Function:
- To form the ultrafiltrate
- To selectively reabsorb tubule fluids or secrete solute into this

Structure: 

What are the 2 types of nephrons?
- Superficial: short loops extending between inner and outer medulla
-Juxtamedullary: play a special role in the production of concentrated urine, have long loops that extend as far as the tip of the medulla.

What is the function of the renal tubules?
- The main function of renal tubules is to recover most of the fluid and solutes filtered at the glomerulus

- Proximal tubule: reabsorbs water & solutes:  NaCl, NaHCO3, filtered nutrients, divalent ions

What is the function of the Loop of Henle?
- Forms a concentrated or diluted urine
- Does this by pumping NaCl into the interstitium of the medulla

   

What is the function of the distal tubule & collecting duct system?
- perform the fine control of NaCl and water excretion

Glomerular filtration rate (GFR) is a calculation that determines how well the blood is filtered by the kidneys, which is one way to measure remaining kidney function.

= a high glomerular filtration rate is essential for maintaining stable and optimal extracellular levels of solutes and water 

Structure/components of glomerulus:
- Basement membrane
        - have mechanisms that keep molecules by charge
        - repels charged particles by having a charge of its own, so we can keep things like proteins
        - if this becomes to thick we will not have proper diffusion 
        - if there is damage to the integrity of the membrane we lose molecules we want to keep (proteins, maybe even blood)

- Podocytes -> have foot processes (protrusions)
        - these protrusions are part of the filtering system
        - must then have them be healthy and in shape
        - we need to filter what we don't want, but keep the  rest i.e. cellular components (this is why erythrocytes in urine is a sign of malfunction)

- Slit diaphragm:

- 

Pay attention to these small but important structures!


      

→ Four factors that modulate renal blood flow and glomerular filtration:

Inorganic ion balance (electrolytes):

The kidneys regulate the salt balance in the blood by controlling the excretion and the reabsorption of various ions.

Acid-base balance:

The kidneys have the predominant role in regulation the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance

→ This function of the kidneys has two components: 

Normal arterial pH is between 7.36 and 7.44; intracellular is ~7.2

--> Where does this regulation happen?

Removal of metabolic waste products:
Kidneys excrete toxins and waste products into the urine as fast as they are produced
- keeps products from accumulating
- waste products include urea, uric acid, creatinine

Removal of foreign chemicals:

Gluconeogenesis:
→ During prolonged fasting, the kidneys synthesize glucose from amino acids and other precursors and release it into the blood 

→ gluconeogenesis occurs in the cells of the proximal tubule

Hormone production:
the kidneys act as endocrine glands, releasing at least two hormones: erythropoietin, and 1,25-dihydroxyvitamin D

→ The kidneys also secrete an enzyme, renin, that is important in the control of blood pressure and sodium balance

→ potassium:

→ chloride:

→ bicarbonate:

→ calcium:

→ magnesium:

→ phosphate:

→ (BUN, urine osmolality, urine sodium concentration):

*During hyperventilation/vomiting = Net loss of H+ = kidneys replenish H+ to restore balance

*Increased arterial H+ concentration = stimulates ventilation = lowers arterial PCO2 that = reduces H+ concentration

*Decreased plasma H+ concentration = inhibits ventilation =  increasing arterial PCO2 = increases the H+ concentration

The anion gap is the difference between primary measured cations (sodium Na+ and potassium K+) and the primary measured anions (chloride Cl- and bicarbonate HCO3-) in serum. 

→ How do we calculate it
The anion gap = (Na+ + K+) - (Cl- + HCO3-)


→ The anion gap can be normal, high, or low. A high anion gap indicated metabolic acidosis, the increased acidity of the blood due to metabolic processes. 

→ A low anion gap is relatively rare but may occur from the presence of abnormal positively charged proteins, as in multiple myeloma.

What are the two distinct categories?

→ Respiratory acidosis or alkalosis:

→ Metabolic acidosis or alkalosis:

-> Disorder that affects respiration
-> can cause changes in pH and pCO2

What are the causes of respiratory acidosis? (use table in article)
-> Often caused by various lung diseases
-> Anything that can cause hypoventilation 

What are the Clinical Findings (signs & symptoms) of respiratory acidosis?
→ The characteristic features of hypercapnia and the resultant respiratory acidosis range from fatigue, irritability, headache, confusion, stupor, and obtundation to coma and are dependent on the severity and chronicity of the hypercapnia. 

→ A Pco2 of 70 may result in coma when secondary to an acute respiratory acidosis, while a person with chronic respiratory acidosis may tolerate Pco2 levels higher than this without a decrease in mental status.

What is the Physiology of respiratory acidosis (acute & chronic)?

→ The increased protons resulting from an acute respiratory acidosis are buffered by intracellular proteins. 

→ This results in a rise in [HCO3−] of 1 mEq/L for every 10 mm Hg increase in Pco2 up to a maximum [HCO3−] of 30 mEq/L and a decrease in pH of 0.08. 

