Aldosterone is a steroid hormone produced in the adrenal cortex’s zona glomerulosa. It is the most important mineralocorticoid hormone in the control of blood pressure. It does so primarily by promoting the synthesis of Na+/K+ATPases and the insertion of more Na+/K+ATPases into the basolateral membrane of the nephron’s distal tubules and collecting ducts, as well as stimulating apical sodium and potassium channel activity, resulting in increased sodium reabsorption and potassium secretion. This results in sodium conservation, potassium secretion, water retention, and a rise in blood volume and blood pressure.

Aldosterone is produced in response to the following stimuli:

Angiotensin II levels have risen.
Potassium levels have increased.
ACTH levels have risen.
Aldosterone’s principal actions are as follows:
Na+ reabsorption from the convoluted tubule’s distal end
Water resorption from the distal convoluted tubule (followed by Na+)
Cl is reabsorbed from the distal convoluted tubule.
K+ secretion into the convoluted distal tubule’s 
H+ secretion into the convoluted distal tubule’s 

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

Hyperkalaemia causes a rapid reduction in resting membrane potential leading to increased cardiac depolarisation and muscle excitability. This in turn results in ECG changes which can rapidly progress to ventricular fibrillation or asystole. Very distinctive ECG changes that progressively change as the K+level increases:
K+>5.5 mmol/l – peaked T waves (usually earliest sign of hyperkalaemia), repolarisation abnormalities
K+>6.5 mmol/l – P waves widen and flatten, PR segment lengthens, P waves eventually disappear
K+>7.0 mmol/l – Prolonged QRS interval and bizarre QRS morphology, conduction blocks (bundle branch blocks, fascicular blocks), sinus bradycardia or slow AF, development of a sine wave appearance (a pre-terminal rhythm)
K+>9.0 mmol/l – Cardiac arrest due to asystole, VF or PEA with a bizarre, wide complex rhythm.

Chronic kidney disease (CKD) is a disorder in which kidney function gradually deteriorates over time. It’s fairly prevalent, and it typically remains unnoticed for years, with only advanced stages of the disease being recognized. There is evidence that medication can slow or stop the progression of CKD, as well as lessen or prevent consequences and the risk of cardiovascular disease (CVD).

CKD is defined as kidney damage (albuminuria) and/or impaired renal function (GFR 60 ml/minute per 1.73 m2) for three months or longer, regardless of clinical diagnosis.

A prolonged decline in GFR of 25% or more with a change in GFR category within 12 months, or a sustained drop in GFR of 15 ml/minute/1.73 m² per year, is considered accelerated CKD progression.
End-stage renal disease (ESRD) is defined as severe irreversible kidney impairment with a GFR of less than 15 ml/minute per 1.73 m² and a GFR of less than 15 ml/minute per 1.73 m².

Bartter’s syndrome is an autosomal recessive renal tubular disorder characterized by hypokalaemia, hypochloraemia, metabolic alkalosis, and hyperreninemia with normal blood pressure. The underlying kidney abnormality results in excessive urinary losses of sodium, chloride, and potassium.

Bartter’s syndrome does not cause an elevated potassium level, but instead causes a decrease in its concentration (hypokalaemia). The other choices are causes of hyperkalaemia or elevated potassium levels.

Renal failure, Addison’s disease (adrenal insufficiency), congenital adrenal hyperplasia, renal tubular acidosis (type 4), rhabdomyolysis, burns and trauma, tumour syndrome, and acidosis are non-drug causes of hyperkalaemia. On the other hand, drugs that can cause hyperkalaemia include ACE inhibitors, angiotensin receptor blockers, NSAIDs, beta-blockers, digoxin, and suxamethonium.

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 glomerular filtration membrane is composed of fenestrated capillary endothelium, basement membrane, and filtration slits. It is an organized, semipermeable membrane preventing the passage of most of the proteins into the urine.

The anatomical arrangement of the glomerular filtration membrane maximizes the surface area available for filtration. The arrangement of its arterioles results in high hydrostatic pressures and facilitates filtration.

