Week 1 Flashcards
kidney functions
elimination of nitrogenous waste
regulation of body fluid content, body fluid composition, blood pressure, acid/base balance, RBC volume, Calcium (bone) metabolism
elimination and metabolism of endogenous and exogenous “active molecules”
Filtration pressure formula
GCP -COP - CP
GCP = glomerular capillary pressure
COP = colloid osmotic pressure… osmotic pressure from solutes drawing water back into capillaries
CP = capsule pressure
significance of urea concentration
-not apparently toxic in itself, but marker for other small molecules that have toxic effects when they build up
autoregulation of renal blood flow
keeps RBF and GFR ~ constant over wide range of MAPs
-accomplished by juxtaglomerular apparatus (tubal-glomerular feedback)
sequence of events in sudden increase in Na+ intake
- intake jumps
- output lags behind (hormonal adaptive mechanisms are slow) = positive balance –> thirst stimulated and water intake inc –> weight gain
- as output catches up, reach new steady state and weight plateaus
- when intake decreased to original levels, output lags for a time = negative balance –> water excretion –> weight loss
proximal tubule
- “leaky epithelium” that reabsorbs vast majority of filtered volume
- achieved by transport of solutes with osmotic flux of water
distal nephron
-“tight” epithelium that is mostly under hormonal control, is able to establish steep gradients, has a high electrochemical potential, is generally water impermeant, and provides fine regulation of final urinary excretion. Steady state balance is hormonally regulated at the distal tubule
hormonal control of free water reabsorption by the kidney
Sensor = hypothalamus
Feedback to posterior pituitary
Message = ADH
Responding organ = collecting duct (aquaporin expression)
role of kidney in acid-base regulation
- kidney adds bicarb into blood to keep pH high
- (pK of buffer system is 6.1, but pH of blood is 7.4)
- compensation w/i 24 hrs
significance of kidney size
chronic injury –> fibrosis –> shrunken kidneys and echodensity on ultrasounds (helps differentiate chronic from acute kidney injury)
Effective vascular volume
The ability to appropriately load arterial space.
No single measure, but a combination of CO, SVR, plasma volume.
Main determinant of plasma volume
ECF volume
total body water components and major cations
ECF (Na+) 1/3 + ICF (K+) 2/3
components of ECF
interstitial fluid (3/4) + plasma (1/4)
osmolality
ratio of particles/water
Tonicity
Tonically active osmoles are confined to one side of cell membrane or the other (“effective osmoles”) i.e. cause fluid shift
Effective: Na, K, Cl, Mannitol
Ineffective: Urea, Ethanol (cross cell membrane)
Glucose can be either, depending on presence of insulin
–cannot be directly measured; derived.
–important because it dictates water distribution
Basic regulation of ECF and tonicity
-ECF regulated by Na intake/excretion (via RAAS)
-Tonicity regulated by Water (via ADH/thirst)
-implications for IV fluids
(Cross-talk between these two systems:see double-loop slide)
How do we evaluate effective vascular volume and tonicity
- Effective Vascular volume: Labs are unreliable. use clinical evaluation (JVP, crackles, edema, acute change in weight, axillary sweat).
- Tonicity: clinical exam unreliable. use lab for serum sodium and osmolality (under special circumstances)
“Serum sodium” vs total body sodium
serum sodium is RATIO of Na/H20. Measure of tonicity. Too low = hyponatremia. too high = hypernatremia
Total body sodium is measure volume. Too little = hypovolemia, too much = hypervolumia
Isotonic saline
- tonicity comparable to aqueous portion of blood
- used to give Na and volume (increased volume with same [Na])
D5W
5M dextrose. used to give water b/c pure water will lyse RBCs locally. Dextrose metabolized, excreted as CO2, so not osmotically active.
