Pathophysiology of kidney.kidney insufficiency

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M.D., PhD. Marta R. Gerasymchuk,
Pathophysiology Department
Ivano-Frankivsk National
Medical University

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  • Renal transport systems
    Lots of transporter proteins for different molecules/ions so they can be reabsorbed.
    They all have maximum transport (TM) capacities where transport saturates i.e. 10mmol/l for glucose.
    Over this value, you excrete the excess in urine, so can be useful sign of disease either in kidneys or other systems.
    Amino acids also have a high TM value because you try and preserve as much of these useful nutrients as possible.
    Na+ absorption
    Na+ absorbed by active transport mechanisms, NOT by TM mechanism. Basolateral ATPases establish a gradient across the tubule wall.
    Proximal tubule is very permeable to Na+, so ions flow down gradient, across membranes.
    Microvilli create large surface area for absorption.
    Electrical gradient created also draws Cl- across.
    H2O follows Na+ due to osmotic force.
    Means fluid left in tubule is concentrated.
    Glucose handling
    - Glucose absorption also relies upon the Na+ gradient.
    - Most reabsorbed in proximal tubule.
    - At apical membrane, needs Na+/glucose cotransporter (SGLT)
    - Crosses basolateral membrane via glucose transporters (GLUT’s), which do not rely upon Na+.
    Amino acid handling
    - Preserve as much of these essential nutrients as possible.
    - Can be absorbed by GI tract, products of protein catabolism, or de novo synthesis of nonessential amino acids.
    - TM values lower than that of glucose, so can excrete excess in urine.
    - Amino acid transporters rely upon Na+ gradient at apical membrane, but a couple of exceptions don’t.
    - Exit across basolateral membrane via diffusion , but again, some exceptions rely on Na+.
    K+ handling
    - K+ is major cation in cells and balance is essential for life.
    - Small change from 4 to 5.5 mmoles/l = hyperkalaemia = ventric. fibrillation = death.
    - To 3.5 mmoles/l = hyperpolarise = arrhythmias and paralysis = death.
    - Reabsorb K+ at proximal tubule.
    - Changes in K+ excretion due to changes in K+ secretion in distal tubule
    - Medullary trapping of K+ helps to maximise K+ excretion when K+ intake is high.
    - K+ reabsorption along the proximal tubule is largely passive and follows the movement of Na+ and fluid (in collecting tubules, may also rely active transport).
    K+ secretion occurs in cortical collecting tubule (principal cells), and relies upon active transport of K+ across basolateral membrane and passive exit across apical membrane into tubular fluid.
  • Glomerular filtration rate - is a volume of plasma of blood which is filtered in kidney tubules per time unit.
    It is calculated after a formula:
    GFR = PeffKfF
    where Peff is effective filtration pressure; Kf – is a hydraulic conductivity (coefficient of filtration), F – filtering surface.
    Peff = HP – (Ponc + Ptis)
    where HP - is hydrostatical pressure in the capillaries of glomerulus (45 mmHg); Ponc is oncotic pressure of blood (20 mmHg); Ptis is hydrostatical pressure in the capsule of glomerulus or, so-called tissue pressure (10 mmHg).
    Going out from these formulas, it is possible to select 2 groups of mechanisms of violation of glomerular filtration: 1) diminishing of glomerular filtration. 2) Multiplying glomerular filtration
  • The daily ultrafiltrate amount, which gets into canalicules makes equal 99 % of this volume is exposed to a converse absorption mainly in proximal canalicules
    Reabsorption proteins, glucose, aminoacids, electrolytes, bicarbonates, phosphates and water almost completely are exposed
    The reabsorbtion selectivity provides kidneys epithelium ability to reabsorp one substance and simultaneously prevents the other. This function is executed by specific molecules – which are the carriers
    The dependence of reabsorbtion processes on molecules membrane – carriers means the limited canaliculus epithelium ability to transport reabsorbed substance
    If the concentration of substance in glomerulus filtrat exceeds possibilities transport system, then given substance threshold exceeding
    Takes place maximal reabsorption substrate speed is named as a maximal tubular one
  • Violation of reabsorption of amino acids.
    In a norm for days with urine secreted to 1 g of amino acid.
    Distinguish two types of aminoaciduria: a) renal and b) extrarenal.
    à) Aminoaciduria of renal origin is observed at the damages of kidney tubules and inherited conditioned defects of the systems of transport of amino acid through a cellular membrane (Fanconi's syndrome).
    b) Aminoaciduria of extra renal origin is observed at inherited violations of metabolism of amino acid and increase of their concentration in blood, at increased catabolism of albumens in the conditions of the different pathological states (hypoxia, starvation, damage of liver).
    Violation of reabsorption of electrolytes (Ê+, Na+, Ñà2+, Ñl–) and phosphates
    The decline of reabsorption of electrolytes is observed:
    - at diminishing of products of aldosterone
    - at the damages of epithelium of kidney tubules (inflammatory, dystrophic characters)
    - at the use of some medicinal preparations – inhibitors of reabsorption of electrolytes in kidney tubules (lasix and other diuretics).
    - at the inherited and purchased defects of transport systems (phosphatic kidney diabetes, Fankoni syndrome, poisoning by phlorhizin).
  • Mechanism of reabsorption. In primary urine (filtrate), as well as in blood, albumins are in a complex with free fat acids (FFA). Such complex co-operates with the epithelium of kidney tubules. FFA diminishes surface tension of cell membrane of epytheliocytes, that lead to penetrate this complex into the cell. Phagosome will be appearing as result. Phagosome co-operates with lysosome. Lysosomal proteases break up albumins to amino acids, which enter into blood.
    The disorder of proteins reabsorption appears as tubular proteinuria
    It is observed due to poisoning cadmium, hypoxia, burns, septicemia
    Moderate tubular insufficiency is characterized by the rather low contents in urine of albumins and other proteins with weight up to 40 kD (selective proteinuria).
    Dystrophic defeats canaliculus lead to in urine appearence proteins with molecular weight more than 40 kD (unselective proteinuria)
  • Disorder sodium and water reabsorbtion
    The increase of reabsorption is observed in fallowing case: hyperaldosteronism, oliguri stage of acute kidney insufficiency, reabsorption decrease – hypoaldosteronism, diabetes insipidus
    Sodium and water reabsorption is decreased as a result of canalicules epithelium metabolism inhibition by some poisons, including medicines, in particular, mercury diuretics. Reabsorbtion is limited because of glomerulus filtrate osmotic active substances (glucose, urin), increase owing to that so-called osmotic diuresis arises (example, diabetes mellitus)
    The heavy disorders of sodium and water resorbtion arise in case dystrophic and inflammatory canaliculus epithelim changes, so canalicules lose the ability to liquid concentration and cultivation. Loss of concentration ability is called hypostenuria, relative density aqual in state changes within the limit of 1,006-1,012 (norma – 1,002-1,035). If density urine is kept at 1,010 level and is not changed with influence water load, it is called isostenuria (monotone diuresis)
  • Prerenal causes of renal failure are those resulting from inadequate blood flow to the kidney. These include intravascular volume depletion, structural lesions of the renal arteries, drug effects on renal blood flow, and hypotension from any cause that results in renal hypoperfusion.
    Intrarenal causes are those disorders that result in damage to the nephron directly rather than indirectly as a secondary consequence of inadequate perfusion or obstruction. As mentioned, intrarenal causes include specific disorders of the kidney as well as systemic diseases with prominent manifestations in the kidney. Some of these disorders are manifested as glomerular injury, whereas others involve primarily the tubules. Within each category, disorders can be approached according to their specific cause or their phenotype and manifestations.
    Postrenal causes are those related to urinary tract obstruction, from either kidney stones, structural lesions (eg, tumors, prostatic hyperplasia, or strictures), or functional abnormalities (eg, spasm or drug effects). 
  • Decrease of phosphates excretion lead to increase their level in blood.
    Result hydroxiapatite is derivation and ionized calcium level is decreased, thus it stimulates parathyroid glands. If GFS falls below 25 % of norm, secondary hyperparathyreosis become obvious.
    Resorbtion of bones is increased and their density is decreased. When weight nephrones is less than 25 %, the 25-ОН- vitamin D transformation to the active form – 1,25 (OH)2-vitamin D transformation is decelerated. It is the reason of calcium delay absorbtion in alimentary channel
  • Uremic toxins is nitrogen metabolism products.
    They are: urea, guanidine derivatives (methylguanidine, guanidinsuccinic and guanidinacetative acids, kreatine and kreatine), aromatic compounds (phenole, indole, aromatic amines), conjugated aminoacids, lowmolecular peptides.
    In uremia development significance is peptides hormones accumulation – parathhormone, insuline, glucagone, gastrine, vasopressine, adrenocorticotropic and somatotropic hormones. In the kidneys is catabolysed 25 % of peptide hormones. Some effects is stipulated compounds deficiency, which are not synthesized due to uremia. Examples – erythropoietine and 1,25-dioxyеnolecalciferol deficiency.
  • http://arirusila.cafebabel.com/en/cbtag/14920
    The organ trafficking is negotiated by an elaborate network of criminals.For about $150,000, an organ broker connects a buyer and seller to a "broker-friendly" U.S. hospital, where surgeons are either complicit in the scheme or willing to turn a blind eye.The organ seller typically gets a few thousand dollars, plus a chance to see a U.S. city.
    Reputable U.S. medical centers transplant kidneys and other human organs they get illegally through the black market, a university anthropologist asserts. Surgeons take black-market kidneys from people in the world's most impoverished slums and put them into wealthy dialysis patients from the United States, Europe and and Israel, Nancy Scheper-Hughes of the University of California at Berkeley told Newsweek. (Source Newsweek 10th Jan 2009)
    The transplant tourism goes also opposite direction e.g. to China.One example about this global business and tourism is a case, when a New Yorker paid $60,000 to receive a kidney in a South African hospital from a Brazilian who was paid $6,000 for it; an Israeli businessman set up the deal.
    The bottom line
    With organ trafficking one can see inequality at its cruellest form.The main discriminative feature is between wealthy upper-class and the rest of the population.The other distinctive line goes between developed rich countries and the rest of the world.
    Transplantation is a growing problem in rich states because waiting lists are growing far faster than the supply of organs.Adding the trend of changing population-structure in developed countries one can easily estimate that the need of new transplants is growing creating bigger market for illegal organ trade.
    Is there anything to stop this trend?Short term I don’t believe so.Future can however change situation when research brings new solutions e.g. through gene, stem cell or material innovations.Even then the problem is who can pay these new treatments.
