Pathophisiology of Pathophisiology of kidneys. kidneys.

Renal insufficiency.Renal insufficiency.

M.D., PhDM.D., PhD, Associate Professor, Associate Professor Marta R. Gerasymchuk, Marta R. Gerasymchuk,

Pathophysiology DepartmentPathophysiology DepartmentIvano-Frankivsk National Ivano-Frankivsk National

Medical UniversityMedical University

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, reasons.Insufficiency of kidneys: definition, classification, reasons.3.3. Violation of glomerulus filtration: reasons and Violation of glomerulus filtration: reasons and

mechanisms. Changes of obligate diuresis: kinds, reasons mechanisms. 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 of reasons, consequences. Nycturia: kinds, mechanisms of development.development.

4.4. Violation of processes of reabsorbtion in tubulus. Violation Violation of processes of reabsorbtion in tubulus. Violation of tubular secretion.of tubular secretion.

5.5. Pathological components of urine. Functional tests of Pathological 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 of pathogenesis, 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.

Content Content

Actuality of the themeActuality of the theme

Kidneys play important role in regulation of constancy of internal Kidneys play important role in regulation of constancy of internal environment. Most functions of kidneys related to the processes of environment. Most functions of kidneys related to the processes of uropoiesis uropoiesis and urination. Due to these processes kidneys take part in and urination. Due to these processes kidneys take part in support of water-electrolyte and acid-base balances. The excretion support of water-electrolyte and acid-base balances. The excretion function of kidneys provides the release of organism from the finished function 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 of Violation of uropoiesis and urination is accompanied by violation of vital functions uropoiesis and urination is accompanied by violation of vital functions of organism.of organism.

The renal failure depend to severe pathological states. The disorder of The 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, which often demand emergency treatment. To the most often causes, which one cause disturbance of functions of kidney, the disorder of their one 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 and of urine concern. Knowledge of etiology and pathogenesis of kidney diseases, mechanisms of disturbance, which pathogenesis of kidney diseases, mechanisms of disturbance, which one arise in renal failure, are necassary for selection pathogenetic one arise in renal failure, are necassary for selection pathogenetic based methods of preventive maintenance and treatment.based methods of preventive maintenance and treatment.

Functions of the kidneyFunctions of the kidney

EliminationEliminationof waste/surplusof waste/surplus

Carbohydrate-derived Carbohydrate-derived NitrogenousNitrogenousOther Other

Water, acidWater, acidUrea creatinine, uric acid, Urea creatinine, uric acid,

guanidine, amines, etcguanidine, amines, etcSulphate, phosphate, Sulphate, phosphate,

exogenous toxins, etc.exogenous toxins, etc.

Regulation Regulation of fluid and of fluid and

electrolyte electrolyte balancebalance

Total body waterTotal body waterPlasma osmotic pressure, pHPlasma osmotic pressure, pHNa, K, Ca, Mg, etc.Na, K, Ca, Mg, etc.Chloride, bicarbonate, Chloride, bicarbonate,

phosphate, etc.phosphate, etc.

Endocrine Endocrine homeostasishomeostasis

Blood pressureBlood pressureCalcium and bone metabolismCalcium and bone metabolismRBC productionRBC production

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+ excretionNa+ reabsorptionNa+ reabsorptionHH22O excretionO excretion

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

Kidney Kidney is major is major organorgan, which determine , which determine outcell liquid of an organism outcell liquid of an organism persistance and regulates structure persistance and regulates structure surroundy cells environmentalsurroundy cells environmental

The kidney prevent internal changes The kidney prevent internal changes and provide maintenance such main and provide maintenance such main homeostasis parametershomeostasis parameters as: as:

iisovolemia sovolemia – blood volume constancy – blood volume constancy isotonia isotonia – osmotic pressure – osmotic pressure

constancy constancy isoionia isoionia – ionic structure constancy – ionic structure constancy isohydriaisohydria – concentration hydrogen – concentration hydrogen

ions constancyions constancy

Homeostasis maintenance includes three processesthree processes:

plasma filtering by glomerulus selective canalicules reabsorbtionreabsorbtion ions of hydrogen secretionsecretionammonium and other substances secretion

Structural and functional unit of a kidneyunit of a kidney, which provides these functions is nephronnephron

NEPHRONNEPHRON

Disorders of the Disorders of the excretoryexcretory functions of kidneys lead to:functions of kidneys lead to:

