Fung: Renal Pathology Flashcards by Megan Foggia

Due to defects in collagen Type IV
Clinically manifested as familial asymptomatic hematuria
Normal renal function and excellent prognosis

Thin basement membrane lesion

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X-linked syndrome of defective collagen Type IV characterized by
Hematuria with progression to renal failure
Nerve deafness
Ocular disorders

Alport syndrome

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One of the leading causes of chronic kidney failure 
Associated with 3 glomerular syndromes
Non-nephrotic proteinuria
Nephrotic syndrome
Chronic renal failure
Also affects other portions of the kidney
Hyalinizing arteriolar sclerosis
Pyelonephritis 
Tubular lesions

Diabetic nephropathy

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Characterized by IgA deposits in the mesangial region of the glomerulus
Increased levels of polymeric forms of IgA1
Believed to be due to a genetic or acquired abnormality of immune regulation upon exposure to environmental agents in the lungs and GI tract

IgA and IgA immune complex are trapped in the mesangium and then activate the complement pathway leading to glomerular injury

Clinical features
Present with gross hematuria after a respiratory or gastrointestinal infection
May also present with microscopic hematuria with or without proteinuria or acute nephritic syndrome
Many retain renal function for decades

IgA nephropathy

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Most common type of glomerulonephritis worldwide
Patients present with recurrent gross or microscopic hematuria
Henoch-schonlein purpura is a systemic form

IgA nephropathy

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Patients present with 
Nephrotic symptoms
Nephritic-nephrotic symptoms
Nephritic symptoms
Asymptomatic hematuria
Characterized by 
Alterations of the GBM
Proliferation of glomerular cells (mesangium)
Leukocyte proliferation

Membranoproliferative glomerulonephritis

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This form of membranoproliferative glomerulonephritis has immune complex deposition with activation of the classical and alternative complement pathways
May be due to Hep B/C antigens
Forms Subendothelial deposits (C3 on IF)

Type 1 membranoproliferative glomerulonephritis

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This form of membranoproliferative glomerulonephritis is rare
Causes intramembranous deposition of immune complexes
Results from dysregulation of the alternative complement pathway
Autoantibody to C3 convertase (C3 neprhtic factor – C3NeF ) leading to persistent C3 activation and hypocomplementemia

Type II

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Can you treat membranoproliferative glomerulonephritis with steroids?

no - these have a poor response to steroids and usually progress to chronic renal failure

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What will you see on immunofluouresence with membranoproliferative GNs?

granular deposition

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Characterized by focal and segmental sclerosis of the capillary tuft
Causes
Idiopathic
Secondary (HIV, heroin, sickle-cell, obesity)
Complication of focal glomerulonephritis
Adaptive response to loss of renal tissue

Thought to possibly be a phase in the evolution of minimal change disease
An accentuation of the diffuse epithelial cell change of minimal change disease
Cytokine mediated or defects of slit diaphragm proteins
Hyalinosis and sclerosis due to entrapment of plasma proteins

Focal segmental glomerulosclerosis

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What will you see on IF with focal segmental glomerulosclerosis?

nothing!

no immune complex deposits, negative IF

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Common cause of nephrotic syndrome in adults
Immune complex mediated disease
Primary
Secondary (SLE, infections, drugs, malignant tumors)
Characterized by diffuse thickening of the glomerular capillary wall
Accumulation of Ig deposits along the SUBEPITHELIAL side of the basement membrane
Insidious onset of nephrotic syndrome (nonselective proteinuria)
Mild hypertension and hematuria possible
Progression of disease leads to sclerosis of glomeruli
Doesn’t respond to steroids

Membranous nephropathy

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What will you see on EM with membranous nephropathy? What will you see on H&E?

spike and dome appearance

thick glomerular BM on H&E

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Most frequent cause of nephrotic syndrome in children
Characterized by diffuse effacement of podocyte foot processes
Glomeruli appear normal on light microscopy
Immune dysfunction leads to an elaboration of cytokine that damages visceral epithelial cells and causes proteinuria
Association with respiratory illness or post immunization
Response to corticosteroid therapy
Association with other atopic disorders
Prevalence of HLA haplotypes
Increased incidence with Hodgkin lymphoma
Highly selective proteinuria (albumin)

Minimal change disease

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Syndrome by which patients present with
Massive proteinuria (>3.5 gm)
Hypoalbuminemia (<3 gm/dL)
Generalized edema
Hyperlipidemia/hyperlipiduria

Nephrotic syndrome

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3 kidney diseases that are entirely nephrotic

membranous glomerulopathy
minimal change disease
focal segmental glomerulosclerosis

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Combined nephrotic/nephritis diseases

Membranoproliferative GN

IgA nephropathy

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Syndrome associated with severe glomerular injury
Not a specific etiologic form of glomerulonephritis
Characterized by
Rapid and progressive loss of renal function
Oliguria
Nephritic syndrome symptoms

Rapidly progressive GN

What will you see on immunofluoresence with rapidly progressive GN?

crescents - made up of fibrin and macrophages

Three types of rapidly progressive GN?

