Renal Disorders

Introduction
 Functions of the Kidneys in Homeostasis
 Excretion of metabolic waste products, foreign
chemicals, drugs, and hormone metabolites
 Regulation of water and electrolyte balances
 Regulation of erythrocyte production
 Regulation of arterial pressure
 Regulation of acid-base balance
 Regulation of 1,25–Dihydroxyvitamin D3 (calcitriol)
production
 Gluconeogenesis
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 Cont
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Cont…
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Acute Kidney Injury
 Introduction
 Definition: AKI is a decrease in glomerular filtration rate (GFR)

 Generally occurring over hours to days, sometimes over weeks,

 Associated with an accumulation of waste products (urea and
creatinine), disturbance in extracellular fluid volume and
electrolyte and acid base homeostasis.
 Diagnostic criteria
 Increase in SCr by at least 0.3 mg/dL within 48 hours or
 Increase in SCr by at least 1.5 times baseline within the prior 7
days or
 Decrease in urine volume to < 0.5 mL/kg/h for 6 hours
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Cont…
 Based on the amount of urine output acute renal

failure may be classified as:

 Anuric: if urine volume is <100 ml/day
 Oliguric: if urine volume is <400 ml/day
 Non-oliguric: if urine volume is ≥400 ml/day

7
 Risk Factors
 Older age
 Higher baseline serum creatinine (SCr)
 Chronic kidney disease (CKD)
 Diabetes
 Chronic respiratory illness
 Underlying cardiovascular disease
 Prior heart surgery
 Dehydration resulting in oliguria
 Acute infection
 Renal outflow obstruction, and
 Exposure to nephrotoxins
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 Pathophysiology
 Prerenal AKI

 Intrinsic AKI

 Post renal AKI

 Functional/Pseudo-renal/AKI

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 Prerenal AKI
 Prerenal AKI is the most common (55%) form of AKI

 Represents a physiologic response to mild to moderate

renal hypoperfusion
 Prerenal AKI is rapidly reversible upon restoration of renal

blood flow and glomerular ultrafiltration pressure.

 More severe hypoperfusion may lead to ischemic injury of

renal parenchyma and intrinsic renal AKI

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Major causes of Prerenal AKI
1. Hypovolemia
 Hemorrhage, burns, dehydration
 GI fluid loss: vomiting, surgical drainage, diarrhea
 Renal fluid loss: diuretics, osmotic diuresis (e.g., diabetes
mellitus), hypoaldestronism
 Sequestration in extravascular space: pancreatitis,
peritonitis, trauma, burns, severe hypoalbuminemia

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 Cont…
2. Low cardiac output
 Diseases of myocardium, valves, and pericardium;
arrhythmias; tamponade
 Other: pulmonary hypertension, massive pulmonary
embolus
3. Systemic vasodilatation: sepsis, anaphylaxis

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 Intrinsic AKI
 Acute intrinsic AKI results from damage to the kidney itself

 Account for nearly 40% of all AKI

 Disease of glomeruli or renal microvasculature

 Acute tubular necrosis (ATN): Ischemia, toxins
 Interstitial nephritis (inflammation within the renal
parenchyma)

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 Cont…
 It can be categorized on the basis of the structures within

the kidney that are injured: glomeruli, tubules, and the

interstitium.
 Glomerular damage results from severe inflammatory

processes specific to the glomerulus and it accounts about

5% of the case of intrinsic AKI

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 Cont…
Tubule damage/acute tubular necrosis/ATN
 Approx. 85% of all cases of intrinsic ARF are caused by ATN

 From these 50% are a result of renal ischemia, often arising

from an extended prerenal state.

 The remaining 35% are the result of exposure to direct tubule

toxins, which can be

 Endogenous (myoglobin, hemoglobin, or uric acid) or
 Exogenous (contrast agents, heavy metals, or
aminoglycoside antibiotics)

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 Cont…
Interstitial Damage
 The interstitium of the kidney is rarely the primary cause of

ESRD, but it can become severely inflamed and lead to ARF.

 Acute interstitial nephritis (AIN)is most commonly caused

by medications, or bacterial or viral infections.

 Up to 30% of cases have no identifiable cause

 It is cxzd by lesions comprised of monocytes, macrophages,

B cells, or T cells, clearly identifying an immunologic

response as the injurious process affecting the interstitium
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 Post Renal AKI (Obstruction)
 Account for ~5% of AKI.

 Ureteric: Calculi, blood clot, sloughed papillae, cancer,

external compression (e.g., retroperitoneal fibrosis)
 Bladder neck: Neurogenic bladder, prostatic hypertrophy,
calculi, cancer, blood clot
 Urethra: Stricture, congenital valve, phimosis

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 Functional/Pseudo-renal/AKI
 In functional ARF, a decline in GFR secondary to a reduced

glomerular hydrostatic pressure, which is the driving force

for the formation of ultrafiltrate, can occur without damage
to the kidney itself
 The decline in glomerular hydrostatic pressure may be a

direct consequence of changes in glomerular afferent

(vasoconstriction) and efferent (vasodilation) arteriolar
circumference

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Cont…
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 Cont
 Cont
 Cont

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 RIFLE Criteria
 The categories of kidney dysfunction in the RIFLE
classification include
 Patients at risk (R),
 Those with kidney injury (I), and
 Those with kidney failure (F).
 Two additional categories of clinical outcomes are
 Sustained loss (L) of kidney function, which requires RRT
for at least 4 weeks; and
 End stage renal disease (E), which necessitates RRT for at
least 3 months
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Algorithm for classification of AKI. The classification system
includes separate criteria for Cr/GFR and UOP
 Prerenal Intrinsic Postrenal
/Functional
History/ Volume depletion Ischemic failure Kidney
Presentation Renal artery Nephrotoxic stones
stenosis Vasculitis BPH
Hypercalcemia Glomerulonephritis Cancers
NSAID/ACEI use
Cyclosporine
Physical Hypotension Rash, Fever Distended
examination Dehydration bladder
Petchia if Enlarged
thrombotic prostate
Ascites
Serum BUN/ > 20:1 15:1 15:1
SCr ratio
 Cont… Prerenal Intrinsic Postrenal
/Functional
 It
Urine Yes No No
Concentrated? Low urine Na (<20 Urine Na >40 Urine Na>40
mEq/L) mEq/L mEq/L
Low FENa (<1) FENa >2 FENa >2
High Uosm Low Uosm Low Uosm
Urine Normal Muddy-brown Variable, may
Sediment granular casts; be normal
tubular epithelial
casts
Urinary WBC Negative 2-4+ Variable
Urinary RBC Negative 2-4+ 1+
Proteinuria Negative Positive Negative

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Signs and Symptoms of AKI
 Peripheral edema
 Weight gain
 Nausea/vomiting/ diarrhea/anorexia
 Mental status changes
 Fatigue
 Shortness of breath
 Pruritus
 Volume depletion (prerenal)
 Colored/foaming urine
 Anuria alternating with polyuria (postrenal)
 Colicky abdominal pain radiating from flank to groin (postrenal)

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 Diagnosis
Laboratory Evaluation
1. GFR: measures of overall kidney function

 GFR ranges from approximately 90 to 120 mL/minute

with normal kidney function.
 Decreased creatinine clearance in AKI
 Direct measurement of CrCl requires collection of urine
over an extended time interval (24 hrs) with
measurement of urine volume, urine creatinine and
serum creatinine levels
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 Cont…
Cockcroft-Gault
Urine Collection Method Equation for Adults

