Glomerular diseases Flashcards
What are glomerular diseases? What two types are there?
Diseases of the glomeruli
Glomerulonephritis: inflammation of the glomeruli
Glomerulopathies: non-inflammatory disease of glomeruli
What is a glomerulus?
Draw the structure of a nephron + glomerulus.
A network of capillaries located at the beginning of a nephron in the kidney, next to the Bowman’s capsule
http://www.ivyroses.com/HumanBody-Images/Urinary/Kidney_Nephron_cIvyRose.png
What is focal glomerular disease?
When some but not all the glomeruli are affected
What is diffuse glomerular disease?
When most of the glomeruli are affected
What is segmental glomerular disease?
When only part of each glomerulus is affected
What is proliferative glomerular disease?
There is hyperplasia of the glomerular cells (increase in cell numbers)
Describe the structure of a glomerulus?
Afferent arteriole gives rise to the capillary bundle, which gives rise to the efferent arteriole
The capillary bundle is next to/within the Bowman’s capsule
The capillary endothelium is specialised for filtration
Podocytes are cells that surround each capillary vessel
Between the capillaries is the mesangium
The macula densa is found between the afferent and efferent arterioles at the point they enter the Bowman’s capsule, adjacent to this is the ascending limb of the nephron
What is the mesangium?
What does it do?
The space between the cells of a glomerulus is occupied by mesangial cells.
They are not part of the filtration barrier
The cells participate indirectly in filtration by contracting and reducing the glomerular surface area, and therefore filtration rate, in response mainly to stretch
What do podocytes do?
They are an extra barrier to aid filtration
They have slits
They are able to contract and reduce the filtration rate by closing their slits
What is the macula densa?
What does it do?
It is found between to the ascending limb of the nephron and the afferent + efferent arterioles
It is a network of specialised cells
Which are sensitive to the concentration of NaCl in the thick ascending limb. Low NaCl indicates GFR is too low
A decrease in NaCl concentration initiates a signal from the macula densa
The signal causes dilation of the afferent arterioles resulting in increased blood flow through glomerulus, increasing the GFR
The signal also increases renin release from the juxtaglomerular cells of the afferent and efferent arterioles, which are the major storage sites for renin
What are the juxtaglomerular cells?
Cells that store renin and are found next to the afferent and efferent arterioles
What is the difference between the afferent and efferent arterioles?
Afferent: brings blood to the glomerulus
Efferent: takes blood away from the glomerulus
Remember the Latin: ex = from, ad = to
Pyelonephritis and glomerulonephritis can be easily confused. What is the difference?
Pyelonephritis: infection in the urinary system, can only affect one kidney
Glomerulonephritis: autoimmune disease, autoantibodies attack the glomerulus, always affects both kidneys since it’s a systemic disease
What evidence is there that glomerulonephritis is an immune condition?
Deposits of immunoglobulin are found in the kidneys
Inflammatory cells are found: macrophages, neutrophils
Positive response to immune system treatment
What two syndromes can glomerulonephritis result in?
Nephritic Syndrome
Nephrotic Syndrome
One or both
What can glomerulonephritis cause?
Leaky glomeruli: protein and haematuria
Hypertension
Deteriorating kidney function
Why does glomerulonephritis cause hypertension?
Because inflammation causes damage and thus reduced renal perfusion
The body compensates by raising blood pressure
What is acute nephritic syndrome?
A group of symptoms that occurs in some cases of glomerulonephritis
Destruction of epithelial barrier lining the glomeruli
What are the clinical features of acute nephritic syndrome?
Haematuria
Proteinuria
Hypertension, raised JVP
Oliguria
Oedema: peripheral + pulmonary
Uraemia
What are some diseases associated with the development of acute nephritic syndrome?
ANCA associated vasculitis
Streptococcal infection
Goodpasture’s disease
SLE
Systemic Sclerosis
Henoch Schoenlein purpura
How does ANCA associated vasculitis cause damage to the kidneys?
ANCA: anti-neutrophil cytoplasmic antibodies
Attack the small blood vessels including the glomeruli, cause necrosis of blood vessel walls
Inflammatory cells infiltrate
How do you treat ANCA associated vasculitis?
Immunosuppression
Steroids
Rituximab
What does ANCA stand for?
Anti-neutrophil cytoplasmic antibodies
How does a streptococcal infection cause damage to kidneys?
