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 cortexand inner

region calledthe 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 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) PPeffeff = = РРblbl – – (Р(Рonconc+Р+Рcapscaps))

PPeffeff – – effective filtration effective filtration pressurepressure

РРblbl – – gglomerular blood hydrostatic pressure

РРonconc – – bblood oncotic pressure

РРcapscaps – – ccapsular hydrostatic pressure

PeffPeff = 25 = 25 mm Hgmm 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 1.008 and 1.012 (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 Depending on clinical courseclinical course

aquteaqute chronicchronicprerenal

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 – 100-140 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

DehydrationExcessive loss of gastrointestinal tract fluidsExcessive loss of fluid due to burn injury

Decreased vascular fillingAnaphylactic shockSeptic 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 failureProlonged 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

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 factorspostrenal

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 50-70 %, other form – approximately 10-35 %

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 30-10 % 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

The clinical manifestations of uremia: Gastrointestinal Disorders

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

Thank you for attention!