Renal & Urinary Tract Disease

Functions of Kidney

Excrete soluble waste products in form of urine

Regulate bp

Maintain ion balance - absorb water and salts - regulating concentration in plasma

Secrete hormones - erythropoietin and renin

Produce enzyme alpha hydroxylase

a-hydroxylase

Produce active form of vitamin D

Erythropoietin

Essential for production of RBCs - regulate hematocrit

Renin

Produced in response to reduced arterial flow or pressure and activates angiotensin

Maintains plasma volume and bp

Angiotensin

Constricts peripheral vessels

Stimulates aldosterone

Aldosterone

Acts on tubules to reabsorb sodium ions and water from glomerulus

Maintains plasma volume and bp

Nephron

Functional unit of the kidney

Glomerulus - filtrates

Tubule - reabsorbs

Interstitium - supports

Blood vessels - deliver arterial blood & return venous blood

Damage to all 4 results in end-stage renal disease

Tubule

Reabsorbs

Interstitium

Supports

Blood Vesles of Nephron

Deliver arterial blood & return venous blood

End-Stage Renal Disease

Damage to glomerulus, interstitium, tubule, and blood vessels

Glomerulus

Anastamosing network of capillaries surrounded by 2 layers of epithelium

Visceral and parietal epithelium

Capillary wall is filtering macheinsm

Visceral Epithelium

Made of podocytes

Become part of the capillary wall

Critical to maintenance of barrier function

Diffusion barrier to protines

Responsible for synthesis of glomerulus basement membrane components

Parietal Epithelium

Lines Bowman space where plasma filtrate collected first

Continous with tubular epitehlium

Thin Layer of Fenestrated Endothelial Cells

Allows small molecules, antibodies, proteins to pass through

Blood cells not allowed

Glomerular Basement Membrane

Made of type IV collagen, prevents large molecules & anionic proteins into Bowman space

Visceral Epithelial Cells (Podocytes)

Possess foot process and bridged by thin slit diaphragm

Mesangial Tuft

Supported by mesangial cells found in between capillaries

Mesangial Cells

Contract, proliferate, lay down collagen & other matrix components

Can promote leukocyte recruitment & growth factors support glomerular tuft

Glomerular Filtration

Permeable to water, small solutes, and solutes that are cationic

If molecule size and charge of albumin (large and anionic) - not permeable

Nephrin

Major component of slit diaphragms between adjacent foot processes (podocytes)

Glycoprotein bind together by disulfide bridges

Plays critical role in selective permeability of glomerular basement membrane

Abnormalities allow abnormal leakage of plasma proteins (nephrotic syndrome)

Glomerulopathy

Caused by immune mechanisms

Glomerular deposits of immunoglobulins

Type III hypersensitivity reaction

Antigen Not Glomerular

Circulating immune complex nephritis

Can be endogenous (SLE)

Can be exogenous (bacterial, viral)

Circulating Immune Complex

Antigen-antibody trapped in the glomerulus and produce injury

Injury results in - activation of complement and leukocyte infiltration

Eventually degraded by macrophages with repeated cycles leading to chronic glomerulopathology

Forms of Antibody Injury

Antibodies reacting in situ within glomerulus

Deposition of circulating antigen-antibody complex

Antibodies Reacting in situ Within Glomerulus

Membranous nephropathy

Pattern is granular rather than linear on immunofluorescence

Thickened basement membrane

Deposition of Circulating Antigen-Antibody Complex

Pattern is linear deposition

Goodpasture disease

Nephrotic Syndrome

Caused by derangement in capillary walls of glomerulus

Fusion of epithelial foot processes

Structural change or alteration of glomerular basement membrane or mesangium

Protein escaped from blood into urine

Increase glomerular permeability

Clinical Presentation of Nephrotic Syndrome

Proteinuria

Hypoalbuminemia

Generalized edema

Lipiduria

Hyperlipidemia

Nephrotic Syndrome in Kids

Lesion primary to kidney

Nephrotic Syndrome to Adults

Related to systemic disease

Diabetes, amyloidosis, SLE

Minimal Change Nephropathy

Lipoid nephropathy

Most frequent cause of nephrotic syndrome in children

Pathology detected only with electron microscope

Loss or damage of foot processes (podocytes)

