ICS Objectives for Renal and Male Repro-2009-2010
The parts of the syllabus containing the Cases (ICS) we covered in conferences will have the (case # and conference #) in green.
Normal Values of Laboratory Tests & Renal Physiology (pgs 1-2)-Kasinath
Renal Physiology (pgs 3-18)-Kasinath
1) overview of the functions of the kidney
1) Excretion of: waste products, acid, water
2) Reabsorption of: solutes, bicarbonate, water
3) Secretion of substances: Uric acid, Penicillin, Salicylates
4) Endocrine Functions: secretion of EPO and rennin, conversion of 25(OH) vit D3 to 1:25(OH)2 vit D3
2) Process and regulation of glomerular filtration
Ultrafiltration of plasma at the glomerulus-glomerular capillary wall has size-selective and charge selective barrier preventing loss of plasma
proteins. (nl protein excretion~150mg/24hrs)
Clearance: UV/P (U=[urinary] V=volume of urine P=[plasma])= volume of plasma from which the substance is totally removed by glomerular
filtration. According to the definition then, the amount excreted (UxV)= amount filtered (PxC)
Transcapillary hydrostatic pressure difference: ∆P=Pgc-Pt (gc=glomerular capillary t=tubule)
Transcapillary oncotic Pressure difference: ∆∏=∏gc-∏t
GFR decreased by: ↓ capillary wall area or permeability (glomerulonephritis), Hypotension (↓Pgc↓ sngfr), Obstructive uropathy
(↑Pt↓sngfr), ∆vascular resistance or RPF ∆Pgc∆SNGFR
RPF: 25% of CO per minute. Kept stable by autoregulation,
FF: proportion of RPF that forms the glomerular filtration rate=GFR/RPF x 100 (nl 20-25%)
3) Endocrine functions of the kidney including the renin-angiotensin system
EPO: secreted by tubulointerstitial cells ↑ RBCs
25(OH) vit D3 converted to 1:25 (OH)2 vit D3 by proximal tubules ↑ absorption of Ca and Phosphorous in the gut
RAAS system: juxtaglomerular apparatus includes renin secreting juxtaglomerular cells in the afferent arterioles, extraglomerular mesangial
cells, and columnar epithelial cells of distal tubule.
Renin (RAAS): converts (cleaves) angiotensinogen to angiotensin I. ACE removes 2 AA from ATI to form ATII. ATII vasoconstrictor ↑
BP. Also ATII stimulates secretion of aldosterone and direct stimulation of Na transport in the early PT Na Reabsorption followed by H20
reab (so no overall change in [Na]↑BP. ATII causes ↑ADH release, and ↓ GFR causing ↑ Na reab.
Aldosterone: ↑ Na and K channels in collecting duct ↑ reab of NaCl and secretion of K (↑ plasma K+ causes aldo release).
4) Physiologic handling of Na by the kidney
Proximal Tubule: Nearly 65-70% of filtered Na and H2o are reabsorbed here. Pay attention to the Na-H+ exchanger-isoform 3 (antiporter).
TUBULAR LUMEN PROX TUBULAR EPI CELL CAPILLARY
• Tubular fluid is iso-osmotic as it leaves the proximal tubule.
K+ K+ • Carbonic Anhydrase and Osmotic diuretics work in this
Na+ Na+ Na/K Na+ portion.
H+ H+ ATPas
Base Base Base Base
- - - -
Loop of Henle: active and passive Na and Cl Reabsorption. ~25% of Na reabsorbed here. Transport via the electroneutral Na+, K+, 2CL-
transporter. Descending limb is not permeable to Na so filtrate gets concentrated. The ascending limb less permeable to H2o so filtrate becomes
diluted (50-60mOsm) compared to plasma (300mOsm) “major diluting segment” (loop diuretics: furosemide work here)
Distal Convoluted Tubule: 5-8% of Na Reabsorption in electroneutral manner by NaCl co-transporter. Relatively H2o impermeable. (thiazide
diuretics acting on the NaCl transporter work here).
Collecting Tubules: 2-5% of Na reab. Final site of Na regulation, Contain principal cells and type A and B intercalated cells. Principal cells are
sensitive to mineralocorticoid and aldosterone (1)↑ Na reab via ENaC (principal cells) 2)↑ Na-K ATPase in basolateral membrane (principal
cells) 3)↑ K secretion by principal cells by K channel in apical memb (principal cells) 4) ↑ secretion of H+ by ↑ H+ATPase in apical memb
(type A intercalated cells) (spironolactone, triamterene, and amiloride interfere w/ Na Reabsorption here)
TUBULAR LUMEN PRINCIPAL CELL CAPILLARY
Urinary [Na] <20mEq indicates need for Na conservation by the kidney. Prerenal azotemia (<20-kidney function is normal) Acute Tubular
Necrosis (Na >20)-direct damage to the kidney.
5) Physiologic handling of H2o by the kidney
Kidney is the major water regulator of TBW content.
Urinary dilution requires: 1) Adequate GFR 2) Intact function of the water-impermeable “diluting segment” 3) ADH secreted by the supraoptic
and paraventricular nuclei of the hypothalamus. (binds V2 recepror in collecting duct basolateral membrane Camp releaseact
PKAphosphorylation of aquaporin 2 fuses w/ apical membraneH20 reabsorption. In absence of ADH the collecting duct is impermeable
to H20dilute urine (minimal urine osmolality is 50-60mOsm/kg)
Diabetes Insipidus: lack of ADH action. Central DI: Lack of ADH production. Nephrogenic: resistance of renal tubules.
• 60-75% of filtered H20 is reab w/ Na in proximal tubule.
• Descending limb: water leaves but no NaCl
• Ascending limb: H20 impermeable but NaCl permeable-dilution
• Collecting tubules: permeability of H20 is under ADH control.
Total urine volume (V): osmotic clearance (Cosm) + free water clearance
• Cosm=Uosm/Posm xV
• Ch2o=V-Cosm (+Ch20=excretion)(-Ch2o=reabsorption)
6) Overview of urinary acidification
TUBULAR LUMEN PROXIMAL TUBULAR CAPILLARY LUMEN
Nearly 70-80% filtered Hco3 is reabsorbed
H+ secretion is primary event that leads to Hco3 reab
H+ + HCO3- HCO3
CO2 + H2O ANHYDRASE
CO2 + H2O
TUBULAR LUMEN COLLECTING DUCT TYPE A CAPILLARY LUMEN
HPO-4 HCO-3 Remaining 20-30% of hco3 is reabsorbed
3 Apical H+ATPase H+ secretion is primary event
Aldosterone ↑ the ATPase activity
H+ATPase H+ + HCO3- H+ secretion creates luminal pH of 4.5-5.0
NH4 H2PO4 H2CO3
More H+ secretion occurs in this segement
producing more Hco3 then is initially
H2CO3 filteredrepairs base deficit created by Hco3
buffering of acid created by metabolic processes
CO2 + H2O H2PO4 traps H+ and ensures secretion from
RTA type I: inability to generate steep H+ gradient in distal tubuleshypokalemia and ↓ ammonium secretion, and hyperchloremic metabolic
acidosis. (Sjogrens, SLE, Ampho-B)
RTA type II abnormal H+ secretion in Proximal tubulesimpaired reab of filtered HCO3maximally acidified urine in academia,
hypokalemia, Hyperchloremic metabolic acidosis. (acetazolamide, MM, Wilsons disease)
7) Short review of handling of Ca and K by the kidney
Calcium: either ionized, complexed w/ ions, or protein bound (not filtered). Nearly 70% reab in PT and 20% in TAL. Reab is passive and
dependent on Na reab. 5-10% reab in DT by active process tim by PTH and Vit D.
Potassium: freely filtered and 90% reab by PT & ascending loop. Reab not regulatable so excess K gets secreted in CD and is controlled by
Sodium Metabolism (pgs 19-40)-Abboud
1) Body fluid compartments, normal Na end ECV and the concept of effective arterial blood volume (EABV)
Compartment % of body weight Volume (L)
Body 60 45
ICF 40 30
ECF 20 15
Instertitial 16 12
Plasma 4 3
Blood 7 5
Na is the main solute in the ECF (2550meq) while K is the main solute in the ICF (4500meq). These are maintained by Na-K-ATPase. Na is
the main osmotically active solute and therefore dictates H2o distribution between ICF and ECF. Electrolyte free water expands both ICF and
ECF (2/3 and 1/3 respectively) whereas giving isotonic saline (.9% nacl) will only expand the ECF. Giving .45% saline (.5L isotonic + .5L
H20) will result in .67L ECF ↑ (.5 isotonic + .33 of the .5L free h20) and .33L ICF ↑ (.66 of .5L free h20).
Increasing Na content in ECF causes fluid accumulation in: interstitial space (edema), peritoneal space (ascites), and pleural/pericardial spaces
EABV: (unmeasurable) part of the ECF that is in the arterial system and actively perfusing tissues. It is a reflection of 1) absolute plasma
volume (intravascular volume) 2) CO 3) Arterial BP (systemic vascular resistance) 4) neural and endocrine factors that govern 1-3. It varies
directly w/ ECF volume and Na content. In CHF there is a ↓EABV independent of ECF volume because ↓ CO causes Na retention↑ plasma
and total ECF volume.
A ↑ in EABV causes Na excretion by the kidney whereas a ↓ in EABV causes Na conservation.
In Cirrhosis there is a ↑ in ECF including plasma volume and CO is often elevated, yet most of the fluid is ascites and is hemodynamically
ineffective. Behave as if they are volume depleted.
Urea exists in equal concentration in both ICF and ECF so does not influence water movement.
2) The physiological responses to low and high Na intake, renal handling of Na through glomerular filtration and tubular
Reabsorption and the systemic and renal responses to changes in Na intake and/or ECF volume.
