Adult-Gerontology Acute Care

Understanding mechanisms lets the AGACNP anticipate disease progression, interpret findings, and choose interventions that target the underlying derangement. This chapter moves from cellular injury and inflammation to the organ-system disorders most often tested in acute care.

Cellular Adaptation and Injury

Adaptation	Defni ition	Example
Hypertrophy	Increasedcellsize	Leftventricularhypertrophyfrompressureoverload(hypertension aortic ,
		stenosis)
Hyperplasia	Increasedcellnumber	Compensatory liver regeneration; hormone-stimulated endometrial growth;
		benignprostatichyperplasia
Atrophy	Decreasedcellsize	Disuse denervation inadequatenutrition lossofhormonalstimulation , , ,
Metaplasia	Onedifferentiatedcelltypereplacedby	Barrettesophagus:squamousepitheliumreplacedbycolumnarepithelium
	another	fromacidexposure
Dysplasia	Disorderedgrowthwithatypicalcells;	Cervicaldysplasia;dysplasiaarisinginBarrettesophagus
	precancerous

Reversible injury appears as cellular swelling and fatty change. ATP depletion impairs the sodium-potassium pump, so sodium and water accumulate inside the cell. Prolonged or severe injury becomes irreversible, marked by membrane damage, mitochondrial dysfunction, and nuclear degradation (pyknosis, karyorrhexis, karyolysis). Release of intracellular contents (troponin, CK, transaminases) is the laboratory evidence of cell death.

Type	Features	ClassicSettings
Coagulative	Tissuearchitecturepreserved;proteinsdenatured	Ischemicinfarctionofsolidorgans(heart kidney , ,
		spleen) exceptthebrain ,
Liquefactive	Enzymaticdigestiontoaliquid viscousmass ,	Braininfarction;bacterialabscesses
Caseous	Combination of coagulative and liquefactive; cheese-like ,	Tuberculosis;somefungalinfections
	surroundedbygranuloma
Fat	Lipasedigestionofadiposetissue;fattyacidsbindcalcium	Acutepancreatitis(cancontributetohypocalcemia);
	(saponification)	breasttrauma
Fibrinoid	Immunecomplexesandfibrindepositedinvesselwalls	Vasculitis;malignanthypertension
Gangrenous	Coagulativenecrosisofalimb(dry);withsuperimposed	Peripheralarterydisease diabeticfoot ,
	infection(wet)

Apoptosis is programmed cell death that removes damaged or unwanted cells without inflammation (cell shrinkage, intact membrane, phagocytosis of apoptotic bodies). Too little apoptosis contributes to autoimmune disease and cancer (malignant cells evade apoptotic signals); too much contributes to degenerative disease and ischemic injury.

Inflammation and Immune Response

Acute inflammation is the immediate vascular and cellular response to injury. Its cardinal signs are rubor (redness), calor (heat), tumor (swelling), dolor (pain), and functio laesa (loss of function). Vasodilation increases blood flow, and increased permeability allows a protein-rich exudate into tissue.

➜

➜

➜

➜

Slowed flow moves

Selectin-mediated loose

Integrins bind firmly to

Diapedesis between

Movement along a

leukocytes to the vessel

binding

endothelium

endothelial cells

chemical gradient to the

wall

injury

Neutrophils predominate in acute bacterial infection. Leukocytes then phagocytose, degranulate, and generate reactive oxygen species.

Mediator	PrincipalActions
Histamine	Immediatevasodilationandincreasedvascularpermeability(mastcells);keyintypeIhypersensitivity
Prostaglandins	Vasodilation painsensitization fever(PGE2);blockedbyNSAIDsviacyclooxygenaseinhibition , ,
Leukotrienes	Bronchoconstriction increasedpermeability neutrophilchemotaxis(LTB4);targetedbymontelukast , ,
Cytokines (IL-1 IL-6 TNF- , ,	Fever acute-phase proteins (CRP) endothelial activation systemic response in sepsis , , ,
α) Complement Bradykinin	1 C3b opsonization; C3a and C5a anaphylatoxins; C5a chemotaxis; C5b –9 membrane attack complex lysescells Vasodilation permeability pain;accumulateswithACEinhibitors(cough angioedema) , , ,

Chronic inflammation persists for weeks to months, with mononuclear cell infiltration (macrophages, lymphocytes, plasma cells) and tissue destruction and repair occurring simultaneously. Granulomatous inflammation is a distinct pattern: activated macrophages form epithelioid cells and multinucleated giant cells surrounded by lymphocytes. Granulomas occur in tuberculosis, sarcoidosis, Crohn disease, and foreign body reactions.

Sepsis and Septic Shock (Sepsis-3)

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Organ dysfunction is identified as an acute increase of 2 or more points in the Sequential (Sepsis-related) Organ Failure Assessment (SOFA) score, which scores six systems: respiratory (PaO2/FiO2), coagulation (platelets), liver (bilirubin), cardiovascular (MAP and vasopressor need), central nervous system (GCS), and renal (creatinine or urine output). Septic shock is the subset of sepsis with circulatory and cellular-metabolic abnormalities severe enough to substantially increase mortality: vasopressors required to maintain MAP ≥65 mmHg and serum lactate >2 mmol/L despite adequate fluid resuscitation. The term "severe sepsis" is no longer used.

Concept	Criteria	CurrentRole
Sepsis	SuspectedordocumentedinfectionplusacuteSOFA	Diagnosticdefinition
(Sepsis-3)	increase≥2
Septicshock	SepsisplusvasopressorstokeepMAP≥65mmHgand	Diagnosticdefinition;hospitalmortalityexceeds40%
	lactate>2mmol/Ldespiteadequatefluids
qSOFA	Any2of:respiratoryrate≥22/min alteredmentation SBP , ,	Bedsideprompttolookfororgandysfunction;nota
	≤100mmHg	diagnosticcriterionandnotrecommendedasasingle
		screeningtool
SIRS	≥2of:temperature>38°Cor<36°C;HR>90/min;RR	Nonspecificmarkerofinflammation;mayappearin
(historical)	>20/minorPaCO2<32mmHg;WBC>12000or<4000/ , ,	screeningprotocolsbutnolongerdefinessepsis
	µLor>10%bands

If a question offers "SIRS plus infection" or "severe sepsis" as the definition of sepsis, it is outdated. Sepsis = infection + organ dysfunction (SOFA ≥2). Septic shock requires both vasopressor dependence for MAP ≥65 mmHg and lactate >2 mmol/L after adequate fluid resuscitation.

