The main Na+ reabsorbing cells in the late distal convoluted tubule and collecting duct are the principal cells. These make up the majority of the tubular cells.

The exchange is driven by the Na.K.ATPase pumps on the basolateral membrane.

A plasma potassium less than 3.5 mmol/L defines hypokalaemia.

Excessive liquorice ingestion causes hypermineralocorticoidism and leads to hypokalaemia.

Gitelman’s syndrome causes metabolic alkalosis with hypokalaemia and hypomagnesaemia. It is an inherited defect of the distal convoluted tubules.

Bartter’s syndrome causes hypokalaemic alkalosis. It is a rare inherited defect in the ascending limb of the loop of Henle.

Type 1 and 2 renal tubular acidosis both cause hypokalaemia

Type 4 renal tubular acidosis causes hyperkalaemia.

When you take too much aspirin, you have a mix of respiratory alkalosis and metabolic acidosis. Respiratory centre stimulation produces hyperventilation and respiratory alkalosis in the early phases. The direct acid actions of aspirin tend to create a higher anion gap metabolic acidosis in the latter phases.
Below summarizes some of the most common reasons of acid-base abnormalities:

Respiratory alkalosis:
– Hyperventilation (e.g. anxiety, pain, fever)
– Pulmonary embolism
– Pneumothorax
– CNS disorders (e.g. CVA, SAH, encephalitis)
– High altitude
– Pregnancy
– Early stages of aspirin overdose

Respiratory acidosis:
– COPD
– Life-threatening asthma
– Pulmonary oedema
– Respiratory depression (e.g. opiates, benzodiazepines)
– Neuromuscular disease (e.g. Guillain-Barré syndrome, muscular dystrophy
– Incorrect ventilator settings (hypoventilation)
– Obesity

Metabolic alkalosis:
– Vomiting
– Cardiac arrest
– Multi-organ failure
– Cystic fibrosis
– Potassium depletion (e.g. diuretic usage)
– Cushing’s syndrome
– Conn’s syndrome

Metabolic acidosis (with raised anion gap):
– Lactic acidosis (e.g. hypoxaemia, shock, sepsis, infarction)
– Ketoacidosis (e.g. diabetes, starvation, alcohol excess)
– Renal failure
– Poisoning (e.g. late stages of aspirin overdose, methanol, ethylene glycol)

Metabolic acidosis (with normal anion gap):
– Renal tubular acidosis
– Diarrhoea
– Ammonium chloride ingestion
– Adrenal insufficiency

The inability to produce concentrated urine is a symptom of diabetes insipidus. Excessive thirst, polyuria, and polydipsia are all symptoms of this condition. There are two forms of diabetes insipidus: Nephrogenic diabetes insipidus and cranial (central) diabetes insipidus.

A lack of ADH causes cranial diabetic insipidus. Patients with cranial diabetes insipidus can have a urine output of up to 10-15 litres per 24 hours, however most patients can maintain normonatraemia with proper fluid consumption. Thirty percent of cases are idiopathic, while another thirty percent are caused by head injuries. Neurosurgery, brain tumours, meningitis, granulomatous disease (e.g. sarcoidosis), and medicines like naloxone and phenytoin are among the other reasons. There is also a very rare hereditary type that is linked to diabetes, optic atrophy, nerve deafness, and bladder atonia.

Renal resistance to the action of ADH causes nephrogenic diabetes insipidus. Urine output is significantly increased, as it is in cranial diabetes insipidus. Secondary polydipsia can keep serum sodium levels stable or raise them. Chronic renal dysfunction, metabolic diseases (e.g., hypercalcaemia and hypokalaemia), and medications, such as long-term lithium use and demeclocycline, are all causes of nephrogenic diabetes insipidus.

The best test to establish if a patient has diabetes insipidus vs another cause of polydipsia is the water deprivation test, commonly known as the fluid deprivation test. It also aids in the distinction between cranial and nephrogenic diabetes insipidus. Weight, urine volume, urine osmolality, and serum osmolality are all measured after patients are denied water for up to 8 hours. At the end of the 8-hour period, 2 micrograms of IM desmopressin is given, and measures are taken again at 16 hours.

The following are the way results are interpreted:
Urine osmolality after fluid deprivation : Urine osmolality after IM desmopressin
Cranial diabetes insipidus
<300 mosmol/kg : >800 mosmol/kg
Nephrogenic diabetes insipidus
<300 mosmol/kg : <300 mosmol/kg
Primary polydipsia
>800 mosmol/kg : >800 mosmol/kg

Glucose reabsorption occurs exclusively in the proximal convoluted tubule by secondary active transport through the Na.Glu co-transporters, driven by the electrochemical gradient for sodium.
The co-transporters transport two sodium ions and one glucose molecule across the apical membrane, and the glucose subsequently crosses the basolateral membrane by facilitated diffusion.

Lactic acidosis is a common finding in critically ill patients and commonly associated with other serious underlying pathologies. It occurs when pH is <7.35 and lactate is >5 mmol/L. Anion gap is increased in lactic acidosis.