1) violation of 1) violation of water homeostasiswater homeostasis. It is changes of . It is changes of volume of extracellular liquid (volume of extracellular liquid (hyperhyper-- and and hypohydriahypohydria););

2) violation of 2) violation of osmotic homeostasisosmotic homeostasis - - hyperhyper-- and and hypoosmiahypoosmia;;

3) violation of balance of 3) violation of balance of electrolyteselectrolytes in a in a extracellular liquid (extracellular liquid (dysioniadysionia););

4) violation of 4) violation of acid-base balanceacid-base balance (more frequent in (more frequent in all is nongaseous acidosis);all is nongaseous acidosis);

5) violation of chemical composition of plasma of 5) violation of chemical composition of plasma of blood which shows up, from one side, piling up of blood which shows up, from one side, piling up of the finished goods of metabolism (azotemia the finished goods of metabolism (azotemia [uremia]), from other, - by the loss of necessary to [uremia]), from other, - by the loss of necessary to the organism of organic compounds the organism of organic compounds ((hypoproteinemia, hypoaminoemia, hypoglycemiahypoproteinemia, hypoaminoemia, hypoglycemia).).

Disorders of incretory functions of Disorders 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 and production of erythropoietins and inhibitors of erythropoiesisinhibitors of erythropoiesis;;3) transformation of vitamin D to hormonal 3) transformation of vitamin D to hormonal of active form.of active form.

Disorders of incretory function of Disorders of incretory function of kidneys can stipulate development: kidneys can stipulate development: 1) arterial hypertension; 1) arterial hypertension; 2) anemias; 2) anemias; 3) kidney osteodysrtrophy - violation of 3) kidney osteodysrtrophy - violation of phosphoric-calcium metabolism.phosphoric-calcium metabolism.

Intensity of kidney blood stream (Intensity of kidney blood stream (QQ) in ) in a norm is ever-higher: about a norm is ever-higher: about 1100 1100 ml/minml/min, or to a 25% volume of blood , or to a 25% volume of blood which is pumped over for a minute by which is pumped over for a minute by a heart in a state of rest It is calculated a 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

where where QQ is volume speed of is volume speed of kidney blood stream; kidney blood stream; PaPa is pressure at the beginning; is pressure at the beginning; Pv Pv - 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.

After that formula diminishing of After that formula diminishing of intensity of kidney blood stream it can intensity of kidney blood stream it can

be conditioned by:be conditioned by:► 1) 1) diminishing of arterial pressure (Pa)diminishing of arterial pressure (Pa) below 80 mmHg below 80 mmHg

(the mechanism of myogenic autoregulation don’ (the mechanism of myogenic autoregulation don’ work). 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 Reason of it can

be: a) general violations (right ventricle insufficiency of be: a) general violations (right ventricle insufficiency of heart which results in multiplying central and heart which results in multiplying central and peripheral venous pressure), peripheral venous pressure),

b) b) local disorderslocal disorders (venous hyperemia, for ex. as result (venous hyperemia, for ex. as result of inflammation of kidney tissue); r4of inflammation 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 kidneys is at atherosclerosis and arterial hypertension);hypertension);

► 4) 4) multiplying viscidity of bloodmultiplying viscidity of blood (η) (η) (at a disseminate (at a disseminate blood clotting). blood clotting).

► All noted violations lead to diminishing of filtration All noted violations lead to diminishing of filtration pressure in kidney glomerulus, that shows up pressure in kidney glomerulus, that shows up diminishing of speed of filtration and, consequently, by diminishing of speed of filtration and, consequently, by the signs of insufficiency of kidneys.the signs of insufficiency of kidneys.

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.

Filtration Filtration disorderdisorder

GlomerulesGlomerules filt filtration ration processprocess is possible to is possible to consider asconsider as water and moleculeswater and molecules pushing pushing through through sieve under infuence of arterialsieve under infuence of arterial pressure in a pressure in a remote capillaryremote capillaryThis 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 Filtrational Filtrational pressurepressure, which predetermines glomerules filtrate derivation, is equal to 15-15-25 mm 25 mm HgHgIn case such filtrational pressure in healthy person Broumen capsule 120 ml of filtrate per 1 min is derivated, that is 180 l per one dayThe glomerules filtation can be decreased or decreased or increasedincreased

GGeriatric Considerationeriatric Consideration 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

