23. Background Science (Glomerulonephritis) Flashcards
In someone with new onset of odema what systems/conditions could this be related to
heart failure liver failure kidney failure cor pulmonale DVT pericardial effusion
what does protein 3+ suggest clinically within the kidney
there is glomerular disease as there is damage to the filtration barrier
which specific kind of odema is often a feature of GN
periorbital
normal excretion of proteins in the urine is less than _________ and of these, albumin excretion is ______ or less
150 mg
30mg
name some other proteins that are excreted into the urine apart from albumin
horsfall protein (aka uromodulin)
b2 microglobulin
immunoglobulin light chains
Why might we get abnormal values of Urine ACR or PCR
if the urine creatinine is too low or too high or
after a heavy protein meal
at what numerical value does a urine dipstick turn positive for albuminuria
greater than 300
note that this is why you send urine to the labs to check ACR (also important for early identification of early and reversible glomerular damage as in diabetic nephropathy
what blood tests would you want to order to investigate for renal glomerular disease
o FBC o Renal Profile o Bone profile o Lipid profile o Coagulation screen o Hba1c o ESR CRP o Immunology screen o Myeloma screen o Hepatitis Serology
what do we look for in the urine when sending it off to the lab which suggestive of multiple myeloma or waldenstoms macroglobulinemia (malignant disorder of the bone marrow and lymphatic tissues)
bence jones proteins
what is the management of GN
- Salt restriction – advised no salt diet
- Fluid restriction to 1-1.5 L over 24 hours
- Diuretics- add to remove the peripheral oedema. Over diuresis may cause prerenal AKI. Therefore, monitor fluid loss by daily weights. Loss of weight should be no more than 500-750 mls a day
- Add ACEi/ARB
- Role of anticoagulation
why does heavy proteinuria lead to making the blood prone to clotting
causes loss of antithrombin III, protein C and S through the tubules and these proteins normally help the blood to remain anti-coagulated in the body
what is glomerular filtration, where does it occur and what is it driven by
process by which cells and large proteins are removed from the blood to create ultra filtrate
occurs within the renal corpuscle
driven by opposing pressure exerted by the contents of the blood and ultra filtrate
what is glomerulonephritis
inflammation of the filtration membrane which alters its permeability and inhibits proper filtration
current evidence suggests that most cases of GN are due to immunological response to a variety of etiologic agents which are largely unknown
name some of the known causes of GN
group A streptococci
viral infections like hepatitis C
some drugs
very briefly what immunological process may be involved in GN
o Immunoglobulin and compliment activation within the glomeruli (where the antigen is a structural component of the glomeruli eg good pastures antigen in the glomerular basement membrane)
o The antigens may be trapped or deposited within the glomeruli
when abnormalities occur in the glomerulus patients can present with which clinical syndromes
- Isolated haematuria /proteinuria OR haematoproteinuria
- Nephrotic Syndrome
- Acute glomerulonephritis (acute nephritic syndrome)
- Rapidly progressive glomerulonephritis (RPGN)
- Chronic Kidney Disease including ESRD
• Note that in patients with haematuria it is important to consider urological disease and refer appropriately
Nephrotic vs Nephritic syndrome
- what is the mechanism in nephrotic syndrome
for some reason the podocytes aren’t working or they get lost, as a result they aren’t able to keep the protein in and so there is loss of protein and is quite substantial (can lose up to 3.5 a day)
Nephrotic vs Nephritic syndrome
- what is the mechanism in nephritic syndrome
have immune complexes, an antibody and antigen complex which lodged itself in the capillary and illicit and immune response against the capillaries and antigens.
A number of white cells are recruited and the inflammatory response causes breakdown of the endothelial layer
so red blood cells leak through, white cells and proteins
Nephrotic vs Nephritic syndrome
in which syndrome do you get the following findings
- in urine you get haematuria, sediment due to the WBC aka pyuria, proteinuria
- Get oliguria as the glomerulus is damaged so cant filter as much
- High BP due to lack of filtration
- Will see granulocasts and more inflammation
nephritic (think inflammation is -itis and itic is similar)
Nephrotic vs Nephritic syndrome
in which syndrome do you get the following findings
- Frothy urine due to protein
- loosing protein so isn’t enough in the intravascular space and so periorbital and ankle odema
- liver compensates for lack of albumin so liver releases more lipids
- AT-III decreased and so hyper coagulable state
nephrotic ( phrodocytes sounds like podocytes ?)