    More my articles one may find from Archives:Blog!
  • Pathophysiology of kidney.kidney insufficiency

    1. 1. Pathophisiology ofPathophisiology of kidneys.kidneys. Renal insufficiency.Renal insufficiency. M.D., PhDM.D., PhD, Associate Professor, Associate Professor Marta R. Gerasymchuk,Marta R. Gerasymchuk, Pathophysiology DepartmentPathophysiology Department Ivano-Frankivsk NationalIvano-Frankivsk National Medical UniversityMedical University
    2. 2. 1.1. Disorders of secretory and incretory functions of kidneys.Disorders of secretory and incretory functions of kidneys. 2.2. Insufficiency of kidneys: definition, classification,Insufficiency of kidneys: definition, classification, reasons.reasons. 3.3. Violation of glomerulus filtration: reasons andViolation of glomerulus filtration: reasons and mechanisms. Changes of obligate diuresis: kinds, reasonsmechanisms. Changes of obligate diuresis: kinds, reasons and consequences of oliguria and anuria. Polyuria: kinds,and consequences of oliguria and anuria. Polyuria: kinds, reasons, consequences. Nycturia: kinds, mechanisms ofreasons, consequences. Nycturia: kinds, mechanisms of development.development. 4.4. Violation of processes of reabsorbtion in tubulus.Violation of processes of reabsorbtion in tubulus. Violation of tubular secretion.Violation of tubular secretion. 5.5. Pathological components of urine. Functional tests ofPathological components of urine. Functional tests of kidneys, their using in a clinic.kidneys, their using in a clinic. 6.6. Acute and chronic glomerulonephritis. Etiology,Acute and chronic glomerulonephritis. Etiology, pathogenesis, clinical symptoms and mechanism ofpathogenesis, clinical symptoms and mechanism of development of them. Experimental models.development of them. Experimental models. 7.7. Acute and chronic pyelonephritis. Etiology, pathogenesis,Acute and chronic pyelonephritis. Etiology, pathogenesis, clinical symptoms.clinical symptoms. 8.8. Urolithiasis. Theories of stone formation. Clinical picture.Urolithiasis. Theories of stone formation. Clinical picture. ContentContent
    3. 3. Actuality of the themeActuality of the theme  Kidneys play important role in regulation of constancy of internalKidneys play important role in regulation of constancy of internal environment. Most functions of kidneys related to the processes ofenvironment. Most functions of kidneys related to the processes of uropoiesisuropoiesis and urination. Due to these processes kidneys take part inand urination. Due to these processes kidneys take part in support of water-electrolyte and acid-base balances. The excretionsupport of water-electrolyte and acid-base balances. The excretion function of kidneys provides the release of organism from the finishedfunction of kidneys provides the release of organism from the finished goods of metabolic and different toxic substances.goods of metabolic and different toxic substances. Violation ofViolation of uropoiesis and urination is accompanied by violation of vital functionsuropoiesis and urination is accompanied by violation of vital functions of organism.of organism.  The renal failure depend to severe pathological states. The disorder ofThe renal failure depend to severe pathological states. The disorder of constance of internal environment of organism, which one thus arise,constance of internal environment of organism, which one thus arise, often demand emergency treatment. To the most often causes, whichoften demand emergency treatment. To the most often causes, which one cause disturbance of functions of kidney, the disorder of theirone cause disturbance of functions of kidney, the disorder of their blood supply, infections deseases, intoxication, autoallergy damages,blood supply, infections deseases, intoxication, autoallergy damages, violation of outflowviolation of outflow of urine concern. Knowledge of etiology andof urine concern. Knowledge of etiology and pathogenesis of kidney diseases, mechanisms of disturbance, whichpathogenesis of kidney diseases, mechanisms of disturbance, which one arise in renal failure, are necassary for selection pathogeneticone arise in renal failure, are necassary for selection pathogenetic based methods of preventive maintenance and treatment.based methods of preventive maintenance and treatment.
    4. 4. Functions of the kidneyFunctions of the kidney EliminationElimination of waste/surplusof waste/surplus Carbohydrate-derivedCarbohydrate-derived NitrogenousNitrogenous OtherOther Water, acidWater, acid Urea creatinine, uric acid,Urea creatinine, uric acid, guanidine, amines, etcguanidine, amines, etc Sulphate, phosphate,Sulphate, phosphate, exogenous toxins, etc.exogenous toxins, etc. RegulationRegulation of fluid andof fluid and electrolyteelectrolyte balancebalance Total body waterTotal body water Plasma osmotic pressure, pHPlasma osmotic pressure, pH Na, K, Ca, Mg, etc.Na, K, Ca, Mg, etc. Chloride, bicarbonate,Chloride, bicarbonate, phosphate, etc.phosphate, etc. EndocrineEndocrine homeostasishomeostasis Blood pressureBlood pressure Calcium and bone metabolismCalcium and bone metabolism RBC productionRBC production
    5. 5. 1. Water balance1. Water balance Osmoreceptor (hypothalamus)Osmoreceptor (hypothalamus) ADH, Vasopressin (Pituitary)ADH, Vasopressin (Pituitary) Collecting ductCollecting duct Absorption of HAbsorption of H22OO FunctionFunction of Kidneyof Kidney 2. Acid-base balance2. Acid-base balance Carbonic anhydrase (Distal tubules)Carbonic anhydrase (Distal tubules) Carbonic acid-bicarbonate buffer systemCarbonic acid-bicarbonate buffer system H+ excretionH+ excretion Na+ reabsorptionNa+ reabsorption HH22O excretionO excretion
    6. 6. 3. Excretion of waste product3. Excretion of waste product - Acid - base - H- Acid - base - H22OO - creatinine- creatinine - Metabolites- Metabolites 4. Others4. Others - erythropoeitin- erythropoeitin Conclusion : renal functions Filtration Reabsorption Secretion
    7. 7.  KidneyKidney is majoris major organorgan, which determine, which determine outcell liquid of an organismoutcell liquid of an organism persistance and regulates structurepersistance and regulates structure surroundy cells environmentalsurroundy cells environmental  The kidney prevent internal changesThe kidney prevent internal changes and provide maintenance such mainand provide maintenance such main homeostasis parametershomeostasis parameters as:as:  iisovolemiasovolemia – blood volume constancy– blood volume constancy  isotoniaisotonia – osmotic pressure– osmotic pressure constancyconstancy  isoioniaisoionia – ionic structure constancy– ionic structure constancy  isohydriaisohydria – concentration hydrogen– concentration hydrogen ions constancyions constancy
    8. 8. Homeostasis maintenance includes three processesthree processes: plasma filtering by glomerulus selective canalicules reabsorbtionreabsorbtion ions of hydrogen secretionsecretion ammonium and other substances secretion Structural and functional unit of a kidneyunit of a kidney, which provides these functions is nephronnephron
    9. 9. NEPHRONNEPHRON
    10. 10. Disorders of theDisorders of the excretoryexcretory functions of kidneys lead to:functions of kidneys lead to:  1) violation of1) violation of water homeostasiswater homeostasis. It is changes of volume. It is changes of volume of extracellular liquid (of extracellular liquid (hyperhyper-- and hypohydriaand hypohydria););  2) violation of2) violation of osmotic homeostasisosmotic homeostasis -- hyperhyper-- andand hypoosmiahypoosmia;;  3) violation of balance of3) violation of balance of electrolyteselectrolytes in a extracellularin a extracellular liquid (liquid (dysioniadysionia););  4) violation of4) violation of acid-base balanceacid-base balance (more frequent in all is(more frequent in all is nongaseous acidosis);nongaseous acidosis);  5) violation of chemical composition of plasma of blood5) violation of chemical composition of plasma of blood which shows up, from one side, piling up of the finishedwhich shows up, from one side, piling up of the finished goods of metabolism (azotemia [uremia]), from other, - bygoods of metabolism (azotemia [uremia]), from other, - by the loss of necessary to the organism of organicthe loss of necessary to the organism of organic compounds (compounds (hypoproteinemia, hypoaminoemia,hypoproteinemia, hypoaminoemia, hypoglycemiahypoglycemia).).
    11. 11. Disorders of incretory functions ofDisorders of incretory functions of kidneys show up by violations:kidneys show up by violations: 1) secretions of renin by the JGA of kidneys,1) secretions of renin by the JGA of kidneys, and also kidney depressor factors;and also kidney depressor factors; 2)2) production of erythropoietins andproduction of erythropoietins and inhibitors of erythropoiesisinhibitors of erythropoiesis;; 3) transformation of vitamin D to hormonal3) transformation of vitamin D to hormonal of active form.of active form. Disorders of incretory function of kidneysDisorders of incretory function of kidneys can stipulate development:can stipulate development: 1) arterial hypertension;1) arterial hypertension; 2) anemias;2) anemias; 3) kidney osteodysrtrophy - violation of3) kidney osteodysrtrophy - violation of phosphoric-calcium metabolism.phosphoric-calcium metabolism.
    12. 12.  Intensity of kidney blood stream (Intensity of kidney blood stream (QQ) in) in a norm is ever-higher: abouta norm is ever-higher: about 11001100 ml/minml/min, or to a 25% volume of blood, or to a 25% volume of blood which is pumped over for a minute bywhich is pumped over for a minute by a heart in a state of rest It is calculateda heart in a state of rest It is calculated after a formula:after a formula: Pa – Pv 8Pa – Pv 8ηηll  Q = ; R =Q = ; R = RR ππr4r4  wherewhere QQ is volume speed ofis volume speed of kidney blood stream;kidney blood stream;  PaPa is pressure at the beginning;is pressure at the beginning;  PvPv - at the end of the system of- at the end of the system of perfusion of kidney vessels;perfusion of kidney vessels;  RR - is resistance of kidney- is resistance of kidney vessels;vessels;  ηη -- is viscosity of blood;is viscosity of blood;  ll - is length of vessels;- is length of vessels;  rr - is a radius of vessels.- is a radius of vessels.
