Renal

Question 1

What are the 3 areas of the nephron upon which renal disease can be classified?

Answer 1

1) Glomerulus
2) Tubules & Interstitium
3) Blood vessels

Question 2

Which renal diseases effect the glomerulus?

Answer 2

1) Nephrotic syndrome - breakdown of selectivity of glomerular filtration barrier
2) Nephritic syndrome

Question 3

Which renal diseases effect the Tubules & interstitium?

Answer 3

1) Acute tubular necrosis

2) Tubulointerstitial nephritis

Question 4

Which renal diseases effect the Blood vessels?

Answer 4

1) Thrombotic microangiopathies

Question 5

What are the 2 thrombotic microangiopathies?

Answer 5

1) Haemolytic uraemic syndrome

2) Thrombotic thrombocytopenic purpura

Question 6

What are the 3 types of tubulointerstitial nephritis?

Answer 6

1) Acute pyelonephritis
2) Chronic pyelonephritis & reflux nephropathy
3) Interstitial nephritis

Question 7

Nephrotic syndrome is characterised by:

Answer 7

Proteinuria (>3g/24h) +
Hypoalbuminaemia +
Oedema
(+ Hyperlipidaemia)

Keywords: Frothy urine
Swelling - facially in kids and peripheral in adults

Question 8

Primary causes of Nephrotic Syndrome are:

Answer 8

1) Minimal Change disease
2) Membranous Glomerular disease
3) Focal Segmental Glomerulosclerosis (FSGS)

Question 9

Secondary causes of nephrotic syndrome are:

Answer 9

1) Diabetes

2) Amyloidosis

Question 10

What is seen on light microscopy for primary causes of Nephrotic syndrome?

Answer 10

MC: No changes

MG: Diffuse glomerular basement membrane thickening

FSGS: Focal and segmental glomerular consolidation and scarring, Hyalinosis - abnormal accumulation of a clear (hyaline) substance in body tissue

Question 11

What is seen on electron microscopy for primary causes of Nephrotic syndrome?

Answer 11

MC: Loss of podocyte foot processes

MG: Loss of podocyte foot processes
Subepithelial deposits ('Spikey')

FSGS: Loss of podocyte foot processes.

Question 12

What is seen on immunofluorescence for primary causes of Nephrotic syndrome?

Answer 12

MC: No immune deposits

MG: Ig and complement in granular deposits along entire GBM

FSGS: Ig and complement in scarred areas

Question 13

What is the prognosis of primary causes of Nephrotic syndrome?

Answer 13

MC:

Question 14

How do primary causes of Nephrotic syndrome respond to steroids?

Answer 14

MC: 90% respond

MG: Poorly

FSGS: 50% respond

Question 15

What is the epidemiology of primary causes of Nephrotic syndrome?

Answer 15

MC: Most common in children (75%) with 2nd peak in elderly

MG: Common in adults (~30%)

FSGS: Common in adults (~30%). Most common in Afro-Caribbean

Question 16

Minimal Change disease

Answer 16

Common in children (2-3 yrs) and elderly
Loss of podocyte foot processes
No immune deposits
90% respond to steroids

Question 17

Membranous Glomerular disease

Answer 17

Affecting adults between 30 - 50 years
Caucasian
Caused by immune complex formation in the glomerulus by binding of antibodies to antigens in the GBM. The antigens may be part of the basement membrane, or deposited from elsewhere by the systemic circulation.
The immune complex serves as an activator that triggers a response from the C5b - C9 complements, which form a membrane attack complex (MAC) on the glomerular epithelial cells. This, in turn, stimulates release of proteases and oxidants by the mesangial and epithelial cells, damaging the capillary walls and causing them to become “leaky”.
Diffuse GBM thickening on light microscopy
Loss of podocyte foot processes
Ig and complment in granular deposists along entire GBM
Can be 1o or 2o to SLE, infection, drugs and malignancyAffecting adults between 30 - 50 years
Caucasian

Question 18

Focal Segmental Glomerulosclerosis (FSGS)

Answer 18

Leading cause of kidney failure in adults
Focal—only some of the glomeruli are involved (as opposed to diffuse), Segmental—only part of each glomerulus is involved (as opposed to global), Glomerulosclerosis—refers to scarring of the glomerulus
Most common in Afro-Carobbeans
Focal and segmental glomerular consolidation and scarring
Loss of podocyte foot processes on electron microscopy
1o but can be 2o to HIV nephropathy and obesity