Respond well to steroids

Recurrence happens in more than 2/3 of cases

Primary Nephrotic Disease

Minimal change nephropathy

Membranous nephropathy

Focal segmental glomerulosclerosis

Secondary Nephrotic Diseases

Diabetes mellitus

Lupus erythematosus

Amyloidosis

Infections (Hep-B, HIV, Malaria, Syphilis)

Preeclampsia

Membranous Nephropathy

Forms of chronic immune-complex mediated disease

Slowly progressive

Ages 30-60

Primary and secondary variants

Primary Membranous Nephropathy

Autoimmune condition

Antibodies reacting to endogenous or implanted glomerular antigens against podocytes

Secondary Variant

Associated with infections (Hep-B, syphilis, malaria), autoimmune (SLE), exposure to gold or merucry, cancers, drugs

Sub-epithelial immunoglobulin deposits along glomerular basement membrane

• Diffuse thickening of capillary wall - granular appearance on immunofluorescence

Does not respond well to steroids

Focal Segmental Glomerulosclerosis

Most common cause of nephrotic syndrome in adults

Primary disorder of podocytes (epithelial injury)

Affects focal areas and segments of glomeruli

Primary (idiopathic)

Secondary - HIV, heroin, response to nephron loss (obesity or chronic kidney disease)

Progress to end stage disease

Nephritic Syndrome Clinical Presentation

Hematruia

Azotemia - increase in blood urea nitrogen and serum creatinine levels

Oliguria

Hypertension

Proteinuria

Pathogenesis of Nephritic Syndrome

Proliferation of cells within glomerulus

Leukocytic infiltration

Injury to capillary walls - RBCs escape into the urine

Reduced glomerular filtration rate (GFR) and glomerular inflammation

Rapidly Progressive Glomerulonephritis (Crescentic Glomerulonephritis)

Rapid loss of renal function (acute renal failure)

Typical findings of nephritic syndrome (severe oliguria)

Presence of crescent0shaped epithelial cells fill Bowman capsule

Can be immune-mediated or idopathic

Breaks in glomerular basement membrane - leakage of blood proteins

Renal failure if not treated with immunosuppressive drugs

Goodpasture Syndrome

Autoimmune disease

Affects both lungs and kidneys simultaneously

Example of type II hypersensitivity

Type of rapidly progressive glomerulonephritis

Antibodies directed against fixed antigens in glimerular basement membrane & cross react with basement membrane of lung alveoli (antibodies against collagen IV)

Antibodies have linear pattern on immunofluorescence

Treatment of Goodpasture

Plasmapheresis

Toxic substances removed from blood plasma

Nephrotic Syndrome

Abnormal loss of protein in urine

Structural change in glomerular basement membrane or excessive mesangial matrix

Nephritic Syndrome

Blood in urine (hematuria)

Glomerular damage with proliferation of endothelial or mesangial cells

Lower Urinary Tract

Extends from calyces in the kidneys to distal end of urethra

Trasmit urine from kidney to the exterior with bladder as reservoir

Lined by transitional epithelium (urothelium)

Lower Urinary Tract Disorders

Infection

Obstruction

Urinary calculi

Tumors

Congenital diseases

Routes of Infection

Bacteria reaches kidney through hematogenous and ascending paths

Hematogenous Route

Seen in elderly

Infective bacterial endocarditis

Sepsis

Bloodstream

Ascending Route

Most common

Involves lower urinary tract

Common cause of pyelonephritis

Pyelonephritis

Common disease of kidney

Inflammation affect tubules, interstitium, renal pelvis

Serious complication of UTI

• Affect bladder (cystitis), kidneys, collecting systems

Acute or chronic

Acute Pyelonephritis

Caused by bacterial infection

Associated with UTI (85% is gram negative E. coli)

