Kideny in systemic disease Flashcards
Myeloma
overproduction of Ig by a cloncal expansion of cells from the b-cell lineage
WHat should happen normally in bone marrow?
Antibodies against antigens –> priming the cells to produce Ig
What happens in myelomas?
One particular cloncal group that produces abnormal antibodies. No differentiation of the cells
Cancer of the plasma cells
Myeloma features:
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
Clinical symptoms of myeloma
Pain, weakness, fatigue, weight loss, recurrent infection
What is the classic presentation for myeloma?
back pain and renal failure
Clinical signs of myeloma
Anaemia
Hypercalcaemia
Renal Failure
Lytic bone lesions
Why does myeloma cause renal disease?
Multifactorial
- glomerular immunoglobulin deposition - blocking it
- tubular Ig deposition - light chain cast nephropathy
- dehydration/ hypercalcaemia. contrast/ bisphosphonates, NSAIDs
How is myeloma diagnosed?
Bloods -
- serum protein eletrophoresis (measures the Ig in blood)
- serum free light chains
Urine:
1.Bence Jones Protein: dip in urine (can have a negative urinalysis)
Bone Marrow biopsy
Skeletal survey
Renal biopsy
What is the management of myeloma?
Stop nephrotoxics Manage hypercalcaemia (saline +/- bisphosphonates)
Chemotherapy
Stem cell transplant
Plasma exchange
To remove light chains
Supportive - Dialysis
What is amyloidosis?
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
How do you get amyloidosis ?
Inherited and acquired forms
What are the 4 types of amyloidosis?
- Primary / Light chain (AL)
- Secondary / Systemic / Inflammatory (AA)
- Dialysis (Aβ2M)
- Hereditary and old age (ATTR)
Why are the features of AL amyloidosis?
Production of abnormal immunoglobulin
light chains from plasma cells
Light chains enter the bloodstream and cause amyloid deposits
Who and What does AL amyloidosis affect commonly?
55-60 years
heart, bowel, skin, nerves, kidneys
What is AAA amyloidosis?
Amyloid associated amyloidosis
Causes of AA amyloidosis?
Production of acute phase protein – serum amyloid A protein (SAA)
produced normally but then the body is stimulated continuously and it continuously present
Who does AAA present in commonly?
In those with chronic inflammatory conditions or chronic infection:
RA, inflammatory bowel disease, psoriasis
TB, osteomyelistis, bronchiectasis
What does AAA affect commonly?
liver, spleen, kidneys, adrenals
What are the presentation of amyloidosis?
Renal – (nephrotic range) proteinuria
+/- impaired renal function
Cardiac – Cardiomyopathy
Nerves – peripheral or autonomic neuropathy
Hepatomegaly / Splenomegaly
GI - malabsorption
What investigation is done in AAA?
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
What is the treatment for amyloidosis?
No cure
reduce deposition and preserve organ function
Innumotherapy, steroids, chemotherapy, stem cell transplant
What is small vessel ANCA associated vasculitis?
Necrotising polyangiitis that affects capillaries, venules and arterioles
When does vasculitis present the most?
5th, 6th and 7th decade
60 y/o farmer during springtime
What are the constitutional symptoms in vasculitis?
fever, migratory arthralgia, weight loss, anorexia and malaise
Microscopic polyangitis antibodies
anti-MPO(p-ANCA)
GPA antibodies
anti-PR3 (c-ANCA)
Eosinophilic GPA
asthma and eosinophilia
Highest sensitivity for GPA
ANCA
Is antibody titre a good marker of disease severity?
No
How is vasculitis managed?
Steroids, cyclophosphamides/ Rituximab
Plasma exchange
supportive - dialysis/ ventilation
Why is vasculitis more concentrated in kidneys, lungs and skin?
concentration of small blood vessels in these areas
What is SLE?
autoimmune inflammatory condition
affects everything –> skin, joints, kidneysm lungs, nervous system
who does SLE affect the most?
women in 20s -30s
African Americans and Hispanics
What is the diagnosis of lupus?
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
How is the diagnosis of SLE made?
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
What are the common differential diagnosis for SLE?
Sjogren’s syndrome
Fibromyalgia
Primary anti-phospholipid syndrome
Thrombotic micro-angiopathies
What is lupus nephritis?
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
How to differentiate types of renal nephritis?
Renal biopsy - key investigation
What are the classifications of Lupus nephritis?
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
