Renal Pathology

1.         Review the basic anatomy and physiology of the urinary system.  Note which types of disease tend to disrupt glomerular function versus tubular function.

Vince B

review basic AP

Zen Seeker S&L 350

The glomerulus is responsible for filtration of urine, retaining proteins and other large molecules in the blood.  The property of selective filtration lies in the structure and ionic charge of the glomerular basement membrane (GBM).  Structural abnormalities in the membrane and neutralization of anionic sites cause it to lose this property.

The tubular and ductular systems have several main functions, each of which is dependent upon normal cellular function of tubular epithelial cells.  These systems are responsible for resorption of glucose and amino acids filtered by the glomerulus, selective resorption of water under the control of ADH, and selective resorption or secretion of sodium, potassium, calcium, phosphate and hydrogen ions to maintain homeostasis.

Glomerular diseases are caused by disturbances of structure, whereas tubular diseases are mainly caused by metabolic disturbances.

Functionally, the activity of the glomerulus is mostly determined by the integrity of its structure.  In contrast, the activity of the renal tubule is mostly determined by the metabolic activity of the lining epithelial cells.

Glomerular function tends to be disrupted by diseases that alter glomerular structural arrangements (seen with structural damage to basement membrane, endothelium, epithelium or mesangium), and tubular function tends to be disrupted by metabolic insult to the tubular cells (e.g. hypoxia or toxins).

As both glomerular and tubular function are highly dependent on adequate perfusion by blood, if this is disrupted both functions are impaired.  Once function is disturbed in one part of the nephron, secondary abnormalities often develop in other parts because of the close structural and functional relationships in the nephron.

Tim Martini A&P, and Stevens&Lowe, Ch. 17, pgs. 351-353 

Blood enters the glomerulus of the nephron via the afferent arterioles and enters the glomerular capillary system where waste material is filtered into the tubule system of the nephron.  Blood leaves the glomerulus via the efferent arterioles and transitions into the peritubular capillaries that wrap around the tubular component of the nephron.  The peritubular capillaries interact  selectively with the tubule at different sections:

a.)    Prox. Convoluted Tubule- Reabsorption of water, proteins, amino acids, glucose and carbs.

b.)    Loop of Henle- Creation of hypertonicity gradient between ducts and IF.

c.)    Dist. Conv. Tubule- Acid-base and water balance, absorption of water, Na+, and HCO3-. Excretion of K+ and H+.

d.)    Collecting tubule and duct- Controlled reabsorption of water via ADH.

From there the contents of the tubules pass into the pelvicalyceal systems, into the ureters, into the bladder and out the urethra.

The types of disease that tend to disrupt glomerular function are ones that alter the structural arrangements (endothelium, basement membrane) whereas tubular disease is associated with disruption by metabolic insult to the tubular cells (hypoxia or toxins).

2.         Compare and contrast nephritic syndrome versus nephrotic syndrome.

Vince B

353. Nephrotic vs.nephritic syndrome.

Nephrotic- partial/glomerular permeability increase/severe protein loss in urine, leading to hypoalbuminemia and edema.

Nephritic- partial/glomerular perfusion failure usually transient/rising blood pressure and urea, hematuria, mild edema.

Zen Seeker S&L 351

Nephritic Syndrome - is the result of disturbance of glomerular structure that involves reactive cellular proliferation.  This causes reduced glomerular blood flow (leading to reduced urine output - oliguria), leakage of red cells from damaged glomeruli (hematuria), and consequent retention of waste products (uremia).  The low renal blood flow activates the rennin-angiotensin system, with fluid retention and mild hypertension.  Small amounts of proteins are also lost in the urine, but this is usually trivial.  The hematuria is not gross and is usually manifest as a smoky brown discoloration of urine.

Nephrotic syndrome - is the result of abnormality in the glomerual basement membrane or mesangium, such that the glomerulus loses the capacity for selective retention of proteins in the blood.  This leads to loss of very large amounts of proteins in the blood.  This leads to loss of very large amounts of protein, mostly albumin, in the urine (proteinuria), with consequent loss of protein from the blood (hypoalbuminemia) leading to edema.  There is susceptibility to infections because of low levels of immunoglobulins and complement, susceptibility to thrombosis because of increased levels of fibrinogen in the blood, and hyperlipidemia due to reduced levels of serum apolipoproteins (protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism).

Tim Stevens&Lowe, Ch. 17, pg. 351

Nephritic syndrome is the result of disturbance of the glomerular structure that involves reactive cellular proliferation leading to reduced blood flow and reduced urine flow (oligouria), hematuria and uremia (waste in the blood).

Nephrotic syndrome is the result of an abnormality of the glomerular basement membrane which leads to the inability to selectively retain proteins in the blood which leads to proteinuria, hypoalbuminemia and resultant edema. 

3.         Compare and contrast acute renal failure versus chronic renal failure, including typical causes, mechanisms, and consequences.

