CSI 9.2 Flashcards
What are ACE inhibitors used for?
the treatment of hypertension and heart failure
What are some examples of ACE inhibitors?
- ramipril
- lisinopril
- enalapril
What do ACE inhibitors do?
- inhibit the action of angiotensin converting enzyme and so reduce the levels of angiotensin II within the body
- Reduces activity of RAAS in body
What are the physiological effects of RAAS?
- Decreased arteriolar resistance
- Decreased arteriolar vasoconstriction
- Decreased cardiac output
- Reduced potassium excretion in the kidneys
Which conditions are helped by ACE inhibitors?
lower blood pressure in hypertensive patients and also help to improve outcomes in conditions such as heart failure
What are some side effects of ACE inhibitors?
dry cough,hyperkalaemia, headache, dizziness, fatigue, renal impairment and rarely, angioedema
What are the two most important prognostic factors in CKD?
- hypertension
2. proteinuria
What does it mean if creatine in urine?
Creatine is non protein molecule, not reabsorbed and secreted and so high blood serum something wrong in filtration from glomerulus
What is saturable?
protein reabsorption
How much protein is reabsorbed?
-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
What are the three difference classification of proteinuria?
overflow, glomerular, tubular
What is an example of overflow proteinuria?
Rhabdomylosis
What is an example of glomerular proteinuria?
Diabetic nephropathy
What is an example of tubular proteinuria?
Acute tubulointestial nephritis
Which arteriole is affected in hyperglycaemia? What happens here?
afferent where non-enzymatic glycation of endothelial cells results in stiffening and narrowing of the vessel
What can hyperglycaemia also affect?
-Activate the RAA system within the kidney regardless of the volume status of the individual
What does efferent arteriole narrowing due to AG2 increase?
upstream pressure in the glomerulus
What does hypertension as a result of diabetes lead to?
- 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
What is the result of the excess glucose?
- The proximal tubules work hard to reabsorb this excess glucose which also leads to increased sodium reabsorption (as sodium is cotransported with glucose)
- Therefore less sodium is delivered to the macula densa in the distal tubule
- Lower sodium uptake by macula densa cells leads to less stimulation of afferent arteriole vasoconstriction
- . Combining all these effects, afferent and efferent arteriolar deregulation initially results in increased filtration pressure across the glomerulus which results in greater protein loss
What happens in early diabetic nephropathy?
-Increased filtration rates or hypo filtration
What happens to the blood supply?
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
What does the relative iscahemia recruit?
- 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
What is the glomerular filtration barrier made up of?
- glomerular capillary endothelial cells
- Glomerular basement membrane
- podocytes
What happens to the endothelial cells and basement membrane?
- Both hypertensive changes and changes from hyperglycaemia can damage the glomerular capillary endothelial cells
- Diabetes can also result in intrisict changes to the glomerular basement membrane
- This becomes thickened in diabetic nephropathy however structural change means it also becomes leaky
How are podocyte foot press interconnected?
- 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
What happens in diabetic enphropathy?
- Reduced nephron expression
2. Podocytes can be damaged directly by advanced glycation end products, a result of hyperglycaemia
What can affect protein loss?
- 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
- Presence of albuminuria represent a defect in at least one of these layers