 Ucr = urine creatinine

concentration, mg/dL
 V = volume of urine, mL
 Scr = serum creatinine
concentration, mg/dL
 T = time of urine
collection, minute
 (Note: time equals 1440
minutes for a 24-hour
collection)
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 Cont…
2. Elevated serum creatinine concentration
 Normal 0.6 to 1.2 mg/dL
3. Elevated BUN concentration
 Normal 8 to 20 mg/dL)
4. BUN: creatinine ratio
 Elevated in prerenal AKI: >20:1
 Intrinsic or postrenal AKI: < 20:1

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 Cont…
5. Urinalysis
 Red cell casts - vasculitis or glomerulonephritis
 Muddy brown granular casts and epithelial cell casts in a
patient - acute tubular necrosis
6. Radiologic/imaging studies
 To assess urinary tract obstruction, kidney stones, renal
cyst or mass
 Renal ultrasonography, plain film of the abdomen (KUB)

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Prevention and Treatment
Desired Outcome
 To prevent AKI
 Avoid or minimize further renal insults that would
worsen the existing injury or delay recovery, and
 Provide supportive measures until kidney function
returns

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 General Approach to Treatment
 Prerenal and postrenal AKI can be reversed if the underlying

problem is promptly identified and corrected, while treatment of

intrinsic renal failure is more supportive in nature
 Supportive therapy such as fluid, electrolyte, and nutritional

support, renal replacement therapy (RRT), and treatment of non-

renal complications such as sepsis and gastrointestinal bleeding
while regeneration of the renal epithelium occurs.
 In addition, prevention of adverse drug reactions by

discontinuing nephrotoxic drugs or adjustment of drug dosages

based on the patient’s renal function is desired
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 Prevention of AKI
 The best treatment of AKI is prevention!
 Sometimes, risk is predictable, such as d perfusion 2˚ to coronary
bypass surgery or 2˚ to administration of a radiocontrast dye prior
 In these situations, the potential insult to the kidneys cannot be
avoided but may be preventable with aggressive hydration and
removal of any additional insults
 In outpatient, educate pt on preventive measures
 Optimal daily fluid intake (~2 L/day) to avoid dehydration, especially if
they are to receive nephrotoxic medication
 In inpatient
 Adequate hydration, standardized hemodynamic support in critically

ill, & avoidance of nephrotoxic medications

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 Pharmacologic Therapy
 Prerenal azotemia: Correct primary hemodynamic abnormalities

 Normal saline if volume depleted

 Pressure management if needed

 Blood products if the cause is blood loss

 Post renal azotemia – relieve obstruction

 Consult Urology

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 Cont…
 Intrinsic: no universal therapy

 Avoid insult

 Consider fluid bolus (perfusion/urine production)

 Loop diuretics for oliguric/euvolemic or hypervolemia

 Furosemide 40-80 mg IV every 6-8 hrs or

 Furosemide infusion 40-80 mg IV bolus; then, 10-20 mg/hr iv

 Dopamine therapy 1-2 mcg/kg/min

 Acidosis: restrict dietary protein

 HCO3 to maintain arterial pH > 7.2

 Dialysis if needed
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Cont…
Management of Fluid in AKI
 "Maintenance" is IRRELEVANT in ARF!!!

 If euvolemic: Give insensibles + losses + UOP

 Insensibles = 30 cc/100 kcal or 400cc/M2/day

 Concentrate all meds; limit oral intake

 Furosemide +/- thiazides

 Monitoring (wt, BP, I/O)

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 Cont…
1. Loop Diuretics
 Furosemide, bumetanide, torsemide, and ethacrynic acid
 Diuretics currently have no role in preventing AKI progression or
reducing mortality,
 But they can prevent complications, such as pulmonary edema.
 Loop diuretics are limited to instances of volume overload &
edema
 A usual starting dose of IV furosemide for the treatment of AKI is
40 mg
 For edema, IV furosemide (80 to 120 mg) is preferred because of
its potency
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 Cont…
 If urine output does not increase to about 1mL/kg/hr, the

dosage can be increased to a maximum of 160 to 200 mg of

furosemide or its equivalent
 Torsemide has excellent oral BA and is unaffected by gut

edema
 Closely monitor patient vital signs (weight, temperature, BP,

pulse, and respirations) several times per day

 Diuresis should aim for a weight loss of 0.5 to 1.0 kg per day

 The patient’s volume status should be assessed daily

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Cont…
 Other methods to improve diuresis can be initiated

sequentially, such as:

 Shortening the dosage interval;
 Adding HCT and
 Switching to a continuous infusion loop diuretic
 Thiazide diuretics, when used as single agents, are
generally not effective for fluid removal when creatinine
clearance is less than 30 mL/minute

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 Cont…
 Potassium – sparing diuretics, which inhibit sodium

reabsorption in the distal nephron and collecting duct, are

not sufficiently effective in removing fluid.
 In addition, they increase the risk of hyperkalemia in
patients already at risk.
 Thus, loop diuretics are the diuretics of choice for the

management of volume overload in AKI

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 Cont…
2. Dopamine ???
 Low-dose dopamine, in doses ranging from 0.5 to 3 mcg/kg
per minute
 Predominantly stimulates D1 receptors, leading to renal
vascular vasodilation and increased renal blood flow
 "Renal dose" dopamine could increase renal perfusion, esp.
with concurrent norepinephrine

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Complications of ARF
Fluid accumulation leads to
 Hypertension
 Hyperkalemia
 Hyperphosphatemia vs. hypocalcemia
 Acidosis
 Anemia……..decreased EPO production
 Uremic bleeding……BUN interferes w/platelet function

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 Hypertension
 Cause:

 Volume overload; Intrinsic renal disease

 Volume overload: direct vasodilators

 Calcium channel blockers, clonidine, nicardipine drip,

nitropruside, etc.
 Goal is to prevent stroke, CHF

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 Hyperkalemia
 Other risk factors:
 Infection, hemolysis, acidosis
 The most serious manifestations of hyperkalemia are muscle
weakness or paralysis, cardiac conduction abnormalities, and
cardiac arrhythmias.
 These manifestations usually occur when the serum potassium
concentration is ≥ 7.0 meq/L
 Indications for treatment includes
 Patients with hyperkalemia and ECG changes
 Patients with a serum potassium greater than 6.5 to 7 meq/L
 A lesser degree of hyperkalemia in patients with a serum potassium that
is rapidly increasing
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 Cont…
 Treatment options include

