>
physiology
>
Overview
>
Body compartments
>
principles
*
similar osmolality maintained because water moves
*
osmolality = 2[Na] + [glucose] + [BUN]
>
Tonicity = 2[Na] + [glucose]
*
these are the effective osmoles
*
BUN doesn’t matter because it moves across membrane
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Intraceulluar Fluid (66%)
*
high osmolality -> low ICF visa versa
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Extracellular Fluid (33%)
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interstitial (75%)
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plasma (25%)
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arterial
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vascular
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sodium content dependent
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thirst
*
lightheadedness
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paliptation
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signs
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orthostasis
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>20 systolic pressure drop
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>10 diastolic pressure drop
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>20 pulse rate increase
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decreased BP
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low JVP
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urine output
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skin turgor
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axillary sweat
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dry mouth
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regulators
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RAS
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sympathetic
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natriuretic peptide
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ADH
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osmolarity sensor
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lack of volume
>
volume trumps all
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diagram
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Pasted_Graphic_12
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urine should reflect the body fluid
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Sodium
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filter a lot of sodium
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resorb a lot of sodium
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most control is in CCD
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Potassium
>
rapid uptake into liver and muscle
*
insulin helps K+ absorption via Na/K ATPase
V
beta2 adrenergic stimulates potassium uptake when exercising, because muscles leak potassium
*
action potentials leave potassium extracellularly
>
H+ ions have variable effect depending on the anion of the acid
V
if the anion passes leaves cell, potassium will follow
*
mineral anions can pass
*
organics like lactic acids and ketoacids do not
V
distal tubule regulation (10% of K+ remains)
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secretion matches potassium intake
>
increased urinary flow increases K+ secretion
*
more Ca++ absorption
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aldosterone
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increases sodium uptake and potassium secretion
V
sodium intake doesn’t matter
*
increased Na diet will increase distal tubule K wasting and decreased aldosterone K wasting
*
decreased Na diet will increase aldosterone K wasting, but decrease distal tubule K wasting
V
high K diet
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Pasted_Graphic_8
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leads to decreased AngII, leading to less Na uptake the DCT (more in collecting)
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more aldosterone increases potassium channel opening
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Calcium
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in serum
*
50% bound
*
50% free
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kidney reabsorption
*
Pasted_Graphic_17
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Corrected Ca accounts for
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albumin
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pH
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phosphorous
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Other factors
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PTH
*
mobilizes Ca from bones and kidney reabsorption
>
vitamin D affects absorption of Ca++
*
Pasted_Graphic_20
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phosphate
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diagram
*
Pasted_Graphic_21
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regulation (high phosphate or low ca -> PTH released -> bone resorption of Ca and Phos and kidney excretion of Phos -> phos down, ca up)
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Pasted_Graphic_22
*
Pasted_Graphic_23
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PTH tells kidney to not resorb phosphate in proximal tubule
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enhances uptake of phosphate from bones and blood
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net drop
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low levels stimulate bone resorption and prevent bone mineralization
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FGF-23
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needs co-factor Klotho
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pH regulation
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net
>
diagram
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Pasted_Graphic_14
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30 mmole intake from diet
*
40 mmols intake from metabolism
>
70 mmol excreted from urine
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secretes protons by ɑ-intercalated cells in collecting duct (ammonium as the buffer/carrier) creating bicarb
*
Pasted_Graphic_15
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ammonium reabsorbed in proximal and secreted in distal
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buffers
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ECF
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bicarb (majority of buffering)
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H+HCO3- <=> H2O + CO2
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kidney makes bicarb
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glutamine -> ammonium + bicarb in distal tubule
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proximal tubule reabsorbs it
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CO2 can leave via lungs
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Pasted_Graphic_13
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plasma proteins
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phosphate
>
ICF
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hemoglobin
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protein
*
phosphate
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Bone (40%)
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bicarbonates released
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Red Cell Mass regulation
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oxygen sensor to signal EPO
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Glomerulus
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diagram
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*
Pasted_Graphic_29
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filtration
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myoglobin >> hemoglobin >> albumin gets through
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anionic drugs less filtered because of negative glycocaylyx and on podocytes
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nephrin and podocin
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GBM has heperan sulfate (negatively charged)
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GFR
*
elimination of nitrogenous waste
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oncotic pressure opposes filtration
>
hydrostatic pressure leads to filtration
V
systemic vascular pressure
*
regurgitation will oppose that
>
local afferent arteriole resistance
V
myogenic response
*
baroreceptors will constrict afferent if BP is too high or relax if BP is too low
V
local feedback control by ascending limb (tubuloglomerulo feedback)
V
macula dense cells of ascending limb send signals
*
detects Cl-
V
leads to vasoconstriction of afferent and renin release if there’s too much chlorine via adenosine
*
adenosine is vessels is a vasodilator
*
ultimately less GFR
V
efferent arteriole resistance
V
renin and AII constrict triggered by
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sympathetics
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myogenic response
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macula densa
>
glomerulotubular balance
