Plasma protein Dr.Buthainah Abbas

Plasma protein Protein are present in all body fluid but it is the protein of the blood plasma that are examined most frequently for diagnostic purposes. Quantitatively the single most important protein is albumin the other protein are known collectively as globulins. Changes in the concentrations of individual proteins occur in many conditions and their measurement can provide useful diagnostic information

Measurement of plasma protein In very general terms variation in plasma protein concentration can be due to any of 3 changes:- 1- in the rate of protein synthesis. 2-rate of removal 3- volume of distribution. the concentration of proteins in plasma is affected by posture an increase in concentration often to twenty percent occurs within thirty minute of becoming up right after a period of recumbency

Plasma proteins Except when patient have been given blood or proteins intravenously a rapid increase in the total plasma protein is always due to a decrease in the volume of distribution (in effect to dehydration). A rapid decrease in concentration is most usually due to increase in the volume of plasma.

Plasma protein Thus changes in plasma protein concentration provide a valuable aid to the assessment of patients state of hydration. The total protein concentration of plasma can also fall rapidly if capillary permeability increases, since protein will diffuse out into the interstitial space. This is seen for e.g in some patients with septicemia or generalized inflammatory conditions.

Causes of changes in total plasma protein concentration Increase: - 1- hypergammaglobulinemia increase 2- paraproteinaemia protein 3- artefactual hemoconc.due to stasis of blood during venepuncture 4- dehydration decrease vol. of distribution

Changes in plasma protein Decrease: - 1- malnutrition decrease 2- liver disease protein 3- humeral immunodeficiency synthesis 4- over hydration increase 5- increase capillary permeability vol. distribution 6- protein losing states increase 7- catabolic state excretion / catabolism

Urea synthesis Deamination The removal of the amino groups of all twenty amino acids begins with the transfer of amino groups to just one amino acid - glutamic acid (or glutamate ion). This is catalysed by transaminase enzymes which transfer the amino group from amino acids to a compound called alpha-ketoglutarate by the help of pyridoxal phosphate at the catalytic site of the enzyme . The product is an alpha-keto acid formed from the amino acid and glutamate (formed from the addition of the amino group to alpha-ketoglutarate. Serum transaminase increased in liver disease, heart disease, muscular dysatrophy , collagen disease and trauma

Urea synthesis most a.a undergo transamination except lysine, threonine and cyclic imino acids proline and hydroxyproline. Once the amino groups have all been "collected" in the form of the one amino acid, glutamate, this amino acid has its amino group removed (termed "oxidative deamination"). This reaction reforms alpha-ketoglutarate with the other product being ammonia (NH4 +).

Ammonia and urea Ammonia is toxic to the nervous system and its accumulation rapidly causes death. Therefore it must be detoxified to a form which can be readily removed from the body. Ammonia is converted to urea, which is water soluble and is readily excreted via the kidneys in urine. Symptom of ammonia intoxication

Urea cycle A human subject who consumes 300 gm of CHO, 100gm of fat and 100gm of protein daily excretes about 16.5 gm of nitrogen each day 95% in the urine and 5% in the feces. For subjects consuming accidental diets, urea synthesized in the liver released into the blood and cleared by the kidneys constitutes 80 – 90% of the nitrogen excreted . urea is formed from NH4, CO2 and aspartate. Synthesis of 1mole of urea requires 3 mole of ATP and 1mole each of NH4 and amino nitrogen of aspartate. Five enzyme catalyze the reactions. N-acetyl glutamate functions as an enzyme activator. The others serve as carriers of the atoms that ultimately become urea. Urea biosynthesis is a cyclic process. Ornithine consumed in reaction 2 is regenerated in reaction 5 and there is no net loss or gain of ornithine, citrulline, argininosuccinate or arginine. Ammonium ion, CO2, ATP and aspartate are however consumed. Some reactions of urea synthesis occur in the matrix of the mitochondria while others occur in the cytosol. Reaction and intermediates of urea biosynthesis reaction 1&2 occur in the matrix of liver mitochondria and reaction 3&4 and 5 in liver cytosol.

Urea cycle

Metabolic disorder of urea High plasma urea:- 1- high protein diet 2- pre-renal causes:-fever, dehydration, circulating failure 3-post-renal causes:-obstructive and nephropathy Low plasma urea:- I – an increase GFR 1 – pregnancy 2 – over treatment by intravenous therapy 3 – In appropriate secretion of ADH II – due to decrease synthesis :- 1 – extensive liver disease 2 – low protein in take 3 – in born error of urea cycle

Metabolic disorder of urea The urea cycle is a process in which waste (ammonia) is removed from the body. When you eat proteins, the body breaks them down into amino acids. Leftover amino acids turn into ammonia and must be removed from the body. The liver produces several chemicals (enzymes) that change ammonia into a form called urea, which the body can remove in the urine. If this process is disturbed, ammonia levels begin to rise. Symptoms Typically, the baby begins nursing well and seems normal. However, over time the baby develops poor feeding, vomiting, and sleepiness which may be so deep that the baby is difficult to awaken. This usually occurs within the first week after birth. 1- irritability 2- lethargy 3- mental retardation 4- intermittent ataxia

Metabolic disorder of urea Signs and tests The doctor will often diagnose these disorders when the child is still an infant. Signs may include: 1- Abnormal amino acids in blood and urine 2- Abnormal level of orotic acid in blood or urine 3- High blood ammonia level 4- Normal level of acid in blood Tests may include: 1- Genetic tests 2- Liver biopsy 3- MRI or CT scan

Metabolic disorder of urea 1-Hyperammonemia type I due to deficiency of carbamoyl synthetase lead to certain skin manifestation that is due to low arginine level 2-Hyperammonemia type II Deficiency of ornithine transcarbamolyase diagnosis by elevated level of glutamine in blood, urine and CSF 3-Citrullinemia Deficiency of arginine succinate synthase the infant suffer from perioral lower abdominal and buttock region dermatitis 4-argininosucccinicacid uria Deficiency of arginine succinase associated with friable tufted hair 5-Hyperargininemia Low level in arginase enzyme result in a pattern resembling that of lysine cystin uria