Complications

• Papillary necrosis - diabetes, sickle cell anemia, urinary tract obstruction

• Pyonephrosis - pus not drain and fill pelvis, ureter, calyces

• Perinephric abscess

Symptoms of Acute Pyelonephritis

Chills, fever, nausea, malaise-signs of infection

Pain at costovertebral angle

UTI symptoms (dysuria, frequency, and urgency)

Chronic Pyelonephritis

Known cause of chronic kidney disease

Caused by bacterial infection, vesicoureteral reflux, obstruction, repeat episodes of acute pyelonephritis

Causes scarring of calyces and pelvis

Hypertension may be present

Chronic obstructive or reflux nephropathy

Chronic Obstructive

Result of recurrent infection

Can be unilateral or bilateral

Reflux Nephropathy

Common form

Occurs in childhood

Results from kidney stones or unilateral obstruction to ureter

Can be unilateral or bilateral

Vesiculouretheral Reflux

Results from congenital absence or shortening of ureter

Valve is incompetent - does not close properly (allows back flow of urine into bladder)

Ascending infection occurs

Present in 20-40% of children with UTI

Can result from spinal cord injury bladder dysfunction secondary to diabetes in adults

Tubulointerstitial Nephritis

Inflammation of tubules and interstitium

Non-bacterial in origin

Can be caused by immune reactions to drugs, radiation, systemic autoimmune disorders

Type I or IV drug reaction

Removal of drug can bring back normal renal function

Drugs Causing Tubulointerstitial Nephritis

Penicillins

Rifampin

Diuretics

Proton pump inhibitors

NSAIDs

Clinical Presentation of Tubulointerstitial Nephritis

Hematuria

Proteinuria may be present - WBCs including eosinophils

Fever

Eosinophilia

Rash

Acute Tubular Injury

Damage of tubular epithelial cells and reduced blood flow

Most common cause of acute renal injury

Reversible

Ischemic or pehrotoxic

Ischemic Acute Tubular Injury

Most common

Inadequate blood flow - generalized or localized reduction

Results from shock, mismatch blood transfusions, hemolytic processes

Affect epithelial cells of straight portions of proximal tubule & ascending limbs

Nephrotoxic Acute Tubular Injury

Cause injury to proximal tubules

Caused by heavy metals (mercury), organic chemicals, drugs, contrasting agents

Clinical Manifestation of Ischemic ATI

Electrolyte abnormalities

Acidosis

Uremia - clinical signs and symptoms of severe form of azotemia

Decreased GFR/increased serum creatinine

Oliguria/anuria

Outcome determined by duration & extend of injury

Disease of Blood Vessels

Disease of kidneys involve vasculature secondary

Nephrosclerosis

Benign or Malignant

Neprhosclerosis

Sclerosis of renal arterioles & small arteries

Associated with hypertension

Benign Nephrosclerosis

Slow progressive rise in bp

Malignant Nephrosclerosis

Rapid rise in bp (accelerated hypertension

Benign Nephrosclerosis

Associated with hypertension and diabetes mellitus

Slow progressive rise in bp

Kidney may exhibit a granular texture

Present as hyaline arteriosclerosis

Hyaline Arteriosclerosis

Vessel walls thickened

Increase deposit of basement membrane matrix in vessel & plasma proteins move through injured endothelium

Decreased blood flow results in ischemia and diffuse tubular atrophy

Malignant Nephrosclerosis

True medical emergency

Can arise without pre-existing hypertension

Characterized by - papilledema, encephalopathy, cardiovascular abnormalities

Ischemid damage - activates RAS)

Fibrinoid necrosis of arterioles and small arteries

Kidney appears flea bitten - numerous petechial hemorrhage

May be normal in size or atrophied

Results in renal failure

Fibrinoid Necrosis

Afferent arterioles exposed to sudden high pressure and undergo necrosis with fibrin in damaged walls - can be associated with intravascular thrombosis

Complications of Diabetes

Renal ischemia - atherosclerosis in large, medium, and small arteries

Glomerular damage - hyaline arteriosclerosis in efferent arterioles

Susceptible to bacterial infection (acute pyelonephritis) and papillary necrosis

Diabetes Glomerular Damage

Diffuse thickening of glomerular capillary basement membrane

Fibrin caps

Kimmelstiel-Wilson Nodules

Fibrin Caps

Found on surface of glomerulus

Red stained coagulated fibrin protein results from thick basement membrane and abnormal mesangium