Vince B

353. Acute vs. Chronic renal failure.

Acute-total/acute glomerular perfusion failure and tubular epithelial failure (often reversible) /oliguria/anuria,nitrogen retention(uremia),acidosis, potassium retention.

Chronic- total/chronic irreversible nephron failure, both glomerular and tubular failure/ nitrogen retention(uremia) hydrogen ion retention(acidosis), potassium retention, reduced erythropoietin, impaired vit D metabolism.

caused by permanent destruction of nephron.

Zen Seeker S&L 352-353

Tim Stevens&Lowe, Ch. 17, pgs. 351-353 

Acute renal failure is a form of total renal failure in which the majority of nephrons suddenly and simultaneously stop working which leads to oligouria and anuria which can lead to fluid and electrolyte imbalances such as hyperkalemia and metabolic acidosis.  There is no opportunity for metabolic compensation because imbalance is too great.

Causes include; central perfusion failure- conditions such as hypovolemic shock and sudden severe hypotension, tubular and glomerular disease.  Some forms can be reversible if damaging stimuli is resolved.  If untreated can become permanent.

Chronic renal failure is a form of total renal failure caused by progressive destruction of individual nephrons over a long period of time.  Metabolic compensation can occur because nephrons are dying individually and over time.  Conseqences are progressive uremia and progressive failure of tubular function which causes polyuria (inability to [ ] urine) and retention of water and sodium (hypertension) as well as potassium.  Causes include vascular disease, diabetes, hypertension and infectious disease.

4.         Describe the potential consequences of renal artery stenosis.

Vince B

354.  Potential consequences of  renal artery stenosis.

Can lead to chronic ischemia of affected kidney with reduction in function of all nephrons producing an end-stage shrunken kidney.  May lead to renovascular hypertention

Zen Seeker S&L 354

Renal artery stenosis causes renal ischemia and may result in secondary hypertension

Generalized atherosclerosis particularly affects the aorta and the origin of the renal artery, but in severe cases may extend into the main renal arteries and the major branches.  In most cases the atherosclerotic occlusion of the renal artery is most severe at its origin from the aorta.  This renal artery stenosis can lead to chronic ischemia of the affected kidney, with reduction in function of all nephrons on that side, producing an end-stage shrunken kidney.  The unaffected kidney undergoes compensatory hypertrophy, so renal function is largely unaffected in most cases (fig 17.3) Renal artery stenosis is also caused by arterial fibromuscular dysplasia.

Renal artery stenosis may lead to renovascular hypertension, thought to result from abnormal activity in the rennin-angiotensin system in the chronically ischemic kidney.  It is important in that it is one of the recognized causes of hypertension that is amenable to surgical correction.

Tim Stevens&Lowe, Ch. 17, pg. 354 

Renal artery stenosis causes renal ischemia and may result in secondary hypertension (renovascular HTN which leads to abnormal rennin-angiotensin system).

5.         Compare and contrast the renal consequences of long-standing benign hypertension versus accelerated malignant hypertension.

Vince B

354. In long-standing benign hypertension, changes in muscular renal arteries and renal arterioles lead to reduced flow of blood to glomeruli.

Hyaline arteriosclerosis/hyalinization of glomerulus

In acceleraed hypertension, th rise in blood pressure is very rapid, causing a pattern of renal damage different from benign hypertention

Fig 17.4

  fibroid necrosis/tuft necrosis.

Zen Seeker S&L fig 17.4 354-355

Long standing benign hypertension- changes in muscular renal arteries and renal arterioles lead to reduced flow of blood to glomeruli (fig 174.). Renal artery branches within the kidney show thickening of the wall due to a combination of fibroelastic intimal proliferation, elastic lamina reduplication, and muscular hypertrophy of the media (see page 167).  Afferent arterioles undergo hyalinization, their muscular walls being replaced by an amorphous material, which is rigid and inelastic (see page 167).  These thickenings of the vessel wall lead to reduction in the size of the lumen and reduced blood flow.

            Chronic and progressive reduction in blood flow to the nephron leads to chronic ischemia, with slow conversion of individual glomeruli into a mass of hyaline tissue devoid of capillary lumina.  As the blood supply to the tubule is derived from flow through the glomerulus into the efferent arteriole and peri-tubular capillaries, ischemic destruction of the associated tubule occurs.  This process picks off individual nephrons over a period of many years, with no initial clinical symptoms.  Biochemically a gradual increase in blood levels of urea and a reduction in creatinine clearance occur.

            Eventually, sufficient numbers of nephrons become non-functioning for the patient to develop manifestations of chronic renal failure.  This sequence of changes, called benign hypertensive nephrosclerosis, is an important complication of long-standing benign hypertension, chronic renal failure being one of the important sequelae of benign hypertension.