Innate and Adaptive Immunity

Feature	InnateImmunity	AdaptiveImmunity
Speed	Immediate(minutestohours)	Days on first exposure; faster on re-exposure
Specificity	Nonspecificpatternrecognition	Antigen-specific
Memory	None	Immunologicmemory(basisofvaccination)
Components	Skinandmucosalbarriers neutrophils , , macrophages naturalkillercells , , complement	Blymphocytes(antibodies;humoralimmunity);Tlymphocytes(cellular 1 immunity):CD4helpercellsactivateotherimmunecells CD8cytotoxic , cellskillinfectedormalignantcells

Type	Mechanism	Timing	Examples
I–Immediate	IgEonmastcellsandbasophils;	Minutes	Anaphylaxis allergicrhinitis allergicasthma , ,
	degranulationreleaseshistamineand		exacerbation urticaria ,
	leukotrienes
II–Cytotoxic	IgG or IgM against cell -surface or	Minutesto	Acutehemolytictransfusionreaction autoimmune ,
	matrixantigens;complementactivation ,	days	hemolyticanemia Goodpasturesyndrome Graves , ,
	phagocytosis		disease myastheniagravis ,
III–Immune	Antigen-antibody complexes deposit in	Hoursto	Serum sickness post-streptococcal glomerulonephritis , ,
complex	tissuesandactivatecomplement	weeks	lupusnephritis
IV–Delayed	SensitizedTcellsreleasecytokinesor	48–72	Contactdermatitis tuberculinskintestreaction acute , ,
(cell -mediated)	killdirectly;noantibody	hours	cellulartransplantrejection

Cardiovascular Pathophysiology

Heart failure occurs when cardiac output cannot meet metabolic demands or does so only at elevated filling pressures. Systolic dysfunction is impaired contractility with reduced ejection fraction; diastolic dysfunction is impaired relaxation and filling with preserved ejection fraction. Current classification: HFrEF (EF ≤40%), HF with mildly reduced EF (41–49%), and HFpEF (EF ≥50%).

Left-Vsright-Sidedheartfailure

Feature	Left-Sided Failure	Right-Sided Failure
Congestion	Pulmonary	Systemicvenous
Symptoms	Dyspnea orthopnea paroxysmalnocturnal , ,	Peripheraledema abdominalfullness earlysatiety , ,
	dyspnea cough ,
Signs	Crackles S3 pleuraleffusion hypoxemia , , ,	JVD hepatomegaly hepatojugularreflux ascites , , ,
Mostcommon	Ischemicheartdisease hypertension ,	Left-sided failure; also pulmonary hypertension RV ,
cause		infarction PE ,

Neurohormonal compensation initially maintains cardiac output but becomes maladaptive, and every major HFrEF drug class blocks one of these pathways.

Coronary artery disease results from atherosclerotic plaque. Stable angina occurs when a fixed stenosis limits flow during increased demand, producing predictable exertional symptoms relieved by rest or nitroglycerin. Acute coronary syndromes result from plaque rupture or erosion with superimposed thrombus.

Syndrome	Pathology	ECG	Troponin
Unstable	Ischemiawithoutmyocytenecrosis	Normal ST depression or T -wave inversion , ,	Notelevated
angina
NSTEMI	Partialortransientocclusionwith	ST depression T -wave inversion or normal , ,	Elevatedwithriseand/or
	necrosis(subendocardial)		fall
STEMI	Completeocclusionwithtransmural	STelevationincontiguousleadsornewLBBB	Elevated(donotwaitfor
	injury	withischemicsymptoms/criteria	resultstoreperfuse)

Dysrhythmias arise from abnormal impulse generation or conduction. Supraventricular tachycardias originate above the bundle of His (atrial fibrillation, atrial flutter, AV nodal reentrant tachycardia). Atrial fibrillation produces chaotic atrial activity with an irregularly irregular ventricular response; atrial stasis, especially in the left atrial appendage, promotes thrombus and stroke. Ventricular dysrhythmias include premature ventricular contractions, ventricular tachycardia, and ventricular fibrillation; VF is disorganized ventricular activity with no cardiac output and requires immediate defibrillation.

Block	ECGPattern	Level/Signifi cance	Management
First-degree	PR>020s constant;everyPconducted . ,	AVnode;benign	Observe;reviewAV-
			nodalblockingdrugs
Second -degree Mobitz I (Wenckebach)	ProgressivePRprolongationuntilaP waveisnotconducted;groupedbeating	UsuallyAVnode;oftenbenign (inferiorMI vagaltone drugs) , ,	Observe;atropine1if symptomatic

Atrioventricularblocks(Continued)

Block	ECGPattern	Level/Signifi cance	Management
Second -	ConstantPRwithsudden	Infranodal (His-Purkinje); high	Transcutaneouspacingready;permanent
degreeMobitz	nonconductedPwaves;QRSoften	riskofprogressiontocomplete	pacemaker
II	wide	block
Third -degree	AVdissociation:PwavesandQRS	Anylevel;junctionalescape	Pacing(transcutaneous thentransvenous ,
(complete)	complexesindependent;regular	(narrow)orventricularescape	orpermanent);atropinerarelyeffective
	slowescaperhythm	(wide 20–40/min) ,	forinfranodalblock

Valvular disorders alter hemodynamics through stenosis (pressure overload) or regurgitation (volume overload). Aortic stenosis raises LV afterload and causes concentric hypertrophy; severe AS produces the classic triad of angina, syncope, and heart failure, after which survival without valve replacement is short. Aortic regurgitation causes volume overload with eccentric hypertrophy; acute AR from endocarditis or aortic dissection is an emergency because the unprepared ventricle cannot dilate. Mitral regurgitation causes left atrial volume overload and pulmonary congestion. Mitral stenosis, usually rheumatic, raises left atrial pressure, leading to atrial fibrillation, pulmonary hypertension, and eventually right heart failure.

In severe aortic stenosis, the stroke volume is fixed. Preload reduction (nitrates, aggressive diuresis) and vasodilation can precipitate profound hypotension; avoid or use with great caution.

Pulmonary Pathophysiology

Gas exchange failure appears as hypoxemia (low PaO2) and/or hypercapnia (high PaCO2). The alveolar-arterial (A–a) oxygen gradient and the response to supplemental oxygen separate the mechanisms.