→ This compensation is complete within minutes and further compensation is limited until renal excretion of acid occurs, which may take several days.

    2. Chronic Respiratory Acidosis

→ Chronic respiratory acidosis commonly results from chronic obstructive pulmonary disease (COPD) and extreme obesity. 

→ Renal compensation reaches a steady state after 3–4 days and involves the excretion of chloride in addition to acid, with retention of bicarbonate. 

→ An increase in the Pco2 of 10 mm Hg is expected to result in an increase in [HCO3−] of 3.5 mEq/L (to a maximum of 45 mEq/L) and a decrease in pH of 0.03.

What is the treatment for respiratory acidosis?
-> primary: identify and treat underlying pathology
-> support of ventilation

= occurs when the respiratory system eliminates carbon dioxide faster than it is produced 

→ The imbalance of arterial H+ concentrations in such cases is completely explainable in terms of mass action

= Respiratory alkalosis is defined as a Pco2 below 35 mm Hg with an increase in serum pH above 7.44. 

What are the causes of respiratory alkalosis?
-> hyperventilation secondary to other causes
-> ergo anything that causes hyperventilation

What are the Clinical Findings (signs & symptoms) of respiratory alkalosis?

What is the physiology of respiratory alkalosis? (acute & chronic)

→ Compensation for acute hypocapnia begins within minutes and involves the movement of protons from the intracellular to the extracellular space. 

→ For every decrease in Pco2 of 10 mm Hg, [HCO3−] should decrease by 2.5 mEq/L and pH should increase by 0.08.

    2. Chronic Respiratory Alkalosis

→ Renal compensation for chronic respiratory alkalosis results in decreased proton excretion and the retention of chloride for bicarbonate. 

→ Chronically, a decrease in Pco2 of 10 mm Hg will result in a decrease in [HCO3−] of 5 mEq/L. With prolonged hypocapnia (2 weeks or more), pH may be normal.

What is the treatment for respiratory alkalosis?
-> treating underlying pathology

For lecturer: How long do we have to wait and see how the system is compensating?

Defined as a decrease in [HCO3−] to below 22 with a decrease in pH below 7.36. 

What are the causes of metabolic acidosis?
-> overproduction of organic acids
-> loss of bicarbonate through intestinal or renal wasting
-> inability to excrete acids from normal metabolism
-> toxin ingestion

What are the clinical findings of metabolic acidosis?
-> Cardiovascular dysfunctions
-> Neurologic dysfunctions
-> Respiratory dysfunctions
-> largely dependent on underlying cause

What is the physiology of metabolic acidosis?

What is the treatment for metabolic acidosis?

 primary elevation of serum [HCO3−] above 28 mEq/L with an elevation in pH above 7.44

What are the causes of metabolic alkalosis?
-> excess loss of acid
-> (very rarely) gaining base
-> gastric losses via vomiting, diuretic use

What are the clinical findings of metabolic acidosis?

What is the physiology of metabolic alkalosis?

What is the treatment for metabolic alkalosis?
-> primarily guided by concentration of chlorine in the urine

-> Potassium replacement (up to 100–500 mEq) may be needed to correct the alkalosis in certain settings. 

-> Acetazolamide may be used in posthypercapnic metabolic alkalosis if volume status is normal. 

How is body water and fluid distributed within the body?
- depends on the proportions of muscle and fat in body, age, height, etc
- total body water ~ 60% in men, 50% in women
-> decreases with age
-> 2/3rds in intracellular, 1/3rd in extracellular (28% is interstitial, 7% is plasma fluid)

How do we evaluate changes in total body water content?

→ Changes in total body water content are best evaluated by documenting changes in body weight. 

→ Extracellular volume (ECV) may be assessed by physical examination (eg, blood pressure, pulse, jugular venous distention, edema). 

→ Quantitative assessments of ECV and intravascular volume may be invasive (ie, central venous pressure or pulmonary wedge pressure) or noninvasive (ie, inferior vena cava diameter and right atrial pressure by echocardiography). 

→ Intracellular volume (ICV) is assessed using the serum sodium concentration.

What is the importance of determining the urine concentration of an electrolyte?
→ The urine concentration of an electrolyte is helpful to determine whether the kidney is excreting or retaining the electrolyte in response to high or low serum levels. 

Serum Osmolality:

→ units: osmolality = mmol/kg, osmolarity = mmol/L

→ What is plasma osmolality: number of solute particles per Litre of solvent

Hypernatremia is commonly defined as a serum sodium >145 mEq/L (145 mmol/L)

Hypokalemia is typically defined as a serum potassium concentration of <3.5 mEq/L

Hyperkalemia is typically defined as a serum potassium concentration >5.0 mEq/L

Who is most at risk?

→ an impaired ability to excrete water and to dilute urine due to reductions in the number of functioning nephrons and decreased renal blood flow with age, predisposing them to water overload and possible hyponatremia.

What are the 3 different types of hyponatremia (& their aetiologies)?

→ These patients typically exhibit edematous states, resulting from conditions such as congestive heart failure, cirrhosis, or nephrotic syndrome. 