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increase in filtration fraction leads to more absorption
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increased capillary protein concentration (oncotic pressure)
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Solute mass balance
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amount filtered = GFR * concentration of solute
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amount resorbed similar to amount secreted
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total urine = Urine flow * concentration
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tests
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equation
*
C_plasma * GFR = C_urine * Q_urine
*
Clearance of x is flow of plasma that has been filtered of x
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creatinine test
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about 90% is GFR and 10% is secretion so creatinine clearance > GFR
*
but as GFR decreases, more percent is secretion
*
more creatinine concentration implies less GFR
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collect urine over 24h
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determine creatinine excreted in a day
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PAH test (para-aminohippuric acid)
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filtered and secreted 100%, so clearance is equal to effective renal plasma flow
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BUN test (blood urea nitrogen)
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some resorption, so GFR is more than clearance
>
hormones
V
constrictor
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endothelin: both
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adenosine: afferent
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angII: efferent
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catecholamines: afferent
V
dialator
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PGE2:afferent
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can prevent no GFR in crisis against alpha agonist
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NO:afferent
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proximal tubule
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diagram
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Pasted_Graphic
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glucose is taken up greatly
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inulin is not reabsorbed
*
Pasted_Graphic_1
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reabsorb everything besides metabolism end products and excess water, salts (65%)
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glucose and amino acids are absorbed 100%
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control systems
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loose epithelium
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some sodium absorption via AII
V
channels
V
Na/H+ exchanger
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results in bicarb absorption
>
loop of henle
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25% resabsorption of sodium
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diagram
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Pasted_Graphic_2
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concentration along loop
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more sodium pumps near bottom of TAH (countercurrent multiplier)
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filtrate is concentrated by water loss
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ascending pumps out solute against a not huge gradient because it is already concentrated
>
very bottom doesn’t have pumps
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concentration is explained by urea resorption through the medullary collecting duct
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protecting vasa recta from stealing solute (countercurrent exchanger)
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descending limb
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thin ascending
>
thick ascending limb
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sodium actively resorbed
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transporters
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apical.
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ROMK
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potassium secretion to build + charge
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Na-K-2Cl
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needs ROMK working to reabsorb sodium and chlorine
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inhibited by furosemide and other loop diuretics
>
basolateral
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NaK ATPase
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Sodium resoprtion
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Potassium secretion
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CaSR
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detects Ca/Mg and deactivates ROMK
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leading to calcium wasting
>
Distal convoluted tubule
V
diagram
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Pasted_Graphic_4
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portion after macula densa
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aldosterone -> Na resorption
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Steep gradients and tight epithelium
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fine regulation
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thiazide diuretics
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collecting duct
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diagram
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Pasted_Graphic_3
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cortical collecting duct
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medullary collecting duct
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aldosterone -> Na resorption
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K+ secretion
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ADH
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cAMP puts aquaporins in to recollect water
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hypothalamic osmoreceptor
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atrial stretch receptor (decreased stretch)
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carotid baroreceptor (decreased)
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occurs before you become thirsty
>
fine tuning
V
principal
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resorb sodium
V
intercalated A
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secrete H+
V
intercalated B
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secrete bicarb
>
electrolyte pathology
>
hyponatremia
>
Diagnosis: <135 Na
V
overview
*
Pasted_Graphic_5
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low urine sodium tells you there is low kidney circulation
>
check serum tonicity
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[Na] can be low despite high [glucose]
*
proteins and lipids will take up volume that artificially decreases [Na] measurements
V
check GFR
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low = acute injury or kidney failure
V
check urine osmol
*
low osmol means too much water intake
V
>100 mOsm/L indicates kidney malfunction
*
hypovolemic and hypervolemic can lead to decreased urine volume
V
check ADH due to effective volume decrease or something else
V
comprimised diluting segments
V
DCT acts solely on dilution via absorbing sodium
*
TAH absorbs sodium but it also leads to water absorption indirectly, thus not affecting tonicity
V
ADH presence
V
e.g. hypovolemia/hypotension
*
loss of salt like diarrhea
V
e.g. hyervolemia
*
CHF/cirrhosis can causes lack of perfusion in some places leading to ADH release
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e.g. nausea, drugs, pain
V
e.g. Syndrome of Inappropriate ADH action (SIADH)
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cancer of lung, or lung pathology
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Renal cell carcinoma
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Brain damage
>
symptom
*
increased ICF, ICP
*
seizing
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chronically (3-4 days)
>
brain will normalize by extruding salt
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don’t shrink it if it has been compensated
V
treatment
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3% saline if symptomatic
V
restrict water intake if asymptomatic
*
restrict water intake
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loop diuretics
*
Vaptan agents
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give salty stuff to allow them pee
>
hypernatremia
>
diagnosis: >145 Na
*
Pasted_Graphic_6
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access to water?
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loss of water?
