L6 - Renal pathology - Dr Judit Sutak Flashcards
- to look at the basic anatomy and function of the kidney - To further examine the basic structure of the kidney the so called glomerulus - to discuss the clinicopathologic of some major primary and secondary glomerular disease with nephrotic syndrome
How many kidneys do humans normally have, and what is their shap
Humans typically have two kidneys. They are bean-shaped organs.
What are the major structural components of the kidney?
Capsule - composed of tough fubres to help support the kidney mass nad protect it from injury
🧬 Parenchyma – The functional tissue of the kidney, divided into:
🔹 Cortex – The outer layer containing glomeruli and renal tubules (nephrons), where blood is filtered.
🔹 Medulla – Contains the renal pyramids, which house loops of Henle, proximal and distal tubules, and collecting ducts that concentrate and transport urine.
🚰 Pelvicalyceal System – The kidney’s drainage network, responsible for collecting and funneling urine:
🔹 Renal pelvis – A large cavity that collects urine before it passes into the ureter.
🔹 Calyces – Cup-like structures that collect urine from renal pyramids and drain it into the renal pelvis.
🩸 Renal Vasculature – The blood supply system of the kidney:
🔹 Renal artery – Delivers oxygenated blood from the abdominal aorta.
🔹 Afferent arterioles – Supply blood to the glomerulus for filtration.
🔹 Efferent arterioles – Carry filtered blood away from the glomerulus.
🔹 Renal vein – Drains deoxygenated blood from the kidney into the inferior vena cava.
💧 Nephron – The microscopic functional unit of the kidney, composed of:
🔹 Glomerulus – A capillary network where blood filtration occurs.
🔹 Bowman’s capsule – Surrounds the glomerulus and collects the filtrate.
🔹 Proximal convoluted tubule (PCT) – Reabsorbs nutrients, electrolytes, and water.
🔹 Loop of Henle – Concentrates urine by creating a gradient for water and salt exchange.
🔹 Distal convoluted tubule (DCT) – Regulates ion balance and pH.
🔹 Collecting ducts – Transport urine to the renal pelvis for excretion.
What are the primary blood vessels associated with the kidney?
Renal arteries: Supply oxygenated blood.
Renal veins: Drain deoxygenated blood.
What are the major functions of the kidney?
Filtration: Processes 1700 litres of blood per day into approximately 1 litre of urine.
Regulation: Maintains the body’s water and salt concentration, and the acid-base balance.
Endocrine function: Regulates bloo d pressure via the renal-angiotensin system.
What is the glomerulus?
A network of capillary loops (within the Kidney’s nephrons in the cortex ) is responsible for blood filtration, which is enclosed within the Bowman’s capsule.
What are the major components of the glomerulus
- Afferent arteriole: Brings blood into the glomerulus.
- Capillary loops: Provide a large filtration surface.
- Efferent arteriole: Drains blood away.
- Mesangial cells: Provide structural support and regulate filtration.
- Podocytes: Specialised epithelial cells aiding in filtration.
- Bowman’s space: Area where filtrate collects before moving into tubules.
What happens during glomerular filtration?
Blood flows through capillary loops, where waste products and excess substances are filtered out through the capillary walls. This filtrate then enters Bowman’s space and subsequently flows into the proximal tubule.
what can you see when looking at the kidney capillary loops under a scanning electron microscope (SEM)
you can see that the capillaries form a knot like structure with high surface area and are covered by podocytes
What is the role of podocytes in glomerular filtration?
Podocytes have foot processes that encircle capillary loops, creating filtration slits. They help prevent protein loss by preserving the integrity of the glomerular basement membrane (GBM). Damage to podocytes increases permeability, resulting in proteinuria ( protein in the urine - not good )
What is the structure of the glomerular filtration barrier?
