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RENAL ANATOMYGeneral: Outer cortex with inner medulla containing the pyramids Nephron: glomerulus + tubule structure

Glomerulus (located in the cortex and contained w/I Bowman's capsule) - site of most filtration Some glomeruli at the juxtamedullary region

Collecting system: drains to calyx >> renal pelvis to ureter

Kidney is major site ofEPO production

Innervation: sympathetic stimulation >> release of renin from juxtaglomerular cells >>Angiotensin & aldosterone production

Blood supply:from main renal artery (branch of aorta) BaroreceptorsAfferent arteriole >> glomerular capillaries >> efferent arterioles >>

form hairpin loops called vasa recta that extend deep into medulla >> venous circulation

Coretx has high blood flow >> greatly diminishes as vasa recta descends into medulla

Juxtagomerular apparatus: macula densa (portion of distal convoluted tubule)

MD cells sense solute concentration of ultrafiltrate

juxtaglomerular cells communicate with MD >> receive sympathetic innervation >>

Can make renin & Angiotensin AND cause vasoconstriction of arterioles

Corticomedullary osmotic gradients: (300 in cortex >> 1200 in medulla)

Established via: 1. Na/K/2 Cl transport into water impermeable TAL then interstitium

2. Reabsorption of urea in CCD in presence of ADH

3. Slow blood flow through medulla >> removal of solutes minimized

Nephron segments:

Proximal Tubule: Primary function is isoosmotic reabsorption of glomerular ultrafiltrate (2/3rd) Bowmans capsule

Reabsorption: Sodium Water Cl Bicarb Calcium PT - Proximal tubule

Amino acids, glucose and PO4 can also be cotransported with Na DTL - Descending thin limb

3Na/ 2K+ ATP ase in basolateral membrane sets up ionic gradient ATL - Ascending thin limb

Secreted: Ammonia, and H+ TAL - Thick ascending limb

MOI: Na+/H+ antiporter - Na reabsorption, H+ secretion DT - Distal tubule

Bicarb + H+ CO2 + H20 via carbonic anhydrase (CA inhibited by diretics)

DTL: Passive water reabsorption CCD - Cortical collecting duct

ATL: Passive salt reabsorption IMCD Inner Medullary collecting ductTAL: Active NaCl and K absorption

Impermeable to water >> luminal fluid hypotonic

PTH stimulates rate of Calcium reabsorption

MOI: Na/K/2 Cl symporter Rom K K+ channel >> K+ secretion >> (+) lumen potential >>Ca+ and Mg+ reabsorption

Site of loop diuretics

DT: Impermeable to Water

Active NaCl reabsorption (symporter) K secretion Ca+ reabsorption

Symporter blocked by Thiazides

CCD: Na, K & H20 channels K+/H+ pump K secretion K secretion further stimulated by Aldosterone

H+ secretion & bicarb reabsorption Negative lumen potential due to more Na reabsorbed than K being secreted

ADH: Acts on CCD and IMCD >> insertion of water channels into principle cells ADH increases reabsorption of urea

Vitamin D: requires two hydroxylations to become hormone that regulates interstitial calcium reabsorption

One of these occurs in proximal tubule Hydroxylation stimulated by PTH and low phosphate

Renin: From JGA cells >> ultimately to AII >> vasoconstriction, Na reabsorption in PT, Na reabsorption in DT (Aldosterone), h20 reabsorption in CCD (ADH)

Stimulus: 1.renal hypoperfusion in afferent arterioles 2. effective circ vol (barorecptors) >>sympathetic stim 3. NaCl sensed in macula densa cells

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Volume DisordersGeneral: We are 60% salt water - 40% ICF ECF is primarily what changes

3/4 of ECF is interstitial space, 1/4 is plasma

Barrier between ICF and ECF >> largely impermeable to solutes, more permeable to water

Osmolarity: # osmoles/L solute Osmolarity: # osmoles/kg solute

Osmole: osmotic force generated/1 mole of solute

1 L H20 = 1 kg >> osmolarity & osmolality are used interchangeably

Total Body fluid (TBF) osmolarity is tightly regulated by water intake & excretion

ECF volume changes in parallel with total body sodium content & is regulated by renal sodium excretion

Response to water load: Low TBF osmolarity, low serum Na and High TBF volume ADH water excretion, TBF osmolarity and volume restored to n

Response to pure NaCl load: High ECF Osmolarity H20 moves from ICF to ECF High ECF volume/Low ICF volume & High TBF osmolarity

ADH (& thirst) TBF osmolarity, serum Na and ICF volume normal

High ECF volume/Na content

Since TBF osmolarity (~ serum Na): Any alteration in Na content will result in proportional alteration in ECF volume

ECF Vol/Na content:Sensed: Effective Vascular Volume or Effective Circulating Volum Part of ECF in the vascular space AND effectively perfusing the tissues

"fullness & pressure in arterial tree" Determined by ECF volume, CO and vascular tone Closely related to BP

Sensor: Sensed by stretch receptors - not volume receptors

Baroreceptors in carotid sinus, aortic arch and afferent glomerular arterioles

Ex: decreased Na in take >> decreased intravascular volume (and effective arteriole volume) >> decreased stretch >> ACTIVATION

Effector: Angiotensin II, Aldosterone, SNS & ANF >> in urine an excretion

Na restriction >> Angiotensin II and SNS action

Mechanisms to increase effective circulating volume:

vasoconstriction, CO

renal sodium reabsorption (water passively follows)

renal water reabsorption (w/o Na) - not as good >> decrease in osmolarity/hyponatremia

only happens in severe pathology to maintain ECF volume - ADH is activated non-osmotically

SNS - venous & arterial constriction, CO, HR & contractility, renin secretion from kidney, Na reabsorption in PT

>> Increased BP, renal blood flow & GFR

Clinical dx of ECF: JVP - indicative of venous compartment of intravascular volume

Orthostatic BP/HR - index ofarterial volume

Peripheral/pulmonary edema & ascites - excess ofinterstitial fluid volume & total ECF volume

TBF Osmolarity/H20:

Sensed: plasma osmolarity Serum an concentration not = Na content

Sensor: osmoreceptors Can have Na & be volume depleted

Effector: ADH >> urine osmalrity/H20 output & thirst/H20 intakeClinical dx: serum [Na]

65% 35%

Na+Cl-CO3

K+, Mg 2+Phosphates (-)Proteins (-)

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Volume DepletionResult from alterations in Sodium balance

Hx: decreased PO intake postural lightheadedness PE: Decreased JVP Orthostatic hypotension & tachycar

increased fluid losses tired, lethargy Absent edema, decreased turgor

Causes:

GI Losses: vomiting, NG suction

diarrhea, ostomies, tube drainage

bleeding

Renal: Diuretics

adrenal insufficiency

NaCl wasting nephropathy

Skin/ Insensible

Respiratory: Sweat, fever

Burns Bleeding

3rd space Abdominal pathology

Sequestration: Crush injury

Acute pancreatitis

Volume overload:Volume overload: Edematous disorders - pathologic misdistribution of ECF volume

overall ECF (Na & H20), effective arterial volume, interstitial or venous volume

CHF, Cirrhosis & Nephrotic syndrome

CHF: Filling Pressures >> sequestration of blood in venous compartment & mvmt of fluid from vascular to interstitial space (edema)

CO >> effective arterial volume >> activation of SNS and RAAS >> renal Na retention

Result: overall increase in ECF (volume overload) with a misdistribution of the volume

Cirrhosis: intrahepatic and portal venous pressure >> sequestration ofexcess blood volume in splanchnic circulation & ascites

Vasodilation (NO mediated) in splanchnic & peripheral circulations >> further sequestration and decreased effective arterial volume

Hypoalbuminemia contributes to tendency to form peripheral edema ( plasma oncotic pressure)