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urine should be able to concentrate to 600 osm/L
>
symptoms
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high osmolality => shrunken brain
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cause
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hypertonic ampules of bicarb given during a code
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Kidney water loss
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water diuresis (lack of ADH)
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urine osmol < plasma osmol and total osmotic output is low
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diabetes insipidus
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central
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pituitary problem
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nephrogenic = ADH resistance
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congeintal
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drugs
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osmotic diuresis
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urine osmol > plasma osmol and total osmotic output is high
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diabetes, DKA
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urea
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other water loss
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burns
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profuse sweating
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GI loss
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treatment
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fix volume
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fix water deficit
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Pasted_Graphic_7
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give enough water for ongoing losses
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hyperkalemia
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pseudohyperkalemia
V
potassium up due to K+ into ECF after blood transfusion
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hemolysis of blood stored outside of body
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fist clenching with a tourniquet
*
muscle used with tourniquet doesn’t allow K+ to be removed
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thrombocytosis
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if platelet count > 500k
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K+ moves out of platelets during cloting
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leukocytosis
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centrifuging releases potassium so false positive elevated hyperkalemia
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hereditary
>
diagnosis: [K+] > 5.1 mmol/L
V
check for oliguria and other cryptic causes
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Pasted_Graphic_11
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ECG
*
Pasted_Graphic_9
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symptoms caused by resting potential elevation and closing of sodium channels
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cardiac problems
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muscle weakness and flaccid paralysis
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metabolic acidosis
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vasodilation
>
cause
>
decreased excretion
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kidney injury
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decreased GFR
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must be significantly reduced
>
distal tubular Na+ reabsorption decrease
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low effective blood volume
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distal tubule flow
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low effect blood volume
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low aldosterone
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hypoaldosteronism/addisons
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increased cl reabsorption, retain K
>
hyporenin-hypoaldosteronism
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diabetes
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volume expansion
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ARBs, ACEi
*
heparin has toxicity on adrenal zona glomerulosa
>
WNK4/WNK1 kinase
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involved in AII signaling in DCT cell
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spironolactone
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transcelluar shift
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insulinopenia
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diabetic
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beta blocker
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fasting
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somatostatin
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cell breakdown
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rhabdomyolysis
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tumor lysis
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hemolysis
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increased ECF osmolality