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

The most characteristic manifestations of The most characteristic manifestations of filtfiltration ration limitation in glomeruleslimitation in glomerules are are::

nitrogenemianitrogenemia (accumulation in blood of nitrogen (accumulation in blood of nitrogen metabolic and blood residual nitrogen increase) metabolic and blood residual nitrogen increase)

renal nitrogenemic acidosisrenal nitrogenemic acidosis owing to delay in an owing to delay in an organism phosphates, sulfates and organic acids organism phosphates, sulfates and organic acids

Increase of filteringIncrease of filtering performs resulting blood pressure performs resulting blood pressure increase excessive consumption water, decomplication increase excessive consumption water, decomplication edema or oncotic plasma pressure decrease (hepatitis, edema or oncotic plasma pressure decrease (hepatitis, cirrhosis)cirrhosis)

Major increasedMajor increased glomerulus glomerulus filter permeabilityfilter permeability manifestationsmanifestations concern concern::

proteinuriaproteinuria – evacuation with urine of plasma proteins – evacuation with urine of plasma proteins over physiological norm (30-80 mg/day) and in urine over physiological norm (30-80 mg/day) and in urine protein fractions appearance with molecular weight protein fractions appearance with molecular weight more than 70 kD more than 70 kD

hematuriahematuria – erythrocytes kidneys outlet in canalicules – erythrocytes kidneys outlet in canalicules lumen of and their appearance. lumen of and their appearance.

Multiplying of Multiplying of glomerularglomerular

filtrationfiltration 1) 1) Increase of hydrostatical pressureIncrease of hydrostatical pressure in the capillaries in the capillaries

of glomerulus, that is observed at following situations:of glomerulus, that is observed at following situations:a) a) increaseincrease the volume of the volume of intravascular liquidintravascular liquid;;b) b) increaseincrease the volume of the volume of speed of cortical blood streamspeed of cortical blood stream

in connection with diminishing of tone of vas afferens in connection with diminishing of tone of vas afferens (in the (in the stage incrementi of temperature at a feverstage incrementi of temperature at a fever, in , in the conditions of the conditions of multiplying the amount of sodium in multiplying the amount of sodium in a meala meal); );

c) c) increase of tone of taking arteriolesincrease of tone of taking arterioles under neuro- under neuro-reflex and humoral influencing, which are observed in reflex and humoral influencing, which are observed in the early stage of hypertensive illness, after the early stage of hypertensive illness, after transfusion, at introduction of small doses of transfusion, at introduction of small doses of adrenalin.adrenalin.

2) 2) Decline of oncotic pressure of bloodDecline of oncotic pressure of blood, redistribution , redistribution of proteins factions of blood (of proteins factions of blood (increase globulinsincrease globulins, which , which own own low oncotic act – at hepatitis, cirrhosis of liverlow oncotic act – at hepatitis, cirrhosis of liver).).

formation of hyperosmotic urine

Renal Renal ReabsorptionReabsorption

ReabsorptionReabsorption is the is the second process by which second process by which the kidney determines the kidney determines the concentration of a the concentration of a substance filtered from substance filtered from the plasma. the plasma. Reabsorption Reabsorption refers to refers to the active (requiring the active (requiring energy and always being energy and always being mediated by a carrier) or mediated by a carrier) or the passive (no energy the passive (no energy required) movement of a required) movement of a substance filtered at the substance filtered at the glomerulus back into the glomerulus back into the peritubular capillaries.peritubular capillaries. ReabsorptionReabsorption may bemay be totaltotal (e.g., glucose) or(e.g., glucose) or partial partial (e.g., sodium, (e.g., sodium, urea, chloride, and urea, chloride, and water).water).

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 normally All 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 can Because carriers are involved, a transport maximum (Tm) for glucose can

be reached. The Tm is the amount of a substance that can be transported be 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), all For glucose, at a certain filtered load (GFR Г— plasma concentration), all carriers become occupied. Any glucose filtered beyond that load is not carriers become occupied. Any glucose filtered beyond that load is not reabsorbed, but is instead excreted in the urine. The Tm for glucose is reabsorbed, 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 of The 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 concentration 125 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 plasma However, glucose begins to appear in the urine even before this plasma level is reached, because each nephron has a slightly different Tm and the level 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 reached Plasma glucose seldom gets high enough that glucose Tm is reached unless an individual has unless an individual has diabetes mellitusdiabetes mellitus. .

Note that the kidney does not control blood glucose levels; it simply filters Note that the kidney does not control blood glucose levels; it simply filters and reabsorbs all it can. The pancreas, via insulin release, controls blood and reabsorbs all it can. The pancreas, via insulin release, controls blood glucose.glucose.