Accelerated malignant hypertension -

In accelerated ‘malignant’ hypertension the renal vessel walls are acutely damaged

In accelerated hypertension the rise in blood pressure is very rapid, causing a pattern of renal damage different from that seen in benign hypertension.  Larger muscular vessels respond with a loose fibroelastic proliferation of the intima, but the afferent arterioles exposed to the sudden high pressures frequently undergo necrosis, often with fibrin in their damaged walls (fibrinoid necrosis, see page 171).  Similarly, the glomerular capillary network may also undergo segmental tuft necrosis.  When sufficient nephrons are rendered non-functional because of damage to glomerular tufts and afferent arterioles, the patient may develop acute renal failure.

            The renal changes seen in benign and accelerated hypertensive nephrosclerosis are summarized in fig 17.4

Tim Stevens&Lowe, Ch. 17, pgs. 354-355 

Benign HTN;  chronic renal failure due to accumulative nephron destruction over time.

Accelerated malignant HTN; Acute renal failure due to rapid destruction of nephrons.

6.         Identify the most common cause, and sites of origin, of renal infarction.

Vince B

355. Most common cause of renal infarction is the passage of emboli down renal arerial branches.  Infarcts in kidney are usually wedge-shaped subcapsular areas of necrosis with broad base at capsular surface.

Most common cause are emboli from a mural thrombus formed over a recent MI, thrombotic vegitations on mitral and aortic valves, thombus on mitria or aortic valve prostesis, or thombus from left atrium of pt with a-fib.

Zen Seeker S&L 355

Large renal infarcts are usually due to thromboemboli in the systemic circulation

The most common cause of renal infarction is the passage of emboli down renal arterial branches.  Typical embolic infarcts in the kidney are usually wedge-shaped subcapsular areas of necrosis, with the broad base at the capsular surface.

The most common causes are emboli from a mural thrombus formed over a recent myocardial infarct, thrombotic vegetations on mitral and aortic valves, thrombus on a mitral or aortic valve prosthesis, or thrombus from the left atrium of patients with atrial fibrillation.

Janelisa Stevens 355 The most common cause is the passage of emboli down renal arterial branches. These emboli are commonly from a mural thrombus that formed over a recent MI, thrombotic vegetations on mitral and aortic valves, thrombus on a mitral or aortic valve prosthesis, or thrombus from the left atrium of patients with atrial fibrillations.

7.         Note:  pp. 356-370 in your textbook cover the very complex subject of glomerular diseases.  For purposes of this course, you do NOT have to distinguish among the various types of glomerulonephritis.  Your learning objectives for this material are limited to #8-11 below.   

Vince B

Pg 356-370 

8.         Briefly describe the three main immune mechanisms in glomerular disease, and list a typical example of each.  (See p. 358)

Vince B

358.  Three main immune mechanisms in glomerular disrase.

Circulating immune complexes

Trapped circlating antigen (lupus, Hep-B)

Anti-GBM antibodies-(Goodpasture's syndrome).

Zen Seeker S&L 358

Circulating immune complexes - in the most common pattern of immunological disease, immune complexes circulation in the blood are trapped or deposited at the basement membrane or the mesangium, or both.  The pattern of glomerular disease depends on the nature, quantity and distribution of the immune complexes, and the pattern of the reaction to their presence (cell proliferation, necrosis and membrane thickening).  In some cases the reason for the circulating immune complexes is known (e.g. response to a recent infection or tumor), in others it is undetermined.

Trapped circulation antigen - it is speculated that in some diseases a circulation antigen becomes trapped in the glomerulus, subsequent circulation antibodies then bind to the trapped antigen.  This is believed to occur in certain cases of the autoimmune disease systemic lupus erythematosus (SLE) (see page 535), when free DNA in the blood is trapped in the glomerular basement membrane (GBM), subsequently binding to anti-DNA antibodies.  It is also thought to occur in cases of hepatitis B viral infection, in which viral DNA is deposited in the glomerular basement membrane, predisposing to immune complex formation.

Anti-GBM antibodies - in an uncommon form of immune-mediated damage, there are autoantibodies directed to a component of the GBM (anti-GBM disease).  This is the basis of Goodpasture’s syndrome, in which antibodies cause direct damage to the basement membrane (see page 364).  The nature of the antigen involved has been determined.  Type IV collagen, a major constituent of basement membrane, is composed not of a single protein but of a family of at least five chains (termed α1-α), each of which contains a non-collagenous domain.  The Goodpasture antigen is the non-collagenous domain of the α3 Type IV collagen chain, which is the target for anti-GBM autoantibodies in patients with Goodpasture’s syndrome.

Janelisa See p. 358The first is due to circulating immune complexes that get trapped or deposited at the basement membrane or the mesangium, or both. The pattern of glomerular disease depends on the nature, quantity and distribution of the complexes and the pattern of the reaction to their presence (cell proliferation, necrosis, and membrane thickening). An example would be a response to a recent infection or tumor. The second is due to circulating antigen that gets trapped in the glomerulus. Circulation antibodies then bind to the antigen. Examples of this are SLE and Hep B. The third mechanism is the most uncommon and involves autoantibodies against the glomerular basement membrane (GBM). This is known as Goodpasture’s syndrome.