 10 units of regular insulin in 500 mL of 10 percent

dextrose, given over 60 minutes
 Membrane stabilization with Calcium for patients with
ECG abnormalities(calcium gluconate 1 gm (10 mL of a
10 percent solution)
 Beta-2-adrenergic agonists can be used if treatment with
insulin fails
 Removing K from body with Lasix, Kayexalate, dialysis
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 Calcium and Phosphate
 Metastatic calcification: Ca+2 x PO4 > 60-70
 Often are reciprocal: PO4 Ca+
 Symptoms of hypocalcemia:
 Irritability, tetany
 If hypoalbuminemic:
 Check ionized Ca or
 Correct (0.8 increase of Ca for each 1.0 of albumin below 4)
Hypocalcemia and hyperphosphatemia
 Reduce PO4 with calcium acetate if can swallow pills, calcium
carbonate if needs liquid
 Diet restriction
 Avoid exogenous PO4
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 Acidosis
 Metabolic acidosis is common among patients with AKI.
 In general we dialyze patients with AKI who are volume
overloaded and have a pH <7.1 meq/L.
 Dialysis is preferred to the administration of bicarbonate
among such patients because bicarbonate administration
results in a large sodium load that may cause or contribute
to volume overload.
 Among patients with AKI who are not volume overloaded
and have no other indication for acute dialysis, bicarbonate
may be used.
 We do not use bicarbonate therapy in patients with a less
severe organic acidosis (pH 7.1 or greater)
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 Indications for Dialysis
 Fluid overload that is refractory to diuretics
 Hyperkalemia (serum K concentration >6.5 meq/L) or rapidly
rising K levels, refractory to medical therapy.
 Metabolic acidosis (pH less than 7.1) in patients in whom the
administration of bicarbonate is not indicated
 Signs of uremia, such as pericarditis, neuropathy, bleeding or an
otherwise unexplained decline in mental status
 BUN greater than 100 mg/dL
 Magnesium greater than 9.7 mg/dL
 Pulmonary edema and anuria
 Toxins which can be removed by dialysis
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 Cont…
Indications for RRT – AEIOU

Acid–base abnormalities Metabolic acidosis resulting from the

accumulation of organic & inorganic acids

Electrolyte imbalance Hyperkalemia, hypermagnesemia

Intoxications Salicylates, lithium, methanol, ethylene

glycol, theophylline, phenobarbital

Fluid Overload Postoperative fluid gain/overload

Uremia High catabolism of uremic toxins

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Drug-Induced AKI
 Prevention of Acute Kidney Injury
 Avoidance: The best preventive measure for AKI, especially
in individuals at high risk, is to avoid medications that are
known to precipitate AKI.
 Nephrotoxicity is a significant side effect of
 Aminoglycosides,
 Angiotensin-converting enzyme inhibitors,
 Angiotensin receptor antagonists,
 Amphotericin B,
 Nonsteroidal anti-inflammatory drugs,
 Cyclosporine, tacrolimus, and
 Radiographic contrast agents
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 Drug-Induced AKI: Aminoglycosides
 Treatment with aminoglycosides (gentamicin, tobramycin, and
amikacin) can cause non-oliguric intrinsic AKI.
 Injury is due to the binding of aminoglycosides to proximal
tubular cells, and subsequent cellular uptake and cell death
 A prolonged course of aminoglycoside therapy (typically longer
than 7 to 10 days) is a risk factor for the development of AKI,
especially in those with preexisting CKD and in the elderly
 Methods to minimize drug exposure include
 Maintaining trough concentrations less
 Short length of therapy
 Avoiding repeated courses of aminoglycosides
 Utilizing extended-interval dosing methods
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 Drug-Induced AKI: Amphotericin B
 Amphotericin B–induced AKI occurs in as many as 40% to 65% of
patients treated with the conventional desoxycholate
formulation
 Nephrotoxicity is due to renal arterial vasoconstriction and distal
renal tubule cell damage
 Risk factors include high doses, tx for at least 7 days, preexisting
kidney dysfun & concomitant use of other nephrotoxic drugs
 Three lipid-based formulations of amphotericin B have been
developed in an attempt to decrease the incidence of AKI:
 Amphotericin B lipid complex,
 Amphotericin colloidal dispersion, and
 Liposomal amphotericin B
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 Drug-Induced AKI: Amphotericin B
 The range of nephrotoxicity reported is 15% to 25% for these

formulations.
 The mechanism for decreased nephrotoxicity is thought to

be due to preferential release of amphotericin B from

macrophages at the site of infection, with less of an affinity
for the kidney
 The liposomal preparation does not contain deoxycholate,

which has direct tubular toxicity.

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 Drug-Induced AKI: Radiocontrast Agents
 Patients at risk for developing AKI include patients with

chronic kidney disease, diabetic nephropathy, dehydration,

and higher dose of contrast dye

 The mechanism of nephrotoxicity is not fully understood;

however, direct tubular toxicity, renal ischemia, and tubular

obstruction have been implicated

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 Drug-Induced AKI: Radiocontrast Agents
 The incidence of nephrotoxicity with ionic and non-ionic

agents is similar in patients at low risk for developing AKI;

however, in high-risk patients, nephrotoxicity is
significantly greater when ionic contrast agents are used
 Therapeutic measures to decrease the incidence of contrast-

induced nephropathy include:

 Extracellular volume expansion,
 Minimization of the amount of contrast administered
 Treatment with oral acetylcysteine.
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 Drug-Induced AKI: ACEIs and ARBs
 In instances of decreased renal blood flow, production of
angiotensin II increases, resulting in efferent arteriole
vasoconstriction and maintenance of glomerular capillary
pressure and GFR
 In patients initiated on ACE inhibitors or ARBs, angiotensin II
synthesis decreases thereby dilating efferent arterioles and
decreasing glomerular capillary pressure and GFR.
 Risk factors for developing AKI are preexisting renal dysfunction,
severe atherosclerotic renal artery stenosis, volume depletion, and
severe CHF
 Discontinuation of the drug usually results in return of renal
function to baseline
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 Drug-Induced AKI: NSAIDs
 Cause prerenal AKI through inhibition of prostaglandin-

mediated renal vasodilation.

 Risk factors: preexisting renal dysfunction, severe
atherosclerotic renal artery stenosis, volume depletion,
severe CHF, hepatic disease with ascites, and advanced age
 It is usually reversible with drug discontinuation

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 Drug-Induced AKI: NSAIDs
 Cause prerenal AKI through inhibition of prostaglandin-

mediated renal vasodilation.

 Risk factors: preexisting renal dysfunction, severe
atherosclerotic renal artery stenosis, volume depletion,
severe CHF, hepatic disease with ascites, and advanced age
 It is usually reversible with drug discontinuation.

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 Patient Care and Monitoring
1. Assess kidney function by evaluating a patient’s signs and
symptoms, laboratory test results, and urinary indices.
Calculate a patient’s CrCl to evaluate the severity of kidney
disease.
2. Obtain a thorough and accurate drug history including the
use of nonprescription drugs such as NSAIDs.

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 Cont…
3. Evaluate a patient’s current drug regimen to:
 Determine if drug therapy may be contributing to AKI.
Consider not only drugs that can directly cause AKI (e.g.,
aminoglycosides, amphotericin B, NSAIDs, cyclosporine,
tacrolimus, ACE inhibitors, and ARBs) but also drugs that can
predispose a patient to nephrotoxicity or prerenal AKI (i.e.,
diuretics and antihypertensive agents).
 Determine if any drugs need to be discontinued, or alternative
drugs selected, to prevent worsening of renal function.
 Adjust drug dosages based on the patient’s CrCl or evidence of
adverse drug reactions or interactions
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 Cont…
4. Develop a plan to provide symptomatic care of
complications associated with AKI, such as diuretic
therapy to treat volume overload. Monitor the patient’s
weight, urine output, electrolytes (such as potassium), and
blood pressure to assess efficacy of the diuretic regimen.