Reabsorption disorderReabsorption disorder ReabsorptionReabsorption of glucose takes place by it phosphorilation on the membranes of glucose takes place by it phosphorilation on the membranes

of epitheliocytes of of epitheliocytes of tubulestubules by the enzyme of glucokinase (hexokinase) and by the enzyme of glucokinase (hexokinase) and glucosoglucoso-6--6-phosphatase, which are produced by epithelial cells. If the phosphatase, which are produced by epithelial cells. If the concentration of glucose in blood and primary urine (filtrate) does not exceed concentration 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 = 0R e a s o n s of R 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 concentration diminishing of products of insulin lead to grows concentration

of glucose in blood over 180 mg%, in addition, there is a decline of activity of of glucose in blood over 180 mg%, in addition, there is a decline of activity of glucokinase of epithelium cells of kidney glucokinase of epithelium cells of kidney tubulestubules), ),

c)c) damage of epithelium of damage 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 floridzin poisoning 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 of conduces to blocking of processes of phosphorilation glucose in the epithelium of kidney kidney 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.

Reabsorption of the Amino AcidsReabsorption of the Amino Acids Amino acids filtered at the glomerulus are actively reabsorbed Amino acids filtered at the glomerulus are actively reabsorbed

in the proximal tubule. All reabsorption of amino acids is in the proximal tubule. All reabsorption of amino acids is carrier-mediated. carrier-mediated.

The Tm The Tm ((transport maximumtransport maximum) ) for the carriers is well above the for the carriers is well above the amounts of amino acids normally filtered, so none are amounts 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 the Those that are filtered are actively reabsorbed across the proximal tubule. Because the GFR is so high, the filtration of proximal tubule. Because the GFR is so high, the filtration of even a few molecules of plasma protein, such as even a few molecules of plasma protein, such as albuminalbumin, , would result in a significant daily loss of protein if would result in a significant daily loss of protein if reabsorption reabsorption did not occurdid not occur..

The few proteins filtered at the glomerulus are not The few proteins filtered at the glomerulus are not reabsorbed. They are degraded by tubular cells and excreted reabsorbed. They are degraded by tubular cells and excreted in the urine. in the urine.

Examples Examples of these proteins include the protein hormones, of these proteins include the protein hormones, such as growth hormone and luteinizing hormone, both of such as growth hormone and luteinizing hormone, both of which are secreted from the anterior pituitary.which are secreted from the anterior pituitary.

30 mg% of albumins is a normal concentration in primary urine, in 30 mg% of albumins is a normal concentration in primary urine, in secondary urine of proteins are absent, because albumins fully secondary urine of proteins are absent, because albumins fully absorption in kidney absorption in kidney tubulestubules..

The presence of albumines in the second urine is called The 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 tracts is 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,tubulopathy nephrosis,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 Proteinuria Proteinuria can be can 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- and unselective, for which characteristic appearance in urine both low- and high-molecular proteins.high-molecular proteins.

The loss of albumen conducts to hypoproteinemia, decreasing of The loss of albumen conducts to hypoproteinemia, decreasing of oncotic pressure and to development of edema.oncotic pressure and to development of edema.

Violation of Violation of reabsorptionreabsorption of water and concentration ability of kidneys of 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. Loss Loss

of concentration abilityof concentration ability is called is called hypostenuriahypostenuria, relative, relative density aqual density aqual in in state changes within the limit of 1,006-1,012 (norm state changes within the limit of 1,006-1,012 (normaa – 1,002- – 1,002-1,035). If 1,035). If density urine density urine is kept at 1,010is kept at 1,010 level and is not changed level and is not changed withwith influence water load, itinfluence water load, it is called is called isostenuriaisostenuria (monotone (monotone diuresisdiuresis))

RReabsorptioneabsorption of water (obligatory) takes place in proximal convoluted of 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 become In ascending part of loop of Henle of Na+ mainly resorb as result urine become hypotonic. There is optional hypotonic. There is optional reabsorptionreabsorption of water (depends on maintenance of of water (depends on maintenance of water and Na+ in blood) in distal convoluted water 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 more hypertonic 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 of Reasons 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 its of maintenance of matters which stipulate its

osmotic concentration (glucose, urea and other).osmotic concentration (glucose, urea and other).

