Electrolyte and Acid-Base Regulation

What is the normal sodium (Na⁺) range?

136–145 mEq/L

What is the normal chloride (Cl⁻) range?

98–106 mEq/L

What is the normal bicarbonate (HCO₃⁻) range?

22–26 mEq/L

What is the normal potassium (K⁺) range?

3.5–5.0 mEq/L

What is the normal calcium (Ca²⁺) range?

4.5–5.3 mEq/L

What is the normal magnesium (Mg²⁺) range?

1.4–1.7 mEq/L

What is the normal phosphate (HPO₄²⁻) range?

1.2–2.3 mEq/L

What are the causes of hyponatremia?

GI losses, sweating, fever, diuretics, ascites, congestive heart failure (CHF), and kidney failure

What are the clinical manifestations of hyponatremia?

Weakness, lassitude, apathy, headache, orthostatic hypotension, and tachycardia

What are the causes of hypernatremia?

Net sodium gain, net water loss, increased aldosterone, and steroid therapy

What are the clinical manifestations of hypernatremia?

Tremulousness, irritability, ataxia, confusion, seizures, and coma

What are the causes of hypochloremia?

GI losses and diuretics

What are the clinical manifestations associated with hypochloremia?

Metabolic alkalosis, muscle spasms, and coma

What conditions are associated with hyperchloremia?

Dehydration, metabolic acidosis, and respiratory alkalosis

What are the causes of hypokalemia?

Diuretics, steroid therapy, renal tubular disease, vomiting, diarrhea, malnutrition, and trauma

What are the clinical manifestations of hypokalemia?

Muscle weakness, paralysis, ECG abnormalities, supraventricular arrhythmias, circulatory failure, and cardiac arrest

What are the causes of hyperkalemia?

Chronic renal disease, hemorrhage, tissue necrosis, NSAIDs, ACE inhibitors, cyclosporine, and potassium-sparing diuretics

What are the clinical manifestations of hyperkalemia?

ECG changes, ventricular arrhythmias, and cardiac arrest

What causes of hypocalcemia are listed in your notes?

Hyperparathyroidism, pancreatitis, renal failure, and trauma

What are the clinical manifestations of hypocalcemia?

Hyperactive tendon reflexes, muscle twitching, spasms, abdominal cramps, ECG changes, and seizures

What are the causes of hypercalcemia?

Hyperthyroidism, hyperparathyroidism, metastatic bone cancer, and sarcoidosis

What are the clinical manifestations of hypercalcemia?

Fatigue, depression, muscle weakness, anorexia, nausea, vomiting, and constipation

What are the causes of hypomagnesemia?

Inadequate intake, impaired absorption of magnesium, pancreatitis, and alcoholism

What are the clinical manifestations of hypomagnesemia?

Muscle weakness, irritability, tetany, ECG changes, arrhythmias, delirium, and seizures

What are the causes of hypermagnesemia?

Dehydration, renal insufficiency, tissue trauma, and lupus erythematosus

What are the clinical manifestations of hypermagnesemia?

ECG changes, hyperkalemia, cardiac arrest, and respiratory muscle paralysis

What are the causes of hypophosphatemia?

Starvation, malabsorption, hyperparathyroidism, hyperthyroidism, and uncontrolled diabetes mellitus

What is a major respiratory manifestation of hypophosphatemia?

Diaphragmatic weakness

What are the causes of hyperphosphatemia?

Endocrine disorders, acromegaly, chronic renal insufficiency, acute renal failure, and tissue trauma

What are the five major functions supported by renal electrolyte regulation?

Acid-base regulation, fluid volume maintenance, nerve impulse transmission, muscle contraction, and cellular function

What is the kidney's primary priority when regulating fluid and electrolytes, according to the notes?

Maintaining fluid volume, even when this compromises electrolyte or acid-base balance

Approximately how much fluid is filtered by the kidneys per day?

180 L/day

What is the normal daily urine output given in the notes?

Approximately 1.5–3 L/day

What percentage of filtered fluid must be reabsorbed by the kidneys?

More than 99%, approximately 178 L/day

Why is sodium reabsorption important for water retention?

Sodium creates an osmotic gradient, causing water to follow sodium back into the circulation

What percentage of sodium reabsorption is attributed to primary active transport in the notes?

