23. Background Science (Glomerulonephritis)

Question 1

In someone with new onset of odema what systems/conditions could this be related to

Answer 1

heart failure
liver failure 
kidney failure 
cor pulmonale 
DVT
pericardial effusion

Question 2

what does protein 3+ suggest clinically within the kidney

Answer 2

there is glomerular disease as there is damage to the filtration barrier

Question 3

which specific kind of odema is often a feature of GN

Answer 3

periorbital

Question 4

normal excretion of proteins in the urine is less than _________ and of these, albumin excretion is ______ or less

Answer 4

150 mg

30mg

Question 5

name some other proteins that are excreted into the urine apart from albumin

Answer 5

horsfall protein (aka uromodulin)
b2 microglobulin
immunoglobulin light chains

Question 6

Why might we get abnormal values of Urine ACR or PCR

Answer 6

if the urine creatinine is too low or too high or

after a heavy protein meal

Question 7

at what numerical value does a urine dipstick turn positive for albuminuria

Answer 7

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

Question 8

what blood tests would you want to order to investigate for renal glomerular disease

Answer 8

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

Question 9

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)

Answer 9

bence jones proteins

Question 10

what is the management of GN

Answer 10

• 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

Question 11

why does heavy proteinuria lead to making the blood prone to clotting

Answer 11

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

Question 12

what is glomerular filtration, where does it occur and what is it driven by

Answer 12

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

Question 13

what is glomerulonephritis

Answer 13

inflammation of the filtration membrane which alters its permeability and inhibits proper filtration

Question 14

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

Answer 14

group A streptococci
viral infections like hepatitis C
some drugs

Question 15

very briefly what immunological process may be involved in GN

Answer 15

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

Question 16

when abnormalities occur in the glomerulus patients can present with which clinical syndromes

Answer 16

1. Isolated haematuria /proteinuria OR haematoproteinuria
2. Nephrotic Syndrome
3. Acute glomerulonephritis (acute nephritic syndrome)
4. Rapidly progressive glomerulonephritis (RPGN)
5. Chronic Kidney Disease including ESRD
   • Note that in patients with haematuria it is important to consider urological disease and refer appropriately

Question 17

Nephrotic vs Nephritic syndrome

- what is the mechanism in nephrotic syndrome

Answer 17

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)

Question 18

Nephrotic vs Nephritic syndrome

- what is the mechanism in nephritic syndrome

Answer 18

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

Question 19

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

Answer 19

nephritic (think inflammation is -itis and itic is similar)

Question 20

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

Answer 20

nephrotic ( phrodocytes sounds like podocytes ?)

Question 21

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

Answer 21

renal biopsy for pattern recognition of the renal disease ie the histopathological changes

Question 22

what are the 4 main causes of nephrotic syndrome

Answer 22

minimal change
focal segmental glomerulosclerosis (FSGS)
membranous glomerulonephritis
membranoproliferazive glomerulonephritis

Question 23

which of the following nephrotic syndromes are most common in children

minimal change
focal segmental glomerulosclerosis (FSGS)
membranous glomerulonephritis
membranoproliferazive glomerulonephritis

Answer 23

minimal change

Question 24

which of the following nephrotic syndromes are most common in adults

minimal change
focal segmental glomerulosclerosis (FSGS)
membranous glomerulonephritis
membranoproliferazive glomerulonephritis

Answer 24

focal segmental glomerulosclerosis (FSGS)

Question 25

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

Answer 25

membranoproliferazive glomerulonephritis

Question 26

Name some secondary causes of glomerular injury

Answer 26

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)

Question 27

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

Answer 27

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

Question 28

what group of bacteria is the usual cause of Poststreptococcal glomerulonephritis (PSGN)

Answer 28

group A beta-haemolytic streptococcus

Question 29

in Poststreptococcal glomerulonephritis (PSGN) what clinical findings do you get

Answer 29

haematuria, proteinuria, oliguria and also peripheral and periorbital odema

Question 30

typically, PSGN affects children either _______ weeks after a skin infection (impetigo) or ______ weeks after a throat infection (pharyngitis)

Answer 30

6 weeks

1-2 weeks

Question 31

in someone with PSGN what would blood tests show

Answer 31

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

Question 32

in IgA nephropathy

• what does it commonly present with
• what does urinalysis show
• what can confirm the diagnosis

Answer 32

• 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

Question 33

what is rapidly progressive GN (RPGN) and what is another name for it

Answer 33

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)

Question 34

what are the main types of rapidly progressive GN

Answer 34

type 1
type 2
type 3
idiopathic

Question 35

tell me more about type 1 RPGN and give example

Answer 35

production of anti-GBM antibodies aka good pastures syndrome

Question 36

tell me more about type 2 RPGN and give example

Answer 36

production of immune complexes with antigen and antibody

• poststreptococcal GN
• lupus
• IgA nephropathy
• Henoch-schonlein pura pura

Question 37

tell me more about type 3 RPGN and give examples

Answer 37

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

Question 38

in RPGN what does immunofluorence show for the following
type 1
type 2
type 3

Answer 38

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

Question 39

for RPGN what age group does it normally affect and what is the treatment

Answer 39

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