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)

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 canalicules canalicules function function is called as tubulartubular insufficiency insufficiency

It can be hereditary or hereditary or acquiredacquired The selective disorders reabsorption of separate ultrafiltrate

components are convenient to separate considering

Violation of tubular secretionViolation of tubular secretion

Combined tubulopathia.Combined tubulopathia. TThe most known exahe most known exammple of ple of ssuchuch disorders is disorders is

thethe Fankony Fankony syndrome. syndrome. In basisIn basis of of thisthis symptomocomplex symptomocomplex lies kidneys lies kidneys

canalicules canalicules function function generalizedgeneralized disorder. disorder. ItIt includesincludes glucosuria, aminoaciduria, glucosuria, aminoaciduria,

phosphaturia, hypercalciuria,hypernatriuria, phosphaturia, hypercalciuria,hypernatriuria, proteinuria, proximal renal canalicules acidosis proteinuria, proximal renal canalicules acidosis withwith bicarbonaturia, rachitis with resistantion bicarbonaturia, rachitis with resistantion to to vitamin D.vitamin D.

Disoder of secretionDisoder of secretion The main mThe main manifestationanifestation – c – canaliculus acidosisanaliculus acidosis;;

amammmonium- and acidogenesis onium- and acidogenesis inhibition inhibition and and secretion H+-ions lsecretion H+-ions lieiess it is it is basis.basis.

HHyperuricemia, which develops owing toyperuricemia, which develops owing to urinary urinary acid secretionacid secretion disorder disorder and lead toand lead to gout (renal gout (renal form). form).

KKidneys functionsidneys functions disordersdisorders of can be completed of can be completed withwith their insufficiency their insufficiency..

Changes of obligatory Changes of obligatory diuresisdiuresis

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 of b) renal - related to decreasing of glomerularglomerular filtration and increasing of filtration and increasing of

tubular tubular reabsorptionreabsorption of water and electrolytes (during the surplus of water and electrolytes (during the surplus selection of aldosterone and vasopressin);selection of aldosterone and vasopressin);

• c) c) subrenal subrenal is violation of outflow of urine (blocking urinary tracts by a is violation of outflow of urine (blocking urinary tracts by a stone, tumor);stone, tumor);

• d) d) reflexive-renal reflexive-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 vessels renal 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-peripheral reflexive-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) hemolytic hemolytic - 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.

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].

PoliuriaPoliuria is increase of diuresis more than is 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 development In dependence on the mechanisms of development poliuriapoliuria select the select the followings kinds:followings kinds:

a) a) Aquatic diuresisAquatic diuresis conditioned by decreasing of facultative conditioned 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 is At 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 of unresorpted 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 at matters (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 urine In the conditions of maximal osmotic polyuria the selection of urine can achieve a 40% from can achieve a 40% from glomerularglomerular filtration (about 25 l per day). filtration (about 25 l per day).

Mechanisms of the Mechanisms 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 is hypertension, when the rate of movement of blood is multiplied in the direct vessels of cerebral layer of multiplied in the direct vessels of cerebral layer of kidneys (these vessels go parallel the knees of loop kidneys (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" from As result sodium, chlorine, urea is "washing" from interstitial tissue. It conduces to diminishing of interstitial tissue. It conduces to diminishing of osmotic pressure of extracellular liquid, as a result osmotic pressure of extracellular liquid, as a result reabsorptionreabsorption of water diminishes in descending part of water diminishes in descending part of loop of Henle and of loop of Henle and polyuria polyuria develops.develops.

d) d) Compensate diuresisCompensate diuresis. It related to increase of . It related to increase of concentration in blood of urea (at the initially concentration in blood of urea (at the initially shrunken [pursy] kidney), which stimulates healthy shrunken [pursy] kidney), which stimulates healthy glomerulus and multiplies uropoiesis. glomerulus and multiplies uropoiesis.

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 a In a norm 60-80% day's amount of urine selected in a period from 8 to 20 hour, that correlation nightly diuresis to period 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 failure in connection heart failure edema developsedema develops. At . At nightnight in horizontal position a venous outflow is improved in horizontal position a venous outflow is improved and loading on a heart decreasing. It causes the selection and 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 blood It is explained by improvement of the broken kidney blood stream at night. As a result motion of blood is accelerated stream 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.

