Lecture 6 : Renal Disease

Nephron

What is the structural and functional unit of the kidney?

It is responsible for filtering plasma

What is the function of the nephron ?

metanephric cap

From which embryonic structure does the nephron arise?

Reabsorption and secretion

What are the main processes that occur in the nephron after filtration?

Intestines

where does absorption first occur?

Kidneys

Where does reabsorption occur?

Mesonephric duct (mesonephros)

From which embryonic structure does the yellow part of the kidney arise?

Aorta → Renal Artery → Afférent artérioles →Glomerulus → Proximal Convoluted Tubule → Loop of Henle → Distal Convoluted Tubule → Collecting Tubules → Collecting Ducts → Minor Calyces → Major Calyces → Renal Pelvis → Ureteral → Urinary Bladder

What is the correct flow of urine through the urinary system?

It flows down the Ureter to the urinary bladder

Where does urine go after draining into the renal pelvis?

20-25 %

What percentage of the cardiac output does the kidney receive?

5 liters per minute

What is the normal cardiac output ?

1 liter per minute (20-25%)

If the cardiac output is 5L/min, how much of it reaches the kidneys?

55%

Of the renal blood flow, how much is Renal Plasma Flow?

20 %

Of the Renal plasma flow, how much goes to the glomerulus (GFR)?

About 20 mL per minute from approximately 500-600 mL of renal plasma flow

If 20-25% of the 5 L cardiac output goes to the kidneys, how much plasma reaches the GFR?

120 mL per minute

What is the normal glomerular filtration rate?

• Filtration and Regulations of Plasma

• Regulations of Acid-Base Balance

• Endocrine Function

What are the three main functions of the kidney?

Plasma, Buffy coat, and Red blood cells

What are the three parts of blood?

Albumin and globulin

What are the main plasma proteins?

Albumin

Smallest and most abundant protein

• water

• Nutrients

• Waste products

Which components of plasma can pass through the glomerular filtration barrier?

No, their presence indicates a renal disease

Should plasma proteins or any type of cells be seen in the kidney filtrate?

The “specialized capillary tuft”

What is another name for glomerulus?

• Fenestrated endothelium

• Glomerulus Basement membrane

• Podocyte foot processes

What are the three layers that make up the glomerular filtration barrier?

Fenestrated endothelium

What type of endothelium does the glomerulus have?

Negatively charged

What is the charge of the glomerular basement membrane ?

It repels proteins and cells, since both are also negatively charged.

What is the function of the negative charge of the basement membrane ?

• Narrow Fenestrated NSS

• Negatively charged basement membrane

Why can’t RBCs and WBCs pass through the glomerular filtration barrier?

It may indicate the foundation of renal disease

What happens if proteins or cells pass through the glomerular barrier?

• Glomerular diseases

• Tubulointerstitial diseases

What are the two main classifications of renal diseases?

• Immune complex deposition

• Antibody response

• Cytokines activity

What is the main cause of glomerular diseases?

Chemicals and toxins

What are non-immunologic causes of glomerular diseases?

• Nephrotic syndrome

• Nephritic syndrome

What are the two main types of glomerular diseases?

Protenuria ++++

What is the key feature of nephrotic syndrome ?

Hematuria ++++

What is the key feature of nephritic syndrome?

Nephritic syndrome,

It can lead to acute kidney disease and chronic kidney disease (CKD)

Which of the two (nephrotic or nephritic) is more severe?

And why?

• Nephrotic = proteins in urine

• Nephritic = Cells (RBCs and WBCs) in urine

How can you differentiate nephrotic from Nephritic syndrome through urine?

Sterile pyuria

What type of pyurie is found in nephrotic and nephritic syndromes?

Humoral immune system

Which part of the immune system mainly contributes to glomerular diseases?

• Neutralization

• Opsonization

• Promotion of cell-mediated immunity

• Complement activation

What are the four main functions of antibodies or immune responses in glomerular injury?

