The Kidney

Pregunta	Respuesta
Name the 4 components of the urinary system	1. Kidneys 2. Ureters 3. Bladder 4. Urethra
The function of the urinary system is _________ of the ______. What 3 specific things does it do?	homeostasis of the blood 1. Regulates plasma composition 2. Regulates BP (Renin) 3. Regulates production of RBCs (erythropoietin)
What is the functional unit of the kidney?	The nephron
What is the renal corpuscle?	Bowman's capsule and glomerulus
What are the 5 parts of the renal tubule?	1. Proximal Convoluted Tubule 2. Thin limb of Loop of Henle 3. Thick limb of Loop of Henle 4. Distal convoluted tubule 5. Collecting tubule
Where do all the nephrons empty into?	The collecting ducts
What occurs at the glomerulus?	Ultrafiltration
What are the 3 layers of the glomerular filter? (From inside out)	1. Fenestrated capillaries 2. Basement membrane 3. Filtration slits between podocytes
The fenestrated capillaries allow _______ ______ to remain in the blood, but allow everything else through. The basement membrane is a thick, fused ______ ________ which allows fewer substances through. The filtration slits are so small they allow _______ and ______ _________ through, but anything larger than _________ cannot pass through (4nm).	blood cells, basal lamina, water, small molecules, albumin
Which parts of the tubule is responsible for selective reabsorption?	Proximal convoluted tubule and thin limb of Loop of Henle.
What are the 3 methods by which filtrate can be reabsorbed here?	1. Active transport 2. Pinocytosis 3. Passive flux
What type of epithelium do the walls of the PCT have?	cuboidal
Describe the histological features of the epithelium of the PCT	Lots of microvilli on apical membrane, folds on basolateral membrane, multiple lysosomes, Na+/K+ ATPase pumps, many mitochondria
How do these features assist the cells function?	Microvilli and folds to give more surface area for reabsorption. Na+/K+ ATPase pumps drive the active transport of many of the substances being reabsorbed. Mitochondria supply the energy for these pumps. Lysosomes can break down incoming proteins.
What molecules are reabsorbed in the PCT by active transport?	Na+ ions, glucose, amino acids
What else is transported here and how?	1. Macromolecules such as proteins which travel by pinocytosis to then be broken down in lysosomes 2. Water and Cl- ions leave freely by passive flux
What is different about the thin limb of Loop of Henle?	It has only squamous epithelium and only allows passive flux of ions and water. The ascending limb, however, is relatively impermeable to water.
What occurs in the thick ascending loop of Henle and the distal convoluted tubule?	Regulated reabsorption and secretion of ions
What kind of epithelium is present here?	Cuboidal
What are the characteristics of this epithelium?	Highly folded basal membranes, few microvilli on apical surface, many mitochondria
What is the predominant process taking place in the thick ascending limb of the loop of Henle?	Reabsorption of Cl- and Na+ ions
What is the predominant process occurring in the DCT?	Exchange of Na+ for K+ and H+ for HCO3-
What is the purpose of these exchanges?	To maintain body sodium and pH levels
What occurs in the collecting ducts?	Passive reabsorption of water
What is the epithelium of the collecting ducts?	simple cuboidal to columnar
What is one special feature of this epithelium?	Thick, dense lateral membrane
What controls the water permeability of the collecting duct?	ADH
What are the 3 components of the juxtaglomerular apparatus?	1. Juxtaglomerular cells 2. Macula densa 3. Lacis cells
What are the juxtaglomerular cells?	A group of modified smooth muscle cells in the walls of the afferent arteriole near the glomerulus. They contain and secrete granules of renin.
What is the macula densa and what is its function?	A group of more columnar epithelial cells in the wall of the DCT near to the glomerulus. It senses the Na+ concentration in the DCT and signals in a paracrine fashion to the juxtaglomerular cells, possibly to affect GFR.
What are the lacis cells?	A group of extraglomerular cells between glomerulus and DCT, similar to fibroblasts. Their function is unknown.
The ureters and the bladder are both ____________ and ____________.	distensible, contractile
What is the special epithelium that is only found here?	Transitional epithelium - a special stratified epithelium
What is transitional epithelium specialised to be?	1. impermeable to urine and protect cells from the toxicity of urine 2. Distensible
Transitional epithelium can stretch, and it changes appearance on doing so. Cells become ________ and ________ (more squamous), and the number of ________ may appear less.	wider and flatter, layers
Why are urinary infections common?	The transitional epithelium is highly impermeable and so immune cells cannot get to the area easily.
Why are UTIs more common in women?	Female urethra is shorter, so germs have less distance to travel to reach the bladder and infect it.
