PATHOPHYSIOLOGY PATHOPHYSIOLOGY OF KIDNEY.KIDNEY OF KIDNEY.KIDNEY

INSUFFICIENCYINSUFFICIENCY

PATHOPHYSIOLOGY PATHOPHYSIOLOGY OF KIDNEY.KIDNEY OF KIDNEY.KIDNEY

INSUFFICIENCYINSUFFICIENCY

Prof. Yu.I. BondarenkoProf. Yu.I. Bondarenko

KidneyKidney is major is major organorgan that regulates that regulates maintenance of outcell liquid amount maintenance of outcell liquid amount and persistance of constancy inner and persistance of constancy inner environmental in an organism environmental in an organism

The kidneys provide such main The kidneys provide such main homeostatic parametershomeostatic parameters: :

iisovolemiasovolemia – blood volume – blood volume constancy constancy

isotoniaisotonia – osmotic pressure – osmotic pressure constancy constancy

isoioniaisoionia – ionic structure constancy – ionic structure constancy isohydriaisohydria – concentration hydrogen – concentration hydrogen

ions constancyions constancy

Function of kidney includes three processes:

Plasma filtration in glomerulus Selective canalicules reabsorbtion Hydrogen ions, ammonium and other

substances secretion

Structural and functional unit of a kidney, that provides these functions

is nephrone

NEPHRON

NEPHRON

Filtration disorder Glomerules filtration process is pushing of water and

saltes through molecular sieve under action of arterial pressure in the capillaries

It is passive process depending on hydrostatic pressure

Filtration pressure displace liquid from capillary

blood into canaliculus lumen and does not require energy

Filtrational pressure, which predetermines glomerules filtrate derivation, is equal 15-25 mm Hg

Filtrational pressure in Bowman’s capsula of healthy person is formated 120 ml of filtrate per 1 minutes, that is 180 l per one day

The glomerules filtation can be decreased or increased

Reasons 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, stenosic 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 by cylinders or urinary tract by stones

• 4. Glomerulus filter disorder – quantity functioning glomerulus decrease, glomerulus membrane thickening, an pores amount and diameter decrease, basal membrane glycoproteid components autoallergic damage.

Consequences of filtration disorder

• The most characteristic manifestations of filtration disorder are:

• azotemia (accumulation in blood of nitrogen metabolic and blood residual nitrogen increase)

• renal azotemic acidosis owing to delay in an organism phosphates, sulfates and organic acids

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

• Glomerulus filter permeability increased manifestations:• proteinuria –evacuation with urine of plasmatic proteins

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

• hematuria – issue erythrocytes into canalicules lumen and their appearance in urine.

HEMATURIA – presence of erythrocytеs in urine(in norm erythrocytes dont pass through glomerular filter and absent in urine !!!) Hematuria renal (in glomerulonephritis) extrarenal (in nephrolithiasis, trauma of kidney)Erythrocytеs that passed through basal membrane of glomerulus is changed, deformed as their “shadow”. It evidence of glomerular origin.

Consequence of increased permeability of renal filter

Reabsorption disorder 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 of proteins, glucose, aminoacids, electrolytes, bicarbonates, phosphates and water almost completely are accomplished

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

Disorder of the canalicules function

Disorder of the canalicules function is called as tubular insufficiency

It may be hereditary or acquired

Disorder of 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)

Disorder of protein reabsorption The disorder of proteins reabsorption

displays with tubular proteinuria

Poisoning cadmium Hypoxia Burns Septicemia Tubular insufficiency is characterized by

the increasing of contents in urine of albumins and other proteins with weight up to 40 kD (selective proteinuria).

Dystrophic defeats canaliculus lead to appearence proteins with molecular weight more than 40 kD (unselective proteinuria) in urine

The glucose reabsorbtion disorders

Dayly norm of glucose loss with urine- up to 1g There are renal and extrarenal glucosuria.

Renal glucosuria arises as a result : Hereditary anomalia membrane carriers

deficiency enzymes hexokinase and glucose-6-phosphatase, which provide glucose canalicules reabsorption.

Equired decrease of these enzymes activity in case of chronic poisonings with lead, mercury, uranium compounds.

Experimentally it is possible to resynthesis by means of floridsine,which oppresses phosphorilation in canalicules cells.

Extrarenal glucosuria stipulated hyperglycemia which exceeds renal threshold (9.0 – 10 mmol/l). More often it is observed due to diabetes mellitus.

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)

The aminoacids reabsorbtion disorder Renal aminoaciduria develops due to of the normal

aminoacids contents in blood and is explained by hereditary transport or membrane molecules-carriers deficiency.

Extrarenal aminoaciduria is observed in case of increase catabolism proteins (disintegration tumor, inflammation), phenylketonuria, cystinosis, hyperglycinemia

Combined tubulopathy The most known example of such disorders is the Fankony syndrome.

In basis of this symptomocomplex lies kidneys canalicules function generalized disorder.

It includes glucosuria, aminoaciduria, phosphaturia, hypercalciuria, hypernatriuria, proteinuria, proximal renal canalicules acidosis with bicarbonaturia, rachitis with resistantion to vitamin D.

Disoder of secretion The main manifestation – canaliculus acidosis due to inhibition ammonium- and acidogenesis and secretion H+-ions.