Abrupt High Na intake: enhanced Na excretion which lags several days before excretion rises to levels on increased intake so there is retention
of some excess Na. This causes a ↑ in ECF volume. Fig 8-p26
Abrupt Low Na intake: the opposite is true. There is a ↓ in Na excretion that requires several days to adjust to levels of intake resulting in Na
wasting. This causes a ↓ in ECF volume. Fig 9-p26
Low pressure Sensors: Low pressure/high volume. Cardiac atria, pulmonary vasculature. ↑ intravascular volume↑ atrial natriuretic peptide &
↓ SNS activityenhanced Na excretion.
High Pressure Sensors: arterial side of circulation. Carotid sinus and aortic arch. ↓ arterial pressure↑ renal SNS Na retention.
Juxtaglomerular apparatus: ↓ wall tension in afferent arteriole or ↓ salt delivery in the macula densa renin secretion
Normal daily Na intake ~150mEq and about 140mEq is excreted by the kidney, and 5 mEq by stool and 5 by sweat. About 25000 mEq is
filtered per day (so <1% is excreted).
Atrial Natriuretic Peptide: released from atria in response to stretch from volume expansion. It’s a vasodilator lowering systemic BP, and it ↑
urinary Na and H20 excretion suppresses release of renin and Aldosterone from the adrenals.
(Case 1, Conference 1)
Increase in NaCl intake
Increase in effective circulating volume
High pressure baroreceptors Low pressure baroreceptors
Decrease Ang II Decrease SNA Increase ANP
Increase GFR and decrease tubular Na+ reabsorption
Increase Na+ excretion
3) Hypovolemic and Hypervolemic disorders
Assessment of total body Na content or volume status is based on clinical criteria and Cannot be estimated from plasma [Na].
“effective” arterial Hypovolemia: ECF volume overload causing edema as seen w/ CHF and Cirrhosis. Expansion of interstitial space w/ an
intravascular volume depletion (capillary leak syndrome or severe hypoalbuminemia).
Na depletion: prerenal azotemia (BUN/creatinine ratio >20:1) and hyperuricemia. When renal losses are not the cause we see oliguria, low
urine Na, and concentrated urine).
ECF volume Overload: Edema. Signs of LV overload (↑ JVP and distension), S3 gallop and pulmonary edema.
1) CHF (Case 2, Conference 1) (↑ Na reab to ↑ ECF volume↑CO) 2) Nephrotic Syndrome (inability to excrete Na TX w/ Na restriction)
3) Hepatic cirrhosis (↑ intrahepatic pressure stimulates Na reab directly or by causing vasodilation) 4) Renal Failure ( ↓ functioning nephrons
↓GFR↓ Na excretion).
ECF volume overload w/ intravascular volume depletion: 1) Capillary leak syndrome (edema w/ findings of IV volume depletion due to toxic
insults or damage to capillary endothelium) 2) Severe Hypoalbuminemia (↓ oncotic pressure causes fluid shift from Intravascular to interstitial
ECF volume depletion: tachycardia, postural hypotension, dry mucous membranes, skin tenting. 1) renal Na losses (urine Na >20 w/ signs of
ECF contraction)-most commonly caused by diuretics or diuresis caused by hyperglycemia. 2) Extrarenal Na losses-vomiting or diarrhea,
burns, exercise, hot climates. Volume depletion may also be caused by hemorrhage.
Urine Electrolytes in a Patient
Hypervolemic states with ECF Volume Contraction
All values are in mmol/L; these numbers will be lower in a polyuric state.
Effective circulating volume Condition Na+ Cl- K+
Congestive heart failure Electrolyte in the Urine
Nephrosis Non renal or previous 0-15 0-15 Variable
renal loss of NaCl
Effective circulating volume Vomiting
Recent >20 0-15 >50
ECV solute Remote 0-15 0-15 Variable
NaCl intoxication Diuretics
Recent >20 >20 >20
Renal Na+ excretion
GFR Remote 0-15 0-15 Variable
Renal Disorders >20 >20 Variable
Tubular Na+ reabsorption involving wasting
Mineralocorticoid of salt
Water Metabolism I-Hyponatremia-(pgs 41-50)-Nolan
1) Understand the fundamental difference total body Na and TBW
Serum Na provides no information on absolute amounts of Na or water in body fluids.
TBNa: determines volume status (ECF volume). ECF depletion means deficient TBNa, and fluid overload excess TBNa.
TBH2o: determines osmolality ([Na] dissolved in ECF). Hyponatremia (Na <135)=excess H2O relative to Na, Hypernatremia
(Na>145)=deficient H2o. Since Na is the main cation in ECF, serum [Na] is an indirect measure of the osmolality of all body fluid
2) Understand that pure excess of TBW does not cause fluid overload
Excess of TBW leads to hyponatremia but no fluid overload.
2/3 of TBW is ICF and 1/3 is ECF. Of the 1/3 ECF, ¾ is interstitial fluid and ¼ is Intravascular fluid. So only 1/12 of TBW is in the vascular
space. This means that only 1/12 of every liter of free water put into the body increases the intravascular volume.
So basically, the distribution of TBW explains why TBW content determines osmolality of body fluids but does not determine volume status.
3) Etiologies and mechanisms of impaired free water clearance in 3 categories of hyponatremia.
Hyponatremia means the ECF osmolality is ↓ (more water content compared to Na). this causes water movement and shift from ECF to ICF
cellular swelling. (GI-nausea, vomiting, anorexia. CNS-altered mental status, seizures, coma)
First step in hyponatremia is determining volume status.
Hypovolemic Hyponatremia: ↓↓TBNa/↓TBH2o. TX volume repletion w/ normal saline decreases stimulus for ADHcan now excrete
excess water to correct hyponatremia. (hypovolemia is the underlying stimulus for ADH secretion in this category)
Extrarenal: Una or Ucl <10mEq/L. vomiting, nasogastric suction (Una high b/c dumping of NaHCO3 as result of met alkalosis), blood
loss, diarrhea, blood loss, sweating, burns. Bowel obstruction, Rhabdomyolysis, pancreatitis (all 3 cause sequestration)
Renal: Una and Ucl >20mEq/L. Diuretic use, Addison’s disease (impaired mineralocorticoid -aldo release) (case 2 conference 2),
acute/chronic interstitial nephritis (renal NaCl wasting).
Euvolemic Hyponatremia: NL TBNa/↑↑TBH2o. urine [Na] >20. TX w/ fluid restriction to a level less then pts insensible water loss. (giving
extra salt will only cause the Na to be excreted b/c the [Na] is already normal.
Causes: drugs that impair free water clearance by causing non-osmotic release of ADH ,or directly making tubules more permeable to
water. Also, SIADH caused by CNS tumors, Lung disorders/tumors (oat cell) (case 1-conference 2), post-op pain, hypothyroid, glucocorticoid
Hypervolemic Hyponatremia:↑TBNa/↑↑TBH2o. inability of kidney to excrete salt and free water. TX: salt restriction and diuresis to ↓ excess
TBna/ fluid restriction to fix excess TBwater.
Exra-Renal: (case 2, conference 1) CHF, Nephrotic syndrome, decompensated Cirrhosis. (in all cases there is ↓ EABV (by different
mechanisms causing non osmotic ADH releaseimpaired free water clearance).
Renal: ARF, CRF. (Loss of functional renal mass).
In all 3 cases there is no sign of fluid overload because although there is ↑ in free TBH2o, only 1/12th of it is intravascular.
4) Know causes of hyponatremia with normal plasma osmolarity.
Hyperglycemia: measured serum [Na] is low b/c ECF glucose cannot get into the cell water shifts out of the cell and dilutes ECF
Nahyponatremia. For every 100mg/dl that serum glucose is above nl the serum [Na] should drop by 1.6mEq/L. however, pOsm is either
normal or high.
Mannitol: (similar mechanism as hyperglycemia). Large amounts of IV contrast. Hyperlipidemia and hyperproteinemia.
5) Know how to use osmolar gap in the DX of methanol, ethylene glycol, and isopropyl alcohol intoxication.
pOsm=2[Na] + Glucose/18 + BUN/2.8 + EtOH/4.6
osmolar gap=difference of measured and calculated pOsm of >10.
Osmolar gap not elevated in salicylate, or sedative-hypnotic overdose (large MW compounds).
Disorders of Urinary Concentration—Polyuria and Hypernatremia (pgs 51-58)-Nolan
1) Understand the urinary concentrating mechanism (countercurrent multiplication) and the role of AVP and aquaporin-2 in
Reabsorption of NaCl in the TAL of the loop of Henle generates a hypertonic interstitial osmotic gradient where there is 200mOsm difference
b/t the intra-tubular and interstitial fluid.
When there is water deprivation there is a release of ADH which causes tubular fluid to become more concentrated.
AVP: produced by supraoptic and paraventricular nuclei in hypothalamus. Regulated by plasma osmolality and intravascular volume and
EABV. Releaseact on V2 receptor on basolateral membraneinsertion of AQP2 into apical membrane of collecting ductwater enters the
cell and is able to cross the basolateral membrane through the AQP3 and AQP4 water channels water Reabsorption.
2) Learn the etiologies and underlying pathophysiology of central and nephrogenic DI
Central DI: is a disorder of urinary concentration causes by inadequate production of ADH (↓) by the hypothalamic-pituitary axis—AQP2 in
collecting ducts is ↓ impaired urinary concentration and ↑ polyuria with polydipsia to compensate for excessive urinary loss of water.
(massive polyuria >12-15L w/ Uosm ~50). Causes: AD central DI, traumatic, idiopathic, iatrogenic, neoplasms, sarcoidosis, eosinophilic
Nephrogenic DI: appropriate ADH release in response to ↑ pOsm, but failure of collecting ducts to respond. Causes: congenital (Xlinked
recessive-mutation in V2 receptor.)(Autosomal recessive-mutation in AQP2)- Uosm~50mOsm-unresponsive to exogenous AVP.
3) Know how to use classical osmolar clearance and free water clearance formulae to determine whether polyuria is due to osmotic
diuresis, water diuresis, or both.
Osmotic diuresis: (case 4 conferencce 2)↑ in obligatory water loss secondary to ↑ urinary solute excretion. DM most common-
(glycosuriawater excretion), non-resorbable solutes (mannitol, urea, radiocontrast agents).