60
 Key concepts
 Equations to estimate CrCl that incorporate a single serum
creatinine concentration (e.g., Cockcroft-Gault) typically
overestimate kidney function.
 There is currently no drug therapy that hastens patient recovery
in AKI, decreases length of hospitalization, or improves survival.
 Loop diuretics are the diuretics of choice for the management of
volume overload in AKI.
 There is no indication for the use of low-dose dopamine in the
treatment of AKI.
 Identifying patients at risk for development of AKI and
implementing preventive methods to decrease its occurrence or
severity is critical
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Chronic Kidney Disease
 Cont…
Definition
 Kidney damage for more than 3 months, as defined by

structural or functional abnormality of the kidney, with or

without decreased GFR, manifested by either pathologic
abnormalities or markers of kidney damage, including
abnormalities in the composition of blood or urine or
abnormalities in imaging tests
 CKD is classified based on Cause, GFR category (G1-G5),

and Albuminuria category (A1-A3), abbreviated as CGA.

63
KDIGO GFR and albuminuria Persistent albuminuria

Cont…
categories and prognosis of CKD by A1 A2 A3
category Normal to Moderately Severely
mildly increase increased increased
 Cont
<30mg/g 30 -300 mg/g >300 mg/g
G1Cont Normal or high ≥90
Cont
G2 Mildly 60 – 89
decreases
(mL/min/1.73m2)

 Cont
GFR categories

G3a Mild to 45 – 59
 Cont moderate
G3bModerate
Cont to 30 – 44
severe
G4 Severely 15 – 29
decreased
G5 Kidney failure < 15

Low risk High risk

Moderately increased risk Very high risk

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 Cont…
 Normal kidney function in adults is about 120 mL/min/1.73

m2 of GFR
 Even though a GFR of >90 mL/min/1.73 m2 is considered

normal kidney function, a patient can be diagnosed with

CKD if the patient has proteinuria, hematuria, or evidence
of structural damage from a kidney biopsy
 Stage 5 CKD is referred to as end-stage renal disease

(ESRD) or end-stage kidney disease.

65
 Etiology
1. Susceptibility Factors
 Associated with an increased risk, but not proven to directly
cause CKD
 Advanced age,
 Low income or education,
 Racial/ethnic minority status,
 Reduced kidney mass,
 Low birth weight,
 Family history of CKD,
 Systemic inflammation,
 Dyslipidemia

 Mostly not modifiable

66
 Cont…
2. Initiation Factors
 Initiation factors are conditions that directly result in kidney
damage
 Modifiable by pharmacologic therapy
 Diabetes mellitus,
 Hypertension,
 Autoimmune diseases,
 Polycystic kidney disease,
 Systemic infections,
 Urinary tract infections,
 Urinary stones,
 Lower urinary tract obstructions, and
 Drug toxicity
67
 Cont…
3. Progression Factors
 Progression risk factors are those associated with further

kidney damage
 The most important predictors of progressive CKD
 Proteinuria,
 Elevated blood pressure,
 Hyperglycemia,
 Hyperlipidemia, and
 Smoking

68
 Pathophysiology
 Damage to the kidney results from any of the initiation
factors which resulting in loss of nephron mass.
 The resultant effect is hypertrophy of the remaining
nephrons to compensate for the loss of renal function and
nephron mass
 These adaptive changes result in an increase in glomerular
filtration and tubular function, both reabsorption and
secretion, in the remaining nephrons
 As time progresses, glomerular capillary pressure is
increased, mediated by angiotensin II, to maintain the
hyper filtration state of the functioning nephrons.
69
 Cont…
 Increased glomerular capillary pressure expands the pores
in the glomerular basement membrane, altering the size-
selective barrier and allowing proteins to be filtered
through the glomerulus
 Filtered proteins are reabsorbed in the renal tubules, which
activates the tubular cells to produce inflammatory and
vasoactive cytokines and triggers complement activation
 These in turn cause interstitial damage and scarring within
the renal tubules, leading to damage and loss of more
nephrons
70
 Clinical Presentation
Symptoms
 Stages 1 and 2 CKD are generally asymptomatic

 Stages 3 and 4 CKD may be associated with minimal

symptoms
 Typical symptoms associated with stage 5 CKD include

pruritus, dysgeusia, nausea, vomiting, constipation, muscle

pain, fatigue, and bleeding abnormalities.

71
 Cont…
Signs
 Cardiovascular: worsening hypertension, edema,
dyslipidemia, left ventricular hypertrophy,
electrocardiographic changes and chronic heart failure
 Genitourinary: changes in urine volume and consistency,

“foaming” of urine (indicative of proteinuria), and sexual

dysfunction

72
 Laboratory tests
1. Increased BUN and SCr and decreased GFR
2. Increased K, P, and Mg; decreased bicarbonate (metabolic
acidosis); calcium levels are generally low in earlier stages
of CKD and may be elevated in stage 5 CKD, secondary to
the use of calcium-containing phosphate binders
3. Decreased albumin, if inadequate nutrition intake in
advanced stages
4. Decreased RBC count, Hgb and Hct

73
 Cont…
5. Protienurea/albuminurea: urine positive for albumin or
protein
 Normal: <30mg/24hrs
 Microalbuminurea: 30-300mg/24hrs
 Macroalbuminurea (overt protienurea): >300mg/24hrs
 Nephrotic range proteinurea: >3g/24hrs.
6. Increased parathyroid hormone (PTH) level
7. Decreased vitamin D levels (stages 4 or 5 CKD)

74
Treatment of CKD
Desired Outcomes
 The primary goal is to slow and prevent the
progression of CKD

75
 Nonpharmacologic Therapy
 Dietary Protein Restriction:
 Shown to slow the progression of kidney disease
 However, protein restriction must be balanced with the risk
of malnutrition in patients with CKD
 Patients with a GFR less than 25mL/minute/1.73m2 received
the most benefit from protein restriction; therefore, patients
with a GFR above this level should not restrict protein
intake

76
 Cont…
 Patients who have a GFR <25 mL/min /1.73 m2 who are not

receiving dialysis should restrict protein intake to 0.6 g/kg

per day
 Malnutrition is common in patients with ESRD due to:
 Decreased appetite
 Hypercatabolism
 Nutrient losses through dialysis
 For this reason, patients receiving dialysis should maintain

protein intake of 1.2 – 1.3 g/kg per day

77
Pharmacologic Therapy
1. Intensive Blood Glucose Control:
 Intensive insulin therapy to maintain preprandial blood
glucose levels between 70 and 125 g/dL and postprandial
blood glucose levels less than 180 g/dL
2. Optimal Blood Pressure Control:
 Stages 1-4: goal BP of less than 130/80 mm Hg
 Stage 5: receiving hemodialysis, goal BP of <140/90 mm Hg
before hemodialysis and <130/80 after hemodialysis

78
Cont…
3. Reduction in Proteinuria
 ACE inhibitors and ARBs:
 Decrease glomerular capillary pressure and volume because
of their effects on angiotensin II.
 This, in turn, reduces the amount of protein filtered through
the glomerulus, independent of the reduction in blood
pressure
 Antihypertensive agents of choice for all patients with CKD

79
Cont…
4. Hyperlipidemia Treatment
 CKD patients are among the highest-risk group for

cardiovascular conditions (i.e., equivalent to that of

patients with known coronary heart disease)
 Should be treated aggressively for dyslipidemia to an LDL

cholesterol goal below 100 mg/dL

80
 COMPLICATIONS OF CKD
1. Fluid and Electrolyte Abnormalities
A.Impaired Sodium and Water Homeostasis

 Sodium and water balance are primarily regulated by the

kidney
 Reductions in nephron mass  GF  reabsorption of sodium

and water  edema

 Treatment

 Nonpharmacologic: Sodium and fluid restrictions

 Pharmacologic: Loop diuretics therapy
81
 Cont…
B.Impaired Potassium Homeostasis
 Potassium balance is primarily regulated by the kidney via

the distal tubular cells.

