What does fenestrated mean?
Large pores in endothelium (like in glomerular capillaries)
Which type of nephron is responsible for making concentrated urine?
Juxtamedullary
Their long limbs into medulla can create high solute concentrations in peritubular fluid
Where are NKCC2 cells found?
Na-K-Cl cotransporter cells
Found only in the thick ascending loop of Henle
What % of glucose should a normal healthy kidney reabsorb?
100%
What are the osmolarity differences between the top and bottom of the loop of Henle?
Top: 300 mOsm/L
Bottom: 1200 mOsm/L
What is the role of ROMK channels?
Move potassium back into urine
K channels
What % of K+ within the body is inside cells? Where is it excreted?
98% found inside cells
8% lost from the colon
92% lost via kidneys
How is calcium reabsorbed in the kidney?
91%- Prox conv tubule/ loop Henle via paracellular route
6-7%- Distal convoluted tubule via TRPV5 channel
What is the TRPV5 channel?
Moves Ca2+ out of urine in dist conv tubule
Responds to levels of PTH/ vitamin D and sex hormones
What are paracellular and transcellular routes?
Para- Through interstial spaces beside a cell
Trans- Passes through the cell
What is the role of TRPM6?
Moves Mg2+ back into cells (reabsorbes) in distal convoluted tubule
How is magnesium reabsorbed in the kidney?
89%- Prox conv tubule/ loop Henle via paracellular route
6-7%- Distal convoluted tubule via TRPM6 channel
Name two factors that can regulate water reabsorbtion and where they act?
ADH/ vasopressin (on aquaporin channels)
Aldosterone (on Na reabsorption)
How do glomerular capillaries allow water and small solutes to pass through but not larger ones?
Fenestrations between the feet of podocytes allow things to get through
The basement membrane beneath the endothelium stops larger proteins etc from passing through
What is the myogenic stretch reflex (in relation to the kidney)
When an arteriole is stretched it automatically contracts (to maintain constant GFR)
What is tubuloglomerular feedback?
Distal tubular flow regulates vasoconstriction of afferent arteriole
Which arteriole is most involved in regulating GFR by constricting in response to changes?
Afferent arteriole (constricts to lower GFR)
What are the two cell types in the kidney collecting ducts?
Principal cells- Mediate sodium and potassium
Intercalated cells- Regulate acid-base homeostasis (also swapping K+)
What is the effect of aldosterone on principal cells in the collecting ducts?
Aldosterone increases no of sodium/potassium ATPase pump (so more sodium in, more potassium out)
What is the effect of ADH on principal cells in the collecting ducts?
Increases number of aquaporin channels
Increased water reabsorbtion
What is the action of aldosterone in the kidney?
Acts on prinicipal cells to increase sodium (and therefore water) reabsorbtion
What would increased aldosterone levels do to the concentration of potassium in urine?
Increase it (Aldosterone promotes K+ secretion)
What would a decrease in Na+ within the filtrate do to the pH of the tubular fluid?
Increase
Fewer hydrogen ions in as they come in cotransported with Na+
How would a lack of juxtamedullary nephrons affect urine concentration?
You would be unable to create concentrated urine
What would a decreased Na+ level in the DCT do to blood pressure?
Increase it
Macula densa detects low osmolarity then stimulates renin release from JG cells
Where is the majority of HCO3- reabsorbed? How much comes out in urine?
80% in proximal convoulted tubule
Less than 0.01% is lost
What is the AE2 transporter?
Cl- and HCO3- antiporter
Where would V-ATPase be found?
Apical membrane of intercalated cells (H+ pump)
What are the apical and basolateral membranes?
Apical: Side towards the lumen
Basolateral: Side towards base
What is Proximal renal tubular acidosis (RTA)?
Impaired ability to reabsorb HCO3-
Rare autosomal-recessive disease
NOT treatable by HCO3- supplimentation
What is Distal renal tubular acidosis (dRTA)?
Impaired ability to acidify urine
Treatable by HCO3- supplementation
What is the function of the NKCC1 channel?