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h2o drags K+ with it
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exercise
*
mineral acidosis
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increased potassium intake (rare)
>
example of multiple linked things
*
Pasted_Graphic_10
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treatment
>
urgent treatment if symptomatic
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antagonize ECG effects with Calcium gluconate
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stabilizes the heart
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move K into cells
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insulin
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also give glucose to avoid hypoglycemia
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b2 agonist
>
NaCO3
*
should make H+ leave cells and K+ enter
>
remove K
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loop or thiazidediuretic
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cation exchange resin
>
underlying cause
*
thiazide for Gordon’s syndrome
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chronic
*
reduced dietary intake
>
hypokalemia
>
symptoms
*
lowered resting membrane, leading higher action potential threshhold
*
heart arrhythmias
*
rhabdomyolysis
*
breathing problems
*
ileus
>
Diagnosis
*
Pasted_Graphic_16
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K/Creatinine ratio
*
high ratio implies loss from kidneys
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creatinine is excreted in consistent amounts compared to water
>
cause
>
chronic renal loss of K
>
high aldosterone leads to K+ secretion
*
also leads to alkalosis
*
bushings, conns, licorice
*
liddle’s syndrome
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diuretics
>
bartter’s syndrome
*
like loop diuretic
>
gitelmans syndrome
*
like thiazide diuretic
>
acute shift of K into ICF
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insulin
*
epinepherine
*
aldosterone
>
alkalemia
*
H+ leaves cell, exchanging with K+
>
treatment
*
IV
V
PO
*
kcl
*
k citrate
*
k phos
>
acidosis/alkalosis
>
diagnosis
*
pH: 7.4
>
PCO2: 40 mm Hg
*
low indicates high CO2 clearance
>
HCO3-: 24 meq
*
deviation indicates metabolic problem
>
anion gap
*
unmeasured anions is largely due to albumin
*
expected anion gap = 4 albumin * 2.5 = 10 mmol
>
high anion gap implies too much acid
*
gap acidosis
*
delta gap = anion gap - expected anion gap
>
delta gap should equal bicarb loss
*
delta gap = delta bicarb
>
non-gap acidosis
>
check urine ammonium
*
low ammonium -> RTA
*
high ammonium -> diarrhea loss
>
if delta bicarb greater delta gap
*
non-gap acidosis in addition to gap
>
if delta bicarb is less than delta gap
*
metabolic alkalosis
>
osmolar gap
*
alcohol also contributes to osmolarity
>
metabolic
>
acidosis
>
cause
>
acid overproduction (anion gap>10)
>
lactic acidosis
>
A
*
anaerobic glycolysis due to low blood pressure or anemia
>
B
>
biochemical problem
*
thiamine deficiency
*
liver dysfunction
>
D
*
bacteria makes D-Lactate which is not metabolized
*
ketoacidosis
>
toxic alcohols
>
methanol
*
use fomepizole to block alcohol anhydrase from forming toxic metabolites
*
ethylene glycol
>
salicylate intoxication
*
salicylic acid damages cells leading to ketoacidosis and lactic acidosis
*
alkalization => salicylate more prevalent => does not cross
>
loss of bicarb (delta-delta = 0)
*
diarrhea
*
low ammonium excretion (delta-delta = 0)
>
renal tubular acidosis/uremia
>
try to figure urine ammonium
*
[Cl] - [Na] - [K] = cation gap
*
assume cations are due to ammonium if pH is low
>
proximal (type II)
*
defect in HCO3 reabsorption
*
e.g. carbonic anhydrase inhibitor
*
loss of bicarbonate
*
urine pH initially goes up and the goes down again when lots of bicarb is lost
>
distal (type I)
*
defect in acid excretion for alpha intercalated cell
*
urine pH is >5.5
*
can lead do potassium wasting
>
distal hyperkalemic (type IV)
*
low aldosterone
*
inhibits protons entering cells
*
cell thinks there is low proton content and so does not make ammonium
*
defect in acid excretion
>
compensation
*
in metabolic acidosis, pCO2 = [1-1.5] * HCO3
*
in metabolic alkalosis pCO2 = [.5-1]dBicarb
*
a higher pCO2 than expected means you are not getting rid of CO2
>
alkalosis
>
cause
>
vomitting
*
loss of stomach acid => more stomach acid production => leads to bicarb in serum
>
factors preventing bicarb loss
*
decreased GFR
*
increased aldosterone
*
hypokalemia
*
hypochloremia
*
maintenance of mineralocorticoid effect
>
diagnosis
*
urinary sodium and chloride low implies decreased GFR
*
high bicarb in urine causes sodium and water to be drawn out
>
treatment
*
treat the hypokalemia
>
respiratory
>
alkalosis
*
hyperventilation leads to low CO2
>
acute respiratory alkalosis compensation
*
HCO3 decreases 2 per 10 pCO2
>
chronic respiratory alkalosis (days) compensation
*
HCO3 decreases 5 per 10 PCO2 so pH is maintained
>
symptoms
*
cerebral vasospasm and ICP decrease
*
dizziness
>
acidosis
>
hypoventilation
*
decreased air intake or more dead space
>
acute
*
sedative drug overdose
*
acute exacerbations respiratory disorders
*
hypercapnia
>
chronic
*
sleep apnea
*
emphysema
>
acute compensation
*
HCO3 increases 1 per 10 pCO2
>
chronic (days) compensation
*
HCO3 increases 3.5 per 10 pCO2
>
symptoms
*
confusion
*
cerebral dilation and ICP increase
>
source
*
metabolism
*
food products
*
medications
*