DX: if significant polyuria is present (urine output >3L/day) and the Uosm is above 300. Urinary Na is usually >50-70mEq and the Fractional
excretion of Na (FEna=(Una/Pna)/(Ucreat/Pcreat) x 100 is >1% (in nl individuals and those w/ DI it is usually <1%). Also, solute excretion rate
will be well in excess of the normal 600mOsm/day.
Osmolar clearance: >3ml/min in osmotic diuresis, whereas normal is 1.4ml/min (Cosm=Uosm x urine vol/ Posm x collection time)
4) Be able to use electrolyte-free free water clearance to calculate free water loss.
Daily urine output: Volume needed to excrete normal daily amounts of Na (150mEq) + electrolyte free water (in excess of normal)
Clearance of electrolytes (CLelect)= (2[Una+Uk] x urine volume)/(pOsm x collection time)
Free water clearance (Ch2o)=urine volume-CLelect
5) Understand the 3 categories of Hypernatremia.
↑ ECF [Na] water moves from ICF to ECFcell shrinkage (CNS restlessness, irritability, lethargy, mental status changes, seizure, coma.
Correct slowly!! (rapid correction can cause cerebral edema)
Hypovolemic Hypernatremia: ↓TBna/↓↓TBh2o TX saline for volume depletion, Water for hyper Na.
Extrarenal: Una or Ucl <10mEq/L. vomiting, nasogastric suction (Una high b/c dumping of NaHCO3 as result of met
alkalosis), blood loss, diarrhea, sweating, burns. Bowel obstruction, Rhabdomyolysis, pancreatitis (all 3 cause sequestration)
Renal: Una and Ucl >20mEq/L. Diuretic use, Addison’s disease, acute/chronic interstitial nephritis (renal NaCl wasting).
Euvolemic Hypernatremia: NL TBna/↓↓ TBh2o TX water replacement to slowly correct hypernatremia.
Causes: Renal losses (Central/Nephrogenic DI (Case 3 conference 2)) Extra-renal: unreplaced respiratory and dermal insensible
losses of free water.
Hypervolemic Hypernatremia: ↑↑TBna/↓TBh2o TX diuretics and Salt restriction for fluid overload, water for Hypernatremia.
Causes: inadequate replacement of resp and dermal losses of hypotonic fluid, hypertonic dialysate, hypertonic NaHCO3 admin, NaCl
Potassium Physiology and Disturbances (pgs 59-70)-Fanti
1) Understand the mechanisms by which K shifts in and out of cells to include hormonal and pH changes.
Of the total body K (3500mEq) 90% is IC, 8% is in bone/cartilage, 2% EC.
Insulin and B2-adrenergic agonists (albuterol) increase cellular uptake of K by stimulating Na/K ATPase.
Metabolic acidosis causes H+ to shift from EC space into cells in exchange for K+ (hyperkalemia). Metabolic alkalosis causes the reverse.
K+ is 90% reab in PT. 5-10% reaches DT & CD. In the ladder, Principal cells are responsible for K secretion and intercalated cells are
responsible for K Reabsorption. Secretion is regulated by (1) aldosterone (stim Na/K ATPase on basolateral memb and ENaC on apical
membrane) (2) High dietary intake (stim ROMK and BK channels on principal cells, and on intercalated cells inhibits apical entry and
stimulated apical secretion-p-60) (3) Urine Flow (4) Na delivery to distal segments (5) ECF pH (6) Serum K levels (7) concentration of
impermeable anions (HPO4- and SO4- (making lumen more electronegative favoring K secretion).
2) Describe how K moves along the nephron. Understand how urinary flow, urine pH, electrical neutrality, Na delivery to distal
tubule, dietary K intake, and different hormonal mechanisms play a role in K Reabsorption and excretion.
3) Understand nephrogenic effects of different drugs on K Reabsorption or excretion
4) Understand the mechanisms which can cause hypokalemia-specifically K loss through the nephron.
Serum K <3.5 mEq/L
In Hypokalemia we see ↓ amplitude of T waves and prominent U waves (these may be followed by cardiac arrythmias and death).
Redistribution: from EC to IC space. Due to alkalemia, selective B2 agonists (epinephrine, albuterol), or insulin (p.59)
Total Body Depletion:
Extra-Renal:24hr specimen. K<30mEq/day in presence of >50mEq/day of Na. (diarrhea, burns, poor intake)
Renal: K>30mEq/day then renal cause is suspected. (excessive Aldosterone, diuretics-HCTZ (case 3 conference 1), renal tubular
acidosis, excess anions (penicillin), aminoglycoside antibiotics (gentamicin, tobramycin), High urine flow rates (primary polydipsia), Liddles
syndrome( enhanced tubular absorption of Na in CCTK secretion), Bartter’s syndrome (defect in Na/K/2CL in TALwasting and activation
of aldosterone secretion).
TX. Ideally slow replacement per os. Since distribution goes to ECF first followed by ICF, a high dose could cause fatal cardiac arhythmias.
5) Understand mechanisms which may result in hyperkalemia.
Serum [K] >5.5mEq/L levels >6 are medical emergencies. Early cardiac changes (peaking of T waves, prolongation of PR interval). Very high
K level (widening of QRS complex, loss of P wave, onset of Sine wave pattern and chaotic wave pattern (v fib).
Signs of weakness, fatigue, and respiratory depression.
Pseudohyperkalemia: not a true rise in K. 1) hemolysis of blood sample in test tube. 2) release of K from cells to plasma in the test tube when
sever leukocytosis or thrombocytosis are present.
Redistribution: (Case 4 conference 1) IC to EC (total body K is normal) Cell death (rhabdomyolysis, reab of hematoma, cell lysis during
chemo or transfusion of incompatible blood). Acidemia, use of B blockers (propranolol), lack of insulin, insulin resistance, hyperglycemia, and
digitalis intoxication (block Na/K ATPase)
Total Body Excess: renal failure, inadequate delivery of Na and tubular fluid to CCT (volume depletion), Impaired K excretion by CCT (low
aldosterone (ACE inhibitors (Case 4 conference 1), Heparin), adrenal insufficiency, hyporeninemic hypoaldosteronism (diabetic neuropathy or
renal interstitial disease), spironolactone (block aldo receptor), amiloride, triamterene, trimethoprim (Block ENaC).
TX: immediate and most important therapy is IV calcium gluconate or calcium chloride to stabilize cardiac membrane. Exogenous insulin
(shift K from EC to IC space), b-2 agonists, and possibly NaHCO3. if there is ↑ TB K then use diuretics, mineralocorticoids, or Na/K exchange
resin (kayexalate-absorbs K in exchange for Na).
Acid Base Disorders-(71-92)-Nolan
1) Develop a systemic approach to the analysis of acid-base disorders.
Henderson Hasselbach Equation: pH=6.1 + log ([HCO3]/(.03 x pCO2)). pH directly proportional to [HCO3] and inversely proportional to
pCO2. Acidemia (pH <7.4). Alkalemia (pH>7.4)
The Four Primary Acid-Base Disturbances
Type of Primary Alteration Secondary Mechanism of
Disturbance Response Secondary Response
Metabolic acidosis Decrease in plasma Decrease in Pa CO3 Hyperventilation
Metabolic alkalosis Increase in plasma Increase in PaCO3 Hypoventilation
Respiratory Increase in PaCO3 Increase in plasma Acid titration of tissue buffers; transient increase in acid
acidosis [HCO3-] excretion and sustained enhancement of HCO3-
reabsorption by kidney
Respiratory Decrease in Pa CO3 Decrease in plasma Alkaline titration of tissue buffers; transient suppression
alkalosis [HCO3-] of acid excretion and sustained reduction in bicarbonate
reabsorption by kidney
2) Understand the causes of increased anion gap metabolic acidosis.
Winter’s formula: respiratory compensation for metabolic acidosis should be Winters formula pCO2=1.5[HCO3] +8 +/- 2. (Another formula is
to say that pCO2 should fall 1-1.5 times the change in [HCO3].
Anion Gap: the difference between unmeasured Anions - unmeasured cations = [Na]-[Cl]-[HCO3].
Normal Gap is b/t 8-12 mEq/L
↑ anion gap w/o metabolic acidosis: (1)↑ in unmeasured anion (without addition of H+)-as seen with Na(lactate, citrate, acetate, carbenicillin,
penicillin). (2) decreased unmeasured cations (hypo Ca, Mg, or K)
↓ Anion Gap: (1) ↓ unmeasured anions (hypoalbuminemia) (2) ↑ unmeasured cations (IgG multiple myeloma-others on p74) (3) lab value
↑ Anion Gap Metabolic Acidosis:
(1) Lactic acidosis (p 75) (↓ tissue oxygenationLA production w/ plasma [lactate] >4mEq/L)
Type A: (reduced O2 delivery)-Shock, ↓ CO, Cardiac arrest, sepsis, hypoxemia w/ pO2 <30, CO poisoning, Cyaninde poisoning.
Type B: (toxin induced impairment of cellular metabolism)-ethanol, methanol, ethylene glycol, metformin (when used to TX adult
onset diabetes in pts w/ even mild renal insufficiency-creatinine >2), severe DKA, severe liver disease, pheocromocytoma, HIV
(HAART TX accum of lactate).
D-lactic Acidosis: short bowel syndrome- starch and glucose normally absorbed in small intestine go to colon and are converted to D-
lactate by colon lactobacilli D-Lactate cannot be broken down to pyruvate by LDHaccumulation. L-lactate is normal.
(2) Ketoacidosis: impaired glucose utilization due to fasting, insulin deficiency, or resistanceketone bodies (acetoacetic acid, B-
hydroxybutyric acid, and acetone) serve as alternate energy sourcesaccumulation of these acids causes Metabolic Acidosis.
Diabetic: (case 1 conference 3) uncontrolled type 1 DM. insulin resistance↑ glucagon levelsblock degradation of glucose by
blocking glycolysis and acetyl CoA Carboxylase (ACC) no malonyl CoA productionno inhibition of CAT fatty acyl CoA now
converted to ketoacids. (p 77).