once you have identified the renal syndrome (either nephritic or nephrotic) from the history, examination blood and urine tests and USS kidneys what is the next step for diagnosis
renal biopsy for pattern recognition of the renal disease ie the histopathological changes
what are the 4 main causes of nephrotic syndrome
minimal change
focal segmental glomerulosclerosis (FSGS)
membranous glomerulonephritis
membranoproliferazive glomerulonephritis
which of the following nephrotic syndromes are most common in children
minimal change
focal segmental glomerulosclerosis (FSGS)
membranous glomerulonephritis
membranoproliferazive glomerulonephritis
minimal change
which of the following nephrotic syndromes are most common in adults
minimal change
focal segmental glomerulosclerosis (FSGS)
membranous glomerulonephritis
membranoproliferazive glomerulonephritis
focal segmental glomerulosclerosis (FSGS)
which of the following nephrotic syndromes are the immune deposits also present not only in the membrane, but the mesangium too
minimal change
focal segmental glomerulosclerosis (FSGS)
membranous glomerulonephritis
membranoproliferazive glomerulonephritis
membranoproliferazive glomerulonephritis
Name some secondary causes of glomerular injury
o Primary/Idiopathic
o Secondary
• Autoimmune (e.g. SLE)
• Infections (e..g. malaria, hepatitis B & C, HIV)
• Drugs (e.g. NSAIDs, pencilliamine)
• Heavy metals (e.g. gold, mercury)
• Tumours (solid tumours e.g. lung, colon and haematological malignancies e.g. multiple myeloma)
the natural progression of diabetic nephropathy can result in a nephrotic syndrome in the late stages of the disease
- what would a renal biopsy show
nodules in the mesanigium known as kimmelstiel-wilson lesions
note that if it is clear that the causes is diabetic nephropathy a renal biopsy would be avoided
what group of bacteria is the usual cause of Poststreptococcal glomerulonephritis (PSGN)
group A beta-haemolytic streptococcus
in Poststreptococcal glomerulonephritis (PSGN) what clinical findings do you get
haematuria, proteinuria, oliguria and also peripheral and periorbital odema
typically, PSGN affects children either _______ weeks after a skin infection (impetigo) or ______ weeks after a throat infection (pharyngitis)
6 weeks
1-2 weeks
in someone with PSGN what would blood tests show
antibodies against group A strep- known as DNAase B and decreased compliment
treatment is usually supportive but 1/4 of adults progress to rapidly progressive GN
in IgA nephropathy
- what does it commonly present with
- what does urinalysis show
- what can confirm the diagnosis
- normally presents with bloody urine occurring 1-3 days after the onset of an upper respiratory infection
- urinalysis shows erythrocytes and mild proteinuria
- only biopsy can confirm the diagnosis
what is rapidly progressive GN (RPGN) and what is another name for it
syndrome with glomerular haematuria (RBC casts or dysmorphic RBC) rapidly developing kidney injury over a few weeks to few months progressing to kidney failure if not treated promptly
inflammation of the kidney glomeruli, causing crescent shaped inflammation causing renal failure
aka crescentic glomerulonephritis (CGN)
what are the main types of rapidly progressive GN
type 1
type 2
type 3
idiopathic
tell me more about type 1 RPGN and give example
production of anti-GBM antibodies aka good pastures syndrome
tell me more about type 2 RPGN and give example
production of immune complexes with antigen and antibody
- poststreptococcal GN
- lupus
- IgA nephropathy
- Henoch-schonlein pura pura
tell me more about type 3 RPGN and give examples
you are termed ‘PUACI- immune” which means you have no anti-GBM and no immune complexes
- there are ANCAs in the blood (anti-neutrophilic cytoplasmic antibodies)
- examples are Wegener granulomatosis, microscopic polyangitits, churg-strauss syndrome
in RPGN what does immunofluorence show for the following
type 1
type 2
type 3
type 1 - linear as the anti-GBM binds to collagen of GBM
type 2 - granular as the immune complexes deposit in the sub endothelium
- type 3 is negative as there are no anti-GBM and no immune complexes
for RPGN what age group does it normally affect and what is the treatment
usually affects adults in 50s-60s and poor prognosis if not treated early
- treatment is; anticoagulant to reduce fibrin, plasmapheresis and immunosuppressants and dialysis or kidney transplant