PolakyuriaPolakyuria is increasing of frequent of urination is increasing of frequent of urination. . Specific gravity of urine equals 1.016 – 1.020 for a healthy Specific gravity of urine equals 1.016 – 1.020 for a healthy

man at an ordinary diet. man at an ordinary diet. рН рН of urine equal 6,0.of urine equal 6,0. HypersthenuriaHypersthenuria is increasing specific gravity of urine more is increasing specific gravity of urine more

than 1.028.than 1.028. HyposthenuriaHyposthenuria is decreasing specific gravity of urine lesser is decreasing specific gravity of urine lesser

then 1.012then 1.012 Combination of Combination of hypostenuria with polyuriahypostenuria with polyuria testifies to the testifies to the

damage of damage of tubulestubules at relatively to the stored function of at 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 of olyguria, it is a sign of damage of all structures of nephrones (glomerulus and nephrones (glomerulus and tubulestubules).).

At a complete loss by the kidneys of ability to concentrate At a complete loss by the kidneys of ability to concentrate and conduct urine and conduct urine isohyposthenuriaisohyposthenuria develops. Its develops. Its characterized by stability of specific gravity per day, but it characterized 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 functional is the sign of heavy structurally functional violations of kidneys.violations of kidneys.

Thus, there are the followings high-Thus, there are the followings high-quality changes of urine at kidney quality 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.

AzotemiaAzotemia AzotemiaAzotemia refers to abnormal elevation of nitrogenous refers to abnormal elevation of nitrogenous

waste products in the blood such as urea, uric acid, and waste products in the blood such as urea, uric acid, and creatinine. creatinine.

Azotemia indicates a decrease in GFR, occurring either Azotemia indicates a decrease in GFR, occurring either acutely or with chronic renal failure. acutely 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 (a is not a single event, but rather a syndrome (a

constellation of symptoms) that develops in an individual constellation of symptoms) that develops in an individual who has end-stage renal disease. Because the kidney is who has end-stage renal disease. Because the kidney is pivotal in maintaining water, acid-base, and electrolyte pivotal in maintaining water, acid-base, and electrolyte balance and in removing toxic waste products, the balance and in removing toxic waste products, the symptoms of uremia are widespread and affect all the symptoms of uremia are widespread and affect all the organs and tissues of the body. 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 vomiting, and lethargy. Intractable itching (pruritus) may occur. Hypertension, osteodystrophy, and uremic occur. Hypertension, osteodystrophy, and uremic encephalopathy develop as well, with central nervous encephalopathy develop as well, with central nervous system changes, including confusion and psychosis, system changes, including confusion and psychosis, characterizing end stages. 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 anemia from decreased erythropoietin, and the buildup of all waste products.all waste products.

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.

EDEMAEDEMA

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.

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.

Acute renal insufficiency Acute renal insufficiency (ARI)(ARI) It is a clinical syndromeIt is a clinical syndrome of of various ethiology various ethiology ( (ARIARI)), which , which

is is characterized by significant and characterized by significant and acuteacute decrease of decrease of glomerulglomerular filtration speedar filtration speed ((GFSGFS))

NormalNormal GFGFSS significance significance – – 100-140 ml/mines100-140 ml/mines Acute renal Acute renal insufficiencyinsufficiency develops, when develops, when GFGFSS is reduced is reduced

toto 1-10 ml/mines 1-10 ml/mines Osmotic active Osmotic active substancessubstances amountamount is is derivatedderivated which is which is

easily excrete in easily excrete in volumevolume water of water of 1,5-2 l (daily diuresis1,5-2 l (daily diuresis) ) for one day with, the for one day with, the normal diet and normal metabolism normal diet and normal metabolism out ofout of organism organism

The minimum quantity The minimum quantity ofof liquid, from which they can still liquid, from which they can still be excretedbe excreted makes makes 500 ml500 ml

AAcute cute renalrenal insufficiencyinsufficiency is is characterizedcharacterized by by such such disorderdisorder renal renal functionsfunctions whenwhen diuresisdiuresis is reduced to is reduced to 500 500 mlml. . This state This state is called asis called as oliguria oliguria

If daily If daily urineurine does not exceed does not exceed 100 ml,100 ml, takes place takes place anuriaanuria

• 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)

• 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)

PostrenalPostrenal factors include: factors include: UUreters reters oobstruction uretersbstruction ureters (canaliculus(canaliculus, ,

bloodblood clots, tumor) clots, tumor) and urinal channel and urinal channel obstruction (prostat hypertrophy, carcinoma)obstruction (prostat hypertrophy, carcinoma)..

