Urinary System Midterm Review

• potassium secretion (CCD)
• hydrogen ion secretion (CCD)
• sodium reabsorption (CCD)

effective renal plasma flow

• ~13% of US pop. has CKD
• most in stage 3/5
• most in E coast and South

• urea
• uric acid
• creatinine
• urobilinogen
• (drugs)
• (chemicals)

• blood pressure
• volume status
• osmolality
• ion balance (Na, K, etc.)
• pH
• gluconeogenesis

• erythorpoietin
• 1,25-dihydroxy Vit. D
• renin

nephron: renal medulla

risk: papillary necrosis; acute tubular necrosis

• ischemic renal disease
• activation of renin-angiotensin system --> HTN

• vasa recta and Loop of Henle --> countercurrent system
• -hairpin shape
• -slow blood flow

• podocyte epithelium with diaphragms
• basement membrane
• fenestrated capillary endothelium (w/ glycocalyx)

• 1. filtration
• 2. reabsorption
• 3. secretion

• fractional excretion = % of filtered substance in urine
• FE of water = 1%
• FE of Na = 0.5%

• majority of filtrate "loss": reabsorption
• diuretics --> secretion
• PCT: reabsorption

• glucose: 0%
• urea: ~50%
• penicillin: 100%

• water (65%)
• sodium (65%)
• potassium (65%)
• HCO3 (80-90%)
• Calcium (80%)
• phosphate (90%)
• glucose (100%)
• uric acid (90%)

• cations: creatinine, drugs (tremethoprim, cimetidine)
• anions: hippurate, drugs (diuretics, penicillin, cephalosporins, salicylates)

• ammoniagenesis (from glutamine, utilizes Na-H antiporter into tubule)
• calcitriolgenesis (i.e. 1,25(OH)Vit. D generation)

• stimulates adenosine release --> stimulates smooth muscle cells of afferent arteriole
• vasoconstriction --> decreased capillary hydrostatic pressure
• decreased RBF, decreased ultrafiltration

• macula densa senses low Cl- concentration --> PGE2 release
• decreased baroreceptor stretching
• increased sympathetic tone from hypotension

• Cl- concentration in DCT
• DCT flow

Mg

fine tuning of Ca2+ concentration

thiazide-sensitive NaCl cotransporter (regulated by PTH and calcitriol)

principal cells: secrete K via ROMK hannels

intercalated cells: secrete H+ via H-ATPase

• ADH inserts aquaporin 2 channels into tubule membrane
• stimulates water reabosrption in MCD

Medullary collecting duct

• ultrafiltration
• -convective transport
• -semi-permeable filtration barrier
• -"solvent drag"
• -Starling forces

NOT a series of filtration (i.e. not a strainer/colander)

• freely filtered:
• <7,000 MW
• water
• electrolytes
• aminoacids
• monosachharides
• higher FE

• NOT freely filtered:
• >7,000 MW
• small molecules not bound to large proteins
• large proteins (e.g. albumin)
• cells
• lower FE

• Kf: filtration coefficient = permeability x surface area
• hydrostatic pressure of capillary
• oncotic pressure of capillary
• hydrostatic pressure of Bowman's space
• oncotic pressure of Bowman's space (~0)

• capillary hydrostatic pressure: increases
• renal blood flow: decreases
• net ultrafiltration pressure: increases

• capillary hydrostatic pressure: decreases
• renal blood flow: increases
• net ultrafiltration pressure: decreases

• capillary hydrostatic pressure: decreases
• renal blood flow: decreases
• net ultrafiltration pressure: decreases

• capillary hydrostatic pressure: increases
• renal blood flow: increases
• net ultrafiltration pressure: increase

perfusion pressure: 90-200mmHg

• constircts the efferent arteriole more than the afferent arteriole
• increases capillary hydrostatic pressure
• increases GFR

• constricts the efferent arteriole as much as afferent arteriole
• decreases capillary hydrostatic pressure
• decreases GFR
• maintains BP
• systemic vasoconstrictor
• increases aldosterone secretion
• increases ADH secretion
• increases thirst