 Reduction in nephron mass decreases tubular secretion of

potassium, leading to hyperkalemia.

 Nonpharmacologic: avoid abrupt increases in dietary intake

of potassium, dialysis

82
 Cont…
B. Impaired Potassium Homeostasis
Pharmacologic
 Patients who present with cardiac abnormalities caused by

hyperkalemia should receive calcium gluconate or chloride (1 g

IV) to reverse the cardiac effects
 Temporary measures can be employed to shift extracellular

potassium into the intracellular compartment to stabilize cellular

membrane effects of excessive serum potassium levels
 The use of regular insulin (5 to 10 units IV) and dextrose (5% to

50% IV), or nebulized albuterol (10 to 20 mg)

83
 Cont…
B. Impaired Potassium Homeostasis
 These measures will decrease serum potassium levels within 30 to 60
minutes after treatment, but potassium must still be removed from
the body
 Shifting potassium to the intracellular compartment, however,
decreases potassium removal by dialysis
 Often, multiple dialysis sessions are required to remove potassium
that is redistributed from the intracellular space back into the serum
 Sodium polystyrene sulfonate (SPS, 15 to 30 g orally), a sodium-
potassium exchange resin, promotes potassium excretion from the
GI tract
84
 Cont…
2. Metabolic Acidosis
 Normal metabolism of ingested food produces approximately

1 mEq/kg of metabolic acid daily, which must be excreted by

the kidneys (primarily as ammonium ion) to maintain acid-
base balance
 Reduced bicarbonate reabsorption and impaired production of

ammonia by the kidneys are the major factors responsible for

development of metabolic acidosis in advanced kidney disease
 Treatment: Na bicarbonate, Dialysis

85
 Cont…
3. Anemia of CKD
 The progenitor cells of the kidney produce 90% of the hormone

erythropoietin (EPO), which stimulates red blood cell (RBC)

production
 Reduction in nephron mass  decreases renal production of EPO

 anemia in patients with CKD

 Anemia of CKD  decreased oxygen delivery and utilization, 

increased cardiac output and left ventricular hypertrophy (LVH)

 the cardiovascular risk and mortality in patients with CKD.
 The result is a normochromic, normocytic anemia.
86
 Cont…
 Uremia decreases the lifespan of RBCs from a normal of 120

days to as low as 60 days in patients with stage 5 CKD

 Iron deficiency and blood loss from regular laboratory

testing and hemodialysis also contribute to the

development of anemia in patients with CKD

87
 Cont…
Treatment
 The goal of treatment for anemia of CKD is to increase Hgb
levels greater than 11 g/dL
Nonpharmacologic Therapy
1. Sufficient dietary iron intake must be maintained in
patients with anemia of CKD.
 Approximately 1 to 2 mg of iron is absorbed daily from
the diet.
 This small amount is generally not adequate to preserve
adequate iron stores to promote RBC production.
2. RBC transfusions
88
 Cont…
Pharmacologic Therapy
 Iron supplementation to correct and prevent iron
deficiency caused by ongoing blood loss and increased iron
demands associated with the initiation of erythropoietic
therapy
 ESA to correct erythropoietin deficiency: epoetin alfa,

epoetin beta and darbepoetin alfa

 The first-line treatment for anemia of CKD involves
replacement of erythropoietin with ESAs
89
 Cont…
 Darbepoetin alfa differs from epoetin alfa by the addition of
carbohydrate side chains that increase the half-life of darbepoetin
alfa compared to epoetin alfa and endogenous EPO, allowing for
less frequent dosing than that of epoetin alfa
 The most common adverse effect seen with ESA is increased
blood pressure
 The starting doses of epoetin alfa are 80 to 120 units/kg per week
for SC administration and 120 to 180 units/kg per week for IV
administration, divided two to three times per week
 The starting dose of darbepoetin alfa is 0.45 mcg/kg administered
SC or IV once weekly
90
 Cont…
4. Secondary Hyperparathyroidism & Renal Osteodystrophy
 As renal function declines in patients with CKD, decreased

phosphorus excretion disrupts the balance of calcium and

phosphorus homeostasis
 The rise in serum phosphate causes increased binding of

phosphate with calcium in the plasma, thus decreasing the

plasma serum ionized calcium concentration
 The parathyroid glands release PTH in response to decreased

serum ionized calcium and increased serum phosphorus levels.

91
 Cont…
 The actions of PTH include:
 Increasing calcium resorption from bone
 Increasing calcium reabsorption from the proximal tubules
in the kidney
 Decreasing phosphorus reabsorption in the proximal
tubules in the kidney
 Stimulating activation of vitamin D by 1-a-hydroxylase to
calcitriol (1,25-dihydroxyvitmin D3) to promote calcium
absorption in the GI tract and increased calcium
mobilization from bone
92
 Cont…
 Calcitriol : the active form of vitamin D

 Increases gut absorption of calcium

 Suppress PTH release (negative feedback)
 As kidney function continues to decline and the GFR falls

less than 60,

 Phosphorus excretion continues to decrease
(hyperphosphatemia)
 Calcitriol production decreases

 Secondary hyperparathyroidism (sHPT).

93
 Nephron loss

Impaired phosphate  Production of

excretion 1,25dihydroxyvitamin D3

↑[Ca]×[PO4] Phosphate  intestinal Impaired bone

product retention Ca absorption mineralization

Soft tissue Hypocalcemia Hypocalcemia Osteomalacia

calcification

↑PTH Production
(sHPT)
94
 ↑PTH production
(sHPT)

↑d Ca mobilization *↑d renal Ca * d renal tubular

from bone reabsorption reabsorption of PO4

Osteitis Renal Osteomalacia

fibrosa cystica osteodystrophy

Metabolic acidosis Aluminum overload

95
Cont…
Treatment
 Nonpharmacologic Therapy
 Dietary phosphorus restriction
 Restriction of aluminum exposure and
 Parathyroidectomy

96
Cont…
 Pharmacologic Therapy

1. Phosphate-Binding Agents
 Used to bind dietary phosphate in the GI tract to form an
insoluble complex that is excreted in the feces
A. Calcium-based phosphate binders:

 Calcium carbonate (40% elemental Ca) and calcium

acetate (25% elemental Ca)
 Starting Dose 0.5–1 g elemental Ca 3xday
 Adverse effects: constipation and hypercalcemia
97
Cont…
B. Aluminum/magnesium-based phosphate binders:
 Aluminum hydroxide, aluminum carbonate, Magnesium
hydroxide, magnesium carbonate
 Not recommended for chronic use
C. Lanthanum carbonate:
 Quickly dissociates in the acidic environment of the
stomach, where the lanthanum ion binds to dietary
phosphorus, forming an insoluble compound that is
excreted in the feces
98
 Cont…
2. Vitamin D (calcitriol)
 Vitamin D occurs naturally as ergocalciferol (vitamin D2) and
cholecalciferol (vitamin D3), both of which are inactive precursors of
active forms of vitamin D.
 An intermediate activation step (25-hydroxylation) occurs in the liver to
produce 25-hydroxy vitamin D (25-hydroxycalciferol), which is also
relatively inactive.
 Final activation (1-hydroxylation) occurs in the kidney, yielding calcitriol
(1,25-dihydroxycholecalciferol), the active form of vitamin D
 Exogenous vitamin D compounds that mimic the activity of calcitriol
decrease PTH secretion. (calcitriol, paricalcitol, doxercalciferol,
alfacalcidiol)
 Dosing: usually 0.25–0.5 mcg/day
99
 Renal Replacement Therapy
 Patients who progress to ESRD require renal replacement

therapy (RRT)
 The modalities that are used for RRT are

 Dialysis
 Kidney transplantation

100
Glomerulonephritis
 Introduction
 The glomerulus consists of two important components:

1. The filtration barrier (capillary wall)

 Consists of three well-defined layers:
 Fenestrated endothelium,
 Glomerular basement membrane (GBM),
 Epithelial cell layer (podocytes)
2. The mesangium
 Provides support for the glomerular capillaries