Fenestrated capillary endothelium of the glomerular filtration membrane is with relatively large pores. It allows the free movement of plasma proteins and solutes but still restricts the movement of blood cells.

Filtration slits are the smallest filters and restrict the movement of plasma proteins but still allow free movement of ions and nutrients.

The glomerular basement membrane (GBM) is a critical component of the glomerular filtration membrane. Thus, it is not true that its absence will reduce the resistance of flow. The basement membrane is true to be more selective and contains negatively charged glycoproteins. However, it still allows free passage of water, nutrients, and ions. Severe structural abnormalities of the GBM can result in protein (albumin) leakage.

The interpretation of arterial blood gas (ABG) aids in the measurement of a patient’s pulmonary gas exchange and acid-base balance.
The normal values on an ABG vary a little depending on the analyser, but they are roughly as follows:
Variable
Range
pH
7.35 – 7.45
PaO2
10 – 14 kPa
PaCO2
4.5 – 6 kPa
HCO3-
22 – 26 mmol/l
Base excess
-2 – 2 mmol/l

The patient’s history indicates that she has taken an overdose in this case. Because her GCS is 11/15 and she can communicate with slurred speech, she is clearly managing her own airway, there is no current justification for intubation.

The following are the relevant ABG findings:

Hypoxia (mild)
pH has been lowered (acidaemia)
PCO2 levels are low.
bicarbonate in its natural state
Lactate levels have increased

The anion gap represents the concentration of all the unmeasured anions in the plasma. It is the difference between the primary measured cations and the primary measured anions in the serum. It can be calculated using the following formula:
Anion gap = [Na+] – [Cl-] – [HCO3-]

The reference range varies depending on the technique of measurement, but it is usually between 8 and 16 mmol/L.

The following formula can be used to compute her anion gap:
Anion gap = [143] – [99] – [22]
Anion gap = 22

As a result, it is clear that she has a metabolic acidosis with an increased anion gap.

The following are some of the causes of type A and type B lactic acidosis:
Type A lactic acidosis
Type B lactic acidosis
Shock (including septic shock)
Left ventricular failure
Severe anaemia
Asphyxia
Cardiac arrest
CO poisoning
Respiratory failure
Severe asthma and COPD
Regional hypoperfusion
Renal failure
Liver failure
Sepsis (non-hypoxic sepsis)
Thiamine deficiency
Alcoholic ketoacidosis
Diabetic ketoacidosis
Cyanide poisoning
Methanol poisoning
Biguanide poisoning

Antidiuretic hormone (ADH), commonly known as vasopressin, is a peptide hormone that controls how much water the body retains.

It is produced in the magnocellular and parvocellular neurosecretory cells of the paraventricular nucleus and supraoptic nucleus in the hypothalamus from a prohormone precursor. It is subsequently carried to the posterior pituitary via axons and stored in vesicles.

The secretion of ADH from the posterior pituitary is regulated by numerous mechanisms:
Increased plasma osmolality: Osmoreceptors in the hypothalamus detect an increase in osmolality and trigger ADH release.

Stretch receptors in the atrial walls and big veins detect a decrease in atrial pressure as a result of this (cardiopulmonary baroreceptors). ADH release is generally inhibited by atrial receptor firing, but when the atrial receptors are stretched, the firing reduces and ADH release is promoted.
Hypotension causes baroreceptor firing to diminish, resulting in increased sympathetic activity and ADH release.
An increase in angiotensin II stimulates angiotensin II receptors in the hypothalamus, causing ADH production to increase.

The main sites of action for ADH are:
The kidney is made up of two parts. ADH’s main job is to keep the extracellular fluid volume under control. It increases permeability to water by acting on the renal collecting ducts via V2 Receptors (via a camp-dependent mechanism). This leads to a decrease in urine production, an increase in blood volume, and an increase in arterial pressure as a result.