-increases ECF somewhat, but not nearly as effective as giving normal saline. Decreases [Na]
(2/3 goes into ICF, 1/3 goes into ECF)
ultrafiltration
-process of moving plasma ultrafiltrate across glomerulus into bowman’s space. concentration of filterable solutes is very close to that in blood
adsorption (reabsorption)
moving something from intraluminal space back into blood stream. Can be between or through cells
diuresis
loss of water through urine
oncotic pressure
pressure from proteins/large molecules
osmotic pressure
pressure from small solutes
RPF
RBF- erythrocyte flow
GFR
sum of each individual nephron’s filtration
~180L/d for adult
typically expressed in in mL/min or mL/min/1.73m2 BSA
selectivity of glomerular barrier
- size: bigger < smaller
- charge: anionic < neutral, cationic
significance of capillary oncotic pressure
-opposes exuberant increase in filtration (magnitude increases as you move along capillary segment and/or increase filtration)
effect of Angiotensin II on renal arterioles
-predominantly constricts efferent arterioles
effect of catecholamines on renal arterioles
-predominantly constricts afferent areterioles
effect of catecholamines on renal arterioles
predominantly dilates afferent arterioles
myogenic reflex
autoregulatory reflex to adjust afferent arteriolar resistance based on pressure
-tubero-glomerular feedback: macula densa cells release AtII locally to constrict afferent arterioles in the presence of lots of sodium
Kidney Solute Mass Balance
assume no metabolism /synthesis in kidney…
Arterial input = venous output + Urine output
PxaRPFa = PxvRPFv + UxV
or
GFRPx + amount secreted - amount reabsorbed = UxV
inulin and GFR
-not reabsorbed, not secreted
Pin*GFR = UinV
GFR = UinV/Pin
“clearance”
apparent rate at which solute is being excreted in urine
“how much plasma would have to give up all of its solute in order to attain measured urine excretion rate?”
if clearance decreases, plasma concentration increases
UV/P = clearance
For non-reabsorbed/secreted substance, Clearance = GFR
Creatinine and GFR
- secreted a little bit, so CCr > GFR, but pretty close
- not a very sensitive marker of renal failure, b/c can lose a lot of kidney function without seeing a huge increase in urinary Cr
- As GFR decreases, tubular secretion of Cr increases, so measure of Cr will over-estimate GFR
urea and GFR
Cu < GFR because urea reabsorbed
clinical measurement of GFR
-Average of GFR measured w/ urea and GFR measured with Cr, and error will mostly cancel.
serum creatinine and GFR
-must be put into context for individual (correct for weight, BSA, muscle mass, etc)
relationship of ureteric buds and undifferentiated renal mesenchyme in embryo
-mesenchyme secretes growth factors to extend ureteric bud. Buds secrete proliferation/differentiation factors
Potter’s sequence
- in utero kidney dysfunction –> oligohydramnios
- -> increased pressure on fetus –> sloped forehead, parrot beak nose, shortened fingers, lung damage
Pelvic kidney, horseshoe kidney, supernumerary arteries
disorders of kidney ascent (from tail up to adult position)
Drainage system of kidney
efferent arteriole–> vasa recta
each pyramid drains into minor calyx
minor calices –> major calyx –> ureter
kidney lobule
centered around medullary ray
consists of glomeruli and all tubules contributing to collecting ducts within medullary ray
Radially running arteries/veins are located at the borders of lobules
Medullary ray
arrangement of parallel tubes. Thick descending limb, loop of Henle, think ascending limb, collecting duct.
Proximal and distal convoluted tubules are outside of ray
Proximal tubes vs distal tubules on H&E
proximal have abundant eosinophilc cytoplasm and brush border (reabsorption)
outer/inner zone of medulla
outer has thick ascending limbs, loops of Henle and collecting ducts
inner has just loops of Henle, collecting ducts
(see slide for two types of glomeruli and zones)
blood supply to kidney
renal artery –>interlobar artery –> arcuate artery (junction of cortex/medulla) –>interlobular arteries –>intralobular arteries –> afferent arterioles
components of filtration barrier
- fenestrations in endothelial cell cytoplasm
- slit diaphragm between podocyte foot processes (nephrin and other proteins)
- glomerular basement membrane network
mesangial cell
sits between capillary cells.
-supports, can secrete ECM, can contract
Juxtaglomerular apparatus
point of contact of distal tubule/glomerulus
- macula densa cells sense salt in distal tubule and signal to JG cells with PGE2/NO
- JG cells directly sense pressure in afferent arterioles
- JG cells integrate signals and secrete renin
EPO generation in kidney
Specialized interstitial cells. hypoxia inducible factor pathway. constitutive degradation after O2-dependent modification of Pro residues. under hypoxia –> activation of hypoxia-inducible genes, including EPO
proximal tubule absorption
absorbs ~2/3 of ultrafiltrate. Largely via primary and secondary active transport. Sodium driving water.
