L37. Kidney (3) Flashcards
(15 cards)
What is filtered load?
- To measure the total amount of a substance filtered into Bowman’s space: we can multiply GFR and plasma concentration for a substance = filtered load of that substance
- A comparison of filtered load and excretion of a substance will tell you is that substance undergoes net secretion or reabsorption in the nephrons
- If excreted amount is less than filtered load, then reabsorption has occurred
- If excreted amount is more than filtered load, secretion has occurred
- If we consider the filtered load to be the starting point or 100% of the substance in the nephron, this allows us to compare the amount of a substance reabsorbed along the nephron
What is the filtered load of glucose?
GFR x plasma glucose concentration
Plasma concentration of glucose: 1g/L = 100mg/100mL
Normal GFR: 125mL/min
0.125L/min x 1g/L = 0.125g/min
(baseline to compare to how much of a substance is secreted or reabsorbed along the nephron)
What is glucose reabsorption?
- Glucose is 100% reabsorbed across kidney proximal tubule epithelia by two transport sequential mechanisms
1. SGLTs (apical, sodium dependent)
2. GLUTs (basolateral, sodium independent) (only dependent on glucose gradient)
Compare to the intestinal absorption: glucose is only absorbed via SGLT1, and GLUT2, genetic changes in SGLT1 may cause glucose-galactose malabsorption
Tell me about glucose reabsorption in the proximal tubule?
- In the early proximal tubule SGLT2 re-absorbs 90% of the filtered glucose
- In the late proximal tubule SGLT1 only re-absorbs 10%
- The main glucose transporter in the kidney is SGLT2 and in the intestine SGLT1
Tell me about plasma glucose concentration and rate of glucose (filtered load), reabsorbed or excrete?
- Filtered load not saturable - as freely filtered from plasma
- Glucose transport can be saturated resulting in excretion of excess glucose in the urine, if the plasma concentration increases (diabetes mellitus)
- 0.125g of glucose filtered per minute = 125mg of glucose; this is the normal range
- If more than ~400 mg per minute, glucose capacity of the transporters is reached - they don’t work fast enough to reabsorb all the glucose - glucose will be excreted in the urine
- Diagnostic for diabetes mellitus
What are the effects of inhibition glucose reabsorption?
- Jardiance or empagliflozin
- Specific for SGLT2
- Lowers blood glucose
- Popular diabetic drug
- Improves outcomes for people with kidney and/or cardiovascular disease
How is cardiac blood pressure controlled/medication?
- Sympathetic and parasympathetic nervous system heart (systolic) and the arteries (diastolic)
- Blood pressure regulated mainly by the heart and arteries but depends on blood volume
- Cardiac medication (hypertension) anti-hypertensive drugs (Ca2+ antagonists, B-blocker)
What is renal blood volume control/medication?
- Osmoreceptors in the brain (vasopressin/ADH) and baroreceptors in the arteries and heart
- Regulation is mainly executed by the kidneys
- Medication (hypertension) anti-hypertensive drugs (diuretics)
Tell me about sodium homeostasis?
The kidney is responsible for the excretion of sodium that we take up with the diet
What happens with sodium/Na+ re-absorption in the kidney?
There are 4 important places within the nephron, where sodium is reabsorbed:
1. PCT (66%)
2. TAL (25%)
3. DCT (5%)
4. CCT (3%)
How does sodium reabsorption occur at the PCT?
Na+ reabsorption is 66% of the filtered load:
- Leaky epithelium (tight junction is permeable for Na+ and water)
- Trans and paracellular reabsorption of Na+
- Provides gradient for the absorption of essential nutrients
- Isotonic reabsorption (equal amount of salt and water)
How does sodium reabsorption occur at the TAL?
Na+ reabsorption is 25% of filtered load:
- Semi-tight epithelium (tight junction is only permeable for Na+ not water)
- Trans (50%) and paracellular (50%) reabsorption of Na+
- Loop diuretics (furosemide) inhibit NIKCC2, diuresis increases
- Application of loop diuretics (furosemide is used to treat:
* Hypertension (high blood pressure) to reduce blood volume
* Edema in the lungs (heart failure) or edema in the legs
What is the counter-current multiplier system?
- The TAL is semi-tight and reabsorbs Na+ into the interstitium via NKCC2
- The tDLH is leaky epithelium facilitating water reabsorption into the interstitium
- 25% Na+ and water (45L/day) reabsorption
–> inhibiting NKCC2 with furosemide controls 25% of the water reabsorption - The final osmolarity of the urine is determined in the collecting tubule, but the counter-current system helps to keep the intersitium hypertonic. This is further supported by urea re-absorption
How does sodium reabsorption occur at the DCT?
Na+ reabsorption is 5% of filtered load:
- Tight epithelium (NO paracellular transport)
- Only transcellular reabsorption of Na+
- Diuretics (thiazides) inhibit sodium chloride cotransporter/NCC, to induce mild diuresis
How does sodium reabsorption occur at the CCT?
Na+ reabsorption is 3% of filtered load:
- Tight tight epithelium (NO paracellular transport)
- Only transcellular reabsorption of Na+
- Na+ reabsorption is regulated by hormones (aldosterone)
- Diuretics (amiloride) inhibit ENaC, very mild diuresis