102
Cont…
 Cont
 Cont
 Cont
 Cont
 Cont
 Cont

103
 Introduction
 The passage of solutes through the glomerular
membrane is impacted by both the size and charge of
the solute
 The unique capillary bed of the glomerulus;
 Allows free passage of small nonprotein plasma
constituents up to the size of inulin (MW of 5.2 kDa)
 Excludes macromolecules equal to or larger than albumin
(MW of 69 kDa)

104
Introduction
 Fixed, negatively charged sites are found within the

glomeruli in all three layers of the capillary wall

 The movement of negatively charged molecules is thus

restricted more than that of neutral or positively

charged molecules
 Different glomerular diseases affect this size - and

charge-selective barrier to different extents

105
 Pathogenesis
 Genetic mutations producing familial disease
 Systemic hypertension and atherosclerosis can produce
pressure stress, ischemia, or lipid oxidants that lead to chronic
glomerulosclerosis
 Diabetic nephropathy: thickening of the GBM secondary to the
long-standing effects of hyperglycemia, advanced glycosylation
end products, and reactive oxygen species.
 Infections: Bacteria, fungi, and viruses can directly infect the
kidney producing their own antigens.
 Poststreptococcal glomerulonephritis (PSGN)
 Autoimmune diseases
106
 Clinical Presentation
 Patients with glomerular disease are often categorized into

one of two broad classifications:

 Nephritic syndrome
 Reflects glomerular inflammation and frequently
results in hematuria
 Nephrotic syndrome
 Noninflammatory injury to the glomerular structures
and results in few cells or cellular casts in the urine

107
 Nephritic Syndrome
 Acute nephritic syndromes classically present with

 Hypertension,
 Hematuria,
 Red blood cell casts,
 Pyuria, and
 Mild to moderate proteinuria
 Extensive inflammatory damage to glomeruli causes a fall

in GFR and eventually produces uremic symptoms with salt

and water retention, leading to edema and hypertension
108
 Nephritic Syndrome
 Poststreptococcal Glomerulonephritis
 Affects children between the ages of 2 and 14 years
 Skin (impetigo) and throat infections (pharyngitis) with
particular M types of streptococci (nephritogenic strains)
antedate glomerular disease
 PSGN due to impetigo develops 2–6 weeks after skin infection
and 1–3 weeks after streptococcal pharyngitis.
 Treatment is supportive, with control of hypertension, edema,
and dialysis as needed
 Antibiotic treatment for streptococcal infection should be given
to all patients and their cohabitants
109
 Nephritic Syndrome
 Other causes

 Subacute Bacterial Endocarditis

 Lupus Nephritis
 Antiglomerular Basement Membrane Disease
 IgA Nephropathy

110
 Nephrotic Syndrome
 Nephrotic syndrome classically presents with

 Heavy proteinuria (>3.5 g/day per 1.73 m2),

 Urine dipstick 3+/4+
 Hypoalbuminemia, <2.5g/dL
 Hypercholesterolemia, >200mg/dL
 Edema
 Hypertension
 Hypercoagulable state

111
Nephrotic Syndrome
 Causes
 Minimal Change Disease: alters capillary charge and
podocyte integrity
 Focal Segmental Glomerulosclerosis
 Membranous Glomerulonephritis: malignancy (solid
tumors of the breast, lung, colon), infection (hepatitis B,
malaria, schistosomiasis), or rheumatologic disorders like
lupus or rarely rheumatoid arthritis
 Diabetic Nephropathy

112
 Diagnostic Tests
Laboratory evaluation
 Urinalysis
 To determine nephrotic nature of glomerular disease
 Proteinuria, >3.5 g/day/1.73 m2
 Lipiduria
 To determine nephritic nature of glomerular disease
 Hematuria
 Pyuria
 Cellular, granular casts
 Glomerular filtration rate
 To determine extent of glomerular damage
113
 Diagnostic Tests
Other tests
 To identify type and etiology of glomerular disease

 Serum complement concentration

 Antinuclear and anti-DNA antibodies
 Antistreptolysin antibodies: PSGN
 Circulating antiglomerular basement membrane antibodies
 Cryoglobulins
 Percutaneous renal biopsy

 To provide definitive diagnosis of glomerular disease

114
 Treatment
Supportive Therapy
 Edema:
 Salt restriction, bed rest, and use of support stockings
 Diuretics:
 Furosemide: 160 to 480 mg

 Hypertension
 Goal: < 130/80 mm Hg
 ACEI/ARBs
 CCB (non dihydropyridines)
 Proteinuria
 Dietary protein restriction
 ACEI/ARB
115
 Treatment
 Hyperlipidemia

 A low-fat diet
 Statins: lovastatin, pravastatin, simvastatin, and fluvastatin
 Anticoagulation

 Warfarin
 Patients who have documented thromboembolic
episodes
 Albumin < 2.0 to 2.5 g/dL

116
 Treatment
 Prednisolone
 Initial: 2 mg/kg/day or 60 mg/m2/day (max: 80 mg/day) in
divided doses until urine is protein free for 3 consecutive days
(max: 28 days); followed by 1-1.5 mg/kg/dose or 40
mg/m2/dose given every other day for 4 weeks
 Maintenance (for frequent relapses): 0.5-1 mg/kg/dose given
every other day for 3-6 months with tapering
 Nonsteroidal therapy
 Cyclophosphamide at a dose of 2 mg/kg per day

117
 Treatment
 Common definitions of patients with nephrotic syndrome

related to steroid treatment outcome

 Remission: urine protein: creatinine ratio < 0.2 or dipstick
negative or trace reading for 3 consecutive days
 Corticosteroid responsive: attainment of complete
remission with corticosteroid therapy

118
 Treatment
 Corticosteroid resistance: inability to induce a remission

within 4 weeks of daily corticosteroid therapy

 Relapse: increase in first morning urine protein: creatinine

ratio to ≥2 or dipstick reading of ≥2+ for 3 of 5 consecutive days

 Infrequent relapse: 1–3 relapses annually
 Frequent relapse: ≥2 relapses within 6 months after initial
therapy or ≥4 relapses in any 12-month period
 Corticosteroid dependent: relapse during taper or within 2

weeks of discontinuation of corticosteroid therapy

119
 Treatment
 Patients who relapse are treated with another course of
prednisone with the goal of decreasing the chance of
corticosteroid toxicity by weaning soon after the patient is in
remission
 60 mg/m2 per day of corticosteroids as with initial presentation
with weaning to alternate-day therapy (40 mg/m2 per dose)
after a urine dipstick test result is negative or trace for protein
for 3 consecutive days
 Infrequent relapsers: 4-week alternate-day therapy
 Frequent relapse: 3-month alternate-day therapy
 Corticosteroid resistant MCNS:
 Cyclophosphamide, levamisole, cyclosporine
120
 Evaluation of Therapeutic Outcomes
 For therapeutic response and treatment-related toxicities

