Kidney Flashcards
Kidney functions
Excretion (urea, Uric acid, creatinine, urobilinogen, metabolites of hormones, foreign chemicals)
Body fluid composition (volume regulation, osmoregulation, ph)
Endocrine
Renal capsule is made of
Glomerulus + Bowman’s/renal corpuscle
Layers and characteristics of renal corpuscle
- Fenestrated capillary endothelium (leaky af)
- Basement membrane (lamina densa, interna rara, externa rara; fixed polyanions-> negative charge -> cations filter faster
- Podocytes (foot processes interdigitate-> filtration slits; nephrin and podocin are important proteins)
Path of filtrate in nephron
Glomerulus -> Bowman’s space-> pct -> proximal straight tubule (MEDULLA)-> descending thin limb -> ascending thin limb -> thick ascending limb -> dct (CORTEX) -> cd
Nephron types
- Cortical (85%): in outer 2/3 of cortex; short LOH
2. Juxtamedullary (15%): in inner 1/3 of cortex; Long LOH
Juxtaglomerular apparatus location and parts
- Juxtaglomerular cells (around afferent arterioles)
- Mesangial cells (in between glomerulus and dct)
- Macula densa (between loh and dct)
Percentage of plasma in glomerulus filtered
20%
Infection, damage to glomerulus and high bp can cause
Proteinuria
Haemoglobinuria
Haematuria
Gfr definition and factors affecting
Volume of fluid filtered from glomeruli per minute
Dependent on: starling forces/ sa/ permeability of capillaries
Starling forces pressures and values; net glomrrular filtration pressure
Hydrostatic: capsular pressure towards interface=15mmhg; hydrostatic pressure towards interface=60mmhg
Oncotic: pressure away at glomerular end = 29mmhg; away at capsular end=0mmhg
Net pressure= (60-15)-(29-0)= 16mmhg
What happens to hydrostatic pressure gradient and gfr when aa/ea constricts or dilates
Aa dilate-> hydrostatic pressure gradient increases-> gfr increases
Aa constrict-> hydrostatic pressure decreases-> gfr decreases
Ea dilate-> hydrostatic pressure decreases-> gfr decreases
Ea constricts-> hydrostatic pressure increases -> gfr increases
How is sa of filtration interface changeable
Mesengial cells have actin -> innervated by sns -> bp drops-> contraction of actin -> decreased sa
Glucose reabsorption
Luminal: sglt
Basolateral: glut
Na/k atpase
Aa reabsorption
In proximal tubule
6 na dependent
Secretion of organic anions in prox tubule; why aren’t they filtered
Bound to protein in blood, not filtered
Basolateral: OAT1/3 (in exchange for dicarboxylate) ; na/dc antiporter maintains dc conc; na/k atpase maintains na conc
Luminal: Pri AT
Secretion of organic cations , eg
Basolateral: oct2
Luminal : mate antiporter (exchange h+); OCTN
Clearance definition and formula
Volume of plasma cleared of a substance in a give. Time
Clearance = [urine] x [volume of urine per min] / [plasma]
How is GFR measured and why use these substances
Inulin/ creatinine (but overestimate as it is slightly secreted in pct)
Freely filtered, Not secreted, not reabsorbed, not metabolites, easily measured
clearance Values for substances reabsorbed/neither reabsorbed Nor secreted/ secreted
Reabsorbed <120ml/min
Neither reabsorbed Nor secreted 120ml/min
Secreted >120ml/min
Measuring effective renal plasma flow
Use PAH, it is filtered and completely secreted but not reabsorbed
Completely removed from blood that passes through kidneys
An underestimate as some blood to kidneys flows through perirenal fat region, not processed by nephrons
Renal plasma flow value , percentage of plasma in blood, renal blood flow
Renal plasma flow= 600ml/min
% plasma = 55%
Renal blood flow= 1100 ml/min
Normal plasma osmolality
290 mosm/kg
Sites of sodium reabsorption
Most of it : proximal tubule + thick ascending limb
Parts influenced by hormones: distal tubule + cd
Proximal tubule Na reabsorption on luminal/basolateral/paracellular; percentage reabsorbed
65%
Luminal: Na/h antiporter (NHE3) ; Na/ nutrient symporter
Basolateral: Na/k atpase
Paracellular: cl- (luminal membrane is negatively charged)
Thick ascending limb Na reabsorption on luminal/basolateral/paracellular; percentage reabsorbed
25%
Luminal: na/k/2cl symporter; k+ channel
Basolateral: Na/k atpase
Paracellular: ca2+, mg2+, Na+, nh4+ (k+ channel-> luminal membrane is positively charged)
Distal tubule Na reabsorption on luminal/basolateral/paracellular; percentage reabsorbed
2-5%
Luminal: na/cl symporter
Basolateral: Na/k atpase
Paracellular: cl- (luminal membrane is negatively charged)
Collecting duct Na reabsorption on luminal/basolateral/paracellular; percentage reabsorbed
