COMPOSITION OF THE BODY FLUIDS mirka rovenskalfmotol cuni

COMPOSITION OF THE BODY FLUIDS mirka. rovenska@lfmotol. cuni. cz

Body fluids: n n n n Digestive juices (saliva, gastric juice, pancreatic secretions, bile, secretions of the small intestine) Plasma Cerebrospinal fluid Urine Sweat Tears Amniotic fluid

Compartmentalization of the body water H 2 O [l] H 2 O [% of body weight] H 2 O [portion of total body water] Intracelullar fluid 28 40 ~ 2/3 Extracellular fluid 14 20 ~ 1/3 - interstitial fluid 11 16 26 % - intravasal fluid: plasma, lymph 3– 4 5 7% 1 -2 2 2% 42 60 Compartment - transcellular fluid Total Note: transcellular fluid includes pleural, peritoneal, and cerebrospinal fluid, fluid in the urinary tract, and in the lumen of GIT. Under pathological conditions, originally small amount of water can increase several folds (e. g. ascites. . . ).

Extra- versus intracellular fluid Important for homeostasis! Deviations of the levels are dangerous!!!

Composition of digestive juices Digestive juice Saliva Gastric juice Pancreatic secretion Bile Secretion of small int. Feces

Saliva n n Function: initiation of food digestion; excretion of certain drugs (morphine) and inorganic substances (I, Hg, Pb) 99, 5% water; the rest consists of: inorganic salts (1/3): chlorides, phosphates, bicarbonate, sodium, potassium org. compounds (2/3): Ø glycoproteins (mucins) acting as lubricants facilitating mastication and swallowing; have a high content of O-linked (to Ser, Thr) oligosaccharides, usually containing Neu. Ac, Gal. NAc Ø antibodies – secretory Ig. A Ø enzymes

Enzymes in saliva n -amylase: partial hydrolysis of starch and glycogen, yielding maltose, maltotriose, and (1 -6)-oligosaccharides – dextrines; in saliva not very significant (rapid inactivation of the enzyme in stomach) n lysozyme – hydrolyzes the glycosidic bonds in peptidoglycan of bacterial cell walls (and thus helps to fight bacteria)

Gastric juice n n n Water – 99, 4%; inorganic salts (chlorides) HCl – creates the acid environment (p. H~1 -2 in adults), denatures proteins (making them more susceptible to proteolysis), and kills bacteria Mucins – form mucus which protects the stomach from the gastric juice Peptides: gastrin – produced by G-cells of the stomach, stimulates secretion of HCl and pepsinogen Proteins: Ø albumin, Ig. A, amylase from saliva (denaturated) Ø intrinsic factor (glycoprotein secreted by parietal cells of the gastric mucosa, binds vitamin B 12 and facilitates its absorption in the ileum) Ø proenzymes (zymogens) Protein concentration – low (<50 mg/ml); the amount of albumin is elevated in gastropathies

Enzymes of the gastric juice n Pepsin: Ø inactive zymogen pepsinogen is activated to pepsin by H+ which is followed by rapid autocatalysis; Ø p. H optimum ~1 -3 Ø endopeptidase – cleaves proteins into polypeptide fragments, mainly between Tyr/Phe and Glu/Asp…most important digestive process in stomach n Acid-stable lipase – cleaves triacylglycerols, yielding fatty acids and 1, 2 -diacylglycerols

Pancreatic secretion n Alkaline (p. H = 7, 5 -8, 9), together with the bile and secretion of the intestine neutralizes HCl from the stomach HCO 3 - concentration is higher than in plasma Contains various enzymes participating in cleavage of high-molecular dietary constituents; many of these enzymes are secreted as zymogens: Ø trypsinogen – activated to trypsin by enterokinase; then trypsin itself activates other zymogens: Ø chymotrypsinogen, proelastase, procarboxypeptidase

Enzymes of the pancreatic juice n Endopeptidases: trypsin, chymotrypsin, elastase; cleave proteins/polypeptides into oligopeptides n Exopeptidases – carboxypeptidases: cleave off amino acids from the C-terminus of oligopeptides n Endoglycosidases: -amylase n RNAses (ribonucleases), DNAses (deoxyribonucleases) n Pancreatic lipase – hydrolyzes triacylglycerols in the presence of the bile salts, phospholipids (emulsification), colipase and phospholipase A 2. Products: mixture of 2 -monoacylglycerols, FAs, and glycerol n Cholesterol esterase – hydrolysis of cholesteryl esters

