DIAGNOSTICS OF KIDNEY DISEASES Ph. D., M D. Svitlana Dzyha

The kidneys are a pair of bean-shaped organs that lie on either side of the spine in the lower middle of the back. They are connected to the urinary bladder by tubes called ureters Parenchyma of each kidney consists of two zones: outer area called the cortex and inner region called the medulla

The main function of the kidneys is to help keep the body in homeostasis by controling the composition and volume of blood: Remove waste products (urea, ammonia, drugs, toxic substances) and excess water from the blood in the form of urine Keep the concentrations of various ions and other important substances constant Keep the volume of water in the body constant Keep the acid/base concentration of the blood constant The kidneys also produce certain hormones that have important functions in the body: Renin, which regulates blood volume and blood pressure Erythropoietin, which stimulates the bone marrow to produce red blood cells Erythropoietinbone marrow Active form of vitamin D, which controls calcium uptake and helps make strong bones The functions of kidneys

The functional unit of the kidney is the nephrone Each nephron is made of a glomerulus and a tubule Urine formation requires 3 principal processes: glomerular filtration, tubular reabsorption, and tubular secretion

The filtering of the blood depends on a number of opposing pressures Glomerular blood hydrostatic pressure Blood oncotic pressure Capsular hydrostatic pressure Condition of endothelial-capsular membrane (depends on amount of functioning capillaries and permeability of basement membrane) P eff = Р bl – (Р onc +Р caps ) P eff = Р bl – (Р onc +Р caps ) P eff – effective filtration pressure P eff – effective filtration pressure Р bl – g Р bl – glomerular blood hydrostatic pressure Р onc – b Р onc – blood oncotic pressure Р caps – c Р caps – capsular hydrostatic pressure Peff = 25 mm Hg Structure of filter Podocytes Basement membrane Endothelium of glomerulus The consequences of reduced glomerular filtration : azotemia, metabolic acidosis Abnormalities of Glomerular Function

Protein is normally absent or present in only a trace quantity in the urine If the integrity of the glomelular filter is impaired, and plasma proteins can gain access to the capsular space (proteinuria) If massive proteinuria (>3,5 g/day), hypoproteinemia and peripheral edema occur together, this is termed nephrotic syndrome Violation of glomerular filtration: proteinuria

These are damaged red blood cells in the urine under electron microscope Violation of glomerular filtration: hematuria Hematuria is the presence of red blood cells in the urine If the integrity of the glomelular filter is impaired, and red blood cells can gain access to the capsular space (hematuria)

The worst disorders of sodium and water reabsorption occur in dystrophic and inflammatory changes of tubular epithelium. So kidneys lose the ability to concentrate the urine Loss of concentration ability is called hyposthenuria, specific gravity of urine is fixed between and (The specific gravity of normal urine ranges from 1,008 to 1,030) Isosthenuria is an excretion of urine that has not been concentrated by the kidneys and has the same osmolality as that of plasma. Specific gravity of the urine becomes fixed around 1.010, irrespective of the fluid intake tubular reabsorption retains substances needed by the body, including water, glucose, amino acids, and ions Violation of tubular reabsorption

Depending on clinical course aqutechronic prerenal Depending on etiology of renal failure renal postrenal CLASSIFICATION Renal failure is a condition in which the kidneys fail to remove metabolic end-products and maintain the main parameters of homeostasis

It is a clinical syndrome of various ethiology, which is characterized by significant and acute decrease of glomerular filtration rate (GFR) Acute renal failure develops, when GFR is reduced to 1-10 ml/min (Normal GFR – ml/min) The kidneys fail to remove metabolic end-products from the blood and regulate the fluid, electrolyte, and pH balance of extracellular fluids The reasons of acute renal failure are divided into 3 groops PRERENAL RENAL POSTRENAL Acute Renal Failure: the sudden interruption of renal function

FILTRATION REABSORPTION URINARY EXCRETION The effective filtration pressure Prerenal factors diminish blood flow to the kidney Postrenal factors interfere with the elimination of urine from the kidney Renal factors lead to damage to structures within the kidney Causes of acute renal failure

Hypovolemia Hemorrhage Dehydration Excessive loss of gastrointestinal tract fluids Excessive loss of fluid due to burn injury Decreased vascular filling Anaphylactic shock Septic shock Heart failure and cardiogenic shock Decreased renal perfusion due to vasoactive mediators, drugs, diagnostic agents Prerenal failure ensues when a condition that diminishes blood flow to the kidneys leads to hypoperfusion. The impaired blood flow results in decreased glomerular filtration rate Prerenal ARF accounts for approximately ~55% of ARF cases Prerenal factors cause hypoperfusion

Acute tubular necrosis (ATN) – is the most common cause of intrinsic renal failure Prolonged or severe renal ischemia (the lack of blood flow by ischemia may lead to renal damage; ischemic ATN occurs most frequently in persons who have major surgery, severe hypovolemia, sepsis, trauma, and burns) Exposure to nephrotoxic drugs (antimicrobial agents, particularly aminoglycoside antibiotics, analgesics, anesthetics, chemotherapeutic agents, heavy metals, radiocontrast media, and organic solvents) Intratubular obstruction resulting from hemoglobinuria, myoglobinuria, uric acid casts Acute renal disease (acute glomerulonephritis, pyelonephritis) Obstetric complications (eclampsia, septic abortion, or uterine hemorrage) Intrinsic ARF directly involve the renal parenchyma ~40% of the cases Renal factors cause the damage to the filtering structures of the kidneys

