CKD Flashcards
What are the functions of the kidneys?
- Regulate water balance
- Regulate acid-base balance
- Regulate electrolyte balance
- Remove wastes
- Release hormones
What is Chronic Kidney Disease?
Is the decline is renal function for greater than or equal to 3 months
How do we determine renal function?
Using GFR- the rate at which blood is filtered through the kidneys per minute
What are the causes of CKD?
- Diabetes ( Diabetic nephropathy )
- Hypertension
- Glomerulonephritis
- Poly cystic kidney disease
- NSAIDS overuse
How does Diabetes cause CKD?
Diabetes causes a rise in blood glucose
This Glucose combine with proteins and lipids by a non enzymatic glycation process to form pro inflammatory molecules
These pro inflammatory molecules get deposited in arteriolar endothelial cells causing vascular damage
This results to arteriosclerosis, either hyaline arteriosclerosis or arthesclerosis
Due to this, the arterioles thicken and stiffen therefore making it difficult for oxygen to diffuse and supply nearby tubular cells and tissues causing ischemia and eventually necrosis that leads to decreased GFR
Also Ateriosclerosis on efferent arterioles results to an increase in back pressure therefore causing an increase in GFR
This increase in GFR stimulates the mesangial cells to release Transforming Growth Factor -Beta ( TGF-beta), this cytokine triggers fibroblasts to produce extracellular matrix therefore causing fibrosis which eventually leads to Glomeruloseclerosis. Overtime this decreases GFR.
Kimmelstiel-Wilson lesion
This is a hallmark of diabetic nephropathy.
They are discrete, round, solid nodules of sclerosis found in glomerular of kidneys.
How does Hypertension cause CKD?
Hypertension causes damage in arteriolar endothelial cells leading to hyaline arteriosclerosis
This causes thickening and stiffening of of vascular walls resulting in difficulty of oxygen perfusion to nearby tubular cells and tissues
This triggers the mesangial cells proliferate and releaseTGF-beta which stimulate fibroblasts to produce extracellular matrix that lead to fibrosis and eventually glomerular sclerosis, overtime it leads to gradual decrease in GFR resulting in CKD
How doe’s Glomerulonephritis cause CKD?
Antibody antigen complexes due to autoimmune response or infection formed are deposited in the glomerular this causes inflammation leading to Glomerulonephritis
This impairs the Glomerular basement membrane which results in it’s increased porosity which causes larger molecules like proteins to be filtered and found in the urine
The ongoing inflammation will stimulate the mesangial cells to proliferate and produce TGF-beta which triggers fibroblasts to produce extracellular matrix leading to fibrosis and eventually glomerular sclerosis. This causes a progressive decrease in GFR
How does polycystic kidney disease cause CKD?
PCKD is characterized by numerous fluid-filled cyst of the kidney tubules
This then results in compression of nearby blood vessels
The compression of these vessels impairs their ability to regulate blood flow therefore reducing oxygen perfusion to nearby tissues, this leads to ischemia and eventually necrosis of nephrons causing progressive loss of kidney function thus CKD
Furthermore
Compression of the arterioles decreases blood flow to the glomeruli therefore decreasing GFR, this stimulates the juxtaglomerular complex to release Renin which triggers the RAAAS
Angiotensin II from this process causes vasoconstriction in an attempt to increase blood pressure
This results in secondary hypertension which inturn leads to progressive further decrease in GFR.
How does NSAIDs overuse lead to CKD?
NSAIDs work by inhibiting the activity of Cyclooxygenase enzymes involved in the production of prostaglandins, therefore reducing their formation.
Prostaglandins have a vasodilatory effect on the afferent arterioles of the kidneys, this helps to maintain a normal GFR.
NSAIDs inhibit this function therefore leading to vasoconstriction of afferent arterioles and eventually causing a decrease in GFR which subsequently leads to CKD.
Pathophysiology of CKD
- Electrolyte abnormalities
- Water imbalance
- Uremia
- Hormone imbalances
- Metabolic acidosis
- Hyperlipidemia
Explain the pathophysiology of electrolyte abnormalities in CKD
- Hyperkalemia and hyperphospathemia
These occur as a result of decreased GFR, therefore the body retains a lot these electrolytes instead of excreting them
Also it occurs as a result of tubular damage impairing their function to secrete potassium and phosphate ions - Hypocalcemia
This occurs as a result of destruction of tubular cells therefore decreasing the conversion of vitamin D to calcitriol( it’s active form)
This in turn decreases calcium absorption in the small intestines therefore decreasing levels of free calcium ions in the blood
Also the high levels of phosphate ions usually combine with calcium ions in the blood to form precipitates further decreasing calcium ions
Explain water imbalance pathophysiology in CKD
Decreased GFR lead to overall water retention
Albuminuria due to damaged tubular cells lead to water escaping from vessels into the interstitial spaces
These bring about : Pulmonary edema in the lungs, Hypertension due to fluid overload as well as peripheral edema
Explain uremia pathophysiology in CKD
Due to decreased GFR, there will be waste accumulation in the body, wastes such as urea this this is called azotemia
Once azotemia starts causing damage to other organs, it’s called uremia
1. In the brain: it cause’s encephalopathy which is characterized by Asterixis, seizures and in severe cases Coma
- In the heart: it causes uremic pericarditis that could potentially develop to pleural effusions and in severe cases cardiac tamponade
- In the skin: it accumulates in sweat glands and leads to formation of urea frosts on the skin
- On platetelets: It causes platelet dysfunction as it impairs their ability to stick together ( platelet aggregation and adhesion) this leads to bleeding ( coagulopathies)
Explain hormone imbalance pathophysiology of CKD
- Tubular cells damage lead to hormone imbalance such as :
a) Decreased production of Erythropoietin ( EPO)
This leads to decreased production of Red Blood Cells causing Anemia due to Chronic disease
b) Secondary hyperparathyroidism:
Destruction of tubular cells lead to decrease activation of Vitamin D to calcitriol which helps the absorption of calcium in the gut, this causes decrease in calcium levels in the blood which triggers Parathyroid glands to release parathyroid hormone so as to increase calcium in the blood.
The PTH acts on bones causing an increase in osteoclastic activity inorder to release calcium. This causes diseases such as Renal osteodystrophy.
- Decreased GFR causes
Renin release which activates rhe RAAAS, this system releases Angiotensin II which nduces vasoconstriction so as to raise the blood pressure, this causes secondary hypertension
