CSI Case 9 Flashcards
What causes kidney disease?
- High blood glucose and blood pressure
- Leak
What are symptoms of kidney disease?
- swollen ankles, feet and hands
- blood in your pee (urine)
- feeling really tired
- being short of breath
- feeling sick.
How can reduce risk of kidney disease?
- Keep your blood sugar (glucose) levels within your target range
- Keep yourblood pressure down
- Get support to stop smoking
- Eat healthily and keep active
- Go to all your medical appointments.
What is ACR urine test?
albumin: creatinine ratio (ACR) looks for signs that protein is leaking into the urine
What is eGFR blood test?
creatinine level and other information (such as age, sex and ethnicity) are used to estimate your glomerular filtration rate (eGFR)
what tablets may be given?
Both ACE inhibitors and ARBs help to protect the kidneys from further damage, as well as lower blood pressure
What are the 3 components of the filtration barrier?
- Endothelial cells of glomerular capillaries
- Glomerular basement membrane
- Epithelial cells of Bowman’s Capsule (podocytes)
What are fenestrae?
- The glomerular capillary endothelium has many perforations calledfenestraewhich are pores about 70nm in size
- These pores actually do not restrict the movement of water and proteins or large molecules but instead is thought to limit the filtration of cellular components (eg: RBCs)
What surrounds the luminal surface of endothelial cells?
glycocalyxconsisting of negatively charged glycosaminoglycans which function to hinder the diffusion of negatively charged molecules
What is the basement membrane surrounding endothelium made of?
- collagentype IV
- heparan sulfate proteoglycans (restrict the movement of negatively charged molecules across the basement membrane)
- lamina
What layers do the basement membrane consist of?
- An inner thin layer(lamina rara interna)
- A thick layer(lamina densa)
- An outer dense layer(lamina rara externa)
What are podocytes?
specialised epithelial cells of Bowman’s capsule which form the visceral layer of the capsule
What projects from the podocytes?
- Foot-like processes project from these podocytes and interdigitate to form filtration slits
- These filtration slits are bridged by a thin diaphgram (the slit diaphragm) which has very small pores preventing large molecules from crossing. 3. Similar to the glycocalyx around the endothelial cells, negatively charged glycoproteins cover the podocytes, restricting filtration of large anions.
What is the filtration rate of molecules the same as?
charge across the filtration barrier is inversely related to their molecular weight
What is freely filtered and what is not?
Small moleculeslike glucose (180 Da) are freely filtered whereas albumin (69 kDa) is barely able to cross the barrier
What charge of the molecule filters better?
Negatively charged large molecules are filtered less easily than positively charged ones of the same size
What is the nephrotic syndrome triad?
- proteinuria
- hypoalbuminemia
- oedema
What happens in minimal change disease?
the glomeruli appear normal under a light microscope but under an electron microscope, the pathology of the podocytes can be detected
What also happens in minimal change disease again?
There is diffuse effacement of the foot processes of podocytes (causing the widening of filtration slits) and microvillous change seen on the podocytes
What is the treatment for minimal change glomerulonephritis?
- respond well to steroids but the symptoms may relapse if the patient comes off steroid therapy
- Some patients become steroid dependant but most do not progress to chronic renal failure and those that do usually have focal segmental glomerulosclerosis as well
What is Alport Syndrome?
genetic diseasecharacterised by progressive chronic kidney disease with symptoms of haematuria, sensorineural deafness and ocular abnormalities
What is the inheritance of Alport syndrome ?
X-linked with mutations of the gene coding for α5 chain of type IV collagen
What happens in the basement membrane with Alport syndrome?
thinning of thelamina densaof the glomerular basement membrane, with areas of multi-layering producing a basket weave appearance
What happens in later stages of Alport syndrome?
- glomerulosclerosis
- interstitial fibrosis
- tubular atrophy
What treatment is available for Alport syndrome?
ACE Inhibitors are given to reduce proteinuria and progression of renal disease as well as to control hypertension
What is the Renin-Angiotensin-Aldosterone System (RAAS)?
hormone system within the body that is essential for the regulation of blood pressure and fluid balance
What are the three hormones in RAAS?