9.         Briefly describe the pathogenesis of post-streptococcal acute glomerulonephritis.  (See p. 360)

Vince B

360. Pathogenesis of  post-streptococcal acute glomerulonephritis.

-most common cause is pharyngeal infection with Beta-hemolytic streptococci of Lancefield group A.

-immune complexes develop and circulate to be filtered out in the glomerulus.  

-activation of complement is reason for attraction of neutrophils into glomerulus.

-these degranulate and damage endotheliul cells

-if damage is severe, fibrin and blood leak into Bowman's space and stimulate epithelial cell preliferation, resulting in crescent which permanently effaces the glomerulus.

Zen Seeker S&L 360

The most common cause of acute diffuse glomerulonephritis is pharyngeal infection with β-hemolytic Streptococci of Lancefield group A.  Not all strains cause this disease and there are certain so-called nephritogenic strains (Griffith’s types 12, 4, 1, 25 and 49).  Children are most commonly affected, with onset 1-2 weeks after the primary infection.  Immune complexes develop and circulate in the blood to be filtered out in the glomerulus.  Immunofluorescence shows granular deposition of IGG and C3 in the glomerular basement membrane (GBM) and mesangium.  Ultrastructurally these deposits are sited beneath the epithelium.

            The activation of complement is the reason for attraction of neutrophils into the glomerulus.  These degranulate and damage endothelial cells, stimulating their proliferation.  Mesangial cell proliferation is mediated by factors derived from complement and platelets, and is accompanied by increased expression of PDGF and PDGF-receptor proteins, resulting in an autocrine mechanism of cell proliferation.

            If damage to the glomerular capillaries is severe, fibrin and blood leak into Bowman’s space and stimulate epithelial cell proliferation, resulting in a crescent which permanently effaces the glomerulus.  If 80% of glomeruli have crescents, this is associated with rapid progression to renal failure with a poor prognosis (see page 367).

Janelisa See p. 360Children are most commonly affected, with onset 1-2 weeks after the primary infection. Immune complexes develop and circulate in the blood to be filtered in the glomerulus. Granular deposits of IgG and C3 occur in the GBM and mesangium. The activation of complement attracts neutophils which degranulate, damage endothelial cell, and stimulate their proliferation. Mesangial cell proliferation is mediated by complement and platelets. If damage to the glomerular capillaries is severe, fibrin and blood leak into Bowman’s space and stimulate epithelial cell proliferation, resulting in a crescent which permanently effaces the glomerulus. If 80% of them have crescents, a rapid progression to renal failure with poor prognosis occurs.

10.       Describe three forms of renal disease which are associated with diabetes mellitus.

Vince B

368.  Three forms of renal disease associated with DM.

-DM most common cause of end-stage renal failure.

Three forms:

Complications of diabetic vascular disease

Diabetic glomerular damage- involves diffuse thickening of gloerular capillary basement membrane leading to increase on permeability, proteinuria and nephrotic syndrome.

Increased susceptibility to infection and papillary necrosis- tips of papillae undergo necrosis and may be shed in urine, causing acute renal failure.  Renal papillary necrosis may also be associated with severe acute pyelonephritis caused by inflammatory thrombosis in vasa recta supplying renal papillae; obstructive uropathy; analgesic nephropathy

Zen Seeker S&L 368

Diabetic vascular disease

            Diabetes causes increased severity of atherosclerosis in large, medium and small arteries, predisposing to renal ischemia.  In addition, diabetes causes hyaline arteriolosclerosis in afferent arterioles, resulting in ischemic glomerular damage.

Diabetic glomerular damage

            Involves diffuse thickening of the glomerular capillary basement membrane (fig 17.18a), leading to an increase in permeability, proteinuria and, occasionally, the nephritic syndrome.  Exudative lesions due to a combination of thick permeable basement membrane and abnormal mesangium may be visible as masses of red-staining coagulated fibrin protein (fibrin caps) on the surface of the glomerulus (fig 17.18b).  Changes in masangium lead to excess mesangial matrix formation.  This initially occurs in an even pattern throughout the glomerulus (diffuse diabetic glomerulosclerosis), but later takes the form of laminated spheres, which are known as ‘Kimmelstiel-Wilson nodules’ (nodular diabetic glomerulosclerosis) (fig 17.18c).

            Diabetic glomerulosclerosis causes progressive hyalinization of glomeruli, with obliteration of capillary loops and death of individual nephrons.  Over a period of years this leads to chronic renal failure.

Increased susceptibility to infection and papillary necrosis

            Predisposition to bacterial infection - acute pyelonephritis is an important and common complication of diabetes mellitus, being the result of relative immune suppression seen in diabetics, together with reduced neutrophil function.

            Papillary necrosis - the tips of the papillae undergo necrosis and may be shed in the urine, causing acute renal failure (fig 17.19).  This is frequently seen in association with severe acute pyelonephritis and is thought to be caused by inflammatory thrombosis in vasa recta supplying the renal papillae.  Renal papillary necrosis may also occur in association with:

• Severe acute pyelonephritis, when it is thought to be caused by inflammatory thrombosis in vasa recta supplying the renal papillae

• Obstructive uropathy, with or without associated infection

• Analgesis nephropathy (see page 372); phenacetin (analgesic; antipyretic) was formerly the major cause, but is no longer prescribed or available.