intermediate products like lactic acid
>
hypercalcemia
>
diagnosis
*
Pasted_Graphic_19
>
symptom
*
weakness
*
coma
*
short QT
*
acute kidney injury
>
cause
*
pseudo: hyperalbumin
>
high PTH (PTH is cause)
*
hyperparathyroidism
>
FHH Thiazides (low urine Ca++)
*
kidney sensor doesn’t detect Ca++, so you make PTH and don’t pee out Ca++
*
no treatment needed
>
low PTH (other reason)
*
acidosis kicking ca off of albumin
>
malignancy
*
metastasis in bone
*
PTHrP releasing tumor (lung)
>
granulomatous disease
*
macrophages make calcitrol(1,25 vit D)
*
vitD/A intoxication
*
milk-alkali syndrome
*
lithium
*
thiazide
>
treatment
*
severe: volume repletion via IV NS
*
calcitonin
*
bisphosphonates
>
hypocalcemia
>
diagnosis
*
Pasted_Graphic_18
>
symptoms
*
trousseau sign
>
neuromuscular
*
strider
*
seizures
*
tetany
*
psychiatric disorders
>
CV
*
prolonged QT
*
arrhythmia
>
causes
>
pseudo
*
IV gadolinium
*
hypoalbuminemia
>
low PTH (PTH is the problem)
>
removal of parathyroid
*
hungry bone syndrome
>
hypoparathyroidism
*
primary
*
polyglandular synd
*
di-george
*
leads to high phosphate
>
high PTH (something else is the problem)
>
Vit D deiciency
*
lack of light
*
lack of intake
V
liver disease or kidney disease
*
they are involved in the metabolism
*
chronic kidney disease
>
tissue damage
*
leading to phosphate leak and binding to Ca
*
blood transfusions (citrate and EDTA bind to Ca)
>
alkalosis
*
increases Ca++ binding
*
resistance to PTH
*
deposition of Ca elsewhere
>
treatment
*
symptomatic: IV calcium
*
asymptomatic: oral vit D and Ca++ supplement
>
hypophosphatemia
V
cause
*
insulin
*
low phosphate diet (rare)
*
re-feeding syndrome
*
alkalosis (causes more glycolysis and consumption of phosphate)
>
reduction of cell ATP
*
phosphate is needed for glycolysis
>
magnesium
*
necessary for PTH release
*
hyper causes hypocalcemia
*
hypo causes hypocalcemia
>
pathology
>
diagnosis
>
urinalysis
>
color
*
red
>
microscopy
*
casts indicate renal origin
>
hematuria
*
RBC cast -> nephritis
>
pyuria
*
infection
>
epithelial cells
*
skin cells in urine is normal in the initial few drops
*
tubular version indicates glomerular damage
>
fat droplets
*
indicate protineuria and damage to cells
>
crystals
*
uric acid
*
calcium oxalate
>
mg ammonium phosphate
*
coffin lid
*
alkaline urine
>
electropheresis for proteinuria
*
Pasted_Graphic_25
*
<150 mg/day total
*
45% tamm hosftall
>
<30 mg/day albumin
*
albuminuria indicates foot process effacement
*
proteinuria without albuminuria could indicate lack of proximal tubule absorption or overload proteinuria
>
immunofluoresence
*
IgG,A,M heavy chain
*
kappa, lambda light chain
*
complement activation/deposition
>
kidney stones
>
diagnosis
*
flank pain
*
topiramate
*
calcium supplement, vitamind D/C
*
HT, obesity, diabetes, gout associated
>
symptoms
*
stone obstruction leads to pain
*
hematuria
V
fever
*
implies infection
*
emergency risk for sepsis
>
type of stones
>
calcium oxalate with a ca/phosphate core
*
Pasted_Graphic_24
*
calcium phosphate
>
uric acid
*
Pasted_Graphic_25
>
infectious (struvite)
*
Pasted_Graphic_27
*
bacteria makes urease => ammonia and alkaline urine
*
must remove stone because bacteria is protected by stone
>
cystine
*
Pasted_Graphic_26
*
could be due to aa transport defect
>
formation
>
randall’s plaques
*
Ca phosphate plaques on renal papilla
>
activity product ratio (concentration in a sense)
*
low urine volume (<1L)
>
high concentration of ca
*
urine calcium over >250 in men. >200 in women
*
95% idiopathic, mostly overweight white
*
maybe increased vit D absorption
*
bone resorption
*
renal excretion
*
high protein diet
*
acid load causes bone resorption
>
high sodium
*
more sodium is excreted, ca follows sodium
*
hyperparathyroidism
>
oxalic acid
>
fat malabsorption causes more oxalic acid
*
Pasted_Graphic_28
*
give calcium supplements
>
uric acid
V
usually due to insulin resistance
*
insulin resistance => less ammonia (buffer) => more acidic
*
uric acid precipitates
>
inhibitor
>
citrate (makes Ca more soluble)
>
metabolic acidosis leads to absorption of citric acid
*
less citrate => more stones
*
can be caused by lots of things
>
high calcium diet (paradoxical!?)
*
decreases oxalic acid absorption
*
BUT supplements can increase risk
>
treatment
*
diet
>
thiazide diuretic
*
lower calcium concentration
*
K-citrate supplement
>
glomerular disease
>
glomerulonephritis
>
nephritic syndrome presentation
>
hematuria
*
RBC cast
*
dysmorphic RBCs
>
glomerular proliferation on microscopy
*
focal vs diffuse (refers to population of glomeruli affected)
*
global vs segmental (refers to individual glomeruli)
*
Pasted_Graphic_30
*
hypertension
*
edema
>
there is a rapidly progressive glomerulonephritis version
*
increase in serum creatinine
>
summary
*
Pasted_Graphic_32
>
linear IF/anti-GBM ab
*
RPGN presentation
>
antibody to collagen IV in glomerular basement membrane
*
good pastures syndrome if this and pulmonary involvement
>
light
*
crescent
*
fibrinoid necrosis
>
treatment
*
steroid
*
plasmapheresis
>
granular IF/immune complexes
V
post-strep GN
*
Light: endocapillary proliferative GN
*
EM: sub-epithelial deposits
*
treatment: supportive
>
lupus nephritis
*
full house: IgG, IgM, IgA, kappa, lambda, complement
>
class determines treatment
*
Pasted_Graphic_31
>
immunosuppresants
*
steroids
>
IgA nephropathy
>
in asians and most common
*
mostly subclinical
*
synpharagytic
>
IgA vasculitis/Henoch Schonlein Purpura (HSP)
*
