T3 L3 Formation of urine Flashcards
What are the 5 processes of urine formation?
1) Glomerulus - filtration of blood
2) Proximal tubule - reabsorption of filtrate and secretion into tubule
3) Loop of Henle - concentration of urine
4) Distal tubule - modification of urine
5) Collecting duct - final modification of urine
What are the 3 major functions of the nephron?
Filtration of blood to produce a filtrate
Reabsorption of water, ions and organic nutrients from filtrate
Secretion of waste products into tubular fluid
What is the force for filtration?
Blood pressure
Differing diameter of afferent and efferent arterioles
What molecules are filtered in glomerular filtration?
All small molecules Electrolytes Amino acids Glucose Metabolic waste Some drugs, metabolites
What molecules remain in the blood after glomerular filtration?
Red blood cells
Lipids
Proteins
Most drugs, metabolites
What does the filtrate have to pass through in glomerular filtration?
1) Pores in glomerular capillary epithelium
2) Basement membrane of Bowman’s capsule - includes contractile mesangial cells
3) Epithelial cells of Bowman’s capsule via filtration slits into capsular space
What is glomerular filtration rate (GFR?)
Rate at which filtrate is produced in the kidneys
125ml/min
What are the 2 hypothesises for autoregulation of renal blood flow?
Myogenic - auto regulation due to a response of renal arteries to stretch
Metabolic - renal metabolites modulate vasodilation such as nitric oxide, endothelin
What happens when the afferent arteriole dilates?
GFR decreases due to decreased BP
Efferent arteriole constricts (due to Ang II)
Increases GFR back to normal
What causes the afferent arteriole to dilate?
Prostaglandins Dopamine ANP NO Kinins
What happens when afferent arterioles constrict?
GFR increases due to increased BP
Efferent arteriole will dilate (due to adenosine)
GFR decreases back to normal
What causes the afferent arteriole to constrict?
Noradrenaline
Endothelin
Adenosine
ADH
What happens to GFR when there is a drop in filtration pressure?
1) Drop in filtration pressure causes a drop in glomerular filtration rate
2) Lower GFR means less Na+ enters proximal tubule
3) Macula densa senses a change in tubular Na+ levels
4) Stimulates juxtaglomerular cells to release renin into the blood
5) Increased blood pressure causes filtration pressure to increase & GFR returns to normal
What is reabsorbed from the glomerular filtrate in the proximal tubule?
60-70% of filtered water, Na+, HCO3-, Cl-, K+, urea, glucose, amino acids, small amounts of filtered proteins
What is the driving force for reabsorption from the glomerular filtrate in the proximal tubule?
Na+/K+ ATPase
Describe sodium reabsorption from the proximal tubule
Cells have a low intracellular sodium concentration due to Na+/K+ ATPase - overall negative charge due to presence of intracellular proteins
Goes against concentration gradient
Cl- follows Na+ by facilitated diffusion
Phosphate & sulphate are co-transported with sodium
What is the driving force for water reabsorption in the proximal tubule?
Active transport of Na+ out of the cell
What are the main aquaporins in the kidney?
AQP1
AQP2
AQP3
AQP4
Describe aquaporin 1
Abundance distribution in proximal tubule
Wide distribution - also found in lungs and brain
Describe aquaporin 2
Present in collecting duct on apical surface
AQP2 channel expression is controlled by ADH
Describe aquaporin 3 & 4
Present on basolateral surface of collecting duct cells
How does glucose move into the proximal tubule cell?
Cotransported with sodium
What are SGLT2 inhibitors?
New drugs for controlling type 2 diabetes
Make diabetic patients excrete more glucose
Causes sugary urine which could increase risk of UTI
How is potassium reabsorbed?
70% of filtered potassium is reabsorbed in the proximal tubule
Mostly by passive transport through tight junctions - paracellularly
How is urea reabsorbed?
40-50% of filtered urea is absorbed passively in proximal tubule
How are amino acids reabsorbed?
7 independent transport processes for reabsorption
High Tm for transport to maximise the amount reabsored
How are proteins reabsorbed?
From the proximal tubule via receptor-mediated endocytosis
Small amounts of protein pass into filtrate via glomerulus
Reabsorbed by pinocytosis
Only a limited transport capacity - low Tm
What does proteinuria suggest?
Sign of glomerular damage and impending renal failure
Describe the process of pinocytosis for protein reabsorption?
Vesicles transported into cell
Degraded by lysosomes
Amino acids returned to blood
Describe the secretion of PAD into the proximal tubule
PAD is secreted into the proximal tubule from the blood with alpha-ketoglutarate or other di/try carboxylates
Not an endogenous compound so can be used to measure tubular secretion
Transported out of proximal tubule cells in exchange for another anion present in proximal tubule lumen
What are some endogenous organic acids secreted into the urine?
cAMP Bile salts Hippurates Oxalate Prostaglandins Urate (uric acid)
What are some organic acid drugs secreted into the urine?
Acetazolamide Chlorothiaze Furosemide Hydrochlorothiazide Bumentaide Penicillin Probencid Salicylate
What are some endogenous organic bases secreted into the urine?
Creatinine Dopamine Adrenaline Noradrenaline Histamine Choline Thiamine, guanide
What are some organic base drugs secreted into the urine?
Atropine Isoproterenol Cimetidine Morphine Quinine Amiloride Procainamide