How do you prevent cystitis?	Drink plenty of fluid so the bladder is regularly emptied
Glomerular filtration occurs according to the same principles as in what law?	Starling's principle of fluid exchange
What is GFR?	Glomerular Filtration Rate
What sets the GFR? (2)	1. Autoregulation 2. Renal sympathetic vasomotor nerve activity
What are podocytes?	Invaginations of the Bowman's capsule epithelium which coat the endothelium of the glomerular capillary.
What are 3 key features of glomerular filtration?	1. The concentration of small molecules such as urea and glucose are the same in the plasma and the glomerular filtrate 2. The concentration of larger molecules such as proteins should be zero in the glomerular filtrate. 3. There is always a net pressure drop across the membrane which drives filtration (according to Starling's principle).
In the peritubular capillaries, plasma _________ _________ becomes greater than __________ ________ so favours ___________. This causes a reverse of Starling's principle to cause ___________ _____________.	oncotic pressure, capillary pressure, reabsorption, selective reabsorption
How could proteins end up in the urine? (proteinuria)	If the molecular sieves become damaged and allow proteins to be filtered into the tubule. (Basement membrane or filtration slits between podocytes)
What are the 2 intrinsic controls of GFR?	1. Bayliss myogenic response 2. Tubulo-glomerular feedback (TGF)
What is the bayliss myogenic response?	When there is an increase in perfusion pressure in the kidney, this causes a temporary distension of the blood vessels, causing increased blood flow (BRIEFLY). This results in quick contraction of the smooth muscle, causing decreased radius and therefore increased resistance, bringing the blood flow back to normal value quickly.
What is the equation linking blood flow to the pressure and resistance of vessels?	Flow = Change in pressure/resistance
When is this response effective?	When BP is within autoregulation range (80-200 approx.)
What is TGF?	The macula densa detect high levels of NaCl in the lumen of the tubule of the ascending LoH or the DCT, and signal the GFR to slow down.
How does the macula densa decrease GFR?	NaCl causes the macula dense to give off an ATP signal that constricts the afferent arteriole. (decreased radius = increased resistance = decreased flow)
What is the extrinsic control of GFR?	Neurohormonal from renal vasoconstrictor nerves and noradrenergic signals.
How do they control GFR?	They reset autoregulation to a lower level in certain circumstances
When does this take place? (3)	1. When standing up 2. During heavy exercise 3. In haemorrhage or other forms of clinical shock
What are other vasoconstictor hormones which aid this control?	1. adrenaline 2. vasopressin 3. angiotensin
What are 2 major clinical disorders of the kidney?	1. Chronic glomerulonephritis 2. Nephrotic syndrome
What is glomerulonephritis?	Non-functioning of the glomeruli. Reaches chronic renal failure when GFR <30ml/min - then needs dialysis/transplant
What is nephrotic syndrome?	When the glomeruli become 'leaky' and therefore permeable to proteins.
What are 3 characteristics of nephrotic syndrome?	1. Proteinuria 2. Hypoproteinaemia 3. Oedema
Give 4 main functions of the kidney.	1. Control volume and composition of body fluids 2. Remove waste material from the body 3. Acid-base balance 4. Endocrine organ - secreting EPO, renin etc.
What are the transport mechanisms present on the apical surface of the tubular epithelial cells? (3)	1. Na+/glucose symporter 2. Na+/amino acid symporter 3. Na+/H+ antiporter
What transport mechanisms are present on the basolateral surface of the tubular epithelial cells? (2)	1. Na+/K+ ATPase pumps 2. Passive glucose flux
How do the symporters/antiporters work?	One substance enters the cell down its concentration gradient (passively), and this movement generates energy which brings in/draws out another substance against its concentration gradient.
What is the name of the Na+/glucose symporter and how can it be used clinically?	SGLT2 - drugs can target it to inhibit glucose reabsorption in conditions such as diabetes to prevent hyperglycaemia.
Name 3 test methods for investigating tubular function.	1. Clearance studies using creatinine 2. Micropuncture 3. Electrophysiological studies measuring potential difference
How does micropuncture work?	Some oil is injected into part of the tubule, then some fluid which is to be tested. The oil, as it is hydrophobic, will be pushed apart and create an isolated section of tubule only containing the fluid you want to investigate. A sample of this fluid can be taken further along the tubule and analysed for its composition, to see what is being reabsorbed/secreted.
What are the 2 types of nephron and which is most common?	1. Cortical nephron (most common = 85%) 2. Juxtamedullary nephron (15%)
What are the differences between them? (2)	1. The cortical nephrons have short Loops of Henle, not extending far into the medulla, whereas juxtamedullary nephrons have long Loops of Henle extending deep into the medulla 2. The capillary network in cortical nephrons exist around the tubules (peritubular) only, whereas the capillaries in the juxtamedullary nephrons are surrounding the loop of Henle and are called the vasa recta.