- 3/4 water transport is paracellular. “leaky” with low membrane potential
- Glucose/amino acids/water reabsorbed avidly. HCO3 and Cl less so.
- urine ~ less so
6-box blood test display
- sodium over potassium
- chloride over bicarb
- BUN over creatinine
- glucose
primary secondary and tertiary active epithelial transport in nephron
- primary: on basolateral membrane, 2K pumped in, 3 Na pumped out (ATPase)
- secondary: on apical membrane, Na in/H out
- Tertiary: HCO3 out (driven by H+)/Cl- in
Proximal tubule transport
- driven by Na (Na/K exchanger on BLM)
- no Na/Cl contransporters here, but Cl/CO3 cotransport and paracellular Cl
phosphate PT reabsorption
- apical Na/H2PO4 cotransporters
- reduced by PTH
- increased by growth hormone
Amino Acid reabsorption
-Some are linked to Na, some to H
urate reabsorption in PT
- tertiary transport (bicarb exchange)
- much is secreted, then absorbed again (not known why)
bicarb reabsorption in the PT
H+ secreted into lumen, reacts with HCO3 to form H2CO3. CAH –> H2O+CO2.
CO2 diffuses back into PT cell, reacts with OH- –> HCO3. Cotransport with Na across BLM
Ca++/Mg++ reabsorption in PT
- passive paracellular diffusion
- Caludin-2 functions as paracellular channel
- 50-60% of Ca, 5-15% of Mg
K+ handling in PT
- “solvent drag” paracellularly with H2O
- minimal secretion to lumen (b/c of high IC K+)
- later in tubule, where lumen is (+), paracellular diffusion
megalin-cubulin complex
- transport of solutes other than electrolytes (protein, etc)
- mediates endocytosis –> processing via lysosomes
- can mediate iatrogenic kidney injury (e.g. aminoglycosides)
PT ammoniagenesis
- Gln metabolized in PT
- generates NH2 and HCO3
- NH2 excreted in urine or reenters blood –> liver –> urea
Fanconi Syndrome
- defect in PT function (many etiologies)
- variable degrees of PT Pi, gluc, AA, bicarb wasting
- in children: rickets and growth impairment
- in adults: osteomalacia and osteoporosis
character of fluid entering the thin limb of Henle’s loop
- Na is ~ plasma
- Cl is higher due to HCO3 reabsorption in PT
- no glucose, AA, or protein
- high K, secreted into pars recta
- high in NH4, synthesized in PT
thin limb of Henle permeability
- descending: permeable to water, but v low than Na/Cl. allows water extraction w/o Na
- ascending: opposite.
- integrated: lots of reabsorption of Na/water. facilitated by solute gradient (increasing concentration deeper in medulla)
thick ascending limb properties
-water impermeable (like thin ascending limb)
-powerful NaCl transporter
=”diluting property”
-Lumen positive potential
-properties due to NKCC2
NCKK2
Thick ascending limb transports Na, K, 2Cl from urine into cell Na pumped into blood, Cl follows K recycled through ROMK channel inhibited by furosemide
Ca++/Mg++ in tALH
paracellular movement to blood (positive lumen potential due to ROMK)
character of fluid entering the distal tubule
- hypotonic due to powerful NaCl reabsorption in the tALH
- dilution due to concomitant H2O impermeability in the tALH
- very little K, NH3, HCO3
- moderate Ca, Mg
- about 10% filtered NaCl
nature of distal nephron transport
- steep chemical gradients
- hormonally regulated transport pathways serving systemic needs
- separate pathways for sodium and other ions, although sodium dependence is often a feature
- NCCT cotransporter Na/Cl
- weakly (+) lumen due to K recycling
Mg and Ca transport in distal tubule
specific TRP channels allow them into cell.