 Serum creatinine concentration and creatinine clearance

 Blood pressure should be monitored periodically
 Serum lipid concentrations
 Urinalysis and a complete blood count
 Patient's appetite and energy level

121
Reading Assignment
Acid–Base Disorders

6/25/2025
 Introduction
124

Acid–Base Chemistry
 Acid: donate proton
 Base: accept protons
 Acid–base pairs commonly encountered in clinical
practice

Acid-Base Disorders By Tewodros 6/25/2025

 Cont…
125

 pH of blood is maintained at 7.40

 A pH of less than 6.7 & greater than 7.7 incompatible with life
 Alterations in blood pH serve as the basis for the diagnosis of
acid–base disorders
 Henderson-Hasselbalch equation

pH = pKa + log([base]/[acid])
 Buffers
 H2CO3/HCO3: the principal EC buffer
 Plasma proteins,
 Hemoglobin, and phosphates
Acid-Base Disorders By Tewodros 6/25/2025
 Cont…
126

Carbonic acid/bicarbonate buffer system

 Most abundant extracellular buffer
 Components are under dynamic regulation by the body
 H2CO3: ventilation
 Bicarbonate: regulated by the kidney
 pH = 6.1 + log([HCO3 ]/(PCO2 × 0.03))
 In normal physiology
 HCO3: 24 mEq/L
 PCO2: 40 mmHg

Acid-Base Disorders By Tewodros 6/25/2025

 Regulation of Acid–Base Homeostasis
127

Sources of Acids
 Cellular Metabolism: CO2 (main acid product)
 Catabolism of proteins, FAs, Glucose
 Phosphates
 Acetoacetic acid and β-hydroxybutyric acid
 Lactic and Pyruvic Acid
How the body maintains Acid-Base balance
 Extracellular buffering,
 Ventilatory regulation of carbon dioxide elimination, and
 Renal regulation of hydrogen ion and bicarbonate excretion

Acid-Base Disorders By Tewodros 6/25/2025

 Cont…
128

 Body’s first defense against a sudden increase in hydrogen

ion concentration
 Bicarbonate/carbonic acid, most important of
 Proteins, and the body’s buffers

 Phosphates

Acid-Base Disorders By Tewodros 6/25/2025

 Renal Regulation
129

 Bicarbonate reabsorption occurs primarily in the proximal

tubule

Acid-Base Disorders By Tewodros 6/25/2025

 Cont…
130

 Excretion of metabolic fixed acids and generation of new HCO3

 Ammoniagenesis: For each ammonium ion excreted in the
urine, one bicarbonate ion is regenerated and returned to
the circulation
 Distal tubular hydrogen ion secretion

Acid-Base Disorders By Tewodros 6/25/2025

 Cont…
131

 Metabolic or respiratory in origin

 In metabolic acid–base disorders, the primary disturbance
is in the plasma bicarbonate concentration
 Respiratory acid–base disorders are caused by alterations
in alveolar ventilation that produce corresponding changes
in PaCO2
 Each disturbance has a compensatory (secondary) response
that attempts to correct the [HCO3⁻]:PaCO2 ratio toward
normal
Time course is different
Acid-Base Disorders By Tewodros 6/25/2025
Interpretation of Simple Acid–Base Disorders
132

Acid-Base Disorders By Tewodros 6/25/2025

 Analysis of Arterial Blood Gas Data
133

Normal Blood gas values

Acid-Base Disorders By Tewodros 6/25/2025

 1. Metabolic Acidosis
134

Pathophysiology
 Metabolic acidosis is characterized by a decrease in pH as the
result of a primary decrease in serum bicarbonate
concentration
 Consumption of HCO3-: buffering
 Accumulation of organic acids: lactic acid
 Accumulation of endogenous acids: phosphates
 Serum HCO3– Loss: diarrhea

Acid-Base Disorders By Tewodros 6/25/2025

 Cont…
135

 Serum anion gap (SAG) used to infer whether an organic or

mineral acidosis is present
 SAG: [Na+] – [Cl–] – [HCO3–]
 SAG: [UAs] – [UCs]

 Normal 9 mEq/L

Acid-Base Disorders By Tewodros 6/25/2025

 Hyperchloremic Metabolic Acidosis
136

 The SAG remains normal.

 Result from increased GI bicarbonate loss, renal bicarbonate
wasting, impaired renal acid excretion, or exogenous acid gain
 Renal bicarbonate wasting
 Disturbance in proximal renal tubular acidosis
 A complication of therapy with carbonic anhydrase
inhibitors

Acid-Base Disorders By Tewodros 6/25/2025

 Renal Tubular Acidosis
137

Distal RTA
 Type I: Hypokalemia
 Patients unable to maximally acidify their urine
 primary tubular defect

 Secondary to: hypercalcemia, MM, SLE, SCA

 Type IV: Hyperkalemic

 Characterized by hypoaldosteronism or generalized distal

tubule defects
Acid-Base Disorders By Tewodros 6/25/2025
 Cont…
138

 Hyporeninemic hypoaldosteronism
 Able to maximally acidify their urine
 Primary defect in acid excretion is impaired ammoniagenesis due
to mild renal insufficiency
Proximal (type II) RTA
 Characterized by defects in proximal tubular reabsorption of
bicarbonate
 Present with a chronic, nonprogressive hyperchloremic
metabolic acidosis
 Patients are able to acidify their urine in response to an acid
load
Acid-Base Disorders By Tewodros 6/25/2025
 Elevated Anion Gap Metabolic Acidosis
139

 Results from increased endogenous organic acid production

 Lactic acidosis: Anaerobic respiration

 β-hydroxybutyric acid and acetoacetic acid: DM

 Renal failure (acute or chronic)

 Methanol ingestion
 Ethylene glycol ingestion
 Salicylate over dosage

 Starvation

Acid-Base Disorders By Tewodros 6/25/2025

 140

Acid-Base Disorders By Tewodros 6/25/2025

 Compensation
141

 Patient’s primary means to compensate for metabolic acidosis

is to increase carbon dioxide excretion by increasing
respiratory rate

Acid-Base Disorders By Tewodros 6/25/2025

 Treatment
142

Chronic Metabolic Acidosis

 Asymptomatic patients with mild to moderate degrees of
acidemia do not require emergent therapy
 Usually managed with oral NaHCO3

 Primary therapy should target underlying disease state

 Proximal RTA requires the administration of large

maintenance doses of alkali (10 - 15 mEq/kg/day)

Acid-Base Disorders By Tewodros 6/25/2025

 Cont…
143

 Classic distal RTA requires enough alkali to buffer the amount

of acid generated from dietary intake & metabolism, 1 to 3
mEq/kg per day
 Type IV RTA:

 Treating hyperkalemia
 Dietary restriction of potassium

Acid-Base Disorders By Tewodros 6/25/2025

 Cont…
144

Acid-Base Disorders By Tewodros 6/25/2025

 Acute Severe Metabolic Acidosis
145

 When Bicarbonate < 8 mEq/L and PH < 7.2

 Mgt. depends on underlying cause & the patient’s CV status

 In some cases patients will require emergent hemodialysis

 Patients with hyperchloremic acidosis, intravenous alkali

therapy is often required

Therapeutic alternatives
 Sodium bicarbonate

Acid-Base Disorders By Tewodros 6/25/2025

 Cont…
146

 Tromethamine: acts as proton acceptor, combines with

hydrogen ions from carbonic acid to form bicarbonate and a
cationic buffer
 Carbicarb: mixture of (Na2CO3) and (NaHCO3), Given that

the carbonate ion is a stronger base than bicarbonate

 Dichloroacetate: facilitates aerobic lactate metabolism by
stimulating the activity of lactate dehydrogenase