5%
Luminal: na+
Basolateral: Na/k atpase
Paracellular: cl- (luminal membrane is negatively charged )
How do tight junctions affect tubule permeability
Increase
Descending vs ascending limb of LOH
Descending: permeable to water
Ascending: impermeable to water
medullary interstitial gradient/Counter current multiplier explained, osmolality of blood entering DCT, what maintains gradient
Ascending limb pumps out salt-> descending limb loses water in response-> fluid moves-> recalibration-> numbers on descending limb are increasing, decreasing (upwards) on ascending
Vasa recta
Osmolality leaving loh is hypotonic
Urea recycling; % of urea filtered that is excreted
- Pct : passive reabsorption due to solvent drag between cells
- LOH: apical secretion due to UT-A2
- CD: reabsorption due to UTA1 (luminal side) ; UTA3 (basolateral)
40%
Adh mechanism
Adh-> v2 receptor -> camp pathway activated-> vesicles with AQP2 fuse with luminal membrane-> increased water uptake -> water exits at basolateral membrane with AQP3/4
Osmolar clearance formula and definition
Osmolar clearance = vol of plasma cleared of all osmotically active particles per unit time
Urine osmolarity x urine flow rate / plasma osmolarity
Free water clearance formula and definition ;
Implication of values
Ability of kidneys to excrete dilute/concentrated urine
Free water clearance= urine flow rate - osmolarity of urine x urine flow rate/plasma osmolarity
=0 isomotic urine
>0 dilute urine
<0 concentrated urine
Osmoreceptors in hypothalamus
SFO: subformical organ
MPN : median Preoptic nucleus
OVLT: organum vasculosum terminalis
Why is adh so effective
Short half life
Rapid release
Rapid effect
What else controls adh levels other than osmoreceptors
Nicotine (stimulates) Nausea (stimulates) Pain (stimulates) Stress (stimulates) Alcohol (inhibits)
Diabetes inspidus characteristics and types
Types: neurogenic (no adh secreted; congenital/ head injury)
Nephrogenic (Inherited mutated aqp 2/ acquired from infection/drug)
Characteristics: polyuria; polydipsia; nocturia
Osmotic diuresis characteristics and mechanism
Characteristics: polyuria/ polydipsia
Mechanism: increased blood glucose-> increased glomerular filtration of glucose-> increased osmolarity of filtrate-> decreased water reabsorption
Reabsorption of k+
PCT: 65% paracellular solvent drag
Thick ascending limb: 30% by k/Na/2cl symporter+paracellular (luminal); k channels + k/cl + na/k atpase (basolateral)
Dct: 5% by k/h antiporter + paracellular (luminal) ; k channels + k/cl + na/k atpase (basolateral)
CD: k/h antiporter (luminal); k channels (basolateral)
Secretion of k+
By principal cells in collecting duct
Luminal: k+ channels (renal outer medullary k+ channel ROMK / ca2+ activated big conductance k+ channel BK) + kcl symporter
Basolateral: Na/k atpase
Hypokalemia + hyperkalemia levels
Hypokalemia mild= 3.0-3.5mM Moderate= 2.5-3.0 Severe= <2.5 Hyperkalemia mild= 5.5-6.5 Moderate= 6.5-7.5 Severe >7.5
Hypokalemia causes
External losses via GI/skin (severe sweating)/ kidney (high tubular flow or hyperaldosteronism)
Redistribution into cells (alkalosis/insulin excess)
Inadequate k intake
What does aldosterone do , where is it produced
zona glomerulosa Increases activity of k/Na atpase K+ channels Na channels Altogether enhancing k+ secretion, Na+ reabsorption in dct/cd/gut/sweat glands
What contributes to high tubular flow rates
Loop diuretics : target thick ascending limb -> inhibits Na/k reabsorption -> inhibits water absorption
Thiazide diuretics: proximal tubule-> inhibits na reabsorption
Transported mutations : inhibit Na+ reabsorption
Osmotic diuresis
How does alkalosis and insulin excess increase k+ redistribution into cells
Alkalosis: k/h antiporter -> k in h out to buffer ; increased k+ secretion due to electrochemical gradient changes
Insulin excess: insulin increases Na/k atpase activity
Hypokalemia signs and symptoms
Very Negative rmp Cardiac dysrythmias Muscle weakness Nausea Polyuria
Hypokalemia treatment
Diet rich in k+
Kcl administration
Alkalosis correction
K-sparing diuretics
Hyperkalemia causes
Decreased external losses: hypoaldosteronism/ drugs/ renal failure
Redistribution out of cells: acidosis/lack of insulin/ cell lysis
Signs and symptoms of hyperkalemia
High rmp with Long refractory
Cardiac dysthymia
Muscle weakness and paralysis
Nausea
Hyperkalemia treatment
Long term: Diuretics
Intermediate term: Insulin
