Kideny in systemic disease

Question 1

Myeloma

Answer 1

overproduction of Ig by a cloncal expansion of cells from the b-cell lineage

Question 2

WHat should happen normally in bone marrow?

Answer 2

Antibodies against antigens –> priming the cells to produce Ig

Question 3

What happens in myelomas?

Answer 3

One particular cloncal group that produces abnormal antibodies. No differentiation of the cells

Cancer of the plasma cells

Question 4

Myeloma features:

Answer 4

Cancer of plasma cells

Overproduction of protein and antibodies

collection of abnromal plasma cells in the bone marrow

Impairment of production of normal blood cells

Monoclonal production of a paraprotein (abnormal antibody)
Potentially cause renal dysfunction

Question 5

Clinical symptoms of myeloma

Answer 5

Pain, weakness, fatigue, weight loss, recurrent infection

Question 6

What is the classic presentation for myeloma?

Answer 6

back pain and renal failure

Question 7

Clinical signs of myeloma

Answer 7

Anaemia
Hypercalcaemia
Renal Failure
Lytic bone lesions

Question 8

Why does myeloma cause renal disease?

Answer 8

Multifactorial

1. glomerular immunoglobulin deposition - blocking it
2. tubular Ig deposition - light chain cast nephropathy
3. dehydration/ hypercalcaemia. contrast/ bisphosphonates, NSAIDs

Question 9

How is myeloma diagnosed?

Answer 9

Bloods -

1. serum protein eletrophoresis (measures the Ig in blood)
2. serum free light chains

Urine:
1.Bence Jones Protein: dip in urine (can have a negative urinalysis)

Bone Marrow biopsy
Skeletal survey
Renal biopsy

Question 10

What is the management of myeloma?

Answer 10

Stop nephrotoxics
Manage hypercalcaemia (saline +/- bisphosphonates)

Chemotherapy
Stem cell transplant

Plasma exchange
To remove light chains

Supportive - Dialysis

Question 11

What is amyloidosis?

Answer 11

Deposition of extracellular amyloid (insoluble protein fibrils) in tissues or organs

Occurs due to abnormal folding of proteins which then aggregate and become insoluble.
Breakdown of usual degradation pathways for abnormally folded proteins

Question 12

How do you get amyloidosis ?

Answer 12

Inherited and acquired forms

Question 13

What are the 4 types of amyloidosis?

Answer 13

1. Primary / Light chain (AL)
2. Secondary / Systemic / Inflammatory (AA)
3. Dialysis (Aβ2M)
4. Hereditary and old age (ATTR)

Question 14

Why are the features of AL amyloidosis?

Answer 14

Production of abnormal immunoglobulin
light chains from plasma cells

Light chains enter the bloodstream and cause amyloid deposits

Question 15

Who and What does AL amyloidosis affect commonly?

Answer 15

55-60 years

heart, bowel, skin, nerves, kidneys

Question 16

What is AAA amyloidosis?

Answer 16

Amyloid associated amyloidosis

Question 17

Causes of AA amyloidosis?

Answer 17

Production of acute phase protein – serum amyloid A protein (SAA)

produced normally but then the body is stimulated continuously and it continuously present

Question 18

Who does AAA present in commonly?

Answer 18

In those with chronic inflammatory conditions or chronic infection:

RA, inflammatory bowel disease, psoriasis
TB, osteomyelistis, bronchiectasis

Question 19

What does AAA affect commonly?

Answer 19

liver, spleen, kidneys, adrenals

Question 20

What are the presentation of amyloidosis?

Answer 20

Renal – (nephrotic range) proteinuria
+/- impaired renal function

Cardiac – Cardiomyopathy
Nerves – peripheral or autonomic neuropathy
Hepatomegaly / Splenomegaly
GI - malabsorption

Question 21

What investigation is done in AAA?

Answer 21

Urinalysis + uPCR

Renal biopsy - congo red staining (apple green under polarised light)

Abdominal fat pad or **rectal biopsy

SAP scan - Scintigraphy with radiolabelled serum amyloid – shows extent of diseas

Question 22

What is the treatment for amyloidosis?

Answer 22

No cure
reduce deposition and preserve organ function

Innumotherapy, steroids, chemotherapy, stem cell transplant

Question 23

What is small vessel ANCA associated vasculitis?

Answer 23

Necrotising polyangiitis that affects capillaries, venules and arterioles

Question 24

When does vasculitis present the most?

Answer 24

5th, 6th and 7th decade

60 y/o farmer during springtime

Question 25

What are the constitutional symptoms in vasculitis?

Answer 25

fever, migratory arthralgia, weight loss, anorexia and malaise

Question 26

Microscopic polyangitis antibodies

Answer 26

anti-MPO(p-ANCA)

Question 27

GPA antibodies

Answer 27

anti-PR3 (c-ANCA)

Question 28

Eosinophilic GPA

Answer 28

asthma and eosinophilia

Question 29

Highest sensitivity for GPA

Answer 29

ANCA

Question 30

Is antibody titre a good marker of disease severity?

Answer 30

No

Question 31

How is vasculitis managed?

Answer 31

Steroids, cyclophosphamides/ Rituximab Plasma exchange supportive - dialysis/ ventilation

Question 32

Why is vasculitis more concentrated in kidneys, lungs and skin?

Answer 32

concentration of small blood vessels in these areas

Question 33

What is SLE?

Answer 33

autoimmune inflammatory condition affects everything --> skin, joints, kidneysm lungs, nervous system

Question 34

who does SLE affect the most?

Answer 34

women in 20s -30s African Americans and Hispanics

Question 35

What is the diagnosis of lupus?

Answer 35

presence of 4 or more of the following criteria gives 96% sensitivity and specificity for the diagnosis for lupus: ``` Malar rash discoid rash photosensitivity oral ulcers non-erosive ulcers pleuropericarditis renal disease nerulogic disease anaemia positive LE cell prep, raised Anti-DNA antibody positive ANA ```

Question 36

How is the diagnosis of SLE made?

Answer 36

Blood tests: Raised inflammatory markers Immunology – ANA +ve, anti-dsDNA ab (~70%) Complement – low levels (sensitive marker) Urinanlysis - renal involvement is better picked up with it, dip stick as well

Question 37

What are the common differential diagnosis for SLE?

Answer 37

Sjogren’s syndrome Fibromyalgia Primary anti-phospholipid syndrome Thrombotic micro-angiopathies

Question 38

What is lupus nephritis?

Answer 38

renal involvement in lupus 50% of lupus patients will have renal involvement at presentation and up to 60% during the course of their disease abnormality - proteinuria

Question 39

How to differentiate types of renal nephritis?

Answer 39

Renal biopsy - key investigation

Question 40

What are the classifications of Lupus nephritis?

Answer 40

Class I: Minimal mesangial Class II: Mesangial Proliferative (chalk coloured) Class III: Focal Proliferative Class IV: Diffuse Proliferative(more proliferation, more stimulation) Class V: Membranous Class VI: Advanced sclerosing