons body surface area?
1.73/BSA (m^2)
BSA formula?
•BSA (m^2) = SQRT [height(cm) x weight (kg) ] / 3600)
•BSA (m^2) = SQRT [height(in) x weight (lb)] / 3131)
Creatinine clearance x BSA (m^2)
Three methods for creatinine measurements
•Jaffe’s reaction
•Enzymatic Creatinine amidohydrolase & Creatinine deaminase
•Partial enzymatic
Jaffe’s reaction is conducted at _____ degrees Celsius
30 or 37
Increase temperature can cause picrate to react with glucose, uric acid, ascorbic acid, cephalosporin, guanidine, ketone body, pyruvate, protein.
Jaffe’s reaction….
Creatinine + picrate ——OH- ——-> Janovoski complex (orange-red) absorbance 510-520 nm
What does Jaffe’s reaction require?
A protein free filtrate
-Fullers earth (Floridin) Added to increase Specificity

Oldest clinical chemistry method that is still in use?
Jaffe’s reaction
What is the advantage of Jaffe’s reaction?
Automated and low cost
Disadvantage of Jaffe’s reaction?
-Fuller’s earth needs to be added “manually”
-pyruvate and oxaloacetate at high concentrations can interfere
Enzymatic creatinine deaminase impartial enzymatic:
-can monitor NADPH reaction
-use dry slide technology to assay NH3 (Immobilized aminohydrolase Converts creatinine to NH3 —-> Detected via__________________.
Bromophenol Blue dye complex (670 nm)
-Requires Centribution Of endogenous NH3 to be subtracted
Used as a point of care testing device
Enzymatic-creatinine deaminase and partial enzymatic
Enzymatic creatinine Deaminaseand partial enzymatic: 
Dry slide technology has shown that __________ Creatinine from patients on 5-fluorocytosine (fungal medication) 
Increased
Creatinine is cleared and _______ Reabsorbed.
Not
What is the specimen collection in handling for creatinine?
-serum, plasma or diluted urine (1:100)
-No interference from fluoride, but NH4-heparin Should be avoided
-If using NH3 Detecting methodology, remove RBC ASAP 
Four Jaffe’s assay, Samples are stable for _____ week at ____ Degrees Celsius
1, 4
Can you function can be assessed by the ability of the kidney to….. 
Clear a substance
Definition of clearance? 
Volume (ml) Of plasma from which a substance completely removed / Unit of time (1 min) **
Why does serum sodium decrease when the liver is not working?
Decrease in albumin, more free sodium that then gets filtered out (not bound to proteins so gets Eliminated faster) 
What are the three renal disease clearance test?
-para-amino hippurate
-Inulin
-Creatinine (Does not buying to protein in free filters) 
para-amino hippurate and Inulin are exogenous substances, need to be injected by IV
What is the criteria That makes a good marker for renal disease determination? 
-  renal tubular secretion and reabsorption do not contribute to elimination of the compound
- Plasma protein binding should be negligible
For the clearance test it requires?
-accurate measurement of both plasma and urinary marker
- reliable urine collection (Urine flow must be adequate, collection. Should be long enough duration (More than four hours), Complete bladder emptying achieved
Collection. Should be more than ______ hours For clearance tests.**
Four
How is para-amino hippurate (PAH) cleared?
By binding to proteins
para-amino hippurate (PAH) is not good for GFR because?
Carrier proteins mediated excretion
how is para-amino hippurate (PAH) administered? 
By IV infusion, cannot eat for this test
Exogenous substance used to determine Reno plasma slow/amount of blood passing through the kidney
para-amino hippurate (PAH)
PAH is both filtered and secreted to such an extent that
greater than ______ % of the substances removed from the blood
in a single pass through the kidney
90
why does para-amino hippurate (PAH) not need to be calculated for body surface area?
Comes from a plant source
Exogenous substance that is the reference molecule for assessing GFR it must be infused
Inulin 
Anyone is freely filtered by glomerulus and is neither….
Reabsorbed nor secreted 
Faster and better than Creatinine clearance test
Inulin clearance test*
Creatinine can be ___________ by tubule. 
Secreted
When is Cystatin C elevated?
When increased Inflammation, increase in heart and brain conditions, increased very high in renal disease
Neither PHA nor inulin or quick laboratory measurements, the leaves __________ As the next best convenient tool
Creatinine clearance (Cystatin C or cysteine 3)
Creatinine is an ______________ Substance and tests are easy to perform
Endogenous
What prohibits creatinine from being the perfect marker for GFR?**
Tubular secretion of creatinine
Creatinine clearance is used to diagnose…..
Acute and chronic renal failure
Results closely parallel inulin until renal failure progresses where
[creatinine] serum ___________ significantly and then creatinine clearance
decreases as renal functions fail.