What is Fanconi's syndrome and what are the symptoms?	Defective reabsorptive mechanisms in the walls of the PCT, resulting in glycosuria and high Na+ in the urine.
How does the countercurrent multiplier work?	In the thick limb of the loop of Henle, active transport of salts (NaCl) out of the tubule into the medullary interstitial space causes an osmotic gradient in this space, which drives the passive flux of water out of the thin limb of the loop of Henle.
How do 'loop' diuretics work?	They inhibit the transporters in the thick ascending loop of Henle, therefore causing higher concentration of salts in the tubule which will also lead to more water being excreted.
What does hypoosmotic mean?	Low concentration of solutes
How else can the medullary osmotic gradient be maintained?	By the vasa recta in juxtamedullary nephrons, which are also permeable to water and salts and have low blood flow to minimise solute loss from the interstitial space.
What are the 2 types of cell found in the collecting ducts?	1. Intercalated cells 2. Principal cells
What is the function of the intercalated cells?	Acid-base balance/acidification of urine
What is the function of the principal cells?	Na+ balance and regulation of ECF volume
What is the collecting duct permeable to?	1. water (controlled by ADH) 2. urea
What triggers the secretion of ADH from which endocrine gland?	Increased plasma osmolarity, from posterior pituitary gland
What effect does ADH have?	Stimulates Gs pathway - PKA causes synthesis of aquaporins and fusion of them into the cell membrane. This causes the collecting duct to become more permeable to water and thus more water is reabsorbed in times of dehydration.
Inflammation of the glomeruli is known as ________________________	glomerulonephritis
What can cause obstruction of the kidney tubules?	Protein fragments from some leukaemias
Name 3 acquired kidney diseases	1. As a result of hypertension 2. As a result of congestive heart failure 3. Diabetic nephropathy
What is glomerular filtration rate?	The volume of filtrate removed from the blood each minute
What is the urinary excretion rate equal to?	urinary excretion rate = GFR - reabsorption rate + secretion rate
What is a good substance to use to measure GFR and why?	Inulin, because it is completely filtered into the tubule and none is reabsorbed or secreted - all is excreted.
Why is this not used clinically, however?	Inulin needs to be infused over a period of time and multiple plasma samples need to be taken - it is time consuming and not particularly pleasant for the patient.
What is the equation for GFR using inulin?	GFR = (Uin x V)/Pin
What is renal clearance?	Volume of plasma per minute needed to excrete the quantity of solute appearing in the urine in a minute
What is the formula for clearance of a substance?	Cs = (Us x V)/Ps
Which substance is more commonly used to measure GFR and why?	Creatinine, as it is made within the body naturally so does not need to be infused, yet is also freely filtered and not reabsorbed, as in inulin.
What is the slight disadvantage of using this?	Some creatinine is secreted into the renal tubule, so the Ccreat is often slightly greater than the actual value of GFR.
What is GFR directly proportional to?	The reciprocal of Pcreat (1/Pcreat)
What else can be used to estimate GFR?	eGFR - 'estimated GFR' using equations incorporating many factors involved in GFR.
How does this estimate GFR?	It uses age, sex, race and creatinine levels to estimate GFR
When can this be useful?	It is easier to conduct than measuring the GFR, and the GFR values can be useful in monitoring CKD stages, and therefore deciding on care/treatment options.
What does it mean if a substance has clearance equal to GFR?	It is filtered freely and not reabsorbed/secreted.
What does it mean if a substance has clearance > GFR?	Some substance is being secreted into the renal tubule.
What does it mean if the substance has clearance < GFR?	The substance is either: 1. not being filtered freely or 2. some is being reabsorbed.
At normal blood glucose concentrations, what is the clearance of glucose and how is this achieved?	All reabsorbed into the capillaries but SGLT2 symporters.
At what concentration of plasma glucose is the renal threshold reached? And what happens at concentrations above this point?	15mM - above this, glucose starts to appear in the urine (glycosuria)
What is Tm?	Transport maximum - indicates the plasma glucose concentration at which all the SGLT2 transporters are saturated, so no more glucose can be reabsorbed.
Why is there often some glucose in the urine at plasma concentrations between 15 and 20 mM?	Because not all nephrons have the same number of SGLT2 transporters.
Why would glucose not be a good substance to use in measuring GFR?	Because no matter how high a concentration of glucose you give, the clearance of it will never reach the maximum as there will always be reabsorption.
