SUGER: Renal & Urinary Flashcards
The glomerulus is composed of a network of capillaries. What vessel leaves the glomerulus?
Efferent arteriole
What specialised part of the distal convoluted tubule detects changes in sodium chloride levels?
Macula densa
What does the macula densa do when low NaCl levels detected?
Signals to juxtaglomerular (AKA granular) cells of afferent arterioles to release renin
Why do heparan sulfate proteoglycans on glomerular basement membrane, and the negative charge on slit diaphragm between podocyte foot processes, prevent albumin from entering filtrate (and hence urine)?
Albumin is negatively charged, so the negatively charged barriers repel negatively charged particles such as albumin.
What three features of molecules in plasma affect whether or not they enter the filtrate in the Bowman’s space?
Size of molecule
Charge of molecule
Protein-bound or not
What three Starling forces affect glomerular filtration and how are they used to calculate net filtration pressure?
Hydrostatic pressure of glomerulus
MINUS hydrostatic pressure in Bowman’s space
MINUS oncotic pressure of glomerulus
Which arteries give rise to the afferent arterioles in the kidney?
Interlobular arteries
Net filtration pressure is calculated by:
hydrostatic pressure of glomerulus
MINUS hydrostatic pressure in Bowman’s space
MINUS oncotic pressure of glomerulus
What is net filtration pressure multiplied by to calculate glomerular filtration rate?
Ultrafiltration coefficient (permeability of membrane to water)
An increase in renal blood flow results in an increase or decrease of GFR?
Increase
What is the glomerular filtration rate (GFR)?
The total amount of filtrate formed by all the renal corpuscles of both kidneys per minute (ml/min).
How is glomerular filtration rate measured?
It can’t be measured directly, so an estimate is calculated by measuring excretion of a marker, usually creatinine.
What hormonal regulation affects GFR?
RAAS (renin angiotensin aldosterone system)
ANP (atrial natriuretic peptide)
What two autoregulation mechanisms affect GFR?
Myogenic mechanism
Tubuloglomerular feedback
In myogenic autonomic regulation, an increase in arterial pressure causes stretch of afferent arteriole. What affect does this stretch have on the afferent arteriole muscle cells that results in arteriole constriction, reducing blood flow to glomerulus?
Stretch cause increase of cell permeability to calcium (by opening calcium channels) which increases intracellular calcium causing muscle contraction.
(contraction increases vascular resistance, decreasing blood flow to glomerulus)
What tubular effect does sympathetic stimulation have in the nephron?
Increased Na+ reabsorption
Does angiotensin II mainly cause vasoconstriction in the afferent or efferent arteriole of the glomerulus?
Efferent arteriole
What causes ANP (atrial natriuretic peptide) to be released?
Atrial stretch, due to high pressure/volume
Where is ANP (atrial natriuretic peptide) released from?
Atrial myocytes of right atrium
What effects does ANP (atrial natriuretic peptide) have on the nephron?
Inhibits sodium and water reabsorption
Dilates afferent arteriole, constricts efferent arteriole
What triggers prostaglandin release in the kidney?
Reduced O2 delivery to the kidneys
What effect does prostaglandin have in the kidney?
Dilates glomerulus afferent arterioles, causing increased renal blood flow and increased GFR.
Does constriction of the glomerulus efferent arteriole result in increased or decreased hydrostatic pressure in the glomerulus?
Does this then increase or decrease the GFR?
Increased hydrostatic pressure.
Increases GFR initially, but if severe/prolonged will decrease GFR.
How do the kidneys help regulate acid-base balance?
Reabsorbing bicarbonate that has entered the filtrate
Excreting H+ ions
How is H+ excreted in the kidneys?
H+ ions are excreted in the form of urea
What does a negative base excess suggest on an ABG?
Less base, therefore suggests acidosis.
(normal BE is -2 to 2+)
Why does hypokalaemia cause metabolic alkalosis?
Hypokalaemia increases renal ammoniagenesis. Excess ammonia then binds more H+ and is excreted as urea.
Which have smaller, less-developed (or even absent) glomeruli; freshwater fish or marine fish? Why?