systemic IgA vasculitis presenting in child hood with colitis and skin rash
*
abnormal IgA results in abnormal complement and immune activation
*
EM: mesangial deposits of IgA
*
light: mesangial hypercellularity
>
treatment
*
ACEI/ARBs
*
steroids
>
pauci-immune IF
>
Anca diseases
*
antibody to neutrophils causes them to explode
*
MicroscopicPolyAngitis
*
GranulomatosisPA
*
EosinophilicGPA
*
LM-cresents
>
nephrotic (non inflammatory)
>
nephrotic syndrome
*
defined by proteinuria (>3.5 gm/d)
*
hypoalbuminemia
*
edema
*
hyperlipidemia
>
risk for
*
hypercoagulable
*
infection
*
atherogenesis
>
summary
*
Pasted_Graphic_33
>
normal (minimal change disease)
*
most common nephrotic cause in children
V
secondary causes:
*
Nsaids
>
focal segmental glomerulosclerosis
*
progresses to CKD
>
secondary causes:
*
low nephron mass
*
transplant: graft loss
>
membranous
>
PLA2R+ antibody
*
antibody to podocyte in a granular pattern
*
thickened
*
sub epithelial deposits
>
secondary causes
*
malignancy
*
infections
*
medications
*
lupus class V
>
other LM
*
amyloid
>
diabetic nephropathy
>
stages
>
prenephropathy
*
hyperfiltration
>
incipient nephropahty
*
non-detectable proteinuria
*
decreasing GFR
*
hypertrophy
>
overt nephropathy
*
>300mg albumin
*
>500mg protein
*
GFR decreases
*
kidney fibrosis
>
advanced nephropathy
*
low GFR
*
mesangial expansion = nodular glomerulosclerosis
>
pathophys
>
hyperglycemia
*
glycalation end products that damages the kidney
*
more oxidative stress
>
high kidney pressure
*
give ACEi to decrease glomerular pressure
*
hypertension
>
treatment
*
acei/arb
>
tubulo-interstital disease
*
ATN
>
toxins
V
hypersensitivity reaction: acute interstitial nephritis
*
much more interstitial space
*
eosinophils + other inflammatory cells
V
slow cumulative damage (analgesic abuse)
*
risk for acute papillary necrosis
*
direct toxicity (gentamycin)
*
contrast
*
rhabdo
>
metabolic
>
oxalate nephropathy
>
causes
*
autosomal recessive disease
*
fat malabsorption + vit c + oxalate foods
*
ethylene glycol poisoning
>
uric acid nephropathy
>
acute
*
rapid cell turnover
>
chronic
*
hyperuricemia
*
precipitation of crystals
>
nephrocalcinosis
*
hypercalcemia
*
staghorn calculus
>
infection
>
acute pyelonephritis (pelvis + nephrons)
>
gram negative rods in tubules and interstitium
*
UTI
*
reflux
*
diabetes
*
route can be hematogenous or ascending
>
chronic pyelonephritis
>
presentation
*
atrophic tubules (thyroidization)
*
scarring with distortion of calyces and pelvis
*
not necessarily infection related
>
types
*
chronic obstructive
>
secondary to reflux
*
polar scars
*
xanthogranulomatous pyelonephritis
>
immune disorders
>
sarcoidosis
>
granulomas for unknown reasons
*
post infectious immune activity
*
also lungs, LNs, heart, liver...
*
elevated ACE
>
IgG4 related disease`
*
infiltration of IgG4 plasma cells
*
whirling fibrosis
*
Crohns
>
neoplasia
>
multiple myeloma
>
cast nephropathy - light chain in tubules with giant cell reaction
*
Pasted_Graphic_26
>
amyloidosis (congo red)
>
cause
*
rheumatoid arthritis
*
multiple myeloma
>
vascular disease
>
Decreased renal blood flow
>
renal artery stenosis
*
FMD
*
atherosclerosis
>
atheroemboli
*
cholesterol embolus
>
infarction
*
wedge zone of coagulative necrosis
>
HTN
>
arterionephrosclerosis = HTN nephrosclerosis
*
dimpled shrunken kidneys
*
arteriolar hyalinosis
*
wrinkinling and global sclerosis
*
intimal fibrosis/sclerosis
>
malignant hypertensive nephropathy
*
flea bitten kidney with hemorrhages
*
fibrinoid necrosis
*
glomerular collapse
*
hemorrhage from vessel rupture
>
chronic:
*
hyperplastic arteriopathy (onion skin lesion)
>
scleroderma
*
fibrinoid necrosis
*
onion sknning (advanced intimal hyperplasia)
>
thrombotic microangiopathy
>
presentation
>
lowered haptoglobin
*
it binds to hemoglobin
*
endothelial injury
>
summary
*
Pasted_Graphic_27
>
classification
>
HUS
*
vessel wall damage
*
shiga-like toxin
*
thombocytopenia
*
kidney failure due to thrombosis of kidneys
>
atypical HUS
*
no diarrhea
*
caused by complement factor mutation, cancer, or auto immune
*
mostly children
>
TTP
*
fever
*
microangiopathic hemolytic anemia
*
thrombocytopenia
*
fluctuating neurological abrnomalities
*
renal disease
*
DIC
>
Pre-eclampsia
*
massive swelling of endothelial cells
*
subendothelial widening
>
acute kidney injury
>
diagnosis
*
decline in GFR over hours/days
*
increase Cr, available nephrons ~ 1/Cr
>
cause
>
Prerenal
>
presentation
*
RAAS, and higher creatinine
>
contraction alkalosis
*
reabsorb bicarb
>
low FENa < 1%
*
kidney is keeping salt appropriately
>
BUN/creatinine > 20:1
*
urea is reabsorbed in tubule
*
ECF volume depletion
*
low cardiac output
*
low systemic vascular resistance
>
increased renal vascular resistance
*
nsaids
>
Post renal (least common)
*
bilateral blockage
*
unilateral would be asymptomatic
>
Intrinsic
>
acute tubulointerstitial nephritis
*
focal loss of tubular epithelial cells -> urine sediment
>
ATN
>
paradoxical afferent vasoconstriction
*
increased chloride delivery to macula densa (less resorption)
*
increased Ca++
*
toxins
>
ischemia
*
epithelial cell injury
*
vascular effects
*
muddy brown casts
>
AIN (acute interstital nephritis)
*
WBCs
>
acute glomerulonephritis
*
proteinuria, dysmorphic RBC casts
*
acute vascular nephropathy
>
Sx
*
reversible, high mortality, could lead to CKD
*
ischemic damage
>
Rx
*
supportive
>
chronic kidney injury
>
causes
*
diabetes
V
kidney function declines with age
*
mechanical damage over time
*
oxidative stress, apoptosis, etc.