This barrier consists of fenestrated endothelium, the glomerular basement membrane (GBM), and podocytes. It allows water and small solutes to pass while restricting proteins, preventing excessive protein loss in the urine.
what can you see when you look at the glomerular basement membrane under EM
It is a thick band with gaps to selectively allow the passage of water, small molecules and ions, but preventing larger molecules e.g. proteins from entering urine
What can you see about foot processes of podocytes when looking at EM imaging
numerous extentions (which branch out into pedicles) with narrow gaps (filtration slits) which help regulate passage of molecules across the filtration barrier)
what are some clinical manifestations of renal diseases
- Acute nephritic syndrome and nephrotic syndrome
- Asymtomatic hematuria or proteinuria
- Acute renal failure
- Chronic renal failure
- Urinary tract infection
What are the key differences between nephritic and nephrotic syndrome?
Nephritic syndrome is characterised by haematuria (blood in the urine), mild to moderate proteinuria (less than 3.5g/day), and hypertension. Nephrotic syndrome, on the other hand, presents with heavy proteinuria (greater than 3.5g/day), hypoalbuminemia, severe oedema, and hyperlipidaemia.
What conditions can be associated with nephrotic syndrome?
- Asymtomatic hematuria / proteinuria
- Acute renal failure
- Chronic renal failure
- Urinary tract infection
What are some common renal diseases and their presentations?
Some diseases present as asymptomatic haematuria, where mild blood is found in the urine without significant symptoms. Acute renal failure results in a sudden loss of kidney function, whereas chronic renal failure involves a gradual decline in function. Urinary tract infections (UTIs) can also occur, often presenting with symptoms of infection
What causes nephrotic syndrome?
Nephrotic syndrome results from increased permeability of the capillary wall to plasma proteins, which normally acts as a size and charge barrier.
What are primary causes for nephrotic syndrome
The primary causes include minimal change disease, focal segmental glomerulosclerosis, and membranous glomerulopathy.
What is focal segmental glomerulosclerosis (FSGS)?
FSGS is a kidney disorder causing scarring (sclerosis) in parts of some glomeruli which can cause progressive kidney failure if left untreated.
What are secondary causes for nephrotic syndrome
Secondary causes involve systemic diseases such as diabetes mellitus, amyloidosis, and systemic lupus erythematosus (SLE), which all affect the kidney.
What is minimal change disease (MCD)?
Minimal change disease is the most common cause of nephrotic syndrome which is most commonly seen in children aged 2 to 6 years. It is characterised by podocyte food process fusion, which alters the charge and permeability of the membrane, allowing proteins to leak into the urine.
What causes minimal change diseaes (MCD)
unknown but it could possible be due to immunologic responses to infection
What is the long term prognosis for minimal change disease
The prognosis for MCD is generally excellent, with most patients achieving complete remission with corticosteroid therapy (although some cases can show steroid resistance)
why is elecron microscopy essential for diagnosing minimal change disease?
Despite the significant proteinuria, light microscopy shows no structural changes, making electron microscopy essential for diagnosis.
What does minimal change disease look like under the microscope?
Under light microscopy, the glomerulus appears normal, with no thickening of the basement membrane or increase in cellularity. However, electron microscopy reveals podocyte foot process fusion, making the filtration barrier more permeable and leading to heavy proteinuria.
What is membranous glomerulopathy?
Membranous glomerulopathy involves immune complex deposition along the basement membrane. It is one of the most common causes of nephrotic syndrome
How does Membranous glomerulopathy cause nephrotic syndrome
electron dense deposits along the epithelial side of the basement membrane increase capillary permeability, allowing proteins to leak into the urine, leading to heavy proteinuria, hypoalbuminemia, oedema, and hyperlipidaemia (nephrotic syndrome).
What are the primary causes of membranous glomerulopathy?
Primary membranous glomerulopathy (85% of cases) is caused by autoantibodies against PLA2 receptors or thrombospondin receptors on podocytes along the basement membrane which results in podocyte injury, and increases glomerular permeability –> neprhoic syndrome (proteinuria, hypoalbuminemia and edema)
How does PLA2R antibody testing help in diagnosing membranous glomerulopathy?
🧪 PLA2R antibodies are present in 70-80% of cases, making them a key diagnostic marker.
📉 Antibody levels correlate with disease activity and can help monitor treatment response.
What is the secondary cause of membranous glomerulopathy
Secondary causes include drugs, malignancies, infections, and systemic diseases.