Hyperuricemia, which develops owing to urinary acid secretion disorder and lead to gout (renal form).

Kidney functional disorders can be completed with their insufficiency.

Acute renal insufficiency

• It is a clinical syndrome (ARI), which is characterized by significant and acute decrease of glomerular filtration rate (GFR)

• Normal GFR significance – 100-140 ml/mines• Acute renal insufficiency develops, when GFR

is reduced to 1-10 ml/mines • Osmotic active substances in amount which is

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

• The minimum quantity of liquid, from which they can still be excreted makes 500 ml

• Acute renal insufficiency is characterized by such disorder renal functions when diuresis is reduced to 500 ml. This state is called as oliguria

• If daily urine does not exceed 100 ml, takes place anuria

Acute renal isufficiency

• Reasons of the acute renal insufficiency are divided into three groups – prerenal, renal and postrenal

Prerenal factors include: circulatting liquid decrease (traumatic shock, blood loss, burns, vomiting, diarrhea), dilatation of vessels and vessels capacity increase (sepsis, anaphylaxia), heart insufficiency (myocardium infarction)

Reasons of ARI Renal factors include:• ischemia of kidneys, action

nephrotoxines (antibiotics, heavy metals, organic solvents, X-ray contrast substances), intravessels erythrocytes hemolysis, glomerulonephritis, states assosiated to pregnancy (septic abortion, eclampsia in pregnant, bleeding)

Reasons of ARI

Postrenal factors include: • Ureters obstruction (canaliculus,

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

• Postrenal reasons of diuresis decrease are reduced of urine outflow due to obstruction of any level of urinary way.

CClinical phaseslinical 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 GFdecrease of GFRR. It . 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 GFGFR R 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 %

Chronical renal insufficiency (CRI)Symptoms chronical renal insufficiency develops in case GFR

25 % over norm 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 of metabolism (gout, diabetes mellitus), obstructive nephropathy (urolithiasis, hydronephrosis),

hereditary anomalies ( kidneys polycystic)

Pathogenesis of chronical renal failure

Renal functions decrease arise due to decrease of acting nephrons amount

The signs initial chronical renal insufficincy arise owing to decrease of acting nephrons mass to 50-30 %

The expressed clinic signs arise due to decrease of acting nephrons to 30-10 %

Further decrease of acting nephrons weight (is lower than 10 %) results in terminal kidneys insufficiency stage – uremia

Complications of renal failure Anemia – is the most characterized sign of chronical

renal insufficiency. Decrease of erythropoietin formation. Increase of erythrocytes hemolys. Uremia oppress bone marrow ability to

erythropoietin reaction. Alimentary channel bleeding. Continuous loss blood result in deficiency iron

which promotes anemia development. Thrombocylopathy. Chronical renal insufficiency in

the patients have a qualitative changes of thrombocytes. It appears as bleeding duration increase.

Complications of renal failure Heart is damaged owing to hypertension. The combination

of hypertension, anemia, liquid overloading and acidosis promotes heart insufficiency development. In half of patients chronical renal terminal insufficiency stage pericarditis develops

The lung damage is performed with so-called uremic pneumonitis, which is the stagnant phenomen in vessels of peritracheal

Arterial hypertension is observed in 50 % of terminal chronical renal insufficiency stage. It arises is connected with hyperproduction renine,and synthesis decrease of vasodilatative prostaglandins, oppression limitation sodium excretion of extracellular liquid volume increase

Gastrointestinal disorder – anorexia, nausea, vomiting. The bleeding from alimentary channel is often phenomenon.Their source are the small surface ulcers, which bleeding slowly

Uremic encephalopathy

Sleepiness Inability to concentration Absent-mindness Amnesia Hallutinations Delirium Cramps

Osteoporosis Decrease of phosphates excretion lead to

increase their level in blood. Result hydrooxiapatite is derivation and ionized

calcium level is decreased, thus it stimulates parathyroid glands. If GFR decrease 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

Osteodistrophy It is includes such disorders: а) fibrosis-cystoses osteitis as result of

secondary hyperparathyreosis; it appears subperiosteol bone resorbtion;

b) osteomalation – bones defeat which organic matrix mineralisation process mineralisation infringed;

c) osteosclerosis –bone density increase; d) osteoporosis – bone weight decrease and microstructural, which increase bone fragility.

Bones change are capable to cause destructive action on organism:

Delay growth in children Painful fractures bones in adult Compressed necrosis of head femoris Skeleton deformation Calcification of arterial medial layer Skin calcification with intolerable itch Periarteriitis owing to calcium oxyapatitis

precipitation, calcification

Uremia Uremia is a term, which is used for chronical

renal insufficiency in terminal phase. The majority of symptoms become well expressed in GFR ratio below than 10 ml/min.

Uremic syndrome pathogenesis has become subject of intensive learning for a long time. The numerous attempts were made to identify substances, which are accumulated in renal insufficiency terminal stage and reach dangerous to the vital function.

Uremic toxins is nitrogen metabolism products.

1. Urea; 2. Guanidine derivates (methylguanidine, guanidinsuccinic

and guanidinacetative acids, kreatine and kreatinin); 3. Aromatic compounds (phenole, indole, aromatic amines);

4. 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 in uremia. Examples – erythropoietine and 1,25-dihydroxycholecalciferol deficiency.

TO YOU !!! THANKS A LOT !!!