Vascular system: Vasoconstriction is a secondary function of ADH. ADH causes vasoconstriction via binding to V1 Receptors on vascular smooth muscle (via the IP3 signal transduction pathway). An increase in arterial pressure occurs as a result of this.

Angiotensinogen is an alpha-2-globulin generated predominantly by the liver and released into the blood. Renin, which cleaves the peptide link between the leucine and valine residues on angiotensinogen, converts it to angiotensin I.

Angiotensinogen levels in the blood are raised by:
Corticosteroid levels have risen.
Thyroid hormone levels have risen.
Oestrogen levels have risen.
Angiotensin II levels have risen.

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.

Diabetes insipidus is the inability to produce concentrated urine. It is characterised by the presence of excessive thirst, polyuria and polydipsia. There are two distinct types of diabetes insipidus:
Cranial (central) diabetes insipidus and;
Nephrogenic diabetes insipidus
Cranial diabetes insipidus is caused by a deficiency of vasopressin (anti-diuretic hormone). Patients with cranial diabetes insipidus can have a urine output as high as 10-15 litres per 24 hours, but adequate fluid intake allows most patients to maintain normonatraemia. 30% of cases are idiopathic, and a further 30% are secondary to head injuries. Other causes include neurosurgery, brain tumours, meningitis, granulomatous disease (e.g. sarcoidosis) and drugs, such as naloxone and phenytoin. A very rare inherited form also exists that is associated with diabetes mellitus, optic atrophy, nerve deafness and bladder atonia.
Nephrogenic diabetes insipidus is caused by renal resistance to the action of vasopressin. As with cranial diabetes insipidus, urine output is markedly elevated. Serum sodium levels can be maintained by secondary polydipsia or can be elevated. Causes of nephrogenic diabetes insipidus include chronic renal disease, metabolic disorders (e.g. hypercalcaemia and hypokalaemia) and drugs, including long-term lithium usage and demeclocycline.
In view of the history of long-term lithium use, in this case, nephrogenic diabetes insipidus is the most likely diagnosis.

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.

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.

ADH, or antidiuretic hormone, is a hormone that regulates water and electrolyte balance. It is released in response to a variety of events, the most important of which are higher plasma osmolality or lower blood pressure. ADH increases plasma volume and blood pressure via acting on the kidneys and peripheral vasculature.
ADH causes extensive vasoconstriction by acting on peripheral V1 Receptors.

ADH binds to B2 Receptors in the terminal distal convoluted tubule and collecting duct of the kidney, increasing transcription and aquaporin insertion in the cells that line the lumen. Aquaporins are water channels that allow water to pass through the tubule and into the interstitial fluid via osmosis, lowering urine losses.
The permeability of the distal collecting duct (the section within the inner medulla) to urea is likewise increased by ADH. More urea travels out of the tubule and into the peritubular fluid, contributing to the counter current multiplier, which improves the Loop of Henle’s concentrating power.

Overall, there is enhanced urea and water reabsorption in the presence of ADH, resulting in modest amounts of concentrated urine. There is minimal urea and water reabsorption in the absence of ADH, resulting in huge amounts of dilute urine.

Plasma potassium greater than 5.5 mmol/L is hyperkalaemia or elevated plasma potassium level. Among the causes of hyperkalaemia include congenital adrenal hyperplasia.

Congenital adrenal hyperplasia is a general term referring to autosomal recessive disorders involving a deficiency of an enzyme needed in cortisol and/or aldosterone synthesis. The level of cortisol and/or aldosterone deficiency affects the clinical manifestations of congenital adrenal hyperplasia. When it involves hypoaldosteronism, it can result in hyponatremia and hyperkalaemia. While hypercortisolism can cause hypoglycaemia.

The other causes of hyperkalaemia may include renal failure, excess potassium supplementation, Addison’s disease (adrenal insufficiency), renal tubular acidosis (type 4), rhabdomyolysis, burns, trauma, Tumour lysis syndrome, acidosis, and medications such as ACE inhibitors, angiotensin receptor blockers, NSAIDs, beta-blockers, digoxin, and suxamethonium.

