Renal: GN Flashcards

Question

What does renal biopsy depict in FSGS? [1]

Answer 1

Renal biopsy shows **focal and segmental sclerosis** and **hyalinosis** on **light** **microscopy**, and **effacement of foot processes on electron microscopy**. Sclerosis is seen in this light microscopy image next to the bowmans capsule.

Answer 2

Treat underlying cause **ACE inhibitor**: **enalapril** or **lisinopril** to reduce proteinuria Steroids; **prednisolone** (only in primary disease) **Furosemide** **simvastatin** / **atorvostatin** to control hyperlipidaemia

Answer 3

Membranous nephropathy (MN) is an immunologically mediated disease characterised by glomerular basement membrane thickening in the absence of significant cellular proliferation on histology

Answer 4

**Autoimmune** **reaction** against important antigens in the filtration barrier. This causes development of **autoantibodies**: directed against the **phospholipase A2 receptor (PLA2R)** that are highly expressed on podocytes are a major cause of primary MN seen in up to 80% of case Causes the formation of **immune** **deposits** and **subsequent thickening of the glomerular basement membrane.** Histology shows **IgA** **deposits** and **mesangial** **proliferation**.

Answer 5

Primary: **Autoimmune** Secondary: - Infection: **Hep B, malaria, syphilis** - Malignancy: **lung cancer, lymphoma, leukemia** - Drugs: **gold, penicillamine, NSAIDs** - Other autoimmune: **SLE (class V disease), thyroiditis, rheumatoid** - Sarcoidosis

Answer 6

**HLA-DR3**

Answer 7

A thickened GBM with **subepithelial electron-dense droplets.** This creates a **‘spike and dome’** appearance. It is thought these subepithelial deposits are **immunoglobulins**, as it is primarily an autoimmune disease. There will also be **thickened capillary loops**

Answer 8

- Low salt and protein diet - **ACEin** (**enalapril** or **lisinopril**) & **ARB** (**losartan**) to reduce proteinuria - Statin (**simvastatin** or **atorvostatin**) to reduce lipid levels - **Furosemide** / hydrchlorothiazide to treat oedema - Corticosteroids: **Prednisilone** or **cyclophosphamide** - Immunosuppressant: **Rituximab**

Answer 9

- one third have **spontaneous remission** - one third remain **proteinuric** - one third develop **end-stage renal failure**

Answer 10

:**Initially**: * · Haematuria + proteinuria in the urine dip * · Urine microscopy may show red cell casts * · Proteinuria is likely to be milder and not in the nephrotic range, < 1-1.5 g/day **Worsening nephritic syndrome** * · Hypertension * · Oedema * · Acute kidney injury

Answer 11

Urinary casts are **microscopic** **clusters** of **urinary** **particles**, such as cells, fat bodies, or microorganisms, wrapped in a **protein** **matrix** and found in the **urine**. Urinary casts serve as **clinical indicators of kidney condition** and can be assessed to determine the functioning of the kidneys.

Answer 12

Definitive of **glomerulonephritis**

Answer 13

**Acute interstitial nephritis**

Answer 14

**Acute tubular necrosis**

Answer 15

Mesengial deposits of **IgA** **immune** complexes Often accompanied by **C3 and IgG** (in association with a mesangial proliferative glomerulonephritis of varying severity) Causes **mesengial** **hypercellularity** and **proliferation**

Answer 16

**macroscopic haematuria in young people following an upper respiratory tract infection** occurs **1/2 days after URTI** + - Aged 20 to 30 yrs old - Recurrent haematuria - Male - Does NOT commonly present with nephrotic syndrome - 1/3rd patients present with asymptomatic invisible haematuria

Answer 17

**Kidney biopsy**: * Mesangial IgA deposition either by immunofluorescence or immunoperoxidase studies.

Answer 18

Similar: * Recent **URTI** * **Haematuria** Differences: **IgA nephropathy:** - Develops **1-2 days** after URTI - Macroscopic haematuria}} **Post-streptococcal glomerulonephritis** - Develops after **1-2 weeks** - Proteinuria - Low complement

Answer 19

1. **ACE inhibitors / ARBs** for proteinuria 2. **Oral prednisolone & Fish oil** if persistant proteinuria (> 1g for 3-6months): **prevents the immune** **reaction making defective IgA & IgG**

Answer 20

**Post-streptococcal glmoerulonephritis** - A glomerular condition mediated by an immunological response to a group A streptococci (GAS) infection: **impetigo / throat infection**

Answer 21

**Pathophysiology:** 1. Throat or skin GAS infection 2. Production of antibodies against streptococcal antigens 3. Nephritogenic streptococcal antigens become lodged in glomerular membrane 4. Anti-streptococcal antibodies bind to form immune complexes 5. Activation of complement and inflammation 6 Damage to glomerulus → clinical features of PSGN

Answer 22

**Pharyngitis or skin infection** (impetigo / tonsilittis)

Answer 23

**Subendothelial** **deposits** activate **complement**, leading to the infiltration of inflammatory cells: **neutrophils**! and **proliferative** **glomerulonephritits** **Subepithelial 'humps' of deposits trigger inflammation**, leading to epithelial cell damage, which allows the protein to filter more freely into the urine.

