Kidney Question and Answers

Kidney

Question 1. Write characteristic features of nephritic syndrome and nephrotic syndrome.
Answer:

Characteristic features of nephritic syndrome

• Hematuria
• Azotemia
• Proteinuria
• Oliguria
• Edema
• Hypertension

Read and Learn More Preparatory Manual of Pathology Question and Answers

Characteristic features of nephrotic syndrome

• Massive proteinuria: >3.5 gm/day
• Hypoalbuminemia
• Hyperlipidemia
• Lipiduria

Question 2. A 12-year-old boy presented with fever, oliguria, and high-colored urine. He had a sore throat three weeks back.

1. What is your probable diagnosis?

2. Describe the etiopathogenesis of the condition.

3. What are the relevant investigations?
Answer:

Poststreptococcal glomerulonephritis

• Appears 1 to 4 weeks after streptococcal infection of the pharynx or skin
• Most commonly affects children between 6 and 10 years f age

Etiology and pathogenesis

• Caused by group A β-hemolytic streptococci, the most common subtypes include types 12, 4, and 1

Clinical features

• A young child abruptly develops malaise, fever, nausea, oliguria, and hematuria (smoky or cola-colored urine), 1 to 2 weeks after recovery from sore throat
• Peri-orbital edema, mild to moderate hypertension

Laboratory findings

• Elevated anti-streptococcal antibody titers
• The decline in serum concentration of C3 and other components of the complement cascade

Morphology

• Enlarged, hypercellular glomeruli (diffuse and global)
• Hypercellularity is caused by:

1. 1. The proliferation of endothelial and mesangial cells
   2.  Infiltration by leukocytes

Electron microscopy

• Discrete, amorphous, electron-dense sub-epithelial deposits give it the appearance of humps (sub-epithelial humps)

Immunofluorescence microscopy

• Granular deposits of IgG and C3, in the mesangium and along the GBM

Question 3. Write a note on crescentic glomerulonephritis.
Answer:

Rapidly progressive (crescentic) glomerulonephritis

• Characterized by rapid and progressive loss of renal function
• The most common histologic picture is the presence of crescents in most of the glomeruli (Crescentic glomerulonephritis)
• Crescents are produced due to the proliferation of parietal epithelial cells

Classification

1. Type I

• Goodpasture syndrome

2. Type II (immune complex)

• Post-infectious glomerulonephritis
• Lupus nephritis
• Henoch-Schönlein purpura
• IgA nephropathy

3. Type III (pauci-immune)

• ANCA-associated
• Granulomatosis with polyangiitis (formerly called Wegener granulomatosis)
• Microscopic polyangiitis

Microscopy

• Glomeruli show the presence of crescents

Electron microscopy

• Shows ruptures in the glomerular basement membrane (GBM)

Mechanism of crescent formation

• GBM rupture allows leukocytes, plasma proteins, and inflammatory mediators to reach the urinary space, where they trigger the formation of crescents

Question 4. Write a note on Goodpasture syndrome.
Answer:

Goodpasture syndrome

• The basement membrane is made up of type IV collagen
• Type IV collagen has non-collagenous domains
• If noncollagenous domains of type IV collagen act as an antigen, these individuals are prone to suffer basement membrane damage
• In anti-GBM antibody-induced nephritis, antibodies are formed against the noncollagenous (NC1) domain of α3 chains of type IV collagen
• Goodpasture disease/syndrome: These anti-GBM antibodies cross-react with other basement membranes, especially in the lung alveoli, resulting in simultaneous lung and kidney injury

Morphology

• Produces a characteristic crescentic glomerulonephritis
• Electron microscopy shows a rupture in the glomerular basement membrane
• Immunofluorescence: It shows a diffuse linear pattern due to the deposition of antibodies along the entire length of the glomerular basement membrane

Question 5. Enumerate the causes of nephrotic syndrome.
Answer:

Causes of nephrotic syndrome

1. Primary glomerular diseases

• Membranous nephropathy, minimal-change disease, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, dense deposit disease, IgA nephropathy

2. Systemic diseases

• Systemic lupus erythematosus, diabetes mellitus, amyloidosis, drugs (NSAIDs, penicillamine, “street heroin”), infections (malaria, syphilis, hepatitis B and C, HIV), malignancy (carcinoma, lymphoma)

Question 6. Write a note on the pathology of manifestations of nephrotic syndrome.
Answer:

Pathology of manifestations occurring in nephrotic syndrome patients

• Heavy proteinuria depletes serum albumin levels with resultant hypoalbuminemia
• Decreased intravascular colloid osmotic pressure results in generalized edema
• Highly selective proteinuria: There occurs loss of low-molecular-weight proteins, albumin, transferrin, and anti-thrombin III
• Increased synthesis of lipoproteins in the liver and decreased lipid catabolism results in hyperlipidemia with resultant lipiduria
• Due to the loss of immunoglobulin in urine, patients are prone to develop staphylococcal and pneumococcal infections
• Loss of endogenous anticoagulants (antithrombin III) in urine, results in thrombotic and thromboembolic complications

Question 7. The thirteen-year-old female child had massive edema with puffiness of the face with decreased urine output.

1. What is the most probable diagnosis?

2. What can be the most probable renal pathology in this child?

3. Write in detail about minimal change disease.
Answer:

1. The most probable diagnosis is nephrotic syndrome. b and c.

Minimal change disease – Nephrotic Syndrome In Children

• Benign disorder, characterized by diffuse effacement of foot processes of visceral epithelial cells
• The most frequent cause of nephrotic syndrome in children
• Follows a respiratory infection or routine prophylactic immunization

Morphology

Light microscopy

• Glomeruli appears normal

Electron microscopy

• GBMappears normal
• Occurs uniform and diffuse effacement of foot processes

Immunofluorescence

• Shows no Ig or complement deposits

Nephrotic Syndrome In Children

Question 8. Write a note on Alport’s syndrome.
Answer:

Alport’s syndrome (X-linked trait)

• Patient presents as
• Hematuria, which can progress to chronic renal failure
• Nerve deafness
• Lens dislocation, posterior cataracts, and corneal dystrophy

Alport’s Syndrome Pathogenesis

• Mutation of α5 chain of type IV collagen (COL4A5): X-linked form is seen in 85% of patients
• Mutations of COL4A3 or COL4A4 are seen in AR and AD forms

Alport’s syndrome Electron microscopy

• GBM shows irregular foci of thickening alternating with attenuation (thinning), and pronounced splitting of lamina, producing a distinctive basket weave appearance

Question 9. Discuss in detail diabetic nephropathy.
Answer:

Diabetic Nephropathy

Lesions seen in diabetic kidney patients include:

1. Glomerular lesions
2. Renal vascular lesions
3.  Pyelonephritis, including necrotizing papillitis

1. Glomerular lesions include

1. Capillary basement membrane thickening

• Widespread thickening of the glomerular capillary basement membrane
• Thickening of tubular basement membranes

2. Diabetic Nephropathy Diffuse mesangial sclerosis

• Diffuse increase in the mesangial matrix, depositions of which are PAS-positive

3. Diabetic Nephropathy Nodular glomerulosclerosis:

• Also known as Kimmelstiel-Wilson kidney disease or inter-capillary glomerulosclerosis
• Glomeruli show nodular deposits situated at the periphery of the glomerulus, which are PAS-positive
• Nodular lesions are accompanied by accumulation of hyaline material in the capillary loops (“fibrin caps”) or adherent to the Bowman capsules (“capsular drops”)
• Glomerular arteries undergo ischemia, resulting in contraction of the kidney or shrunken kidney

2. Diabetic Nephropathy Renal vascular lesions include atherosclerosis and arteriolosclerosis

3. Diabetic Nephropathy Pyelonephritis: Acute pyelonephritis, necrotizing papillitis (or papillary necrosis) is much more prevalent in diabetics

Question 10. Write a note on diffuse lupus nephritis.
Answer:

Diffuse lupus nephritis (Class IV)

• The most common and severe form of lupus nephritis
• Half or more of the glomeruli are affected
• Wire loop structures: Sub-endothelial immune complex deposits leading to circumferential thickening of the capillary wall, on light microscopy

Question 11. Write a note on acute tubular necrosis.
Answer:

Acute tubular necrosis

Acute Tubular Injury/necrosis (ATI/ATN)

• Characterized by necrosis of tubular epithelial cells

Acute Tubular Injury Types

1. Ischemic ATI

• Causes: Marked hypotension and shock
• Morphology: Tubular necrosis is patchy, with straight segments of proximal tubules (PST) and ascending limbs of Henle’s loop (HL) being most commonly affected