Marine fish, because they live in a hypertonic solution (the sea!) and need to conserve water to prevent dehydration, so they don’t want to produce lots of filtrate. NaCl is excreted mainly in the gills.
What has a longer loop of Henle; rabbit, beaver, or kangaroo mouse? Why?
Kangaroo mice (and other desert mammals) have longest loops of Henle, because they need to reabsorb as much water as possible.
Beavers (and other water-dwelling mammals) have the shortest because they live in water, so there is no evolutionary pressure to conserve water.
How does an antiporter differ from a symporter?
Antiporter = moving two different molecules in different directions across a membrane.
Symporter = moving two different molecules in the same direction across a membrane.
What are the two routes that molecules can move between filtrate and blood?
Transcellular
Paracellular
What route of reabsorption is affected by the permeability of tight junctions?
Paracellular
Where in the nephron is most of the filtrate reabsorbed?
Proximal convoluted tubule (65%)
Where in the nephron is bicarbonate reabsorbed?
Proximal convoluted tubule
In the proximal convoluted tubule, different symporters move Na+ into the cell from the filtrate. What antiporter then moves Na+ from the cell into the blood?
Na/K ATPase
How is water reabsorbed in the proximal convoluted tubule?
Transcellular route through aquaporins, but mainly the paracellular route through tight junctions, via osmosis.
Large volumes of solute reabsorption occurs early in the proximal convoluted tubule, so as filtrate progresses along the tubule, ↓ osmolarity in tubule while ↑ osmolarity in interstitial fluid and blood.
How is chloride reabsorbed in the proximal convoluted tubule?
Paracellular route, diffuses freely from filtrate to blood.
Why does the thin descending limb of the loop of Henle have fewer mitochondria than the thick ascending limb?
Little active transport occurs in the descending limb, whereas more active transport occurs in the ascending limb.
Why is the thick loop of Henle (ascending) impermeable to water?
Does not have any aquaporins.
What stimulates the parathyroid gland to release parathyroid hormone? Why?
Low calcium levels.
Because parathyroid hormone causes more calcium channel insertion in the distal convoluted tubule, so more calcium can be reabsorbed.
Where in the neprhon are the most “tight” tight junctions?
Collecting duct
Which part of the nephron does aldosterone mainly affect?
The collecting duct
What affect does aldosterone have on the collecting ducts in the nephron?
Increases transcription rate of sodium channel (ENaC) & potassium channel (ROMK), and activity of Na-K ATPase.
This increases potassium excretion, and increases sodium reabsorption.
ANP mainly affects the medullary collecting ducts. How does ANP counteract the affects of aldosterone?
Inhibits sodium channels (ENaC) and Na-K ATPase, to reduce sodium reabsorption.
What affect does ADH have on the distal convoluted tubules and the collecting ducts in the nephron?
Increases transcription rate for aquaporins, so more water is reabsorbed.
What are the two key types of cells that line the collecting ducts of the kidneys
Principal cells
Intercalated cells (alpha and beta)
The collecting duct in the kidney is lined by principal cells and intercalated cells. Which cells are mainly involved with reabsorption of sodium & water, and excretion of potassium?
Principal cells
The collecting duct in the kidney is lined by principal cells and intercalated cells. Which cells are mainly responsible for hydrogen secretion in the urine, to maintain acid-base balance?
Intercalated cells (alpha)
The collecting duct in the kidney is lined by principal cells and intercalated cells. Which cells are mainly involved with bicarbonate secretion to maintain acid-base balance?
Intercalated cells (beta)
What cells in the kidneys secrete erythropoietin?
Pericytes; cells around the vasa recta vessels (in both the medulla and the cortex).
In normal conditions, HIF (hypoxia-inducible factors) is degraded. What does HIF do in hypoxic conditions?
Induces gene expression changes to cause the kidney and liver to produce more erythropoietin (HIF is transcription factor).
(HIF also causes angiogenesis and other changes to adapt to hypoxic conditions).
What key effect does erythropoietin (EPO) have?
Stimulates immature cells to develop into erythrocytes.
Amino acids are reabsorbed by specific transporters in which part of the nephron?