RBF = 20% of cardiac output = volume/time

RPF = RBF x plasma volume = RBF x (1-hematocrit)

normal RPF = 600 mL/min

GFR = filtration fraction x RPF = ~20% x RPF

normal GFR = 125 mL/min

• fluid balance
• electrolyte balance
• acid-base-balance
• elimination of metabolic products

defective GFR --> edema

clinical sign of volume overload

can be caused by defective GFR

• renal function
• i.e. how well are kidneys filtering plasma

• stool
• metabolism into an inactive form
• renal clearance (i.e. kidney excretion)

• GFR
• RPF
• (measurements depend on substances)

• entirely passive process --> no ATP demand
• filtrate: ~180 L/day
• urine: ~2 L/day
• dependent on Starling forces

clearance method: meaure clearance rate of certain substance with certain qualities

substance: freely filtered, constant/stable plasma level, not metabolized, not reabsorbed, not secreted

creatinine clearance*: freely filtered and not reabsorbed but some secretion --> clinical GFR

• 1. eyeball
• 2. 24 hr rine collection --> creatinine clearance
• 3. lothalamate clearance (research)
• 4. Cockcroft-Gault Equation
• 5. MDRD Equation

• males: 20-25 mg/kg of body weight
• females: 15-20 mg/kg of body weight

• GFR clearance: substance NOT secreted
• RPF clearance: substance completely secreted

• renal clearance: substance freely filtered and not reabsorbed but completely secreted
• amount delivered to kidney = amount excreted

substance: PAH (para-aminohippurate)

not useful clinically like GFR is

• muscle mass
• renal function: GFR
• (drugs/medications)

if GFR >55 mL/min: large change in clearance relates to small change in serum level

if GRF <55 mL/min: small change in clearance relates to large change in serum level

i.e. GFR dysfunction has exponential relationship to serum creatinine concentration

• inadequate collection
• overestimates of GFR at lower levels because of creatinine secretion

variables: age, sex, serum concentration, weight

• pros:
• used for drug dosing
• measures creatinine clearance

• cons:
• may overestimate GFR in obese/edematous
• does not measure GFR

variables: serum creatinine, age, sex, +/- African American

• pros:
• measures GFR (iothalamate clearance)
• weight not a variable
• measures steady state creatinine
• works well at low levels of renal function

• cons:
• based on biased study (mostly whites, no diabetics, avg GFR 40 mL/min)
• does not measure acute renal failure
• inaccurate at high levels of renal function
• not valid for body extremes (e.g. <18yo, >70yo, pregnant women, obsese, starved, amputees)
• not valid for Asians

(requires 2+ GFR measurements 3mo apart)

• I/II: proteinuria, hematuria (GFR: >60 mL/min)
• III: complications possible (GFR: 30-60)
• IV: complications iminent (GFR: 15-30)
• V: renal replacement therapy (GFR: <15)

ECV = plasma volume + interstitial volume

• plasma volume = 5% of body weight
• interstitial volume = 15% of body weight

• TBW = 60% of body weight (men)
• ICV = 40% of body weight
• ECV = plasma + interstitium = 20% of body weight

ECV volume changes = increases/decreases in water and sodium concentrations

• ICV volume changes = increased/decreased movement of water between ECV and ICV
• i.e. based on osmolarity of ECV

plasma sodium levels reflect free water status (i.e. osmolality)

plasma sodium levels do NOT reflect total body sodium concentration

analysis of the ECV

history and physical exam

increased sodium intake --> increased sodium in ECV --> increased ECV osmolality

• increased ECV osmolality --> increased movement of water from ICV to ECV
• i.e. ECV swelling and ICV shrinkage

• - increased BP
• - increased central venous pressure
• - increased edema

decreased sodium intake --> decreased sodium in ECV --> decreased ECV osmolality

• decreased ECV osmolality --> increased movement of water from ECV to ICV
• i.e. ECV shrinkage, ICV swelling

• - decreased BP
• - orthostatic hypotension
• - increased HR

• albumin in plasma
• sodium in plasma

• capillary hydrostatic pressure increases
• edema (lower extremeties)

• capillary Oncotic pressure decreases (decrease in plasma albumin)
• edema (face, upper exteremities)

• increased central venous pressure (JVP)
• edema and anasarca (i.e. extreme generalized edema)
• fluid in lungs (i.e. pulmonary edema)
• increased transcellular space (e.g. ascites, pleural effusion, etc.)