PAO2 = FiO2 × (Patm − PH2O) − PaCO2 ÷ 0.8 (room air, sea level: 150 − PaCO2 ÷ 0.8)

A–a gradient = PAO2 − PaO2

A normal gradient is roughly (age ÷ 4) + 4 mmHg on room air. Example: PaCO2 40, PaO2 60 on room air: PAO2 = 150 − 50 = 100; gradient = 40 mmHg (elevated).

Mechanism	A–a Gradient	Correctswith O2?	Examples
Hypoventilation	Normal	Yes(PaCO2	Opioidorsedativeoverdose neuromuscularweakness obesity , ,
		elevated)	hypoventilation
LowinspiredO2	Normal	Yes	Highaltitude
Diffusionimpairment	Increased	Yes	Interstitiallungdisease emphysema(reducedsurfacearea) ,
V/Qmismatch(most	Increased	Yes	COPD asthma pneumonia PE(deadspace) heartfailure , , , ,
common) Shunt	Increased	No(poor response)	1 Bloodperfusesnonventilatedalveoli:consolidation atelectasis ARDS , , , intracardiac right-to-left shunt

Acute respiratory distress syndrome (ARDS) is inflammatory lung injury with diffuse alveolar damage, increased capillary permeability, and noncardiogenic pulmonary edema. Berlin criteria: onset within 1 week of a known insult or new or worsening respiratory symptoms, bilateral opacities not fully explained by effusion, collapse, or nodules, and respiratory failure not fully explained by cardiac failure or fluid overload. Severity is graded by PaO2/FiO2 on PEEP or CPAP ≥5 cm H2O. The newer global definition also allows SpO2/FiO2 ≤315 (with SpO2 ≤97%) and includes patients on high-flow nasal oxygen.

Severity	PaO2/FiO2	KeyManagement
Mild	201–300	Low tidal volume ventilation: 6 mL/kg predicted body weight (range 4–8) plateau pressure ≤30 cm H2O ,
	mmHg
Moderate	101–200	Adequate PEEP (higher PEEP for moderate-severe); conservative fluid strategy once shock resolves
	mmHg
Severe	≤100mmHg	Pronepositioningatleast12–16hoursdailywhenP/F<150;neuromuscularblockadeinselectedpatients;
		ECMOreferralforrefractoryhypoxemia

COPD: emphysema (alveolar wall destruction, loss of elastic recoil) and chronic bronchitis (mucus hypersecretion, airway inflammation) cause fixed airflow limitation (post-bronchodilator FEV1/FVC <0.70). Exacerbations bring increased dyspnea, sputum volume, and sputum purulence, most often triggered by infection. Target SpO2 88–92% in patients at risk of hypercapnia.

Asthma: airway inflammation, hyperresponsiveness, and reversible bronchoconstriction; mast cell mediators cause smooth muscle contraction and mucus production. Status asthmaticus is a severe exacerbation unresponsive to initial bronchodilator therapy. A normal or rising PaCO2 in an asthmatic who is tachypneic signals fatigue and impending respiratory failure.

Pulmonary embolism: thrombus, usually from lower-extremity DVT, lodges in the pulmonary arteries; consequences depend on clot burden and cardiopulmonary reserve. High-risk (massive) PE causes RV failure with sustained hypotension (SBP <90 mmHg for 15 minutes or requiring vasopressors). Intermediate-risk (submassive) PE shows RV strain on imaging or elevated troponin/BNP without hypotension.

Pneumonia: community-acquired organisms include Streptococcus pneumoniae (most common), Haemophilus influenzae, Mycoplasma pneumoniae, and respiratory viruses. Hospital-acquired pneumonia arises ≥48 hours after admission and ventilator-associated pneumonia ≥48 hours after intubation; both involve resistant organisms (MRSA, Pseudomonas) more often.

Pleural effusion accumulates from increased hydrostatic pressure, decreased oncotic pressure, increased pleural permeability, or impaired lymphatic drainage. Transudates (low protein and LDH) occur in heart failure, cirrhosis, and nephrotic syndrome. Exudates meet any one of Light criteria and occur with infection, malignancy, PE, and inflammation.

Pleural protein ÷ serum protein > 0.5

Pleural LDH ÷ serum LDH > 0.6

Pleural LDH > two-thirds of the upper limit of normal serum LDH

A parapneumonic effusion with pH <7.2, glucose <60 mg/dL, positive Gram stain or culture, or frank pus (empyema) requires drainage.

Renal and Electrolyte Pathophysiology

Acute kidney injury (AKI) is a rapid decline in glomerular filtration. KDIGO criteria: serum creatinine rise ≥0.3 mg/dL within 48 hours, rise to ≥1.5 times baseline within 7 days, or urine output <0.5 mL/kg/h for 6 hours. Causes are grouped by location. Acute tubular necrosis (ATN) is the most common intrinsic cause and results from a prolonged prerenal state or nephrotoxic agents.

Aki:Prerenal,Intrinsic,Andpostrenal

Feature	Prerenal	Intrinsic(ATN)	Postrenal
Mechanism	Decreasedrenalperfusion;	Parenchymaldamage:ischemia ,	Obstructionofurineoutflow
	tubulesintact	nephrotoxins orinflammation ,
Common	Hypovolemia hypotension , ,	ATN(prolongedischemia IVcontrast , ,	Prostatichypertrophy bilateral ,
causes	cardiacdysfunction	aminoglycosides vancomycin , ,	ureteralobstruction ,
	(cardiorenal) NSAIDsorACE ,	rhabdomyolysis);acuteinterstitialnephritis	neurogenicbladder ,
	inhibitors in low-flow states	(drugs);glomerulonephritis	obstructedurinarycatheter
BUN/creatinine ratio FENa	>20:1 <1%	10–15:1 >2%	1 Variable Variable

Aki:Prerenal,Intrinsic,Andpostrenal(Continued)

Feature	Prerenal	Intrinsic(ATN)	Postrenal
Urinesodium/	<20mEq/L;	>40mEq/L;isosthenuric(about300mOsm/kg)	Variable
osmolality	concentrated(>500
	mOsm/kg)
Urinalysis	Bland;hyalinecasts	Muddybrowngranularcasts(ATN);WBCcastsand	Oftenbland;hematuriawith
		eosinophiluria(interstitialnephritis);RBCcasts	stones
		(glomerulonephritis)
Keytest/first	Volumechallengeif	Removenephrotoxins;supportivecare	Bladder scan for post-void
step	hypovolemic		residual;renalultrasoundfor
			hydronephrosis

FENa (%) = (Urine Na × Plasma Cr) ÷ (Plasma Na × Urine Cr) × 100

Diuretics raise urine sodium and make FENa unreliable; a fractional excretion of urea <35% then supports a prerenal state.