2. Nephrotoxic ATI

• Causes: Drugs (gentamicin), radiographic contrast agents, poisons, including heavy metals (mercury), organic solvents (carbon tetrachloride)
• Morphology: Extensive necrosis is present along the proximal convoluted tubule segments (PCT)

Question 12. Describe the etiopathogenesis, gross, and microscopy of chronic pyelonephritis.
Ansure:

Chronic Pyelonephritis

• Disorder in which chronic tubulointerstitial inflammation and scarring involves the calyces and pelvis

Chronic Pyelonephritis Etiopathogenesis

• Acute pyelonephritis is the initiating factor, which occurs following a urinary tract infection
• Urinary tract infection is caused by gram-negative bacilli, most commonly by Escherichia coli, Proteus, Klebsiella, and Enterobacter

Chronic Pyelonephritis Two forms

1. Reflux nephropathy:

• Vesicoureteral reflux with added infection leads to chronic pyelonephritic scarring

2. Chronic obstructive pyelonephritis:

• Obstruction predisposes the kidney to infection

Chronic Pyelonephritis Morphology

Gross

• Kidneys are irregularly scarred
• Asymmetrical involvement of bilateral kidneys (Note: Diffuse and symmetrical scarring of both kidneys is seen in chronic glomerulonephritis)
• Coarse, discrete, corticomedullary scars with overlying dilated, blunted, or deformed calyces, and flattening of the papillae
• Scars are most commonly seen in the upper and lower poles

Chronic Pyelonephritis Microscopy

• Tubules may be atrophic or hypertrophied
• Thyroidization of tubules: Dilated tubules filled with casts resembling thyroid colloid
• Chronic interstitial inflammation and fibrosis in the cortex and medulla

Question 13. Write a note on xanthogranulomatous pyelonephritis.
Answer:

Xanthogranulomatous pyelonephritis

• Associated with proteus infections
• Gross: Lesions may produce large, yellowish-orange nodules that may be grossly confused with renal cell carcinoma
• Microscopy: Characterized by the accumulation of foamy macrophages, plasma cells, lymphocytes, polymorphonuclear leukocytes, and occasional giant cells

Question 14. Discuss in detail benign nephrosclerosis.
Answer:

Benign nephrosclerosis

• Associated with sclerosis of renal arterioles and small arteries
• Strongly associated with hypertension
• Affected vessels have thickened walls and narrowed lumens, resulting in focal parenchymal ischemia

Pathogenesis

Arterial lesions occur due to:

• Medial and intimal thickening, due to hemodynamic changes, aging, genetic defects
• Hyalinization of arteriolar walls, due to extravasation of plasma proteins through injured endothelium

Benign Nephrosclerosis Morphology

Gross

• Cortical surfaces have fine, even granularity that resembles grain leather
• Loss of mass is due to cortical scarring and shrinking

Benign Nephrosclerosis Microscopy

Hyaline arteriolosclerosis

• Thickening and hyalinization of the arterial walls with resultant narrowing of the lumens of arterioles and small arteries
• Vascular narrowing leads to patchy ischemic atrophy of the renal parenchyma
• The finely granular surface appears microscopically as sub-capsular scars

Question 15. Discuss in detail Malignant Nephrosclerosis.
Answer:

Malignant nephrosclerosis:

• A renal vascular disorder associated with malignant or accelerated hypertension

Malignant Nephrosclerosis Pathogenesis

• The characteristic lesion in malignant nephrosclerosis is vascular injury

Malignant Nephrosclerosis Clinical features

• Characterized by systolic pressures greater than 200 mm Hg and diastolic pressures greater than 120 mm Hg

Malignant Nephrosclerosis Morphology

1. Gross

• Small, pinpoint petechial hemorrhages on the cortical surface, give the kidney a peculiar “flea-bitten” appearance

2. Microscopy

Two histologic alterations characterize blood vessels in malignant hypertension:

1. Fibrinoid necrosis of arterioles: Vessel wall shows a smudgy eosinophilic appearance due to fibrin deposition
2. Hyperplastic arterioles (onion-skin lesion): Intimal thickening due to the proliferation of elongated, concentrically arranged smooth muscle cells of the intima

Question 16. Write a note on polycystic kidney disease.
Answer:

Autosomal Dominant (adult) Polycystic Kidney Disease

• A hereditary disorder characterized by multiple expanding cysts of both kidneys
• Cysts destroy renal parenchyma and cause renal failure