Nephrotic syndrome: primary renal protein loss >> hypoalbuminemia >> misdistribution of ECF to interstitial space >> effective arterial vol & 2 renal N

hypoalbuminemia may also promote PRIMARY renal Na retention

Result: Expanded total ECF volume/Na content - edema

Rx: Treat underlying disorder

Na restriction in combo with diuretics

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l

-

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ia

retention

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Acute Renal FailureGeneral: abrupt deterioration in the ability of the kidney to excrete nitrogenous waste

Lab values lag behind the dz and may be unchanged for awhile

kidney function/GFR must 30-40% before creatinine rises

Small creatinine represents significant kidney injury

ARF has high mortality

Poor prognostics: age, severe underlying dz, multiple organ failure

Leading cause of deaths:

infx, underlying dz progression, fluid/electrolyte imbalanceClassification: Prerenal azotemia

Acute parenchymal RF:

ATN (acute tubular necrosis) - most common

Glomerular, tubuloinerstitial or Vascular inflammation

Thrombotic or Embolic RV occlusion

Postrenal azotemia ( a.k.a) Obstructive uropathy

Pre & postrenal azotemia almost always treatable by treating underlying cause

Urinalysis:

Oliguria: < 400 ml/24 hr

prerenal ARF

Acute parenchymal ARF

Urinary tract obstn

Normal: .5 - 2L /24hr

Nephrotic ATN

Polyuria: > 2L/24 hr

Hyperosmolar stress, diabetes insipidus

Catabolic pts receiving high protein load

partial urinary tract obstn

Anuria: < 100 ml/24hr

urinary tract obstnbilateral renal cortical necrosis

(septic miscarriage)

Acute glomerulonephritis, vascular occlusion or massive ATN event

Acute vs. Chronic? Prerenal vs. Renal/ATN

Factors suggesting chronic: fine hyaline casts dirty brown coarse casts

Small kidney size SG RTE (renal tubular epithelial cells)

hx of kidney dz, HTN or abnormal urinalysis Urine Osm Urine Osm

Anemia, metabolic acidosis, hyperkalemia, hyperphosphatemia usually present Urine Na ( 40)

Creatinine (> 40) Creatinine (< 20)

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Obstructive or Postrenal ARF

Causes: Intrinsic obstn: blood clots, stones, sloughed papillae, fungal balls Extrinsic obstn: malignancy, retroperoneal fibrosis, iatr

Bladder: Stones, blood clots, prostatic hypertrophy or malignancy, carcinoma Urethral: strictures, phimosis

Clinical: History of previous UTO or UTI

predisposing to papillary necrosis (DM, sickle cell, analgesic abuse)

Pelvic or retroperitoneal dz or surgery

Sign & sx: Dysuria, nocturia, frx, hesitation, weakening stream Anuria or wide range in urine output

Enlarged prostate Distended bladder

Many asymptomatic Flank masses or tendernessNormal urinalysis in setting of progressive renal failure - suggests the problem is in the plumbing

Prerenal Azotemia Decrease in effective blood volume - volume depletion

ECF may be decreased or also may be increased (cardiac failure, cirrhosis), but effective blood volume is decreased

Renal hypoperfusion - kidney take their cue exclusively from renal artery P - they assume you are volume depleted and tries to compensate

>> RAAS, SNS & ADH >> cortical blood flow >> Na, water & urea reabsorption >> Oliguria, Azotemia & urine osmola

Osmolarity of urine increases b/c there is < water respectively

NSAIDS & ACEI >> cortical blood flow & GFR >> ATN

Causes: Intravascular Vol Reduced CO Systemic Vasodilation Systemic or renal Vasoconstn Impaired renal autoregulation

Hemorrhage CHF, cardiogenic shock Anaphylaxis Anesthesia, Surgery

GI, renal, skin losses Pericardial tamponade Drug OD Dopamine Hyperviscosity syndromeSequestration PE Sepsis or drugs Alpha agonist

Clinical: Hx & Sx: Hx of fluid loss, use of NSAIDs or ACEI, thirst

Signs: Fluid deficit, weight loss, oliguria, orthostatic hypotension Tachycardia

Flack neck veins when supine Lack of sweat, dry mucosa and decreased turgor

Renal/ATN:

Ischemic or toxic injury to kidney >> imbalance in vasoactive hormones

>> persistent intrarenal vasoconstriction >> medullary hypoxia

in renal hemodynamics >> in total RBF & redistribution away from outer cortex

Death of tubule cells - dieing cells slough off >> block tubules >> may lead to oliguria

Cells can recover from insult and regenerate/restore normal functionBack-leak of filtered tubular fluid due to damaged tubular epithelium

In hospital setting, ATN is most common cause of ARF

Clinical Course:

Initiating Phase: b/t onset of renal function & establishment of renal failure

usually reversible

Maintenance Phase: renal failure not immediately reversible

last few hours to 6+ weeks

most complications occur during this phase

Recovery Phase: renal function begins to improverecovery w/i 4 weeks and is usually complete

some pts have polyuric phase >> serious fluid/electrolyte imbalance

Rhabdomyolysis: muscle breakdown >> muscle pain & dark brown urine w/o RBC are diagnostic clues

creatine kinase should be elevated, coupled with myoglobin in the urine

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Management of ARFGeneral: ID & correct all reversible factors

Attempt conversion of oligouric >> nonoligouric ATN by administering diuretics

Monitor fluid/electrolyte imbalance

Complications: Biochemical Monitoring:

Hypervolemia Serum Na - avoid hyponatremia by restricting free water

Hyperkalemia - can lead to asystole Serum K - rx w/ sodium bicarb, glucose plus insulin or dialysis

High anion gap metabolic acidosis Serum bicarb - maintain above 15 mEq (for acidosis)Hyponatremia >> CNS dysfunction Serum phosphate - control hyperphosphatemia w/ phosphate binders (aluminum hydroxide

Uremia >> neuro dysfunction, GI bleed or platelet dysfunction Serum Ca - Rx only if symptomatic or if IV sodium bicarb used

Infx (sepsis, pneumonia & UTI) leading cause of mortality

Fluids & Diet: Fluids: Restrict fluids to match measured + insensible losses

Diet: Electrolytes - restrict to match measured losses

Protein - restrict

Carbs - provided at least 100 g/day

Weight - allow for loss of .5 lb/day due to catabolism

Dialysis: Early dialysis simplifies management and nutritional support Pneumonic AEIOUIndications for dialysis in Oliguric patients: A - acidemia

1. Severe hyperkalemia (monitoring EKG better guide than K) E - electrolyte (K+)

2. Volume overload resulting in CHF or HTN I - ingestion

3. Sever metabolic acidosis (pH < 7.2) O - Overload (volume)

4. Symptomatic uremia (encephalopathy, hemorrhagic gastritis) U - Uremia

5. BUN > 100 mg/dl

6. Uremic pericarditis

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genic

rity, Na

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Acid Base DisordersEndogenous acid production: catabolism of glucose & fatty acids >> CO2 and H20 >> pulmonary excretion

metabolism of sulfur containing amino acids, phospholipids & phosphoproteins >>kidney metabolism

CO2 CO2 + H20 H2CO3 H+ + HCO3-

Acidemia: Arterial pH < 7.37

Normal values: pH H+ pCO2 HCO3- Acidosis: Process that results in acidemia if left unopposed

Arterial 7.37-7.43 37-43 36-44 22-26 Alkalemia: Arterial pH > 7.43

Venous 7.32-7.38 42-48 42-50 23-27 Alkalosis: process that results in alkalemia if left unopposed

Metabolic: From primary alteration in [H+] or [HCO3-]Respiratory: From primary alteration in pCO2 due to in CO2 elimination