Chronic kidney disease (CKD) is abnormal kidney structure or function present for more than 3 months. It is staged by GFR category (G1–G5) and albuminuria category (A1: <30, A2: 30–300, A3: >300 mg/g urine albumin-to-creatinine ratio). GFR is estimated with the CKD-EPI creatinine equation without a race coefficient; adding cystatin C improves accuracy when creatinine is misleading (low muscle mass, amputation).

Stage	GFR (mL/min/1 .73 m²)	Description
G1	≥90	NormalorhighGFRwithotherevidenceofkidneydamage(albuminuria structuralabnormality) ,
G2	60–89	Mildlydecreased withevidenceofdamage ,
G3a	45–59	Mildlytomoderatelydecreased
G3b	30–44	Moderatelytoseverelydecreased
G4	15–29	Severelydecreased;prepareforkidneyreplacementtherapy
G5	<15	Kidneyfailure

Urgent dialysis indications (AEIOU): refractory Acidosis, refractory hyperkalemia or other Electrolyte emergency, Intoxication with a dialyzable toxin (methanol, ethylene glycol, lithium, salicylates), volume Overload unresponsive to diuretics, and Uremic complications (pericarditis, encephalopathy, bleeding).

Sodium and Water

Sodium disorders are disorders of water balance. For hyponatremia (Na <136 mEq/L), first confirm hypotonicity (serum osmolality <275 mOsm/kg) to exclude pseudohyponatremia (hyperlipidemia, hyperproteinemia) and hyperglycemia (correct sodium upward by about 1.6 mEq/L for each 100 mg/dL of glucose above 100), then classify by volume status.

Volume Status	Mechanism	Causes	Treatment
Hypovolemic	Sodiumlosses	Vomiting diarrhea(urineNa<20);diuretics(especially ,	Isotonicsaline
	exceedwaterlosses	thiazides) cerebralsaltwasting mineralocorticoiddeficiency , ,
		(urineNa>20)
Euvolemic	Waterretention	SIADH(mostcommon:CNSdisease pulmonarydisease , ,	Fluidrestriction;treat
	withoutedema	malignancy SSRIs carbamazepine pain nausea) , , , , ,	cause;salttabletsor
		hypothyroidism glucocorticoiddeficiency primarypolydipsia , , ,	vaptansinselectedSIADH
		lowsoluteintake
Hypervolemic	Reducedeffective	Heartfailure cirrhosis nephroticsyndrome advancedkidney , , ,	Fluidandsodium
	arterialvolumewith	disease	restriction;loopdiuretics
	ADHrelease

Acute severe hyponatremia causes cerebral edema with headache, altered mental status, seizures, and herniation; give 3% saline (for example, a 100–150 mL bolus, repeated up to three times as needed) to raise sodium 4–6 mEq/L promptly. Rapid correction of chronic hyponatremia risks osmotic demyelination syndrome (dysarthria, dysphagia, quadriparesis, "locked-in" state, appearing days later). Limit correction to about 8 mEq/L in 24 hours in high-risk patients (sodium ≤105 mEq/L, alcohol use disorder, malnutrition, hypokalemia, advanced liver disease) and to 10–12 mEq/L in others; if overcorrection occurs, relower with free water and desmopressin.

Hypernatremia (Na >145 mEq/L) indicates a water deficit relative to sodium: inadequate water intake (impaired thirst or no access to water, common in frail older adults), diabetes insipidus (central: decreased ADH after head injury or neurosurgery; nephrogenic: lithium, hypercalcemia, hypokalemia), and hypertonic sodium administration. Findings include lethargy, weakness, irritability, and seizures. Correct chronic hypernatremia gradually (no more than about 10 mEq/L per 24 hours) to prevent cerebral edema.

(women); use 0.5 and 0.45 in older adults

Example: 70-kg younger man, Na 161 mEq/L: TBW = 42 L; deficit = 42 × (1.15 − 1) ≈ 6.3 L, replaced gradually with ongoing losses added.

Potassium, Calcium, and Magnesium

Serum potassium is held in a narrow range of 3.5–5.0 mEq/L; about 98% of body potassium is intracellular, so transcellular shifts change serum levels quickly. Calcium exists in ionized (physiologically active, about 45%), protein- bound, and complexed forms; measure ionized calcium or correct total calcium for albumin.

Corrected Ca = measured Ca + 0.8 × (4.0 − albumin)

Example: Ca 7.6 mg/dL with albumin 2.0 g/dL: 7.6 + 1.6 = 9.2 mg/dL (normal). Ionized calcium is preferred in critical illness.

Electrolytedisorders:Causes,Ecgfindings,Andmanagement

Hypokalemia

Decreased intake; GI losses (diarrhea,

Weakness, ileus, cramps;

Oral or IV KCl (peripheral IV

(<3.5)

vomiting); renal losses (loop and thiazide

severe: respiratory muscle

usually ≤10 mEq/h, central line

diuretics, hyperaldosteronism,

weakness, rhabdomyolysis.

up to about 20 mEq/h with

hypomagnesemia); shift into cells (insulin,

ECG: flattened T waves, U

monitoring); replace

beta-agonists, alkalosis)

waves, ST depression,

magnesium or hypokalemia will

prolonged QT (QU), ectopy and

not correct

dysrhythmias

Hyperkalemia

Decreased excretion (kidney failure,

Weakness, paresthesias,

Stabilize: IV calcium gluconate

(>5.0)

hypoaldosteronism, potassium-sparing

paralysis. ECG: peaked T

for ECG changes. Shift: regular

diuretics, ACE inhibitors/ARBs); shift out of

waves→ PR prolongation and

insulin 10 units IV with dextrose;

cells (acidosis, insulin deficiency, beta-

P-wave flattening → QRS

nebulized albuterol; bicarbonate

blockers, tissue breakdown); excessive

widening → sine wave → VF or

if acidotic. Remove: loop

intake. Exclude pseudohyperkalemia

asystole

diuretics, potassium binders,

(hemolyzed sample)

hemodialysis

Hypocalcemia

Hypoparathyroidism (post-thyroidectomy),

Neuromuscular irritability:

