Liver, kidney, metabolism inter-organ

1. Liver, kidney, metabolism inter-organ

2. bodies are an integrated system of organs, • each with its own requirements for nourishment and energy utilization. • tissues share a common circulation system. • Strict limits on the blood levels of ions, lipids and sugars must be upheld in healthy situation • restrictions are at rest, while work and after meals. • Control by feedback and feed-forward mechanisms on the • enzymatic level, • central nuclear control of protein synthesis • hormonal messaging and signaling all play a part in the integration of metabolism

4. LIVER

7. Functions of the liver 1. Uptake of nutrients supplied by the intestinesvia the portal vein. 2. Biosynthesis of endogenous compoundsand storage, conversion, and degradation ofthem into excretable molecules (metabolism).In particular, the liver is responsible for thebiosynthesis and degradation of almost allplasma proteins. 3. Supply of the body with metabolites andnutrients. 4. Detoxification of toxic compounds bybiotransformation. 5. Excretion of substances with the bile.

9. Hepatic metabolism • Carbohydrate metabolism. • The liver takesup glucose and other monosaccharides fromthe plasma. • Glucose is then either stored inthe form of the polysaccharide glycogen orconverted into fatty acids. • When there is adrop in the blood glucose level, the liver releasesglucose again by breaking down glycogen. • If the glycogen store is exhausted, glucosecan also be synthesized by gluconeogenesis from lactate, glycerol, or the carbon skeletonof amino acids. • The conversion of lactate to glucosein the Cori cycle and • the conversionof alanine to glucose with the help of the alanine cycle

11. Hepatic metabolism 2. Lipid metabolism. • The liver synthesizesfatty acids from acetate units. The fatty acidsformed are then used to synthesize fats andphospholipids, which are released into theblood in the form of lipoproteins. The liver’sspecial ability to convert fatty acids into ketonebodies and to release these again is alsoimportant • Like other organs, the liver also synthesizescholesterol, which is transported to other tissuesas a component of lipoproteins. Excesscholesterol is converted into bile acids in theliver or directly excreted with the bile

15. Hepatic metabolism 3. Amino acid and protein metabolism. • Theliver controls the plasma levels of the aminoacids. Excess amino acids are broken down.With the help of the urea cycle,the nitrogen from the amino acids is convertedinto urea and excreted via the kidneys. • The carbon skeleton of the amino acids entersthe intermediary metabolism and serves forglucose synthesis or energy production. • In addition , most of the plasma proteins are synthesizedor broken down in the liver

17. UREA CYCLE

18. Hepatic metabolism 4. Biotransformation. Steroid hormones andbilirubin, as well as drugs, ethanol, and otherxenobiotics are taken up by the liver and inactivatedand converted into highly polarmetabolitesby conversion reactions 5. Storage. The liver not only stores energyreserves and nutrients for the body, but alsocertain mineral substances, trace elements,andvitamins, including iron, retinol, and vitaminsA, D, K, folic acid, and B12.

19. Biotransformation • Hydrolytic cleavages of ether, ester, andpeptide bonds. Example (1) shows hydrolysisof the painkiller acetylsalicylic acid. • Oxidations. Hydroxylations, epoxide formation,sulfoxide formation, dealkylation,deamination. For example, benzene is oxidizedinto phenol, and toluene (methylbenzene)is oxidized into benzoic acid. • Reductions. Reduction of carbonyl, azo-, ornitro- compounds, dehalogenation. • Methylations. Example (2) illustrates theinactivation of the catecholamine norepinephrineby methylation of a phenolic OHgroup • Desulfurations. The reactions take place inthe hepatocytes on the smooth endoplasmicreticulum.

