BIOL 2200 Module 10: Excretory Systen & pH and Electrolyte Disorders

Kidney stones (urinary calculi)

Frequently causes upper urinary tract obstruction, often composed of calcium oxalate or phosphate

Renal colic

EXCRUCIATING pain from kidney stones caused by a stone (1-5mm) stretching the ureter

Treatment for kidney stones

Removing stones, managing pain, increasing fluid and altering diet

Lower urinary tract obstruction

Related to storage of urine in the bladder. May be caused by neurogenic bladder or physical obstruction

Neurogenic bladder

Bladder dysfunction from neurologic disorders

Glomerulonephritis

Inflammation in the glomerulus

Common causes of glomerular disorders

Type II hypersensitivity in glomerulus (Goodpasture syndrome) or Type III hypersensitivity in glomerulus (post-streptococcal glomerulonephritis)

Goodpasture syndrome

Type II hypersensitivity where Ab reacts with Ag in glomerulus

Post-streptococcal glomerulonephritis

Type III hypersensitivity with deposition of Ab-Ag complexes in the glomerulus

Nephritic syndrome

Sudden excretion of blood cells and protein. Caused by inflammation

NephrOtic syndrome (nephrosis)

Massive proteinuria and lipiduria. Caused by increased permeability in glomerulus

How is glomerular filtration rate typically measured?

With either serum creatinine concentration (preferred) or injected inulin

Blood Urea Nitrogen (BUN)

Urea concentration in blood. Shows degree of glomerular filtration and urine-concentrating capacity

Plasma creatinine concentration

Indicates amount of filtration at the glomerulus (GFR), since it is never reabsorbed

Relationship between glomerular filtration and plasma creatinine concentration

If the glomerular filtration rate decreases, the plasma creatinine concentration increases and vice versa

Acute Kidney Injury (AKI)

A sudden decline in kidney function

RIFLE

Spectrum measuring severity of AKI

• Risk

• Injury

• Failure

• Loss

• End stage kidney disease

Pre-renal acute kidney injury

Common cause of AKI, where the decrease in GFR is caused by renal hypoperfusion

What causes a high BUN:creatinine ratio?

From low filtration and slow tubular flow. Allows MORE urea reabsorption

Post-renal acute kidney injury

Typically occurs when urinary tract obstruction affects both kidneys. Normal BUN:creatinine ratio

GFR

Glomerular Filtration Rate

Intrarenal acute kidney injury

Typically results from tubular necrosis, as a result of ischemia or sepsis (etc). Lower BUN:creatinine ratio

How is AKI treated?

Through maintaining life until renal function recovers, or with continuous renal replacement therapy or hemodialysis

Chronic Kidney Disease (CKD)

Defined by kidney damage or a GFR <60ml/min for 3+ months

How many stages in CKD?

There are five stages in CKD

Intact nephron hypothesis

Proposes that unaffected nephrons can hypertrophy and hyperfunction to compensate for declining GFR. Symptoms only become apparent past 25% renal function decline

Clinical manifestations of CKD

1. Azotemia

2. Uremic syndrome (uremia)

3. Disturbed levels of fluids/electrolytes/acids/bases

Azotemia

Increased serum urea and other nitrogenous compounds

Uremic syndrome

Signs associated with accumulation of toxins and nitrogenous wastes in the plasma from kidney failure

Anasarca

General accumulation of fluid in body tissues and cavities

How does CKD affect the cardiovascular system?

• Through excess sodium/water → hypertension

• Excess LDL → atherosclerosis

How does CKD affect the pulmonary system?

• Through complications associated with fluid overload

• Acidosis from Kussmaul respirations

Kussmaul respirations

Deep, rapid, labored breathing when the blood is too acidic.

How does CKD affect the immune system?

Through suppressing it with high levels of metabolic wastes and urea

How does CKD affect the neurologic system?

Through the effects of uremic toxins, which affect both the PNS and CNS (headache, seizures, etc)

How does CKD affect the gastrointestinal system?

Through leading to anorexia and vomiting (possibly from urea breakdown by intestinal bacteria)

How does CKD affect the endocrine and reproductive systems?

Through decreasing levels of sex steroids, which can lead to insulin resistance and alterations in thyroid hormone metabolism

How is CKD managed?

Through drugs to treat hypertension, dialysis, and dietary control

Obstructive uropathy

Anatomic changes in the urinary system caused by obstruction

Unilateral renal damage vs bilateral renal damage

Unilateral → one kidney

Bilateral → both kidneys

Hydronephrosis

Backup of urine causing dilation of renal collecting ducts and tubules. Occurs from renal damage

Hydroureter

Swelling of a ureter

Compensatory hypertrophy and hyperfunction

Where an unobstructed kidney compensates for lost function in an obstructed kidney by hypertrophy of glomeruli and tubules

Which kidney stones may spontaneously pass?

When they are smaller, as smaller kidney stones (<5mm) have a ~50% chance of spontaneous passage

What causes renal hypoperfusion?