IV calcium gluconate if

vitamin D deficiency, CKD, acute

perioral and digital

symptomatic; correct

pancreatitis, massive transfusion (citrate),

paresthesias, Chvostek sign,

magnesium; oral calcium and

hypomagnesemia

Trousseau sign, tetany,

vitamin D for chronic cases

laryngospasm, seizures. ECG: prolonged QT Hypercalcemia

Malignancy (PTH-related peptide, bone

"Stones, bones, groans,

Aggressive IV isotonic saline;

metastases; most common in hospitalized

moans": nephrolithiasis, bone

calcitonin (rapid, short-lived); IV

patients) and primary hyperparathyroidism

pain, constipation and

bisphosphonate (zoledronic

(most common in outpatients); thiazides,

abdominal pain, weakness,

acid) or denosumab; loop

vitamin D excess, granulomatous disease

altered mental status; polyuria

diuretic only after volume

and dehydration. ECG:

repletion; stop thiazides

shortened QT Hypomagnesemia

Alcohol use disorder, diuretics, proton

Tremor, hyperreflexia,

IV magnesium sulfate (2 g IV for

pump inhibitors, diarrhea, malnutrition

seizures; refractory

torsades); oral replacement for

hypokalemia and

mild deficits

hypocalcemia. ECG: prolonged QT, torsades de pointes

Acid-Base Disorders

Arterial pH is maintained between 7.35 and 7.45 (normal PaCO2 35–45 mmHg, HCO3 22–26 mEq/L). Metabolic acidosis results from acid accumulation or bicarbonate loss; metabolic alkalosis from acid loss (vomiting, nasogastric suction) or bicarbonate gain; respiratory acidosis from hypoventilation with CO2 retention; respiratory alkalosis from hyperventilation with CO2 elimination.

➜

➜

➜

➜

<7.35 acidemia; >7.45

PaCO2 moves with pH

Expected or a second

Always calculate in

Hidden metabolic

alkalemia

direction? Respiratory.

disorder?

metabolic acidosis

alkalosis or normal-gap

HCO3? Metabolic

acidosis?

PrimaryDisorder	ExpectedCompensation
Metabolicacidosis	Winter formula: expected PaCO2 = (1 .5 × HCO3) + 8 ± 2
Metabolicalkalosis	PaCO2risesabout07mmHgper1mEq/LriseinHCO3 .
Respiratoryacidosis	HCO3 rises 1 mEq/L per 10 mmHg PaCO2 (acute) or 3 .5–4 mEq/L (chronic)
Respiratoryalkalosis	HCO3falls2mEq/Lper10mmHgPaCO2(acute)or4–5mEq/L(chronic)

Example: Na 140, Cl 100, HCO3 10: AG = 30 (high). Winter formula: expected PaCO2 = 15 + 8 = 23 ± 2; a measured PaCO2 of 35 indicates a concurrent respiratory acidosis.

Highaniongapmetabolicacidosis:Mudpiles

Normal anion gap (hyperchloremic) metabolic acidosis: diarrhea, renal tubular acidosis, early renal failure, large- volume normal saline, acetazolamide, ureteral diversion.

Osmolal gap: measured minus calculated osmolality [2 × Na + glucose ÷ 18 + BUN ÷ 2.8]; a gap >10 mOsm/kg with AG acidosis suggests methanol or ethylene glycol.

Metabolic alkalosis: chloride-responsive (urine Cl <20: vomiting, NG suction, prior diuretics; treat with saline) versus chloride-resistant (urine Cl >20: hyperaldosteronism, active diuretics, severe hypokalemia).

Respiratory acidosis: opioid or sedative overdose, COPD, neuromuscular weakness, obesity hypoventilation, chest wall disease.

Respiratory alkalosis: anxiety, pain, hypoxemia, PE, early sepsis, salicylate toxicity, pregnancy, hepatic failure.

Hepatic Pathophysiology

Acute liver failure is rapid hepatic dysfunction with coagulopathy (INR ≥1.5) and encephalopathy, within 26 weeks of illness onset, in a patient without preexisting liver disease. Causes include acetaminophen toxicity (the most common cause in the United States), viral hepatitis, ischemic hepatitis, and idiosyncratic drug reactions. Complications include coagulopathy, hypoglycemia, cerebral edema with intracranial hypertension, AKI, and susceptibility to infection. Give N- acetylcysteine for acetaminophen toxicity (use the Rumack-Matthew nomogram for a single acute ingestion with a known time, at least 4 hours after ingestion) and refer early to a transplant center.

Cirrhosis is irreversible hepatic fibrosis with nodular regeneration. Increased intrahepatic resistance produces portal hypertension, which drives varices, ascites, and hepatorenal syndrome. Ascites results from portal hypertension, hypoalbuminemia, and renal sodium retention; a serum-ascites albumin gradient (SAAG) ≥1.1 g/dL indicates portal hypertension.

Complication	KeyFeatures	ManagementEssentials
Esophagealvariceal	Life-threatening upper GI bleeding	IVoctreotide antibioticprophylaxis(ceftriaxone) endoscopicband , ,
hemorrhage	fromportosystemiccollaterals	ligationwithin12hours;restrictivetransfusion(Hgbtargetabout7
		g/dL); nonselective beta-blocker or banding for prevention
Ascites	Shiftingdullness fluidwave; ,	Sodiumrestriction(about2g/day);spironolactoneplusfurosemide
	diagnosticparacentesisfornew	(100:40 ratio); large-volume paracentesis with albumin
	ascitesorclinicalchange
Spontaneous	Fever abdominalpain , ,	Ascitic fluid analysis whenever infection is suspected; third -
bacterialperitonitis	encephalopathy orsilentdecline; ,	generationcephalosporinplusIValbumin(15g/kgday1 1g/kgday . ,
	asciticPMNcount≥250cells/mm³	3)
Hepatic	Neurotoxins(ammoniacentralbutnot	Treatprecipitants;lactulosetitratedto2–3softstoolsdaily;add
encephalopathy	theonlyfactor);asterixis	rifaximinforrecurrence Ammonialevelsarenotneededto .
		diagnoseormonitor
Hepatorenal	Functionalrenalfailurewithout	Stopdiureticsandnephrotoxins;albumin;vasoconstrictor
syndrome(HRS-AKI)	intrinsickidneypathology	(terlipressinornorepinephrineplusalbumin);livertransplantis
		definitive

Hepatic encephalopathy ranges from subtle cognitive changes through asterixis to coma (West Haven grade 1: shortened attention, altered sleep; grade 2: lethargy, disorientation to time, asterixis; grade 3: somnolence, gross disorientation; grade 4: coma). Precipitants include GI bleeding, infection, constipation, medications (sedatives, opioids), dehydration, hypokalemia, and alkalosis.