Cotransport of 2Cl-, 1Na+, 1NH4+
What is the function of the ROMK2 channel?
Absorbtion NH4+
What are the two ways H+ is secreted in the kidney?
As titrateable acid (filtered)
As NH4+ (synthesised)
Which channels are most involved in H+ secretion?
NHE3
V-ATPase
H+/K+-ATPase
Which two channels are most important in replenishing plasma HCO3- from kidney reabsorbtion?
Basolateral HCO3- exit via:
kNBCe1
AE2
What is a PAK transplant?
Pancreas after Kidney Transplant
P first receives a kidney transplant from a living or deceased donor. This is then followed by a pancreas transplant from a deceased donor.
What is a PAT transplant?
Pancreas Alone Transplant
This is a treatment for patients with very poorly controlled type 1 diabetes who have hypoglycaemic attacks without warning, and which may threaten their life.
What is the outlook for SPK transplants?
90% still function at 1yr
50% at 10yrs
What are the exclusion criteria for SPK transplants?
T2DM (only type 1 can receive as T2 is resistant)
Malignancy
Chronic infection
Not compliant with treatment
What are the main causes of chronic renal failure?
Hypertension
Diabetes
Pyelonephritis / glomerulonephritis
What causes itching in CKD?
High levels of urea
What is shown by raised creatinine?
Marked damage to functioning nephrons
What is the alternative name for a urea test?
BUN (Blood urea nitrogen test)
What two non-disease factors can affect urea levels?
Age= increased urea
High protein diet= Increased urea
Low protein diet= Decreased urea
Ureters are retroperitoneal. T or F?
True
Why do F tend to have more UTI’s than males?
Shorter urethra’s
What effect would a high protein diet have on the composition of urine?
Urea comes from metabolism of AA’s
Therefore urine will contain a higher conc of urea
There may also be increased urine vol (to flush more urea out)
What is the main muscle you need to be able to control in order to control the micturation reflex?
External urethral sphincter
ring of skeletal muscle formed by urogenital diaphragm
Glomerular capillary membranes have what 3 layers?
Endothelium- Perforated by fenestrae
Basement membrane- Collagen mesh with spaces to allow water and small solutes to filter
Podocyte layer- With gaps between feet to allow fluid in
How does the glomerular capillary use charge to prevent movement of large proteins?
Fenestae in endothelium, proteoglycans in BM and podocytes all have -ve charge so help repel proteins
What effect does SNS activation have on GFR?
Decreases GFR
As SNS causes constriction of renal arterioles, this decreases blood flow
What effect does angiotensin II have on GFR and kidney arterioles?
Constricts efferent arteriole
This reduces blood flow (and therefore GFR) but raises glomerular hydrostatic pressure
What does the juxtaglomerular complex consist of?
Juxtaglomerular cells and macula densa cells
How do macula densa cells help regulate GFR?
MD cells detect NaCl composition to distal tubule, if GFR is decreased, movement is slowed, reabsorbtion of electrolytes increases and tubual fluid has low osmolarity. When they detect this MD cells stim dilation of afferent arteriole + stim JG cells to release renin
How do macula densa cells stimulate juxtaglomerular cells?
They release prostaglandins which cause JG cells to release renin (JG cells can also use baroreceptors to release renin independantly)
What effect does a reduced blood pressure have on GFR?
Lowered BP = lowered peritubular capillary pressure = lower capillary hydrostatic pressure = decreased GFR
What effect does lowered GFR have on urine concentration?
Low osmolarity in urine and it’s passing slower through the tubular system allowing more absorption
What is myogenic autoregulation?
BV’s respond to stretch or increased wall tension by contraction of vascular smooth muscle
(Stretch allows increased movement of calcium ions into the cells)
What effect does a high protein diet have on GFR?
Increased AA’s in blood, increased AA reabsorbtion which also increases Na reabsorbtion. This lowers Na at macula densa so increased GFR (makes sense as you want to clear more urea if eating more protein)
Why is PAH (para-aminohippuric acid) used to calculate renal plasma flow?
Secreted so rapidly that you can clear 90% of PAH from plasma into the urine
Glucosuria is an important clinical sign for what?