Question 19

Diabetes in secondary Nephrotic syndrome

Answer 19

Diffuse GBM thickening on histology

Mesangial matrix nodules - aka Kimmelstiel Wilson nodules

Question 20

Amyloidosis in secondary Nephrotic syndrome

Answer 20

Apple green birefringence with congo red stain
Patient may also have:
Chronic inflammation - rheumatoid, chronic infections (TB) causing AA protein deposition
Immunoglobulin light chain deposition - AL protein deposition from multiple myeloma

Clinical clues: Macroglossia, heart failure, hepatomegaly

Question 21

Define nephritic syndrome

Answer 21

A manifestation of glomerular inflammation (i.e. glomerulonephritis)

Question 22

Nephritic syndrome is characterised by:

Answer 22

1) Haematuria (coca-cola urine)
2) Dysmporphic RBCs and red cell casts in urine

May also have:

3) Oliguria
4) Increased urea and creatinine
5) Hypertension
6) Proteinuria

Question 23

Causes of nephritic syndrome

Answer 23

1) Acute postinfectious (post streptococcal) glomerulonephritis
2) IgA Nephropathy (berger disease)
3) Rapidly progressive (crescentic) GN
4) Hereditary nephritis (alports syndrome)
5) Thin basement membrane disease (benign familial haematuria)

Question 24

What is the main difference between nephrotic and nephritic syndrome?

Answer 24

Nephrotic syndrome is characterized by only proteins moving into the urine. In contrast, Nephritic syndrome is characterized by having a thin glomerular basement membrane and small pores in the podocytes of the glomerulus, large enough to permit proteins (proteinuria) and red blood cells (hematuria) to pass into the urine. Both may involve hypoalbuminemia due to protein albumin moving from the blood to the urine.

Question 25

How does acute postinfectious GN cause damage?

Answer 25

Glomerular damage is thought to be due to immune complex deposition Occurs 1-3 weeks after streptococcal throat infection or impetigo (usually Group A alpha-haemolytic strep = strep pyogenes)

Question 26

How is acute postinfectious GN diagnosed?

Answer 26

Haematuria (red cell casts) Proteinuria Oedema HTN Bloods: antistreptococcal antibody (ASOT) titre is raised, C3 decreased Biopsy: Light microscope - increased cellularity of glomeruli Flurescence microscope - granular deposits of IgG and C3 in GBM Electron microscope - Subendothelial humps

Question 27

Symptoms of IgA nephropathy (Berger disease)

Answer 27

Persistent or recurrent frank haematuria, or microscopic haematuria Presents 1-2 days after a URTI with frank haematuria

Question 28

What causes IgA nephropathy (berger disease)

Answer 28

Deposition of IgA immune complexes in the glomeruli This is the most common GN worldwide It can progress to ESRF

Question 29

How is IgA nephropathy diagnosed?

Answer 29

Biopsy Fluroescence microscopy shows granular deposition of IgA and complement in mesangium (the thin membrane supporting the capillary loops in renal glomeruli).

Question 30

How does hereditary nephritis present?

Answer 30

Nephritic syndrome + sensorineural deafness + eye disorders (lens dislocation, cataracts) Presents at 5-20 years with nephritic syndrome, progressing to ESRF

Question 31

How is hereditary nephritis caused?

Answer 31

X linked | Caused by a mutation in type IV collagen alpha 5 chain

Question 32

How is thin basement membrane disease caused?

Answer 32

Diffuse thinning of GBM caused by mutation in type IV collagen alpha 4 chain Autosomal dominant

Question 33

What are the symptoms of thin basement membrane disease (benign familial haematuria)?

Answer 33

Very rarely a cause of nephritic syndrome - normally exclusively asymptomatic haematuria Usually asymptomatic - incidentally diagnosed with microscopic haematuria Renal function is usually normal

Question 34

3 causes of asymptomatic haematuria

Answer 34

1) Thin basement membrane disease (benign familial haematuria) 2) IgA nephropathy (berger disease) 3) Alports syndrome

Question 35

How does rapidly progressive (crescentic) GN present

Answer 35

Presents as nephritic syndrome but: | Oliguria + renal failure are more pronounced

Question 36

How is rapidly progressive (crescentic) GN classified?

Answer 36

Classification is based upon immunological findings: Type 1: Anti-GBM antibody against COL4-A3 (collagen type IV) Type 2: Immune complex type 3: Pauci-immune/ANCA-associated Regardless of causes, all are characterised by presence of crescents in the glomeruli.

Question 37

How is rapidly progressive (crescentic) GN caused?

Answer 37

Type 1: Goodpastures syndrome - HLA-DRB1 association Type 2: SLE, IgA nephropathy, post infectious GN Type 3: c-ANCA - Wegener's granulomatosis p-ANCA - microscopic polyangitis

Question 38

How does rapidly progressive (crescentic) GN present under fluorescence microscopy?