Janelisa Stevens 368-369 The first form is complications of diabetic vascular disease. Diabetes increases the severity of atherosclerosis in all arteries predisposing to renal ischemia. Additionally, it causes hyaline arteriosclerosis in afferent arterioles, resulting in ischemic glomerular damage. The second is diabetic glomerular damage which involves thickening of the glomerular capillary basement membrane leading to an increase in permeability, proteinuria, and nephrotic syndrome. The glomerularsclerosis causes progressive hyalinization of glomeruli, with obliteration of capillary loops and death of individual nephrons. Over the years, this leads to chronic renal failure. The third is increased susceptibility to infection and papillary necrosis. Acute pyelonephritis is a common complication of DM being the result of relative immune suppression seen in diabetics along with reduced neutrophil function. This is frequently associated with papillary necrosis where the tips of papillae are necrotized and shed in the urine causing acute renal failure.

11.       Describe the potential renal consequences of amyloidosis.

Vince B

370. Renal consequences of amyloidosis.

Amyloidosis- conditon in which extracellular fibrillar protein is deposited in variety of tissue.  As amyloid is deposited in basement membrane membrane, membrane thickens and permebility increases leading to proteinuria.  Protein loss increases until pt develops nephrotic syndrome/ chronic renal failure.

Zen Seeker S&L 370

The kidney is a target organ in amyloidosis a condition in which extracellular fibrillar protein is deposited in a variety of tissues.  For a more detailed discussion, see chapter 25.  The amyloid is deposited as fibrils in the glomerular basement membrane (GBM) and in the mesangium.  As amyloid is deposited in the basement membrane, the membrane thickens and its permeability is increased, so that the first manifestation is proteinuria.  With heavy deposition of amyloid, the protein loss increases until the patient develops features of the nephritic syndrome.

            Amyloid is an important cause of the nephritic syndrome in adults.  Heavy amyloid deposition in the mesangium, in combination with increased mesangial matrix formation, can eventually lead to expansion of the mesangium, ultimately leading to compression of the glomerular capillary system, and transition into chronic renal failure.  Amyloid is also deposited in the walls of intrarenal vessels, particularly afferent arterioles.

Greg R.  Stevens & Lowe p. 370.  Amyloidosis (a condition in which extracellular fibrillar protein is deposited in tissues) is an important infiltrative disease of the glomerulus.  The amyloid is deposited as fibrils in the glomerular basement membrane and in the mesangium (suspensory structure of the glomerulus).  As amyloid is deposited in the basement membrane, the membrane thickens and its permeability is increased, so that the first manifestation is proteinuria.  As the more amyloid is deposited protein loss increases until the patient develops nephritic syndrome.  Amyloid is an important cause of nephritic syndrome in adults.  It can progress into chronic renal failure, as the mesangium, expanded by amyloid deposition, compresses the  glemerular capillary system.

Deb B./S&L, pg.370

            Amyloidosis (condition in which extracellular fibrillar protein is deposited in variety of tissues)  Conseq.=as amyloid is deposited in basement membrane, membrane thickens and its permeability is increased---leads to proteinuria, then protein loss increases till pt develops features of nephritic syndrome

12.       For acute pyelonephritis, identify the two most common routes of infection, most common pathogen, and potential consequences.

Vince B

370.  Pyelonephritis is caused by bacterial infection which enter kidney by two routes.

Ascending infection from lower urinary tract: most common

Bloodstream spread in bacteremic or septicemis states: unusual.

Most common caused by E.coli.

Pt develop fever, rigors and pain in back often associated with signs of lower UTI.

-if untreated, infection may spread to cause Gram-negative septicemia with shock.

-may be renal papillary necrosis

-perinephric abscess may develop if infection spreads to perinephric fat and pyonephrosis

Zen Seeker S&L 370

Routes of infection

• Vesicoureteric reflux - Ascending infection from the lower urinary tract (most common).  Predisposing factors that lead to ascending urinary tract infection are pregnancy, diabetes mellitus, stasis of urine, e.g. due to lower urinary tract destruction by a calculus, enlarged prostate, or malignant invasive tumor in the pelvis, structural defects of the urinary tract, and reflux of urine from bladder into ureters (vesicoureteric reflux).

• Bloodstream spread in bacteremic or septicemic states (unusual). Although less common, this seems to be the most likely cause in elderly patients who develop pyrexia of unknown origin, often with rigors, and acute renal failure.

Pathogen

            Most cases of infection are caused by E. coli, other enteric organisms being seen less frequently.

Potential consequences.