Postrenal reasonPostrenal reasonss of diuresis of diuresis decreasedecrease are reduced are reduced ofof urineurine outflow outflow due to due to obstacle obstacle any level any level of of urinary urinary wayway. .

Pathophysiological mechanismsPathophysiological mechanisms, which , which act in act in acute renal acute renal insufficiencyinsufficiency are caused more are caused more complicated complicated and can not beand can not be put into common put into common universal mechanism.universal mechanism.

There areThere are four clinical phases four clinical phases of ARI. of ARI. Initial phaseInitial phase – is a – is a periodperiod, which courses from , which courses from

lesion of lesion of kidneys kidneys untill untill oliguria development. oliguria development. It takesIt takes several hours (ischemia) several hours (ischemia) up to about up to about one one week (after week (after actionaction nephrotoxine) nephrotoxine)

Oliguric phaseOliguric phase is characterized by acute is characterized by acute decrease of GFS. It decrease of GFS. It course lastcourse last several days several days up to up to several weeks (two weeksseveral weeks (two weeks in in average). average). The patients The patients perishperish just in this phase just in this phase

Diuretic phaseDiuretic phase is characterized by gradual is characterized by gradual increase of increase of urine volumeurine volume.. Phase of recovery Phase of recovery –– period, during which renal function completely period, during which renal function completely are restored, though easy are restored, though easy or or moderatemoderate GFS GFS decreasedecrease can be saved can be saved in in some patientssome patients

AAcutecute renal insufficiency renal insufficiency is is accompanied by accompanied by highhigh deathdeath, data , data ischemic and traumaticischemic and traumatic form form aboutabout 50-70 %50-70 % other formother form – about – about 10-35 %10-35 %

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 andObstruction 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 tubulesMedullary blood flow

Renal function

Medullary oxygen sufficiency

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)

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

• 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

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.

Heart Heart is damaged owing to hypertension. The combination is damaged owing to hypertension. The combination of hypertension, anemia,of hypertension, anemia, liquidliquid overloading overloading and acidosis and acidosis promotes promotes heartheart insufficiency insufficiency development. development. I Inn half of half of patients chronical renal terminal insufficiencypatients chronical renal terminal insufficiency stage stage pericarditis develops pericarditis develops TheThe lunglung damage damage is performed is performed with so-called uremic with so-called uremic pneumonitis, whichpneumonitis, which is is the stagnant phenomen in vessels of the stagnant phenomen in vessels of peritracheal peritracheal Arterial hypertensionArterial hypertension is observed in 50% of is observed in 50% of terminalterminal chronical chronical renal renal insufficiency stage. insufficiency stage. It arises is connected toIt arises is connected to hyperproduction reninehyperproduction renine vasodilatative prostaglandinsvasodilatative prostaglandins, , oppression limitationoppression limitation sodium sodium excretionexcretion of of extracellularextracellular liquidliquid volume volume increaseincreaseGastrointestinal disorderGastrointestinal disorder – anorexia– anorexia, nausea, vomitis. The, nausea, vomitis. The bleeding from alimentbleeding from alimentaary cry chhannelannel is is often often phenomenon.phenomenon.Their Their sourcesource are the smallare the small surfacesurface ulcers, ulcers, which bleedwhich bleeding ing slowly slowly

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.

Uremic encephalopathyUremic encephalopathy appears appears withwith sleepiness, inability to concentrationsleepiness, inability to concentration,, absent- absent-mindness, and then mindness, and then – amnesia– amnesia, hallutinations, , hallutinations, delirium, delirium, crampscramps

These bones change are capable to render These bones change are capable to render destructive destructive actionaction on organism on organism

Delay Delay growthgrowth in children in children inin adult adult bones bones delaydelay pain fractures, compression vertexpain fractures, compression vertex os femoris os femoris head, necrosis anhead, necrosis and d skskeeleton deformationleton deformation

Arterial medial layer Arterial medial layer calcification calcification can be can be observedobserved with with ischemicischemic necrosisnecrosis soft tissue skin soft tissue skin calcification with intolerable itch, periarteriitis calcification with intolerable itch, periarteriitis owing toowing to calciumcalcium oxyapatitis precipitation, oxyapatitis precipitation, calcificationcalcification

UremiaUremia

Uremia Uremia is ais a term, which is used term, which is used for chronical for chronical renal insufficiency terminal phase descriptionrenal insufficiency terminal phase description. . The majority of symptoms become well The majority of symptoms become well expressed expressed in GFS ratio below thanin GFS ratio below than 10 10 ml/min.ml/min.