Alcoholic: ↓ diet and ↑ ethanol intake lipolysisketones
Starvation: may produce ketoacidosis but is not severe because ketonemia stimulates insulin production blocking FFA synthesis (p77)
(3) Renal Failure: if there is a ↓ in GFR and tubular function H+ and SO4- will be retained Met acidosis. (p 78)
(4) Salicylate Intoxication: (case 4 conference 3) rapidly converted to salicylic acid. Therapeutic (20-35mg/dl) (toxic 40-50). Positive urine
dipstick for phenylketonuria early clue to dx of salicylate intoxication. Otherwise dx by symptoms (tinnitus, vomiting, mental status
changes, coma, diarrhea). Alkalinize blood and urine to reduce drug accumulation in the CNS.
(5) Ethylene glycol, methanol, isopropyl alcohol intoxication: Methanol (↑ formic acid production)-visual blurring, nausea, vomiting, retinal
edema (sheen). Ethylene glycol (glycoaldehyde, glycolic acid, oxalic acidARF)-calcium oxalate crystals seen in urine. Ethanol
prevents conversion of these 2 to their toxic metabolites. We see ↑ anion gap but no metabolic acidosis w/ isopropyl alcohol.
Osmolar Gap: pOsm=2[Na]+glucose/18 +BUN/2.8 +EtOH/4.6 Osmolar Gap= measured pOsm-calculated pOsm
(↑ osmolar gap w/ anion gap met acid= Ethylene glycol or Methanol intoxication) (↑ osmolar gap w/o met acidosis= isopropyl OH
3) Understand the causes of hyperchloremic metabolic acidosis including proximal (type 2), distal (type 1), and type 4 Renal Tubular
The Anion Gap is normal in this case because the lost HCO3 is replaced with Cl. In pts w/ diarrhea the Urine Anion Gap (Na + K + NH4=Cl)
is measured without NH4 (so, Na + K – Cl) will be very negative. In patients w/ RTA the Anion gap will be positive since NH4 excretion is
defective. In diarrhea we see low Serum K w/ low Urinary K (<25mEq) (extrarenal k loss). In RTA we see ↓ serum K w/ ↑ urinary K (renal
RTA: caused by ↓ acid excretion per nephron or by renal loss of HCO3.
Distal: 1) defect in H+ pump in intercalated cells 2) ↑ permeability of CT so that a large pH gradient cannot be maintained due to back-
diffusion of H+ 3) ↓ DT Na reabsorption so the electrical gradient favoring H+ secretion is ↓ (this causes hyper K). Causes: Sjogrens and RA
(adults) and hereditary (children). Since H+ secretion is ↓ there is no generation of HCO3 (may be <10mEq)
Proximal: defect in PT reabsorption of HCO3 (serum threshold set abnormally low 15-18mEq/L with normal being >25). Causes: 1) ↑
excretion of monoclonal Ig due to multiple myeloma 2) use of carbonic anhydrase inhibitors (in adults). In children 1) idiopathic 2) ifosfamide
Type IV: Aldosterone deficiency or tubular resistance. This causes defective secretion of both H+ and K+ hyperkalemia↓ renal NH3
production ↓ production of ammonia (limiting acid secretion as ammonia)inability to excrete daily acid loadhyperchloremic acidosis.
Urine is maximally acidified.
Diagnose between Proximal and distal w/ infusion of NaHCO3 to a normal [HCO3]. Measure HCO3 excretion in urine. If HCO3 excretion
<3% then the excretion is normal (distal), if the excretion is >15-20% then there is ↓ reab due to the ↓ setpoint (proximal)
4) Understand the difference between Chloride responsive and chloride resistant metabolic alkalosis.
Chloride Responsive: Cl is normally the main anion reab w/ Na. if there is Cl depletion and volume depletion, Na must be reabsorbed w/
HCO3 to restore volume. This causes persistence of Alkalosis.
1)Vomiting and NG suction: (case 2 conference 3) excess removal of HCl leads to net generation of HCO3. there is hypokalemia due to
Na reab b/c of volume loss. In this scenario, which wasn’t explained in class, we see high Urine Na (>50mEq) and low urine Cl (<15mEq).
This is because Na is lost in urine as NaHCO3 in order to correct the alkalosis, and Cl is low due to vomiting induced Cl depletion.
2)Diuretic Administration: ↑ delivery of NaCl to distal tubule + volume depletion ↑ Na reab by mech of aldosterone both lead to H+
and K secretion. Cl and volume depletion maintain the alkalosis (HCO3 reab w/ Na). Urine Cl will be high (>20mEq/l).
Others on p 88.
Chloride Resistant: Pt seen in clinic w/ HTN, unexplained Hypokalemia, & Cl unresponsive Metabolic Alkalosis.
1) Hyperaldosteronism: Causes on P 90. ↑ Na reab and ↑ K secretion. This causes ↑ H+ secretion and therefore a ↑ in
HCO3 reabcausing the alkalosis. Volume (Cl) depletion is generally absent and therefore Cl unresponsive.
2) Barters syndrome: defect in Na-K-2Cl transporter. ↑ distal delivery of Na & volume depletion hyperaldoH and K secretion.
3) Gitellman’s syndrome: defect in thiazide sensitive Na-Cl transporter in DT. hypocalciuria w Mg wasting.
5) Develop basic understanding of respiratory acidosis and respiratory alkalosis.
Respiratory Acidosis: (Case 3 conference 3) (heroin caused resp depression). hypoventilation w/ ↑pCO2. acute respiratory acidosis ([HCO3] ↑
1mEq/L for every 10mmHg ↑ in pCO2) in chronic ([HCO3] rises 3 meq/L for every 10mmHg ↑). Central Sleep apnea is a common cause of
Respiratory Alkalosis: ↓ in pCO2. in acute ([HCO3] ↓ by 2mEq/L for every 10mmHg ↓) in chronic ([HCO3] ↓ 5mEq/L for every 10mmHg ↓)
Gram negative sepsis. This is the only acid-base disorder where the compensatory response can normalize the pH.
A Systemic Approach to Analysis of Acid-Base Disorders-(pgs 93-102)-Nolan
*** This lecture was the “idiots guide” to diagnosing acid base disorders. There were no Objectives. Use these notes and the
steps therein to diagnose acid base complications. ***
Pediatric Urology (pgs 103-106)-Leslie
1) Describe common congenital anomalies of the GU system seen in children and their treatment options.
Hydronephrosis: Most common etiology of abdominal mass in newborn. It is a dilation of the upper tract collecting system. Caused by:
1) Ureteropelvic Junction Obstruction (UPJ): most common. Usually asymptomatic mass, 30% have UTI, flank pain w/ diuresis,
hematuria, severe pain/hematuria after trauma. Due to either intrinxic obstruction or extrinsic crossing over vessels. Can cause pain, calculi,
loss of function, or infection. DX by ultrasound, VCUG, Diuretic renal scan. TX: 1) may get better over time. 2) endopyelotomy 3) pyeloplasty
2) Uretero-vesical Junction (UVJ):
3) Posterior urethral valves (bladder outlet): present as pre-natal hydronephrosis, usually w/ midline abdominal mass (distended
bladder), UTI, and failure to void w/ in 24hrs after birth. prognosis: Good if post valve ablation Cr level is < .7mg/dl, there is unilateral/ high
grade reflux/dysplasia, or there is urinary ascites or perinephric urinoma. Bad if Cr >.7mg/dl, there is bilateral reflux, or bladder dysfunction.
1) Vesicoureteral Reflux- seen in up to 70% of kids <1yr, usually found postnatally after UTI. Primarily due to shortened intramural
tunnel. Can be secondary to failed reimplant, neurogenic bladder, or dysfunctional voiding. TX: 1) tx underlying etiology, antibiotics,
anticholinergics, intermittent catheterization, or ureteral reimplant surgery.
2) Prune-Belly Syndrome-dilated urinary tract, deficient abdominal wall musculature, bilateral-intra-abdominal testes
2) Describe common genital tract anomalies in boys and treatment options.
Hypospadias: Abnormal prepuce (normally dorsal hood), urethral opening along ventral side anywhere from glans to the perineum, often have
ventral curvature (chordee). NEVER circumsize! TX is surgery.
Hydrocele: Communicating (children): patent processus vaginalis (inguinal hernia). Non-communicating (adults). Found in 10% of males. 90%
resolve spontaneously. Surgical repair after age 1-2
Cryptochordism (“one ball”): 3% of all full term males. 2/3 of undescended testis will descend by 3-6mo of age. Unilateral>>bilateral. Occurs
in 30% of premature infants suggesting descent of testis in 3rd trimester. Testicular cancer risk ↑ by 40 fold (1:2500)-seminoma most common.
Orchiopexy does not diminish cancer risk but it does allow testicular examination. Orchiopexy and hormone tx have been shown to ↑ fertility.
Earlier tx is better, usually by 1yr. Unilateral have 75-90% paternity (normal). Bilateral have 33-65% paternity. Cryptochordism may be
associated w/ hernia (90%-patent processus vaginalis) or torsion. Testes are palpable in 80%. Rule out intersex disorder. TX: 1) tincture of
time, if less then 6 months 2) surgery 3) Hormonal therapy.
Varicocele: abnormally dilated spermatic veins. 90% left sides. 10% bilateral. Seen in 15% of peri or post-pubertal males. Indication for
intervention: abnormal semen analysis, testicular hypotrophy (10-20% difference b/t L and R). Ligation or transvenous embolozation of
spermatic vein. (grade: 1) palpable w/ valsava 2) bag of worms palpable w/o valsalva 3) visible through scrotum)
Ambiguous genitalia: on exam of genitals the sex of pts cannot be determined. 70% caused by congenital Adrenal Hyperplasia.
CAH: deficiency of 1 of 5 enzymes involved in synthesis of cortisol and aldosterone from cholesterol (21-hydroxylase deficiency in
90% of cases)shunting to testosterone synthesisDHT
Medical emergency because 50% will have salt wasting (hyponatemia, hyperkalemia, hypovolemia, hypotensionSHOCK.
3) Describe common bladder disorders seen in children and treatment options.