- renin
- angiotensin II
- aldosterone
Where is renin released from?
granular cells of the renaljuxtaglomerular apparatus(JGA)
What three factors stimulate renin release?
- Reduced sodium delivery to the distal convoluted tubule detected bymacula densacells.
- Reduced perfusion pressure in the kidney detected bybaroreceptorsin the afferent arteriole.
- .Sympathetic stimulation of the JGA via β1adrenoreceptors.
What is the release of renin inhibited by?
atrial natriuretic peptide(ANP), which is released by stretched atria in response to increases in blood pressure
How is angiotensin I formed?
Angiotensinogenis a precursor protein produced in the liver and cleaved byrenin
How is angiotensin II formed?
- Angiotensin I is then converted to angiotensin II byangiotensin converting enzyme(ACE)
- This conversion occurs mainly in thelungswhere ACE is produced by vascular endothelial cells, although ACE is also generated in smaller quantities within the renal endothelium.
What does angiotensin II bind to?
one of two G-protein coupled receptors, the AT1 and AT2 receptors
What is the effect of angiotensin II on arterioles?
vasoconstriction
What is the effect of angiotensin II on kidneys?
stimulates Na+ reabsorption
What is the effect of angiotensin II on SNS?
Increased release of NA
What is the effect of angiotensin II on adrenal cortex?
Stimulates release of aldosterone
What is the effect of angiotensin II on hypothalamus?
Increase thirst sensation and stimulates ADH release
What is the cardiovascular effects of angiotensin II?
acts onAT1 receptorsfound in the endothelium of arterioles throughout the circulation to achievevasoconstriction
How is signalling achieved for AG2 in cardiovascular systems?
This signalling occurs via aGqprotein, to activate phospholipase C and subsequently increase intracellular calcium
What is the net effect of AG2 on the cardiovascular system?
an increase intotal peripheral resistanceand consequently, blood pressure
What is the neural effect of AG2?
- increase in fluid consumption
- so raise the circulating volume and in turn, blood pressure
- Increases thesecretion of ADHfrom theposterior pituitary gland
- resulting in the production of more concentrated urine to reduce the loss of fluid from urination
How does NA affect RAAS?
- Increase in cardiac output.
- Vasoconstriction of arterioles.
- Release of renin.
How does AG2 affect the renal artery and afferent arteriole?
- Vasoconstriction
2. Voltage gated calcium channels open and allow and influx of calcium ions
How does AG2 affect the efferent arteriole?
- Vasoconstriction (great than the afferent arteriole)
2. Activation of AT1 receptor
How does AG2 affect the mesangial cells?
- Contraction leading to a decreased filtration area
2. Activation of Gq receptors and opening of voltage-gated calcium channels
How does AG2 affect the proximal convoluted tubule?
- Increased Na+ reabsorption
- Increased Na+/H+ anti porter activity and adjustment of the Starling forces in particular capillaries to increase paracellular reabsorption
How is AG2 important in tubuloglomerular feedback?
- helps to maintain a stable glomerular filtration rate
- The local release of prostaglandins, which results in a preferential vasodilation to the afferent arteriole in the glomerulus, is also vital to this process
Where is aldosterone rebased from?
Aldosterone is amineralocorticoid, a steroid hormone released from thezona glomerulosaof the adrenal cortex
Where does aldosterone act?
acts ontheprincipal cellsof the collecting ducts in the nephron
What does aldosterone do?
- increases the expression of apical epithelial Na+ channels (ENaC) to reabsorb urinary sodium
- the activity of the basolateral Na+/K+/ATPase is increased
What is the result of aldosterone actions?
- This causes the additional sodium reabsorbed through ENaC to be pumped into the blood by the sodium/potassium pump
- In exchange, potassium is moved from the blood into theprincipal cellof the nephron
- This potassium then exits the cell into therenal tubuleto be excreted into the urine
- As a result,increasedlevels of aldosterone causereducedlevels of potassium in the blood.