Answer 38

Type 1: Linear deposition of IgG in GBM Type 2: Granular (lumpy bumpy) IgG immune complex deposition on GBM/mesangium Type 3: Lack of/scanty significant immune complex deposition

Question 39

Additional organ involvements with crescentic GN

Answer 39

Type 1: Lungs - pulmonary haemorrhage Type 3: Vasculitis - particularly presenting as skin rashes or pulmonary haemorrhage

Question 40

Define Acute Tubular Injury/Necrosis (ATI/ATN)

Answer 40

A severe form of acute renal failure that develops in people with severe illnesses (such as sepsis) or with very low blood pressure. Patients may need dialysis.  Most common cause of acute renal failure

Question 41

What is the mechanism of ATI/ATN?

Answer 41

Damage to tubular epithelial cells --> Blockage of tubules by casts --> reduced flow and haemodynamic changes --> acute renal failure

Question 42

What causes ATI/ATN?

Answer 42

Ischaemia - burns, septicaemia | Nephrotoxins - drugs (gentamicin, NSAIDs), radiographic contrast agents, myoglobin, heavy metals

Question 43

What is the histopathology of ATI/ATN?

Answer 43

Necrosis of short segments of tubules

Question 44

Define tubulointerstitial nephritis

Answer 44

A group of renal inflammatory disorders that involve the tubules and intersitium

Question 45

4 types of tubulointerstitial nephritis

Answer 45

1) Acute pyelonephritis 2) Chronic pyelonephritis & reflux nephropathy 3) Acute Interstitial nephritis 4) Chronic interstitial nephritis/Analgesic nephropathy

Question 46

Describe acute pyelonephritis

Answer 46

Bacterial infection of the kidney , usually as a result of ascending infection - E.coli ``` Presents with: fever chills sweats flank pain renal angle tendernesss luekocytosis +/- frequency, dysuria and haematuria ``` Leukocytic casts are seen in urine

Question 47

Describe chronic pyelonephritis and reflux nephropathy

Answer 47

Chronic inflammation and scarring of the parenchyma caused by recurrent and persistent bacterial infection ``` Can be due to: Chronic obstruction - posterior uretheral valves, renal calculi Urine reflux (=reflux nephropathy) ```

Question 48

Describe Acute interstitial nephritis

Answer 48

A hypersensitivity reaction, usually to a drug e.g. Abx, NSAIDs, diuretics Usually begins days after drug exposure ``` Presents with: fever skin rash haematuria proteinuria eosinophilia ```

Question 49

Describe Chronic interstitial nephritis/Analgesic nephropathy

Answer 49

Seen in the elderly with long-term analgesic consumption (NSAIDs/paracetamol) Symptoms occur only in late disease: HTN, anaemia, proteinuria and haematuria

Question 50

What are 2 thrombotic Microangiopathies?

Answer 50

1) Haemolytic Uraemic Syndrome (HUS) | 2) Thrombotic Thrombocytopaenic Purpura (TTP)

Question 51

What are thrombotic microangioplasties characterised by?

Answer 51

``` Thrombosis Triad of: - Microangiopathic haemolytic anaemia (MAHA) - Thrombocytopenia - Renal failure ```

Question 52

What is the pathophysiology of thrombotic microangiopathies

Answer 52

widespread fibrin deposition in vessels -> formation of platelet-fibrin thrombi which damage passing platelets and RBC's -> platelet and RBC destruction (i.e. thrombocytopenia and MAHA)

Question 53

Signs & symptoms of HUS and TTP:

Answer 53

decreased platelets -> bleeding (petechiae, haematemesis, melena) MAHA -> pallor and jaundice

Question 54

Define thrombotic microangiopathy

Answer 54

thrombotic microangiopathies are microvascular occlusive disorders characterized by systemic or intrarenal aggregation of platelets, thrombocytopenia, and mechanical injury to erythrocytes. It results in thrombosis in capillaries and arterioles, due to an endothelial injury.

Question 55

Define Hemolytic uremic syndrome (HUS)

Answer 55

Hemolytic uremic syndrome (HUS) is a condition that results from the abnormal premature destruction of red blood cells. it is characterized by hemolytic anemia (anemia caused by destruction of red blood cells), acute kidney failure (uremia), and a low platelet count (thrombocytopenia).

Question 56

Define thrombotic thrombocytopenic purpura (TTP)

Answer 56

Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that causes blood clots to form in small blood vessels. This leads to a low platelet count (thrombocytopenia).

Question 57

How to diagnose HUS and TTP

Answer 57