Ca2+ binds carrier proteins
character of fluid leaving DCT
- hypotonic
- less Na/Cl
- little K
- minimal Ca, Mg
- low bicarb (acidic)
Collecting duct Na/K transport
ENaC – inducible allows Na in
Na/K pumps sodium out
K+ excreted into urine via ROMK, into blood by other channels
-Aldosterone stimulates ENaC when sodium deficient
Aldosterone
- stimulates by Na/volume depletion
- synthesis of ENaC
- leads to K wasting
functions of collecting duct
- regulate urine composition of Na, K, bicarb (via aldosterone)
- allows water retention or elimination depending on needs
- allows formation of high osmolality in the renal interstitium so concentration of urine is possible
how is solute in inner medulla not washed out by bloodflow?
vasa recta are bent on themselves forming countercurrent exchanger
-slow blood flow (hypoxic environment)
actions of vasopressin/ADH
- insertion of AQP2
- lower threshold lower than thirst threshold
effective circulating volume
-volume that body is actually sensing
=/=ECF when lots of ascites, edema.
Osmolarity calculation
2*Na + Glu/18 + BUN/2.8
Tonicity calculation
2*Na + Glu/18
cause of hypotonicity
Water intake > water excretion
determinants of excretion: Effective blood volume, ADH
regulators of ADH
non-physiologic: pain, nausea, hypoxia, drugs (morphine)
physiologic: low BP, low EABV
Free H2O clearance
Total urine volume = vol of electrolyte free urine (free H2O) + Volume of isotonic saline
Free water clearance = urine vol x (1-(Urine Na + K)/(Serum Na + K))
normal tonicity intracellular vs extracellular
both 290(!)
key point in clinical management of hypotonicity
go slow! brain has defense mechanisms. If you correct too rapidly will –> herniation
normal GFR
~144 L/D
Principles of Tx for hypotonic hyponatremia
- Treat Sx not #s. When PNa central pontine myelinolysis
- Hypovolemic: give volume (saline)
- euvolemic: correct underlying disorder. Restrict water. block ADH
- Hypervolemic: Treat underlying disorder. Water Restrict. Block ADH.
basic causes of hypertonicity
- increased plasma concentrations of one or more effective osmototic solutes (sodium, glucose, mannitol etc)
- ICF volume contraction (cellular dehydration)
physiologic responses to hypertonicity
- ADH release
- thirst
therapeutic implications of hypertonicity
- time course of organic osmolytes is unknown
- danger of cerebral edema (with herniation) if correction is too rapid
- correct hypertonicity, especially chronic, slowly (over days not hours)
How can you determine total body Na content?
- Physical exam!
- Urine volume, gravity, osmolality, electrolytes
- Blood urea, nitrogen, creatinine
causes of euvolemic hypernatremia
-Extrarenal water losses + water intake deficit
-renal water losses + water intake deficit
-Primary hypodipsia
NB losing water is still euvolemic because a very small amount comes from intravascular compartment
Tx euvolemic hypernatremia
- Replace water deficit (oral/D5W)
- Correct slowly to prevent cerebral edema
hypovolemic hypernatremia pathogenesis and causes
Loss of Na leads to ECF volume depletion
Loss of water in excess of Na leads to hypernatremia
Insufficient water intake often exacerbates
Causes: Diuretics, osmotic diuresis (e.g. diabetes mellitus). GI loss, cutaneous loss.
hypovolemic hypernatremia Tx
- Saline First!! Restore volume
- slowly correct hypernatremia, prevent cerebral edema
Hypervolemic Hypernatremia causes and cosequences
- Often Iatrogenic (hypertonic Na-containing fluids). Sea water/powdered milk ingestion.
- Acute ECF/IV volume expansion
- Acute pulmonary edema
- Acute ICF volume contraction (neuro)
- life-threatening emergency!
Tx hypervolemic hypernatremia
- first: stabilize CV system
- then correct hypernatremia
Hyperosmolar hyperglycemic non-ketosis
-complication of uncontrolled diabetes
-older pts, relatively prolonged period of polyuria and secondary polydipsia, may have no history of diabetes, many precipitating factors (pancreatitis, steroids, infection)
-Lx: severe hyperglycemia, no ketosis
Phase 1: hyperglycemia/hyponatremia
Phase 2: osmotic diuresis. hypertonicity.
Phase 3: continued Na and H2O depletion. hypertonicity and ICF contraction, hypernatremia
Tx: Don’t give insulin! will contract the ECF and –> shock. Give salt, then insulin.
-Hyperglycemia is essentially masking the severity of volume depletion.