Hepatorenal syndrome results from extreme splanchnic vasodilation with compensatory renal vasoconstriction. The rapidly progressive form (formerly type 1, historically defined by creatinine doubling within two weeks) is now termed HRS-AKI: AKI by creatinine criteria that does not improve after 2 days of diuretic withdrawal and albumin (1 g/kg), without shock, nephrotoxins, or structural kidney disease. The gradual form with diuretic-resistant ascites (formerly type 2) is now classified as non-AKI HRS.

Hematologic Pathophysiology

Anemia is hemoglobin below the normal range. Classification by mean corpuscular volume (MCV) narrows the differential; the reticulocyte count separates underproduction from blood loss or hemolysis.

Category	MCV	Causes
Microcytic	<80fL	Irondeficiency(mostcommon) thalassemia anemiaofchronicdisease(somecases) , , ,
		sideroblasticanemia(lead alcohol) ,
Normocytic	80–100	Acutebloodloss anemiaofchronicdisease CKD hemolysis marrowfailureorinfiltration , , , ,
	fL
Macrocytic megaloblastic ,	>100fL	VitaminB12orfolatedeficiency;drugs(methotrexate hydroxyurea someantiretrovirals) , ,
Macrocytic ,	>100fL	Liverdisease alcoholuse hypothyroidism myelodysplasticsyndromes marked , , , ,
nonmegaloblastic		reticulocytosis

Iron deficiency anemia results from chronic blood loss (GI loss must be excluded in men and postmenopausal women), inadequate intake, or malabsorption. Anemia of chronic disease occurs in inflammatory states, malignancy, and chronic infection: inflammatory cytokines raise hepcidin, which blocks intestinal iron absorption and traps iron in macrophages.

Condition	Ferritin	Serum Iron	TIBC	TransferrinSaturation
Irondeficiency	Low(<30ng/mLis	Low	High	Low(<20%)
	diagnostic)
Anemiaofchronic	Normalorhigh	Low	Lowor	Lowornormal
disease			normal
Thalassemiatrait	Normal	Normal	Normal	Normal(RBCcountnormalorhigh;target
				cells)
Sideroblasticanemia	High	High	Normalor	High(ringedsideroblastsinmarrow)
			low

Ferritin is an acute-phase reactant: in inflammation, a ferritin up to about 100 ng/mL can still reflect iron deficiency. Megaloblastic anemia from B12 or folate deficiency shows hypersegmented neutrophils and elevated homocysteine; methylmalonic acid is elevated only in B12 deficiency. B12 deficiency also causes neurologic disease (peripheral neuropathy and subacute combined degeneration of the dorsal columns and corticospinal tracts) that may occur without anemia; folate alone corrects the anemia but not the neurologic damage.

Hemolytic anemias involve premature red cell destruction. Intravascular hemolysis releases free hemoglobin, causing hemoglobinuria and elevated LDH; extravascular hemolysis occurs in the reticuloendothelial system (spleen, liver). Laboratory findings: elevated indirect bilirubin, elevated LDH, decreased haptoglobin, and reticulocytosis. Causes include autoimmune hemolysis (positive direct antiglobulin test), microangiopathic hemolytic anemia (schistocytes: TTP, HUS, DIC, HELLP, mechanical valves), and hereditary conditions (G6PD deficiency, hereditary spherocytosis, sickle cell disease).

Thrombocytopenia results from decreased production (marrow failure, chemotherapy, alcohol), increased destruction (immune, consumptive), or sequestration (hypersplenism).

Disorder	Mechanism	KeyFindings	Management
Immune	Autoantibody-mediated	Isolatedthrombocytopenia;normal	Treatifplatelets<30000/µLor ,
thrombocytopenia	plateletdestruction	PT/aPTT;noschistocytes;diagnosisof	bleeding:glucocorticoids IVIG; ,
(ITP)		exclusion	platelet transfusion only for life-
			threateningbleeding
Thrombotic	SevereADAMTS13	ThrombocytopeniaplusMAHA	Emergentplasmaexchange ,
thrombocytopenic	deficiency(usually	(schistocytes highLDH);fever , ,	glucocorticoids caplacizumab , ,
purpura(TTP)	autoantibody)leaves	neurologicandrenalfindingsvariably	rituximab;avoidplatelettransfusion
	largevonWillebrand	present;normalPT/aPTT;ADAMTS13	unless life-threatening bleeding
	multimers;platelet	activity<10%
	microthrombi
Heparin-induced	IgGantibodiesagainst	Platelet fall >50% typically 5–10 days ,	Stopallheparin(includingLMWH
thrombocytopenia	heparin–platelet factor 4	afterheparinstarts(soonerwith	and flushes); start a non-heparin
(HIT)	complexesactivate	exposureinthepast100days);	anticoagulant(argatroban ,
	platelets	paradoxicalvenousandarterial	bivalirudin fondaparinux ora , ,
		thrombosis; 4Ts score anti -PF4 ,	DOACinstablepatients);no
		immunoassay serotoninreleaseassay ,	warfarinuntilplateletsrecover
Disseminated	Systemicactivationof	ProlongedPTandaPTT lowfibrinogen , ,	Treattheunderlyingcause;if
intravascular	coagulationconsumes	elevated D -dimer low platelets , ,	bleeding replaceplatelets plasma , , ,
coagulation(DIC)	plateletsandclotting	schistocytes;triggeredbysepsis ,	andcryoprecipitate(fibrinogen)
	factors:microvascular	trauma malignancy obstetric , ,
	thrombosisandbleeding	complications

Coagulopathies involve clotting factor deficiencies or inhibitors. The vitamin K–dependent factors (II, VII, IX, X, plus proteins C and S) fall with vitamin K deficiency, liver disease, and warfarin therapy, prolonging PT/INR first because factor VII has the shortest half-life. Hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) are X-linked and prolong the aPTT with a normal PT.