Answer 24

**Generalised oedema** Due to salt and water retention due to renal insufficiency Can progress to respiratory distress due to pulmonary oedema **Hypertension** Due to salt and water retention due to renal insufficiency **Gross haematuria (40%)** **Oliguria** NB: PSGN can be asymptomatic(unknown proportion), diagnosed incidentally with microscopic haematuria. }}

Answer 25

**Evidence of strep infection:** - **Antistreptolysin O titer (ASOT)** increases - **anti DNAse** - **low C3** **Culture** - **Throat or skin swab for culture to confirm GAS** (although only positive in 25% of cases because of the delay from initial GAS infection to the clinical presentation of PSGN (usually 1-3 weeks depending on the site of infection) **Renal biospy:** - **Light microscope**: shows diffuse glomerular cellular infiltration and endocapillary proliferation - **Immunofluorescence**: shows diffuse granular deposits of complement (C3) and immunoglobulin G (IgG) - **Electron microscope**: shows immune complexes characteristically localised to subepithelial deposits, commonly called dome-shaped 'humps' and subendothelial deposits. **Serology**: - The **Streptozyme** **test** is a combined test measuring the levels of the following 5 antibodies that can be produced in response to a recent GAS infection;

Answer 26

Rare autoimmune disease where **antibodies** attack the **alpha-3 subunit of type IV collagen found in the basement membrane of the lungs and kidneys**. This anti-glomerular basement membrane (anti-GBM) disease leads to **small vessel vasculitis in the kidneys and lungs** causing **bleeding** in the **lungs** and **renal** failure; leading to permanent damage to both organs

Answer 27

**Autoimmunity against the alpha-3 chain of type IV collagen in basement membranes**. Type IV collagen is in all basement membranes but the alpha-3 chain is found primarily in the basement membranes of alveoli and glomeruli. There are three main mechanisms: **Anti-GBM antibodies** These attack the basement membranes of alveoli and glomeruli by binding to them and activating the complement cascade, leading to their death. **Auto-reactive T cells** These contribute to anti-GBM disease. Circulating T cells that are specific to epitopes in the alpha-3 chain of type IV collagen contribute to the formation of crescent formation. **Genetic component** There have also been rare cases of familial anti-GBM disease where patients with HLA-DR15 and -DR4 are at increased risk.

Answer 28

**Acute**: * **Intensive plasmapheresis** (Plasma exchange 4 L daily for 10 to 14 days) Removes the pathogenic antibody and inflammatory mediators 4 litres per day for 10-14 days, or until anti-GBM is undetectable * **Prednisone** The dose is tapered over the course of 3 months - **Cyclophosphamide** **Long term:** - Less toxic drugs such as **azathioprine** and **low dose prednisolone**

Answer 29

**Any aggressive GN, rapidly progressing to renal failure over days or weeks.** presents with an acute severe illness but tends to respond well to treatment.**Histology shows glomerular crescents.**

Answer 30

**Thromboembolism**: * Increase in clotting factors * Decrease in anti-thrombin III * Platelet abnormalities * Treat w/ heparin & warfarin **Infection**: - urine losses of immunoglobulins and immune mediators: increase risk of UTIs, respiratory and CNS infections **Hyperlipidaemia**: - Increase cholesterol, LDLs and triglycerides - Decreased HDLs - Hepatic synthesis in response to decrease in oncotic pressure and defective lipid breakdown

Answer 31

DM nephropathy

Answer 32

Hyperglycaemia leads to increase **growth factors, RAAS activation, AGE products and oxidative stress** Causes: - **Increase in glomerular capillary pressure** - **podocyte damage** - **endothelial dysfunction** - **Glomerulosclerosis** - **Nodule** **formation** (Kimmelstein-Wilson) - **Fibrosis** - leads to loss of renal function

Answer 33

**Microalbuminuria**: **A:CR 3-30mg/mmol**

Answer 34

**Glycaemic control** **BP < 130 / 80**: - ACEin / ARB **Na restriction to < 2 g/ day** **Statins to reduce CV risk**

Answer 35

**raised anti-streptolysin O titres** are used to confirm the diagnosis of a recent streptococcal infection This **measures antibodies against streptolysin O,** a substance produced by group A streptococcus bacteria

Answer 36

Type IV collagen is also found in the alveoli, so causes pulmonary haem. Also presents with nose bleeds

Answer 37

**IgG** deposits in **linear fashion**

Answer 38

Membranous nephropathy

Answer 39

White cell casts Eisonophil infiltration

Answer 40

Focal sclerosis glomerulosclerosis

Answer 41

Loss of anti-thrombin III (which antagonises action of thrombin, so get unopposed action of thrombin)

Answer 42

Hyperlipidaemia Infection (loss of IgG) VTE | HIV

Answer 43

**Tubular cell necrosis**