UTIs: boys>girls 1st year of life. Uncircumcised>>circumcised . In newborns with fever, up to 14% have a UTI (Acute UTI usually presents w/
low-grade fever). DX: constipation, imperforate hymen, labial adhesions, epididymitis, Urinalysis/culture. Most UTIs due to
Cystitis/Pyelonephritis: cystitis is result of infrequent or incomplete emptying of the bladder. Fever + UTI= pyelonephritis. DX: renal and
bladder ultrasound, Voiding cystourethrogram. Can cause renal scarring, insufficiency, HTN, and ESRD.
Unstable bladder: most common form of bladder dysfunction. bladder instability during filling.
Dysfunctional elimination: freq seen w/ constipation. Recurrent UTIs. Must treat both constipation and voiding behaviors. Can have
hydronephrosis, reflux, renal failure.
Nocturnal enuresis: Familial. Not addressed till age 7. 15% spontaneous resolution rate/year. Do a history and physical and urinalysis. If
normal, nothing else is required. Bedwetting alarm is the most successful therapy.
Urinary Tract Infections (pgs 107-122)-Johnson-INFECTIOUS DISEASE CASES
1) What is the pathophysiology of upper and lower UTIs?
Ascending: colonized bacteria (perineum, periurethral space, vaginal epithelium (low estrogen))ascend via the urethrabladder
(cystitis)ureteral valves loose competence and bacteria ascend to involve the ureter and kidney.
Hematogenous: Kidney infected from bloodstream (usually S. aureus) in a patient w/ bacteremia often as a result of edocarditis (septic emboli
to the kidney).
2) What are the risk factors for the development of upper and lower UTIs?
Urethral trauma: post mechanical traumafacilitates movement from periurethral space into bladder. Urine stasis: Inability to completely
empty the bladder (1)neurologic: diabetic neuropathy or paraplegia, 2) Obstruction: urethral strictures, prostate hypertrophy, ureter
compression by tumor or obstruction by renal calculi). Urinary reflux: anatomic malformations. Catheterizations: traumaadherence of
uropathogens to uroepithelial cells. Children: Uncircumsized males have ↑ risk (1:100) for infection in first year of life (foreskin promotes
3) What populations are at greatest risk for UTIs? Why are asymptomatic bacteriuria and cystitis of particular concern during
pregnancy and how should they be managed?
Pregnancy: dilatation of ureters w/ ↓ peristalsis hydronephrosisascension of bacteria to upper tract. Also, we see ureteral obstruction
caused by the uterus. This is the most likely cause of “asymptomatic bacteriuria”.
4) What are the organisms that commonly cause UTIs? What bacterial virulence factors contribute to the development of UTIs?
Virulence Facors: 1) bacterial adherence to uroepithelial cells. (type 1 pili bind to mannose receptors). 2) Urease produced by Proteus spp. And
Providencia spp. Splits urea↑ urine pH precipitates Mg and ammonium phosphatesStruvite calculi.
1) Uncomplicated “community acquired” UTI in women: E.coli most common. Other gm (-) and S. saprophyticus less common.
2) Complicated UTI in women: women w/ underlying co-morbidity-illness, HAQ infection, structural abnormalities, indwelling catheters,
recent UT instrumentation. E. coli, Proteus spp., Enterobacter spp., Psuedomonas spp., Klebsiella spp., Enterococcus spp., yeast.
3) UTI in men: (by definition complicated)- men >50yrs w/ prostatitis or prostatic hypertrophy. E. coli, Proteus spp., Enterobacter spp.,
Pseudmonas spp., Klebsiella spp., Enterococcus spp.
4) UTI in children: same pathogens as adults w/ E. coli being most common.
S. Aureus- very rare cause usually results from hematogenous seeding of the kidney from another source ( endocarditis).
5) What are the clinical features of upper and lower UTIs and how is this DX made?
Lower UTI: Dysuria, urinary frequency, small volume voiding, urinary urgency, suprapubic discomfort. TX-short course antibiotics.
Upper UTI: Fever, chills, flank pain and tenderness, +/- Lower tract symptoms, +/- nausea/vomiting. TX-long course antibiotics.
Pyuria: WBC in the urine usually due to infection, STDs, vaginitis, irritation, or allergic reactions. 5 Leukocytes per HPF is upper limit of
normal. WBC cast are strong indicator of Upper UTI in pt w/ symptoms of pyelonephritis.
Bacteriuria: 1) dipstick: detect presence of nitrite in urine formed when bacteria reduce nitrate that is present.
2) microscopic exam: gram stain. No bacteria per oil immersion of spun urine means <10 ↑4th organisms per ml. >1
bacterium per oil immersion means >10 ↑5th organisms/ml (> 10 ↑5th = clinical infection).
3) Culture: obtain clean catch mid stream specimen for culture to prevent contamination. Patients w/ infection usually have >
10 ↑5th bact/ml whereas pts w/ <10 ↑4th usually do not have infection. However, appx 1/3 of women w/ Lower UTI symptoms present w/ < 10
↑5th bact/ml. this is called “acute urethral syndrome (most have mild cystitis while some have urethritis secondary to N. gonorrhea or
6) What are the possible complications of UTIs? In what situations do imaging studies help in the management of patients with UTI?
Post-void residual: insertion of catheter after voiding. Residual urine post-voiding prostatic hypertrophy, urethral stricture, valve or
neurogenic bladder dysfunction.
X-ray: detect urinary calculi, calcification. Soft tissue masses, or gas.
Ultrasound: evaluation of renal collecting system, renal parenchyma, and retroperitoneal tissue. Used in pts w/ higher chance of having
correctable abnormality (all children w/ UTI, all men w/ UTI, pts relapsing after therapy, infections complicated by bacteremia).
CT: most sensitive but more expensive the US.
Voiding cystourethrogram: identifies vesicoureteral reflux.
Anatomic evaluation is warranted in 1) all men after first UTI 2) pts relapsing after therapy 3) pts whose infection is complicated by bacteremia
4) consider in women w/ > 3-4 UTIs 5) all infants after first UTI 6) boys any age after first UTI 7) girls <3yrs after 1st UTI 8) girls >3yrs when
suggesting anatomical abnormality, abnormal voiding, HTN, poor physical development. 9) older children w/ recurrence
Complications: 1)asymptomatic bacteriuria in 10% pregnant women. This is associated w. pyelonephritis later in preg predisposes to
premature labor and delivery, ↑ maternal morbidity, ↑ fetal morbidity and mortality. 2) Kidney infection- most common source of gm (-)
septicemia (40% mortality) 3) Upper UTI: papillary necrosis 4) intrarenal or peronephric abscess--> complicate severe upper UTI. Pts w/ fever
and flank pain who fail to respond to antibiotic therapy. Drainage usually necessary. 5) renal scarring from reflux and recurrent infection can
lead to CRF.
7) How are UTIs treated?
1) Hydration to flush the GU system. 2) Antibiotic therapy directed against gm (-) enteric organisms. Oral therapy is adequate unless pt is
severely ill or in pt w/ nausea/vomiting. Uncomplicated: Trim-sulfa (probably best b/c in ↓ periurethral colonization, nitrofurantoin,
cefalexin, amoxicillin-clavulanic acid, FQs. TX 3-days Complicated: FQs, 3rd generation cephs, axtreonam, aminoglycosides. TX women
14 days. TX men w/ acute prostatitis 4 wks.
Urinary Incontinence (pgs 123-129)-Arisco
1) Understand the basic physiology of normal urine storage and emptying the urinary bladder as well as alterations in function that
lead to incontinence.
Detrusor muscle (bladder wall) remains relaxed during filling. The bladder outlet (sphincter and pelvic floor) remains closed through
maintenance of tonic sympathetic tone. There is a continuous central subconscious inhibition of micturition reflex. With bladder emptying we
see 1) volitional control 2) sphincter/pelvic floor relaxation remaining relaxed until voiding is complete 3) detrusor contraction throughout
duration of emptying.
2) Recall and understand the different types of urinary incontinence.
1) Stress incontinence: loss of urine w/ ↑ abdominal pressure. Can be due to bladder neck/sphincter hyper mobility, lax support of bladder,
↓ function of muscle/nerve of sphincter (neuromuscular disease or injury). More common in women and predisposing factors including
age, parity, vaginal delivery, obesity. Rare in men unless they have prostate surgery, neurologic injury, trauma.
2) Urge Urinary Incontinence: involuntary bladder contraction (detrusor overactivity), more common in elderly men (↑ w/ age), risk
factors include age, obesity, diabetes, long standing outlet obstruction (BPH in men), neurological conditions.
3) Mixed Urinary Incontinence: both stress and urge leakage.
4) Overflow Incontinence: Obstructed retention of urine (BPH, urethral stricture, cytocele/kinking of urethra (pelvic prolapse, prior
incontinence surgery). Unobstructed retention of urine ( detrusor hypocontractility or areflexic detrusor “cardiomyopathy of the bladder”)
(decompensated bladder after prolonged obstruction, DM, neurogenic bladder, less common in females).
5) Functional Incontinence: environmental issues prohibit emptying. Normal GU tract. More common in elderly due to restricted mobility,
and cognitive impairment.
6) Transient Incontinence: Potentially reversible. Common in elderly. Caused by UTI, Illness, delirium. DIAPERS (Delirium, Infection,
Atrophic vaginitis, Pharmacological/psychological, Excessive urine output, Restricted mobility, and Stool impaction).
7) Continuous incontinence: could be from overflow, fistula (vesico-vaginal, uterovaginal, iatrogenic after gynecologic surgery (developed
country), obstetric fistula resulting from obstructive labor (third world)), or ectopic ureter.
3) Be familiar with evaluation of patients for incontinence
Focus on medical conditions, medications, prior incontinence TX, medical and surgical history. Ask all the who where when why how how
often questions. Labs: UA, culture, cytology. PE: bladder palpation, urethral meatus location. Make pt bear down w/ empty bladder. Cath and
fill to check for leakage or urethral stricture. Other studies: Cystourethroscopy (eval of urethral stricture, bladder foreign body, trabeculation
(enlarged bladder muscle fibers or large prostate), ultrasound to check for hydronephrosis, serum creatinine if suspected long standing
obstruction, Uroflow in more complicated cases.