• causes:
• hemorrhage
• vomiting
• diarrhea

• effects:
• low blood volume (weakess, diziness, orthostasis, nausea)
• insufficient blood volume (orthostatic hypotension)

water levels in body

• dilute urine reflects hypernatremia
• concentrated urine reflects hyponatremia

• water not reabsorbed into blood vessel: dilute urine
• increased plasma sodium levels: hypernatremia

• excessive intake
• increased ADH influence (e.g. SIADH)
• increased reabsorption of water from kidneys

• decrease in plasma volume (e.g. hemorrhage)
• baroreceptors signal posterior pituitary

decreased ECV osmolarity --> ICV swelling --> cells swell

• neuron damage
• brain compression within cranium
• intracranial swelling --> death
• chronic: loss of electrolytes, osmolytes, ICV osmolarity decreases

• intracranial swelling and neuron damage:
• headache
• confusion
• coma
• convulsions

slowly: avoid neurological consequences from rapid swelling/shrinking of neurons --> demyelination

• slowly increase osmolarity of ECV --> increase sodium intake (<12 mEq/L)
• restrict free water intake

• treat with IV saline to increase plasma volume without increasing osmolarity --> stops ADH release
• (often plasma sodium will slowly increase on own)

• osmotic demyleination
• central pontine myelinosis

• dehydration
• increased water loss with age (skin, lungs, kidneys)
• decreased water reabsorption

hypernatremia does not reflect an increase in total body sodium

therefore, BP and edema levels are unaffected

increase in plasma osmolarity --> increase in ECV osmolarity --> water moves out of ICV

ICV shrinkage --> neurologic confusion

neurological symptoms (e.g. confusion)

yes

low ECV treated with free water

• sodium intake
• angiotensin II
• aldosterone
• sympathetic nervous system
• natriuretic peptides (ANP, BNP, dopamine)

• 1. sodium reabsorption (renal tubule)
• 2. sodium retention (low GFR, high angiotensin II, activation of sympathetic NS, high aldosterone)

based on intravascular volume, cardiac output, and vascular capacitance

• abstract term that refers to the adequacy of the arterial blood volume to "fill" the capacity of
• the arterial vasculature.

Normal EABV exists when the ratio of cardiac output to peripheral resistance maintains venous return and cardiac output at normal levels

• reduce actual arterial blood volume (e.g. hemorrhage, dehydration)
• increase arterial vascular capacitance (e.g. cirrhosis, sepsis)
• reduce cardiac output (e.g. congestive heart failure)

• reduced renal blood flow --> triggers macula densa --> renin release -->--> sodium retention in CCD
• stimulates ADH release

• stimulates sodium retention mechanisms
• ADH released

• increased GFR
• dopamine (acts on PCT)
• natriuretic peptides (e.g. ANP, BNP) (act on CD)

• medullary concentration gradient:
• sodium exits ascending LOH
• urea exits CD

increase sodium reabsorption from renal tubule

stimulate ADH --> increase water reabsorption from the CD tubule

• no:
• pressure higher at beginning
• pressure very low in venules (where much of interstitial fluid is reabsorbed)

• local factors (e.g. venous obstruction, lympyhatic obstruction)
• heart failure (diastolic and systolic)
• cirrhosis
• kidney disease (e.g. volume overload, nephrotic syndrome)

• (forward)
• heart failure: decreased cardiac output --> decreased EABV --> sodium retention mechanisms activated

• (backward)
• heart failure: increased right atrial pressure --> increased central venous pressure --> increased capillary pressure

• i.e. "forward" heart failure --> --> sodium retention --> edema
• i.e. "backward" heart failure --> --> increased hydrostatic pressure --> edema

1. glomerular injury --> proteinuria --> decreased serum protein --> decreased capillary oncotic pressure --> edema

2. glomerular injury --> increased sodium retention --> edema

• treat underlying cause
• salt (NaCl) restriction
• mechanical measures (e.g. compression hose, limb elevation)
• diuretics (i.e. block Na reabsorption)

• 1. carbonic anhydrase inhibitors: PCT
• 2. osmotic diuretics: PCT (and other places)
• 3. loop diuretics: LOH
• 4. thiazide diuretics: DCT
• 5. K-sparing: CCD

