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

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.It causes vasoconstriction by binding to peripheral V1 Receptors on vascular smooth muscle via the IP3 signal transduction and Rho-kinase pathways. The systemic vascular resistance and arterial pressure rise as a result. High levels of ADH appear to be required for this to have a major impact on arterial pressure, such as in hypovolaemic shock.

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 desmopressinCranial diabetes insipidus800 mosmol/kgNephrogenic diabetes insipidus<300 mosmol/kg : 800 mosmol/kg : >800 mosmol/kg

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.

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.

Lactic acidosis is a common finding in critically ill patients and commonly associated with other serious underlying pathologies. It occurs when pH 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 andType B: due to non-hypoxic processes affecting the production and elimination of lactateSome causes of type A and type B lactic acidosis include:Type A lactic acidosisLeft ventricular failureSevere anaemiaShock (including septic shock)AsphyxiaCardiac arrestCO poisoningRespiratory failureSevere asthma and COPDType B lactic acidosis:Regional hypoperfusionRenal failureLiver failureSepsis (non-hypoxic sepsis)Thiamine deficiencyAlcoholic ketoacidosisDiabetic ketoacidosisCyanide poisoningMethanol poisoningBiguanide poisoning

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.

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 insipidusCranial 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.

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.

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.