4) Recognize various treatments for the different types of urinary incontinence.
1) Stress: pad usage, pelvic floor muscle therapy, Minimally invasive therapies (trans-urethral bulking agents like collagen), sling surgery for
women (mid-urethral, open surgeries) and men, artificial urinary sphincter (for moderate to severe-post prostatectomy in men).
2) Urge: conservative (pads, avoid bladder irritants such as caffeine ect.), pelvic muscle therapy, guarding reflex (relaxation of detrusor muscle-
tightening of pelvic floor), medications (anticholinergics), surgery (remove obstruction-TURP, stricture incision, urethrolysis (in female if sling
felt tight), sacral neuromodulation (stimulates S3 nerves without inhibiting voluntary detrusor activity), urinary diversion (last resort).
3) Mixed: treat components separately. Most bothersome first.
4) Overflow: Obstructed: TURP, address any stricture, urethrolysis (if prior sling surgery), catheterize if bladder not decompensated. Non
onsctructed: catheterization (chronic or intermittent) because impaired detrusor function.
5) Functional: difficult to tx. Prompted voiding for dementia pts, mobility aids to help those w/ immobility problems make it to the bathroom,
pad or catheter usage.
6) Transient: address root cause and give supportive care.
7) Continuous: de-obstruct if obstructive overflow, surgical tx for fistulae or ectopic ureter.
Benign Prostatic Hyperplasia-(pgs 129-132)-Arisco
1) Understand the basic anatomy of the prostate and anatomical changes occurring w/ BPH.
Most common neoplastic condition in men. BPH occurs in transition zone of prostate. Usually occurs late 5th decade. 50% of men >70 are
Urethral Lumen narrowing due to growth of prostate (stromal-epithelial cell proliferation and/or impaired programmed cell death). Another
view: ↑ alpha-1 receptors in prostate SM ↑ tone of SM↑ outlet resistance.
2) Understand the basic pathophysiologic alterations of BPH
HypothalamusGnRHLH and FSH release from pituitary LH causes leydig cells to make testosteroneprostatic growth.
3) Understand consequences of BPH on bladder and kidneys.
↑ pressure needed to effect bladder emptying ↑ collagen content and detrusor muscle hypertrophy (↑ storage pressure and ↑ irritability due to
stimulation of nerve endings). ↑ bladder storage pressure may cause renal failure or detrusor muscle failure over time. Also, BPH may cause
Hematuria, bladder stones, UTI, and incontinence, urge, or overflow.
4) Recognize symptoms of BPH.
Irritative: 1) nocturia (waking >1 time to void). 2) frequency (>2 times/hr). 3) Urgency
Obstructive: 1) weak stream. 2) Hesitancy of urination (delay in start of stream). 3) Intermittancy (stream starts then stops) 4) straining.
5) Be familiar with evaluation of patient for BPH
H&P. Questionnaires. Labs (urinalysis, culture, serum creatinin, PSA), Studies (Post void residual, Uroflow, Urodynamics (bladder storage and
emptying), Upper UT imaging.
6) Recognize various treatments for BPH.
Watchful waiting, medications (alpha blockers, 5 alpha reductase inhibitors), Minimally invasive/ endoscopic ( intraprostatic stents, TUNA-
radiofrequency ablation, microwave, laser, or TUIP (transurethral incision of prostate, or TURP (transurethral resection of prostate-gold
standard), Open surgical TX for BPH (retropubic and suprapubic prostatectomy).
Acute Kidney Injury (pgs 133-146)-Kasinath
1) Mechanisms by which renal function is acutely impaired.
Prerenal: due to ↓ in renal perfusion (blood loss, GI losses, burns, CHF).
Intrinsic AKI: Due to diseases of the 1) Blood vessels (vasculitis), 2) glomeruli (acute post-step GN, diffuse lupus GN), 3)Tubules (ATN), 4)
Tubulointerstitium (tubulointerstitial nephritis)(drug induced-NSAID, Rifampin, Sulfonamides).
Post Renal AKI obstruction of BOTH kidneys or of a single functioning kidney. (prostatic hypertrophy (case 2 conference 4),Bladder and
uterine tumors, Kidney stones).
2) How to distinguish between various types of kidney injury, especially between ATN and prerenal causes
Prerenal Azotemia: ↓ GFR due to renal hypoperfusion. 1) external losses of fluid (GI, diuretics, bleeding, burns), 2) Internal sequestration of
fluid ( peritonitis, pancreatitis), 3) ↓ effective circulating volume ( CHF, cirrhosis), 4) Renal vasoconstriction (NSAIDS, hepatorenal syndrome)
• Inadequate perfusion. Kidneys are normal.
• Clinical: Oliguria, high urine osmolality (>500mOsm), Una <10mEq (suggests kidney is functioning normally), Fractional excretion
of Na <1% (1% is normal), NO abnormal casts or cells ( used to distinguish from ATN), disproportionate rise in BUN compared to
serum creatinine. Once underlying problem is resolved kidney recovery of function is prompt.
Acute Tubular Necrosis (ATN): injury to tubulesimpaired tubular fxn and glomerular filtration in absence of prerenal, postrenal causes.
Caused by 1) hemodynamic mechanisms (Ischemia (severe hypotension), 2) Nephrotoxic mech. (aminoglycoside antibiotics-gentamicin,
ampho-B, radiocontrast material).
• Ishemic Type: patchy necrosis of the nephron. Toxic Type: (ex. Gentamicin) (case 1 conference 4) injury is more proximal. Mitotic
figures indicate PT cells are regenerating.
• (One of the causes (1 or 2) from above) 1) back diffusion (leakage of filtrate into tubulointerstitium through breaks in the tubular
basemement membrane, 2) Mechanical obstruction (1) debris cause casts micro obstruction in tubule, or 2) ↑ extrinsic pressure
from interstitial edema ↑ tubular pressure that opposes capillary hydrostatic pressure). 3) Vasoconstriction of afferent arteriole
due to TG feedback from cell injury ↓ glomerular plasma flow. 4) ↓ glomerular capillary permeability due to Kf (hydrostatic vs
oncotic pressure) reduction (↓ filtration).
• In ATN we see: 1) disruption of cell junctions, 2) Maldistribution of Na/K ATpases (↑ Na to DT/CDafferent vasoconstriction due
to TG feedback), 3) disruption of actin fibers and intergrins (disrupts tight junctionscell detachmentsgranular cell casts).
• Una >20. FEna >1%. Elevated BUN and [Creat]. Uosm low (because cannot concentrate urine).
3) Clinical presentation and manifestations of acute kidney injury.
Acute kidney injury: abrupt ↓ in kidney fxn defined by ↑ of serum creatinine of .3mg/dl or a 50% ↑ over baseline, or a ↓ in urine output to ~ .
5ml/kg/hr for 6 hours).
Asymptomatic AKI: evidence of ↓ GFR by elevation of BUN and serum creatinine.
Symptomatic AKI: symptoms of uremia-symptoms of renal failure-(nausea, vomiting, itching, ↓ mentation, coma, seizures, bleeding).
With ↑ kidney fxn we see: inability to: 1) regulate volume (edema, HTN, CHF), 2) regulate electrolyte composition ( hyper Kalemia,
hypoCalcemia, hyperphosphatemia, hyperuricemia, metabolic acidosis), 3) excrete nitrogenous waste (↑ BUN and serum creatinine).
4) Diagnostic approach including urinary parameters of acute kidney injury.
History: volume losses, UT obstruction, surgery, nephrotoxic agents (NSAIDS), diabetes, lupus (diseases that commonly involve kidneys)
Physical: volume status (BP, orthostatics, pulse, skin turgor), CHF workup, evaluation of prostate, bladder, and GU system
Labs: Urinalysis and urine electrolytes: 1) proteinuria, hematuria, and RBC casts-Glomerulonephritis. 2) White cells, WBC casts and negative
culture-Acute tubulointerstitial nephritis. 3) Brown sediment w/ granular casts-ATN. 4) no active sediment- Prerenal azotemia and obstructive
Urine osmolality: (nl 300mOsm). Pre-renal azotemia (>500 mOsm)-whatever gets filtered is able to be concentrated because the kidneys
themselves are normal. ATN ( 300 mOsm)-unable to concentrate urine. Urine Na: <20mEq in Pre-renal azotemia (normal kidney fxn) and
>20mEq in ATN (abnl kidney fxn/reab). FEna: <1% in pre-renal azotemia (normal), >1% in ATN.
Ultrasound: test of choice to exclude obstruction. CAT scan: used to delineate obstruction. MRI: used to delineate UT anatomy.
History & Physical
UA, UOsm, UNa, FENa
UNa < 20 UNa > 20
FENa < 1% FENa > 1%
Renal Acute Special Cases Acute Acute On
Hypoperfusion GN Of ATN TIN CRF
5) How to distinguish between acute kidney injury and chronic kidney injury.
CRF features: Chronic history of nocturia, polyuria, edema, hematuria, uremic symptoms (neuropathy), underlying illness (HTN, Diabetes).
Objective Findings: renal osteodystrophy, band keratopathy or conjunctival calcification, bilaterally small kidneys, carbamoylated Hgb, anemia
not contributed to any other cause, sustained abnormal creatinine levels in the past. Chronic kidney disease is irreversible, AKI is not.
If a patient presents w/ ↑ serum creatinine for the first time, assume AKI until proven otherwise.
6) Complications of ARF and prognosis of acute kidney injury.
ACUTE KIDNEY INJURY - COMPLICATIONS
• Pulmonary edema Asterixis
• Arrhthmias Neuromuscular
• Hypertension Mental status changes
• Pericardial effusion Somnolence
• Myocaridial infarction Coma
• Pulmonary embolism Seizures
• Hyponatremia • Nausea
• Hyperkalemia • Vomiting
• Acidosis • Gastritis
• Alkalosis • Gastroduodenal ulcers
• Hypocalcemia • Bleeding
• Pneumonia • Anemia
• Septicemia • Hemorrhagic diathesis
• Urinary tract infection ,
• Wound Infection
Worse prognosis in older pts w/ systemic disease or emergency cardiovascular surgery. Mortality: pre-renal azotemia (7%), Post-op AKI
(80%), sepsis and multi-organ failure (50-80%). Causes of death in AKI (50% due to infections).