Kimmelstiel-Wilson Nodules (Nodular Glomerulosclerosis)

Excess mesangial matrix formation that become laminated spheres seen throughout glomerulus

Chronic Renal Failure

Hyalinization of glomerulus with obliterated capillary loops and death of individual nephrons

Papillary Necrosis (Necrotizing Papillitis)

Tips of papillae undergo necrosis

Shed in urine and cause acute renal failure

Caused by inflammatory thrombosis in vasa recta supplying renal papillae

Associated with - acute pyelonephritis, obstructive uropathy, analgesic nephropathy

Bacterial infection - reduced neutrophil function and acute polynephritis

Granular texture to kidneys

Chronic Kidney Disease

Progressive loss of nephrons

Extensive scarring of glomeruli

Usually asymptomatic - late discovery

Electrolyte disturbances

Hypertension can cause rapid decline in function

Homeostasis tries to be maintained

Can die from uremia

Compensation of CKD

Hyperfiltration by remaining glomeruli but hemodynamic changes can lead to more damage

Diagnosis of CKD

Proteinuria

Hypertension

Azotemia

Oral Manifestation of CKD

Gingivitis/periodontitis

Hyperpigmentation of lips

Halitosis

Uremic stomatitis

Glossitis

Renal osteodystrophy

Polycystic Disease

Can be hereditary, developmental or acquired

Chromsomes 4 (PKD2) and 16 (PKD1) - AD

Multiple expanding cysts

Clinical Signs of Polycystic Disease

Flank pain

Hematuria

Hypertension

UTI

Can result in chronic renal failure

Autosomal Dominant Variant (Adult Polycystic)

Affects both kidneys

Have renal function until 4th or 5th decade

Symptoms occur in 4th

Causes renal failure (will need dialysis or transplant)

May have saccular aneurysms, mitral valve prolapse, and 1/3 may have liver cysts

Autosomal Recessive Variant (Childhood)

Rare

Four subcategories - perinatal, neonatal, infantile, juvenile

Depend on age and presence of liver lesions

Mutation on PKHD1 gene

Can die from liver kidney failure

IF survive, develop liver cirrhosis

Urinary Tract Obstruction Causes

Congenital anomalies

Stones

Benign prostate hypertrophy

Malignant tumors

Inflammation

Blood clots

Pregnancy

Functional disorders

Unilateral Obstruction

Affects at or above ureters

Bilateral Obstruction

Affects below ureters

Renal Obstruction Not Treated

Causes renal atrophy and obstructive uropathy

Urinary Calculi (Urolithiasis)

Form anywhere in urinary collecting system

Results frmo increased urinary concentration that exceeds solubility

Common locations - renal pelvis, calyces, bladder

Male predilection

Factor for Formation of Stones

Increase concentration of stone constituents

Changes in urine pH

Bacterial infecton

Risks Factors of Stones

Diet

Dehydration

Infection

Genetics

Urolithiasis

Can obstruct urine flow

Causes bleeding or ulceration

Symptoms of Urinary Calculi

Excruciating pain

Flank pain

Hematuria

Calcium Oxalate

Most common stone

5-10% caused by hypercalcemia

Calcium absorbed from gut in large amounts & excreted un urine

Hyperparathyroidism

Vitamin D excess

Sarcoidosis

Struvite (Triple Stone)

Composed of magnesium ammonia phosphate

Associated with lower UTI

• Urea converted to ammonia

• pH alkaline

Can be associated with infections of urea-splitting bacteria (staph aureus or proteus vulgaris)

Can create large stones -staghorn-cast of renal pelvis & calyceal system

Uric

Acidic urine

6 to 7%

Predisposing by gout or acute leukemia (treatment modalities)

50% do not have hyperuricemia

Appear radiolucent

Cystine

Form due to acidic urine

1-2%