            Macroscopically, the kidneys show variable numbers of small, yellowish white cortical abscesses, which are usually spherical, under 2 mm in diameter, and are sometimes surrounded by a zone of hyperemia; the cortical abscesses are often most prominent on the sub-capsular surface, after the capsule has been stripped away (fig 17.20a).  In the medulla the abscesses tend to be in the form of yellowish white linear streaks that converge on the papilla.  The pelvicalyceal mucosa may be hyperemic or covered with fibrinopurulent exudates.  Histologically the kidney show focal infiltration with neutrophils (fig 17.20b).

            If untreated, infection may spread to cause Gram-negative septicemia with shock.  In severe infections, particularly in diabetics, there may be renal papillary necrosis caused by inflammatory thrombosis of vasa recta supplying the papillae.  Perinephric abscess may develop if infection spreads to perinephric fat, and pyonephrosis (distension of the pelvicalyceal system with pus) may be present if there is obstruction at the pelviureteric junction or lower.

Greg R.  Stevens  & Lowe p. 370.  The two most common routes of infection causing acute pyelonephritis are:  Ascending infection from the lower urinary tract (most common).  Predisposing factors are pregnancy, diabetes mellitus, stasis of urine, or malignant invasive tumor in the pelvis, structural defects of the urinary tract, and reflux of urine from bladder into ureters (vesicoureteric reflux).  Bloodstream spread in bacteremic or septicemic states (unusual).  Less common, this seems to be the most likely cause in elderly patients who develop pyrexia of unknown origin, often with rigors, and acute renal failure.

            Most common pathogen: E. coli

            If untreated, infection may spread to cause Gram-negative septicemia with shock.  In severe infections there may be renal papillary necrosis caused by inflammatory thrombosis of vasa recta supplying the papillae.  Perinephric abscess may develop if infection spreads to perinephric fat, and pyonphrosis may be present if there is obstruction at the pelviureteric junction or lower. 

Deb B./S&L,pg.370

            2 most common routes of infection=Ascending infection from lower urinary tract (most common) and Bloodstream spread in bacteremic or septicemic states (unusual)

            Most common pathogen=E.coli, other enteric organisms being seen less frequently

            Potential conseq.=infection may spread to cause gram-neg. septicemia with shock/in severe infections, may be renal papillary necrosis/ Perinephric abscess may develop if infection spreads to perinephric fat   

13.       Describe the causes and potential consequences of chronic pyelonephritis.

Vince B 371

Chronic pyelonephritis is common cause of ene0stage chroic renal failure.

-characterized by interstitial chroic inflammation and scarring which destroys nephrons.

Two forms of chronic pyelonephritis:

- reflux-associated- reflux of urine from bladdre up ureters predisposes to recurrent bouts of inflammation.  Occurs in childhood, manifests in early adult

-obstructive -recurrent episodes of infection occur in kidney in which there is obstruction to pelvicalyceal drainage at any level in lower urinary tract due to anatomical abnormality or renal tract stone.

Zen Seeker S&L 370-371

Chronic pyelonephritis is a common cause of end-stage chronic renal failure, accounting for about 15% of all cases.  The disease is characterized by interstitial chronic inflammation and scarring, which destroys nephrons.  The areas of scarring are associated with distortion of the pelvicalyceal system of the kidney.  Renal-induced hypertension may develop and hypertensive-induced vascular damage (page 355) can increase renal damage.

            There are two forms of chronic pylonephritis: reflux-associated and obstructive.

            In the most common form, reflux-associated chronic pyelonephritis, reflux of urine from the bladder up the ureters predisposes to recurrent bouts of inflammation, leading to scarring.  This occurs in childhood, and disease becomes manifest in early adult life, with progressive impairment of renal function.

            In obstructive chronic pyelonephritis, recurrent episodes of infection occur in a kidney in which there is obstruction to the pelvicalyceal drainage.  The obstruction, which can be at any level in the lower urinary tract, may be due either to anatomical abnormality or to renal tract stone.

            Kidneys have irregular areas of scarring, seen as depressed areas, 0.5-3 cm in size.  The scars are sited over a club-shaped distorted renal calyx and are associated with fibrous scarring of the renal papilla.  The most common site for these areas of scarring is the renal calyces at the poles of the kidney.

            Histologically the kidney has irregular areas of interstitial fibrosis with chronic inflammatory cell infiltration.  Tubules are atrophic or may be dilated and contain proteinaceous material.  Glomeruli show periglomerular fibrosis and many demonstrate complete hyalinization.

Greg R.  Stevens & Lowe p. 370-371.  Chronic pyelonephritis is characterized by interstitial chronic inflammation and scarring, which destroys nephrons.  The areas of scarring are associated with distortion of the pelvicalyceal system of the kidney. There are two forms of chronic pyelonephritis: Reflux-associated chronic pyelonephritis (most common)-reflux of urine from the bladder up the ureters predisposes to recurrent bouts of inflammation, leading to scarring.  This occurs in childhood, and manifests in early adult life, with progressive impairment of renal function.  Obstructive chronic pyelonephritis-recurrent episodes of infection occur in a kidney in which there is an obstruction to the pelvicalyceal drainage.  The obstruction may be due either to anatomical abnormality or to renal tract stone.