Genetics and pathogenesis

1. PKD1 gene:

• Located on chromosome 16p and encodes polycystin-1
• PKD1 gene mutation accounts for 85% of cases

2. PKD2 gene:

• Located on chromosome 4q and encodes polycystin-2
• Polycystin-2 is expressed in all segments of renal tubules and in many extrarenal tissues

Morphology

Gross

• Kidneys are bilaterally enlarged
• External surface—composed of multiple cysts, varying up to 3 to 4 cm in diameter, with no intervening parenchyma
• Cysts may be filled with clear, serous fluid or with turbid, red to brown, sometimes hemorrhagic fluid

Extra-renal congenital anomalies seen in patients with polycystic kidney disease:

• Polycystic liver disease
• Cysts may occur in the spleen, pancreas, and lungs
• Intracranial berry aneurysms
• Mitral valve prolapse

Question 17. Write a note on Henoch–Schönlein purpura.
Answer:

Henoch–Schönlein purpura

• The age group affected is 3–8 years
•  Patients have a history of atopy
• The disease starts after the onset of acute respiratory infection
• The patient presents with purpuric skin lesions, abdominal pain, intestinal bleeding, and arthralgias along with renal abnormalities
• Purpuric skin lesions occur on the extensor surfaces of arms, legs, and buttocks
• Abdominal manifestations include pain, vomiting, and intestinal bleeding
• Renal manifestations include gross or microscopic hematuria and can present as
• nephritic syndrome, nephrotic syndrome, or rarely crescentic glomerulonephritis
• Patients have IgA deposits in their mesangium (the resultant picture resembles IgA nephropathy)

Question 18. Enumerate different types of renal stones.
Answer:

Four main types of calculi:

1.  Calcium stones, composed of calcium oxalate or calcium oxalate mixed with calcium phosphate
2. Triple stones or struvite stones, composed of magnesium ammonium phosphate (form the largest stones, so-called stag horn calculi)
3. Uric acid stones
4. Cystine stones

Question 19. Classify renal cell carcinoma. Enumerate its risk factors. Discuss in detail
the morphology of clear cell carcinoma.
Answer:

Classification of renal Cell Carcinoma

• Clear cell carcinoma
• Papillary carcinoma
• Chromophobe carcinoma
• Chromosome Xp11 translocation carcinoma
• Collecting duct carcinoma
• Medullary carcinoma

Risk factors for Renal Cell Carcinoma

• Smoking, obesity (in women), hypertension, unopposed estrogen therapy, exposure
  to asbestos, petroleum products, and heavy metals
• Increased risk in patients with end-stage renal disease, chronic kidney disease, acquired cystic disease and tuberous sclerosis Morphology of clear cell carcinomas

Morphology of clear cell carcinomas

Arise from the proximal tubular epithelium

Gross

• Solitary unilateral lesions
• The cut surface appears bright yellow
• Allow color is due to prominent lipid accumulation in tumor cells
• Areas of hemorrhage and necrosis can be seen
• Margins are sharply defined and are confined within the renal capsule

Microscopy

• Growth pattern varies from solid to trabecular (cordlike) or tubular (resembling
  tubules)
• Tumor cells have rounded or polygonal shapes and abundant clear or granular
• cytoplasm, which contains glycogen and lipids
• Tumors have delicate branching vasculature
• Most tumors are well-differentiated, but tumors can show nuclear atypia with bizarre nuclei and giant cells
• Tumors can invade the renal vein and can extend up to IVC

Question 20. Discuss molecular genetics of renal cell carcinoma. Add a note on paraneoplastic syndromes associated with renal cell carcinoma.
Answer:

Molecular Genetics of Renal Cell Carcinoma

• Sporadic and hereditary clear cell carcinomas: Chromosome 3 deletion, loss of VHL, mutational inactivation of VHL, hypermethylation of VHL
• Sporadic papillary renal cell carcinoma: Trisomy 7 and 17; loss of Y and mutated, activated MET
• Hereditary papillary renal cell carcinomas: Trisomy 7 and mutated, activated MET
• Xp11 translocation carcinoma: Translocations of the TFE3 gene located at Xp11.2

Paraneoplastic syndromes associated with renal cell carcinoma

Polycythemia, hypercalcemia, hypertension, Cushing syndrome, eosinophilia, leukemoid reactions and amyloidosis, feminization or masculinization