``` Low Haemaglobin Low platelets Signs of haemolysis (Increased bilirubin, increased reticulocytes, increased LDH) Fragmented RBC's on blood smear Coomb's test negative (as not AIHA) ```

Question 58

HUS pathophysiology

Answer 58

Usually affects children Usually associated with diarrhoea caused by E.coli (outbreaks caused by children visiting petting zoos) can be non-diarrhoea associated due to abnormal proteins in complement pathway/endothelium - can be familial Thrombi confined to kidneys Usually involves renal failure

Question 59

TTP pathophysiology

Answer 59

Usually affects adults Thrombi occur throughout circulation (esp in CNS) Usually no renal failure Neuro symptoms (headache, altered consciousness, seizures, coma)

Question 60

Define acute renal failure

Answer 60

the abrupt loss of kidney function, resulting in the retention of urea and creatinine

Question 61

Complications of acute renal failure are:

Answer 61

``` Metabolic acidosis Hyperkalaemia Fluid overload HTN low calcium Uraemia ```

Question 62

3 ways to characterise acute renal failure:

Answer 62

1) Pre-renal: Most common. Caused by renal hypo-perfusion e.g. hypovolaemia, sepsis, burns, acute pancreatitis and renal artery stenosis 2) Renal: Acute tubular necrosis is the most commenest cause but can also include acute glomerulonephritis and thrombotic microangiopathy 3) Post-renal: obstruction to urine flow as a result of stones, tumours (primary & secondary), prostatic hypertrophy and retroperitoneal fibrosis.

Question 63

Define chronic renal failure

Answer 63

Progressive, irreversible loss of renal function characterised by prolonged symptoms and signs of uraemia (fatigue, itching, anorexia and if severe eventually confusion)

Question 64

Signs & symptoms of uraemia in CKF

Answer 64

Fatigue Itching Anorexia Confusion - if severe

Question 65

Causes of CRF

Answer 65

``` Diabetes (19.5%) Glomerulonephritis (15.3%) HTN & Vascular disease (15%) Reflux nephropathy (chronic pyelonephritis) (9.5%) Polycystic kidney disease (9.4%) ```

Question 66

Staging classification of CRF

Answer 66

5 stages depending on GFR: ``` Stage 1: (>90) Kidney damage with normal renal function (often proteinurea) Stage 2: (60-89) Mildly imparied Stage 3: (30-59) Moderaterly impaired Stage 4: (15-29) Severly impaired Stage 5: ( ```

Question 67

Define adult polycystic kidney disease (APCKD)

Answer 67

a multisystemic and progressive disorder characterized by cyst formation and enlargement in the kidney and other organs (eg, liver, pancreas, spleen). It is autosomal dominant

Question 68

What mutations are present in APCKD?

Answer 68

There is autosomal dominant inheritence. 85% due to mutations in PKD1 on chromosome 16 (encoding polycystin-1) 15% in PKD2 on chromosome 4 (encoding polycystin-2)

Question 69

Clinical features of APCKD

Answer 69

Haematuria Flank pain UTI Clinical features are usually due to cyst complications such as cyst rupture, cyst infection and cyst haemorrhage

Question 70

Pathogical features of APCKD

Answer 70

Large multicystic kidneys with destroyed renal parenchyma Liver cysts (in PKD1) Berry aneurysms

Question 71

Define Lupus Nephritis

Answer 71

Lupus nephritis is inflammation of the kidney that is caused by systemic lupus erythematous (SLE). Also called lupus, SLE is an autoimmune disease. With lupus, the body's immune system targets its own body tissues. Lupus nephritis happens when lupus involves the kidneys.  It is a type of glomerulonephritis in which the glomeruli become inflamed.

Question 72

Clinical presentation of lupus nephritis

Answer 72

Depending on site and intrsnity of immune complex deposition, presentation may be: Isolated urinary abnormalities Acute renal failure Nephrotic syndrome Progeressive chronic renal failure

Question 73

Classification of lupus nephritis

Answer 73

Class I: minimal mesangial lupus nephritis - immune complexes but no structural alteration Class II: mesangial proliferative lupus nephritis - immune complexes and mild/moder increase in mesangial matrix and cellularity Class III: focal lupus nephritis - active swelling and proliferation in less than half the glomeruli Class IV: Diffuse lupus nephritis - involvement of more than half the glomeruli Class V: membranous lupus nephritis - subepitherlial immune complex deposition Class VI: advanced sclerosising - complete sclerosis of >90% of the glomeruli.