Urologic Cancers (pgs 147-152)-Thompson
1) list the most common GU cancers
Prostate cancer (186,320), Bladder (68,810), Kidney (54,390), Testis (8,090).
2) Understand the presentation and diagnosis of these tumors and management (included question 3)
Prostate: no symptoms until metastatic (metastasismedian survival 30-36 months). Men have about a 60% lifetime risk of prostate cancer
although only ~17% are diagnosed. 5-alpha reductase inhibitors (Finasteride and Dutasteride) can significantly ↓ the risk of developing prostate
cancer. PSA and DRE are the two primary screening tests. PSA>4.0ng/ml needs a biopsy according to current guidelines.
PSA, DRE, Race/Ethnicity (African Americas have ↑ risk), Family HX (1st degree relative ↑ risk), and Prior Prostate Biopsy (previous negative
biopsy ↓ risk) all affect risk for prostate cancer.
If cancer is suspectedneedle biopsy (graded according to Gleason scoring system (5-10)). If a man has high PSA (~50) (Nl =4.0mn/ml) and
Bone pain you must suspect metastatic prostate cancer (Do bone scan).
TX: Localized cancer: 1) active surveillance. 2) Radiation therapy (brachytherapy or external beam). 3) Radical Prostatectomy.
Advanced: 1) Hormonal therapy (most important-↓ serum testosterone to “castrate” range). 2) Orchiectomy. 3) LHRH agonists (S/E)
Bladder: more common in men-caucasians. Common etiologies (genetic, Occupational exposure (aniline dyes, aromatic amines), Smoking (4x
↑ risk). 75% present w/ superficial disease. 25% present w/ aggressive (muscle invasive).
TX: superficial:BCG (living TB attenuated mycobacterium) placed into bladder for carcinoma in-situ and recurrent high risk tumors.
Advanced: radical cystectomy w/ pelvic lymphadenopathy. This requires urinary diversion (ileal conduit or neobladder).
Kidney: symptoms of flank pain, hematuria, and a palpable mass. pts w/ Von Hippel Lindau Syndrome are at very high risk of recurrent,
multiple tumors (renal cell carcinomas).
TX; removal of primary principle tumor. Ablative techniques (cryotherapy) is also used. For extensive local tumors radical
nephrectomy is required.
Testicular: peaks late adolescence to early adulthood (20-40). Most common solid tumors of men 20-34. Most common type is seminoma
(40%), embryonal (20-25%), teratocarcinoma (25-30%), teratoma (5-10%), choriocarcinoma (1%). ↑ risk if HX of cryptochordism (3-14%) w/
(5-10% risk) in contralateral testis tumor. Mass in the testis is testicular tumor until proven otherwise.
PE and ultrasound (occasionally) to DX testicular tumor.
TX: radical orchiectomy (removal of testis from level of spermatic cord at internal inguinal ring).
Spread: testislymphatics (stage 1) retroperitoneal nodes (stage 2)lung via cisterna chili (stage 3)lungs. (staging DX by CXR and CT)
AFP: produced in embryonal carcinomas, teratocarcinomas, and yolk sac tumors (never by choriocarcinoma or seminoma)
HCG: 100% of choriocarcinomas, 40-60% of embryonal carcinomas, and 5-10% of seminomas have HCG.
TX: Seminoma: 75% present in stage 1 (excellent survival). radiation to retroperitoneum or short course chemo. For those w/
metastasis platinum –based chemo.
Non-seminoma: surveillance, retroperitoneal node dissection, primary chemo (platinum), radiation.
Cis-Platinum provided the cure for testicular cancer!!
Fluid and Electrolyte Therapy (153-162)-Arar
(at least 1 TQ will be a calculation) Holliday-Seger method for MAINTENANCE FLUID:
3 to 10 kg 100 ml/kg/day 4ml/kg/hr
11 to 20 kg 1000 ml + 50 ml/kg/d* [40 + 2/kg/hr*]
>20 kg 1500 ml + 20 ml/kg/d** [60 + 1/kg/hr**]
* For each kg>10
** For each kg>20
Metabolic rate per unit of body weight ↓ w/ increasing age.
Maintenance requirements for Na are 3-4 mEq/100ml of maintenance fluid. K requirements are 2-3mEq/100ml of maintenance fluid.
Addition of 5gm of dextrose per 100ml provides for 20% of caloric need. So for the purpose of maintenance therapy a solution of D5 1/4NS
plus 20mEw/L of K is the recommended maintenance fluid (this is based on maintenance fluid for a 10Kg child-100ml/kg fluid=1000ml, 30-40
mEq Na, and 20-30mEq K)
Know the different types of fluids:
CHO Na K+ HCO3-
Fluid (g/100 ml) (mEq/L) (mEq/L) (mEq/L)
D5W 5 - - -
D10W 10 - - -
NS (0.9%) - 154 - -
0.45% NaCl - 77 - -
D5 0.2% NaCl 5 34 - -
3% Saline - 513 - -
Ringer’s 0-10 147 4 -
0-10 130 4 28
Plasmanate - 110 2 29
Albumin 25% -
3% (30 mL/kg)
100-160 (60 mL/kg)
9% (90 mL/kg)
required in dehydrated patient: 1) estimate degree/severity of dehydration. (the best way(150 this is by acute weight changes) 2)
5% (50 mL/kg) 10% (100 mL/kg) 15% to do mL/kg)
Determine the type of dehydration (based on [Na] 3) calculate fluid/electrolyte requirements for degree/type of dehydration.
Dehydration Mild Moderate Severe
Water deficit determined by acute wt loss over <24hrs.
Skin turgor Normal Tenting None
Skin-touch Normal Dry Clammy
mucosa/lips Moist Dry Parched/cracked
Eyes Normal Deep Set Sunken
Crying/tears Present Reduced None
Fontanelle Flat Soft Sunken
CNS Consolable Irritable Lethargic/obtunded
15 Pulse Regular Slightly increased Increased
Urine Output Normal Decreased Anuric
For the same clinical observations, fluid deficit is greater in hypernatremic dehydration and
smaller in hyponatremic dehydration.
The main goal is to stabilize the patient hemodynamically which is done by initially giving an isotonic fluid (0.9%NS) as a bolus of 20-40
ml/kg until normal BP and perfusion are restored. After stabilizingcalculate which type of fluid to administer. In dehydration the amount of
fluid needed is IVF + fluid deficit. In dehydration (isotonic) ½ of the deficit is given in the 1st 8 hours and the other ½ over the next 16hrs.
Know how to do the calculations. You have to know the amount of Na needed in order to decide which fluid to give. Examples in syllabus and
the powerpoint. (in his powerpoint he uses 10% in the moderate dehydration of a CHILD. I think he means INFANT. (They are different as
Common Pediatric Renal Disorders (pgs 163-172)-Arar
There are no Objectives listed for this lecture!
Hematuria: >5RBC per High power field. (Confirm over 3 fresh specimens over a few weeks).
Hematuria w/ coexistent proteinuria is suggestive of glomerular bleeding. RBC casts indicate glomerular bleeding such as glomerulonephritis
(present only 50% of cases). In glomerular hematuria the RBC morphology is irregular (dysmorphic) in size and shape (in >10% of cells),
whereas in lower tract bleeding the RBCs are normal.
Glomerular: 1) Benign recurrent or persistent hematuria (50-75% of all cases) (Sporadic, Familial-Thin Basement Membrane
Disease). 2) Primary glomerulopathy (Acute Glomerulonephritis, Chronic Glomerulonephritis, Hereditary Nephritis (Alports), IgA
Non-Glomerular: 1) UTI. 2) Idiopathic hypercalciuria. 3) Nephrolithiasis. 4) Renal malformations (Cystic kidneys). 5) Urinary tract
obstruction (UPJ obstruction). 6) Sickle cell trait/disease. 7) Tumors (Wilm’s, Leukemia). 8) Trauma (local inflammation, foreign body,
External Injury). 9) Interstitial Nephritis (drug induced “allergic”).
Indicators for non-benign cause of hematuria: 1) family history of glomerulonephritis, nerve deafness, CRF, kidney transplantation. 2)
recurrent episodes of gross hematuria. 3) systemic complaints such as fever, arthritis or arthralgia, and skin rash. 4) coexistent proteinuria. 5)
Elevated BUN or creatinine.
Proteinuria: Qualitative: 1+ (30-99mg/dl) on dipstick exam of 2/3 random urine specimens collected one week apart w/ specific gravity
<1.015. 2+ (100-299mg/dl) if urine specific gravity >1.015. Semiquantitative: Urine protein/creatine ratio of >0.2 on early morning specimen.
Range of >1.8 is considered nephrotic range proteinuria. Quantitative: normal (<4mg/m/hr in 12-24hr urine specimen). Abormal (4-40).
Transient: (75% of cases in children) exercise, fever, dehydration.
Orthostatic proteinuria: (rare in pts <6 yrs) (accounts for 60+% of older children w/ persistent, isolated proteinuria and greater %
Primary glomerular Disease: Minimal change disease, Focal Segmental Glomerulosclerosis (FSGS), membranous nephropathy,
acute post-strep glomerulonephritis, membranoproliferative GN, Hereditary nephritis (Alports), IgA nephropathy.
Primary Tubulointerstitial disease: reflux nephropathy, Renal hypoplasia, Acute interstitial nephritis.
Secondary Renal Disease: Systemic Lupus Erythematosis, Vasculitis.
Initial screening is urinalysis. Dipstick of first void (morning) and repeat sample several hours later (if equivocal then a timed 12-hour
recumbent and upright specimens should be obtained. Additional studies (BUN, creatinine, serum proteins, cholesterol, complement levels,
ANA, Hepatitis B&C Ab.