What other substances have clearance values < GFR? (9)	1. Amino Acids 2. Na+ 3. Ca++ 4. PO4-- 5. Mg++ 6. Water soluble vitamins 7. Cl- 8. urea 9. some drugs
What substances have clearance > GFR? (6)	1. weak organic acids/bases 2. adrenaline 3. dopamine 4. steroids 5. penicillin 6. Paraaminohippuric acid (PAH)
What can PAH be used for?	Measuring renal plasma flow
Using the same equation as in clearance and GFR, _______ ________ ______ can be calculated.	renal plasma flow
Why is this?	At low enough concentrations of plasma PAH, all of it can be completely cleared in one pass through the kidney.
What is the filtration fraction?	The fraction of plasma which is filtered through the glomeruli.
How is it calculated?	Fraction = GFR/RPF x 100 (gives a %)
What role does the kidney play in drug excretion?	Charged drugs are readily excreted as they are harder to be reabsorbed (need an ion exchanger), whereas uncharged drugs can be reabsorbed readily as they can travel through a lipid membrane.
What does ADME stand for in relation to drugs?	Absorption (of drugs in the gut) Distribution (to peripheral tissues) Metabolism Excretion
What is the difference between pharmacodynamics and pharmacokinetics?	Pharmacodynamics is the effect the drug has on the body. Pharmacokinetics is what our bodies do to the drug.
What determines whether a drug can be filtered through the kidneys or not?	The size of the molecule
A lot of drugs do not travel ________ in circulation, but _______ to _________ such as ____________. An example of this is ___________.	freely, bound, proteins, albumin, warfarin
What is the clinical relevance of this in the context of warfarin?	This means that warfarin stays in the circulation for a long time (has a long half-life). It must therefore be monitored closely to avoid excessive bleeding.
How do charged drugs get secreted into the tubule to be excreted?	On the basolateral surface of the tubular membrane there are non-specific anion or cation protein carriers.
What is the clinical significance of the carriers being non-specific?	Competition can occur between drugs of the same charge, e.g. probenecid can compete with penicillin to be secreted into the tubule, so that penicillin stays in the circulation for longer.
How is passive reabsorption of drugs assisted by water movement?	Reabsorption of water makes the tubular filtrate hyperosmotic, with a higher [drug] in the tubule, and therefore a steeper concentration gradient to encourage reabsorption.
What are 2 major groups of diuretics?	1. Diuretics that increase electrolyte excretion (and thus encourage water to follow by osmosis) 2. Diuretics that mainly effect water excretion (by decreasing ADH release)
Where are the 6 possible sites of action of diuretics?	1. PCT - Active reabsorption of Na+ with passive movement of Cl- and water. 2. PCT - Na+/H+ antiporter (driven by carbonic anhydrase - also involved in HCO3- reabsorption). 3. Loop of Henle - Na+/K+/Cl- transporter (Causes tubular fluid to become hypertonic as ascending limb is not permeable to water). 4. DCT - Active reabsorption of Na+ and passive transport of Cl- and water. 5. DCT - Na+/K+ exchangers on the basolateral surface (stimulated by aldosterone) cause activation of ENaCs on apical surface. 6. DCT - Na+/H+ exchanger on apical surface (stimulated by aldosterone) 3.
What is one example of a diuretic that only affects water excretion? How does it work?	Mannitol - freely filtered and not reabsorbed, causes increased osmolarity within the tubule, to encourage water excretion.
What are the 4 types of diuretic that affect eletrolyte excretion?	1. Loop diuretics 2. Thiazides 3. K+ sparing 4. Carbonic anhydrase inhibitors
What do carbonic anhydrase inhibitors do? An Example?	Acetazolamide - prevents formation of H2CO3 from H2O and CO2, thus also preventing formation of H+ within the epithelial cells. This results in decreased activity of the Na+/H+ transporter on the luminal membrane and thus more Na+ is excreted (as NaHCO3).
Give an example of a loop diuretic and explain how they work.	Furosemide - blocks the Na+/K+/Cl- exchanger in the thick ascending limb of the LoH. This causes less reabsorption of electrolytes which causes the osmolarity of the medullary interstitial fluid to remain low, thus decreasing osmotic drive of water, also decreasing the effect of ADH.
What are potential side effects of this?	Increased Na+ load in the DCT causes increased activity of the Na+ transport mechanisms, causing increased excretion of K+ and H+ (can lead to alkalosis and hypokalaemia).
Give 2 examples of K+ sparing diuretics and explain how they work.	1. Spironolactone - competitive antagonist of aldosterone, so decrease the activity of the Na+/K+ pump and the Na+/H+ antiporter, thus also downregulating ENaCs, preventing the reabsorption of Na+ while also preventing loss of K+. 2. Amiloride - Blocks ENaCs on apical surface of DCT, thus also decreasing the activity of the Na+/K+ pump, allowing sparing of K+.

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