Renal - Glomerular and Tubular Function Flashcards
What is renal blood flow?
The volume of blood delivered to the kidneys every minute (ml/min or L/min)
How is plasma filtered?
Blood must enter the glomerulus of the nephron through the afferent arteriole and the fluid formed after the filtration process is called the glomerular filtrate.
The renal tubules then modify the composition of this fluid to become the tubular fluid and then urine
Structure of the renal corpuscle? and how is it specialised for filtration?
- glomerulus consists of a ball of capillaries enclosed within Bowman’s capsule
- epithelium of Bowman’s capsule consists of specialised cells called podocytes, each one having a bulbous cell body and thick extensions called pedicels
- pedicels interdigitate with each other to create gaps between them known as filtration slits
- a proteoglycan membrane separates the epithelium of the Bowman’s capsule and the capillary endothelium
- large pores - fenestrations - perforate the glomerular capillary epithelium
What is glomerular filtration?
a process in which water and some solutes pass from the plasma in the glomerular capillary into the Bowman’s capsule.
fluid formed - glomerular filtrate
there are three barriers substances must pass through, known as the filtration membrane
Barrier 1 of glomerular filtration
- glomerular capillary endothelium
- endothelial cells of glomerular capillaries have relatively large pores - fenestrations - 70-90nm in diameter
Barrier 2 of glomerular filtration
- basement membrane
- composed of proteoglycan gel, which excludes any particles bigger than 8nm. some smaller particles are also held back because the membrane is negatively charged
Barrier 3 of glomerular filtration
- Bowman’s capsule epithelium
- filtration slits are negatively charged and approximately 30nm wide, forming an obstacle to large anions (+plasma proteins)
- the filtered substances include: water, electrolytes, glucose, fatty acids, amino acids, nitrogenous wastes and vitamins
- some low molecular weight substances retained in the blood because they are bound to plasma protein, e.g. calcium and thyroid hormones
- proteinuria is protein in urine, haematuria is blood in urine, can occur from a UTI and associated inflammation
Forces involved in glomerular filtration
- filtration is favoured at the glomerulus because blood hydrostatic pressure in the glomerular capillaries is greater in comparison to most other capillaries (approx. 60 mmHg in comparison to 10-15 mmHg). The blood hydrostatic pressure is elevated like this due to the differences in the diameters of the arterioles, the outlet (efferent) arteriole being narrower than the inlet (afferent) arteriole
What is the Glomerular Filtration Rate?
the volume of fluid filtered from the renal glomerular capillaries into the Bowman’s capsule per unit time (GFR, mL/min)
- for every 1 mmHg of net filtration pressure the kidneys produce 10.5-12.5mL of filtrate every minute
- this value is the filtration coefficient (Kf) and depends on the permeability and surface area of the filtration membrane.
- Kf is lower in women than men
- If the net filtration pressure is about 10 mmHg then a GFR value for an average male at rest is 125 mL/min (10 x 12.5), and a value for an average female at rest is 105 mL/min (10x 10.5)
Regulation of the Glomerular Filtration Rate
- important for GFR to be controlled,
- if it’s too high the tubular fluid flows too quickly and normal reabsorption can not occur - this could lead to dehydration and electrolyte depletion
- if it’s too low, wastes that should have been eliminated can be reabsorbed
- Keeping the GFR constant can be achieved by varying afferent arteriolar diameter to keep blood flow into the glomerulus constant, or by varying efferent arteriolar diameter to keep glomerular hydrostatic pressure constant. at very low and very high blood pressures GFR can deviate from normal values
If arterial blood pressure increases…(GFR)
- afferent arteriolar constriction prevents additional blood from entering the glomerulus
- afferent arteriolar constriction occurs due to myogenic auto-regulation. This refers to the ability of the nephron to adjust it’s own blood flow in the absence of nervous or hormonal control. Thought to be associated with a direct contractile response to stretch of vascular smooth muscle
If arterial blood pressure decreases… (GFR)
- afferent arteriolar dilation prevents a decrease in the volume of blood entering the glomerulus
- afferent arteriolar dilation occurs due to myogenic auto-regulation i.e. when stretch on arteriolar walls decreases the smooth muscle relaxes
- at times of very low arterial blood pressure, a peptide called angiotensin II is produced - this is a vasoconstrictor and it preferentially constricts the efferent arteriole to maintain glomerular hydrostatic pressure and therefore the GFR
What is tubular reabsorption?