Acquired lactic acidosis is classified into two subtypes:
Type A: lactic acidosis due to tissue hypoxia and
Type B: due to non-hypoxic processes affecting the production and elimination of lactate

Some causes of type A and type B lactic acidosis include:
Type A lactic acidosis
Left ventricular failure
Severe anaemia
Shock (including septic shock)
Asphyxia
Cardiac arrest
CO poisoning
Respiratory failure
Severe asthma and COPD

Type B lactic acidosis:
Regional hypoperfusion
Renal failure
Liver failure
Sepsis (non-hypoxic sepsis)
Thiamine deficiency
Alcoholic ketoacidosis
Diabetic ketoacidosis
Cyanide poisoning
Methanol poisoning
Biguanide poisoning

GFR can be estimated by:
GFR = UCr x V / PCr
Where:
UCr = urine concentration of creatinine
PCr = plasma concentration of creatinine
V = rate of urine flow

In this case GFR = (18 x 2) / 0.25 = 144 ml/min

Note: Creatinine is used to estimate GFR because it is an organic base naturally produced by muscle breakdown, it is freely filtered at the glomerulus, it is not reabsorbed from the nephron, it is not produced by the kidney, it is not toxic, and it doesn’t alter GFR.

Polydipsia is the feeling of extreme thirstiness. It is often linked to polyuria, which is a urinary condition that causes a person to urinate excessively. The cycle of these two processes makes the body feel a constant need to replace the fluids lost in urination. In healthy adults, a 3 liter urinary output per day is considered normal. A person with polyuria can urinate up to 15 liters of urine per day. Both of these conditions are classic signs of diabetes.

The other options are also types of diabetes, except for psychogenic polydipsia (PPD), which is the excessive volitional water intake seen in patients with severe mental illness or developmental disability. However, given the patient’s previous head injury, the most likely diagnosis is cranial diabetes insipidus.

By definition, cranial diabetes insipidus is caused by damage to the hypothalamus or pituitary gland after an infection, operation, brain tumor, or head injury. And the patient’s history confirms this diagnosis. To define the other choices, nephrogenic diabetes insipidus happens when the structures in the kidneys are damaged and results in an inability to properly respond to antidiuretic hormone.

Kidney damage can be caused by an inherited (genetic) disorder or a chronic kidney disorder. As with cranial diabetes insipidus, nephrogenic diabetes insipidus can also cause an elevated urine output.

Diabetes mellitus is classified into two types, and the main difference between them is that type 1 diabetes is a genetic disorder, and type 2 diabetes is diet-related and develops over time. Type 1 diabetes is also known as insulin-dependent diabetes, in which the pancreas produces little or no insulin. Type 2 diabetes is termed insulin resistance, as cells don’t respond customarily to insulin.

Glomerular filtration is a passive process. It depends on the net hydrostatic pressure across the glomerular capillaries, the oncotic pressure, and the intrinsic permeability of the glomerulus.

The mean values for glomerular filtration rate (GFR) in young adults are 130 ml/min/1.73m2 in males and 120 ml/min/1.73m2in females.

The GFR declines with age after the age of 40 at a rate of approximately 1 ml/min/year.

The Cockcroft and Gault formula overestimates creatinine in obese patients. This is because their endogenous creatinine production is less than that predicted by overall body weight.

Creatinine is used in the estimation of GFR because it is naturally produced by muscle breakdown, not toxic, not produced by the kidney, freely filtered at the glomerulus, not reabsorbed from the nephron, and does not alter GFR.

The Loop of Henle connects the proximal tubule to the distal convoluted tubule and lies parallel to the collecting ducts. It consists of three major segments, including the descending thin limb, the ascending thin limb, and the ascending thick limb. These segments are differentiated based on structure, anatomic location, and function.

The main function of the loop of Henle is to recover water and sodium chloride from urine. When fluid enters the loop of Henle, it has an osmolality of approximately 300 mOsm, and the main solute is sodium.

The thin descending limb has a high water permeability but a low ion permeability. Because it lacks solute transporters, it cannot reabsorb sodium. Aquaporin 1 (AQP1) channels are used to passively absorb water in this area. The peritubular fluid becomes increasingly concentrated as the loop descends into the medulla, causing water to osmose out of the tubule. The tubular fluid in this area now equalizes to the osmolality of the peritubular fluid, to a maximum of approximately 1200 mOsm in a long medullary loop of Henle and 600 mOsm in a short cortical loop of Henle.

The thin ascending limb is highly permeable to ions and impermeable to water. It allows the passive movement of sodium, chloride, and urea down their concentration gradients, so urea enters the tubule and sodium and chloride leave. Reabsorption occurs paracellularly due to the difference in osmolarity between the tubule and the interstitium.

The thick ascending limb is also impermeable to water but actively transports sodium, potassium, and chloride out of the tubular fluid. The osmolality of the tubular fluid is lower compared to the surrounding peritubular fluid. This area is water impermeable. This results in tubular fluid leaving the loop of Henle with an osmolality of approximately 100 mOsm, which is lower than the osmolality of the fluid entering the loop, and urea being the solute.