Renal Biochemistry Flashcards
creatine kinase; levels, when its released, different from what
- High levels in the skeletal muscle and cardiac muscle
- When muscle is damaged, Creatine Kinase is released, just like other specific enzymes discussed previously (ALT, AST etc.)
- This is different from the release of creatinine which occurs normally at a relatively fixed rate
what is creatinine
Creatinine: NOT an enzyme, but a byproduct of muscle metabolism, produced at a relatively constant rate.
creatinine; formation, diffusion, filtrate, secretion, compared to what
*Creatinine is irreversibly formed from creatine by its nonenzymatic dehydration
*It rapidly diffuses into the plasma at a relatively constant rate proportionate to muscle mass
- It freely enters the glomerular filtrate
- Because of its relatively constant secretion rate in any individual animal and the fact that it is not reabsorbed it becomes an excellent “marker” of kidney function.
- Because it is relatively constant in the filtrate, it can also be compared to other filtered molecules as an “internal” standard (urinary creatinine clearance ratios for calcium, albumin etc.)
nitrogen containing components of normal urine
urea = 86% excreted
creatinine = 4.5%
ammonium = 2.8
uric acid = 1.7
other compounds = 5.0
details of urea cycle
- Metabolism of proteins results in the production of ammonia
- Ammonia/ammonium is produced primarily by the enzyme glutamate dehydrogenase (GDH) from glutamate or glutamine
- Ammonium is toxic (N = 15 - 40μM , max 70μM)
- As a result, ammonia is used as a substrate to synthesize urea, which is substantially less toxic.
- In avian and reptiles, uric acid is synthesized.
- Urea is synthesized by the urea cycle
urea cycle; enzymes and where, amino acids, secretion, diffusion
- 5 Enzymes in the urea cycle – 2 in mitochondria, 3 in cytosol.
- 3 important amino acids – glutamine (endproduct of breakdown of many AA, metabolized to ammonia by GDH), aspartate that gets metabolized to arginine en route then combines with the ammonia to form urea.
- Urea secreted into ECF/blood and then filtered out by glomeruli. However, since it diffuses easily, it can easily move back into ECF/blood etc. as it passes through the tubular system
- Also diffuses into the urine as it passes through the collecting duct and concentrated medulla.
nutritional regulation can affect urea levels; long term regulation, what happens to enzymes, starvation, change, what can dietary changes show up as
Long term regulation – Nutritional and metabolic changes can affect levels in blood independent of changes in renal function. Another reason it is a less reliable indicator of true renal function.
- Five Urea Cycle enzymes all ↓ with low protein diets & ↑ with high protein diets. Therefore regulated nutritionally (over the long term)
*Note also ↑ during starvation due to ↑ AA catabolism therefore although muscle and liver protein ↓ the level
of these enzymes ↑ due to increased urea synthesis
- Changes take place over 3-7 days.
- Dietary changes sometimes show up as a LOW BUN in the blood sample, so when you see that, consider what the liver might be doing re:urea synthesis
characteristics of urine
- Creatinine, urea, uric acid will all be present in high amounts. Measuring their concentration in a sample isn’t that useful because concentration depends on their levels and how concentrated or dilute the sample is. Sometimes we do measure the total amount of creatinine over a period of time (creatinine clearance).
- Na+, K+, Cl- will all be present, but again, their concentration is varied by the overall concentration of the urine. These are the principal molecules that contribute to urine specific gravity (SG), so we measure them indirectly
- Protein should be very low or absent. When present suggests a problem with the glomerulus – “leaky” or, at lower levels, an infection in the urinary tract (kidney, ureters, bladder, urethra).
- Glucose should be absent. When present, usually indicates that the blood level is high (eg. diabetes) although rarely increased in renal problems.
types of sample collections with advantages and disadvantages
- Voided (midstream) specimen
– Advantage – easy to obtain
– Disadvantage – contamination from lower urinary tract - Catheterized Specimen
– Advantage – can collect sample when patient cannot void
– Disadvantage – requires sterile technique - introduction of pathogens to urinary tract
- can cause trauma
- Cystocentesis
– Advantage – little chance of contamination, can be performed when voiding or catheterization not possible
– Disadvantage – requires sterile technique - potential for hemorrhage
physical properties of urine; appearance, specific gravity
- Appearance
– Yellow to amber in color
– Generally clear (horse and some birds are exceptions) may become cloudy on standing or refrigeration - Specific Gravity (SG)
– Ratio of the mass of a solution compared with the mass of an equal volume of water
– Ranges from 1.001 to 1.060
– Glomerular filtrate is between 1.008 and 1.012 and values above and below these reading require tubular function
– For example SG > 1.030 in dogs suggests adequate concentrating ability
factors affecting physical properties of urine
- Color
– Concentrated vs dilute urine
– Blood imparts a red color
– Hemoglobin and myoglobin impart a red to red-brown color
– Bilirubin appears dark yellow to brown - Transparency/Turbidity
– Crystals, cells, bacteria
– Fat, mucus - Odor
– Acetone odor suggests ketosis
chemical properties normal and indication; pH, protein, glucose, ketones, blood
pH = Normal is acidic in carnivores, alkaline in herbivores. indication depends on diet
protein = normal is negative, indication is renal disease/altered glomerular activity, hemorrhage, inflammation/infection
glucose = normal is negative, indication is diabetes, defective reabsorption
ketones = normal is negative, indicaion is abnormal CHO or lipid metabolism
blood = normal is negative, indication is hemorrhage, infection
urine sediments (names and their details)
- Casts
– Formed from protein in distal tubules
– Hyaline, granular casts etc at low levels are relatively common and normal.
– Cellular casts are usually abnormal and suggest kidney damage (eg. WBC and RBC casts, bacterial casts) - Cells
– Epithelial cells, erythrocytes, leukocytes (0-4 per high powered field is normal for erythrocytes and leukocytes) - Bacteria
- Crystals
– Precipitation of solutes as crystals depends on pH, temp., solubility and concentration of the solute