Condition	PT/INR	aPTT	Platelets	Fibrinogen
Warfarin vitaminK ,	Prolonged	Normalormildly	Normal	Normal
deficiency		prolonged
Unfractionatedheparin	Normalormildly	Prolonged	Normal(unlessHIT)	Normal
	prolonged
HemophiliaAorB	Normal	Prolonged	Normal	Normal
Advancedliverdisease	Prolonged	Normalorprolonged	Low(splenic	Normalor
			sequestration)	low
DIC	Prolonged	Prolonged	Low	Low
ITP	Normal	Normal	Low	Normal

Endocrine Pathophysiology

Diabetic ketoacidosis (DKA) results from absolute or relative insulin deficiency, typically in type 1 diabetes but also in type 2 diabetes during severe stress. Hyperglycemia causes osmotic diuresis with volume depletion and electrolyte losses; unrestrained lipolysis produces ketoacids and a high anion gap metabolic acidosis. Hyperosmolar hyperglycemic state (HHS) occurs mainly in type 2 diabetes, where enough insulin is present to prevent ketosis but not severe hyperglycemia; profound dehydration and altered mental status predominate.

Dkavshhs

Feature	DKA	HHS
Glucose	≥200mg/dLorknowndiabetes(classically>250);maybenear	≥600mg/dL oftenmuchhigher ,
	normalwithSGLT2inhibitors(euglycemicDKA)
Ketones	Positive: β -hydroxybutyrate ≥3 .0 mmol/L	Absent or minimal (β -hydroxybutyrate <3 .0
		mmol/L)
pH/bicarbonate	pH<73and/orHCO3<18mEq/L;highaniongap .	pH≥73;HCO3≥15mEq/L .
Serum	Variable	Effectiveosmolality>300mOsm/kg(total
osmolality		>320)
Onset/mental	Hourstoaday;alerttoobtunded;Kussmaulrespirations fruity ,	Daystoweeks;alteredmentationtocoma
status	breath abdominalpain ,	common;moreseveredehydration
Mortality	Lower	Higher(older morecomorbidpatients) ,

➜

➜

➜

➜

Isotonic crystalloid about

Hold insulin if K <3.5;

Regular insulin infusion

Add when glucose <250

Give SC basal insulin 1–2

1–1.5 L in the first hour

add K to fluids when K

about 0.1 unit/kg/h

mg/dL; continue insulin

h before stopping the

<5.0–5.3

until acidosis resolves

infusion

Serum osm = 2 × Na + glucose ÷ 18 + BUN ÷ 2.8 Effective osm = 2 × Na + glucose ÷ 18

Normal is about 275–295 mOsm/kg. Insulin drives potassium into cells, so total-body potassium depletion in DKA is unmasked during treatment; bicarbonate is reserved for pH <7.0.

Thyroid storm is severe thyrotoxicosis with systemic decompensation, triggered by infection, surgery, trauma, iodinated contrast, or stopping antithyroid medication. Myxedema coma is decompensated severe hypothyroidism, often triggered by infection, cold exposure, sedatives, or stopping levothyroxine.

Feature	ThyroidStorm	MyxedemaComa
Temperature	Hyperthermia(often>40°C)	Hypothermia
Cardiovascular Neurologic	Tachycardia atrial fibrillation high -output heart failure instability , , , Agitation delirium psychosis seizures coma , , , ,	Bradycardia hypotension pericardial , , Alteredconsciousnesstocoma	1 effusion

Thyroidstormvsmyxedemacoma(Continued)

Feature	ThyroidStorm	MyxedemaComa
Other	Nausea vomiting diarrhea jaundice; Burch -Wartofsky score ≥45 , , ,	Respiratorydepressionwithhypercapnia ,
findings	highlysuggestive	hyponatremia hypoglycemia nonpittingedema , ,
Treatment	Beta-blocker (propranolol); thionamide (PTU or methimazole);	IVlevothyroxine(±liothyronine);IVhydrocortisone
	iodinegivenatleast1hourafterthethionamide;glucocorticoids;	untiladrenalinsufficiencyisexcluded;ventilatory
	coolingwithacetaminophen(avoidaspirin)	support;passiverewarming

Adrenal insufficiency is inadequate cortisol production. Primary insufficiency (Addison disease) destroys the adrenal cortex, so both cortisol and aldosterone are deficient. Secondary insufficiency results from pituitary dysfunction or suppression of the axis by chronic glucocorticoid therapy (the most common cause); aldosterone is preserved because it is regulated by the renin-angiotensin system.

Feature	Primary(Adrenal)	Secondary(PituitaryorExogenousSteroids)
Cortisol	Low	Low
ACTH Aldosterone	High Low:hyperkalemia hyponatremia volumedepletion , ,	1 Loworinappropriatelynormal Preserved:hyperkalemiaabsent(hyponatremiacanoccur)

Primaryvssecondaryadrenalinsufficiency(Continued)

Feature	Primary(Adrenal)	Secondary(PituitaryorExogenousSteroids)
Hyperpigmentation	Present(ACTH/MSHexcess)	Absent
Diagnosis	Lowmorningcortisol;bluntedcortisolresponseto	LowcortisolwithlowACTH;pituitary
	cosyntropin	evaluation

Adrenal crisis occurs when stress (infection, surgery, trauma) meets unrecognized or undertreated adrenal insufficiency: hypotension or shock refractory to fluids and vasopressors, hypoglycemia, altered consciousness, vomiting, and abdominal pain. Draw cortisol and ACTH if it causes no delay, then give hydrocortisone 100 mg IV immediately (then 50 mg every 6 hours or 200 mg/24 hours) with isotonic saline and dextrose. Never delay steroids for testing.

Pheochromocytoma and paraganglioma produce catecholamines, causing paroxysmal or sustained hypertension with the classic triad of headache, palpitations, and diaphoresis. Screen with plasma free metanephrines or 24-hour urine fractionated metanephrines. Recognition before surgical or invasive procedures is essential, because an unrecognized tumor can cause intraoperative hypertensive crisis. Preoperative alpha-blockade first (phenoxybenzamine or doxazosin, for 7–14 days), then a beta-blocker if needed; a beta-blocker given first leaves alpha-mediated vasoconstriction unopposed and can precipitate hypertensive crisis.