• Hypovolemia

• Intense vasoconstriction (NSAIDs)

High BUN:creatinine ratio

Occurs from low filtration and slow flow, allowing more reabsorption of urea. E.g. from renal hypoperfusion

Lower BUN:creatinine ratio

Occurs from poor urea reabsorption in tubules. E.g. from tubular necrosis

Does CKD lead to sodium reabsorption or excretion?

CKD leads to sodium reabsorption

Does CKD lead to potassium reabsorption or excretion?

CKD leads to potassium reabsorption

Does CKD lead to creatinine and urea retention or excretion?

CKD leads to creatinine and urea retention (due to decreased GFR)

Does CKD lead to calcium reabsorption or excretion?

CKD leads to calcium excretion (through calcium loss in bone)

Does CKD lead to protein retention or excretion?

CKD leads to protein excretion (through glomerular membrane damage)

Does CKD lead to LDL retention or excretion?

CKD leads to LDL retention (contributes to atherosclerosis)

Carbonic acid-bicarbonate buffer system

HCO₃^- (bicarbonate) → Basic component

H₂CO₃ (Carbonic acid) → Acidic component

Normal arterial pH

7.35-7.45

Metabolic acidosis

Increase in H⁺ and decrease in HCO₃^-

• E.g. from diabetic ketoacidosis and diarrhea

Results of metabolic acidosis

Nervous system depression and Kussmaul respirations

Anion gap

Calculation used to evaluate acid-base balance in the blood

• Between 8-12 mEq/L

Anion gap equation

Na⁺ - [Cl⁻ + HCO₃⁻]

Metabolic acidosis with normal anion gap

Indicates loss of HCO₃^-, such as from diarrhea

Metabolic acidosis with large anion gap

Indicates excessive acid production, e.g. ketoacidosis

Metabolic alkalosis

Caused by either excessive loss of metabolic acids (vomiting) or gain in bicarbonate 9ingestion)

How does metabolic acidosis lead to its common symptoms (weakness, muscle cramps, etc)

Through decreasing Ca²⁺ concentration, allowing more Na⁺ to cross the membrane and hypopolarize cells

Respiratory acidosis

Hypercapnia, caused by depression of respiratory center. Leads to hyperventilation

Respiratory alkalosis

Hypocapnia, caused by hyperventilation. Excites the nervous system, leading to paresthesias

Mixed acid-base imbalance

When two imbalances arise in the same person!

Hypernatremia

Excess sodium, which causes intracellular dehydration as sodium is mainly in ECF

Clinical manifestations of hypernatremia

• Thirst

• Membrane potential alterations

• Intracellular dehydration and nervous system effects, such as coma

• Hypervolemia or hypovolemia

Hypervolemia

High blood volume, often due to sodium retention (hypernatremia)

Hypovolemia

Low blood volume, often due to fluid loss (resulting in hypernatremia)

Hyponatremia

Decreased sodium concentration, leading to water moving into cells. May lead to neurological alterations (sodium is important here)

Causes of hyponatremia

• Dilutional hyponatremia

• Sodium loss

• Edema

• Gaining more water than sodium

Hyperkalemia causes

• Insulin deficits (insulin promotes K⁺ entry)

• Aldosterone undersecretion

• Kidney dysfunction

Clinical manifestations of hyperkalemia

• Decrease in neuromuscular excitability (parasthesias)

• Slowed heart rate, leading to cardiac arrest or ventricular fibrillation

Hypokalemia causes

• Excessive potassium loss

• Inadequate potassium intake

• Increased entry into cells (e.g. excess insulin in type 1 diabetes)

Clinical manifestations of hypokalemia

• Muscle weakness, fatigue cramps

• Polyuria and thirst

• Arrhythmias (from disruption of electrical system)

Roles of calcium

• Muscle contraction, neurotransmitter release, enzymes

• Neuromuscular excitability

Where in the body is calcium stored?

Calcium is mainly stored in bone (99%), with the remaining in ICF and ECF

Why is only free calcium available for metabolic processes?

Because free calcium is unbound, and is not locked away in bones or by proteins

Clinical manifestations of hypercalcemia

• Decreased excitability of muscles and nerves

• Hypoactive reflexes

• Decreased smooth muscle activity

Causes of hypercalcemia

• Neoplasms → secretions mimic PTH

• Hyperparathyroidism → increased PTH release

Clinical manifestations of hypocalcemia

• Increased excitability of muscles and nerves

• Increased GI motility

• Trosseau’s sign and Chvostek’s sign

Causes of hypocalcemia

• Decreased PTH

• Alkalosis (leads to increased binding of calcium to proteins, decreasing amounts of free calcium)

Roles of magnesium

• Cofactor in enzymatic reactions (ATP)

• Smooth muscle contraction and relaxation

• Nerve conduction

Not compensated

When neither the respiratory or renal systems are compensating for acidosis or alkalosis

Partially compensated

When the respiratory or renal systems are compensating for one another, but pH is still abnormal

Fully compensated

When the respiratory or renal systems are compensating for one another, and pH is normal