MET3 Revision: Renal I Flashcards

Question

Define what the triad of nephrotic syndrome are [3]

Answer 1

A triad of the following: 1. **Proteinuria** (> 3g/24hr) causing 2. **Hypoalbuminaemia** (< 30g/L) and 3. **Oedema**

Answer 2

* Membranous nephropathy * Post streptococcus nephropathy * Focal segmental glomerulosclerosis * IgA nephropathy * Goodpasture's disease

Answer 3

**Haematuria** (blood in the urine), which can be microscopic (not visible) or macroscopic (visible) **Oliguria** (significantly reduced urine output) **Proteinuria** (protein in the urine), but less than 3g per 24 hours (higher protein suggests nephrotic syndrome) **Fluid retention**

Answer 4

Proteinuria: more than **3g per 24 hours** Low serum albumin: **less than 25g per litre**

Answer 5

* **Oedema** (peripheral and facial) * **Proteinuria** (>3g/24hrs) * **Hypercholesterolaemia** * **Hypoalbiminaemia** * **Hypertension** (caused by reduced eGFR and salt & water retention) * **Haematuria** * **Frothy urine** * **Fatigue** * **Recurrent infections** (immune dysfunction) * **A / V thrombosis** (hypercoagulability) * **Xanthelasma** (cholesterol deposit near eyelid) * **Leukonychia**

Answer 6

* Group A Streptococcus pyogenes * Respiratory infections * GI infections * Hep B * Hep C * Infective endocarditis * HIV * SLE * Lung & Colorectal cancer

Answer 7

**Both are clinical syndromes that are at opposite ends of a spectrum of clinical presentations** **Nephrotic syndrome (GN)**: * When the basement membrane in the glomerulus becomes highly permeable resulting in proteinuria & involves * **Proteinuria** (more than 3g per 24 hours) * **Hypoalbuminaemia** / low serum albumin (less than 25g per litre) * **Peripheral oedema** * **Hypercholesterolaemia** **Nephritic syndrome**: is a clinical presentation, and patients with nephritic syndrome may be diagnosed with renal diseases such as glomerulonephritis (a pathological diagnosis made after biopsy), and maybe rapidly progressive glomerulonephritis (RPGN) in which a patient has rapid fall in renal function (RPGN is a subset of glomerulonephritis). A nephritic syndrome is a constellation of symptoms: * **Haematuria** (blood in the urine), which can be microscopic (not visible) or macroscopic (visible) * **Oliguria** (significantly reduced urine output) * **Proteinuria** (protein in the urine), but less than 3g per 24 hours (higher protein suggests nephrotic syndrome) * **Fluid retention**

Answer 8

* **Urinalysis**: haematuria, proteinuria, dysmorphic rbc, leukocytes * **Protein**:Creatinine ratio (PCR): >300mg/mmol * **Microscopy**: investigate infections * **FBC**: normocytic normochromic anemia is a feature of several systemic diseases with GN * **Lipid profile:** hyperlipidaemia * **U&Es** * **LFTs**: hypoalbuminaemia; normal/elevated creatinine; elevated liver enzymes * **Ultrasound of kidneys**

Answer 9

Membranous nephropathy Focal segemental glomerulosclerosis

Answer 10

· Drugs: **NSAIDs, rifampicin** · **Hodgkin**’s **lymphoma**, **thymoma** · **Infectious mononucleosis**

Answer 11

- **Features of nephrotic syndrome** - **Normotension** (HTN is rare) - **Highly selective proteinuria** (i.e. only intermediate-sized proteins such as albumin and transferrin leak through the glomerulus

Answer 12

- Majority (80%) are steroid responsive: **prednisolone** - **Cyclophosphamide** next step for steroid resistant

Answer 13

African-Americans & Hispanics

Answer 14

**Primary FSGS: Idiopathic** - A circulating factor that damages podocytes in the glomeruli leading to **foot** **process** **effacement** - Proteins and lipids pass through BUT ALSO get stuck inside th glomerulus causing **hyalinosis** and eventually **sclerosis**. **Secondary FSGS: SCA, post- HIV / Herion / Lithium** - represents an adaptive response to renal injury that is usually associated with less significant proteinuria and renal impairment.

Answer 15

Nephrotic syndrome Haematuria (microscopic) Hypertension Renal insufficiency

Answer 16

**Viral infection:** - HIV - CMV **Glomerular hyperfiltration:** - Due to reduced renal mass / solitary kidney etc **Drug induced:** - Heroin - Interferon alpha - Lithium **Obesity**

Answer 17

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 18

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

Answer 19

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

Answer 20

**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 21

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 22

**HLA-DR3**

Answer 23

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 24

- 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 25

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

Answer 26

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 27

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

Answer 28

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 29

**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 30

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

Answer 31

**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 32

**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 33

**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 34

**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 35

**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 36

**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 37

**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 38

DM nephropathy

Answer 39

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 40

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

Answer 41

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

Answer 42

**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 43

Hyperlipidaemia Infection (loss of IgG) VTE | HIV

MET3 Revision: Renal I Flashcards

(68 cards)