Neurological Pathophysiology

Stroke results from brain ischemia or hemorrhage. Ischemic stroke (about 85%) follows thrombotic or embolic occlusion of a cerebral vessel. The infarct core is irreversibly injured; the surrounding ischemic penumbra is dysfunctional but salvageable, and tissue survival depends on maintaining penumbral blood flow until reperfusion. Hemorrhagic stroke includes intracerebral hemorrhage, usually from hypertensive rupture of small penetrating vessels, and subarachnoid hemorrhage, usually from a ruptured aneurysm.

Stroketypes

Type	Mechanism/Presentation	AcutePriorities
Ischemic	Thrombosis cardioembolism(atrial ,	NoncontrastCTtoexcludehemorrhage;IVthrombolysis(alteplase	or
	fibrillation) small -vessel (lacunar) ,	tenecteplase)within45hoursoflastknownwellifeligible withBP . ,
	disease;focaldeficitofsudden	<185/110beforeand<180/105for24hoursafter;thrombectomyfor	large-
	onset	vesselocclusioninselectedpatientsupto24hours;ifnottreatedwith
		reperfusion permitBPupto220/120 ,
Intracerebral	Chronichypertension amyloid ,	LowerSBPtowardabout140mmHg(avoidexcessivedrops);reverse
hemorrhage	angiopathy anticoagulation; ,	anticoagulationpromptly;neurosurgicalevaluation
	headache vomiting declining , ,
	consciousness focaldeficit ,
Subarachnoid	Aneurysmrupture;sudden"worst	NoncontrastCT(lumbarpunctureforxanthochromiaifCTisnegativeand
hemorrhage	headacheoflife"(thunderclap) , neckstiffness photophobia , , syncope	suspicionpersists);securetheaneurysm;nimodipinetoreducedelayed 1 cerebralischemiafromvasospasm(peakdays3–14);watchfor hydrocephalusandhyponatremia

Increased intracranial pressure from mass lesions, edema, hemorrhage, or hydrocephalus compromises brain perfusion. Normal adult ICP is about 5–15 mmHg; sustained values above about 20–22 mmHg are treated. The Cushing triad (hypertension with widened pulse pressure, bradycardia, and irregular respirations) is a late sign of brainstem compression.

CPP = MAP − ICP target CPP about 60–70 mmHg

Example: BP 110/65 (MAP ≈ 80) with ICP 25 gives CPP 55 mmHg, below target. Raising MAP or lowering ICP restores perfusion; hypotension is as harmful as intracranial hypertension.

Syndrome	Displacement	ClassicFindings
Uncal	Medialtemporallobe	CompressionofCNIII:ipsilateraldilated nonreactivepupil;compressionofthe ,
(transtentorial)	overthetentorialedge	cerebralpeduncle:contralateralhemiparesis(ipsilateraliftheoppositepeduncleis
		pushedagainstthetentorium afalselocalizingsign);decliningconsciousness ,
Central	Diencephalonand	Decreasing consciousness small then midposition fixed pupils Cheyne-Stokes , ,
	midbraindownward	respirations decorticatethendecerebrateposturing ,
Subfalcine	Cingulategyrusunder	Oftenclinicallysilent;anteriorcerebralarterycompressioncausescontralateralleg
(cingulate) Tonsillar	thefalx Cerebellartonsils throughtheforamen magnum	weakness 1 Medullarycompression:respiratoryarrestandcardiovascularcollapse;neckstiffness

Seizures result from abnormal, synchronized neuronal discharges. Focal seizures originate in networks limited to one hemisphere (with or without impaired awareness, and may become bilateral tonic-clonic). Generalized seizures involve both hemispheres from onset (tonic-clonic, absence, myoclonic, atonic). Status epilepticus is continuous seizure activity lasting 5 minutes or more, or recurrent seizures without recovery between them, and requires emergent treatment to prevent neuronal injury.

Convulsivestatusepilepticus:Time-Basedtreatment

➜

➜

➜

ABCs, oxygen, IV access,

Lorazepam IV 0.1 mg/kg (max 4

Fosphenytoin 20 mg PE/kg,

Intubate; midazolam, propofol, or

fingerstick glucose (thiamine

mg/dose, may repeat) or

valproate 40 mg/kg, or

pentobarbital infusion with

before dextrose if at risk)

midazolam 10 mg IM

levetiracetam 60 mg/kg

continuous EEG

Altered mental status has diverse causes: metabolic derangements (glucose, sodium, calcium, uremia, hepatic failure, hypercapnia), infection (sepsis, meningitis, encephalitis), structural lesions (stroke, hemorrhage, tumor), toxins and drugs (including withdrawal), and psychiatric conditions. Delirium is an acute, fluctuating disturbance of attention and cognition, usually with an identifiable precipitant. Distinguishing delirium from dementia, depression, and psychiatric disorders guides evaluation and treatment.

Feature	Delirium	Dementia	Depression
Onset	Acute(hourstodays)	Insidious(monthstoyears)	Subacute(weekstomonths)
Course	Fluctuating worseatnight ,	Slowlyprogressive	Persistent;mayvarythroughtheday
Attention	Impaired(hallmark)	Usuallypreserveduntillate	Reducedeffortandconcentration
Levelof	Altered(hyperalertordepressed)	Normaluntillate	Normal
consciousness
Perception	Hallucinations(oftenvisual)	Usuallyabsentuntillater	Usuallyabsent(psychoticfeatures
	common	stages	uncommon)
Reversibility	Oftenreversiblewhenthecauseis	Generallyirreversible	Treatable
	treated

Delirium may be hyperactive (agitation), hypoactive (withdrawn, drowsy), or mixed. Hypoactive delirium is the most common form in older adults and the most often missed. Dementia is the strongest risk factor for delirium, and the two often coexist.

Prerenal: BUN/Cr >20:1, FENa <1%; ATN: FENa >2%, muddy

TTP: MAHA + low platelets with normal PT/aPTT, treat with

brown casts.

plasma exchange; HIT: stop all heparin.

Limit chronic hyponatremia correction to about 8 mEq/L per

Adrenal crisis: hydrocortisone 100 mg IV without waiting for

24 h in high-risk patients to avoid osmotic demyelination.

tests; pheochromocytoma: alpha-blocker before beta- blocker.

Hyperkalemia with ECG changes: calcium first, then shift (insulin, albuterol), then remove.

CPP = MAP − ICP (goal 60–70); status epilepticus = seizure

MUDPILES = high anion gap; diarrhea and RTA = normal gap; Winter formula checks compensation.