Increases
What are the disease profiles of renal diseases? **
-chronic renal failure (Uremic syndrome,final stage of renal failure)
-Acute renal failure
-Acute glomerulonephritis
-nephrotic syndrome
-renal tubular defects
-Urinary track infection (pyelonephritis, cystitis)
-Nephrolithiasis (Kidney stone)
-Renal hypertension
What disease causes huge gaps so Albumin can go through, increases osmotic pressure, no osmotic gap, filtration can stop
Nephrotic syndrome
Chronic renal failure is more than _______ months with implications of health
3
chronic renal failure causes metabolic __________.
Acidosis***
Symptoms of chronic renal failure
Weakness, fatigue, loss of appetite, nausea and vomiting, muscle wasting, tremors, abnormal mental function, and shallow respiration and metabolic acidosis
GFR:
<60 ml/min/1.73 m2 =
<15ml/min/1.73 m2 =
Decreased renal function
Renal failure
What results from decreased glomerular filtration and tubular function?
Increase in NPN, hyperphosphateuria, hypocalcemia, acidosis in hyperkalemia
Calcium and phosphorus are _____________ Related. 
Inversely
If increase of calcium and phosphorus = stone 
Caused by inability to secrete normal H+ production
Uremia–acidosis
Retained nitrogenous waste, ____________ both BUN and creatinine in serum. 
Increase
Loss of tubular reabsorption —-> 
Inability to concentrate urine is reflected in decreased urine Osmolality
What happens in chronic renal failure and uremic syndrome?
-Uremia acidosis
-Retained nitrogenous waste
-Loss of tubular reabsorption
-Abnormal endocrine function (Secondary hyperparathyroidism, anemia/EPO)
-Diabetes mellitus
-Increased proteinuria

In chronic renal failure and uremic syndrome:
Which of the following are elevated and which are decreased?
HCO3-, Na+, Ca2+, pH, K+, Cl-, P-, Mg2+
Decreased: HCO3-, Na+, Ca2+, pH
Increased: K+, Cl-, P-, Mg2+
(Na+ due to renin not being produced by damage kidneys) 
Defined as rapid and severe reduction of GFR with oliguria and Edema. 
Caused by prerenal, Renal, post-renal effects
Acute renal failure
What are examples of acute renal failure causes?
Hypovolemia, Heart failure, acute tubular necrosis, or urinary tract obstruction
What are clinical findings associated with acute renal failure?
-Hyperkalemia with cardiac arrhythmia
-Metabolic acidosis (Decreased bicarbonate)
-Increase monophosphate, decreased calcium that leads to secondary hyperparathyroidism
-Bone disease
-Increased BUN and creatinine
-Possible anuria (<100ml/day) 
Where is EPO produced?
At the border line area between the cortex and medulla of kidney
Inflammation of glomerular membrane, sometimes due to ____________ disease
poststreptococcal
acute glomerularnephritis:
Early stage resembles pre-renal __________ With normal tubular function.
Later stage tubular damage resembles __________ Syndrome.
Azotemia
Uremic
Clinical findings of acute glomerulonephritis:
Urine…
Hematuria, RBC cast, proteinuria, Decreased GFR, oliguria
Clinical findings of acute glomerulonephritis:
Serum…
Increased urea and creatinine (Normal ratio)
Decrees complement factors such as C3 and CH 50 (Overall compliment activity and body)
Clinical findings of acute glomerulonephritis:
Overall…
Increase sodium and water retention that results in Edema, hypertension
- anemia also 
Excessive permeability to plasma proteins = 
Renal failure
What happens to BUN and creatinine in nephrotic syndrome? 
Not affected until renal failure (in this case goes up)
How does nephrotic syndrome affect urine?
Massive proteinuria > 3.5 per day, lipiduria (oval fat bodies produced, granulated renal tubular cells)
How does nephrotic syndrome affect serum?
Increase sodium and water retention, offered to macro guardians, TG and cholesterol (secondary to Lipo proteins alterations)
What is the overall effect of nephrotic syndrome?
Loss of serum proteins, decreased oncotic pressure (Caused by proteins) and shifts water from vascular to interstitial (edema) 
Sodium __________ and volume __________ in Nephrotic syndrome. 
Retention, expansion
_______________ and oliguria may be present With nephrotic syndrome.
Hematuria
Renal tubular defects:
Decrease reabsorption or secretion with normal ______.
GFR
What is the most important clinical disorder associated with renal tubular defects?
Renal tubular acidosis (Types one through four)
Renal tubular acidosis type…..