    13. 13. After that formula diminishing of intensity ofAfter that formula diminishing of intensity of kidney blood stream it can be conditioned by:kidney blood stream it can be conditioned by: ► 1)1) diminishing of arterial pressure (Pa)diminishing of arterial pressure (Pa) below 80 mmHgbelow 80 mmHg (the mechanism of myogenic autoregulation don’ work).(the mechanism of myogenic autoregulation don’ work). It is observed at all types of shock and collapse;It is observed at all types of shock and collapse; ► 2)2) multiplying venous pressure (Pv).multiplying venous pressure (Pv). Reason of it can be: a)Reason of it can be: a) general violations (right ventricle insufficiency of heartgeneral violations (right ventricle insufficiency of heart which results in multiplying central and peripheral venouswhich results in multiplying central and peripheral venous pressure),pressure), b)b) local disorderslocal disorders (venous hyperemia, for ex. as result of(venous hyperemia, for ex. as result of inflammation of kidney tissue); r4inflammation of kidney tissue); r4 ► 3)3) diminishing of radiusdiminishing of radius (r)(r) of vesselsof vessels (an ischemia of(an ischemia of kidneys is at atherosclerosis and arterial hypertension);kidneys is at atherosclerosis and arterial hypertension); ► 4)4) multiplying viscidity of bloodmultiplying viscidity of blood (η)(η) (at a disseminate blood(at a disseminate blood clotting).clotting). ► All noted violations lead to diminishing of filtration pressureAll noted violations lead to diminishing of filtration pressure in kidney glomerulus, that shows up diminishing of speedin kidney glomerulus, that shows up diminishing of speed of filtration and, consequently, by the signs of insufficiencyof filtration and, consequently, by the signs of insufficiency of kidneys.of kidneys.
    14. 14. GFRGFR measurement is possible if one has a substance (call it x) that is freely filterable at the glomerulus and then is not reabsorbed, secreted, or changed in any way before it appears in the urine. To calculate the GFR from this substance, one would measure its concentration in a plasma sample (PxPx), its concentration in a urine sample (UxUx), and the urine volume over a certain period of time (VV). Given these values, the equation for GFR, in milliliters per minute, can be solved as shown in: Ux (mg/mL) V (mL/min) GFR (mL/min) = Px (mg/mL) The classic substance that fits the criteria described above for substance xx is the polysaccharide inulininulin. However, inulin is not normally present in the body, which means using inulin to measure GFR involves infusing it into an individual for an extended period. This offers a highly accurate but impractical method for measuring GFR. Instead, what is usually measured in plasma and urine is the concentration of creatinine, which is a naturally produced protein.
    15. 15. Filtration disorderFiltration disorder GlomerulesGlomerules filtfiltrationration processprocess is possible tois possible to consider asconsider as water and moleculeswater and molecules pushingpushing throughthrough sieve under infuence of arterialsieve under infuence of arterial pressure in apressure in a remote capillaryremote capillary This passive process dependsThis passive process depends on hydrostatic exacter filtration pressure, which displace a liquid part from capillary blood into a canaliculus lumen of and does not require energy FiltrationalFiltrational pressurepressure, which predetermines glomerules filtrate derivation, is equal to 15-15-25 mm25 mm HgHg In case such filtrational pressure in healthy person Broumen capsule 120 ml of filtrate per 1 min is derivated, that is 180 l per one day The glomerules filtation can be decreased ordecreased or increasedincreased
    16. 16. GGeriatric Considerationeriatric Consideration • GFR declines with age due to a 30 to 50% loss of functional nephrons and reduced renal blood flow. • Such a decline means that when drugs normally cleared by the kidneys are given to an elderly individual, their dosage should be adjusted to reflect declining renal function. • However, because muscle mass, and therefore serum creatinine, also declines with age, the increase in serum creatinine level that normally indicates a fall in GFR may not be apparent. • Since serum creatinine levels are frequently used to determine drug dosing, elderly individuals may receive inappropriately high doses of drugs despite reduced kidney function. • This problem can have severe toxic consequences. In order to adjust for age on GFR, the following equation has been developed by Cockcoft and Gault: (140 – age) x (body weight in kg) • Creatinine Clearance = 72 x serum creatinine in mg/dL
    17. 17. Reason of filtration decrease:Reason of filtration decrease: • 1. Hydrostatic pressure decrease in glomerules capillaries: in general decreasing of arterial pressure decrease (heart insufficiency, shock, collapse, hypovolemia), narrowing glomerules afferent arterioles (arterial hypertension, pain): aorta and kidneys arteries organic defeats (aorta coarctation, stenosis aorta atherosclerosis due to hypertonic illness), kidneys arteries thrombosis or embolism • 2. Plasma oncotic pressure increase – protein blood substitutes transfusion in large volumes • 3. Intrakidney pressure increase – canalicules block with cylinders or urinary tract with stones • 4. Glomerulus filter disorder – quantity functioning glomerulus decrease, glomerulus a membrane thickening, an pores amount and diameter decrease, basal membrane glycoproteid components autoallergic defeat
    18. 18. The most characteristic manifestations ofThe most characteristic manifestations of filtfiltrationration limitation inlimitation in glomerulesglomerules areare::  nitrogenemianitrogenemia (accumulation in blood of nitrogen metabolic and blood(accumulation in blood of nitrogen metabolic and blood residual nitrogen increase)residual nitrogen increase)  renal nitrogenemic acidosisrenal nitrogenemic acidosis owing to delay in an organismowing to delay in an organism phosphates, sulfates and organic acidsphosphates, sulfates and organic acids  Increase of filteringIncrease of filtering performs resulting blood pressure increaseperforms resulting blood pressure increase excessive consumption water, decomplication edema or oncoticexcessive consumption water, decomplication edema or oncotic plasma pressure decrease (hepatitis, cirrhosis)plasma pressure decrease (hepatitis, cirrhosis) Major increasedMajor increased glomerulusglomerulus filter permeabilityfilter permeability manifestationsmanifestations concernconcern::  proteinuriaproteinuria – evacuation with urine of plasma proteins over– evacuation with urine of plasma proteins over physiological norm (30-80 mg/day) and in urine protein fractionsphysiological norm (30-80 mg/day) and in urine protein fractions appearance with molecular weight more than 70 kDappearance with molecular weight more than 70 kD  hematuriahematuria – erythrocytes kidneys outlet in canalicules lumen of and– erythrocytes kidneys outlet in canalicules lumen of and their appearance.their appearance.
    19. 19. Multiplying ofMultiplying of glomerularglomerular filtrationfiltration  1)1) Increase of hydrostatical pressureIncrease of hydrostatical pressure in the capillaries ofin the capillaries of glomerulus, that is observed at following situations:glomerulus, that is observed at following situations: a)a) increaseincrease the volume ofthe volume of intravascular liquidintravascular liquid;; b)b) increaseincrease the volume ofthe volume of speed of cortical blood streamspeed of cortical blood stream inin connection with diminishing of tone of vas afferens (in theconnection with diminishing of tone of vas afferens (in the stage incrementi of temperature at a feverstage incrementi of temperature at a fever, in the conditions, in the conditions ofof multiplying the amount of sodium in a mealmultiplying the amount of sodium in a meal);); c)c) increase of tone of taking arteriolesincrease of tone of taking arterioles under neuro-reflex andunder neuro-reflex and humoral influencing, which are observed in the early stagehumoral influencing, which are observed in the early stage of hypertensive illness, after transfusion, at introduction ofof hypertensive illness, after transfusion, at introduction of small doses of adrenalin.small doses of adrenalin.  2)2) Decline of oncotic pressure of bloodDecline of oncotic pressure of blood, redistribution of, redistribution of proteins factions of blood (proteins factions of blood (increase globulinsincrease globulins, which own, which own lowlow oncotic act – at hepatitis, cirrhosis of liveroncotic act – at hepatitis, cirrhosis of liver).).
    20. 20. formation of hyperosmotic urine RenalRenal ReabsorptionReabsorption ReabsorptionReabsorption is theis the second process by whichsecond process by which the kidney determinesthe kidney determines the concentration of athe concentration of a substance filtered fromsubstance filtered from the plasma.the plasma. ReabsorptionReabsorption refers torefers to the active (requiringthe active (requiring energy and always beingenergy and always being mediated by a carrier) ormediated by a carrier) or the passive (no energythe passive (no energy required) movement of arequired) movement of a substance filtered at thesubstance filtered at the glomerulus back into theglomerulus back into the peritubular capillaries.peritubular capillaries. ReabsorptionReabsorption may bemay be totaltotal (e.g., glucose) or(e.g., glucose) or partialpartial (e.g., sodium,(e.g., sodium, urea, chloride, andurea, chloride, and water).water).
    21. 21. Reabsorption of GlucoseReabsorption of Glucose  Glucose is freely filtered at the glomerulus.Glucose is freely filtered at the glomerulus.  All of the filtered glucose is normallyAll of the filtered glucose is normally reabsorbed by active transportreabsorbed by active transport,, primarily in the proximal tubuleprimarily in the proximal tubule..  Because carriers are involved, a transport maximum (Tm) for glucose canBecause carriers are involved, a transport maximum (Tm) for glucose can be reached. The Tm is the amount of a substance that can be transportedbe reached. The Tm is the amount of a substance that can be transported per unit of time.per unit of time.  For glucose, at a certain filtered load (GFR Г— plasma concentration), allFor glucose, at a certain filtered load (GFR Г— plasma concentration), all carriers become occupied. Any glucose filtered beyond that load is notcarriers become occupied. Any glucose filtered beyond that load is not reabsorbed, but is instead excreted in the urine. The Tm for glucose isreabsorbed, but is instead excreted in the urine. The Tm for glucose is approximately 375 mg/min of filtered glucose.approximately 375 mg/min of filtered glucose.  The concentration of glucose that results in this filtered load, given a GFR ofThe concentration of glucose that results in this filtered load, given a GFR of 125 mL/min, is 3.0 mg/mL of plasma because glucose concentration125 mL/min, is 3.0 mg/mL of plasma because glucose concentration clinically is frequently expressed as per 100 mL of blood, or, 300 mg/dL.clinically is frequently expressed as per 100 mL of blood, or, 300 mg/dL. However, glucose begins to appear in the urine even before this plasmaHowever, glucose begins to appear in the urine even before this plasma level is reached, because each nephron has a slightly different Tm and thelevel is reached, because each nephron has a slightly different Tm and the carrier transport rate may accelerate at the highest glucose concentrations.carrier transport rate may accelerate at the highest glucose concentrations. Plasma glucose seldom gets high enough that glucose Tm is reachedPlasma glucose seldom gets high enough that glucose Tm is reached unless an individual hasunless an individual has diabetes mellitusdiabetes mellitus..  Note that the kidney does not control blood glucose levels; it simply filtersNote that the kidney does not control blood glucose levels; it simply filters and reabsorbs all it can. The pancreas, via insulin release, controls bloodand reabsorbs all it can. The pancreas, via insulin release, controls blood glucose.glucose.