Type I: anti-GBM antibody
Type 2: immune complex
Type 3: Pauci immune

Characterized by linear deposits of IgG/C3
Treatment
Plasmapheresis
Immunosuppression

Anti-GBM antibody (Type I Rapidly progressive GN)

Complication of 
Postinfectious glomerulonephritis
Lupus nephritis
IgA nephropathy
Granular deposits of immune complex
Idiopathic
Treatment
Treat the underlying disease
No plasmapheresis

Immune complex (Type 2 Rapidly progressive GN)

Circulating (ANCA)
May be a component of a systemic vasculitis
Wegener granulomatosis (PR3-ANCA)
Microscopic polyangiitis (MPO-ANCA)
Most cases or idiopathic
Therapy includes steroids and cytotoxic agents

Pauci-immune (Type 3 RPGN)

A 6 year old male presents to his pediatrician with his mom with complaints of dark discolored urine for 1 day duration. The boy has no significant past medical history but mom states that 3 weeks prior he missed 2 days of school due to a sore throat, cold and fever.

acute proliferative glomerulonephritis

``` Symptoms URI or skin infection 1-6 weeks prior Gross hematuria Oliguria Red blood cell casts Peripheral edema Hypertension Azotemia Mild proteinuria Pathogenesis β-hemolytic group A streptococci Lancefield M Circulating immune complexes are deposited in the glomerulus (subepithelium) Clinical course Most affected children (95%) recover totally with therapy aimed at maintaining Na and water balance In adults only 60% recover ```

Acute proliferative GN

What will the glomeruli look like in nephritic syndrome? What will it look like on immunofluorescence?

hypercellular inflammatory response - increased immune cells | granular look - antibody-antigen complex deposition in glomerular BM

``` Syndrome by which patients present with Hematuria (red cell casts) Azotemia Oliguria Slight proteinuria Characterized by inflammation of the glomeruli ```

nephritic syndrome

Causes of chronic renal failure?

diabetes HTN renal parenchymal disease

Syndrome associated with fluid, electrolyte and hormonal imbalances and metabolic abnormalities Symptoms Nausea, vomiting, fatigue, anorexia, weight loos, muscle cramps, pruritis Mental status change, visual disturbances, increased thirst

uremia

``` Diminished GFR (<60 mL/minute/1.73 m2) for at least 3 months Characterized by Azotemia Fluid and electrolyte imbalance Uremia ```

chronic renal failure

``` Rapid (hours to days) decline in glomerular filtration rate (GFR) Characterized by Azotemia Fluid and electrolyte imbalance Hyponatremia Hyperkalemia Hyperphosphatemia and hypocalcemia Metabolic acidosis Oliguria or anuria ```

acute renal failure

Causes of acute renal failure?

Glomerular injury Interstitial injury Vascular injury Tubular injury

Symptoms of acute renal failure?

Decreased or absent urine output Lethargy Fatigue Nausea

elevation of blood urea nitrogen (BUN) or creatinine (Cr)

azotemia

3 immunologic causes of glomerular injury

1. antibodies react in-situ within the glomerulus 2. circulating antibodies deposit within the glomerulus 3. cytotoxic antibody directed against the glomerulus

Glomerular injury: involving all glomeruli? involving only some glomeruli? involving entire glomerulus? affecting only a part of the glomerulus?

diffuse focal global segmental

4 basic patterns of glomerular injury

Hypercellularity Basement membrane thickening Hyalinosis Sclerosis

How do you tell a distal convoluted tubule from a proximal convoluted tubule on histology?

proximal convoluted tubule will have a pink brush border within the lumen

Describe the blood flow through the kidney

renal artery --> interlobar artery --> arcuate artery --> interlobular artery --> afferent arteriole --> efferent arteriole --> veins

Supports the glomerular tuft and lies between capillaries Contains a matrix similar in composition to the basement membrane Contractile, phagocytic, secrete mediators and lay down matrix Similar to vascular smooth muscle cells and pericytes

mesangial cells - mesangium

3 layers of glomerular basement membrane

Lamina rara interna Lamina densa Lamina rara externa

What is another component of the glomerular basement membrane?

type 4 collagen

Describe the endothelial layer of the capillaries of the glomerulus

fenestrated endothelium | adjacent to the lamina rara interna of the GBM

Also called podocytes Adjacent to the lamina rara externa of the GBM Have foot processes that are separated by filtration slits (20-30 nm)

visceral epithelium

What is the space called between the parietal and visceral layer called

Bowman's space

Functions of the kidney

``` Metabolism Excretion of H2O, Na+, Ca2+, P Maintain acid-base balance Excretion of toxic metabolic waste products Endocrine Secrete erythropoietin, prostaglandins Regulate vitamin D metabolism Regulate blood pressure Secrete renin ```