Acid-Base Disorders By Tewodros 6/25/2025

 2. Metabolic Alkalosis
147

 Simple acid–base disorder that presents as alkalemia with an

increase in plasma bicarbonate
 Points to be considered
 Initial process that generates the metabolic alkalosis
 Excessive losses of H+ from the kidneys or stomach
 Gain of exogenous alkali
 Loop and Thiazide Diuretics
 Increased mineralocorticoid activity
 Bartter,s , gitelman,s and Liddle,s syndrome

Acid-Base Disorders By Tewodros 6/25/2025

 Alterations in renal function that maintain the
alkalemic state
148

Acid-Base Disorders By Tewodros 6/25/2025

 Compensation
149

Hypoventilation
 Increased PaCO2

 The PaCO2 increases 6 to 7 mm Hg for each 10-mEq/L (10

mmol/L) increase in bicarbonate, up to a PaCO2 of
approximately 50 to 60 mm Hg

Acid-Base Disorders By Tewodros 6/25/2025

 Cont…
150

Acid-Base Disorders By Tewodros 6/25/2025

 3. Respiratory Alkalosis
151

 Characterized by a primary decrease in PaCO2 that leads to an

elevation in pH
 Excretion of CO2 by the lungs exceeds the metabolic
production of CO2
 Most frequently encountered acid–base disorder
 Occurring physiologically in normal pregnancy and in
persons living at high altitudes
 Common in hospitalized patients

Acid-Base Disorders By Tewodros 6/25/2025

 Causes: Hyperventilation
152

Acid-Base Disorders By Tewodros 6/25/2025

 Clinical presentations
153

 Most of time asymptomatic

 Symptoms of light-headedness, confusion, decreased
intellectual functioning, syncope, and seizures
 B/c of decreased PaCO2 which decrease in cerebral blood flow
 Nausea and vomiting a result of cerebral hypoxia
 In severe respiratory alkalosis, PH is > 7.6 & cardiac
arrhythmias
 Increased serum chloride concentration
 Serum ionized potassium, calcium and phosphorus
concentration can be slightly decreased.
Acid-Base Disorders By Tewodros 6/25/2025
 Compensation
154

 Initial response of the body to acute respiratory alkalosis is

chemical buffering: hydrogen ions are released from the
body’s buffers
 Metabolic compensation: occurs when respiratory alkalosis
persists for more than 6 to 12 hours
 In fully compensated respiratory alkalosis, the bicarbonate
concentration decreases by 4 mEq/L (4 mmol/L) below 24
for each 10–mm Hg drop in PaCO2

Acid-Base Disorders By Tewodros 6/25/2025

 Treatment
155

 In chronic cases (have few or no symptoms and pH not

exceeding 7.50), treatment is often not required.
 First consideration in acute respiratory alkalosis with pH >
7.50 is the identification & correction of the underlying cause
 Relief of pain,
 Correction of hypovolemia with intravenous fluids,
 Treatment of fever or infection,
 Treatment of salicylate overdose,
 Oxygen therapy should be initiated in patients with severe
hypoxemia
Acid-Base Disorders By Tewodros 6/25/2025
 4. Respiratory Acidosis
156

 Occurs when the lungs fail to excrete carbon dioxide resulting

in a lower pH

Causes of Acute Respiratory

Acidosis

Acid-Base Disorders By Tewodros 6/25/2025

 Cont…
157

Acid-Base Disorders By Tewodros 6/25/2025

 Cont
158

Acid-Base Disorders By Tewodros 6/25/2025

 Compensation
159

 Chemical buffering

 Metabolic compensation

 Results in the plasma bicarbonate concentration

increasing by 4 mEq/L above 24 for each 10–mm Hg

increase in PaCO2 above 40

Acid-Base Disorders By Tewodros 6/25/2025

 Treatment
160

 Depend on the chronicity of the patient’s condition.

 When CO2 excretion is severely impaired (PaCO2 >80 mm Hg)
and/or life-threatening hypoxia ( not acidemia) is present
(PaO2<40 mm Hg), the immediate therapeutic goal is to
provide adequate oxygenation
 Treat underlying cause
 Bronchodilators: severe bronchospasm;
 Narcotic or benzodiazepine antagonists to reverse the
effects of these respiratory depressant drugs

Acid-Base Disorders By Tewodros 6/25/2025

 Mixed Acid-Base Disorders
161

Diagnosis
 To diagnose these conditions , one must know how each of the
four simple disorders alters pH, PaCO2, and [HCO3⁻]

Acid-Base Disorders By Tewodros 6/25/2025

 Cont
162

Acid-Base Disorders By Tewodros 6/25/2025

Examples of common mixed disturbances
163

1. Mixed Respiratory Acidosis & Metabolic Acidosis

 There is a failure of compensation.
 The respiratory disorder prevents the compensatory decrease
in PaCO2 expected in the defense against metabolic acidosis
And vice- versa
 Improved oxygen delivery must be initiated to improve
hypercarbia and hypoxia
 Appropriate amounts of alkali should be given to reverse the
metabolic acidosis (similar to the case of metabolic acidosis).

Acid-Base Disorders By Tewodros 6/25/2025

2.Mixed Respiratory Alkalosis & Metabolic Alkalosis
164

 The most common mixed acid-base disorder

 Occurs frequently in critically ill surgical patients with:
 Respiratory alkalosis caused by mechanical ventilation,
hypoxia, sepsis, hypotension, neurologic damage, pain, or
drugs, and
 Metabolic alkalosis caused by vomiting or nasogastric
suctioning and massive blood transfusions.
 Correction of the metabolic component by administration of:
 Sodium chloride and potassium chloride solutions
Acid-Base Disorders By Tewodros 6/25/2025
3.Mixed Metabolic Acidosis & Respiratory Alkalosis
165

 This is often seen in patients with:

 Advanced liver disease,

 Salicylate intoxication, and

 Pulmonary-renal syndromes.

 The respiratory alkalosis decreases the PaCO2 beyond the

appropriate range of the respiratory compensation for
metabolic acidosis.
 And HCO3- to compensate for respiratory alkalosis

Acid-Base Disorders By Tewodros 6/25/2025

 Cont…
166

Treatment
 Treatment of this disorder should be directed at the

underlying cause.
 Because of the enhanced compensation, the pH is usually

closer to normal than in either of the two simple disorders.

Acid-Base Disorders By Tewodros 6/25/2025

4. Mixed Metabolic Alkalosis And Respiratory Acidosis
167

 Often occurs in patients with:

 Chronic obstructive pulmonary disease

 Chronic respiratory acidosis who are treated with salt

restriction, diuretics, and possibly glucocorticoids
 Treatment May need to be initiated to maintain PaO2 and
PaCO2 at acceptable levels.
 It is helpful to discontinue diuretics

 Administration of sodium and potassium chloride.

Acid-Base Disorders By Tewodros 6/25/2025

 THANK YOU !!

Acid-Base Disorders By Tewodros 6/25/2025