Bartter’s syndrome is characterized by hypokalaemic alkalosis with normal to low blood pressure.

Type 1 and 2 renal tubular acidosis both cause hypokalaemia.

Gitelman’s syndrome is a defect of the distal convoluted tubule of the kidney. It causes metabolic alkalosis with hypokalaemia and hypomagnesemia.

And excessive liquorice ingestion causes hypermineralocorticoidism and hypokalaemia as well. Thus, among the choices, only congenital adrenal hyperplasia can cause hyperkalaemia

.

The loop of Henle connects the proximal tubule to the distal convoluted tubule and lies parallel to the collecting ducts. It is consists of three major segments, the thin descending limb, the thin ascending limb, and the thick ascending limb.

The segments are differentiated based on structure, anatomic location, and function. The main action of the loop of Henle is to recover water and sodium chloride from urine. The liquid entering the loop of Henle is a solution of salt, urea, and other substances traversed along by the proximal convoluted tubule, from which most of the dissolved components are needed by the body, particularly glucose, amino acids, and sodium bicarbonate that have been reabsorbed into the blood.

This fluid is isotonic. Isotonic fluids generally have an osmolality ranging from 270 to 310 mOsm/L. With the fluid that enters the loop of Henle, it is estimated to be 300 mOsm/L. However, after passing the loop, fluid entering the distal tubule is hypotonic to plasma since it has been diluted during its passage.

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.

Antidiuretic hormone (ADH) is produced in the hypothalamus’s supraoptic nucleus and then released into the blood via axonal projections from the hypothalamus to the posterior pituitary.

It is carried down axonal extensions from the hypothalamus (the neurohypophysial capillaries) to the posterior pituitary, where it is kept until it is released, after being synthesized in the hypothalamus.
The secretion of ADH from the posterior pituitary is regulated by numerous mechanisms:
Increased plasma osmolality: Osmoreceptors in the hypothalamus detect an increase in osmolality and trigger ADH release.

Hypovolaemia causes a drop in atrial pressure, which stretch receptors in the atrial walls and big veins detect (cardiopulmonary baroreceptors). ADH release is generally inhibited by atrial receptor firing, but when the atrial receptors are stretched, the firing reduces and ADH release is promoted.

Hypotension causes baroreceptor firing to diminish, resulting in increased sympathetic activity and ADH release.
An increase in angiotensin II stimulates angiotensin II receptors in the hypothalamus, causing ADH production to increase.

Nicotine, Sleep, Fright, and Exercise are some of the other elements that might cause ADH to be released.
Alcohol (which partly explains the diuretic impact of alcohol) and elevated levels of ANP/BNP limit ADH release.

Lactic acidosis is defined as a pH <7.35 and a lactate >5 mmol/L. It is a common finding in critically ill patients and is often associated with other serious underlying pathologies. The anion gap is raised in lactic acidosis.
There are major adverse consequences of severe acidaemia, which affect all body systems, and there is an associated increase in mortality of critically ill patients with a raised lactate. The mortality associated with lactic acidosis despite full supportive treatment remains at 60-90%.
Acquired lactic acidosis is classified into two subtypes:
Type A is due to tissue hypoxia
Type B is due to non-hypoxic processes affecting the production and elimination of lactate
Lactic acidosis can be extreme after a seizure but usually resolves spontaneously within a few hours.
Left ventricular failure typically results in tissue hypoperfusion and a type A lactic acidosis.
Some causes of type A and type B lactic acidosis are shown below:
Type A lactic acidosis
Type B lactic acidosis
Shock (including septic shock)
Left ventricular failure
Severe anaemia
Asphyxia
Cardiac arrest
CO poisoning
Respiratory failure
Severe asthma and COPD
Regional hypoperfusion
Renal failure
Liver failure
Sepsis (non-hypoxic sepsis)
Thiamine deficiency
Alcoholic ketoacidosis
Diabetic ketoacidosis
Cyanide poisoning
Methanol poisoning
Biguanide poisoning