Lecture 3 - Nephron Segments And Tubular Transport Flashcards
What is nephron endowment?
Born with the total number of nephrons you can’t get anymore, which is why premature babies are at more risk of kidney diseases, as they wont have as many a baby that was born at the correct time
How many nephrons does each kidney have?
On average around 1 million
How is the GFR measured?
Glomerular filtration - measured in different ways:
Inject someone with insulin and measure how fast it goes through the kidney and this gives you a measure for GFR
What is the best indicator for GFR?
The calculated clearance of Creatinine
What are some others way you can measure GFR except from insulin?
Have a blood test, or measure the concentration of creatinine which is the product of day muscle breakdown.
What is the test for concentration of creatinine?
Serum creatinine or plasma creatinine
What does it mean if creatinine is high?
Normally means that your kidney is not filtering properly.
Could mean, kidney failure, kidney disease or a urinary track obstruction
In a healthy person is creatinine filtered out of the blood?
Yes Creatinine is filtered out. After these waste products are filtered they are found in the urine - it is considered a waste product
What is a normal eGFR?
Normally over 90 is considered normal, anything below 59 is considered to be an early sign of kidney disease?
How much does the kidney filter a day?
120ml on average GFR x 60 x 24 = 180 L per day
Does alcohol affect the kidney?
No, it is a mild diuretic - it will not contribute to kidney disease
What does the kidney make?
The kidney makes renin, another hormone called erythropoietin and even vitamin D
What is a symptom of kidney failure?
The patient may become anemic as they are not producing enough of the erythropoietin hormone
What animal has the longest loop of henle?
The desert rate - it is able to produce a hyper concentrated urine which is far more concentrated than its blood minimising the need for excessive water intake - due to the long loops of henle. (Open university: the desert environment)
How does the body react to being able to not urinate while running a marathon?
Due to the ADH - plays a crucial role in maintaining fluid balance during exercise. - decreases the amount of urine that flows in the bladder
What is the busiest nephron segment?
The proximal tubule
What happens if the filters in the PCT are damaged?
There will be lots of albumin in the blood
Can the PCT filter albumin?
Yes but only tiniest bit the rest of it doesn’t pass through
What can the PCT filter?
Water, glucose, Na+, K+, Cl-, phosphate, urate
What is the PCT?
It is the filtration unit of the kidney, contains the filtration barrier
What is the kidneys full of?
Mitochondria
What do the mitochondria do in the kidneys?
They are energy producing organelles but also respond to kidney-injury induced oxidative stress and inflammation
What happens if a drug that is prescribed to a patient poisons the mitochondria?
You will get a serve phenotype - in the urine there will be extra phosphate or uric acid which is a sing that the PCT tubules are not functioning properly
What does Bicarboante combine with?
With a protein via an enzyme called carbonic anhydrase
How much bicarbonate reabsorption is filtered in the PCT?
80% - it is converted to lipid-soluble CO2 by apical carbonic anhydrase allowing to be absorbed.
It has a net effect so the process goes round in circles
Why do you measure urine glucose?
To know how high the serum glucose is
What are the 2 transporters for glucose reabsorption?
SGLT2 and SGTL1
What does SGLT2 do?
Combined with Na+ and Glucose into the cell - 98% of glucose is taken up with this transporter
What does SGLT1 do?
Takes up the last 2% of glucose
Why may some patients have glucose in the urine?
May have a mutation in the transporter - so the transporters aren’t being as efficient
Why are SGLT2 inhibitors so important?
They are the biggest thing to happen in the last 30 years - initially used in diabetics, peeing out extra glucose will help lower serum glucose. But also works with people who have kidney disease
What is SGLT2?
It is a diuretic - wasting glucose pulls water along with it - but it is very expensive
What can SGLT2 do?
Lowers blood pressure and reduces the pressure on the kidneys and the heart, changes the pressure of filtration
What is suggested to be used with an ACE inhibitor?
SGLT2
How does an ACE inhibitor work?
They work by blocking an enzyme that produces a hormone called angiotensin II which causes blood vessel to narrow and raises blood pressure
What are the side effects for SGLT2?
Increase risk of UTI, fungal infections like thrush
Are amino acids reabsorbed in the nephron?
Yes - by different Na+/ amino acid cotransporters in the PCT. Most of the transporters can transport drugs
What is the heterodimeric amino acid transporter?
SLC3A1, SLC7A9 which transports cystine and lysine - it is very important in the reabsorption of amino acids in the kidney
What is albumin reabsorption?
The body has a mechanism for filtering and retrieving albumin. The mechanism is by a Endocytosis mechanism
What does the reabsorbed albumin undergo?
It undergoes transcytosis
What does the thick ascending limb do?
It has salt transport NOT water, it contains a major salt transport on the apical side (K+/Cl- transporter - NKCC2) it has a neutral charge
What does Na+ control?
Blood pressure
What happens to K+?
It gets recycled
What is the net absorption for the thick ascending limb?
Na+ and Cl-
What is a drug that interferes NKCC2?
Loop diuretics - it inhibits NKCC2, they increase urine flow.
What are the tight junctions for the thick ascending limbs?
They are a group of proteins that form the tight junction complex, and can transport Mg2+ and Ca2+ in a paracellular route - transports solutes between cells
What is nearly everything in the PCT?
It is transcellular - transports solutes through a cell
What is a thiazide diuretic?
It is a common treatment/ tablet for hypertension
What is the DCT?
It is responsible for maintaining the balance of potassium, sodium and calcium, pH. An important role in the absorption of many ions and in water reabsorption
What does aldosterone do?
Increases Na+ reabsorption in the DCT
How can bowel cancer be helped?
Some targeted drugs like cetuximab and panitumumab - are epidermal growth factor receptor inhibitors and could turn off the tumour. Changing the ability to manage Mg2+ (cancer research.co.uk)
What is the calcium thermostat?
A calcium sensing receptor
What does the calcium sensing receptor play a role in?
Regulating parathyroid hormone secretion and urinary calcium excretion
What can happen if the calcium sensing receptor undergoes mutations?
Hypercalcaemia can occur
What happens in the collecting duct?
Selective water absorption, it has the control for the final Na+
What is found beyond the collecting duct?
Renal pelvis, ureter, bladder and urethra
What happens to brown bears during hibernation in regards to its collecting duct?
It has reduced metabolic rates. The bears are able to conserve water during hibernation. A bears bladder is able to reabsorb most of the urine back to its body. The conversation of fluid helps the bear survive without drinking (rrbigbear.com)
What do intercalated cells secrete?
They secrete acid
What can happen if you eat a lot of meat?
Your pH will be acidic as meat tends to be acidic, the body needs to be able to secrete the acid by the intercalated cells
Do people who are vegetarian need lots of intercalated cells?
They produce lots of alkaline, so the cells do not need to work as hard as someone who eats lots of meat
What can the intercalated cells become?
They can become proton secreting or Bicarboante secreting
What is the principle cell?
ENaC, one na+ goes in but because of the charge it has to swap the charge with either a proton or a K+ ion .
What pore helps with water transport in the collecting duct?
Aqauporin 2 in the apical surface, and aqauporins 3 and 4 in the basolateral surface
What are aqauporins helped by?
Aqauporins are helped by a hormones called vasosupression or ADH which help with insertion and retrieval of water
What is Diabetes mellitus?
Diabetes in the urine - makes the urine sweet (glucose)
What is diabetes insipidus?
It is a disease if you lose the ability to regulate Aquaporins- urine doesn’t tase of anything.
ADH receptor mutations are ….
They are X linked - boys, common symptom is bed wetting
