06-03-23 - Pathology of the kidney, ureters and bladder 1 Flashcards
Learning outcomes
- Describe the classification of renal disease
- Describe common congenital disorders of the kidney
- Classify glomerular renal disease and name common examples
- Know something about tubulointerstitial disease: cause and effects
What are 5 different parts of the GU system?
What are 5 different types of pathologies of the GU system?
- 5 different parts of the GU system:
1) Kidney
2) Ureter
3) Bladder
4) Prostate
5) Urethra - 5 different types of pathologies of the GU system:
1) Trauma
2) Swelling, mass, tumour
* Non-neoplastic
* Benign
* Malignant - Primary or Secondary
3) Chronic
* Chronic inflammatory
4) Acute
* Infection
* Acute inflammation
* Immunological
5) Stone
* Genetic
* Metabolic
What are 4 different functions of the kidney?
How can knowing these functions and anatomy allow us to diagnose?
- 4 different functions of the kidney:
1) Fluid and electrolyte balance
2) Resorption of solutes
3) Excretion eg of conjugated xenobiotics
4) Endocrine
* Renin - regulates blood pressure
* Erythropoietin (EPO) – RBC production (can cause anaemia with renal disease)
- Knowing these functions can help us to understand what renal failure will look like and make a d diagnosis (both acute and chronic)
What are 2 examples of congenital kidney diseases?
- 2 examples of congenital kidney diseases:
1) Hypoplasia
* Can lead to vesicoureteric reflux (urine reflux into kidney) and renal artery stenosis
2) Potter Syndrome – bilateral renal agenesis
* Both kidneys fail to develop so no urine is produced
* There will be no amniotic fluid, leading to the baby being squashed
3) Cystic kidney disease
4) Familial Mediterranean Fever
5) Alport’s Syndrome
How does renal artery stenosis affect the development of the affected kidney?
How can this affect BP and other organs? What is the treatment for this?
- Renal artery stenosis will lead to underdevelopment of the affected kidney
- Since the kidney has low blood flow, it will produce more renin to raise more blood pressure in order to get more blood flow
- This increase in BP can lead to end organ damage in other organs
- The treatment for this is to remove the affected kidney
What are 5 different cystic kidney diseases (in picture)?
Can hey be congenital?
How common is cystic kidney disease?
How does it affect the kidneys?
What is there a risk of?
How can Familial Mediterranean Fever affect the kidneys? W
hat is Alport’s syndrome?
What is it caused by?
- 5 different cystic kidney diseases (in picture)
- Cystic kidney disease can be congenital (e.g polycystic disease – can be autosomal dominant and recessive)
- Cystic kidney disease is common, and accounts for roughly 1/3rd of patients on dialysis
- Cystic kidney disease results in the kidneys becoming cystic and dilated, and can also cause inflammation and scarring
- There is a risk of infection, haemorrhage, and chronic renal failure in cystic kidney disease
- The major renal involvement in FMF (Familial Mediterranean Fever) is the occurrence of amyloidosis that primarily affects the kidneys causing proteinuria and ending in death from renal failure
- Alport syndrome is a rare inherited form of kidney inflammation (nephritis).
- It is caused by a defect (mutation) in a gene for a protein in the connective tissue, called collagen.
- There are three genetic types: X-linked Alport syndrome (XLAS) is the most common type
How common is glomerular disease?
What are 2 primary forms of glomerular disease?
What are 2 secondary glomerular diseases causes?
- Glomerular disease is common – possible 1/3rd of patients on dialysis
- 2 primary forms of glomerular disease:
1) Glomerulonephritis
2) Glomerulopathy - 2 secondary glomerular diseases causes:
1) Vascular
2) Autoimmune eg SLE, amyloid, diabetes, acquired
What is the glomerulus?
What are the 3 layers of glomerular filtration?
How does the glomerulus filter molecules?
What can happen if this filter system is damaged?
What is the role of the mesangial cells of the glomerulus?
- The glomerulus is the filtering unit of the kidney
- 3 layers of glomerular filtration:
1) Endothelial cells of the glomerular capillaries
2) Basement membrane of the capillaries
3) Foot processes of the podocytes
- Think of 3 sieves with decreasing pore size
- The glomerulus filters substances by size (e.g erythrocytes) but also by charge
- The negatively charged glycoproteins that make up the filters of the glomerulus will repel negatively charged substances, such as serum album
- Damage to this filtering system will lead to molecules that getting through the filter when they normally shouldn’t e.g glucose in diabetes
- Mesangial cells are contractile cells that constitute the central stalk of the glomerulus
- Intraglomerular mesangial cells can also act as phagocytosing cells
What are the 4 types of hypersensitivity reactions?
- 4 types of hypersensitivity reactions:
1. Type I: reaction mediated by IgE antibodies.
2. Type II: cytotoxic reaction mediated by IgG or IgM antibodies.
3. Type III: reaction mediated by immune complexes.
4. Type IV: delayed reaction mediated by cellular response e.g T-cells and cytokines
How does Goodpasture’s syndrome occur?
How does it affect the filter of the glomerulus?
If it is an inflammatory site, what can be activated?
What does the presence of fibrin lead to?
How does this affect blood flow to the glomerulus?