→ These conditions decrease effective circulating blood volume, leading to increased antidiuretic hormone (ADH) secretion, which results in water retention. 

→ Dilutional hyponatremia can also be iatrogenic, as a result of administration of excess hypotonic intravenous (IV) fluids, especially in hospitalized patients.

    2. Hypovolemic Hyponatremia

= a state in which the total body water and sodium content are decreased and the relative decrease in total body sodium is greater than the decrease in total body water

→ Hypovolemic hyponatremia can be caused by renal losses (eg, diuretic use) or from extrarenal losses, such as vomiting, diarrhea, laxative abuse, ostomies, or the presence of large burns. 

→ A particular etiology to consider in geriatric patients is restricted sodium intake, especially in the setting of tube feedings.

   3. Euvolemic Hyponatremia

= Euvolemic hyponatremia implies normal sodium stores and a total body excess of free water. This occurs in patients who take in excess hypotonic fluids.

→ Patients with SIADH will generally appear euvolemic.

→ Many diseases that are common in older adults are associated with SIADH such as central nervous system disorders and malignancies

→ Medications are also an important cause of SIADH

→ Other causes of euvolemic hyponatremia include hypothyroidism and adrenal insufficiency. 

→ An elevated serum potassium level in conjunction with hyponatremia and hypotension should increase suspicion for adrenal insufficiency.

What are the symptoms & signs of hyponatremia?
→ Symptoms associated with hyponatremia include anorexia, nausea, vomiting, headache, weakness, loss of coordination, muscle cramps, agitation, tremors, disorientation, psychosis, delirium, seizures, and coma
→ Hypovolemic patients may have dry mucous membranes and tachycardia in addition to relative or true orthostatic hypotension. 

→ Hypervolemic patients may have increased jugular venous pressures, bibasilar pulmonary rales, ascites, and peripheral edema.

How do we diagnose hyponatremia (lab tests)?
- serum osmolality
- urine osmolality
- urine sodium
→ Hyponatremia secondary to pseudohyponatremia or hyperglycemia will have a normal serum osmolality, whereas all other etiologies will demonstrate a low serum osmolality 

→ Urine sodium is useful in differentiating between SIADH and a low effective circulating volume. 

→ A urine sodium of <25 mEq/L suggests hypovolemia, and a value of >40 mEq/L suggests SIADH.

How is hyponatremia treated (acute & chronic)?
→ Based on the presence, severity, and acuity of symptoms
→ The goal of hyponatremia treatment even in the absence of symptoms is to reduce associated mortality and morbidity (eg, gait disturbances, falls, and cognitive impairment).

Acute: hypertonic IV saline to rapidly raise serum sodium
-> however if the patient is already able to compensate for this, and we treat too rapidly, we can get complications

Chronic: focus on underlying aetiology,  3% hypertonic saline infusion is treatment of choice in severe cases

What are the causes of hypernatremia? 

    2. Loss of Water

    → DI is a syndrome characterized by hypotonic polyuria from either inadequate ADH secretion (central DI) or inadequate renal response to ADH (nephrogenic DI). 

    → Nephrogenic DI can be induced by medications such as lithium and cisplatin. 

    → Patients with DI usually compensate by increasing their fluid intake; thus, when they have adequate access to water, most patients maintain normal sodium concentrations
   → Hypernatremia develops when they have limited access to water or have an inadequate intake.

    3. Water Deficiency in Excess of Salt Deficiency

    4. Salt Excess

What are the clinical findings of hypernatremia?

What is the treatment for hypernatremia?
= The main goal of treatment is to administer dilute fluids to replace the water deficit and to limit further water loss. 

→ Replacement should be with hypotonic fluids (0.5% normal saline or 5% dextrose water), with oral route preferable to IV if feasible.
-> be careful with this replacement; can lead to oedema

What are the causes of Hypokalemia? 

-> Extrarenal losses of potassium occur in the GI tract. 

→ Chronic diarrhea can cause a loss of serum potassium due to an increase in stool volume.

→ Among older adults, diarrhea is associated with many commonly prescribed medications, including antibiotics

     2. Intrarenal Losses

     3. Iatrogenic Causes

→ Thiazide and loop diuretics are commonly prescribed to older adults for the management of blood pressure, congestive heart failure, and edema. 

What are the clinical findings of hypokalemia?

What is the treatment for hypokalemia?

-> careful of excessive administration of potassium as this may lead to hyperkalemia

What are the causes of Hyperkalemia?

- Decreased intravascular volume i.e. due to dehydration secondary to hypodipsia
- Increased potassium consumption
- Medication-induced
- Kidney disease; potassium excretion is proportional to glomerular filtration rate (GFR). 

What are the clinical findings of hyperkalemia? 

What is the treatment for hyperkalemia? (Acute & Chronic)
Acute:
- Calcium infusion
- Insulin with glucose
- B2-adrenergic agonists
- Sodium bicarbonate
 
Potassium removal:
- Loop or thiazide diuretics
- Cation exchange resins
- Dialysis