Deb B./S&L,pg.370-371

            Causes=chronic inflammation and scarring, which destroys nephrons

            Potential conseq.=impairment of renal function, tubules are atrophic or may be dilated and contain proteinaceous material, glomeruli show periglomerular fibrosis

14.       List the two main groups of causative factors for acute tubular necrosis, and identify common examples of each.

Vince B

372.  Two main groups of causative factors

Ischemic tuvular necrosis-caused by failure of renal perfuson

Toxic cause: endogenours products, heavy metals, organic solvents, drugs.

Zen Seeker S&L 372

Ischemic tubular necrosis

            Caused by failure of renal perfusion.  This is usually the result of hypotension and hypovolemia in shock, or may occur after extensive acute blood loss.  Clinical situations that carry a high risk of developing ischemic acute tubular necrosis (ATN) are major surgery, severe burns, hemorrhage, and causes of severe hypotension and shock.

Toxic causes of ATN

            Uncommon

Greg R.  Stevens & Lowe p. 372.  Two main groups of causative factors: Ischemic tubular necrosis-caused by failure of renal perfusion.  Usually the result of hypotension and hypovolemia in shock, or may occur after extensive acute blood loss.  Clinical situations that carry a high risk of developing ischemic ATN are major surgery, severe burns, hemorrhage, and causes of severe hypotension and shock.  Toxic causes of ATN (uncommon)-Endogenous products (hemoglobinuria & myoglobinuria), Heavy metals (lead, mercury), Organic solvents (chloroform, carbon tetrachloride), Drugs (antibiotics, NSAID’s, cyclosporine), Other toxins (paraquat, phenol, ethylene glycol, poisonous fungi) 

Deb B./S&L,pg.371-372

            2 main grps causative factors=ischemic (caused by failure of renal perfusion) and toxic (from endogenous products, heavy metals, organic solvents, drugs, other toxins)

           Common ex.=Ischemic=severe burns, hemorrhage, and causes of severe hypotension and shock/ Toxic=lead, mercury, antibiotics, NSAIDS, poisonous fungi

15.       Identify common examples of drugs that cause interstitial nephritis.

Vince B

372. Interstitial nephritis is characterizzed by inflammatin inthe intrstitium.

Main causes is exposure to drugs-analgesics and antibiotics (phenacetin, NSAID).

Zen Seeker S&L 372

Interstitial nephritis is characterized by inflammation in the interstitium, associated with tubular atrophy or damage.  There are many causes, the main one of which is exposure to drugs, particularly certain analgesics and antibiotics.  Less commonly, physical agents such as irradiation cause a similar pattern of tubulointerstitial damage. 

Greg R.  Stevens & Lowe p. 372.  Drugs that cause acute interstitial nephritis are certain analgesics and antibiotics.  Specific analgesic agents include phenacetin and NSAID’s. 

Deb B./S&L,pg.372

            Certain analgesics and antibiotics / (NSAIDS, phenacetin)

16.       Compare and contrast renal adenocarcinoma and nephroblastoma (Wilms’ tumor) regarding presentation, metastasis, and prognosis.

Vince B

Renal adenocarcinoma vs. Nephroblastoma (Wilm's tumor)

-renal adenocarcinoma- accounts for 90% of primary malignant tumors in adults seen after age 50 yrs- present with hematuria and loin pain.

-also associated with paraneoplastic syndromes of hyprcalcemia, hypertetion, polycythemia,Cushing's syndrome.

-Spreads by local expansion and blood-borne metastasis to lungs, bone, brain, liver. Large tumors may grow as a solid core along main renal vein or enter inferior vena cava.

Prognosis- dependson stage at presentation. If confined to renal capsule-70% -10yr survival.  Poor if metastases.

-Nephroblastoma (Wilm's tumor)- embryonal tumor derived from primitive metanephros.  Predominantly a tumor of young children with peak incidnece between 1-4yrs.

-presents as abdominal mass or with hematuria.

-prognosis- related to spread of tumor at diagnosis.  Anaplais-poor prognisis. 

Zen Seeker S&L 374

Renal Adenocarcinoma

            Derived from the renal tubular epithelium, accounts for 90% of primary malignant renal tumors in adults.

            Usually seen after the age of 50 years, they present with hematuria and loin pain, although occasionally the presenting symptom is a mass in the loin or a pathological fracture due to metastases in bone.  Renal carcinomas are often also associated with paraneoplastic syndromes of hypercalcemia, hypertension, polycythemia, or Cushing’s syndrome caused by ectopic or inappropriate hormone secretion.  Renal adenocarcinomas account for around 3% of all carcinomas in adults.

            Macroscopically these tumors are usually rounded masses, with a yellowish cut face marked with areas of hemorrhage and necrosis (fig 17.24).  There are several histological patterns of renal adenocarcinoma, the most common being the ‘clear-cell pattern’, in which the tumor cells have clear cytoplasm due to the high content of glycogen and lipid (fig 17.25).  Tubular and papillary carcinomas are characterized by epithelial cells with a granular cytoplasm.

