Formation of Urine Part 1 Flashcards
Filtration (basic renal process)
Site of renal filtration - glomerulus
Force for filtration: blood pressure and differing diameter of afferent and efferent arterioles
Glomerular Filtration Rate (GFR): 125mL/min - 8L/day - normal plasma volume = 2-3L; rate at which glomerular filtrate is produced - can be measured clinically, and used as an indicator of renal function
Glomerular Filtration
Ultrafiltration - all small molecules are filtered: electrolytes, amino acids, glucose, metabolic waste, some drugs/metabolites; all large molecules and cells remain in the blood: rbcs, lipids, proteins, most drugs/metabolites
Dependent on blood pressure and renal blood flow
Filtrate has to pass through:
- pores in glomerular capillary endothelium; basement membrane of Bowman’s capsule (includes contractile mesangial cells); epithelial cells of Bowman’s capsule - podocytes - via filtration slits into capsular space
Filtration Pressures
Pressure out of blood: Glomerular capillary hydrostatic pressure + Bowman’s space oncotic pressure
Pressure into blood: Glomerular capillary oncotic pressure + Bowman’s capsule hydrostatic pressure (almost 0)
Autoregulation of Renal Blood Flow
Renal blood flow is subject to auto regulation over broad range of systemic BPs (90-200), and persists in denervated and isolated perfused kidneys, so is not a neuronal or hormonal response, but a local effect
2 hypotheses: myogenic (stretch receptors - if BP decreases, renal artery and efferent arterioles automatically constrict to maintain constant renal blood flow of 1200mL/min); and metabolic (renal metabolites modulate afferent and efferent arteriolar contraction and dilation (adenosine, NO)
Most likely a combination of both
Changes in GFR can alter systemic blood pressure
A drop in filtration pressure causes a drop in GFR
Lower GFR means less Na+ enters the proximal tubule
The macula dense senses a change in tubular Na+ levels - which stimulates juxtaglomerular cells to release renin into the blood
Renin release leads to generation of angiotensin II
Ang II is a vasoconstrictor which causes BP to increase
Increased BP causes filtration pressure to increase and GFR returns to normal
Reabsorption from the proximal tubule
Glomerular filtrate enters the proximal tubule (PT) where:
60-70% of filtered water, Na+, HCO3-, Cl-, K+ and urea are reabsorbed from the PT
There is almost complete reabsorption of glucose, amino acids and small amount of filtered proteins
The driving force for this reabsorption is Na+K+ATPase
Na+/K+ ATPase
Na+-K+-ATPase pumps out Na+ into the blood against chemical and electrical gradients
This process requires ATP
Accompanied by entry of K+ ions which rapidly diffuses out of cells into blood
The ratio of transport is 3 Na+ leaving cell: 2 K+ entering cell
Keeps sodium concentration low in proximal tubules (less than 30nM) due to pump
Sodium concentration also low in PTs due to low charge in the cells
Cl- follows Na+ by facilitated diffusion
Phosphate (PO42-) and sulphate (SO42-) are also co-transported with Na+
Water reabsorption from the PT
60-70 % filtered water reabsorbed in the PT - active transport of Na+ out of PT cells is the driving force
Movement of solutes (Na+, HCO3- and Cl-) reduces osmolality of tubular fluid…and increases osmolality of interstitial fluid
A net flow of water from tubule lumen to lateral spaces occurs by transcellular and paracellular routes
Transcellular routes involve aquaporin (AQP) channels located on apical and basolateral surfaces
There is no active water reabsorption along nephron - it occurs by osmosis and it follows sodium
Water reabsorption from the PT (part 2)
PT is highly permeable to water. Water flow from tubule lumen to lateral spaces occurs by paracellular & transcellular routes (aquaporins)
13 different types of aquaporins identified, 6 in the kidney, these are the 4 major renal AQPs:
- Aquaporin-1 (AQP1): Abundant distribution in proximal tubule and other parts of tubule where water is reabsorbed, e.g. descending limb of LOH
- Aquaporin-2 (AQP2): Present in collecting duct on apical surface AQP-2 channel expression is controlled by antidiuretic hormone (ADH)
- Aquaporins-3 & 4 (AQP3 & AQP4): Present on basolateral surface of tubular cells involved in water reabsorption
Further reabsorption in the PT
Potassium (K+) - 70 % of filtered K+ is reabsorbed in the PT, mostly passively via tight junctions (i.e. paracellularly).
Urea - 40–50 % filtered urea is reabsorbed passively in the PT down its concentration gradient.
Amino Acids - 7 independent transport processes for reabsorption of AAs from the PT – depends on type of AA; High Tm for transport so that as much as possible is reabsorbed from PT
Proteins - Reabsorbed from the PT via receptor-mediated endocytosis
Protein reabsorption from the PT
Small amounts of protein pass into filtrate via the glomerulus
These are reabsorbed by pinocytosis - vesicles transported into cell, degraded by lysosomes and amino acids returned to blood
Only limited transport capacity (low Tm)…
Proteinuria is a sign of glomerular damage and impending renal failure
Secretion into the PT
Some endogenous substances /drugs cannot be filtered at the glomerulus - this may be due to their size or protein binding
Specialised pumps in the PT can transport compounds from the plasma into the nephron
Two kinds of “pumps” (includes OAT, URAT):
For organic acids - (e.g. uric acid, diuretics, antibiotics - penicillin)
For organic bases (e.g. creatinine, procainamide)
Secretion of Para-amino hippurate (PAH) into the PT
Para-amino hippurate (PAH) is secreted into PT from blood
Not an endogenous compound so PAH can be used as a tool to measure tubular secretion
Transported into PT cells from blood with alpha-ketoglutarate or other di/tri carboxylates
Transported out of PT cells in exchange for another anion present in the PT lumen