>
stages
>
summary
*
Pasted_Graphic_38
>
<60 ml/min/1.73 m^2 for more than 3 months
*
normal is 100
*
proteinuria incurs additional risk
>
end stage
*
kidney function needs replacement via dialysis or transplant
>
path
*
glomerulosclerosis
*
interstitial fibrosis
*
tubular atrophy
>
symptoms
>
CVD
*
stiffening of vessels from hyperphosphatemia
*
uremic toxins
*
inflammatory state
*
thrombogenic factors
*
less medication tolerance
>
secondary hyperparathyroidism
>
pathway
*
less vitamin d synth -> hypocalcemia
*
nephron loss -> can’t secrete phosphate -> FGF23 -> vit D suppression
>
PTH secretion
*
parathyroid enlargement, which tends to have less CaSR
*
Pasted_Graphic_39
*
hyperphosphatemia (binds free calcium)
*
usually low calcium despite high PTH
>
Sx
>
loss of bone
*
loss of bone in fingers
*
loss of distal third of clavicle
>
medial vascular and cardiac calcification
*
increased phosphate in cells results in changes that make them bone-like
*
stiffening of vessels leading to hypertension and increased afterload
*
worse form is calcific arteriopathy in which calficiation is in soft tissue
>
Uremic syndrome (symptomatic renal failure) [pericarditis, bleeding, encephalopathy]
>
GI
*
loss of appetite, particularly meat
*
metallic taste in mouth
*
uremic fetor (urea -> ammonium in oral cavity leading to ulcers
*
bleeding
>
anemia
*
normocytic hypoproliferative
*
lack of EPO
*
perhaps iron/folic acid deficiency or GI blood loss or bone problems
*
fatigue, dyspnea
*
dysfunctional platelets and lots of procedures with bleeding risk
V
Tx
*
frequent transfusion can lead to transplant rejection
*
recombinant EPO
V
DDAVP (vasopressin mimic)
*
release of wWF factor by endothelial cells
>
lipid
*
more TG because some not understood mechanism
*
decreased HDL
*
increased apolipoprotein-A1 due to less cleanse -> more atherosclerosis
*
statins (be careful of rhabdomyolysis)
*
sexual dysfunction
>
pregnancy
*
be careful of HTN
*
prematurity
*
get a transplant
>
metabolic acidosis
*
cannot excrete acid, loss of bicarb
*
bone disease
>
treatment
>
hyperparathyroidism
>
control hyperphosphatemia
*
low phosphate diet
>
phosphate binders
*
aluminum hydroxide
*
iron one
>
increase vit D
*
fear of increasing vascular calcification
>
suppress PTH
>
calcimimetic drugs
*
CaSR thinks there is calcium
*
expensive
*
surgical removal of parathyroid
>
proteinuria
*
ACEi/ARB to reduce protein filtration into urine
>
dialysis
>
definition
*
passage across membrane to remove solute and then put back desirable solutes
*
Pasted_Graphic_35
>
hemo
*
requires AV fistula or graft or catheter
>
peritoneal
*
use peritoneal space to hold the dialyzer fluid
>
transplant
>
candidate
*
low surgery risk and immunosuppression
*
life expectancy
>
immune respone
*
inate
>
adaptive
*
T cell
*
B cell
>
immune supression
*
T
*
B
*
steroids
>
hereditary
>
Autosomal Dominant Polycystic Kidney Disease
>
cause
>
PKD1 (85%) for polycystin 1 defect is more severe
*
sensor fluid movement
>
PKD2 (15%) for polycystic 2
*
ca channel regulator
>
cAMP in normally inhibited by PKD1/2
*
leads to cell division via RAS and cysts
*
two hit hypothesis as 1-5% tubules have cyst
treatment
>
Sx
>
cysts comprise 95% volume and grow very large
*
nausea
*
vomitting
*
trouble breathing
>
GFR decreases because it is pinched by cyst
*
HTN due to RAS activation
*
urinary stagnation -> stones
*
bleeding of cysts
*
impaired concentrating ability
>
can also have cysts in liver
*
mass effects like shortness of breath, early satiety
>
can also have MV prolapse, cerebral aneurysm, diverticulosis
*
cerebral aneurysm is most concerning
*
diagnose via ultrasound and also often HTN
>
treatment
*
mTOR inhibitor
*
vasopressin antagonist
>
Autosomal Recessibe PKD
>
cause
*
much rarer
*
fibrocystic PKHD1
