CSI 9.2

Question 1

What are ACE inhibitors used for?

Answer 1

the treatment of hypertension and heart failure

Question 2

What are some examples of ACE inhibitors?

Answer 2

1. ramipril
2. lisinopril
3. enalapril

Question 3

What do ACE inhibitors do?

Answer 3

• inhibit the action of angiotensin converting enzyme and so reduce the levels of angiotensin II within the body
• Reduces activity of RAAS in body

Question 4

What are the physiological effects of RAAS?

Answer 4

1. Decreased arteriolar resistance
2. Decreased arteriolar vasoconstriction
3. Decreased cardiac output
4. Reduced potassium excretion in the kidneys

Question 5

Which conditions are helped by ACE inhibitors?

Answer 5

lower blood pressure in hypertensive patients and also help to improve outcomes in conditions such as heart failure

Question 6

What are some side effects of ACE inhibitors?

Answer 6

dry cough,hyperkalaemia, headache, dizziness, fatigue, renal impairment and rarely, angioedema

Question 7

What are the two most important prognostic factors in CKD?

Answer 7

1. hypertension

2. proteinuria

Question 8

What does it mean if creatine in urine?

Answer 8

Creatine is non protein molecule, not reabsorbed and secreted and so high blood serum something wrong in filtration from glomerulus

Question 9

What is saturable?

Answer 9

protein reabsorption

Question 10

How much protein is reabsorbed?

Answer 10

-Small proteins pass glomerular filtration barrier (sometimes medium does and not protein)
PCT, reabsorb proteins by endocytosis, and hydrolysis it and transport it to basolateral membrane and into circulation
-Almost all protein reabsorbed
-Uromogolobulin is secreted (antimicrobial properties) less than 150mg protein is lost over 24 hours

Question 11

What are the three difference classification of proteinuria?

Answer 11

overflow, glomerular, tubular

Question 12

What is an example of overflow proteinuria?

Answer 12

Rhabdomylosis

Question 13

What is an example of glomerular proteinuria?

Answer 13

Diabetic nephropathy

Question 14

What is an example of tubular proteinuria?

Answer 14

Acute tubulointestial nephritis

Question 15

Which arteriole is affected in hyperglycaemia? What happens here?

Answer 15

afferent where non-enzymatic glycation of endothelial cells results in stiffening and narrowing of the vessel

Question 16

What can hyperglycaemia also affect?

Answer 16

-Activate the RAA system within the kidney regardless of the volume status of the individual

Question 17

What does efferent arteriole narrowing due to AG2 increase?

Answer 17

upstream pressure in the glomerulus

Question 18

What does hypertension as a result of diabetes lead to?

Answer 18

• Increased flow through the afferent arteriole, further increasing glomerular pressure
• Usually the glomerulus would be protected from this increased systemic pressure by auto-regulation and afferent arteriolar constriction, however this tubule-glomerular feedback mechanism is altered in diabetes in which glucose is filtereded by the glomerulus

Question 19

What is the result of the excess glucose?

Answer 19

1. The proximal tubules work hard to reabsorb this excess glucose which also leads to increased sodium reabsorption (as sodium is cotransported with glucose)
2. Therefore less sodium is delivered to the macula densa in the distal tubule
3. Lower sodium uptake by macula densa cells leads to less stimulation of afferent arteriole vasoconstriction
4. . Combining all these effects, afferent and efferent arteriolar deregulation initially results in increased filtration pressure across the glomerulus which results in greater protein loss

Question 20

What happens in early diabetic nephropathy?

Answer 20

-Increased filtration rates or hypo filtration

Question 21

What happens to the blood supply?

Answer 21

With time, hypertensive related changes the the afferent arteriole result in vessels thickenng an reduced lumen diameter so supply of blood to kidney become compromised

Question 22

What does the relative iscahemia recruit?

Answer 22

• macrophages which secrete TGF-beta which agues mesangial cells to secrete more ECM
• this process can also be triggered by hyperglycaemia and pressure damage
• The excessive ECM leads to glomeruloscelerosis and eventually results in reduced capacity for filtration

Question 23

What is the glomerular filtration barrier made up of?

Answer 23

1. glomerular capillary endothelial cells
2. Glomerular basement membrane
3. podocytes

Question 24

What happens to the endothelial cells and basement membrane?

Answer 24

1. Both hypertensive changes and changes from hyperglycaemia can damage the glomerular capillary endothelial cells
2. Diabetes can also result in intrisict changes to the glomerular basement membrane
3. This becomes thickened in diabetic nephropathy however structural change means it also becomes leaky

Question 25

How are podocyte foot press interconnected?

Answer 25

• By the slit diaphragm of which nephron is a key protein component
• Damage to the slit diaphragm Amy contribute to protein lead and the mesangial expansion mentioned above (which pushes aport normal structures) may be in part responsible for this

Question 26

What happens in diabetic enphropathy?

Answer 26

1. Reduced nephron expression

2. Podocytes can be damaged directly by advanced glycation end products, a result of hyperglycaemia

Question 27

What can affect protein loss?

Answer 27

1. Following the increase in filtration pressure seen early in diabetic nephropathy, image to endothelial cells, the glomerular basement membrane and podcytes/slit diaphragms can all contribute to continued protein loss at the glomerulus
2. Presence of albuminuria represent a defect in at least one of these layers