Angiotensin I is converted to angiotensin II by the removal of two C-terminal residues by the enzyme angiotensin-converting enzyme (ACE). This primarily occurs in the lungs, although it does also occur to a lesser degree in endothelial cells and renal epithelial cells.
The main actions of angiotensin II are:
Vasoconstriction of vascular smooth muscle (resulting in increased blood pressure)
Vasoconstriction of the efferent arteriole of the glomerulus (resulting in an increased filtration fraction and preserved glomerular filtration rate)
Stimulation of aldosterone release from the zona glomerulosa of the adrenal cortex
Stimulation of anti-diuretic hormone (vasopressin) release from the posterior pituitary
Stimulation of thirst via the hypothalamus
Acts on the Na+/H+ exchanger in the proximal tubule of the kidney to stimulate Na+reabsorption and H+excretion

Molecular weight is the main factor in determining whether a substance is filtered or not – molecules < 7 kDa in molecular weight are filtered freely e.g. glucose, amino acids, urea, ions but larger molecules are increasingly restricted up to 70 kDa, above which filtration is insignificant. Negatively charged molecules are further restricted, as they are repelled by negative charges, particularly in the basement membrane. Albumin has a molecular weight of 69 kDa and is negatively charged, thus only very small amounts are filtered (and all of the filtered albumin is reabsorbed in the proximal tubule), whereas small molecules such as ions, glucose, amino acids and urea pass the filter without hindrance. This means that ultrafiltrate is virtually protein free, but otherwise has an identical composition of that of plasma. The epithelial lining of the Bowman's capsule consists of a single layer of cells called podocytes. The glomerular capillary endothelium is perforated by pores (fenestrations) which allow plasma components with a molecular weight of < 70 kDa to pass freely.

The relative resistance of the afferent and efferent arterioles substantially influences glomerular capillary hydrostatic pressure and consequently GFR. Filtration is forced through the filtration barrier due to high pressure in the glomerular capillaries. Afferent arteriolar constriction lowers this pressure while efferent arteriolar constriction raises it.

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

Buffers are weak acids or bases that can donate or accept H+ions respectively and therefore resist changes in pH. Buffering does not alter the body’s overall H+load, ultimately the body must get rid of H+by renal excretion if the buffering capacity of the body is not to be exceeded and a dangerous pH reached. Bicarbonate and carbonic acid (formed by the combination of CO2 with water, potentiated by carbonic anhydrase) are the most important buffer pair in the body, although haemoglobin provides about 20% of buffering in the blood, and phosphate and proteins provide intracellular buffering. Buffers in urine, largely phosphate, allow the excretion of large quantities of H+.

FUSEDCARS can be used to remember some of the causes of a normal anion gap acidosis:
Fistula (pancreaticoduodenal)
Ureteroenteric conduit
Saline administration
Endocrine (hyperparathyroidism)
Diarrhoea
Carbonic anhydrase inhibitors (e.g. acetazolamide)
Ammonium chloride
Renal tubular acidosis
Spironolactone

Clearance of a substance can provide an accurate estimate of the glomerular filtration rate (GFR) provided that the substance is:freely filterednot reabsorbed in the nephronnot secreted in the nephronnot synthesised or metabolised by the kidney

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.

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

Calcium homeostasis is primarily controlled by three hormones: parathyroid hormone, activated vitamin D and calcitonin.

Parathyroid hormone acts on the kidneys to increase calcium reabsorption in the distal tubule by activating Ca2+entry channels in the apical membrane and the Ca2+ATPase pump in the basolateral membrane (and to decrease phosphate reabsorption in the proximal tubule).

Activated vitamin D acts to increase calcium reabsorption in the distal tubule via activation of a basolateral Ca2+ATPase pump (and to increase phosphate reabsorption).

Calcitonin acts to inhibit renal reabsorption of calcium (and phosphate).

Causes of a raised anion gap acidosis can be remember using the mnemonic MUDPILES:
-Methanol
-Uraemia (in renal failure)
-Diabetic ketoacidosis
-Propylene glycol overdose
-Infection/Iron overdose/Isoniazid/Inborn errors of metabolism
-Lactic acidosis
-Ethylene glycol overdose
-Salicylate overdose

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.