    22. 22. Reabsorption disorderReabsorption disorder  ReabsorptionReabsorption of glucose takes place by it phosphorilation on the membranesof glucose takes place by it phosphorilation on the membranes of epitheliocytes ofof epitheliocytes of tubulestubules by the enzyme of glucokinase (hexokinase) andby the enzyme of glucokinase (hexokinase) and glucosoglucoso-6--6-phosphatase, which are produced by epithelial cells. If thephosphatase, which are produced by epithelial cells. If the concentration of glucose in blood and primary urine (filtrate) does not exceedconcentration of glucose in blood and primary urine (filtrate) does not exceed 180 mg% (10 mmol/l), glucosuria is absent.180 mg% (10 mmol/l), glucosuria is absent.  Reabsorbtion clearance after glucose = 0Reabsorbtion clearance after glucose = 0 R e a s o n s ofR e a s o n s of glucosuriaglucosuria::  a)a) alimentary (surplus use of carbohydrates),alimentary (surplus use of carbohydrates),  b)b) diabetes mellitus (diabetes mellitus (diminishing of products of insulin lead to grows concentrationdiminishing of products of insulin lead to grows concentration of glucose in blood over 180 mg%, in addition, there is a decline of activity ofof glucose in blood over 180 mg%, in addition, there is a decline of activity of glucokinase of epithelium cells of kidneyglucokinase of epithelium cells of kidney tubulestubules),),  c)c) damage of epithelium ofdamage of epithelium of tubulestubules (dystrophic changes, necrosis),(dystrophic changes, necrosis),  d)d) the inherited deficit of glucokinase (hexokinase) and glucose-6-the inherited deficit of glucokinase (hexokinase) and glucose-6- phosphatase,phosphatase,  e)e) poisoning of floridzinpoisoning of floridzin (it is polysaccharide, which contain in glue of fruit trees(it is polysaccharide, which contain in glue of fruit trees conduces to blocking of processes of phosphorilation glucose in the epithelium ofconduces to blocking of processes of phosphorilation glucose in the epithelium of kidneykidney tubulestubules)),,  h)h) complicated pregnancy (accumulation of toxic matters),complicated pregnancy (accumulation of toxic matters),  f)f) stress which is reason of:stress which is reason of: - increase break up of glycogen in a depot- increase break up of glycogen in a depot - increase of glyconeogenesis- increase of glyconeogenesis - increase of products of glucocorticoids, which block glucokinase.- increase of products of glucocorticoids, which block glucokinase.
    23. 23. Reabsorption of the Amino AcidsReabsorption of the Amino Acids  Amino acids filtered at the glomerulus are actively reabsorbedAmino acids filtered at the glomerulus are actively reabsorbed in the proximal tubule. All reabsorption of amino acids isin the proximal tubule. All reabsorption of amino acids is carrier-mediated.carrier-mediated.  The TmThe Tm ((transport maximumtransport maximum)) for the carriers is well above thefor the carriers is well above the amounts of amino acids normally filtered, so none areamounts of amino acids normally filtered, so none are normally present in the urine.normally present in the urine. Reabsorption of Plasma ProteinsReabsorption of Plasma Proteins  Very few plasma proteins are filtered across the glomerulus.Very few plasma proteins are filtered across the glomerulus. Those that are filtered are actively reabsorbed across theThose that are filtered are actively reabsorbed across the proximal tubule. Because the GFR is so high, the filtration ofproximal tubule. Because the GFR is so high, the filtration of even a few molecules of plasma protein, such aseven a few molecules of plasma protein, such as albuminalbumin,, would result in a significant daily loss of protein ifwould result in a significant daily loss of protein if reabsorption did not occurreabsorption did not occur..  The few proteins filtered at the glomerulus are notThe few proteins filtered at the glomerulus are not reabsorbed. They are degraded by tubular cells and excretedreabsorbed. They are degraded by tubular cells and excreted in the urine.in the urine.  ExamplesExamples of these proteins include the protein hormones,of these proteins include the protein hormones, such as growth hormone and luteinizing hormone, both ofsuch as growth hormone and luteinizing hormone, both of which are secreted from the anterior pituitary.which are secreted from the anterior pituitary.
    24. 24.  30 mg% of albumins is a normal concentration in primary urine, in30 mg% of albumins is a normal concentration in primary urine, in secondary urine of proteins are absent, because albumins fullysecondary urine of proteins are absent, because albumins fully absorption in kidneyabsorption in kidney tubulestubules..  The presence of albumines in the second urine is calledThe presence of albumines in the second urine is called proteinuriaproteinuria.. Types of proteinuria:Types of proteinuria: 1) functional: a) alimentary, b) during march1) functional: a) alimentary, b) during march 2) organic: a) extrarenal and b) renal.2) organic: a) extrarenal and b) renal. a)a) ExtrarenalExtrarenal is observed at inflammatory processes in urinary tractsis observed at inflammatory processes in urinary tracts b)b) RenalRenal proteinuria arises up as a result:proteinuria arises up as a result:  - increasing permeability of glomerular filter (glomerular proteinuria).- increasing permeability of glomerular filter (glomerular proteinuria). Reasons are:Reasons are: a)a) acute and chronic glomerulonephritis),acute and chronic glomerulonephritis), b)b) infectious and toxic damages of kidneys,infectious and toxic damages of kidneys, c)c) heart failure;heart failure;  - decreasing of tubular- decreasing of tubular reabsorptionreabsorption of albumen (tubular proteinuria) –of albumen (tubular proteinuria) – nephrosis,tubulopathynephrosis,tubulopathy  - secretory proteinuria pathological entering of albumen from the- secretory proteinuria pathological entering of albumen from the damaged cells of tubular epithelium or from lymphatic liquiddamaged cells of tubular epithelium or from lymphatic liquid  ProteinuriaProteinuria can becan be  a) selective, when low-molecular proteins are determined in urine only, b)a) selective, when low-molecular proteins are determined in urine only, b) unselective, for which characteristic appearance in urine both low- andunselective, for which characteristic appearance in urine both low- and high-molecular proteins.high-molecular proteins.  The loss of albumen conducts to hypoproteinemia, decreasing of oncoticThe loss of albumen conducts to hypoproteinemia, decreasing of oncotic pressure and to development of edema.pressure and to development of edema.
    25. 25.  Violation ofViolation of reabsorptionreabsorption of water and concentration ability of kidneysof water and concentration ability of kidneys..  Specific gravity of primary urine is 1.010. It is equal to plasma of blood.Specific gravity of primary urine is 1.010. It is equal to plasma of blood. LossLoss of concentration abilityof concentration ability is calledis called hypostenuriahypostenuria, relative, relative density aqualdensity aqual inin state changes within the limit of 1,006-1,012 (normstate changes within the limit of 1,006-1,012 (normaa – 1,002-– 1,002- 1,035). If1,035). If density urinedensity urine is kept at 1,010is kept at 1,010 level and is not changedlevel and is not changed withwith influence water load, itinfluence water load, it is calledis called isostenuriaisostenuria (monotone(monotone diuresisdiuresis))  RReabsorptioneabsorption of water (obligatory) takes place in proximal convolutedof water (obligatory) takes place in proximal convoluted tubulestubules and descending part of loop of Henle (about 75-80% primary filtrates).and descending part of loop of Henle (about 75-80% primary filtrates). Hypertonic urine appears.Hypertonic urine appears.  In ascending part of loop of Henle of Na+ mainly resorb as result urine becomeIn ascending part of loop of Henle of Na+ mainly resorb as result urine become hypotonic. There is optionalhypotonic. There is optional reabsorptionreabsorption of water (depends on maintenance ofof water (depends on maintenance of water and Na+ in blood) in distal convolutedwater and Na+ in blood) in distal convoluted tubulestubules, so urine becomes, so urine becomes hypertonic again. This system of kydneys to excrete urine in 4 times morehypertonic again. This system of kydneys to excrete urine in 4 times more hypertonic and in 6 times hypotonic from plasma of blood.hypertonic and in 6 times hypotonic from plasma of blood.  Reasons of decreasing ofReasons of decreasing of reabsorptionreabsorption of water:of water:  -- violation of the hormonal regulationviolation of the hormonal regulation (decreasing of aldosterone and(decreasing of aldosterone and vasopressin, as result diabetes insipidus appears)vasopressin, as result diabetes insipidus appears)  -- insufficiency of aquapurins 1, 2, 3insufficiency of aquapurins 1, 2, 3 – the integrated membrane proteins, which– the integrated membrane proteins, which form the water channels,form the water channels,  -- denervation of kidneysdenervation of kidneys  - introduction to the organism of adrenoblockers- introduction to the organism of adrenoblockers  - inflammatory and dystrophic changes of epithelium of- inflammatory and dystrophic changes of epithelium of tubulestubules  - increase in primary urine- increase in primary urine of maintenance of matters which stipulate itsof maintenance of matters which stipulate its osmotic concentration (glucose, urea and other).osmotic concentration (glucose, urea and other).
    26. 26.  The inorganic phosphate and calcium disorder reabsorbtion have the hereditary character.  Renal phosphate diabetes is manifested with phosphaturia, calciuria, rachitis, resistance to vitamin D, canalicules sensitiviby to parathormone increase (pseudohyperparathyroidism).  Hereditary osteodystrophias are characterized with hypocalciemia, hypophosphatemia, parathormone canalicules resistance because of appropriate receptors absence (pseudohyperparathyroidism)
    27. 27.  Substances, which secreted by kidneys are: a) hydrogen ions (regulation of acid-base balance), b) urea, urinary acid, kreatine, creatinine, toxic matters, c) medicinal preparations (separate sulfanilamids and antibiotics), d) roentgen contrasting matters.  Principal reason of violation of tubular secretion is a damage of epithelium of tubules, especially, distal part which is observed at: a) toxic, metabolic and infectious influencing, b) at the action of physical factors (ionizing a radiation).  Violation of glomerular filtration, tubular reabsorption and tubular secretion is reason of origin of urinary syndrome – quantitative and high-quality changes of urine.  Disorder of theDisorder of the canaliculescanalicules functionfunction is called as tubulartubular insufficiencyinsufficiency  It can be hereditary orhereditary or acquiredacquired  The selective disorders reabsorption of separate ultrafiltrate components are convenient to separate considering Violation of tubular secretionViolation of tubular secretion
    28. 28. Combined tubulopathia.Combined tubulopathia.  TThe most known exahe most known exammple ofple of ssuchuch disorders isdisorders is thethe FankonyFankony syndrome.syndrome.  In basisIn basis ofof thisthis symptomocomplexsymptomocomplex lies kidneyslies kidneys canaliculescanalicules functionfunction generalizedgeneralized disorder.disorder.  ItIt includesincludes glucosuria, aminoaciduria,glucosuria, aminoaciduria, phosphaturia, hypercalciuria,hypernatriuria,phosphaturia, hypercalciuria,hypernatriuria, proteinuria, proximal renal canalicules acidosisproteinuria, proximal renal canalicules acidosis withwith bicarbonaturia, rachitis with resistantionbicarbonaturia, rachitis with resistantion toto vitamin D.vitamin D. Disoder of secretionDisoder of secretion  The main mThe main manifestationanifestation – c– canaliculus acidosisanaliculus acidosis;; amammmonium- and acidogenesisonium- and acidogenesis inhibitioninhibition andand secretion H+-ions lsecretion H+-ions lieiess it isit is basis.basis.  HHyperuricemia, which develops owing toyperuricemia, which develops owing to urinaryurinary acid secretionacid secretion disorderdisorder and lead toand lead to gout (renalgout (renal form).form).  KKidneys functionsidneys functions disordersdisorders of can be completedof can be completed withwith their insufficiencytheir insufficiency..