Proximal convoluted tubule
Which cell type in the collecting duct is important for maintaining acid-base balance?
Intercalated cell (alpha and beta)
Which part of the nephron is impermeable to water but actively reabsorbs sodium and chloride ions?
Ascending (thick) limb of loop of Henle
Which part of the nephron is primarily targeted by parathyroid hormone to increase calcium reabsorption?
Distal convoluted tubule
Which part of the nephron tubule is the longest?
Proximal convoluted tubule
Proximal (type 2) renal tubular acidosis is caused by a defect of the Na+/H+ antiporter in the proximal convoluted tubule. Why does this cause acidosis?
Na/K ATPase moves K+ from blood into the cell, Na+ from cell into blood.
Na/H antiporter moves H+ from cell into filtrate, Na+ from filtrate into cell.
HCO3/H antiporter moves H+ from blood into cell, HCO3- from cell into blood.
Failure of one of these transporters will prevent bicarbonate reabsorption from occurring, and H+ from being excreted, causing acidosis.
Bartter syndrome is a rare loop of Henle disorder. Why is it sometimes referred to as “nature’s loop diuretic”?
Defect in NKCC2 (sodium, potassium, chloride symporter) in the loop of Henle, the same symporter that loop diuretics inhibit, meaning these ions remain in the filtrate and the osmotic gradient needed in the loop of Henle to reabsorb water into the blood does not occur; more water is excreted.
Gitelman syndrome is an autosomal recessive kidney distal convoluted tubule disorder. Why is it sometimes referred to as “nature’s thiazide diuretic”?
Defect in NCCT (sodium and chloride symporter) in the distal tubule, the same symporter that thiazide diuretics inhibit, meaning these ions remain in the tubule and impair reabsorption of water; more water is excreted.
How does aldosterone increase sodium retention and potassium excretion in the late distal tubule and collecting duct?
By increasing expression of sodium channels (Epithelialsodium channels/ENaC)and Na/K ATPase transporters.
How is the bladder adapted for bladder compliance?
It is vesico-elastic; elastin and collagen fibres allow stretching to occur.
Smooth muscle fibres of detrusor increase in length without increase in tension.
What top layer of urothelium in the bladder protects urothelium cells from urine and prevents bacterial adhesion?
GAG layer
(a mucus-like layer of glycosaminoglycan on the inside of the bladder)
What nerve relays information regarding stretch, irritation, and temperature of the bladder to the sacral spinal cord?
Afferent pelvic nerve.
What causes the PMC (pontine micturition centre) in the brain to send inhibitory signals to the hypogastric and pudendal nerves, and stimulates efferent pelvic nerve?
Rapid firing of the afferent pelvic nerve
What mechanisms allows the kidney to compensate for respiratory/metabolic acidosis?
Increased bicarbonate reabsorption
Which transporters is primarily responsible for sodium reabsorption in the thick ascending limb of the loop of Henle?
NKCC2 (sodium potassium chloride co-transporter)
Which genetic disorder is characterised by defective chloride reabsorption in the thick ascending limb leading to hypokalaemic metabolic alkalosis?
Bartter syndrome
Which genetic disorder causes a mutation at ENaC in the collecting duct?
Liddle syndrome
Which genetic disorder causes a mutation in NCCT at distal tubule?
Gitelman syndrome
What genetic disorder causes proximal tubule dysfunction, with loss of glucose, AA, phosphate, bicarbonate?
Fanconi syndrome
Which renal tubular acidosis is characterised by impaired hydrogen secretion in the distal tubule?
Type 1 (distal) renal tubular acidosis
A patient with primary hyperaldosteronism is expected to have hypo/hyperkalaemia, and metabolic acidosis or alkalosis?
Hypokalaemia and metabolic alkalosis.
Angiotensin II causes efferent arteriole constriction. How does this increase water reabsorption in the vasa recta?
Efferent arteriole constriction increases hydrostatic pressure in glomerulus so more water moves out of glomerular capillaries.
This increases concentration of albumin in the capillaries, increasing oncotic pressure of blood entering the vasa recta.
Constriction of efferent arteriole also slows down flow of blood in vasa recta.