>
Sx apparent early in life
>
significant liver dilitation in intrahepatic ducts
*
portal HTN
*
hepatic fibrosis
*
kidney cysts (smaller than ADPKD)
>
fetal oligohydraminos
>
big kidneys compress other things
*
clubbed features
*
altered facial features
>
low urine leads to less amniotic fluid
*
smaller lungs
*
stasis leads to infections in kidney and liver
>
Dx
*
poor differentiation between medulla and cortex
*
enlarged hepatic ducts
>
treatment
*
transplant
>
Alport
>
Cause
*
X-linked mutation of type IV collagen subunits
>
disruption of glomerular basement membrane
*
non uniform and interdigitating electron dense material
*
Pasted_Graphic_24
>
also eye
*
anterior lenticonus
>
also ear
*
hearing loss starting with higher pitches
>
treatment
*
transplant
*
RAAS blockade
>
APOL1
*
offers resistance to African Sleeping Sickness
>
increased kidney disease risk
*
particularly FSGS
>
tumors
>
RCC (lining of tubule)
V
presentation
*
smoker
*
hematuria
*
flank pain
*
renal mass
V
tumor can generate hormones
*
hypertension
*
polycythemia
*
hypercalcemia
V
staging (high chance of metastasis to bone or lungs)
*
Pasted_Graphic_28
V
types
>
clear cell (70%)
V
genetic version and sporadic
V
genetic = Von Hippel-Lindau syndrome
*
2 hit hypothesis
*
cells with out VHL think that they are hypoxic
*
kidney’s affected equally
*
clear (lipid) with web of capillaries
>
can turn into mesenchymal tissue (sarcomatoid change)
*
<1 yr expected survival
*
chromophobe
*
papillary
V
Urothelial Carcinoma
V
epi/presentation
*
exposed to carcinogens
*
male
*
painless hematuria
V
types
V
papillary
*
Pasted_Graphic_36
V
low grade
*
fusion of papilla
V
high grade
*
nuclear pleomorphism and random polarity of cells
*
probably loss 17p’s p53
V
flat (high grade)
*
Pasted_Graphic_37
*
urinary cytology
>
Nephroblastoma (Wilm’s Tumor)
>
malignant embryonal neoplasm -> divergent differentiation
*
WT-1 mutation
V
presentation
*
abdominal mass
*
2-5 y.o.
*
good prognosis (90% cure)
>
gross
*
solid/solitary mass that is delineated
*
rarely bilateral
V
cytology
*
Pasted_Graphic_34
*
diffuse anaplasia is bad
>
secondary hypertension
>
diagnosis
>
make sure it isn’t apparent RHTN (pseudo)
*
uncontrolled BP despite 3 meds, but controlled with 4
*
white coat htn
*
sodium
*
adherence to medications
>
don’t use BP raising drugs
*
nsaids
*
stims
>
cause
>
primary aldosteronism (conn’s)
>
presentation
*
HTN, hypokalemia, alkalosis
*
RAAS activation leads to aldosterone
*
renin, aldosterone levels
>
renal artery stenosis
>
Dx
*
rise in creatinine >30% after ACE/ARB
*
abdominal bruit
>
atherosclerosis
*
Tx: ACEi/ARB or angioplasty
>
FMD
*
distal lesions in women
*
Tx: angioplasty
>
pheochromocytoma (adrenal medulla)
*
diagnosis with metanephrines
*
resection and genetic testing
>
pharmacology
>
Diuretics
>
general
*
protein bound so does not go through GFR
*
require secretion through cells
>
mannitol
*
osmotic diuretic
*
can be used to reduce intracranial pressure and hypotension
>
acetazolamide
*
carbonic anhydrase inhibitor (Na/H)
V
treatment for
*
glaucoma
V
alkalosis
*
decrease bicarb resorption leading to increasing acidity
*
altitude sickness causes alkalosis because decreased pCO2
>
loop diuretic
*
inhibits Na/K/2Cl in TAH, thus impairing ability to dilute and concentrate (messes up medullary gradient) urine
*
leads to loss of Mg and Ca++
>
braking phenomenon after a few days
*
distal and collecting ducts start reabsorbing sodium
*
steady state of water and sodium is lower
*
used for edematous states
>
Sx
*
hypokalemia
*
ototoxitiy
>
thiazide
*
acts on DCT
*
inhibit NaCl resorption
>
Sx
*
hypertension
*
hypercalcemia
*
hyponatremia
>
K+ sparing
>
blocking ENAC in CD
*
corresponding block of ROMK leads to retention of K+
*
spironolactone and eplerenone