Which drugs are associated with secondary membranous glomerulopathy?
Drug-related causes include:
Penicillamine (used in Wilson’s disease & rheumatoid arthritis)
Gold therapy (previously used for rheumatoid arthritis)
NSAIDs (nonsteroidal anti-inflammatory drugs)
How is malignancy linked to membranous glomerulopathy?
Malignancy-associated membranous glomerulopathy occurs when circulating tumor antigen-antibody complexes deposit in the glomerular basement membrane. It is more common in the elderly and may be linked to solid tumors (e.g., lung, colon, or breast cancer).
Which infections can cause secondary membranous glomerulopathy?
Chronic infections
Hepatitis B
Hepatitis C
Malaria (less common)
What systemic diseases are associated with secondary membranous glomerulopathy?
Autoimmune diseases such as systemic lupus erythematosus (SLE) can lead to immune complex deposition, causing membranous glomerulopathy.
What is the underlying mechanism of membranous glomerulopathy?
Antigen-antibody mediated disease—immune complexes deposit along the glomerular basement membrane, leading to immune activation and damage.
How does membranous glomerulopathy typically present?
Insidious onset—patients often develop gradual proteinuria without initial symptoms.
Why is it important to investigate underlying causes of membranous glomerulopathy?
It may be secondary to malignancy or infection, so screening for cancer, hepatitis B/C, and autoimmune diseases is essential.
What is the long-term prognosis of membranous glomerulopathy?
10% of cases progress to chronic kidney disease.
How often does membranous glomerulopathy lead to renal insufficiency?
Less than 40% of patients develop renal insufficiency over time.
What histological findings are seen in membranous glomerulopathy when using silver stain, immunofluorescence and electron microscopy?
Silver stain: Highlights the spiky appearance of the basement membrane, indicating immune deposits.
Immunofluorescence: Shows granular deposits of IgG antibodies along the basement membrane.
Electron microscopy: Reveals electron-dense deposits on the outer epithelial side of the basement membrane
What clinical signs are associated with membranous glomerulopathy
Insidious onset with heavy proteinuria.
Often detected during routine tests in elderly patients.
what are the outcomes associated with membranous glomerulopathy
10% progress to chronic renal disease.
Up to 40% develop renal insufficiency over time.
Why is looking for membranous glomerulopathy particularly important in elderly patients?
Secondary membranous glomerulopathy is often linked to malignancy or chronic infections in older patients.
Diagnosis often requires investigating for underlying tumours or hepatitis infections.
What are the electron microscopy (EM) findings in membranous glomerulopathy?
Electron-dense deposits: Seen as dark, rounded structures on the epithelial side of the basement membrane.
These deposits correspond to immune complexes (IgG and complement proteins).
Basement membrane changes: Thickened and irregular due to the deposits.
Capillary lumen: Visible with red blood cells, showing that filtration is still occurring but is compromised.
EM findings correlate with the granular immunofluorescence pattern seen in immunohistochemistry.
What is focal segmental glomerulosclerosis (FSGS)?
A disease causing nephrotic syndrome that can be primary (idiopathic) or caused by secondary scarring from other glomerulonephritis
What is glomerulonephritis?
A kidney disease where the tiny filters (Glomeruli) become inflamed or damaged, impairing the kidney’s ability to filter blood (potentially leading to kidney failure / complications)
what is some causes for FSGC
HIV infection.
Obesity (associated with nephrotic-range proteinuria and hypertension).
Sickle cell anaemia.
Glomerular ablation (e.g., single kidney or kidney removal): Adaptive response to higher filtration pressure leads to mechanical damage and scarring.
how does FSGC respond to glomerular ablation and corticosteroids
adaptive response to glomerular ablation ( unilateral renal agenesis) and responds poorly to corticosteroids
what do many FSGC progress to
chronic glomerulonephritis
what percent of nephrotic syndrome is caused by focal segmental glomerulosclerosis
10-15%
What is the histological appearance of focal segmental glomerulosclerosis (FSGS)?
Normal-appearing glomerular tufts in most areas.