Buffering: Immediate defense of pH

In acute setting, hemoglobin, albumin, plasma proteins & intracellular phosphates can all accept protons (H+)

In chronic setting, bone can release base into the blood (>>ultimately results in brittle bones)

Renal Handling of Acid Load: Requires base/bicarb reclamation & net acid secretion

Bicarb: Kidneys are stingy with bicarb - < 1% secreted in urine (if tubular abnormalities exist >> spilling of bicarb in urine0

75% of bicarb reclamation occurs in proximal convoluted tubule

Stimulatory factors for bicarb absorption: Volume depletion Intracellular acidosis Hypokalemia

Chloride depletion IntracellularpCO2

Acid: Secretion occurs primarily in distal nephronMust have secretion of H+ into tubule and trapping of the protons by ammonia (NH3 formed in proximal tubule) to form ammonium (NH4)

Stimulatory factors for acid secretion: Na delivery & transport (CCT) K+ deficiency

Aldosterone Increased pCO2

Ammoniagenesis: Enhanced in proximal tubule by chronic acidosis and hypokalemia

Secretion in distal tubule enhanced by chronic acidosis and aldosterone

Clinical Approach: Respiratory Alkalosis: 1in pCO2

Questions to ask: What is primary event (ex. loss of acid via vomiting) Respiratory Acidosis: 1in pCO2

What is the response (from lungs or kidneys)? Is it appropriate? Metabolic Alkalosis: 1in HCO3

How to correct quickly? Metabolic Acidosis: 1in HCO3

Evaluation: Hx & PEObtain simultaneous chemistries and ABGs >> determine primary disorder & appropriate response

Calculate serum anion gap

Common causes:

Respiratory Alkalosis: PE, cirrhosis, sepsis, pregnancy

Respiratory acidosis: COPD

Metabolic Alkalosis: Vomiting, diuretic use (excrete NaCl and tubules hold onto bicarb)

Metabolic Acidosis: Hypotension (perfusion), severe diarrhea (lose bicarb from fluids), renal failure & sepsis

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CompensationPrimary Disorder Primary Defect Effect on pH Compensatory Response Expected Compensation Compensatory Limits

Respiratory Acidosis hypoventilation HCO3 generation [HC03] = 1-4 mEq/L [HC03] = 45 mEq/L

PCO2 for each 10 mm Hg in PCO2

Respiratory Alkalosis Hyperventilation HCO3 consumption [HCO3] = 2-5 mEq/L [HCO3] = 12-15 mEq/L

PCO2 for each 10 mm Hg in PCO2

Metabolic Acidosis Loss of bicarb or Increase in ventilation PCO2 = 1.5 [HCO3-] + 8 (+/- 2) PCO2 = 12-14 mm Hg

gain of H+ PCO2 Winter's formula

Metabolic Alkalosis Gain of bicarb or Decrease in ventilation PCO2 = .6 * in HCO3 PCO2 = 55 mm Hgloss of H+ PCO2

Metabolic AcidosisGeneral: Decreased arterial pH, decreased serum bicarb, decreased arterial pCO2

Respiratory response calculated via winter's formula

Expected PCO2 = 1.5 [HCO3-] + 8 (+/- 2)

Anion Gap: When organic acids (ex. lactic) added to ECF, bicarb falls as acid is buffered

Anion gap increases as organic base is accumulated

Represents the unmeasured anions in serum

[Na] - [Cl + HCO3] Normal is 8-12

If AG is high >> there is an anion not usually present in pt

Ex. salicylate (ASA) or ketones (DKA or starvation)

Normal AG = hyperchloremic High AG = normochloremic

Rx: Should be aimed at underlying cause

In pt w/ nml lung function, PCO2 should decrease in attempt to normalize pH

Parenteral Sodium bicarb if pH < 7.1 & pt hemodynamically unstable

Oral bicarb if loss is due to GI loss or RTA (renal tubule acidosis)

Metabolic AlkalosisGeneral: Increased arterial pH, increased serum bicarb, increased arterial pCO2 DDx Anion Gap

Often accompanied by hypochloremia or hypokalemia MUDPILES

M - MethanolStages: Generation Stage: loss of acid, gain of bicarb, 1 aldosteronism (oversecretion of aldosterone by adrenal medulla) U - Uremia (RF)

Maintenance Stage: Kidney loses ability to excrete bicarb efficiently D - DKA

Cl- deficiency Decreased GFR =/- increased PT bicarb reabsorption P - Paraldehyde

Hypermineralocorticoidism and hypokalemia I - Intoxication (Alcoholic KA)

L - Lactic acidosis

Assess/Rx: What is the source of alkali gain or acid loss? What is preventing renal excretion of HCO3- E - Ethylene glycol (suicide)

Commonly GI HCl loss, diuretics, endogenous or exogenous mineral corticoid excess S - Salycylate (ASA) or Starvation

Volume depletion >> aldosterone secretion >> stimulates DT K+ and H+ secretion

Hypokalemia >> maintenance of metabolic alkalosis >> must correct K+ deficiency to correct alkalosis

Monitor K and Cl depletion Rx often involves administration of K+ and Volume

If urinary [Cl-] , pt will be responsive to saline If urinary [Cl-], pt will be unresponsive to saline

Simple vs. Mixed Simple: One primary disorder with appropriate compensatory responseMixed: If compensation inappropriate, must consider more than one primary disorder

Normal pH in combo with abnormal PCO2 and serum bicarb also suggest mixed

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ACID-BASE BALANCE AND THE KIDNEYSStages of Acid Base Balance: Acid Synthesis >> Buffering >> Excretion

most metabolic processes occurring in the body result in the production of acid

Endogenous Acid Production:

mostly f/ catabolism of glc and FA to CO2 and H2O (cellular respiration) volatile acids excreted by lungs

metabolism of sulfur containing aa, phospholipids/proteins nonvolatile acids excreted by kidneys

Bicarbonate buffering system: CO2 + H2O H2CO3 H+ + HCO3-

Normal Acid Base Values: pH [H+] pCO2 [HCO3]

Arterial 7.37-7.43 37-43 36-44 22-26

Venous 7.32-7.38 42-48 42-50 23-27

Arterial pH < 7.37 = acidemia Arterial pH > 7.43 = alkalemia

Buffering immediate defense of pH; acute - Hgb, albumin, plasma protein, intracellular phosphates; chronic - bonebut, ultimately, the acid produced must be excreted

Renal Handling of Acid Load: base (bicarb) reclamation and net acid secretion

1 mEq/kg H+ (nonvolatile) produced daily

Bicarb: proximal tubule reabsorption

due to presence of carbonic anhydrase

stimulated by volume depletion

chloride depletion

intracellular acidosis

increased intracellular pCO2

hypokalemia

Acid: Distal nephron secretionEliminates hydrogen equivalent to nonvolatile acid prod.