Calculating PNa in hyperglycemia
PNa decreases 2.4 mEq/L per 100 mg/DL increase in Pgluc
Use “corrected PNa when calculating water deficits in HHNK
Diuretics pharmacokinetics
- most are protein-bound so are not filtered (not dependent on GFR)
- travel through the peritubular capillaries to the cell of action (require RBF)
- Secreted by active movement into the target cell through specialized transporters
- dependent on tubular secretion, not GFR
carbonic anhydrase inhibitors
- block CA, inhibiting 85% of HCO3
- osmotic diuresis, but not great natriuresis
- Also promotes K+ excretion (by charge balance in distal tubule)
- Correction of metabolic alkalosis, altitude sickness, glaucoma (not working via kidney). Occasional last-ditch for hyperkalemia
Loop diuretics
- block NKCC
- natriuresis (blocking Na reabsorption in TAL)
- increased Ca2+ excretion because accumulation of K+ in lumen (+) normally drives Ca2+ absorption. Inhibition of NKCC dissipates (+) in lumen.
- furosemide, bumetanide, torsemide, ethacrynic acid
- used to correct Na retention (PE, CHF, renal failure), hyperkalemia, hypercalcemia (sometimes)
- side effects: hypokalemia, hypocalcemia, hypomagnesemia, hyperuricemia–> gout, ototoxicity, sulfa allergy (but no ethacrynic acid)
- braking phenomenon: compensation by other Na reabsorption sites. Return to steady state, but TBW, TBNa are still less than they were before.
thiazide diuretics
- blocks Na/Cl cotransporter in DCT.
- Increase Ca++ reabsorption (BIG CONTRAST TO LOOP DIURETICS)
- increase K+ secretion
- less potent than loop diuretics
- 1st line therapy for HTN. Can be used in combination with loop, but have to be really careful.
- Can be used for hypercalciuric stone disease
- hypokalemia, hyponatremia, hyperuricemia, impaired insulin release(!)
- Relative to loop, have higher risk of hyponatremia, because loops diuretics dissipate medullary gradient and decrease effectiveness of ADH. But loop still more dangerous because so much more potent
K+ sparing diuretics
- Word on cortical Collecting duct principle cells.
- either block ENaC or Aldosterone
- Net effect is inhibition of Na+ reabsorption leading to modest natriuresis and reduced K+ secretion.
- Can be used in combination with loop diuretics to reduce risk of hypokalemia
spironolactone
- K sparing diuretics
- Does not require tubular secretion and works relatively low EABV
- impact mortality in CHF
- use in cirrhosis
- anti-proteinuric effect
- gynecomastia
osmotic diuretics
nonreabsorbable substances. No direct effect on Na transport, but some modest natriuresis
antidiuretic antagonsists
- Block ADH receptor
- Prevents aquaporin II insertion into luminal membrane in collecting duct.
- generates water diuresis
- demeclocycline
response to K+ load
- rapid uptake into ICF, slow release into ECF and renal excretion.
- prevents increase in PK
- accomplished by Na/K ATPase
hormones influencing plasma K
insulin, catecholamines, aldosterone
non-hormonal factors affecting internal K balance
exercise, plasma tonicity, acid-base balance (intracellular H+ disrupts K+ transporters and displaces some K), cell lysis
Internal K balance
-balance between ECF/ICF K
External K balance
-balance between intake/excretion of K
Renal K Handling
PT reabsorbs ~80%
TAL reabsorbs ~10% (NKCC)
If K normal/high, 20-180% secreted in DCT/CT (can exceed filtered load)
If K low, another 2% reabsorbed in DCT/CT
K handling in CT and OMCD
alpha intercalated cell: Potassium absorbing! with H+/K+ antiporter absorbs K and secretes H
Principal cells: Potassium secretory! with luminal K+ channel and K+/Cl- cotransporter
Depending on long-term K intake, will have different balance of principal/intercalated cells
factors affecting distal nephron K secretion
- Aldosterone: stimules excretion
- K flow: more distal flow of filtrate, get MORE K secretion (more flow –> more Na+ reabsorption –> greater driving force for K+)
- Poorly reabsorbable anions: bicarb, sulfate, drugs. Make lumen potential even more (-) –> greater driving force for K+ excretion
general acid-base balance in body
in: metabolism, dietary (> for meat-eaters)
out: lungs (CO2), kidneys (H+)
calculating pH in a buffer system (henderson-hasselbach)
pH = pK + log ([Buf-]/[H-Buf])
Total CO2
HCO3- + dissolved CO2 (not a lot)
acidemia vs acidosis
acidemia = low pH
acidosis (and alkalosis) are processes that tend to raise or lower pH. Can have numerous going on simultaneously
Body Buffers
- ECF: H+ + HCO3 H2CO3 CO2 + H2O. Also plasma proteins, phosphates
- ICF: hemoglobin (RBCs), proteins, inorganic phosphate
- Bone: large buffer reservoir. NaHCO3, KHCO3, etc
CO2 behaves as an acid in aqueous solution?