Segmental sclerosis: Pink, collapsed, and scarred areas in part of the glomerulus, often near the vascular pole.
Sclerosis results from mechanical turbulence and vascular issues.
what percentage of insulin-dependent type I diabetics have nephrotic syndrome
30%
What glomerular changes are seen in diabetic nephrotic syndrome cases?
Basement membrane thickening which is due to non-enzymatic glycation of proteins and increasing permeability which ultimately results in proteinuria
How does the mesangial matrix change in diabetic nephropathy?
Mesangial matrix expansion leads to nodular glomerulosclerosis, forming Kimmelstiel-Wilson lesions (accumulation of extracellular matrix components within the glomeruli, forming nodules that can lead to kidney damage).
What vascular changes occur in diabetic nephropathy?
Arteriosclerosis of medium-sized arteries due to chronic hyperglycemia-induced endothelial damage, worsening kidney function.
What is arteriosclerosis?
he thickening and hardening of the walls of the arteries,
Why are diabetics with nephrotic syndrome more susceptible to infections?
Immune dysfunction from protein loss (IgG, complement factors because they are being deposited) and poor circulation (arteriosclerosis) increases risk of urinary tract infections and kidney infections.
What is papillary necrosis, and why does it occur in diabetic nephropathy?
Renal papillary necrosis results from ischemia and microvascular damage, leading to tissue death in the renal papillae, which can cause hematuria and obstruction.
What is are key histological feature of diabetic glomerulopathy
- Nodular glomerulosclerosis (Kimmelstiel-Wilson nodules).
- Basement membrane thickening (due to non-enzymatic glycation of proteins)
- Increased esangial matrix (leading to sclerosis and reduced filtration efficiency)
What is the underlying pathogenesis of diabetic glomerulopathy?
Metabolic defects from hyperglycemia, causing:
Advanced glycosylation end-products (AGEs) → cross-linking proteins, increasing stiffness
Basement membrane damage → thickening and loss of integrity
What special stains highlight changes in diabetic glomerulopathy?
🧪 Positive staining with:
Periodic acid-Schiff (PAS) → highlights mesangial expansion and nodules
Silver stain → highlights thickened basement membrane and Kimmelstiel-Wilson nodules
EM findings in diabetic glomerulopathy
Basement membrane thickness increases from 250–350 nm (normal) to up to 1000 nm (1 micron) and increased mesangial matrix
What is amyloidosis?
Deposition of amyloid protein (abnormal protein) in between various cells, tissues and organs in a wide variety of clinical settings. There are primary, secondary, hereditary and localised forms
what do amyloid deposits cause
nephrotic syndrome by disrupting kidney filtration
What is primary / AL type amyloidosis caused by
Due to light chains secreted in plasma cell dyscrasias (e.g., multiple myeloma).
What is secondary or reactive / AA type amyloidosis caused by
Reactive to chronic inflammation e.g.
Osteomyelitis.
Bronchiectasis.
Tuberculosis.
Rheumatoid arthritis.
what is hereditary amyloidosis caused by
e.g. Familial Mediterranean Fever
what are localised amyloidosis caused by
Specific deposits (e.g., seminal vesicles).
Histological findings in amyloidosis
Congo red stain shows apple-green birefringence under polarised light.
Amorphous deposits in the glomerulus, disrupting filtration.
Histological and EM findings in amyloidosis
Fibrillar appearance of amyloid deposits between cells.
Subendothelial and mesangial deposits visible.
What is amyloidosis in the kidney caused by
Amyloidosis in the kidney is caused by the extracellular deposition of amyloid proteins. This deposition disrupts normal tissue structure and function. Amyloid is a group of abnormal proteins with a characteristic β-pleated sheet conformation.
amyloidosis histology under light microscopy
On light microscopy it is an amorphous, eosinophilic
extracellular substance that encroaches on adjacent
cells
amyloidosis histology under light microscopy - HE staining
Purpose: General staining technique to observe tissue architecture and pathological changes.
Usage in Amyloidosis: Identifies eosinophilic deposits of amyloid in the kidney - seen in the glomeruli
amyloidosis histology under light microscopy - Congo red stain
Purpose: A specific stain for amyloid proteins.