22. kidney

27. KIDNEY (REN) The kidneys’ main function : • excretion ofwater and water-soluble substances • Homeostatis : • role in regulatingthe body’s electrolyte and water recycling • functions in the acid–base balance (homeostasis) • Involvedin synthesizing several hormones.Both excretion and homeostasis are subject tohormonal control. • play a rolein the intermediary metabolism particularlyin amino acid degradation and gluconeogenesis

28. 1. excretion • Untrafiltration all plasma components with a molecularmass of up to about 15 kDa to pass through • Resorbtion • In the proximal tubule, organicmetabolites (e. g., glucose and other sugars,amino acids, lactate, and ketone bodies) arerecovered by secondary active transport to prevent losses valuable metabolites and electrolytes • In the proximal tubule HCO3–, Na+, phophate,and sulfate are also resorbed by ATP-dependent(active) mechanisms. • The later sections of the nephron mainlyserve for additional water recovery and regulatedresorption of Na+ and Cl–

29. 1. excretion • Secretion. Some excretable substances arereleased into the urine by active transport inthe renal tubules. These substances include H+and K+ ions, urea, and creatinine, as well asdrugs such as penicillin. • Clearance. Renalclearanceisusedasaquantitativemeasureof renal function. It is definedas the plasma volume cleared of a given substanceper unit of time

33. 2. Homeostatis 2a. Electrolyte and water recycling • Electrolytes and other plasmacomponentswith lowmolecular weights enter the primaryurine by ultrafiltration (right). Most of thesesubstances are recovered by energy-dependentresorption • Calcium(Ca2+) and phosphate ions are almost completelyresorbed from the primary urine byactive transport. • The peptide hormone parathyrin (PTH)stimulates Ca2+resorption in the kidneys andinhibits resorptionofphosphate • The steroid hormone calcitriol, which isformed in the kidneys, stimulatesthe resorption of both calciumand phosphateions

34. Sodium ions Controlled resorption of Na+from the primary urine is one of the mostimportant functions of the kidney. Na+ resorptionis highly effective, with more than 97%being resorbed • Water • Water resorption in the proximaltubule is a passive process in which waterfollows the osmotically active particles, particularlythe Na+ ions • peptide hormone vasopressin(antidiuretic hormone, ADH) operates it.

36. 2b. Functions in the acid–base balance • Proton excretion • The renal tubule cells are capable of secretingprotons (H+) from the blood into the urineagainst a concentration gradient, despite thefact that the H+ concentration in the urine isup to a thousand times higher than in theBlood • Ammonia excretion • An important buffer in the urine is thehydrogen phosphate/dihydrogen phosphatesystem (HPO42–/H2PO4–). In addition, ammoniaalso makes a vital contribution to bufferingthe secreted protons.

39. 3. Renal hormones • Calcitriol (vitamin D hormone, 1α,25-dihydroxycholecalciferol)is a hormone closely relatedto the steroids that is involved in Ca2+homeostasis • Erythropoietin is a peptide hormone that isformed predominantly by the kidneys, butalso by the liver. Together with other factorsknown as “colony-stimulating factors” (CSF), it regulates the differentiation ofstemcells in the bone marrow • Renin is an aspartateproteinase. It is formed by the kidneys as a precursor(prorenin), which is proteolyticallyactivated into renin and released into theblood. In the blood plasma, renin acts onangiotensinogen that have an involve in blood pressure regulation

42. 4. Gluconeogenesis • Apart from the liver, the kidneys are the onlyorgans capable of producing glucose byneosynthesis(gluconeogenesis). • The main substrate for gluconeogenesis inthe cells of the proximal tubule is glutamine.other amino acids and also lactate, andglycerol, can be used asprecursors. • As in the liver, the key enzymesfor gluconeogenesis are induced by cortisol • Since the kidneys also have ahigh level of glucose consumption, they onlyrelease very little glucose into the blood.

45. Skeletal Muscle. • about one half of the body's mass • dominates energy metabolism • skeletal muscle uses much of the consumed glucose or produce daily, • muscle does not carry out gluconeogenesis • cannot dephosphorylate G-6-P • cannot generate glucose and stabilize blood sugar levels

46. Skeletal Muscle. • Muscle lacks receptors for glucagon • The relatively large glycogen reserves in skeletal muscle cannot be mobilized to buffer blood sugar • muscle glycogen can only be utilized in the muscle cells where it is found. • activated through the adrenergic nervous system and adrenalin • if it is used in anaerobic metabolism (that is, from glycogen to pyruvate and lactate) the lactic acid formed can be transported to other tissues. (Both the heart and kidneys use quantities of lactate produced in other tissues) • Unlike the liver, skeletal muscle lacks fatty acid synthetase and cannot synthesize fatty acids and triglycerides