    29. 29. Changes of obligatory diuresisChanges of obligatory diuresis OliguriaOliguria is decreasing of diuresis below 700 (500) ml per day.is decreasing of diuresis below 700 (500) ml per day. AnuriaAnuria is complete absence of diuresis or lesser than 50 ml per day.is complete absence of diuresis or lesser than 50 ml per day. • Distinguish the followings types of oligo- and anuria:Distinguish the followings types of oligo- and anuria: • a)a) prerenalprerenal – at violation of blood supply of kidneys (shock, collapse,– at violation of blood supply of kidneys (shock, collapse, thrombosis of kidney arteries);thrombosis of kidney arteries); • b) renal - related to decreasing ofb) renal - related to decreasing of glomerularglomerular filtration and increasing offiltration and increasing of tubulartubular reabsorptionreabsorption of water and electrolytes (during the surplusof water and electrolytes (during the surplus selection of aldosterone and vasopressin);selection of aldosterone and vasopressin); • c)c) subrenalsubrenal is violation of outflow of urine (blocking urinary tracts by ais violation of outflow of urine (blocking urinary tracts by a stone, tumor);stone, tumor); • d)d) reflexive-renalreflexive-renal – at annoying the receptors of one kidney (for– at annoying the receptors of one kidney (for example by a stone), after renalexample by a stone), after renal--renal reflex there is a spasm of vesselsrenal reflex there is a spasm of vessels of the second kidney and a selection urine is halted;of the second kidney and a selection urine is halted; • e)e) reflexive-peripheralreflexive-peripheral – at annoying the of different receptors lead to– at annoying the of different receptors lead to spasm of kidney arteries (cold water and irritancies receptors of skin,spasm of kidney arteries (cold water and irritancies receptors of skin, annoying the pain receptors of abdominal region);annoying the pain receptors of abdominal region); • f)f) traumatictraumatic – arises up at a crush [compression, Bywaters'] syndrome,– arises up at a crush [compression, Bywaters'] syndrome, which conduces to the obstruction of filter of kidney by myoglobin;which conduces to the obstruction of filter of kidney by myoglobin; • g)g) hemolytichemolytic - arises up at massive hemolysis of erythrocytes, which- arises up at massive hemolysis of erythrocytes, which conduces to the obstruction of filter of kidney by hemoglobin.conduces to the obstruction of filter of kidney by hemoglobin.
    30. 30. Consequences of olyguria (anuria)Consequences of olyguria (anuria) are:are: a) increasing the volume of extracellular liquid – hyperhydrationhyperhydration; b) accumulating osmotic active matters in an organism – hypernatremia, hyperkalemiahypernatremia, hyperkalemia [hyperpotassemia]; c) accumulating of the ending products of metabolism in blood – azotemiaazotemia [uremia].
    31. 31. PoliuriaPoliuria is increase of diuresis more thanis increase of diuresis more than 1,8 (2,0) liters per day.1,8 (2,0) liters per day. In dependence on the mechanisms of developmentIn dependence on the mechanisms of development poliuriapoliuria select theselect the followings kinds:followings kinds: a)a) Aquatic diuresisAquatic diuresis conditioned by decreasing of facultativeconditioned by decreasing of facultative reabsorptionreabsorption of water. Arise up:of water. Arise up: - at the considerable aquatic loading (psychogenic polydipsia)- at the considerable aquatic loading (psychogenic polydipsia) - at diabetes insipidus (insufficiency of vasopressin)- at diabetes insipidus (insufficiency of vasopressin) At such polydipsia secreted approximately 15-18 l of urine. Urine isAt such polydipsia secreted approximately 15-18 l of urine. Urine is hypooncotic, because contains few osmotic active matters.hypooncotic, because contains few osmotic active matters. b)b) Osmotic diuresisOsmotic diuresis. Related to increasing maintenance in urine of. Related to increasing maintenance in urine of unresorpted osmotic active matters, that led to disorders ofunresorpted osmotic active matters, that led to disorders of reabsorption of water. Reasons:reabsorption of water. Reasons: - violation of- violation of reabsorptionreabsorption of electrolytes;of electrolytes; - multiplying maintenance in primary urine of the so-called thresholds- multiplying maintenance in primary urine of the so-called thresholds matters (glucose at diabetes mellitus, hydrogen carbonates atmatters (glucose at diabetes mellitus, hydrogen carbonates at alkalosis);alkalosis); - actions of exogenous matters which badly resorbed (mannitol) or- actions of exogenous matters which badly resorbed (mannitol) or violate reabsorption of electrolytes of Na+ and K+ (saluretic drugs).violate reabsorption of electrolytes of Na+ and K+ (saluretic drugs). In the conditions of maximal osmotic polyuria the selection of urineIn the conditions of maximal osmotic polyuria the selection of urine can achieve a 40% fromcan achieve a 40% from glomerularglomerular filtration (about 25 l per day).filtration (about 25 l per day).
    32. 32. Mechanisms of theMechanisms of the poliuriapoliuria development (cont)development (cont) c)c) Hypertensive diuresisHypertensive diuresis. Develops at arterial. Develops at arterial hypertension, when the rate of movement of blood ishypertension, when the rate of movement of blood is multiplied in the direct vessels of cerebral layer ofmultiplied in the direct vessels of cerebral layer of kidneys (these vessels go parallel the knees of loopkidneys (these vessels go parallel the knees of loop of Henle). The convection transport is multiplied.of Henle). The convection transport is multiplied. As result sodium, chlorine, urea is "washing" fromAs result sodium, chlorine, urea is "washing" from interstitial tissue. It conduces to diminishing ofinterstitial tissue. It conduces to diminishing of osmotic pressure of extracellular liquid, as a resultosmotic pressure of extracellular liquid, as a result reabsorptionreabsorption of water diminishes in descending partof water diminishes in descending part of loop of Henle andof loop of Henle and polyuriapolyuria develops.develops. d)d) Compensate diuresisCompensate diuresis. It related to increase of. It related to increase of concentration in blood of urea (at the initiallyconcentration in blood of urea (at the initially shrunken [pursy] kidney), which stimulates healthyshrunken [pursy] kidney), which stimulates healthy glomerulus and multiplies uropoiesis.glomerulus and multiplies uropoiesis.
    33. 33. NocturiaNocturia [nycturia] is a pathological sign,[nycturia] is a pathological sign, when nightly part of diuresis more then daily.when nightly part of diuresis more then daily.  In a norm 60-80% day's amount of urine selected in aIn a norm 60-80% day's amount of urine selected in a period from 8 to 20 hour, that correlation nightly diuresis toperiod from 8 to 20 hour, that correlation nightly diuresis to daily is 1:2.daily is 1:2.  In dependence on reasons select following types:In dependence on reasons select following types:  a)a) cardiac nycturiacardiac nycturia - develops at cardiac insufficiency. In the- develops at cardiac insufficiency. In the day-timeday-time in connection heart failurein connection heart failure edema developsedema develops. At. At nightnight in horizontal position a venous outflow is improvedin horizontal position a venous outflow is improved and loading on a heart decreasing. It causes the selectionand loading on a heart decreasing. It causes the selection of atrium hormone →of atrium hormone → increase diuresisincrease diuresis;;  b)b) kidney nycturiakidney nycturia - characteristic for the damaged kidneys.- characteristic for the damaged kidneys. It is explained by improvement of the broken kidney bloodIt is explained by improvement of the broken kidney blood stream at night. As a result motion of blood is acceleratedstream at night. As a result motion of blood is accelerated on the vessels of kidneys, hypertensive polyuria develops.on the vessels of kidneys, hypertensive polyuria develops.
    34. 34.  PolakyuriaPolakyuria is increasing of frequent of urinationis increasing of frequent of urination..  Specific gravity of urine equals 1.016 – 1.020 for a healthySpecific gravity of urine equals 1.016 – 1.020 for a healthy man at an ordinary diet.man at an ordinary diet. рНрН of urine equal 6,0.of urine equal 6,0.  HypersthenuriaHypersthenuria is increasing specific gravity of urine moreis increasing specific gravity of urine more than 1.028.than 1.028.  HyposthenuriaHyposthenuria is decreasing specific gravity of urine lesseris decreasing specific gravity of urine lesser then 1.012then 1.012  Combination ofCombination of hypostenuria with polyuriahypostenuria with polyuria testifies to thetestifies to the damage ofdamage of tubulestubules at relatively to the stored function ofat relatively to the stored function of glomerulusglomerulus. If hypostenuria arises up on a background. If hypostenuria arises up on a background olyguria, it is a sign of damage of all structures ofolyguria, it is a sign of damage of all structures of nephrones (glomerulus andnephrones (glomerulus and tubulestubules).).  At a complete loss by the kidneys of ability to concentrateAt a complete loss by the kidneys of ability to concentrate and conduct urineand conduct urine isohyposthenuriaisohyposthenuria develops. Itsdevelops. Its characterized by stability of specific gravity per day, but itcharacterized by stability of specific gravity per day, but it index equal primary filtrate (1.010).index equal primary filtrate (1.010).  IsosthenuriaIsosthenuria is the sign of heavy structurally functionalis the sign of heavy structurally functional violations of kidneys.violations of kidneys.