Inorganic bases of nonvolatile acids filtered at glomerulus,

poorly reabsorbed; these bases and ammonia f/ PT cells trap

secreted H+ for elimination in urine

ti l t d b i d N d li d

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Assessment of Acid Base Status: Terminology:

1st: ABG and serum electrolytes Acidemia - blood pH < 7.35

Obtain a minimum diagnosis/primary disorder Alkalemia - blood pH < 7.45

look at pH for acidemia v. alkalemia Acidosis - process that results in

match w/ pCO2/HCO3 for metabolic v. respiratory acidemia if left unopposed

Determine appropriate compensation/response Alkalosis - process that results in

if compensation is inappropriate, consider mixed disorder alkalosis if left unopposed

Calculate anion gaps (serum, urine, delta, osmolar) Metabolic - disorder that results f/

high v. nml is used to aid in the ddx of metabolic acidosis primary alteration in [H] or [HCO3]

Respiratory - disorder that results f/

primary alteration in pCO2

Anion Gap: represents unmeasured anions in serum conventional calculation: [Na] - [Cl + HCO3]

high: indicates loss of bicarb w/o subsequent increase in Cl-; electroneutrality maintained by production of anions like ketones, lactate, SO4 and PO4 (not part of calculation);

so, there is an anion in this pt that is not normally present

normal: (8-12) hyperchloremic metabolic acidosis; drop in bicarb is compensated for by in Cl-

Varieties of Acid Base Disorders: Respiratory Alkalosis ( in pCO2)

pulmonary embolism, cirrhosis, sepsis, pregnancy

Respiratory Acidosis ( in pCO2)

chronic obstructive pulmonary disease

Metabolic Alkalosis ( in HCO3)vomiting, diuretic use

Metabolic Acidosis ( in HCO3)

hypotension, severe diarrhea, renal failure, sepsis

Simple disorder: one primary disorder (including appropriate reponse) Mixed: 2,3,4 primary disorders

METABOLIC ACIDOSIS

Manifested by: arterial pH serum bicarb conc arterial pCO2

Assessment of low serum bicarb: Check ABG to exclude chronic resp alkalosis

Calculate serum anion gap

Classification of Metabolic Acidosis:

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RENAL TUBULAR ACIDOSIS SYNDROMES

group of disorders in which there is a failure of the kidney to either resorb bicarb or excrete hydrogen ions

which is unrelated to advancing renal failure

Proximal RTA - bicarb threshold is reduced from 25 to 18-20; occurs w/ systemic illness or molec defects

(Type II)

Distal RTA - most common type; disease of the intercalated cell of distal nephron

(Type I) usually due to inherited defect in H+ ATPase

always hyperchloremic acidosis

accompanied, b/c of Na loss, by 2ndary hyperaldosteronism, leading to K depletion

Distal RTA - hyporeninemic hypoaldosteronism

(Type IV) disorder of the prinicpal cells, usually in interstitial renal dz

destruction of macula densa >> renin productionimpaired angiotensin production

tendency to develop hyperkalemia

METABOLIC ALKALOSIS

Manifested by: arterial pH serum bicarb conc arterial pCO2

Accompanied by: hypochloremia hypokalemia

Generation Stage loss of acid gain of bicarb primary aldosteronism

Maintenance Stage kidney loses ability to excrete bicarb efficiently

Cl- deficiency (extracellular volume contraction) GFR and/or proximal tubule HCO3 reabsorption

hypermineralocorticoidism and hypokalemia

Diagnostic Categories:

Saline Responsive ( urinary Cl-) Saline Unresponsive ( urinary Cl-)

Normotensive Hypertensive

Vomiting/nasogastric suction Primary aldosteronism

Diuretics Cushing syndrome

Posthypercapnia Renal artery stenosis

K+ depletion NormotensiveVolume expansion = mainstay of therapy Mg++ deficiency

Severe K+ deficiency

Bartter syndrome

Gitelman syndrome

Treat the underlying cause

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Potassium DisordersResting membrane potential: Intracellular K+ far exceeds etracellular K+ Only 2% of total body stores are in ECF

1 mEq decrease in serum K+ is proportional to 200 mEq deficit in total body K+

Membrane more permeabile to K+ than Na >> readily moves down CG to set up RMP

Small change in K on either side of membrane >> significant change in RMP

Acid/base status another determinant of serum K (bc of H+/K+ pump in nephron)

K+ metabolism:

Primarily from diet

Renal excretion is slow >> most K is rapidly redistributed from extracellular to intracellular compartmentInsulin: activates ATPase by recruiting more pumps to cell membrane

B2 agonists: breaks down ATP >> cAMP >> stimulates ATPase

Renal response: bulk of K reabsorption occurs in PT; further reabsorption occurs in TAL

Aldosterone >> K+ secretion in CCD and IMCD via principal cells

w/o Aldosterone - prone to hyperkalemia (asystole & death)

H+/K+ pump in IMCD last gate to reabsorb K in presence of low K+ intake

TAL: Na/2 Cl/K channel moves these ions from lumen back into the cell

An additional K channel (ROM K) allows for K diffusion back to the lumen >> positive electrical potential in the lumen

>> enhances mvmt of Ca+ and Mg+ back to blood

>> enhances absorption of NaCl (because cotransported with K from lumen)

Furosemide (Lasix)blocks Na/2 Cl/K channelK+ secretion enhanced by: 1. Rate of DT flow 3. Presence of poorly reabsorbable anions in tubular fluid

2. Distal delivery of Na 4. Stimulation by aldosterone (NaCl reabsorbed - K secreted)

HyperkalemiaGeneral:

Increased extracellular K >>

CM partially depolarizes>> AP

Na permeabilty decreases

Lethal condition & medical emergency!

Chronic renal insufficiency does not cause hyperkalemia unless advancedSx: muscle weakness & paralysis

EKG: Accelerates repolarization

Peaked T waves decreased or absent P waves

Late stage - inactivation of Na channel >> wide QRS complex

Rx:

ER or need for rapid - give Ca gluconate

(Ca+ antagonizes effects of hyperkalemia - protects conduction system)

Dextrose/Insulin to shift K+ intracellularly

(buys time for the kidneys excretory function to kick in)

K exchange resin (Kayexalate) - enhances K+ secretion from GI tract

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HypokalemiaEtiology: Low serum potassium - may not accurately reflect total body stores

Caused by either inadequate intake, excess secretion or transcellular shift

Transcellular shift: Alkalemia (drop in K+ b/c body hanging on to H+ via pump)

Insulin

B agonists/stress (esp in conjuction with MI, alcohol withdrawl or asthma attack)

Renal loss: Too much K+ leaking into lumen >> Urinary K+ > 20 mEq

Extrarenal loss: Urinary K+ > no positive electriacal gradient to reabsorb Ca+)

Gitelman's Syndrome: Similar to Bartter's syndrome, though only a defect in NaCl transporter (K+ not involved)

Body's compensatory response is to Renin/Aldosterone Accompanied by hypocalciuria

Liddle's syndrome: Hyperabsorption of NaCl (due to faulty channel) >> favors K+ dumping & volume expansion >> renin & aldosterone

Sx: Rhabdomyolysis, muscle weakness & paralysis THIRSTY

Ab pn, bloating & constipation (adynamic ileus) Palpitations

EKG: Increased ventricular excitabilty (extra systoles)

Delayed repolarization >> flattening of T waves and development of U waves

Late development - inactivation of Na channel >> prolonged QRS

Rx: Determine serum Mg >> if hypomagnesemia, Mg must be administered to correct hypokalemia

Oral potassium

IV potassium if severe arrythmias or dig toxicity

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Water DisordersOsmolality: ratio of solute to water in all compartments in plasma Na almost always reflects in H20 balance

in ECF osmolality >> reciprocal in ICF PE findings refelect patient's volume status

ECF osmolality estimated by calculating serum osmolality

= 2 [Na] +[glucose]/18 + [BUN]/2.8

Serum osmolality ~ 290 or 2[Na]

Tubular Fluid - upon arriving at distal tubule = 50 to 100 mOsm/kg

Concentration of Urine:

In response to plasma Osm/ECV >> thirst & ADH

Water retention primarily due to ADH acting on CD

ADH docks on receptor >>

Aquaporin 2 >> from cytoplasm to luminal membrane to form water channels

Water then free to move down isomotic gradient for reabsorption

ADH typically regulated osmotically

Non-osmatic regulation of ADH (in pathologic setting of volume disorder) can

>> extreme stimulatory effect on ADH

Hypoooooonatremia

WATER INTOXICATION!!!!!!!General: Can occur in context of hypovolemia, euvolemia and hypervolemia

Path: Either due to an increase in PT reabsorption of H20 or inability to excrete H20