Membrane Attack Complex (MAC)

A structure formed from complement activation that creates holes or pores in cell membranes, leading to cell lysis.

The excess complexes deposits in tissues, causing diseases such as :

• Rashes

• Arthritis

• Glomerulonephritis

What happens when the production of immune complexes exceeds the body’s ability to clear them?

Glomerulonephritis

What condition results when immune complexes deposit in the glomerulus?

Massive proteinuria greater than 3.5 g/day

What is nephrotic syndrome marked by?

Loss of negativity of Glomerular filtration barrier or injury / dysfunction of podocytes.

What causes the massive proteinuria in nephrotic syndrome?

Spaces between podocyte foot processes widen and gain a positive charge, allowing negatively charged proteins to pass through.

What happens when the GFB loses its negative charge?

Loss of oncotic pressure , leading to fluid leakage into tissues and edema.

What does the loss of albumin cause in nephrotic syndrome?

Anasarca

Generalized body edema due to severe fluid accumulation

• Hypoalbuminemia

• Edema

• lipidemia

• Lipiduria

• Proteinuria

What are the main features of nephrotic syndrome?

Minimal change disease

What is the most common cause of nephrotic syndrome in children (4-8 years old)?

Lipoid nephrosis

What was the previous name for minimal change disease?

Idiopathic - often related to immune factors such as T-cell cytokine release

What is the etiology of MCD?

• Hodgkin’s lymphoma

• URTI

• NSAID use

What conditions are associated with Minimal Change Disease?

Selective proteinuria

What is the unique finding in Minimal Change Disease?

Excellent - responds well to steroids

What is the prognosis for Minimal Change Disease?

No, only focal areas and certain segments of the glomerulus are affected

In Focal Segmental Glomerulosclerosis , is the entire glomerulus affected?

• Adults

• Hispanics

• Africans

• Drug users (Heroin addicts)

What population is commonly affected by Focal Segmental Glomerulosclerosis?

Idiopathic - may involve hyalinosis in focal areas

What is the etiology of Focal Segmental Glomerulosclerosis ?

Nephrotic syndrome + Hematuria

What are the key findings in Focal Segmental Glomerulosclerosis?

Poor

What is the prognosis for Focal Segmental Glomerulosclerosis?

In situ immune complex formation → thickening of the glomerular basement membrane (GBM)

What causes membranous nephropathy?

IgG and complement proteins

What immunologic components deposit along the GBM in membranous nephropathy?

Anti-PLA2R antibodies that target podocytes

What is the main antibody associated with membranous nephropathy?

• HBV

• HCV

• Syphilis

• Sjögren syndrome

• SLE

• And Gold therapy

What are common associated conditions of membranous nephropathy ?

Subepithelial deposits producing a “spike and dome” appearance

What is the characteristic histologic finding of membranous nephropathy?

Diabetic nephropathy

What is the most common cause of nephrotic syndrome and chronic kidney disease in adults?

Non-enzymatic glycosylation of glomerular capillaries

What causes the kidney damage in diabetic nephropathy?

Eyes, and nerves

what other organs are affected by diabetic nephropathy?

They continuously excrete protein through urine, leading to decreased protein levels in the body—especially albumin—causing hypoalbuminemia.

What happens to protein levels in patients with nephrotic syndrome?

Albumin maintains oncotic pressure in the blood vessels. Without it, fluid leaks from the vessels into tissues, causing edema.

Why does the loss of albumin lead to edema?

When the body loses protein, the liver compensates by producing more proteins—including lipoproteins, which are lipid precursors—resulting in high lipid levels and lipiduria.

Why does lipiduria occur in nephrotic syndrome?

liver overproduces lipoproteins to compensate for protein loss, leading to hyperlipidemia.

Why do patients with nephrotic syndrome have high cholesterol levels?

Proteinuria, defined as the excretion of more than 3.5 grams of protein per day.

What is the most important diagnostic feature of nephrotic syndrome?