CO2 + H2O –> H2CO3 (slow
H2CO3 –> H+ + HCO3- (fast)
H-H Equation and calculating blood pH
-pH = 6.1(pK) + log([HCO3]/[pCO2])
-[H] = K([pCO2]/[HCO3])
[H] = 24([pCO2]/[HCO3])
regulation of bicarb buffer system
- HCO3 tightly regulated by kidneys
- pCO2 regulated by lungs (open buffer system)
- Ratio of HCO3 to pCO2 determines pH!! so lungs can hyperventilate to lower PCO2 to mitigate drops in pH.
metabolic H+ prodution
- volatile (CO2) from metabolism of CHO, fat, neutral AAs (200-300 mmoles/kg-day)
- non-volatile (fixed) from metabolism of inorganic acids, cationic AAs, organic acids (1mmole/kg-day)
- oxidation of anionic amino acids and organic anions –> base. in balance, metabolism produces acid.
defense against increased H+ input
- acidosis suppresses rate of endogenous organic acid production
- buffering
- ventilation (CO2)
- renal H+ excretion (slow response)
met/resp alkylosis
high/low pCO2 –> resp acidosis/alkylosis
low/high bicarb –> metabolic acidosis/alkylosis
kidney’s role in mitigating acidemia
- excrete protons, anions of nonvolatile acids
- reabsorb filtered HCO3
- generate new HCO3
reabsorption of filtered HCO3 in proximal nephron and TAL
- Na+/H+ exchanger and H+ ATPase pump protons into lumen
- react with bicarb to generate H2CO3
- broken down by carbonic anhydrase to H2O + CO2
- CO2 diffuses into cells, reacts with H2O (Carbonic anhydrase) –> HCO3
- HCO3 transported into blood via cotransport with Na and antiport with Cl
factors affecting proximal tubule bicarb reabsorption
- ECF volume status. Angiotensin II stimulate Na/H exchange
- endothelin, catecholamines (alpha). increased with acidosis, stimulates apical membrane Na/H exchange
- PTH. Inhibits apical Na/H
- Serum K. hyperkalemia alkylanizes cell by displacing H+ out
bicarb generation in proximal tubule
- H+ secreted and buffered by non-bicarb buffer (e.g. HPO4)
- generates a bicarb via CAn
reclamation of filtered HCO3 in collecting ducts
- K+/H+ exchanger instead of Na+/H+
- Otherwise same process (CAn etc) as proximal nephron
HCO3 generation in collecting ducts
- same process as in proximal tubule.
- occurs in alpha-intercalated cells
factors affecting distal H+ secretion
- aldosterone. stimulates sodium uptake. males lumen more negative. increases driving force for H+ (and K+)
- transepithelial voltage
- buffer availability
- endothelin
ammonia handling in kidney
-NH4 x 2 generated by metabolism of glutamine
in proximal tubule. transported across luminal membrane by H+ transporters (channel and Na/H exchanger)
-complex process of concentrating in urine
-NH4 metabolized in liver. consumes HCO3. So need to excrete as much as possible so it doesn’t consume HCO3 (why glutamine is metabolized in kidney
-in ammoniagenesis in PT, also generate HCO3 (by alpha ketoglutarate metabolism)
-in chronic metabolic acidosis, increase ammonia excretion. increasing bicarb production.
problems of hyperkalemia
-cell volume, intracellular pH, neuromuscular, cardiac, vascular tone, RMP
pseudohyperkalemia
- in vitro phenomenon
- high K reported, but actual K normal
- hemolysis in vitro
- leukocytosis and thrombocytosis. Can be solved by getting plasma K instead of serum K since plasma is anti-coagulated
- fist clenching during blood drawing
hyperkalemia etiologies
-Too much in (transient): diet, medication (KCl, polycitra-K, K-penicillin)
-too little out (sustained): low GFR, impaired RAS axis (Addison’s, genetic, drugs–diuretics, type IV RTAs), aldosterone resistance (damage to distal nephron, spironolactone, trimethoprim) inadequate distal tubule Na+ delivery and urine flow.