Sometimes, after a Strep infection immune complexes (antigen-antibody) are deposited in the kidney
Classically it’s a tonsillitis infection
How does Goodpastures disease cause kidney damage?
Deposits of autoantibodies along basement membrane of glomerulus
They cause in immune response there, damaging the glomerulus
How would you diagnose Goodpasture’s disease?
Anti-glomerular basement membrane antibodies
Lung involvement as well: haemoptysis
How would you treat Goodpasture’s disease?
Remove the antibody
Plasma exchange
Immunosuppression
How does SLE damage the kidneys?
Systemic Lupus Erythematosus
Systemic condition where body attacks its own cells, including renal cells
What is Henoch Schoenlein purpura?
A condition in which blood vessels become inflamed
Causing rash, abdominal pain, AKI
What is Nephrotic syndrome?
A group of symptoms that sometimes occurs as a result of glomerulonephritis
Massively increased filtration of large molecules across the glomerular capillary wall (out of blood into urine)
Due to damaged podocytes
What are the clinical features of nephrotic syndrome?
Heavy proteinuria
Hypoalbuminaemia
Oedema
Hyperlipidaemia
Why does nephrotic syndrome cause heavy proteinuria and hypoalbuminaemia?
Because damage to the glomerular filtration system, especially the podocytes, means proteins can leave the bloodstream and enter the tubules
Leaving protein in the urine
And less albumin is left in the blood
Why does nephrotic syndrome cause oedema?
Hypoproteinaemia
Fluid leaves the blood stream and enters tissues due to a decrease in oncotic pressure
What is oncotic pressure?
Describe its link with oedema.
Pressure exerted by proteins, notably albumin
In a blood vessel’s plasma it pulls water into the circulatory system
So reduced oncotic pressure means no pull into circulatory system
Fluid enters tissues and causes oedema
Why does nephrotic syndrome cause hyperlipidaemia?
Hypoproteinaemia stimulates the liver to make more protein, including lipoproteins
Catabolism of lipids is reduced due to reduced levels of lipases
What is anasarca?
Widespread oedema throughout the body, particularly the face
What are the primary causes of nephrotic syndrome?
Minimal Change Disease: a renal disease of children
Membranous glomerulonephritis: inflammation of glomerular membrane, impaired filtration
Focal Segmental Glomerulsclerosis: scarring of glomerular tissue
What are some secondary causes of nephrotic syndrome?
Diabetes Amyloidosis Infections SLE Malignancy Drugs
What are the key differences between nephritic and nephrotic syndrome?
Nephritic:
- oliguria
- haematuria
- hypertension
Nephrotic:
- oedema
- proteinuria
- hypoalbuminaemia
- hyperlipidaemia
Investigation of glomerulonephritis?
Aim is to find the cause!
Blood:
- FBC, U+E
- ESR/CRP: is it inflammatory
- Serology: autoantibodies, ANCA
Urinalysis:
- Look for RBC casts
- Proteinuria
USS: look for visible damage
CXR: look for pulmonary oedema
Renal biopsy:
- will show what part is damaged, podocytes, mesangium, basement membrane
- will show if focal or diffuse, segmental or global
Management of glomerulonephritis in general?
Refer to a nephrologist!
Treat the underlying cause if you know it
Maintain BP
Prescribe an ACEi or ARB, these can help reduce proteinuria and preserve renal function
Management of nephritic syndrome?
Treat hypertension: diuretics, vasodilators, salt restriction
Treat oedema: diuretics
Fluid restriction in patients with fluid overload + oliguria
Treat causes: antibiotics, immunosupression
Manage life threatening complications: encephalopathy
Management of nephrotic syndrome?
Treat oedema: diuretics
Treat proteinuria: ACEi or ARBs
Treat underlying cause: immunosuppression, cessation of offending drug
What is minimal change disease?
Why is it named this?
A disease that causes nephrotic syndrome, it affects children
For many years doctors couldn’t see any abnormalities on biopsies
What are the 3 hallmarks of minimal change disease?
- Diffuse loss of podocytes foot processes
- Vacuolation (formation of vacuoles)
- Growth of microvilli on the visceral epithelial cells
How can you treat minimal change disease?
Steroid: immunosuppressant, prednisolone
ACEi to help with proteinuria
What is Focal Segmental Glomerulsclerosis (FSG)?
Scarring of the glomerulus
Focal: only affects some of the glomeruli
Segmental: part of each glomeruli affected