UUremic syndromeremic syndrome pathogenesis has become pathogenesis has become subject of intensive learningsubject of intensive learning for a long time for a long time. . The numerous attempts were made to The numerous attempts were made to identify substances, which are accumulated identify substances, which are accumulated inin renal insufficiency terminal phase and renal insufficiency terminal phase and reach dangerous to the vital function data. reach dangerous to the vital function data.

DISORDERS OF DISORDERS OF GLOMERULAR FUNCTIONGLOMERULAR FUNCTION

Two main mechanisms of damage of the glomeruli.Two main mechanisms of damage of the glomeruli.

1. 1. Affection of the basal membrane of the Affection of the basal membrane of the glomeruli of the nephrons by antibodies its glomeruli of the nephrons by antibodies its antigens - nephrotoxic glomerulonephritis (it antigens - nephrotoxic glomerulonephritis (it has a quick progressive course). Glycoprotein has a quick progressive course). Glycoprotein as a carrier of antigenic proteins of the basal as a carrier of antigenic proteins of the basal membrane.membrane.

2. 2. Development of the inflammatory process Development of the inflammatory process in the glomeruli due to fixation of the immune in the glomeruli due to fixation of the immune complexes on the basal membrane -complexes on the basal membrane -immunocomplex glomerulonephritis.immunocomplex glomerulonephritis.

Disorders resulting in glomerular disease, Disorders resulting in glomerular disease, whether manifestations of systemic injury whether 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.

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

Pathogenesis of Glomerular Pathogenesis 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 cases of primary GN and many of thethe secondary casessecondary cases

a) 2 forms of Ab-associated injuryI) injury resulting from soluble Ag-

Ab deposits in glomerulusII) injury from Ab reacting in-situ

with glomerulus- insoluble fixed glomerular

Ag- molecules planted w/in

glomerulus

IgA NEPHROPATHYIgA NEPHROPATHY(BERGER DISEASE)(BERGER DISEASE)

Mild hematuriaMild hematuria Mild proteinuriaMild proteinuria IgA deposits in mesangiumIgA deposits in mesangium

HEREDITARY HEMATURIA HEREDITARY 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 THIN GBM (Glomerular Basement Membrane) Disease, i.e., about HALF Membrane) Disease, i.e., about HALF as uniformly thin as it should beas uniformly thin as it should be

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.

The Nephritic Syndrome The 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.

OBSTRUCTIVE DISORDERSOBSTRUCTIVE DISORDERSLevel of Obstruction Cause

Renal pelvisRenal calculiPapillary 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

Composition, Contributing Factors, and Composition, Contributing Factors, and

Treatment of Kidney StonesTreatment of Kidney Stones Type of Stone Contributing Factors Treatment

Calcium (oxalate and phosphate)

Hypercalcemia and hypercalciuriaImmobilization

Treatment of underlying conditionsIncreased fluid intakeThiazide diuretics

Magnesium ammonium phosphate (struvite)

HyperparathyroidismVitamin D intoxicationDiffuse bone diseaseMilk-alkali syndromeRenal tubular acidosisHyperoxaluriaIntestinal bypass surgery

Dietary restriction of foods high in oxalate

Uric acid (urate) Urea-splitting urinary tract infections

Treatment of urinary tract infectionAcidification of the urineIncreased fluid intake

Cystine Formed in acid urine with pH of approximately 5.5

GoutHigh-purine dietCystinuria (inherited disorder of

amino acid metabolism)

Increased fluid intakeAllopurinol for hyperuricuriaAlkalinization of urineIncreased fluid intakeAlkalinization of urine

Staghorn calculi. The kidney shows hydronephrosis and stones Staghorn 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]. Pathology Pathology [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)

TransplantationTransplantationTransplant tourismTransplant tourismThe Geneva-based The Geneva-based WHO believes that WHO believes that "transplant tourism" is "transplant tourism" is rising, as rich patients rising, as rich patients bypassed bans on bypassed bans on buying organs at home buying organs at home by travelling abroad to by travelling abroad to receive kidneys from receive kidneys from poor donors. poor donors. Beside kidneys also Beside kidneys also trafficking of half-trafficking of half-livers, eyes, skin and livers, eyes, skin and blood is flourishing. blood is flourishing. ((More e.g. More e.g. UPIJan 12th Jan 12th 20092009))

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