Calcium that is not protein bound is freely filtered in the glomerulus, and there is reabsorption along the nephron.About 70% is reabsorbed in the proximal tubule.About 20% is reabsorbed in the thick ascending limb of the loop of Henle.This reabsorption is mainly passive and paracellular and driven by sodium reabsorption. Sodium reabsorption causes water reabsorption, which raises tubular calcium concentration, causing calcium to diffuse out of the tubules. The positive  lumen potential also encourages calcium to leave the tubule.About 5 – 10% is reabsorbed in the distal convoluted tubule.Less than 0.5% is reabsorbed in the collecting ducts.Calcium reabsorption in the distal nephron is active and transcellular and is the major target for hormonal control.Calcium homeostasis is primarily controlled by three hormones: parathyroid hormone, activated vitamin D and calcitonin.Parathyroid hormone acts on the kidneys to increase calcium reabsorption in the distal tubule by activating Ca2+entry channels in the apical membrane and the Ca2+ATPase pump in the basolateral membrane (and to decrease phosphate reabsorption in the proximal tubule).Activated vitamin D acts to increase calcium reabsorption in the distal tubule via activation of a basolateral Ca2+ATPase pump (and to increase phosphate reabsorption).Calcitonin acts to inhibit renal reabsorption of calcium (and phosphate).

The Renin-Angiotensin-Aldosterone System (RAAS) is a hormone system composed of renin, angiotensin, and aldosterone. Those hormones are essential for the regulation of blood pressure and fluid balance.

Cases of hypotension, sympathetic stimulation, or hyponatremia can activate the Renin-angiotensin-aldosterone system (RAAS). The following process will then increase the blood volume and blood pressure as a response.

When renin is released it will convert the circulating angiotensinogen to angiotensin I. The ACE or angiotensin-converting enzyme will then catalyst its conversion to angiotensin II, which is a potent vasoconstrictor. Angiotensin II can constrict the vascular smooth muscles and the efferent arteriole of the glomerulus.

The efferent arteriole is a blood vessel that delivers blood away from the capillaries of the kidney. The angiotensin II-mediated constriction of efferent arterioles increases GFR, reduces renal blood flow and peritubular capillary hydrostatic pressure, and increases peritubular colloid osmotic pressure, as a response to its action of increasing the filtration fraction.

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

Bicarbonate is freely filtered at the glomerulus. Less than 0.1% of filtered bicarbonate is normally excreted in the urine (if plasma [HCO3-] increases, maximum tubular transport is exceeded and some HCO3-is excreted in urine). About 80% of bicarbonate is reabsorbed in the proximal tubule. For each H+secreted into the lumen, one Na+and one HCO3-are reabsorbed into the plasma. H+is recycled so there is little net secretion of H+at this stage. A further 10 – 15% of HCO3-is similarly reabsorbed in the thick ascending limb of the loop of Henle. In the early distal tubule, H+secretion is predominantly by Na+/H+exchange but more distally, the Na+gradient is insufficient so secretion is via H+ATPase and H+/K+ATPase in intercalated cells, which contain plentiful carbonic acid.

As secreted H+is derived from CO2, new HCO3-is formed and returns to the blood.H+secretion is proportional to intracellular [H+] which itself is related to extracellular pH. A fall in blood pH will therefore stimulate renal H+secretion. In the proximal tubule secretion of H+serves to reclaim bicarbonate from glomerular filtrate so it is not lost, but in the distal nephron, secretion leads to net acid excretion and generation of new bicarbonate.

All nephrons have their renal corpuscles in the renal cortex. Cortical nephrons have their renal corpuscles in the outer part of the cortex and relatively short loops of Henle. Juxtamedullary nephrons have their corpuscles in the inner third of the cortex, close to the corticomedullary junction, with long loops of Henle extending into the renal medulla.

Molecular weight is the main factor in determining whether a substance is filtered or not – molecules < 7 kDa in molecular weight are filtered freely e.g. glucose, amino acids, urea, ions but larger molecules are increasingly restricted up to 70 kDa, above which filtration is insignificant. Negatively charged molecules are further restricted, as they are repelled by negative charges, particularly in the basement membrane. Albumin has a molecular weight of 69 kDa and is negatively charged, thus only very small amounts are filtered (and all of the filtered albumin is reabsorbed in the proximal tubule), whereas small molecules such as ions, glucose, amino acids and urea pass the filter without hindrance. This means that ultrafiltrate is virtually protein free, but otherwise has an identical composition of that of plasma. The epithelial lining of the Bowman's capsule consists of a single layer of cells called podocytes. The glomerular capillary endothelium is perforated by pores (fenestrations) which allow plasma components with a molecular weight of < 70 kDa to pass freely.

Decreased blood volume stimulates the secretion of renin (because of decreased renal perfusion pressure) and initiates the renin-angiotensin-aldosterone cascade. Angiotensin-converting enzyme (ACE) inhibitors block the cascade by decreasing the production of angiotensin. Hyperosmolarity stimulates antidiuretic hormone (ADH) [not aldosterone] secretion. Hyperkalaemia, not hypokalaemia, directly stimulates aldosterone secretion by the adrenal cortex. ANP inhibits renin secretion, thereby inhibiting the production of angiotensin and aldosterone.

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.