Usage in Amyloidosis: Highlights amyloid deposits in orange-red hues under light microscopy.
Amyloidosis histology under light microscope - Congo red stain
Purpose: Enhances specificity for amyloid by demonstrating apple - green birefringence.
Usage in Amyloidosis: Differentiates amyloid deposits from other substances.
Amyloidosis histology under light microscopy - Electron microscopy (EM)
Purpose: High-resolution imaging to visualise ultrastructural details of tissues.
Usage in Amyloidosis: Confirms the presence of characteristic amyloid fibrils which are 7.5 - 10nm in diameter
What is systemic Lupus Erythematosis (SLE)
SLE is a systemic autoimmune disease involving multiple organs. The formation of autoantibodies leads to immune complex deposition, causing widespread inflammation and tissue damage.
What is the underlying cause of Systemic lupus erythematosis (SLE)
ailure of regulatory mechanisms that sustain self-tolerance, leading to autoimmunity.
What antibodies are involved in systemic Lupus Erythematosis (SLE)
Anti-nuclear antibody (ANA) – universally positive in SLE.
Anti-double-stranded DNA (anti-dsDNA) – highly specific for SLE.
Anti-Smith (Sm) antigen – pathognomonic for SLE.
What is the significance of the ANA test in SLE?
Immunofluorescence test for ANA is always positive in SLE patients.
What is the pathogenesis of disease in systemic Lupus Erythematosis (SLE)
Failure of regulatory mechanisms disrupts self-tolerance, leading to autoantibodies against nuclear, cytoplasmic, and cell-surface antigens.
what sort of onset is observed in systemic Lupus Erythematosis (SLE)
Acute or insidious in its onset, remitting and
relapsing, often febrile illness
What are the features of systemic Lupus Erythematosis (SLE)
Skin rashes, arthritis, serositis, renal involvement (lupus nephritis), and haematological abnormalities.
Lupus nephritis is a major complication, leading to proteinuria and nephrotic syndrome.
How common is systemic lupus erythematosus (SLE)
Fairly common (1:2500); mostly women
What method is used for diagnosing systemic lupus erythematosus (SLE) and what does it test positive for
Immunofluorescence testing and specific antibody panels.
Immunofluorescence test for ANA is always
positive as well as double stranded DNA and
Smith (Sm) antigen
SLE Histology - Class I
Minimal Mesangial Lupus Nephritis
-Immune complex deposits are limited to the mesangial areas.
-No significant structural abnormalities on light microscopy.
- Usually asymptomatic or with mild proteinuria.
Electron Microscopy:
-Scattered immune deposits in the mesangium.
SLE Histology - Class II
Class II: Mesangial Proliferative Lupus Nephritis
- Increased mesangial matrix and mesangial cell hypercellularity.
- May present with mild haematuria or proteinuria.
Electron Microscopy:
- Immune deposits predominantly in the mesangium
SLE Histology - Class III
Class III: Focal Lupus Nephritis
- Segmental or global involvement of fewer than 50% of glomeruli.
- Immune deposits and intraluminal proliferations are observed.
- Symptoms may include haematuria, proteinuria, or hypertension.
Electron Microscopy:
- Subendothelial immune deposits are predominant.
SLE Histology - Class IV
Class IV: Diffuse Lupus Nephritis
- Almost all glomeruli show marked proliferation, immune complex deposition, and capillary obliteration.
- Presents with severe nephrotic syndrome, haematuria, and renal dysfunction.
Electron Microscopy:
-Extensive subendothelial immune deposits.
SLE Histology - Class V
Class V: Membranous Lupus Nephritis
- Thickened glomerular basement membranes due to subepithelial immune deposits.
- Resembles idiopathic membranous glomerulopathy.
-Presents with nephrotic syndrome and possible thrombotic complications.
Electron Microscopy:
- Prominent subepithelial immune deposits.
What is a “full house” Immunofluorescence staining pattern in Lupus Nephritis
Positive for IgG, IgA, IgM, C3, and C1q.
Useful for identifying the type and distribution of immune deposits.