Indicators for non-benign proteinuria: coexistent hematuria w/ or w/o cellular casts, systemic complaints (fever, arthritis, arthralgias, skin rash),
family history of GN or renal failure, HTN, edema, cutaneous vasculitis, purpura, elevated BUN and creatinine.
Acute Post Streptococcal glomerulonephritis
Abrupt onset of microscopic/gross hematuria (tea/coke colored), edema (periorbital), and HTN with variable degrees of renal insufficiency.
Associated w/ malaise, lethargy, anorexia, fever, abdominal pain, or headache. On labs we see RBC casts in 50% of patients. Dysmorphic
RBC’s. preceeding strep infection w/ ASO titer elevated in 70-80% of cases. Elevated antideoxyribonuclease B (anti-DNAse-B) titer in 90% of
patients w/ preceeding strep skin infection. The complement pathway is activated so we see low CD3, CH50, and C4 levels.
Pathology: enlarged glomeruli w/ proliferative mesangial areas. Deposition of IgG, C3, and C1q along capillary loops. EM shows dense
subepithelial deposits “humpy bumpy” appearance.
Treatment/prognosis: anti-hypertensive drugs, fluid/salt restriction, and TX of potentially life threatening edema, Hyperkalemia, or
hypertensive encephalopathy. Most recover spontaneously and renal failure and HTN are transient. Proteinuria disappears in 1-3 months, gross
hematuria by 2-3weeks, microscopic hematuria in 6-12 months.
Childhood Nephrotic Syndrome:
Nephrotic syndrome is a condition w/ heavy proteinuria, hypoalbuminemia, and edema. Pts are Normontensive. Hyperlipidemia is always seen.
It is synonymous w/ MCD. 1/6000 children will have CNS. 80% are <6 years old (median age 2.5yrs). M:F 3:2. MCNS is associated w/
abnormal charge selectivity (loss of negative charge on GBM caused by T-cell cytokinesalbuminuria). Often preceded by respiratory
infection or routine immunizations.
Pathology: normal size glomeruli w/ normal glomerular tuft. Mesagnium is not expanded. ↑ in mononuclear cells. EM effacement of visceral
epithelial cells and fusion of foot processes.
Clinical: edema due to ↓ oncotic pressure and Na retentioneyelid swelling, ascites, pleural effusion, scrotal/labial edema, pitting edema of the
legs. Infection and thrombosis are the two most serious complications. Peritonitis is the most common and serious infectious complication and
may be assoc w/ sepsis. Cellulitis, measles, and chicken pox are others. Thrombotic complications (arterial and venous) occur due to loss of
ATIII, ↑ Fibrinogen, slowed venous circulation, and platelet hypercoagulability. Occasional hypovolemia due to ↓ oncotic pressurecan cause
renal failure due to ATN.
Labs: Nephrotic range proteinuria (>40 or prot/creat ratio >1.8mg). hypoalbuminemia (<2.5gm/dl). High triglycerides and cholesterol. ↑
hematocrit. Hematuria (microscopic).
Treatment: salt/fluid restriction. Give normal protein supplements. Pts w/ symptomatic hypovolemiaor ↑ hematocrit and very low urine [Na]
may benefit from 25% albumin w/ IV lasix. Prednisone 60mg/m/day or 2mg/kg/day for 4 weeks then 40mg every other day for 4 weeks.
Mortality: 2% with majority due to peritonitis or thrombosis. Most pts w/ MCD eventually outgrow the disease.
Chronic Renal Failure-Part One (pgs 173-196)-Henrich
1) Staging of CRF
Staging and Clinical Presentation of CKD
Stage Description GFR Clinical
1 Kidney damage with normal >90 Well
or GFR Normal Cr Azotemia is absent
2 Mild GFR 60-89 Well, may be hypertensive
3 Moderate GFR 30-59 Chronically ill, anemic,
Increased Cr HTN, SHPT
4 Severe GFR 15-29 Above plus anemia
Increased Cr Dietary restriction needed
for Na, K, PO4
5 Kidney Failure <15 or Dialysis Above plus N, V, High K
Cr is > 5 mg/dL ,Fluid retention
Dialysis or Transplant
2) Natural history of progressive renal disease.
Once the GFR falls below 50 ml/min kidney fxn declines (constant) and progresses to ESKD. The degree of proteinuria is the single most
important predictor of progression (higher proteinuria faster progression).
Uremia: symptomatic stage of renal failure. Indicates retention of constituents of normal urine as renal failure develops. It does not indicate
3) Distinguish between ARF and CRF
Chronic Renal Failure: CRD: kidney damage > 3 months w/ or w/o ↓ GFR or a GFR <60ml/min for >3 months w/ or w/o kidney damage.
CRF: irreversible loss of GFR due to CKD leading to end stage renal disease regardless of etiology.
Look for a history of systemic disease (DM, HTN, SLE, PKD, and vasculitis). Look for nocturia, hematuria, proteinuria, and edema. The most
reliable evidence for CRF is prior sustained elevations of BUN and serum Creatinine. Renal ultrasound is the key DX of CKD (small kidneys,
↓ cortical thickness, scarring, multiple systs all indicate chronic processes-the kidney may be large or small).
Superimposed AKI on CRF: ECF volume loss (volume loss), ↓ EABV (cirrhosis, CHF), nephrotoxic drugs (NSAIDS), radiocontrast, recent
bleeding, UTO, systemic and UTIs.
Causes: DM, GN, HTN, Polycystic kidney disease (case 4 conference 4), CT disease, SLE, analgesic nephropathy, chronic pyelonephritis,
Pathology: Changes in all structures of the kidney: Glomerular sclerosis, interstitial fibrosis, arteriolar hyalinosis, medial thickening, intimal
Glomerulosclerosis mediators: ECM accumulation, ↑ intraglomerular pressure, ↑ mesangial matrix, lipid, and macromolecule accumulation,
cytokine/growth factor mediated damage, alterations of coagulation.
Acute Renal Failure: previous lecture.
4) Mechanisms of adaptation to nephron loss
When nephrons are lost we see ↑ in nephron hypertrophy and hyperfunction.
Steady state fluid and electrolyte balance can be maintained as long as intake=excretion. (excretory capacity is sufficient to accommodate
• Plasma water, Na, and K concentration can be maintained until 75-90% of nephrons are lost. HCO3, Ca, phosphorous are maintained
until 50-75% are lost. Creatinine and Urea plasma concentrations ↑ as nephrons are lost.
• Surviving (functional) nephrons undergo structural adaptations in order to compensate for lost nephrons (could make them non-
functional). This is termed “the final common pathway” of chronic renal injury. There is enlargement of the glomeruli w/o a change
in the number of cells. (hypertrophy of all parts of the nephron, glomerular diameter ↑ by 50%, PT cells ↑ in size↑ size and
diameter, similar but less marked changes in DT). These changes are thought to be caused by the signals: ATII, TGF-B, IGF-1. These
changes cause an ↑ in single nephron plasma flow (due to the vaso-dilator/constrictor effects of PGs), an ↑ in SNGFR (due to ↑ in
glomerular capillary hydrostatic pressure ↑ transcapillary pressure gradient).
• Changes in PT: ↑ Na/K ATPase. ↑ capacity to reabsorb glomerular filtrate. ↑ net acid secretion due to ↑ enzymes that metabolize
glutamine into ammonia.
• TALH, DT, CD: ↑ capcity to reabsord NaCl. ↑ capacity to generate free water. Capacity to concentrate urine impaired due to scarred
interstitium. ↑ capacity of DT and CD to secrete K.
5) Pathophysiology of the complications of CRF
To maintain water balance, the functioning nephrons exhibit enhanced osmotic diuresis. (↑ osmoles excreted↑ water secretion). This causes
impaired concentrating ability in which the patient has to drink more water in order to excrete daily osmolar loadleading to isosthenuria,
polyuria, Nocturia. Because the patient is unable to either concentrate or dilute urine, an ↑ or ↓ in water intake can cause Hyponatremia and
hypernatremia respectively. (patient must drink 2-3 L of water/day).
• Patients w/ CRF have an ↑ FEna of about 5% (nl <1%) b/c GFR is ↓ (~12.5ml/min)(nl 125ml/min). This means less Na is filtered
(2520 compared to 25200), but the same amount (125mEq) is still excreted. This prevents fluid overload. The ECF volume is
maintained at near normal levels until GFR drops to below 10ml/min.
• Hyperkalemia is unusual if GFR>15ml/min. There is ↑ excretion of K in CRF. Due to osmolar diuresis more Na reaches the DT and
CD causing ↑ reab of Na and ↑ secretion of K. (↑ Na/K ATPase activity). Also, the distal colon (Aldosterone sensitive) ↑ fecal K
output by ↑ colon Na/K ATPase (~ 30% of K intake is excreted by the colon).
o B-blockers/digoxin (↓ Na/K ATpase), PG inhibition, spironolactone (aldo inhibitor), Trimethoprim, Amiloride, Triamterene
(inhibitors of distal K secretion), ACE inhibitors (interrupt RAAS). All of these cause drug induced Hyperkalemia in CRF.
6) Approach to management of patients w/ CRF
GFR is the gold standard in determining kidney function. It can be measured by Creatinine levels, but the optimal marker is Inulin (freely
filtered and neither secreted or reabsorbed).
Chronic Renal Failure-Part Two (pgs 197-222)-Qunibi
1) Pathophysiology of complications of CRF
Acid Excretion: Net renal acid excretion: Titratable acid (H2PO4) + NH4 – HCO3 lost in urine. Regulation of Acid-base balance becomes
impaired when 50-70% of nephrons are lost. (acidemia doesn’t occur until GFR falls to < 20-30ml/min. Impaired ammonia production is the
main reason for impaired net acid excretion in CRF patients (even though there is a ↑ in NH3 generation and NH4 excretion, there is an overall
↓ due to loss of NH3 producing nephrons). Since acid excretion is impaired there is retention of H ions causing acidosis. The ↑ H ions have to
be buffered b HCO3 causing the HCO3 plasma concentration to drop. ↓ HCO3- is replaced w/ Cl- to balance anions and cations
(hyperchloremic metabolic acidosis).