            The tumor spreads by local expansion (breaking through the renal capsule into perinephric fat) and by blood-borne metastasis (involving lungs, bone, brain and other sites as a result of tumor invasion of the renal vein).  A characteristic behavior feature is that large tumors may grow as a solid core along the main renal vein, even entering the inferior vena cava.

            Prognosis depends on the stage at presentation: if tumor is confined within the renal capsule, there is a 70% 10 year survival; however, prognosis is very poor if metastases are present at diagnosis.

Nephroblastoma (Wilms’ tumor)

            An embryonal tumor derived from the primitive metanepros (metanephros).  Although it does occasionally occur in adults, it is predominantly a tumor of young children, with a peak incidence between the ages of 1 and 4 years.

            Tumor presents as an abdominal mass or, less frequently, with hematuria.  Macroscopically, tumors are rounded masses that replace large amounts of the kidney, appearing as solid, fleshy, white lesions with frequent areas of necrosis (fig 17.26).  Histologically, there are various combinations of four elements, these being primitive small-cell blastomatous tissue resembling the developing metanephric blastema, immature-looking glomerular structures, epithelial tubules, and stroma composed of spindle cells and striated muscle.

            Prognosis is related to spread of tumor at diagnosis.  The presence of histological features of anaplasia in tumors is associated with poor prognosis. Although these tumors grow rapidly and there is often evidence of spread at the time of diagnosis, treatment by a combination of radiotherapy and intensive chemotherapy achieves a high cure rate.

EChing, S&L. P350                     

Two types of tumor commonly occur in the kidney, renal adenocarcinoma in adults and nephroblastoma (Wilms’ tumor) in children, peak incidence between ages 1 and 4 yrs.

S&L, P374-376

Renal adenocarcinoma

• Presentation:  commonly seen after age 50, present with hematuria and loin pain, occasionally the presenting symptom is a mass in the loin or a pathological fracture due to metastases in bone.

• Metastasis: spreads by local expansion (breaking through the renal capsule into perinephric fat) and by blood-borne metastasis (involvoing lungs, bone, brain, and other sites as a result of tumor invasion of the renal vein).

• Prognosis:  depends on the sate at presentation- if tumor is confined within the renal capsule, 70% 10 year survival; poor prognosis if metastases are present at diagnosis.

Nephroblastoma (Wilms’ tumor)

• Presentation: tumor presents as an abdominal mass or, less frequently, with hematuria.  Macroscopically, they are rounded masses that replace large amounts of the kidney, appearing as solid, fleshy, white lesions with frequent areas of necrosis.

• Metastasis:  grow rapidly and there is often evidence of spread at the time of diagnosis (can’t find much in the book on this!)

• Prognosis:  related to spread of tumor at diagnosis.  Poor prognosis in the presence of histological features of anaplasia(loss of cellular differentiation and function) in tumor

A.T.  Stevens p. 374-376.

Renal Adenocarcinoma- most commo malignant tumor of the kidney, presents with hematuria, lion pain, occasionally lion pain or a metastatic bone fracture.  Can be associated with paraneoplastic syndromes, hycalcemia, HTN, polycythemia, Cushing’s syndrome caused by inappropriate hormone secretion.  Tumors are  rounded, yellowish,marked with areas of hemorrhage and necrosis.  The clear cell pattern is the most common where the tomor cells are clear due to high contents of glycogen and lipid.  Spread by local invasion and by blood to lung, bone, brain, through the renal vein and possibly to the vena cava.  Prognosis- depends on stage at presentation, if confined to renal capsule 70% 10 yr. survival, poor if mets are present.

Nephroblatoma- Wilm’s tumor- Young children, 1-4 yrs. Old.   Follows a ‘two-hit’ entity with the at least three didderent genes. presents with abdominal mass or less frequently hematuria.  Small cell blastomatous tissue, immature glomular structures,  Prognosis related to spread of tumor.  Presence of histological features of anaplasia at dx is poor.  However, with chemo and radiation can achieve high cure rate.  Mets not discussed. 

Deb B./S&L,pg.374-376

            Renal adenocarcinoma:  Presentation=usually seen after age 50, present with hematuria and loin pain, occas. presenting symptom is mass in loin/ Metastasis=spreads by local expansion and by blood borne metastasis (involving lungs, bone, brain)/ Prognosis=depends on stage of presentation: if confined within renal capsule, 70% 10yr. survival, however prog. Very poor if met.s are present at diagnosis

Nephroblastoma (Wilm’s tumor):  Presentation=tumor of young children, peak incid. Between 1-4yr old, presents as abdominal mass or less freq. with hematuria/ Metastasis=grow rapidly and often spread at time of diagnosis/Prognosis=related to spread, presence of histological features of anaplasia in tumors is assoc. with poor prognosis; although grow rapidly, evidence that with combo of radiotherapy and intensive chemo achieves high cure rate