    35. 35. Thus, there are the followings high-Thus, there are the followings high- quality changes of urine at kidneyquality changes of urine at kidney insufficiency:insufficiency: • 1) Proteinuria is a selection of albumen with urine. • 2) Hematuria is appearance of erythrocytes in urine. Reasons: a) damage of glomerulus. The "lixiviated" erythrocytes are determined in urine; b) damage of urinary tracts. • 3) Hemoglobinuria is a presence of Hb in urine. • 4) Cylindruria is appearance in urine of cylinders. Cylinders show by itself molds of kidney tubules. They will appear at the damage of epithelium of tubules and consist of coagulative albumen and lost cells (leucocytes and epytheliocytes). In dependence on a structure distinguish hyaline, grainy [granular], cereous, lipoid, leukocyte and epitheliums cylinders. • 5) Lekocyteuria is appearance in urine of leucocytes over 5 in eyeshot. Pyuria is the state, when the amount of lekocytes in eyeshot is more than 100 cells. Principal reason of leukocyteuria is inflammatory processesprocesses in kidneys and urinary tracts. •6) Crystalluria in a surplus amount: a) crystals of urinary acid as yellow, b) oxalate, c) urates, d) phosphates, e) crystals of oxalic calcium, f) crystals of cystine crystals of tyrosine, g) crystals of cholesterol.
    36. 36. AzotemiaAzotemia  AzotemiaAzotemia refers to abnormal elevation of nitrogenous wasterefers to abnormal elevation of nitrogenous waste products in the blood such as urea, uric acid, and creatinine.products in the blood such as urea, uric acid, and creatinine.  Azotemia indicates a decrease in GFR, occurring either acutelyAzotemia indicates a decrease in GFR, occurring either acutely or with chronic renal failure.or with chronic renal failure.  Azotemia is an early sign of renal damage.Azotemia is an early sign of renal damage. UremiaUremia  UremiaUremia is not a single event, but rather a syndrome (ais not a single event, but rather a syndrome (a constellation of symptoms) that develops in an individual whoconstellation of symptoms) that develops in an individual who has end-stage renal disease. Because the kidney is pivotal inhas end-stage renal disease. Because the kidney is pivotal in maintaining water, acid-base, and electrolyte balance and inmaintaining water, acid-base, and electrolyte balance and in removing toxic waste products, the symptoms of uremia areremoving toxic waste products, the symptoms of uremia are widespread and affect all the organs and tissues of the body.widespread and affect all the organs and tissues of the body.  Common symptoms include fatigue, anorexia, nausea,Common symptoms include fatigue, anorexia, nausea, vomiting, and lethargy. Intractable itching (pruritus) may occur.vomiting, and lethargy. Intractable itching (pruritus) may occur. Hypertension, osteodystrophy, and uremic encephalopathyHypertension, osteodystrophy, and uremic encephalopathy develop as well, with central nervous system changes,develop as well, with central nervous system changes, including confusion and psychosis, characterizing end stages.including confusion and psychosis, characterizing end stages.  The range of symptoms appears to be caused by acidosis,The range of symptoms appears to be caused by acidosis, anemia from decreased erythropoietin, and the buildup of allanemia from decreased erythropoietin, and the buildup of all waste products.waste products.
    37. 37. AnasarcaAnasarca • Defined as a generalized edemageneralized edema in individuals suffering from hypoalbuminemia as a result of nephrotic syndrome or other conditions, anasarca is caused by a systemic decrease in capillary osmotic pressure. • With a decrease in this major force favoring reabsorption of interstitial fluid back into the capillaries, edema of the interstitial space throughout the body occurs. • The edema is usually soft and pitting and occurs early in the periorbital (surrounding the eye) regions, the ankles, and the feet.
    38. 38. EDEMAEDEMA
    39. 39. The Major Renal Syndromes:  Acute nephritic syndrome is a glomerular syndrome dominated by the acute onset of usually grossly visible hematuria (red blood cells in urine), mild to moderate proteinuria, azotemia, edema, and hypertension; it is the classic presentation of acute poststreptococcal glomerulonephritis.  The nephrotic syndrome is a glomerular syndrome characterized by heavy proteinuria (excretion of >3.5 gm of protein/day in adults), hypoalbuminemia, severe edema, hyperlipidemia, and lipiduria (lipid in the urine).  Asymptomatic hematuria or proteinuria, or a combination of these two, is usually a manifestation of subtle or mild glomerular abnormalities.  Rapidly progressive glomerulonephritis results in loss of renal function in a few days or weeks and is manifested by microscopic hematuria, dysmorphic red blood cells and red blood cell casts in the urine sediment, and mild-to-moderate proteinuria.
    40. 40. The Major Renal Syndromes:  Acute renal failure is dominated by oliguria or anuria (no urine flow), with recent onset of azotemia. It can result from glomerular injury (such as crescentic glomerulonephritis), interstitial injury, vascular injury (such as thrombotic microangiopathy), or acute tubular necrosis.  Chronic renal failure, characterized by prolonged symptoms and signs of uremia, is the end result of all chronic renal diseases.  Urinary tract infection is characterized by bacteriuria and pyuria (bacteria and leukocytes in the urine). The infection may be symptomatic or asymptomatic, and it may affect the kidney (pyelonephritis) or the bladder (cystitis) only.  Nephrolithiasis (renal stones) is manifested by renal colic, hematuria, and recurrent stone formation.
    41. 41. Acute renal insufficiencyAcute renal insufficiency (ARI)(ARI) It is a clinical syndromeIt is a clinical syndrome ofof various ethiologyvarious ethiology ((ARIARI)), which, which isis characterized by significant andcharacterized by significant and acuteacute decrease ofdecrease of glomerulglomerular filtration speedar filtration speed ((GFSGFS))  NormalNormal GFGFSS significancesignificance –– 100-140 ml/mines100-140 ml/mines  Acute renalAcute renal insufficiencyinsufficiency develops, whendevelops, when GFGFSS is reducedis reduced toto 1-10 ml/mines1-10 ml/mines  Osmotic activeOsmotic active substancessubstances amountamount isis derivatedderivated which iswhich is easily excrete ineasily excrete in volumevolume water ofwater of 1,5-2 l (daily diuresis1,5-2 l (daily diuresis)) for one day with, thefor one day with, the normal diet and normal metabolismnormal diet and normal metabolism out ofout of organismorganism  The minimum quantityThe minimum quantity ofof liquid, from which they can stillliquid, from which they can still be excretedbe excreted makesmakes 500 ml500 ml  AAcutecute renalrenal insufficiencyinsufficiency isis characterizedcharacterized byby suchsuch disorderdisorder renalrenal functionsfunctions whenwhen diuresisdiuresis is reduced tois reduced to 500500 mlml.. This stateThis state is called asis called as oliguriaoliguria  If dailyIf daily urineurine does not exceeddoes not exceed 100 ml,100 ml, takes placetakes place anuriaanuria
    42. 42. • The acute renal insufficiency reasons are divided into three groups – prerenal, renal and postrenal • Prerenal factors include: circulating liquid decrease (traumatic shock, blood loss, burns, vomiting, diarrhea), dilatation of vessels and vessels capacity increase (sepsis, anaphylaxia), heart insufficiency (infarction of myocardium)
    43. 43. • Renal factors include:Renal factors include: - ischemia kidneys, - action nephrotoxical (antibiotics, heavy metals, organic solvents, X-ray contrast substances), - intravessels erythrocytes hemolysis, - glomerulonephritis, - states assosiated to pregnancy (septic abortion, eclampsia in pregnant, bleeding)
    44. 44.  PostrenalPostrenal factors include:factors include:  UUretersreters oobstruction uretersbstruction ureters (canaliculus(canaliculus,, bloodblood clots, tumor)clots, tumor) and urinal channeland urinal channel obstruction (prostat hypertrophy, carcinoma)obstruction (prostat hypertrophy, carcinoma)..  Postrenal reasonPostrenal reasonss of diuresisof diuresis decreasedecrease are reducedare reduced ofof urineurine outflowoutflow due todue to obstacleobstacle any levelany level ofof urinaryurinary wayway..  Pathophysiological mechanismsPathophysiological mechanisms, which, which act inact in acute renalacute renal insufficiencyinsufficiency are caused moreare caused more complicatedcomplicated and can not beand can not be put into commonput into common universal mechanism.universal mechanism.
