watson - renal scarring

Question 1

what can renal scarring be caused by

Answer 1

glomerulonephritis
diabetes
hypotension
pyelonephritis
urinary blockage

Question 2

what structure in the kidney allows filtration to take place

Answer 2

glomerulus

Question 3

what is the functional unit of the kidney known as

Answer 3

the nephron

Question 4

what does the nephron consist of

Answer 4

glomerulus and tubules

Question 5

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

Answer 5

podocytes

Question 6

the glomerulus is encapsulated by epithelial cells forming what

Answer 6

bowmans capsule

Question 7

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

Answer 7

tubule

Question 8

where are the glomeruli found

Answer 8

in the cortex

Question 9

where are the tubules found

Answer 9

in the medulla

Question 10

what are the 4 main functions of the kidney

Answer 10

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

Question 11

what are the clinical measurement of kidney function

Answer 11

creatinine clearance

glomerular filtration rate

Question 12

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

Answer 12

creatinine

Question 13

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

Answer 13

glomerular filtration rate

Question 14

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

Answer 14

dialysis

Question 15

what are the 2 types of dialysis currently used

Answer 15

• haemodialysis

- peritoneal dialysis

Question 16

what are the additional kidney functions

Answer 16

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

Question 17

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

Answer 17

wasting

Question 18

scarring is the result of imbalance in what

Answer 18

deposition of extracellular matrix

Question 19

growth factors are released from:

Answer 19

damaged endothelial cells

infiltrating lymphocytes

Question 20

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

Answer 20

PDGF

TGF-beta

Question 21

which enzymes are involved in the deposition and degradation of ECM

Answer 21

MMPs and TIMPs

Question 22

what are TIMPs

Answer 22

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

Question 23

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

Answer 23

T

Question 24

what are matrix metalloproteins

Answer 24

enzymes that degrade the ECM

Question 25

- Local delivery of MMP has been shown to reduce collagen content in rat model of liver disease T/F

Answer 25

T

Question 26

overexpression of MMPs causes what in mice

Answer 26

more fibrosis

Question 27

what can tissue transglutaminase be referred to as

Answer 27

natures superglue

Question 28

what does tissue glutaminase fo

Answer 28

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

Question 29

what bond does TG2 form

Answer 29

glutamyl-lysyl dipeptide bond

Question 30

TG2 has 4 domains these are:

Answer 30

sandwich domain catalytic core betabarrel1 betabarrel2

Question 31

what is the sandwich domain of TG2 important for

Answer 31

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

Question 32

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

Answer 32

calcium

Question 33

what is the critical residue in TG2 catalytic core

Answer 33

Cys277

Question 34

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

Answer 34

T

Question 35

TG2 is implicated in many diseases including what

Answer 35

tissue scarring and fibrosis coeliac neurodegenerative cancer

Question 36

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

Answer 36

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

Question 37

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

Answer 37

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

Question 38

name 2 pan transglutaminase inhibitors

Answer 38

NTU 281 | NTU 283

Question 39

what do pan transglutaminase inhibitors do

Answer 39

react with invariant cysteine in catalytic core

Question 40

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

Answer 40

TG1 TG3 - maintain epidermis factor 13 - blood clotting

Question 41

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

Answer 41

T

Question 42

what is a possible therapeutic route for inhibiting TG2

Answer 42

blocking calcium binding so blocking activation