Recurrent infections and hypercoagulability

Aside from HELP (Hypoalbuminemia, Edema, Lipidemia, Proteinuria), what other complications should be remembered in nephrotic syndrome?

Because they lose immunoglobulins (a type of globulin) in the urine, which weakens the immune system.

Why do patients with nephrotic syndrome experience recurrent infections?

Both urine and blood are examined

In evaluating nephrotic syndrome, which specimens are examined to confirm the diagnosis?

• Protein (++++)

• Lipiduria

• Spot protein/creatinine ratio:
   • Children: >200 mg/mmol
   • Adults: >300 mg/mmol

• 24-hour urine specimen showing >3.5 g protein/24h

What are the expected urine findings in nephrotic syndrome?

24-hour urine specimen

What is the best urine specimen for diagnosing nephrotic syndrome?

Numerous proteins and lipids, including oval fat bodies.

What do you expect to see under the microscope in the urine of a nephrotic syndrome patient?

Lipiduria

What does the presence of oval fat bodies in urine indicate?

A condition where only albumin passes through the glomerular barrier while globulins are spared.

What is selective proteinuria?

Minimal Change Disease (MCD)

Which nephrotic syndrome is associated with selective proteinuria?

• Decreased albumin, globulin, and total protein

• Decreased serum calcium

• Increased lipid panel (TAG, LDL, VLDL)

What are the expected blood findings in nephrotic syndrome?

Membranous Nephropathy

A Hepatitis Panel is associated with which renal disease?

Focal Segmental Glomerulosclerosis

A CD4+ Lymphocyte test is associated with which renal disease?

Membranous Nephropathy

A Reactive Plasma Reagin (RPR) test is associated with which renal disease?

Focal Segmental Glomerulosclerosis

Drug abuse screening is related to which renal disease?

Diabetic Nephropathy

Fasting Blood Sugar (FBS) and HbA1c tests are associated with which renal disease?

1. LM – Light Microscopy

2. EM – Electron Microscopy

3. IF – Immunofluorescence Microscopy

What are the three types of renal biopsy microscopy?

1000x

What is the maximum magnification of a light microscope (LM)?

To visualize cellular and ultrastructural details

What is the function of electron microscopy (EM) in renal biopsy?

It uses fluorophores to highlight immune deposits and other structures with fluorescent colors.

What is the purpose of immunofluorescence microscopy (IF)?

• LM: Normal

• EM: Podocyte effacement

• IF: Normal

What are the LM, EM, and IF findings in Minimal Change Disease (MCD)?

• LM: Focal hyalinosis; sclerosis of parts of the glomerulus

• EM: Podocyte effacement

• IF: Normal

What are the LM, EM, and IF findings in Focal Segmental Glomerulosclerosis

• LM: Glomerular basement membrane (GBM) thickening (“Thick and Sick”)

• EM : Podocyte effacement and subepithelial deposition of immune complexes (IC) forming a Spike and Dome appearance.

• IF : Granular subepithelial immune complex (IC) deposits.

What are the LM, EM, and IF findings in Membranous Nephropathy (MN)?

Kimmelstiel-Wilson nodules (PAS-positive due to sugars).

What histologic feature is characteristic of diabetic nephropathy?

Sugars (glycoproteins) — showing highly pink structures with hyalinosis in the mesangium and glomerulus.

What does the PAS (Periodic Acid-Schiff) stain detect in diabetic nephropathy?

• Kimmelstiel-Wilson nodules

• GBM thickening

• Mesangial expansion

What are the light microscopy (LM) findings in diabetic nephropathy?

• Hypertension

• Oliguria (<500 mL/day)

• Azotemia (↑ BUN & creatinine)

• Anemia

• Edema (Na⁺ retention)

• Limited proteinuria (<3.5 g/day)

What are the associated findings in nephritic syndrome?

higher risk of progression to CKD and ESRD (End-Stage Renal Disease)

Why is nephritic syndrome considered more severe?