Approximately 80%

Where does primary active sodium reabsorption occur?

In all tubules except the descending loop of Henle, according to the lecture slides

How does sodium initially enter the renal tubular cell during primary active transport?

It diffuses down its electrochemical gradient through the luminal membrane into the tubular cell

What is the function of the Na⁺/K⁺-ATPase pump?

It uses ATP to pump sodium out of the tubular cell into the interstitial fluid while moving potassium into the cell

How many sodium and potassium ions are exchanged by the Na⁺/K⁺-ATPase pump?

Three Na⁺ ions are pumped out, and two K⁺ ions are pumped into the cell

Where is the Na⁺/K⁺-ATPase pump located in the renal tubular cell?

On the non-luminal (basolateral) membrane

How does the Na⁺/K⁺-ATPase pump maintain sodium reabsorption?

By preventing intracellular sodium accumulation, maintaining the gradient for continued sodium entry

What causes chloride to follow sodium during primary active transport?

The electrochemical gradient created by sodium transport drives passive chloride movement

What is the purpose of microvilli on the tubular brush border?

To increase surface area and promote sodium movement across the luminal membrane

What percentage of sodium reabsorption is attributed to secondary active transport?

Approximately 20%

Which ions are secreted into the filtrate in exchange for sodium during secondary active transport?

Hydrogen (H⁺) or potassium (K⁺)

How does the Na⁺/H⁺ countertransporter function?

It exchanges one intracellular H⁺ into the filtrate for one luminal Na⁺ entering the tubular cell

Why is secondary active sodium transport closely associated with acid-base balance?

Sodium reabsorption is coupled with H⁺ secretion and bicarbonate reabsorption

What determines whether H⁺ or K⁺ is secreted during secondary active sodium transport?

The availability of H⁺ and K⁺ and the kidney's need to maintain sodium reabsorption

Where is the Na⁺/2Cl⁻/K⁺ cotransporter located?

On the luminal membrane of the thick ascending loop of Henle

What ions are transported together by the Na⁺/2Cl⁻/K⁺ cotransporter?

One sodium, two chloride, and one potassium ion

Does chloride require direct ATP expenditure when transported by the Na⁺/2Cl⁻/K⁺ cotransporter?

No. Chloride is pulled along with sodium without direct ATP expenditure

Approximately what percentage of potassium is intracellular?

98%

Why is potassium regulation especially important for cardiac function?

Potassium maintains resting membrane potentials and electrical conduction; small changes can cause fatal arrhythmias

What primarily regulates potassium levels in the body?

Renal potassium excretion

What three factors stimulate potassium uptake into cells?

Insulin, aldosterone, and beta-adrenergic stimulation

Which nephron segments are responsible for the final regulation of potassium excretion?

The distal tubule and collecting duct

How does potassium move from the tubular cell into the filtrate?

The Na⁺/K⁺-ATPase pump increases intracellular K⁺, allowing it to diffuse into the filtrate

What two factors primarily control renal potassium excretion?

Extracellular potassium concentration and aldosterone secretion

Approximately what percentage of filtered potassium is handled by the proximal tubule?

Approximately 65%

What percentages of potassium handling are assigned to the thick ascending loop and distal nephron?

Approximately 25% in the thick ascending loop and the final 10% in the distal tubule and collecting duct

What are the two major effects of angiotensin II?

Direct vasoconstriction and stimulation of aldosterone release from the adrenal cortex

How do ACE inhibitors affect angiotensin II formation?

They inhibit the conversion of angiotensin I into angiotensin II, reducing vasoconstriction and promoting diuresis

Where is aldosterone produced?

The adrenal cortex

What three electrolytes are retained through aldosterone-mediated renal effects in the notes?

Sodium, bicarbonate, and chloride

How does aldosterone increase sodium reabsorption and potassium excretion?

It increases Na⁺/K⁺-ATPase pump activity in distal tubular and collecting duct cells

How can excessive aldosterone affect acid-base balance?

It promotes bicarbonate retention and H⁺ secretion, contributing to metabolic alkalosis

How does increased sodium and water retention affect blood pressure?

Blood volume increases, raising cardiac output and systemic blood pressure

What is Addison's disease, and how can it affect potassium?