H2O excretion impaired due to GFR, NaCl reabsorption in diluting segments of DT, or failure to suppress ADH secretion

Kidneys CANNOT excrete water when they have a volume disorder (hyper or hypovolemia)

Causes of hyposomolar hyponatremia

Hypovolemia: ECF volume, ECV

Hypervolemia: total ECF volume

ECV - Una > 20

ECV - Una < 20

Pseudohyponatremia:

(hyperosmolality)

hyperglycemia

hypertonic mannitol

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Management of Noneuvolemic Hyponatremia

Hypovolemic hyponatremia - volume restoration with isotonic saline

identify and correct cause of H2O and Na loss

Hypovolemic hyponatremia - Na and H2O restriction

Loop diuretics

Treat underlying condition

no saline

Syndrome of Inappropriate ADH Secretion (SIADH)

prototype of primary release of ADH usually pathologic processes of central nervous system or pulmonary system

ADH >> excessive H2O reabsorption >> GFR >> kidney (hey now) Na >> reestablish euvolemia (but, now hyponatremia)

Diagnosis: Essential Supplemental

osmolarity ( 100) no correction of plasma Na w/ vol expansion,

clinical euvolemia but improvement after H2O resriction

U Na conc w/ nml Na/H2O intakeno adrenal, thyroid, pituitary, diuretic use, renal insufficiency

Causes: hypothalamic production of ADH (neuropsych disorders, drugs, pulmonary dz, post op, severe nausea)

ectopic production of ADH (carcinoma - oat cell, bronchogenic)

potentiation of ADH effect (drugs, including NSAIDs)

exogenous administration of ADH

Tx: Symptomatic SIADH Administer Na slowly because rapid infusion

acute hyponatremia (< 48 hrs): serum Na at rate up to 2 mEq/hr until sxs resolve can shrink the brain

chronic hyponatremia (> 48 hrs): don't exceed 1-1.5 mEq/hr

measure serum and urine electrolytes every 2 hrsperform frequent neurologic evaluations

Chronic Asymptomatic SIADH

fluid restriction

solute intake (furosemide + 2-3 g NaCl daily

pharmacologic inhibition of ADH via demeclocycline or V2-receptor antagonist

Signs and Symptoms of Hyponatremia

CNS: Mild - apathy, HA, lethargy most sxs related to brain swelling:

Moderate - agitation, ataxia, confusion, disorientation, psychosis hypoosmolar ECF >> water shift >> brain water content

Severe - stupor, coma, Cheyne-Stokes respirations

GI: anorexia, N/V

MSK: cramps, diminished DTR

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HyperrrrrrrnatremiaWATER DEPLETION, DEHYDRATION!!!!!!!!!!!

General: can be hypervolemic, euvolemic, hypovolemic

most cases - excess H2O loss, not Na gain

Path: usually, primary defect is in urinary concentrating ability + insufficient admin of free H2O

Causes of hypernatremia:

Osmotic Diuresis

lg amt of osmotically active solutes in filtrate

>> H2O loss in urine in excess of electrolytes

Diabetes Insipidus collecting tubule is impermeable to H2O central defect in release of ADH vs. nephrogenic defect w/ responsiveness

Central Causes Congenital Acquired: post-traumatic, tumor, aneurysm, meningitis/encephalitis, Guillain-Barre

Nephrogenic Causes Congenital Acquired: renal dz, hypercalcemia, hypokalemia, drugs (lithium, demeclocycline)

Signs and Symptoms of Hypernatremia

CNS: mild - restlessness, lethargy, altered mental status, irritability

moderate - disorientation, confusion

severe - stupor, coma, seizures, death

Respiratory: labored respirations

GI: intense thirst, N/V

MSK: muscle twitching, spasticity, hypereflexia

Tx: hypernatremia w/ hypovolemia implies Na deficit in addition to H2O deficit >> isotonic saline infusion

other pts >> hypotonic IV solutions (D5W, 1/2 NS, 1/4 NS); administer soln that is hypotonic relative to urine

Rate is important! chronic hypernatremia (> 36-48 hrs) brain makes compounds to raise intracellular osmolarity to minimize shrinkage

rapid correction >> H2O shift to relatively hypertonic intracellular compartment >> brain edema

general rule = correct over 48 hrs not exceeding 0.5 mEq/L/hr, or 12 mEq/L/day

Urinalysis

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Urinalysis

Dip Stick: start with clean catch, note colormeasures: pH, SG, glucose, proteins, ketones, bilirubin, blood, urobilinogen, nitrite

SG: Normal range 1.003-1.035 SG of 1.010 approximates plasma (osmolality of 300 in plasma) = isothenuria

Correlates with osmolality ([urine]) < 1.010 is dilute > 1.010 is concentrated (Water is 1.0)

Specific gravity may be different than osmolality in cases of proteinuria, glycosuria, radiocontrast dyes or increased urea in urine

pH: Normally 4.5 - 6.0 (Physiologic range 4.5 - 8.0)

Proteinuria:Graded on scale from Negative to trace to 1+, 2+, 3+, 4+ (grade correlates with concentration)Detects negatively charged proteins well (albumin) -

Won't detect: microalbuminuria

(+) like Ig in monoclonal gammopathy (ie Bence Jones)

tubular proteins (Tamm - Horsfall proteins)

Large amounts of albumin suggest glomerular dz (normally filtration in glomerulus is restricted by size and charge)

Normal: < 300 mg/day Consisting of Tamm Horsfall proteins = glycoprotein coating renal tubular cells in DT

Dipstick refelects concentration of protein not quantity

Characterizing Proteinuria: Evaluation of Proteinuria

Quantity: > 3.5 g/day = Nephrotic > is freely filteres but later reabsorbedGlucose > 500 exceeds reabsorptive capabilities Damage to PT (even w/ nml glucose) >>low reabsorptive capability

Microscopic Findings: Cells, casts, crystals & bacteriaHyaline casts: Normal finding - are a cast of DT itself, made of Tamm-Horsfall proteins and seen on microscopy as transluscent

Granular casts: Have cellular debris within - suggestive of renal parenchymal damage (may be coarse or fine)

Coarse (dirty brown) suggestive of ATN

Oval fat bodies: Lipid laden macrophages or renal tubule cells - seen in nephrotic syndrome (glomerulonephritis, pyelonephritis or ATN)

RBC casts: pathognomonic for glomerularnephritis WBC casts: Hypersensitivity & interstitial nephritis

Waxy casts: Indicative of more advanced failure or chronic dz Broad casts: Due to tubular enlargement w/ time - chronic dCrystals: Calcium oxylate: (seen in more acidic urine) nml in absnce of other sx, may be seen w/ stones or polyethelene glycol poisoning

Triphosphate: (seen in more alkaline urine)

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tinine ratio

reted/day

sis

z

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Nephrotic Syndrome

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Path: 1. Minimal Change Dz & FSGS due to injury to glomerular epithelial cells 4. Membranoproliferative

2. Membranous Neuropathy due to immune-complex formation & complement activation in subepithelial space 5. Ig A Nephropathy

3. Deposition Dz - diabetic neuropathy , SLE, amyloidosis - affect GBM

Process: loss of interdigitation & foot process effacement >> "swiss cheese" blanket over glomerulus = gaping holes for protein to leak through

Clinical: Proteinuria > 3.5, hyperlipidemia (oval fat bodies), Complications:

Hypoalbumemia >>edema (Na retention), hyperlipoproteinemia, platelet hyperaggregability Thromboembolic

Hyperlipidemia may be both choleterol and/or triglycerides Loss of carrier/binding proteins >>Renal Tubular Injury Mineral, calcium & Vit D deficiencies

Negative nitrogen balance & malnutition in drug metabolism and diuretic resistance