the process by which water and other useful substances are reclaimed by the kidney tubules
- the PCT reabsorbs 100% of filtered glucose and amino acids and 65% of the filtered water and Na+
What is the paracellular path?
this involves the diffusion of water and solutes through the junctional spaces between the tubular cells
What is the transcellular path?
this involves the movement of water and solutes across the tubular epithelial cell membrane and cytosol
- the first structure to be crossed is the membrane on the tubular lumen side of the cell, followed by the membrane on the peritubular capillary side
- water crosses these structures by osmosis, a very small amount of solutes may cross by simple diffusion
- most solutes reabsorbed via the transcellular route are reabsorbed by active transport mechanisms specific to the solute
Reabsorption of glucose and amino acids
- PCT reabsorbs 100% of the filtered glucose and amino acids
- to cross from tubule lumen to PCT cell interior, utilises a secondary active transport mechanism (using the potential energy created by movement of Na+ via the Na+, K+ ATPase pump)
- Transporters are co-transporters as they move the glucose/amino acids in the same direction as Na+
- To cross PCT cell membrane on the interstitial fluid side a facilitated diffusion transporter is utilised. Once in the interstitial fluid around the peri-tubular capillaries the glucose and amino acids are free to cross the capillary walls and enter the general circulation again.
What is the transport maximum?
the limit to the rate at which glucose and amino acids can be transported (Tm) (mmol/min)
the Tm for glucose is important clinically and is 2.1mmol/min
the limit is due to the saturation of the transport systems involved, when the amount of substances exceeds the capacity of the carrier proteins
When Tm is exceeded the additional glucose can’t be reabsorbed and is excreted in urine
What is the renal threshold?
The plasma concentration which exceeds the Tm (mmol/min)
normal mean value for this would be 10mmol/L for capillary blood (normal range 7-13)
Glucosuria is the presence of glucose in the urine, most common cause of this being diabetes mellitus
Reabsorption of Na+ ions
- small number of Na+ ions are reabsorbed by diffusion via the paracellular and transcellular routes
- most are reabsorbed by active transport via the transcellular route
- this is facilitated by the concentration gradient for Na+ established between the tubular cell interior and the interstitial fluid by the Na+, K+ ATPase pump.
- both co-transporters and counter transporters are utilised
- The active transport of Na+ ions is said to exhibit the characteristics of gradient-time limited transport, rather than a Tm. Transport in this case is determined by the electrochemical gradient for Na+ diffusion and the time it is actually in the tubule. It is also regulated by the hormone aldosterone
Water reabsorption
- water is reabsorbed across both para- and transcellualr routes by osmosis, passage of water transcellularly is facilitated by the existence of water channels - aquaporins - present in the cell membrane of tubular epithelial cells
- PCT - 65% of filtered water reabsorbs
- other parts contribute.. descending limb of the loop of Henle - 15%
- DCT and collecting duct - 20% - this is controlled by a posterior pituitary hormone (ADH)
Tubular Secretion Pathway
- substances are transported into the tubular fluid for excretion in urine - without going through the glomerulus
- dual function - as well as riding the body of unwanted substances e.g. some drugs, the secretion of certain ions, including H+ ions, help to regulate the pH of the body fluids.
- the processes of tubular reabsorption and secretion can be modified to produce urine which is specifically tailored by the kidneys to maintain the homeostasis of body fluids