    45. 45.  There areThere are four clinical phasesfour clinical phases of ARI.of ARI.  Initial phaseInitial phase – is a– is a periodperiod, which courses from, which courses from lesion oflesion of kidneyskidneys untilluntill oliguria development.oliguria development. It takesIt takes several hours (ischemia)several hours (ischemia) up to aboutup to about oneone week (afterweek (after actionaction nephrotoxine)nephrotoxine)  Oliguric phaseOliguric phase is characterized by acuteis characterized by acute decrease of GFS. Itdecrease of GFS. It course lastcourse last several daysseveral days up toup to several weeks (two weeksseveral weeks (two weeks inin average).average). The patientsThe patients perishperish just in this phasejust in this phase  Diuretic phaseDiuretic phase is characterized by gradualis characterized by gradual increase ofincrease of urine volumeurine volume.. Phase of recoveryPhase of recovery –– period, during which renal function completelyperiod, during which renal function completely are restored, though easyare restored, though easy oror moderatemoderate GFSGFS decreasedecrease can be savedcan be saved inin some patientssome patients  AAcutecute renal insufficiencyrenal insufficiency isis accompanied byaccompanied by highhigh deathdeath, data, data ischemic and traumaticischemic and traumatic formform aboutabout 50-70 %50-70 % other formother form – about– about 10-35 %10-35 %
    46. 46. Renal medullary hypoxia Renal arteriolar vasoconstriction Delivery of sodium to macula densa Ischemia-induced cytoskeletal rearrangement in renal tubular cells Loss of polarity, integration redistribution, and loss of adhesion in renal tubular cells Sloughing of viable renal tubular cells Inappropriate adhesion and Obstruction of renal tubules Futher tubular damage Acute renal failure Complicating factors (NSAIDs, mioglobin Precipitation, Bence Jones proteins, hypovolemia, sepsis Irreversible renal failureRenal tubular regulation IGF-1 and other protective factors Release of prostaglandins, adenosine, nitric oxide Transport in medullary thick ascending limb of renal tubules Medullary blood flow  Renal function Medullary oxygen sufficiency
    47. 47. ChronicChronicalal renal insufficiency (renal insufficiency (CRICRI)) Symptoms chronical renal insufficiency develops in case GFS 25 % over norm  The main reasons:The main reasons:  primary glomerulus diseases (chronic glomerulonephritis)  the primary canaliculus diseases (chronic pielonephritis tuberculosis)  vascular diseases (hypertonic illness, thrombosis, embolism)  diffuse connective tissue diseases (sclerodermia, nodular periarteriitis)  illness metabolism (gout, diabetes mellitus),  obstructive nephropathia (urolithiasis, hydronephrosis),  hereditary anomalies (kidneys polycystic)
    48. 48. Renal functions decrease occurs due to decrease of functiononal amount of active nephrons • The initial chronical renal insufficincy signs occur owing to mass of acting nephrons decrease to 50-30%50-30% • The expressed clinic develops due to acting nephrons decrease down to 30-10%30-10% • Further acting nephrons weight decrease (is lower than 10%lower than 10%)) results in terminal kidneys insufficiency stage – uremiauremia
    49. 49. • Chronic renal failure: 4 stages • I) ↓ renal reserve: GFR ~ 50% normal BUN & creatinine normal, pt. asymptomatic, more susceptible to develop azotemia • II) renal insufficiency: GFR 20-50% of normal, azotemia, anemia, ↑ BP, polyuria/nocturia (via ↓ concentrating ability) • III) renal failure: GFR less than 20- 25% kidneys cannot regulate volume, ions: edema, hypocalcemia, metabolic acidosis, uremia with neurological, CV and GI complications • IV) end stage renal disease: GFR < 5% of normal, terminal stage of uremia
    50. 50.  Anemia – is obviously the most characteristic sign of chronical renal insufficiency.  The main factor, which cause it is development is lowering of erythropoitin. It’s also important that degree hemolys is increased, which shortens erythrocytes life duration.  Uremia, besides oppress bone marrow ability to erythropoietin reaction, and because even due to it enough amount bone marrow response is not adequate.  The chronical renal insufficiency in patient an alimentary channel bleeding is anusual state. Continuous loss blood result in deficiency iron, which promotes anemia development.  Chronical renal insufficiency in the patients have a qualitative changes of thrombocytes (thrombocylopathy). It appears as bleeding duration increase. Thrombocytes function gets oppressed with guanidinic and oxyphenilacetic acids.
    51. 51. HeartHeart is damaged owing to hypertension. The combinationis damaged owing to hypertension. The combination of hypertension, anemia,of hypertension, anemia, liquidliquid overloadingoverloading and acidosisand acidosis promotespromotes heartheart insufficiencyinsufficiency development.development. IInn half ofhalf of patients chronical renal terminal insufficiencypatients chronical renal terminal insufficiency stagestage pericarditis developspericarditis develops TheThe lunglung damagedamage is performedis performed with so-called uremicwith so-called uremic pneumonitis, whichpneumonitis, which isis the stagnant phenomen in vessels ofthe stagnant phenomen in vessels of peritrachealperitracheal Arterial hypertensionArterial hypertension is observed in 50% ofis observed in 50% of terminalterminal chronicalchronical renalrenal insufficiency stage.insufficiency stage. It arises is connected toIt arises is connected to hyperproduction reninehyperproduction renine vasodilatative prostaglandinsvasodilatative prostaglandins,, oppression limitationoppression limitation sodiumsodium excretionexcretion ofof extracellularextracellular liquidliquid volumevolume increaseincrease Gastrointestinal disorderGastrointestinal disorder – anorexia– anorexia, nausea, vomitis. The, nausea, vomitis. The bleeding from alimentbleeding from alimentaary cry chhannelannel isis oftenoften phenomenon.phenomenon.TheirTheir sourcesource are the smallare the small surfacesurface ulcers,ulcers, which bleedwhich bleedinging slowlyslowly
    52. 52. OsteodistrophyOsteodistrophy, which arises according to mentioned above changes, includes such disorders: а) ffibrosis-cystosesibrosis-cystoses osteitis as result of secondary hyperparathyreosis; it appears subperiosteol bone resorbtion; b) oosteomalationsteomalation – bones defeat which organic matrix mineralisation process mineralisation infringed; c) oosteosclerosissteosclerosis – bone density increase; d) oosteoporosissteoporosis – bone weight decrease and microstructural, which increase bone fragility.
    53. 53.  Uremic encephalopathyUremic encephalopathy appearsappears withwith sleepiness, inability to concentrationsleepiness, inability to concentration,, absent-absent- mindness, and thenmindness, and then – amnesia– amnesia, hallutinations,, hallutinations, delirium,delirium, crampscramps  These bones change are capable to renderThese bones change are capable to render destructivedestructive actionaction on organismon organism  DelayDelay growthgrowth in childrenin children inin adultadult bonesbones delaydelay pain fractures, compression vertexpain fractures, compression vertex os femorisos femoris head, necrosis anhead, necrosis andd skskeeleton deformationleton deformation  Arterial medial layerArterial medial layer calcificationcalcification can becan be observedobserved withwith ischemicischemic necrosisnecrosis soft tissue skinsoft tissue skin calcification with intolerable itch, periarteriitiscalcification with intolerable itch, periarteriitis owing toowing to calciumcalcium oxyapatitis precipitation,oxyapatitis precipitation, calcificationcalcification
    54. 54. UremiaUremia  UremiaUremia is ais a term, which is usedterm, which is used for chronicalfor chronical renal insufficiency terminal phaserenal insufficiency terminal phase descriptiondescription. The majority of symptoms. The majority of symptoms become well expressedbecome well expressed in GFS ratio belowin GFS ratio below thanthan 1010 ml/min.ml/min.  UUremic syndromeremic syndrome pathogenesis has becomepathogenesis has become subject of intensive learningsubject of intensive learning for a long timefor a long time.. The numerous attempts were made toThe numerous attempts were made to identify substances, which are accumulatedidentify substances, which are accumulated inin renal insufficiency terminal phase andrenal insufficiency terminal phase and reach dangerous to the vital function data.reach dangerous to the vital function data.
    55. 55. DISORDERS OF GLOMERULARDISORDERS OF GLOMERULAR FUNCTIONFUNCTION
    56. 56. Two main mechanisms of damage of the glomeruli.Two main mechanisms of damage of the glomeruli.  1.1. Affection of the basal membrane of theAffection of the basal membrane of the glomeruli of the nephrons by antibodies itsglomeruli of the nephrons by antibodies its antigens - nephrotoxic glomerulonephritis (itantigens - nephrotoxic glomerulonephritis (it has a quick progressive course). Glycoproteinhas a quick progressive course). Glycoprotein as a carrier of antigenic proteins of the basalas a carrier of antigenic proteins of the basal membrane.membrane.  2.2. Development of the inflammatory process inDevelopment of the inflammatory process in the glomeruli due to fixation of the immunethe glomeruli due to fixation of the immune complexes on the basal membranecomplexes on the basal membrane -immunocomplex glomerulonephritis.-immunocomplex glomerulonephritis.
    57. 57. Disorders resulting in glomerular disease,Disorders resulting in glomerular disease, whether manifestations of systemic injurywhether manifestations of systemic injury or otherwise, fall into five categories:or otherwise, fall into five categories: • 1.      Acute glomerulonephritis, in which there is an abrupt onset of hematuria  and proteinuria with reduced GFR and renal salt and water retention, sometimes  followed by recovery of renal function. Patients with acute glomerulonephritis are  a subset of those with an intrarenal cause of acute kidney injury. • 2.      Rapidly progressive glomerulonephritis, in which recovery from the  acute disorder does not occur. Worsening renal function results in irreversible and  complete renal failure over weeks to months. Early in the course of rapidly  progressive glomerulonephritis, these patients can be categorized as having a  form of acute kidney injury. Later, with progression of their renal failure over time,  they display all of the features described for chronic renal failure. • 3.      Chronic glomerulonephritis, in which renal impairment after acute  glomerulonephritis progresses slowly over a period of years and eventually  results in chronic renal failure. • 4.      Nephrotic syndrome, manifested as marked proteinuria, particularly  albuminuria (defined as 24-hour urine protein excretion > 3.5 g),  hypoalbuminemia, edema, hyperlipidemia, and fat bodies in the urine. Nephrotic  syndrome may be either isolated (eg, minimal change disease) or part of some  other glomerular syndrome (eg, with hematuria and casts). • 5.      Asymptomatic urinary abnormalities, including hematuria and proteinuria  (usually in amounts below that seen in nephrotic syndrome) but no functional  abnormalities associated with reduced GFR, edema, or hypertension. Many  patients with these findings will develop chronic renal failure slowly over decades.