• case by case
• observe: watch for marked diuresis 2-4 hours post-dosage

suspect diet very high in sodium

• 1. general factors (e.g. sodium intake, compliance, NSAID interaction)
• 2. renal impairment
• 3. nephrotic syndrome

• decreased GFR
• decreased number of funtioning nephrons
• impaired secretion

• binding of free drung in lumen
• increased volume distribution
• tubular resistance

• diet: sodium restriction
• discuss compliance
• bedrest: increases diuretic effect with severe edema
• adjust loop diuretic: increase dosage to threshold, decrease sodium retention rebound, switch to IV
• additive measures: use different types of diuretics to effect more of tubule
• IV albumin infusion

• 98% intracellular
• vast majority in muscle cells (least in plasma)

intracellular/extracellular potassium levels determine resting membrane potential (i.e. excitability)

Na-K-ATPase pump: 3Na out, 2K in

• if K+ stays only in ECV:
• ECV potassium concentration increases
• increased K+ uptake by cells
• increased urinary K+ excretion

• beta-agonists (e.g. epinephrine)
• insulin
• high plasma pH (i.e. alkalosis)

• low plasma pH (i.e. acidosis)
• osmolality
• beta-adrenergic blockers

• 1. directly stimulate Na-K-ATPase pump
• 2. inhibits effect of (thiazide) diuretics (i.e. decreases K+ secretion effect of thiazide diuretics)

1. prevents cellular uptake of K+ (via Na-K-ATPase pump?)

• beta-adrenergic blockers
• low plasma pH (i.e. acidosis)
• osmolality

• beta-agonists (e.g. epinephrine)
• insulin
• osmolality
• high plasma pH

low plasma pH (acidosis) --> K+ out of cell --> increase net positive charge

high plasma pH (alkalosis) --> K+ into cell --> decreses net positive charge

K+ secretion into renal tubule (post-filtration and post-reabsorption)

• TAL (NKCC)
• DCT: principal cells (Na-K-ATPase pump)
• CCD: principal cells: aldosterone (Na-K-ATPase & Na/K channels), distal flow of Na/H2O, plasma K+

aldosterone --> increases K+ secretion in CCD

• 1. increase # of Na/K channels in apical membrane of principal cells
• 2. increases activity rate of basememnt membrane Na-K-ATPase pumps

• low sodium diet
• low BP
• increased renin secretion
• increased plasma angiotensin II

• increased K+ intake
• hyperkalemia
• acidosis

• increased tubular sodium reabsorption (kidney CD)
• increased K+ secretion (principal cells CD)

distal flow of Na/H2O --> increased sodium flow to CCD lumen --> increased uptake by principal cells

increased cellular sodium uptake --> increased K+ secretion

• 1. increased aldosterone release
• 2. increased K+ movement into lumen
• 3. increased activity of Na-K-ATPase in principal cells

cortical collecting duct of distal nephron of kidney

increased sodium reabsorption --> increased K+ secretion into lumen (Na-K-ATPase basement memb.) --> increased (-) charge in lumen

• DCT: secretion of K+ --> reabsorption of K+
• CCD: high secretion of K+ --> low secretion of K+

No

• dual effect counteracts itself:
• 1. increased sodium flow to distal nephron --> increased K+ secretion
• 2. high sodium --> high BP --> decreased aldosterone --> decreased K+ secretion

hyperkalemia: K+ efflux --> less (-)/more (+) --> lower threshold --> more excitable

hypokalemia: K+ influx --> more (-)/less(+) --> higher threshold --> less excitable

• muscle weakness (skeletal and cardiac)
• changes in heart rate
• bradyarrhythmias
• sharp/peaked T waves
• prolonged QRS
• loss of P waves
• sine waves on ECG (pre-death)

• 1. intake
• 2. shift
• 3. excretion

• serum K+ > 6mmol/L
• rate rise
• acidosis
• hypoxia
• hyperglycemia
• cell breakdown
• drugs (e.g beta-blockers and digoxin inhibit Na-K-ATPase)

• cell breakdown
• hemolysis
• leukocytosis

• muscle weakness
• fatigue
• constipation
• ventilatory failure
• cardiac arrhythmias
• rhabdomyolysis (breakdown of muscle fiber)
• polyuria