It begins around what serum glucose level?
Diabetes mellitus
Starts at plasma conc around 160-200mg/dL
How is the solubility of water changed in the ascending and descending loops of Henle?
Descending loop- Very permeable to water
Ascending loop- Virtually impermeable to water
How is the solubility of water changed in the ascending and descending loops of Henle?
Descending loop- Very permeable to water
Ascending loop- Virtually impermeable to water
The permeability of the late distal tubule and cortical collecting duct to water is controlled by concentration of what?
ADH
What are the two main components which contribute to creating concentrated urine?
High levels of ADH
High osmolarity of renal medullary interstitial fluid
What is uremia?
Raised serum urea level (indicating renal failure)
What is prerenal uremia?
Caused by decreased perfusion of kidneys with blood
shock, hemorrhage, heart failure
What effect does kidney function have on serum potassium?
Impaired renal function causes hyperkalaemia
What is postrenal uremia?
Uremia results from obstruction of tract from renal calyces to urethral orifice
What are the classifications of acute renal failure?
Depressed excretory function due to reduced GFR. Raised serum urea is classed as pre-renal, renal or post-renal
Which region of the nephron reabsorbs 2/3 of Na ions?
Prox convoluted tubule
Which 3 structures form the filtration membrane?
Capillary epithelium, basement membrane, and podocytes
Which type of innervation causes micturition?
PNS
What type of channel is NKCC1 and what does it transport?
Cotransporter (Na, K, Cl)
Which hormone increases reabsorption of water from the collecting ducts?
ADH
At what vertebral level are the kidneys found?
Left: T11-L2
Right: T12-L3
Right is lower than left due to liver
L kidney is longer and closer to midline
Are the kidneys intraperitoneal or retroperitoneal?
Retroperitoneal
What is at the inferior pole of each kidney?
R and L coliec flexures
Where would an intercalated cell be found?
Collecting ducts
What is the role of ATPsynthase enzyme?
Uses H+ from ETC to phosporylate ADP creating ATP
uses H+ gradient for energy
What dictates whether a nephron is cortical or juxtamedullary?
The location of it’s glomerulus
When a micturation reflex has occurred but not succeeded what happens?
It remains inhibited for a few mins
Then will start again if enough pressure
What is the role of the higher brain centres in micturation?
Keep the reflex inhibited except for when you want to urinate
How is voluntary urination initiated?
Person contracts abdo muscles (increases pressure on bladder which stimulates stretch receptors)
What is tuberoglomerular feedback?
Macula densa monitors Na+ conc and when it’s low sends a signal to the afferent arteriole to relax (and therefore increase GFR)
What effect does a lowered GFR have on the Na+ concentration in the tubule?
Low GFR = slower movement = more time for reabsorption = lower Na+ conc in tubule
(So macula densa will stimulate GFR increase)
What is myogenic autoregulation?
BV’s respond to increased tension by contracting
Stretch of the wall allows increased movement of Ca2+ causing the contraction
What does high protein intake do to GFR?
Increases AA’s which are reabsorbed in the PCT and also stimulate Na+ reabsorption. Lower Na+ stimulates a raise in GFR
What is glomerulotubular balance?
The ability of the tubules to increase their reabsorption rate in response to increased tubular load (increased tubular inflow)
What effect does increases renin release do to GFR?
Increased renin = increased angiotensin II = constriction of efferent arterioles = reduced blood flow = increased GFR
What is the difference between alpha and beta intercalated cells in the collecting ducts?
Alpha- Secretes H+ and reabsorbs bicarbonate
Beta- Secretes bicarbonate and reabsorbs H+
What is filtration fraction (FF)?
The proportion of the fluid reaching the kidneys which passes into the renal tubules.
Normally about 20%
Ratio of GFR to RPF (renal plasma flow)
What equation is used to work out filtration fraction?
FF = GFR/RPF
What are mesangial cells and what sort of molecules stimulate them (3)?
Support cells which can constrict/ dilate BV’s
- Target for angiotensin II/ ADH and histamine