Decrease proximal tubules bicarbonate reabsorption
Hyperchloremia acidosis with normal AG, also may observe hypouricemia, hypophosphatemia, aminoaciduria, And renal glucosuria
Fanconi syndrome
Proximal RTA type II
Rare, excess glucose (Reabsorption is affected), phosphate, bicarbonate.
Uric acid, potassium and some amino acids can be excreted in urine and bicarb
Fanconi syndrome***
Associated with proximal RTA type two
Renal tubular acidosis type where tubular cells cannot secrete hydrogen that leads to metabolic acidosis
Distal RTA type one
What are the clinical findings in renal tubular defects?
Urine: Normal or slightly decreased GFR, proteinuria (aminoaciduria), glucosuria
and phosphouria
• Serum: increased BUN & creatinine, potassium & H*, hypophosphatemia
RTA type that is secondary to aldosterone deficiency or resistance to aldosterone
 RTA type 4
Mixed RTA proximal and distal
RTA type 3 
Urinary track infection, usually resulting in cystitis. Most severe, associate with fever and pain over her kidneys
Pyelonephritis
Bacterial infection of the bladder
Cystitis
Clinical findings of cystitis and pyelonephritis 
Greater than 100,000 bacterial colonies per ML, increased WBC and WBC cast and pyuria(pus)
Increased number of RBC in urine
Causes of stone formation?
-after urinary track infection
-Increase calcium from primary hyperparathyroidism (Calcium oxalate is the most common)
-Uric acid/gout
-Cystine (cystinuria)
- Magnesium/ammonia/phosphate or xanthine 
What are the effects of renal hypertension?
Decreased renal perfusion, increase renin secretion, increase angiotensin II, increased blood pressure
145/95
Hypertensive nephrosclerosis
Clinical findings of renal hypertension
Urine: increase aldosterone
Serum: Increased renin, aldosterone, hypernatremia, hypokalemia
Chronic renal failure can lead to ________ retention That causes Renal hypertension
Sodium and water
Which Diabetes is insulin dependent?
Diabetes mellitus type one
What is the leading cause of mortality for diabetes mellitus type one patients?
Severe renal system Issues
What are the stages of diabetes mellitus type one?
- Glucosuria and polyuria that leads to proteinuria that develops approximately 17 Years after initial diagnosis
- Decreased GFR and hypertension develops 1 to 2 years later
- Eventually renal failure
High molecular weight proteins enter filtrate-glomerulonephritis, Streptococcal infection, nephrotic syndrome, or diabetic nephropathy (> 2 g/day excreted)
Glomerular proteinuria*
(window is bigger, proteins goes through) 
Initial filtrate, proteins not altered, but defect in reabsorption results in
1 to 3 g per day of low molecular weight proteins and albumin being
excreted
Tubular proteinuria
Hemolysis, hemoglobin diuresis, multiple myeloma (Abnormal antibodies, immunoglobulins), crush injuries
Overload proteinuria
bladder infections and tumors
Post renal protein 
___________ renin released from chronically damage kidneys
Increased
In renal hypertension the cardiovascular system is…..
Normal?
Purines are excreted as…
Uric acid
Major product of Catabolism of the adenosine and guanosine (purines) 
2,6,8-Trihydroxypurin
Uric acid
Net urinary excretion of uric acid is about______% Of amount filtered
6-12
Renal handling of uric acid
-filtration of virtually all uric acid in the capillary plasma entering glomerulus
-almost 100% reabsorption at the proximal tibial
-Subsequent secretion throughout the tubule
-Further reabsorption at the distal tubule 
Inherited disorders of purine metabolism are very rare. Either hyperuricemia or hypouricemia 
Abnormal uric acid could result in…
- Kidney failure or stone (Child or a young adult)
- Gravel in an infant diaper
- Unexplained neurological problems
- Gout (Younger than 30 years of age) 
What are the methods for assessing uric acid?
-phosphotungifstic acid (PTA)
-Uricase
-HPLC 
Method for assessing uric acid:
-PTA —> Reduce by uric acid under alkaline condition —->Tungsten blue (chromongen, blue)
-Absorbance at 650 to 700 nm
-disadvantage: Too many interference
Phosphotungstic acid method
Method for assessing Uric acid:
-More sensitive than PTA method
-High quality and low cost
-Absorbance at 293 nm*
-A reference method, but require high quality spectrophotometer
Uricase method
- The concentration of uric acid in serum increases about 10% between ages of 20 and 60
Method for assessing Uric acid:
• Ion exchange or reversed phase column to separate and quantify uric
acid.
• Column effluent is monitored at 293 nm to detect luting uric acid.
• Retention time of uric acid is less than 6 min.
• Also considered as a reference method.
High performance liquid chromatography
(HPLC)
Increase intracellular calcium results in increased…
Contraction
