CS19 Flashcards
What is diabetic nephropathy?
kidney damage/disease cause by diabetes
-high blood sugar(and high blood pressure) can cause damage to the small blood vessels and tiny filters in you kidneys. This can cause leakage/ dysfunction = high protein in urine(searly sign of kidnay disease)
How many people with daibetes need treatment for diabetic nephropathy?
almost 1 in 5
What are the symptoms of diabetic nephropathy?
no visible symptoms in early stages which is why it is important to have tests for kidney disease.
If kidney disease progresses you could see symptoms like swollen ankles feet and hands, blood in urine, feeling really tired , being short of breath, feeling sick.
How can you reduce the risk of developing kidney disease?
keep blood sugar levels within target range, keep blood pressure down, get support to stop smoking, eat healthily, keep active, go to all medical appointments
What blood test can you use to test for kidney disease?
eGFR-tests for a waste product called creatinine
If you develop late stage idney disease or kidney failure nhow is it treated?
dialysis or kidney transplant
What are the 3 layer of the glomerulus filtration barrier?
- Endothelial cells of glometular capillaries
- Glomerular basement membrane
- epithelial cells of bowmans capsule called podocytes
Describe the glomerular capillary endothelium?
has perforations called fenestrations which are pores about 70nm. These limit the filtration of cellular components e.g. RBCs.
-surounding the luminal surface of the endothelial cells is glycocalyx consisting of negatively charged glycosaminoglycans which hinder the diffusion of negatively charged molecules.
Describe the make-up and structure of the glomerular basement membrane?
made up of mostly:
- collagen type IV
- heparan sulfate proteoglycans -restrict the movement of negaively charged molecules across the basement membrane
- lamina.
Has 3 layers:
- inner thin layer(lamina rara interna)
- thick layer(lamina densa)
- outer dense layer(lamina rara externa)
These layers help limit the filtration of larger molecules
Describe the structure and function of podocytes?
Specialised epithelial cells
- Foot like process projet from these and interdigitate to form filtration slits which are bridges by a thin diaphragm which has very small pores prevent ing large molecules from crossing
- negatively charged gycoproteins cover the podocytes restricting filtration of large negatively charged ions(anions)
What effects the filtration rate of a molecule?
size and charge
- filtration rate of molecules of the same chrge is inversly related to their molecular weight (easier if smaller)
- Negatively charged large molecules are less easily filtered thn positively charged molecules of the same size
What is the responsible for 10-25% of cases of nephrotic syndrome?
Describe?
Minimal change Glomerulonephritis- disease that damges glomeruli but damage cant be seen under a light microscope only under an electron microscope. There is diffuse effacement of podocytes foot processes causing the widening of filtration slits and microvillous change.
-pathology thought to be due to a T-cell derived factor
What are the symptoms of nephrotic syndrome?
- Proteinuria
- hypoalbuminemia
- oedema
What is alport syndrome and symptoms?
genetic disease characterised by progressive chronic kidney disease with symptoms of haematuria, sensorineural deafness and ocular abnormalities.
-the inheritance is mostly x-linked with mutations for α5 chain of type IV collagen. This results in thinning of the lamina densa of the glomerular basement membrane with areas of multi-layering producing a basket weave appearance.
In later stages of the disease, glomerulosclerosis, interstitial fibrosis and tubular atrophy occur
What is the treatment for Alport syndrome?
No definitive treatment but ACE inhibitors are given to reduce proteinuria and progression of renal kidney disease as well as to control hyprtension.
Where is renin released from and waht 3 things stuimulate this release?
- Renin released from granular cells of the renal juxtaglomerular apparatus (JGA) in response to one of three factors:
- Reduced sodium delivery to the distal convoluted tubule detected by macula densa cells
- Reduced perfusion pressure in the kidney detected by baroreceptors in the afferent arteriole
- Sympathetic stimulation of the JGA via β1 adrenoreceptors
What inhibits the release of renin?
ANP -Atrial natriuretic peptide
-this is released in response to increases in blood pressure
How is angiotensin II formed?
Where is angiotensin II formed?
Angiotenisin precursor protein produced in the liver and cleaved by renin to form angiotensin I.
Angiotensin I is then converted to angiotensin II by angiotensin converting enzyme (ACE).
This conversion occurs mainly in the lungs where ACE is produced by vascular endothelial cells, although ACE is also generated in smaller quantities within the renal endothelium.
What are the effect of angiotenisin II?
Cardiovasuclar effects:
-acts on AT1 receptors found on the enothelium of arterioles to achieve vasoconstriction. This signalling occurs via a Gq protein, to activate phospholipase C = increase intracellular calcium = increase in total peripheral resistance and consequently, blood pressure
Neural effects:
-acts at the hypothalamus to increase thirst, = increased fluid consumption= increased blood volume =increased blood pressure.
ADH-secretion increased from the posterior pituitary gland= mess fluid lost in urine=more conventrated urine
NA- stimulates the sympathetic nervous system = increased release of noradrenaline (NA) which is assosiated with “fight or flight” response in stressful situations = Increase in cardiac output, Vasoconstriction of arterioles, Release of renin.
Renal effects:
-increases Na+ reabsorption in PCT and those in the attatched image

How is aldosterine released?
Describe its effects?
Angiotensin II acts on the adrenal cortex to stimulate the release of aldesterone( mineralocorticoid) released from the zona glomerulosa
Acts on the principal cells of the collecting ducts i the nephron to increase the expression of apical epithelial Na+ channels (ENaC) to reabsorb urinary sodium. also increases the activity of the basolateral Na+/K+/ATPase. This leads to more sodium reabsorption and more potassium excretion therefore increased aldesterone causes reduced levels of potassium in blood,
What do ACE inhibtiors do?
treat hypertension and heart failure e.g. ramipril, lisinopril, enalapril
- inhibt ACE so reduces the levels of angiotenis II within the body=- decreases activity of the renin-angiotesin-aldosterone system(RAAS) = decreased arteriolar resistance, Decreased arteriolar vasoconstriction, Decreased cardiac output and Reduced potassium excretion in the kidneys
- reduce blood pressure and urinary protein excretion
What are some side effects of ACE inhibitors?
include dry cough, hyperkalaemia, headache, dizziness, fatigue, renal impairment and rarely, angioedema.