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Biochem basis of human disease > watson - renal scarring > Flashcards

watson - renal scarring Flashcards

1
Q

what can renal scarring be caused by

A 
glomerulonephritis
diabetes
hypotension
pyelonephritis
urinary blockage
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2
Q

what structure in the kidney allows filtration to take place

A

glomerulus

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3
Q

what is the functional unit of the kidney known as

A

the nephron

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4
Q

what does the nephron consist of

A

glomerulus and tubules

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5
Q

the glomerulus is a large capillary network supported by a specialised type of cell called what?

A

podocytes

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6
Q

the glomerulus is encapsulated by epithelial cells forming what

A

bowmans capsule

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7
Q

the bowmans capsule forms forms a capsular space into which glomerular filtrate can drain prior to passage down the what?

A

tubule

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8
Q

where are the glomeruli found

A

in the cortex

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9
Q

where are the tubules found

A

in the medulla

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10
Q

what are the 4 main functions of the kidney

A
  1. clear the body of toxins
  2. regulate body pH
  3. maintain water balance
  4. control sodium/potassium and other electrolyte levels
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11
Q

what are the clinical measurement of kidney function

A

creatinine clearance

glomerular filtration rate

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12
Q

creatine acts as a reservoir of high energy phosphate and this can be used for energy. during the synthesis catalysed by creatine kinase you get the spontaneous conversion to which waste product

A

creatinine

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13
Q

creatinine levels in blood and urine may be used to calculate creatinine clearance which reflects what

A

glomerular filtration rate

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14
Q

Once renal function falls below 10% measured by Creatinine Clearance and GFR the patient will require treatment by what

A

dialysis

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15
Q

what are the 2 types of dialysis currently used

A
  • haemodialysis

- peritoneal dialysis

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16
Q

what are the additional kidney functions

A

produces hormone erythropoietin which stimulates the production of red blood cells
- hydroxylation of vitamin D which causes calcium absorption from gut

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17
Q

Patients under dialysis can lack vitamin D and erythropoietin so the patient has to be supplied with additional supplements to prevent what?

A

wasting

18
Q

scarring is the result of imbalance in what

A

deposition of extracellular matrix

19
Q

growth factors are released from:

A

damaged endothelial cells

infiltrating lymphocytes

20
Q

what are the 2 main growth factors that cause scarring by leading to increased deposition of ECM

A

PDGF

TGF-beta

21
Q

which enzymes are involved in the deposition and degradation of ECM

A

MMPs and TIMPs

22
Q

what are TIMPs

A

tissue inhibitors or matrixmetalloproteins - dampen down the lay down of ECM

23
Q
  • Smoking is pro fibrotic and has negative effects on blood pressure T/F
A

T

24
Q

what are matrix metalloproteins

A

enzymes that degrade the ECM

25
Q
  • Local delivery of MMP has been shown to reduce collagen content in rat model of liver disease T/F
A

T

26
Q

overexpression of MMPs causes what in mice

A

more fibrosis

27
Q

what can tissue transglutaminase be referred to as

A

natures superglue

28
Q

what does tissue glutaminase fo

A

crosslinks components of the ECM covalently forming unbreakable bonds to stabilise ECM from degradation

29
Q

what bond does TG2 form

A

glutamyl-lysyl dipeptide bond

30
Q

TG2 has 4 domains these are:

A

sandwich domain
catalytic core
betabarrel1
betabarrel2

31
Q

what is the sandwich domain of TG2 important for

A

to anchor it to ECM binding site for fibronectin which is an important component of ECM

32
Q

when in the non active form the barrels in TG2 are tight against the catalytic core. what leads to a structural change and the catalytic core to be exposed

A

calcium

33
Q

what is the critical residue in TG2 catalytic core

A

Cys277

34
Q

the catalytic core is conserved between all members of the transglutaminase family T/F

A

T

35
Q

TG2 is implicated in many diseases including what

A

tissue scarring and fibrosis
coeliac
neurodegenerative
cancer

36
Q

Subtotal nephrectomy (rat) is the most widely used model for renal scarring. what does this consist of

A

removing 1 kidney and 2/3 of other. kidney becomes overburdened and fails

37
Q

what is the evidence that TG2 has an important role in scarring

A

the more scarring you have, the more TG2 you have and more crosslinks you have

38
Q

name 2 pan transglutaminase inhibitors

A

NTU 281

NTU 283

39
Q

what do pan transglutaminase inhibitors do

A

react with invariant cysteine in catalytic core

40
Q

existing TG inhibitors are broad spectrum. what do they also inhibit

A

TG1
TG3 - maintain epidermis
factor 13 - blood clotting

41
Q

Current compounds all target the conserved cysteine and are not specific. there are serious side effects of blocking other members of the TG enzyme family prevent their system use T/F

A

T

42
Q

what is a possible therapeutic route for inhibiting TG2

A

blocking calcium binding so blocking activation

Biochem basis of human disease (6 decks)

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