Some of the most notable causes of postrenal ARF include the following: Bladder outlet obstruction due to an enlarged prostate gland or bladder stone Kidney stones in both ureters or in patients with one kidney Kidney stones Tubule obstruction (end channels of the renal nephrons) Renal injury (usually sustained in an automobile accident or while playing a sport) Retroperitoneal fibrosis These factors cause an acute obstruction of urine outflow from the kidneys. The blockage causes pressure to build in all of the renal nephrons (tubular filtering units that produce urine). The excessive fluid pressure ultimately causes the nephrons to shut down Postrenal ARF accounts for approximately ~5% of the cases This illustration tells you how kidney stones could lead to acute renal failure Postrenal factors cause the obstruction of urine outflow from the kidneys

Obstruction of urine outflow from the kidneys Pathogenesis of acute renal failure prerenal factors renal factors postrenal factors Decreased blood flow to the kidneys Damage to the filtering structures of the kidneys A sharp decrease in effective filtration pressure and glomerular filtration rate Excretion of nitrogenous wastes is reduced and fluid and electrolyte balance cannot be maintained

The clinical course of acute renal failure is divided into four phases: Initial phase is a period from the onset of kidney lesion untill oliguria development Oliguric phase is characterized by marked decrease in the GFR. Serum waste products cannot be removed. Fluid retention gives rise to edema, water intoxication and pulmonary congestion. The main threat in the oliguric phase is hyperhydration and hyperkalemia Diuretic phase is characterized by excessive urine output. There is a gradual return of renal function Phase of recovery – is the period during which repair of renal tissue takes place. Renal function are restored Acute renal failure is accompanied by high death, for ischemic and traumatic form approximately %, other form – approximately % The clinical course of acute renal failure is divided into four phases:

The end result of progressive and irreversible destruction of kidney structures Histologic findings of CRF include a reduction in renal capillaries and scarring in the glomeruli (nephrons are replaced with scar tissue, nephrosclerosis develops) Renal insufficiency (Initial signs of CRF) develops when the nephron amount is between 50-30% of normal (kidney has considerable compensatory ability!) Renal failure develops when the nephron amount is between % of normal End-stage renal failure – less than 10 % of normal A decrease in glomerular filtration rate below 10 ml/min leads to the terminal stage of renal failure At this final phase treatment with dialysis is necessary for survival Chronic renal failure

chronic glomerular diseases (chronic glomerulonephritis) the primary canaliculus diseases (chronic infections (chronic pyelonephritis, tuberculosis), interstitial nephritis) metabolic disorders (gout, diabetes mellitus) vascular diseases (arterial hypertension) collagen diseases (systemic lupus erythematosus, sclerodermia, nodular periarteriitis) obstructive processes (kidney stones, cancer) congenital anomalies (polycystic kidney disease, Alport syndrome) Causes of chronic renal failure

The mechanisms of reducing of renal functions include Permanent loss of nephrons A reduction in the GFR in nephrons These mechanisms result in the retention of waste products in the body, rise in plasma level of creatinine, blood urea nitrogen (the tert “azotemia” indicates the accumulation of nitrogenous wastes in the blood) alterations in water, electrolyte and acid-base balance mineral and skeletal disorders anemia and coagulation disorders hypertension and alterations in cardiovascular system neurologic complications etc Uremia – is the term used to describe the clinical manifestations of end-stage renal failure. Uremic syndrome is caused by accumulation of end products of protein metabolism, so-called ‘middle molecules’ (lipids or peptides with a molecular weight of 300–2000 Da), peptides hormons. They poison the body Pathogenesis of chronic renal failure

the accumulation of uremic toxins which suppresses red blood cell production in the bone marrow erythropoietin deficiency iron deficiency bleeding hemolysis of red blood cells Appearance of normal red blood cells Peripheral blood smear examination reveals anemia The clinical manifestations of uremia: Hematologic Disorders pathogenesis of anemia includes

pathogenesis of hypertension includes an increased vascular volume elevation of peripheral vascular resistance decreased levels of renal vasodilator prostaglandins increased activity of the reninangiotensin system The clinical manifestations of uremia: Cardiovascular Disorders

anorexia nausea vomiting diarrhea a metallic taste in the mouth stomatitis ulcers gastrointestinal bleeding develop due to retained uremic products The clinical manifestations of uremia: Gastrointestinal Disorders

decreased levels of active vitamin D lead to a decrease in intestinal absorption of calcium stimulation of the parathyroid glands (secondary hyperparathyroidism) leads to demineralization of bone and teeth there is retention of phosphate, which leads to increased renal excretion of calcium The clinical manifestations of uremia: Mineral Metabolism and Skeletal Disorders The bones become more porous, fragile and more likely to break pathogenesis of renal osteodystrophy includes

Transplantation Hemodialysis Treatment of uremia Patients must have kidney dialysis to cleanse the blood of toxic elements Treatment of uremia

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