Loss of Ig >> depressed cellular immunity

MCD - Corticosteroids Cyclosporine

Rx: Rx edema w/ restricted NaCl & diuresis Dietary protein restriction FSGS - Corticosteroids & Immunosppression

ACE I - reduces proteinuria by 50% NSAIDs - in high doses protein (severe only) Membranous - Steroids & Alkylating agents

Membranous Glomerulonephritis (MGM):

Most common cause of Nephrotic syndrome in adults May be primary or secondary (2ndary to drugs, infx, hepatitis, maliganancy)

Path: Microscopic hematuria w/o RBC casts No inflammatory cells

Thickening of capillaries with BM "spike formation" Granular deposits og IgG and complement

Minimal Change Nephrotic Syndrome (MCNS): "Lipoid Nephrosis"

85-95 % of all kids (2-8) w/ nephrotic syndrome have MCD M:F 2:1 15-20% of adults

Affects visceral epithelial cells (podocytes) >> proteinuria

No Ig or complement deposition to be seen by microscopy or immunoflouresence

Effacement of foot processes only seen on electron microscopy

Bland urine typical of nephrotic syndrome, but good renal function & no HTN

Rx: Responds dramatically to corticosteroids Not considered steroid resistant until fail to respond to 16 wks rx

Relapses common and treated similary to initial episodes Cyclosporine may be valuable in steroid-resistant ptsGood prognosis - 3/4 dz free in 10 years, rarely progresses to kidney failure

Focal Segmental Glomerulosclerosis (FSGS):

Characterized by segemntal sclerosis of only a small % of glomeruli May be primary or secondary (HIV, Heroin, Sickle cell, obesity)

10% of kids, 15% of adults

Same disease process as MCNS, though you do also get HTN and decreased renal function

LM: sclerosis IF: IgM & C3 deposition in mesangium EM: foot process effacement

Rx: Poorer response to corticosteroids 20% adults >> rapid renal failure w/i 2 years

Kids have better prognosis Recurrence in transplant pts 40-50% of time

Rapidly Progressive Glomerulonephritis (RPGN)

d i h li i ll id d i l f l f i d li i

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Syndrome with many causes Clinically rapid and progressive loss of renal function and oliguria

Severe glomerular injury >> formation ofcrescents

Untreated leads to death w/i weeks to months

Classification: Anti-GBM dz (Goodpasture's) Immune complex (SLE, post-infx, Henoch-Schloen, idiopathic)

Path: w/ any underlying cause, imp feature is disruption of GBM

allows leakage of fibrin and blood into Bowman's space

forms crescents of fibrin, epithelial cells, and infl cells

LM: proliferative GN w/ crescents possible focal necrosis of glomerulus

IF: Anti-IgM dz - linear deposition of IgG along entire GBM Immune Complex - granular deposits, Ig depending on cause

Goodpasture's: anti-GBM disease autoimmune disease w/ Ab against collagen type IV

more common in the young and M > F

cross reacts with alveolar basement membranes

clinical pres may include RPGN w/pulmonary hemorrhage/hemoptysis and dyspnea

Rx: high dose oral prednisone, cytotoxic agents, plasmapheresis

Renal Biopsy: Can be used for dx of glomerular, tubular & interstitial dzs; following progression of dz

In atypical presentation to rule out other causes

Usually percutaneous guided by ultrasound - via jugular

3 cores >> 1. Light microscopy 2. Immunofluoresence 3. Electron microscopy

Rarely specific and dx b/c many syndromes have similar pathology

Secondary Glomerulonephritis

Lupus primarily a dz of young women

presents as any of the glomerular dz syndromes from minimal change to crescentic most common = nephrotic w/ active sedimentdiagnosis via serologic evidence of antinuclear antibody production in the presence of inflammation of multiple organs

nephritis = most common cause of death in SLE biopsy to determine stage of disease

Tx: class I and II = no tx

class III = lowest possible does of corticosteroids

class IV = possible addition of cytotoxic drugs

Diabetes characterized by persistent albuminuria, relentless decline in GFR, HTN

microalbuminuria (>30 nd > almost inevitable proteinuria (>350mg/day) w/i next 5 years >> 50% have ESRD w/i 7 to 10 yrs

thickening of GBM

Lesions: Kimmelstiel-Wilson nodular glomerulosclerosis = classic diabetic lesion

nodular in hyaline matl >> massively expands mesangial areas surrounded by dilated/thickened capillary loopsDiffuse glomerulosclerosis = more common, uniform increase in mesangial matrix

Arterioles - accelerated hyaline arteriosclerosis; effects afferent and efferent; accelerated fibroplasia

Tx: control glc, tx HTN, restrict dietary proteins

HIV: many different causes of renal disease

infection (postinfectious, membranous, membranoproliferative), tubular dz, FSGS

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ty

Nonglomerular Disorders

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Nonglomerular Disorders

Tubulointerstitial Nephropathy

disorders that principally affect the renal tubules and interstitium w/ relative sparing of glomeruli and renal vasculature

Acute interstitial Nephritis (AIN): sudden onset days to wks acute inflammatory infiltrate

Etiology: drugs, systemic infx, immune

Clinical: dev of acute renal insuff; often systemic hypersensitivity

Diagnosis: U/A may be 1st clue - hematuria, sterile pyuria, leukocyte casts, mild - mod proteinuria

Also, hyperkalemia, RTA, sodium wasting

Definitive - only by biopsy

Tx: discontinue offending drug; possibly short course of hi dose steroids

Chronic Interstitial Nephropathy: gradual progression yrs predominantly interstitial scarring and fibrosis

Etiology: urinary tract obstruction; drugs (analgesics, usu w/ ASA); cytotoxic/immunosuppressives; hypertensive nephrosclerosis; radiation

nephritis (w/ lg doses); heavy metals; metabolic abn; malignancy (multiple myeloma); immune disorders

Clinical: slow dev of renal insuff; functional tubular defects; interstitial fibrosis w/ atrophy and loss of tubules

interstitial mononuclear cell infiltrate; little or no evidence of active renal infl

Diagnosis: underlying cause

Cystic Diseases

Simple Cysts: increase with age (esp > 50) most asymptomatic; usu incidental finding ultrasound + CT to differentiate benign f/ malignant

Polycystic Kidney Dz: Autosomal Dominant PKD = adult PKD (ADPKD) Autosomal Recessive PKD = infantile (ARPKD)

ADPKD most common hereditary renal dz in US clinical manifestations rarely before age 20-25

Clinical: usu acute abd flank pn and back pain w/ hematuria; also, nonspecific, dull lumbar pn (when kidneys are lg enough to feel)

sharp, localized pn from cyst rupture or infx; initial sign - often microhematuria

Other - HTN, nocturia, impaired salt conservation Complications - UTI, pyelo, cyst infx, hepatic cysts, cerebral aneurysm

ESRF in almost 50% of pts by age 60Diagnosis: radiographic evidence of multiple cysts; renal enlargement, cortical thickness

US shows characteristic bilateral involvement; CT shows degree of cystic involvement

Tx: prevent complications and preserve renal function ESRF - transplant or dialysis

Acquired Cystic Kidney Dz: dev of cysts in pt w/ chronic renal failure or ESRD who are on dialysis; dx w/ CT

Medullary Cystic Disorders: rare inherited dz; small medullary cysts not easily seen; ESRF in adolescence; eye deformities, anemia, prolonged eneuresis

Urinary Tract Obstruction

Unilateral ureteral obstruction - usu no detectable change in urinary flow or renal fxn; azotemia or renal failure only if drainage of both compromised

Clinical: Presenting sign - usu chng in urinary habit True anuria = complete obstruction Polyuria = common inpartial

Total anuria or widely varying output suggest urinary tract destruction

Diagnosis: renal sonography; ID hydronephrosis Tx: ID site and cause; relief of obstruction, usu surgery (may >> post obstructive diuresis