- Goodpasture’s syndrome occurs when there is a type II hypersensitivity (antibody production) reaction to Goodpasture’s antigens on the basement membrane of the glomerulus of the kidneys and the pulmonary alveolus.
- If the antibody fixes complement, there will be generation of membrane attack complex, which will punch holes in the basement membrane, creating a hole in the filter of the glomerulus
- This can be an inflammatory site, which can lead to the activation of protein cascades, so fibrin may be generated and proteases activated
- The presence of fibrin leads to cells in the Bowman’s capsule proliferating and filling Bowman’s space
- The glomerulus will be squeezed, and the perfusion of blood through the glomerulus will decrease, leading to patients presenting with oliguria or anuria
What are 6 clinical effects of Good Pasture’s syndrome?
What are 2 causes of Goodpasture syndrome?
How can Goodpasture syndrome appear in histology?
How can Goodpasture’s syndrome be treated?
How serious is this condition?
- 5 Clinical effects of Good Pasture’s syndrome:
1) Diffuse and rapid process – every glomerulus can be damaged in 5 days, leading to dialysis being needed
2) Renal failure
3) Oliguria/anuria
4) Haematuria if any urine is produced
5) Proteinuria
6) Lung involvement
- 2 Causes of Goodpasture syndrome:
1) Autoimmune e.g Vasculitis (ANCA) or SLE
2) Organic solvents
- In histology, Goodpasture syndrome can appear with crescents due to the proliferation of parietal epithelium and inflammatory cells
- Those with Goodpasture’s syndrome will be treated with a high degree of immunosuppression and plasmapheresis to extra autoantibodies from the blood
- It is a medical emergency
What occurs in type III hypersensitivity reactions?
What dictates where immune complexes are deposited?
- In type III hypersensitivity reactions, an abnormal immune response is mediated by the formation of antigen-antibody aggregates called immune complexes.
- They can precipitate in various tissues such as skin, joints, vessels, or glomeruli and trigger the classical complement pathway
- The size of immune complexes can dictate where they are deposited
What can occur if there are large immune complexes present in the glomeruli?
What conditions does this lead to?
- If there are large immune complexes in the glomeruli, they can fix complement and cause damage
- This can lead to RBCs/proteins going through the glomerular filter, leading to haematuria and proteinuria
- The mesangial cells will try to proliferate in order to phagocytose the immune complexes, leading to proliferative nephropathy/proliferative glomerulonephritis
- These fall under the category of nephritic syndrome
What are 5 clinical effects of Nephritic syndrome?
What are 3 causes of nephritic syndrome?
- 5 Clinical effects of Nephritic syndrome:
1) Tends to present acutely, with quick progression
2) Haematuria
3) More or less urine depending on how severe it is
4) Proteinuria (probably)
5) Pain in the loins - 3 causes of nephritic syndrome:
1) Can occur post strep infection - source of antigen
2) Vasculitis - ANCA
3) SLE
What can occur in type 3 hypersensitivity reactions if the immune complexes are smaller?
What syndrome can this cause?
- In type 3 hypersensitivity reactions where the immune complexes are smaller, they will not fix complement
- They will leak into the basement membrane and destroy its integrity
- As a result, protein will leak through
- The basement membrane will also become thick as it is full of immune complexes
- This condition is known as membranous glomerulonephritis/membranous neuropathy
What is Minimal lesion glomerulonephritis caused by?
Why is it called this?
How does it affect the basement membrane of the glomerulus?
Which groups does it occur in?
How is it treated?
What conditions can it be associated with?
- Minimal lesion glomerulonephritis is nephrotic syndrome caused by a type 4 hypersensitivity reaction
- It is called this as these are no visible lesions
- It leads to the basement membrane leaking proteins, causing marked proteinuria
- Minimal lesion glomerulonephritis occurs in children
- It is treated with steroids
- It is sometimes associated with Hodgkin lymphoma and remission with measles
What are 3 features of nephrotic syndrome?
Describe a flow chart for nephrotic syndrome (in picture)
- 3 Features of nephrotic syndrome:
1) Oedema due to low plasma proteins
2) Raised cholesterol due to loss of proteins
3) High BP - Flow chart for nephrotic syndrome (in picture)
What are 3 other causes of proteinuria?
- 3 other causes of proteinuria:
1) Diabetes
* End-stage glycation of basement membrane material, which destroys the filter
2) Amyloidosis
* Deposition of beta sheets that destroy the integrity of the basement membrane
3) Vascular causes
* Hypertension
* Vasculitis
* Mesangial IgA disease
* TTP - Thrombotic Thrombocytopenic Purpura
* HUS - Haemolytic Uremic Syndrome (HUS)
What are 3 causes of Focal and segmental Necrotising Glomerulonephritis?
- 3 causes of Focal and segmental Necrotising Glomerulonephritis:
1) Proliferative glomerulonephritis
2) Vasculitis
3) SLE
What are 6 causes of Tubulointerstitial disease?
How will patients with this present?
- 6 causes of Tubulointerstitial disease:
1) Drug hypersensitivity
2) Acute tubular necrosis
3) Shock
4) Ascending infection
5) SLE
6) Ischaemia - Patients with this won’t pass urine, as no urine is being produced, so someone who presents with acute tubular necrosis will have no urine output