Abnormal internal balance: insulin deficiency, hypertonicity, drugs, rhabdomyolysis, tissue damage, metabolic acidosis
EKG changes with hyperkalemia
peaking T waves in ant. prechordials due to increased repolarization. Prolonged PR interval, then flattening of P waves, ST depression, eventually sine wave VFib
-Progression is unpredictable. Have to aggressively and rapidly treat hyperkalemia when you see ANY EKG changes.
emergency treatment hyperkalemia
- treat first, then figure out why it’s there!
- Emergency Tx: step 1–antagonize EKG changes (calcium gluconate) Step 2–Move K from ECF into cells (insulin + glucose to prevent hypoglycemia, or inhaled beta agonists, ) Step 3–Remove K from body (Loop diuretics, GI cation exchange, hemodialysis)
TTKG
–TransTubular K Gradient
- Assess K secretion in CD, taking out influence of water.
- TTKG = (urine K)/(plasma K) / (Uosm/Posm)
- normal 7-10
- best for assessing hyperkalemia due to hypoaldosteronism (if TTK normally low but corrects with exogenous mineralocorticoid)
management of chronic hyperkalemia
- reduce intake
- review meds
- increase Na intake
- diuretics
- Gi cation exchange
- Fludrocortisone (mineralocorticoid)
causes of metabolic acidosis
- loss of bicarb – renal or GI
- Failure of kidneys to generate bicarb and excrete endogenous acid
- increased generation of endogenous organic acids
- addition of exogenous acid or acid-generator
Anion Gap
- Unmeasured anions - unmeasured cations
- calculated as Na - (Cl + HCO3)
- high anion gap means acid has been added–DKA, alcoholic ketoacidosis, lactic acidosis, toxic ingestions, fasting ketoacidosis, toluene intoxication, kidney failure
Renal Tubular Acidosis
- Proximal – defect in HCO3 reabsorption. Lowers threshold PHCO3 for HCO3 to appear in the urine.
- Distal – defect in acid excretion (HCO3 regeneration). Increased urine pH
- Distal hyperkalemic – defect in acid excretion (ammoniagenesis, acid excretion, aldosterone resistance, drugs e.g. heparin)
lactic acidosis
lactic acid levels reflect balance of NADH/NAD
- Type A–relative hypoxia shock (septic, cardiogenic), severe hypoxemia, CO poisoning, severe anemia.
- Type B–compromised lactate metabolism: Liver disease, thiamine deficiency, alcohol, drugs, seizures, metabolic defects
Ketoacidosis
- absent insulin (or in starvation/alcoholism), unregulated metabolism of FFA –> acetyl CoA –> Acetoacetic acid + beta-butyric acid
- increases anion gap
Methanol and Ethylene glycol poisoning
- methanol metabolized by ADH to formic acd
- ethylene glycol metabolized to glyoxylic acid
- Can treat with ADH inhibitors to allow for excretion before development of acidosis
Osmolar gap
- difference between calculated and measured plasma osmolarity
- high osmolar gap suggests presence of osmolar particle not included in calculation (Na, BUN, Glucose). Commonly ethanol, can be other toxins.
d(Anion Gap)/d(HCO3)
- adding organic acid (e.g. lactate) should increase anion gap and decrease HCO3 by the same amount.
- A mismatch between d(anion gap) and d(HCO3) could mean there is more than one acid-base disturbance e.g. acidosis superimposed on alkalosis.
clinical features metabolic acidosis
- kussmaul respiration
- hemodynamic compromise
- hyperkalemia
- musculoskeletal manifestations (chronic)
compensation for acid-base disorders
- compensation is NOT a second disorder (not an “…osis”)
- THERE IS NEVER OVERCOMPENSATION. If it appears that there is, then there is another primary acid-base disorder
- can predict expected compensation reasonably- well
Therapy for metabolic acidosis
- treat the underlying cause–in most cases it is the underlying process, not the acidemia, that proves fatal
- When severe (pH <7.1-7.2) buffering capacity is limited
- Oral or IV NaHCO3–but risky. (overshoot alkalosis, CSF acidosis)