Bile n n n n Water: 96 -98% Inorganic salts Bile salts (acids): e. g. cholic acid, deoxycholic acid; may be conjugated with glycine or taurine Bile pigments: bilirubin and products of its conversion: urobilinogen, urobilin, sterkobilin Cholesterol Phospholipids – lecithin Roles of the bile: Ø bile acids facilitate absorption of the products of lipid digestion (FAs, monoacylglycerols) and of the compounds dissolved in lipids, such as vitamins A, K Ø neutralization of chyme (HCO 3 -) Ø excretion of cholesterol, bile pigments, drugs, inorganic substances (Cu, Zn, Hg)

cholic acid glycine bilirubin intestinal bacteria glycocholic acid lecithin = phosphatidylcholin

Secretion of the small intestine n n Water, inorganic compounds – Na. HCO 3 Mucus – formed by mucins, protects the intestinal epithelium Cholecystokinin, secretin – peptides secreted by the cells of the small intestine: cholecystokinin stimulates the secretion of pancreatic juice rich in enzymes, secretin of that rich in Na. HCO 3 Enzymes – mainly anchored in the intestinal surface: Ø disaccharidases, oligosaccharidases (maltase, sucrase, lactase) Ø aminopeptidases and dipeptidases – cleave oligopeptides produced by the action of endopeptidases and carboxypeptidases Ø polynucleotidases – cleave the polynucleotide chain into nucleotides Ø phosphatases – remove phosphate from organic phosphates (glycerolphosphate) and nucleotides Ø nucleosidases – phosphorolysis of nucleosides to bases and pentose phosphates

Amniotic fluid n In early embryogenesis, the composition is being influenced by free transport of compounds between the foetus (extracellular fluid) and AF (before keratinisation of the skin occurs around 25 th week) n Two major sources of AF in the second half of gestation: Ø fetal urine (first enters the amniotic space around the 10 th week) Ø secretion of fetal lungs n As the foetus grows, the volume of AF rises (up to ~800 ml around the 35 th week) n Conc. of cations (Na+, K+, Mg 2+) is slightly lower than in maternal serum, conc. of Cl- is similar, conc. of glucose, triacylglycerols, and total protein is significantly lower. On the other hand, conc. of urea, creatinine, and uric acid is higher than in maternal serum. As a result, osmolality of AF is lower.

Proteins of the amniotic fluid n n n n Mainly those of low molecular weight Albumin Cytokines, growth factors (? regulation of foetal development? ) Foetus itself produces -fetoprotein (AFP): its conc. rises until the 15 th week, then drops down (in AF). AFP level (determined in maternal serum) is increased in neural tube defects; decreased levels may indicate the Down's syndrome Immunoglobulins (Ig. A, Ig. G, Ig. M) Surfactants Enzymes (acetylcholinesterase, -glutamyltransferase) – determination of activity in ACh. E can be used in diagnosis of developmental defects (e. g. : ACh. E activity rises in neural tube defects but not in the Down's syndrome)

Cerebrospinal fluid n n n Isosmotic, but concentrations of particular ions differ from that found in plasma (lower conc. of Na+, K+, Ca 2+, HCO 3 - x higher conc. of Mg 2+, Cl-) Total protein conc. is ~200 -fold lower than in plasma; low amount of cells p. H = 7, 35 -7, 40 Metabolites: glucose (lower than in serum), lactate (higher), urea Proteins: albumin, immunoglobulins, enzymes (lactate dehydrogenase) The levels of these compounds change under pathological conditions: Ø total protein conc. changes in bacterial meningitis, brain tumours τ-protein indicates the Alzheimer's disease n Increased level of n Function: mechanic protection of CNS, protection against pathogens, removal of waste products, delivery of nutrients

Plasma, blood n n Plasma = liquid medium for blood cells Serum, despite plasma, lacks the clotting factors p. H of plasma = 7, 40, p. H of the blood = 7, 36 – 7, 44 Composition of plasma: Ø water (90 -92%) Ø electrolytes – compared to cytoplasm of cells, plasma contains higher conc. of Na+, Ca 2+, and Cl- and lower conc. of K+, Mg 2+, phosphates, and proteins Ø metabolites, nutrients, hormones, vitamins Ø plasma proteins

Plasma composition

Functions of blood/plasma n n n n n Respiration – transport of O 2 and CO 2 Nutrition – transport of absorbed food materials Excretion – transport of metabolic waste to the kidneys, lungs, skin, intestines Maintenance of acid-base balance Regulation of water balance Regulation of body temperature Defense against infection (white blood cells, circulating antibodies) Transport of hormones and regulation of metabolism Transport of metabolites Coagulation