Primary adrenal insufficiency with deficient aldosterone, impairing potassium excretion and potentially causing severe hyperkalemia

What electrolyte and fluid abnormalities can occur with primary hyperaldosteronism?

Sodium and water retention, hypertension, edema, and severe hypokalemia

How can prolonged systemic corticosteroid therapy affect electrolytes and fluid balance?

It can mimic aldosterone, producing fluid retention, edema, and hypokalemia

What physical changes are associated with prolonged corticosteroid use in the notes?

Central weight gain, skin fragility, lower-extremity edema, and upper thoracic fat or fluid deposition

What happens to aldosterone secretion when blood volume increases through normal negative feedback?

Aldosterone secretion decreases, reducing sodium reabsorption and H⁺/K⁺ losses

Which parts of the nephron actively secrete H⁺?

All renal tubules except the thin segment of the loop of Henle

What percentage of renal H⁺ secretion occurs through secondary versus primary active transport?

Approximately 95% secondary active transport and 5% primary active transport

What allows primary active H⁺ transport to produce very acidic urine?

ATP-driven proton pumps move H⁺ against steep concentration gradients

What chemical reaction produces hydrogen and bicarbonate ions inside renal tubular cells?

CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻

Which enzyme facilitates the conversion between CO₂, H₂O, and carbonic acid?

Carbonic anhydrase

What happens when secreted H⁺ combines with filtered bicarbonate?

Carbonic acid (H₂CO₃) forms and is converted to CO₂ and H₂O

Why can CO₂ produced in the tubular filtrate enter tubular cells?

CO₂ is membrane-permeable and diffuses down its partial pressure gradient

What happens to CO₂ after it re-enters the renal tubular cell?

It combines with H₂O to form H₂CO₃, which dissociates into H⁺ and HCO₃⁻

What happens to the bicarbonate generated inside the renal tubular cell?

It is reabsorbed into the peritubular capillary blood

What is the relationship between H⁺ secretion and bicarbonate reabsorption in the notes?

One bicarbonate ion is reabsorbed for each H⁺ ion secreted through the described recovery pathway

How do the kidneys compensate for respiratory acidosis?

By increasing H⁺ secretion, excreting H⁺ with urinary buffers, and increasing HCO₃⁻ reabsorption

How does increased CO₂ contribute to renal compensation during respiratory acidosis?

More CO₂ enters tubular cells, promoting the formation of H⁺ and HCO₃⁻

How do the kidneys compensate for respiratory alkalosis?

By reducing H⁺ secretion and increasing bicarbonate excretion

Why is bicarbonate lost in the urine during respiratory alkalosis?

Insufficient H⁺ is available to react with filtered HCO₃⁻, allowing bicarbonate to remain in the filtrate

Which ions can accompany bicarbonate excretion during respiratory alkalosis?

Sodium (Na⁺) and potassium (K⁺)

Which organ system provides the most powerful long-term acid-base regulation according to the notes?

The kidneys

How long can renal acid-base compensation take?

Hours, days, or even weeks, depending on renal function

What type of acids can the lungs eliminate?

Volatile acid through CO₂ elimination

Why can't the lungs completely correct an accumulation of fixed acids?

Increasing ventilation removes CO₂ but cannot directly eliminate fixed acids such as lactic acid or ketoacids

What factors limit the ability of the respiratory system to compensate for acid-base disturbances?

Respiratory rate limitations, respiratory muscle fatigue, and underlying lung function

What are the two main urinary buffer systems?

Phosphate and ammonia

Why are urinary buffers necessary for H⁺ excretion?

They bind secreted H⁺, preventing excessive free H⁺ accumulation and allowing continued acid excretion

How does the phosphate buffer system remove H⁺?

HPO₄²⁻ combines with H⁺ to form H₂PO₄⁻

Why does phosphate become concentrated in the tubular filtrate?

It is poorly reabsorbed and becomes concentrated as water is reabsorbed

Where is ammonia (NH₃) produced for urinary buffering?

In renal tubular epithelial cells through amino acid metabolism

How does the ammonia buffer system remove H⁺?

NH₃ binds H⁺ to form ammonium (NH₄⁺)

What controls the rate of ammonia synthesis in the renal tubular cells?

The H⁺ concentration within the filtrate