Urinary Tract Infection

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y

Pyelonephritis: bacterial infx of kidney; collecting system + renal parenchyma Cystitis: bacterial infx of bladder either can be acute or chronic

Ascending - spread f/ urethra, usus w/ sex, catheter, post op; more common Hematogenous - spread f/ blood, usu after septicemia

Acute Pyelonephritis - suppurative infx; may see foci of pus/abscesses; pus may permeate entire kidney and fill renal pelvis (pyonephrosis)

mostly females; fever, back pain, dysuria; high WBC, pyuria, positive urine culture

kidneys enlarged and edematous; erythematous, possibly dilated renal pelvis; may have papillary necrosis

inflammatory infiltrate in tubules and interstitium (neutrophils, lymphocytes, plasma cells); yellow streaks in cortex

Chronic Pyelonephritis - destruction of renal parenchyma and broad parenchymal scar formation; ultimately, small and irregularly scarred kidney

usually asymmetric involvement commonly caused by vesicoureteral reflux and renal pelvic reflux

chronic interstitial inflammation; tubular atrophy; interstitial fibrosis; glomerulosclerosis; hydronephrosis; cortical scarring

Acute Cystitis - grossly visible congestion; mucosal hemorrhages; seen on cystoscopy; severe - mucosa covered w/ pus or ulcerated; bx = acute inflammation

Chronic Cystitis - foci of hemorrhage, ulceration, thickening; thick bladder wall UTIs: tx w/ antibiotics +/- sulfa drugs

Nephrolithiasis

Urinary stones/calculi - common in ages 20-45; M > F; more in developed countries b/c high protein, low fiber diet; most pts, 1st episode >> 2nd w/in 2-3 yrs

Clinical: hematuria and sudden onset of colicky pain in flank w/ radiation to groin on same side some polyuria, dysuria, vomiting, ileus

Screening: past hx of stones/ infx, fam hx, diet U/A - pH, hematuria, r/o infx, ID type of stone electrolytes, creatinine, serum Ca, PO4, uric acid

Mngment: requires identification of type of stone b/c of recurrence, all pt should consume 3 L of fluid/day, maintain 2L of urinary vol/day, protein & salt

most pass spontaneously; obstr/fever/pn = surgery; extracorporeal shock wave lithotripsy for pt w/ pelvic/upper ureteral stones; US lithotripsy for lower

Types: Calcium 75% of all stones; calcium oxalate > calcium phosphate (which require alkaline pH)

hyperexcretion of Ca in pts w/ abn metabolism (hyperabsorptive hypercalciuria) restrict salt; consider thiazide

Struvite magnesium ammonia phosphate or sulfate triple phosphate stones radiopaque "staghorn" = lg and irregular

typically a complication of UTIs (>> formation of ammonia f/ urea in urine >> alkaline urine >> precipitation of struvite)

may grow progressively and fill entire renal pelvis

Uric Acid 50% of pts have gout or hyperuricemia precipitated by acidic urine, dehydrationneed to increase vol and alkalinize urine >> oral sodium bicarb

Cystine very rare hexagonal in shape maintain high urine output and alkalinize urine

Developmental Disorders

Renal Agenesis: failure of kidney to develop; M > F; usually unilateral; asymptomatic (hypertrophy of remaining kidney) bilateral = incompatible w/ life

Horseshoe Kidney: solitary kidney caused by fusion of lower poles in the midline; usually asymptomatic; M > F; may cause ureteral obstruction ( risk of infx)

Cystic Dysplasia: disordered dev of kidney; may be sm or lg; cystic and distorted; differentiate f/ ADPKD b/c usually unilateral

Chronic Kidney Disease (CKD)

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Kidney dz: AKA - Azotemia, renal failure or insufficiency, uremia

End stage renal failure (ESRD) - pt is receiving dialysis & is eligible for Medicare Staging: GFR

1 Damage w/ nml or GFR > 90

CKD defined: 1. KD > 3 months - structural or functional abnormalities, w/ or w/o GFR, manifested by: 2 Damage w/ mild GFR 60-89

a. pathologic abnormalities OR 3 Moderate GFR 30- 59

b. markers of kidney damage - abnl blood or urine composition or imaging tests 4 Severe GFR 15 - 29

2. GFR < 60 ml/min for > 3 months, w/ or w/o kidney damage 5 Kidney Failure < 15

Etiology: Most die of Stage 3 due to CV problems or infx (before progressing to 4 r 5) Stage 3 mandates dialysis

Diabetes & HTN are 2 most common causes (2/3rds of population), followed by glomerulonephritis, PCKD &interstitial nephrits

Risk factors: Underlying dz - HTN, diabetes, dyslipidemia Family hx of KD Aging

Lifestyle - tobacco, inactivity, obesity Male

Ethnic - AA (FSGS), native american (diabetes), latin american (diabetic), asian american & pacific islanders (IgA nephropathy)

Prenatal - maternal DM, low birth weight, small for gestational age (born w/ < nephrons)

Exposure to nephrotoxic agemnts - NSAIDs, contrst dye

Diagnosis:General: Srceen: Basic metanolic panel (BMP): Na, Cl, K, CO2, BUN, Creatinine Urinalysis Imaging

Often can dx conditions via: H & P - Diabetic nephropathy & HTN nephrosclerosis

Urinalysis- Interstitial nephritis, glomerular dz

Ulrasound - Polycystic dz, obstructive nephropathy

Indications for renal biopsy: RF of unknown etiology or nephrotic or nephritic syndrome

Spot urine: Dipstick Microscopic Protein/Creatinine ratio FENA = Cl Na/ Cl Cr * 100

Electrolytes (Na, K, Cl, Creatinine) >> 1. Fractional Excretion of Na (FENA) = ( U Na * V)/ (P Na * time) /(U Cr * V)/ (P Cr * time)

2. Anion Gap (to determine acidosis) =[( U Na/ P Na) / (U Cr/ P Cr) ] * 100

In steady state FENA usually 1%

If Pt is hypernatremic or volume overloaded (b/c they can't dump Na) >> FENA will be < 1 %

24 hr urine: Kidney functional has diurnal variation - this can help

Creatine Clearance Protein (Both can be obtained to some degree via spot urine - therfore not an indication for 24 hr sample)

Urine urea nitrogen - protein intake = (6.25 * UNN in g) + (.031 * Kg of body wt) Urine electrolytes

GFR: Indication of renal function - can be estimated by Creatinine clearance Cl Cr = U Cr * V/ P Cr * time

Can be estimated using Cockroft Gault formula (DON"T DO IT) or MDRD =Modification of Diet in Renal dz (DO IT - GO ONLINE)

Imaging: Ultrasound: (nml is 10-12 cm) can be done w/ doppler exam of vasculature or post void bladder volume ( nml is < 100 mL left)

Abdominal CT MRI & angiuography nIrtavenous pyelogram (IVP) - not done anymore

Renal artery angiography ( inject contrast to see vasculature)Functional stidies: Renal scan w/ ACE to evaluate stenosuis

Renal vein sampling - renin & aldosterone

CKD ManagementF t l f ti H fil i (b i i h ) P i i H i Si / f U i

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Factors renal function: Hyperfiltration (by surviving nephrons) Proteinuria Hypertension Signs/sx of Uremia:

Increased intraglomerular P Hypotension Toxics (NSAIDs, contrast) NV, anorexia, dysguesia (mtl taste)

Diarrhea, constipation

Clinical: HTN Anemia Hypocalcemia Hyperphosphatemia Memory loss, D/N sleep pattern

Acidosis Hypervolemia Hyperkalemia Secondary Hyperthyoidism Asterixes, restless leg

Pericarditis

HTN: > 140/90 Due to Volume overload/sodium retention Uremic frost. Pruritis (sweating urea)