    58. 58. PATHOGENESIS • Antibodies against inherent GBM • Antibodies against “planted” antigens • Trapping of Ag-Ab complexes • Antibodies against glomerular cells, e.g., mesangial cells, podocytes, etc. • Cell mediated immunity, i.e., sensitized T- cells as in TB
    59. 59. Pathogenesis of GlomerularPathogenesis of Glomerular Disease/InjuryDisease/Injury • Little is known regarding etiology orLittle is known regarding etiology or triggeringtriggering • Immune mechanisms underlie mostImmune mechanisms underlie most cases of primary GN and many of thecases of primary GN and many of the secondary casessecondary cases a) 2 forms of Ab-associated injury I) injury resulting from soluble Ag-Ab deposits in glomerulus II) injury from Ab reacting in-situ with glomerulus - insoluble fixed glomerular Ag - molecules planted w/in
    60. 60. IgA NEPHROPATHYIgA NEPHROPATHY (BERGER DISEASE)(BERGER DISEASE)  Mild hematuriaMild hematuria  Mild proteinuriaMild proteinuria  IgA deposits in mesangiumIgA deposits in mesangium
    61. 61. HEREDITARY HEMATURIAHEREDITARY HEMATURIA SYNDROMESSYNDROMES • ALPORT SYNDROMEALPORT SYNDROME – Progressive Renal FailureProgressive Renal Failure – Nerve DeafnessNerve Deafness – VARIOUS eye disorderVARIOUS eye disorder – DEFECTIVE COLLAGEN TYPE IVDEFECTIVE COLLAGEN TYPE IV • THIN GBM (Glomerular Basement Membrane)THIN GBM (Glomerular Basement Membrane) Disease, i.e., about HALF as uniformly thin as itDisease, i.e., about HALF as uniformly thin as it should beshould be
    62. 62. The Nephrotic SyndromeThe Nephrotic Syndrome  The The nephrotic syndromenephrotic syndrome is characterized by proteinuria, which results in  is characterized by proteinuria, which results in  hypoalbuminemia and edema.Podocyte injury is an underlying mechanism hypoalbuminemia and edema.Podocyte injury is an underlying mechanism  of proteinuria, and may be the result of nonimmune causes (as in MCD and of proteinuria, and may be the result of nonimmune causes (as in MCD and  FSGS) or immune mechanisms (as in MN).FSGS) or immune mechanisms (as in MN).  MMnimal change disease (MCD)nimal change disease (MCD) is the most frequent cause of nephrotic  is the most frequent cause of nephrotic  syndrome in children; syndrome in children;    -  -  it is manifested by proteinuria and effacement of glomerular foot processes it is manifested by proteinuria and effacement of glomerular foot processes  without antibody deposits; without antibody deposits;    -   -   the pathogenesis is unknown; the disease responds well to steroid therapy.the pathogenesis is unknown; the disease responds well to steroid therapy.  Focal and segmental glomerulosclerosis (FSGS)Focal and segmental glomerulosclerosis (FSGS) may be primary (podocyte  may be primary (podocyte  injury by unknown mechanisms) or secondary (e.g. as a consequence of injury by unknown mechanisms) or secondary (e.g. as a consequence of  prior glomerulonephritis, hypertension or infection such as HIV); prior glomerulonephritis, hypertension or infection such as HIV);    -  -  glomeruli show focal obliteration of capillary lumens, hyaline deposits and glomeruli show focal obliteration of capillary lumens, hyaline deposits and  loss of foot processes; loss of foot processes;    -  -  the disease is often resistant to therapy and may progress to end stage renal the disease is often resistant to therapy and may progress to end stage renal  diseasedisease  Membranous nephropathy (MN)Membranous nephropathy (MN) is caused by an autoimmune response  is caused by an autoimmune response  against an unknown renal antigen; against an unknown renal antigen;    -   -   it is characterized by granular subepithelial deposits of antibodies with GBM it is characterized by granular subepithelial deposits of antibodies with GBM  thickening and loss of foot processes but little or no inflammation; thickening and loss of foot processes but little or no inflammation;    -   t-   the disease is often resistant to steroid therapy. he disease is often resistant to steroid therapy. 
    63. 63. The Nephritic SyndromeThe Nephritic Syndrome  The The nephritic syndromenephritic syndrome is characterized by hematuria, oliguria with  is characterized by hematuria, oliguria with  azotemia, proteinuria, and hypertension.azotemia, proteinuria, and hypertension.  The most common causes are immunologically mediated glomerular injury; The most common causes are immunologically mediated glomerular injury;    -   -   lesions are characterized by proliferative changes and leukocyte infiltration.lesions are characterized by proliferative changes and leukocyte infiltration.  Acute post-infectious glomerulonephritisAcute post-infectious glomerulonephritis typically occurs after streptococcal  typically occurs after streptococcal  infection in children and young adults but may occur following infection with infection in children and young adults but may occur following infection with  many other organisms; many other organisms;    -   -   it is caused by deposition of immune complexes mainly in the subepithelial it is caused by deposition of immune complexes mainly in the subepithelial  spaces, with abundant neutrophils and proliferation of glomerular cells. spaces, with abundant neutrophils and proliferation of glomerular cells.   Most affected children recover; the prognosis is worse in adults.Most affected children recover; the prognosis is worse in adults.  IgA nephropathyIgA nephropathy,, characterized by mesangial deposits of IgA-containing  characterized by mesangial deposits of IgA-containing  immune complexes, is the most common cause of the nephritic syndrome immune complexes, is the most common cause of the nephritic syndrome  worldwide; worldwide;    -    -    it is also a common cause of recurrent hematuria; it is also a common cause of recurrent hematuria;    -    -    it commonly affects children and young adults and has a variable course.it commonly affects children and young adults and has a variable course.  Hereditary nephritisHereditary nephritis is caused by mutations in genes encoding GBM  is caused by mutations in genes encoding GBM  collagen; collagen;  - it manifests as hematuria and slowly progressing poteinuria and declining it manifests as hematuria and slowly progressing poteinuria and declining  renal function; renal function;  -   glomeruli appear normal until late in the disease course. glomeruli appear normal until late in the disease course. 
    64. 64. OBSTRUCTIVE DISORDERSOBSTRUCTIVE DISORDERS Level of Obstruction Cause Renal pelvis Renal calculi Papillary necrosis Ureter • Renal calculi • Pregnancy • Tumors that compress the ureter • Ureteral stricture • Congenital disorders of the ureterovesical junction and ureteropelvic junction strictures Bladder and urethra • Bladder cancer • Neurogenic bladder • Bladder stones • Prostatic hyperplasia or cancer • Urethral strictures • Congenital urethral defects
    65. 65. Composition, Contributing Factors, andComposition, Contributing Factors, and Treatment of Kidney StonesTreatment of Kidney Stones Type of Stone Contributing Factors Treatment Calcium (oxalate and phosphate) Hypercalcemia and hypercalciuria Immobilization Treatment of underlying conditions Increased fluid intake Thiazide diuretics Magnesium ammonium phosphate (struvite) Hyperparathyroidism Vitamin D intoxication Diffuse bone disease Milk-alkali syndrome Renal tubular acidosis Hyperoxaluria Intestinal bypass surgery Dietary restriction of foods high in oxalate Uric acid (urate) Urea-splitting urinary tract infections Treatment of urinary tract infection Acidification of the urine Increased fluid intake Cystine Formed in acid urine with pH of approximately 5.5 Gout High-purine diet Cystinuria (inherited disorder of amino acid metabolism) Increased fluid intake Allopurinol for hyperuricuria Alkalinization of urine Increased fluid intake Alkalinization of urine
    66. 66. Staghorn calculi. The kidney shows hydronephrosis and stonesStaghorn calculi. The kidney shows hydronephrosis and stones that are casts of the dilated calyces.that are casts of the dilated calyces. (Rubin E., Farber J.L.(Rubin E., Farber J.L. [1999].[1999]. PathologyPathology [3rd ed., p. 909]. Philadelphia: Lippincott[3rd ed., p. 909]. Philadelphia: Lippincott Williams & Wilkins)Williams & Wilkins) Hydronephrosis. Bilateral urinary tract obstruction has led to conspicuous dilatation of the ureters, pelves, and calyces. The kidney on the right shows severe cortical atrophy. (Rubin E., Farber J.L. [1999]. Pathology [3rd ed., p. 910]. PhilaIndelphia: Lippincott Williams & Wilkins)
    67. 67. TransplantationTransplantation Transplant tourismTransplant tourism The Geneva-basedThe Geneva-based WHO believes thatWHO believes that "transplant tourism" is"transplant tourism" is rising, as rich patientsrising, as rich patients bypassed bans onbypassed bans on buying organs at homebuying organs at home by travelling abroad toby travelling abroad to receive kidneys fromreceive kidneys from poor donors.poor donors. Beside kidneys alsoBeside kidneys also trafficking of half-trafficking of half- livers, eyes, skin andlivers, eyes, skin and blood is flourishing.blood is flourishing. ((More e.g.More e.g. UPIUPIJan 12thJan 12th 20092009))
    68. 68. Literature:Literature: 1.1. Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead,  Jacquelyn L. Banasik // Elsevier Inc, 4th edition. – 2010. – P. 630–Jacquelyn L. Banasik // Elsevier Inc, 4th edition. – 2010. – P. 630– 719. 719.  2.2. Pathophysiology, Concepts of Altered Health States, Carol Mattson Pathophysiology, Concepts of Altered Health States, Carol Mattson  Porth, Glenn Matfin. – New York, Milwaukee. – 2009. – P. 826–893, Porth, Glenn Matfin. – New York, Milwaukee. – 2009. – P. 826–893,  949–974.949–974. 3.3. General and clinical pathophysiology / Edited by Anatoliy V. General and clinical pathophysiology / Edited by Anatoliy V.  Kubyshkin – Vinnytsia: Nova Knuha Publishers – 2011. – P. Kubyshkin – Vinnytsia: Nova Knuha Publishers – 2011. – P. 566566–– 558888.. 4.4. Robbins and Cotran Pathologic Basis of Disease Robbins and Cotran Pathologic Basis of Disease 88th edition./ th edition./  Kumar, Abbas, FautoKumar, Abbas, Fauto. –. – 200 20077.. – Chapter 14. – P. 541 – Chapter 14. – P. 541––579.579. 5.5. Russell JRussell J.. Greene Greene.. Pathology and Therapeutics for Pharmacists. A  Pathology and Therapeutics for Pharmacists. A  basis for clinical pharmacy practicebasis for clinical pharmacy practice / / Russell J Russell J.. Greene, Norman D Greene, Norman D..   Harris // Published by the Pharmaceutical Press An imprint of RPS Harris // Published by the Pharmaceutical Press An imprint of RPS  Publishing 1 Lambeth High Street, London SE1 7JN, UK 100 South Publishing 1 Lambeth High Street, London SE1 7JN, UK 100 South  Atkinson Road, Suite 200, Greyslake, IL 60030-7820, Atkinson Road, Suite 200, Greyslake, IL 60030-7820, 3rd edition, 3rd edition,  USAUSA. – 2008. – Chapter 14. – P. 869–941.. – 2008. – Chapter 14. – P. 869–941. 6.6. Essentials of Pathophysiology: Concepts of Altered Health States Essentials of Pathophysiology: Concepts of Altered Health States  (Lippincott Williams & Wilkins), Trade paperback (2003) (Lippincott Williams & Wilkins), Trade paperback (2003) // Carol Carol  Mattson Porth, Kathryn J. GaspardMattson Porth, Kathryn J. Gaspard. . – – ССhaptershapters 2 222-25. – -25. – PP. 4. 40101–– 457. 457.  7.7. Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS  medicine Publishing. – 2010. – P. 459–480.medicine Publishing. – 2010. – P. 459–480. 8.8. Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang  // Thieme. Stuttgart. New York. – 2000. – P. 92–1// Thieme. Stuttgart. New York. – 2000. – P. 92–13434.. 9.9. Corwin Elizabeth J. Handbook of Pathophysiology / Corwin Corwin Elizabeth J. Handbook of Pathophysiology / Corwin  Elizabeth J. – 3th edition. Copyright ВElizabeth J. – 3th edition. Copyright В. . – Lippincott Williams & – Lippincott Williams &  Wilkins – 2008. – Wilkins – 2008. – Chapter 18. – P. 604 – 633.Chapter 18. – P. 604 – 633.

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