Short term: Ca iv (stabilise cardiac membrane)
How is na content regulated
- GFR
2. Na reabsorption
SNS control of GFR and renin in response to Low bp
When bp is Low, SNS -> renin release/vasoconstriction of afferent arteriole/ contraction of mesangial cells -> decreased SA of filtration barrier -> decreased GFR -> increased na absorption -> increased bp
Intrinsic control of GFR and purpose
Maintains constant gfr between bp of 90-200 to protect renal capillaries fro, hypertensive damage
Increased bp-> juxtaglomerular apparatus senses this -> vasoconstriction of afferent arteriole-> gfr does not increase
Sensors of bp
NaCl concentration receptors in macula densa
Baroreceptors in central arteriole tree
Baroreceptors in afferent arteriole
Baroreceptors in atrium + intrathoracic veins
Effector pathways in response to changes in bp, linked to sodium reabsorption
Renal sympathetic nerves -> renin release -> increase bp
Direct pressure effect on kidney
RAAS -> increase na reabsorption -> increase bp
ANP-> inhibit enac + renin release -> decreased bp
Dopamine -> synergism with ANP
Macula densa mechanism
High bp-> increased [nacl] detected-> na/k atpase indirectly brings about formation of adenosine -> adenosine binds to A1 receptors of afferent arteriole-> inhibits renin release + increase [ca] -> afferent arteriole vasoconstricts
How’re angiotensin 2 and aldosterone secreted
Low bp-> plasma angiotensinogen (made by liver) -RENIN-> angiotensin 1 (10 peptide) -ACE-> angiotensin 2 (8 peptide) -> causes aldosterone secretion from adrenal cortex
Angiotensin 2 effects
- Aldosterone secretion
- Increased na+ reabsorption from PT (binds to AT1 receptors-> stimulates NHE3 + Na/k-atpase)
- Vasoconstriction of small arterioles
- Thirst (binds to osmoreceptors)
- ADH release (binds to osmoreceptors)
Types of natriuretic peptides, origin, when they are produced, effects
Produced when heart is stretched
ANP (atrium)
BNP (ventricle)
Natriuretic: inhibits ENaC + renin release + aldosterone production; synergism with dopamine to inhibit na/k atpase
Diuretic: inhibit adh release
Hypotensive: vasodilation + dilates afferent arterioles
How h+ is gained
- Production of acids from metabolism
- Hypoventilation
- Loss of bicarbonate in diarrhoea
- Loss of bicarbonate in pee
How is h+ lost
- Hyperventilation
- Loss in puke
- Loss in pee
- Loss in metabolic activity
Ph equation
Ph = pka + lg[hco3-]/[pco2]
Normal pco2 & [hco3-] levels
Pco2= 5.3kpa [hco3-]= 25mM
How is bicarbonate reabsorbed , and where , which pumps are involved
In tubular epithelial cells,
H2O + co2 -> h2co3 -> H+ + Hco3-
Hco3- goes into bs; H+ into lumen by NHE3/H+ atpase/ H+K+ atpase
Luminal H+ combines with filtered hco3- -> h2co3-> h20 + co2 -> passive diffusion into cells
At PCT/ascending LOH/ cd type A
How is hco3- secreted and where
Cd type b
In tubular cell, co2+h2o -> h2co3-> h+ +hco3-
H+ to blood by h+ atpase
Hco3- to lumen by hco3-/cl antiporter PENDRIN
Glutamine and hco3- reabsorption
Acidosis-> liver produces glutamine -> gln enters tubular cell by glutamine-aa exchanger (LAT2)on basolateral side; na/gln symporter on luminal side-> nh4 + hco3- -> hco3- reabsorbed ; nh4 excreted by nh4/na antiporter
H+ excretion, when does this happen
H+ excreted when no more filtered hco3- is present
H20+ co2-> h2co3 -> h+ + hco3- -> hco3- reabsorbed
H+ excreted into Lumen and combines with nonbicarbinate buffer -> excreted OR excreted as H+
Respiratory acidosis causes and responses
high pco2
Causes : acute (asthma/drugs) ; chronic (copd)
Responses : chemical (co2-> hco3-); renal (increases h+ secretion as nh4+; increased hco3- absorption)
Metabolic acidosis causes
Low hco3-
Causes : true hco3- deficit (diarrhea/ renal tubular acidosis) ; h+ gain (nh4cl administration/ lactic acidosis)
Responses: chemical ( increased ph-> increased h+ -> hco3- decreases -> pco2 rises) ; respiratory (hyperventilation) ; renal (increased h+ excretion as nh4+, increased hco3- reabsorption)
Respiratory alkalosis
Low pco2
Causes: hypoxic simulation (altitude ) ; excessive respiratory drive (fever)
Responses: chemical (h+ and hco3- drop) ; renal (decreases h+ secretion-> not all hco3- reabsorbed-> Hco3 in pee)
Metabolic alkalosis
High Hco3
Causes: alkali ingestion / vomiting (H loss)/ aldosterone (stimulates H+ atpase)
Responses: chemical (hco3- and h+ drop by a bit) ; respiratory (hypoxia and co2 stimulate respiration) ; renal (decreased h+ secretion -> hco3- excretion)