Increased afferent input from injured K (sympathetic activation) Vol (edem, rales, S$, ascites)Damaged vascular endothelium BUN/Creatinine

Excessive renin secretion PTH/Calcium ???? Hyperkalemia, Acidosis

Rx: Restrict dietary Na to 2 gm/day (monitor with 24 hour urine) Loop diuretic if GFR < 30 cc/min Hypocalcemia, hyperphosphatemia

Use anti- HTN to control BP - ACEI/ARB (Will GFR & creatinine - 30% ok, > should discontinue) Anemia

Anemia: Result of shortened RBC half-life in uremic env'e and EPO Normochromic, normocytic

Uremia >> Increased tendancy to bleed (prolonged bleeding time)

Rx: Recombinant human EPO Repalce iron Avoid tx (Ag exposure for future tx, tx infx dz)

creen for blood in stool Folate, B12 repletion if needed

Osteodystrophy: Secondary HyperparathyroidismDue to decreased Vit D production (requires a couple of hydroxylations - one of which occurs in kidnay)

Vit D >> Ca absorption in gut >> Serum Ca & [phosphate] >> PTH >> osteoclast activity & Ca release

Rx: Maintain target PTH: Stage 1 2 3 4 5

PTH 35-70 70-110 150-300 Ca+ can >> metastaitic

Lower serum phosphate via dietary restriction or phosphate binders (Al hydroxide, Mg, Ca carbonate, Ca acetate) Calcification in heart & arteries

Raise srum Ca - correct serun [phosphate], Ca supplement, replace Vit D

Acidosis: Bicarb < 24 & pH 7.35) Inability to excrete daily acid load (1 mEq/kg) >> metabolic acidosis & anion gap >> Osteopenia (H+ into bone for Ca out)

Rx: Repalace with bicarb - Sodium bicarn, sodium citrate, calcium carbonate, calcium acetete

Restrict dietary protein inatke (< .6 - .8 g/Kg body wt/day)

Hyperkalemia: Due to K+ secretion: Tubular urinary flow ( >> CG to allow K to diffuse into the lumen)

Aldosterone or impaired response DT intracellular K due to acidosis (H+/K+ pump)

Na delivery to DT (Na exhanged for K 1:1) lumen cations (+) >> unfavorable electrochemical gradient

Rx: Restrict dietary K (60 mEq/day or 2 gm/d) Use K-losing diuretics

Oral Na/K exchange resins

Correct acidosis and hyperglycemia (serum Osm >> H20 leaks out of cell, K follows)

Slowing Progression: Rx underlying condition Control BP

Reduce proteinuria (low carb diet, ACEI, ARBs)

Reduce hyperfiltration/glomerular HTN (inhibit RAAS)Correct CV risk factors

GFR decline is predicatble - plot 1/Serum Cr vs. Time to determine years to ESKD(can also extract from /yr)

CKD Stage 5: Options - Hemodialysis (access via fistula, graft or central line), peritoneal dialysis

Average rx is 4 hr session 3 days/wk Initiate dialysis if GFR < 15 (< 10 for diabetic pt)

Renal tx: Requires same blood tytpe HLA match (6/6) Immunosuppressive rx to prevent rejection (steroid & )

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Hypertension

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General: HTN increases CV Mortality

Joint Nat'l Committee on prevention, Detection, Evaluation & Rx of HTN = JNC VII >> set guidelines Systolic

Highlights: For pts > 50 yo Systolic BP > 140 is more important CVD risk factor than diastolic Normal < 120

Starting at 115/75, CVD risk doubles for each increment of 20/10 PreHTN 120-139

Normotensive pt at age 55 have a 90% lifetime risk of developing HTN HTN I 140-159

Pts w/ preHTN require health-promoting lifestyle modifications HTN II >160

African Americans have increased prevalence in both M & W

CVD risk factors: Target Organ Damage (TOD)

HTN Smoking Obesity (BMI > 30) Heart - LV hypertrophy, angina or prior MI, prior coronary revascularization

DM Microalbuminemia or estimated GFR < 60 Brain - stroke or TIA

Inactivity Dyslipidemia Chronic Kidney dz Peripheral artery dz

Age (>55M, > 65W) Family Hx of premature CVD (M

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Can localize the tumor with CT, MRI or I-MIBG scan

Sx Headache, sweating, palpitations, wt loss, pallor, orthostatic HTN, fundoscopic changes

6 Ps: Paroxysmal - Pressure (HTN), Pain (HA, abd pn), perspiration, palpitation, pallor

Screen: Plasma metanephrines (breakdown product of catecholamines) or catecholamines

Spot urine for metaanephrine

HTN Management:General: Decreased incidence of stroke, MI and heart failure Lifestyle modification:

With everyone you should encourage lifestyle modification Wt loss 5-20 mmHg/ PreHTN: No drug therapy indicated unless compelling indications DASH diet 8-14 mm

Stage I: Thiazide type diuretic for most May consider ACEI, ARB, BB, CCB or combo Limit NaCl 2-8 mm

Stage II: 2 drug combo (thiazide type for most + ACEI, ARB, BB or CCB Activity 4-9 mm

Alcohol 2-4 mm

GOALS: BP < 140/90 Greatest benefit with diastolic 80-85

DBP < 80 for blacks

BP < 130/80 for diabetics and those with chronic kidney dz

SBP of 140-145 for elderly with ISH

Themes: Thiazide type diuretics should be initial therapy of choice for most Certain High risk conditions warrant other

Most pts will require 2 or more drugs to achieve BP goal

If BP is > 20/10 mm above goal, initiate therapy with 2 drugs (one of which should be thiazide - unless contraindicated)

Patients should have monitoring & follow-up until goal reached - more frx visits for stage II

After goal reached, FU at 3-6 month intervals - more frx for comorbid conditions

Compelling Indications for Certain Drug Classes:

Heart Failure: Thiazide, BB, ACEI, ARB, Aldosterone antagonist High CAD risk: Thiazide, BB, ACEI, CCB

Post MI: BB, ACEI, Aldosterone antagonist Diabetes: Thiazide, BB, ACEI, ARB, CCB

Stroke prevention: Thiazide, ACEI CKD: ACEI, ARB

Favorable effects: Unfavorable effects:

Thiazide slow dimineralization in osteoporosis Thiazides - used cautiously in gout or hx of hyponatremia

BB useful in rx of atrial arrhythmias, migraines, thyrotoxosis BB - avoid in pts w/ asthma, reactive airway dz, 2 or 3rd degree heart block

CCBs useful in Reynaud's & certain arrhythmias ACEI & ARBS - contraindicated in pregnant (or soon to be)Alpha blockers useful in prostatism Aldosterone antagonists & K sparing diuretics can >> Hyperkalemia

HTN Urgencies & Emergencies:HTN Urgency: HTN Emergency - Malignant HTN

Accelerated malignant HTN (BP > 200 in asymptomatic pt) Sudden rise in BP w/ HA, change in mental status & neuro sx

Severe HTN in kidney transplant pt Path: cerebral edema, petechial hemorrhages & micro infarcts

Severe HTN (DBP> 120 w/ no impending complications) Eyes: hemorrhages, exudate & papilledema Renal: oliguria, azotemia

Severe epistaxis CNS: HA, confusion, somnolence, stupor GI: N/V

Cardio: LV hypertrophy/dysfunction, ischemia DBP > 140

Heme: Microangiopathic hemolytic anemia

Rx of Emergencies: IV Blood & urineContinuous BP monitoring - reduce BP to 160/100 or MAP by 25% Drugs: Vasodilators, Adrenergic inhibitors

Start Oral maintenance drugs ASAP

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Diastolic

< 80

80-89

89-99

>100

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10 Kg loss

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