• heart failure
• volume depletion (intense)
• decreased sodium intake

• NSAID
• beta-blockers

renin inhibitors (e.g. aliskiren)

ACE inhibitors (e.g. lisinopril)

• heparin
• cyclosporin
• lacrolimus
• spironolactone
• eplerenone
• aldosterone agonists

angiotensin receptor (AT1R) blocker (e.g. losartan)

• amiloride triampterene
• trimethoprim pentamidine

• causes:
• adrenal insufficiency (e.g. Addison's disease)

• tx:
• hormone replacement: mineral- & gluco-corticoids
• hydrocortisone

• hyperkalemia
• low BP
• hyponatremia
• weight loss
• pigmentation
• increased ACTH

acidosis

• causes:
• renin is suppressed because of interstitial disease and hypervolemia
• renal impairment
• diabetic nephropathy
• associated metabolic acidosis (Type IV RTA)

• tx:
• loop diuretics (e.g. lasix)
• fludrocortisone

• drugs (e.g. K-sparing diuretics, trimethoprim, pentamidine)
• tubulo-interstial disease
• (rare) genetic abnormalities

• intake
• shift (e.g. hyperglycemia, acidosis, drugs, cell breakdown)
• decreased nephron # (e.g. renal failure)
• decreased aldosterone action (e.g. primary hypoaldosteronism, hypo-renin hypoaldosteronism, aldosterone resistance, trimethoprim, pentamidine, K-sparing diuretics, tubulo-interstitial disease, genetic disorders)
• decreased distal Na/H2O flow (e.g. hypovolemia, heart failure)

• 1. stabilize (IV Ca2+ gluconate)
• 2. temporary shift (insulin, beta-agonist, albuterol nebulizer, sodium bicarbonate)
• 3. remove K+ (loop diuretic +/- fludrocortisone, ion exchnage resin for GI, Kayexalate, dialysis)

No

metabolic alkalosis

• beta2-agonists (e.g. albuterol, catecholamines)
• alkalosis
• periodic paralysis (e.g. thyrotoxicosis)
• increased K+ excretion (e.g. diarrhea, vomiting, hyperaldosteronism)

vomiting --> loss of H+ --> alkalosis --> more flow of NaHCO3 --> more K+ secretion

vomiting --> volume depletion --> low BP --> increased aldosterone --> more K+ secretion

diuretics (especially loop diuretics and thiazide diuretics)

• increase distal flow of NaCl --> increase K+ secretion
• volume depletion --> increased aldosterone --> increased K+ secretion

loop diuretics: directly stimulate renin by blocking NKCC in macula densa (i.e. illusion of low flow)

net effect of loss of base (i.e. loss of base or addition of acid)

e.g. diarrhea (loss of bicarbonate)

• 1. ventilation : CO2 control
• 2. kidneys: regeneration of HCO3 buffer by excreting acid

• 1. arterial blood gas (ABG)
• 2. anion gap
• 3. delta/delta (mixed acid base disorders)
• 4. identify underlying causes

• 1. what is the arterial pH?
• 2. what is the serum HCO3?
• 3. check arterial PCO2
• 4. compensatory responses: baseline never achieved with compensation
• -lungs: quick compensation (minutes)
• -kidneys: slow compensation (days)

salicylate toxicity (e.g. aspirin)

• lactic acidosis
• ketoacidosis
• renal failure
• poisoning (e.g. methanol, ethylene glycol, aspirin)

• GI HCO3 loss (e.g. diarrhea)
• renal tubular acidosis

• hypotension
• tissue ischemia
• lactate levels (e.g. exercise)

• diabetes
• hyperglycemia
• serum/urine ketones
• starvation
• alcoholic ketoacidosis

metabolic alkalosis

net loss of acid

• volume depletion (e.g. vomiting, diuretics)
• volume expansion (e.g. hypertension)
• hyperaldosteronism --> increased H+ secretion, increased Na/H2O flow

first: treat more critical condition of hypokalemia

• volume replacement (normal saline)
• K+ replacement

angiotensin II

PgE2

NSAID

• physiologic stress (e.g. pain, nausea, etc.)
• increased osmolality
• SIADH
• decreased EABV
• volume depletion
• edema (e.g. CHF, cirrhosis, nephrotic syndrome)

hyperkalemia