Path - Chemical Pathology Flashcards
What is the general underlying pathogenesis of hyponatraemia?
A. Deficiency in salts B. Excess extracellular salts C. Deficiency in water D. Excess extracellular water E. Acid-base imbalance
D. Excess extracellular water
Which of the following is not a function of ADH?
A. Regulation of calcium exchange between cells and serum
B. Re-absorption of sodium in the Loop of Henle
C. Aquaporin insertion into the apical membrane of collecting duct cells
D. Vasoconstriction
E. Stimulation of thirst
(remember ADH actions on V1, V2, V3 (ACTH from pit gland release) functions
A. Regulation of calcium exchange between cells and serum
Which option is a cause of hyponatraemia in a hypervolemic patient?
A. Diarrhoea B. Hypothyroidism C. SIADH D. Vomiting E. Cirrhosis
E. Cirrhosis
Hypovolemic hyponatraemia (losses): Diarrhoea Vomiting Diuretics Salt-losing nephropathy
Euvolemic hyponatraemia (endocrine abnormalities):
Hypothyroidism
Adrenal insufficiency
SIADH (key! - euvolaemic, remember 2ndary natriuretic responses causing Na+ and water loss)
Hypervolemic hyponatraemia (organ failures- think of fluid overload):
Cardiac failure
Cirrhosis
Nephrotic syndrome
Which of the following is true of SIADH?
A. It is only caused by cranial pathology SIADH
B. It affects 5-10% of hospitalised patients
C. It is the most common cause of hyponatraemia
D. It causes a hypovolemic hyponatraemia
E. It is associated with lithium use
C. It is the most common cause of hyponatraemia
The causes of SIADH are implausibly varied: pathologies of most types and organs can cause it, but there are a few causes you should be familiar with because Amir Sam always mentions them.
Various CNS pathologies can cause SIADH (subdural haematoma, subarachnoid haemorrhage, trauma, cavernous sinus thrombosis).
The other frequently mentioned causes of SIADH are lung pathology (generally cancer or infection), a wide range of tumours, a wide range of drugs (SSRIs, PPIs, opiates, TCAs, sodium valproate, carbemazepine), and surgery (ADH rises post-op).
What is the key concern about quickly raising a patient’s sodium (by more than 8-10 mmol/ hour)?
A. Hypernatraemia B. Dehydration C. Renal failure D. Cell lysis E. Central pontine myelinolysis
E. Central pontine myelinolysis
Rapidly elevating serum sodium may, in the worst case, lead to damage to the cells in the Pons of the brain stem, causing central pontine myelinolysis. It is characterised by acute paralysis, dysphagia, dysarthria, and other neurological deficits, and is thought to occur because rapidly rising sodium levels drive water out of cells into the blood, causing damage.
What are the two main stimuli for ADH secretion?
A. Reduced blood volume and reduced serum osmolality
B. Increased blood volume and increased serum osmolality
C. Increased blood volume and reduced serum osmolality
D. Reduced blood volume and increased serum osmolality
D. Reduced blood volume and increased serum osmolality
(remember hypothalamic osmoreceptors detecting osmolality of blood- main stimulation)
Which of the following is not a cause of hyperkalaemia?
A. Renal impairment B. ACE inhibitors C. Addison's disease D. Cushing's syndrome E. Acidosis
D. Cushing’s syndrome
Aldosterone is the key hormone regulating sodium excretion and potassium retention (aldosterone causes hyperNa+ and hypoK+). However mineralocorticoid receptors (e.g. for aldosterone) are non-specific, and are stimulated by cortisol. Hence, Cushing’s patients have high sodium and low potassium.
Renal impairment will impair the secretion of potassium, causing it to rise.
ACE inhibitors prevent the production of angiotensin II from angiotensin I. Angiotensin II stimulates release of aldosterone, hence ACE inhibitors can lead to hyperkalaemia.
Acidosis leads to hyperkalaemia through the body’s attempt to maintain the pH balance of the blood: H+ ions are transported into cells to lower the pH, but this uses a co-transporter which moves potassium into the blood, resulting in hyperkalaemia. REMEMBER acidosis goes the same way as kalaemia (both hyper together or both hypo)
A 90 year-old woman is found on her bathroom floor having fallen and been unable to get up again. She has been on the floor for two days and is delirious. She is taken to hospital where examination confirms she is acutely confused with virtually no urine output. Blood tests show elevated urea and creatine kinase. She is given an I.V. fluid challenge and shows marked improvement. She begins to pass urine but it is tea-coloured. Shortly afterwards she is noticed to be breathing rapidly and reports having palpitations; her ECG shows bradycardia, tented T waves, and a prolonged P-R interval. A rapidly taken VBG shows the following:
pH: 7.22 Bicarbonate: 15 O2 Sat: 76% PaO2: 5.0 kPa PaCO2: 5.5 kPa Na+: 141 K+: 6.8 Glucose: 5mmol/L
What is the most appropriate next step in the patient’s management?
A. Administer another I.V. fluid challenge and monitor urine output. Regularly auscultate the lungs to check for pulmonary oedema, and refer the patient to a specialist renal unit.
B. Continue to rehydrate the patient with I.V. saline, and monitor their potassium regularly for at least 6 hours.
C. Give 50ml 50% saline, beta blockers, and begin a bicarbonate infusion. Refer the patient to a cardiologist.
D. Give 10ml 10% calcium chloride, 10 units soluble insulin in 25g glucose, and nebulised salbutamol
E. Urgently refer the patient to ICU for intensive support and haemofiltration
D. Give 10ml 10% calcium chloride, 10 units soluble insulin in 25g glucose, and nebulised salbutamol
This patient has developed hyperkalaemia, which has affected her heart’s rhythm and carries a significant risk of causing cardiac arrest. Her hyperkalaemia could be caused either by the toxic cell products released during rhabdomyolysis from her fall and extended down time, or by the AKI resulting from her extreme dehydration from not drinking for two days. Either way, she has an acute kidney injury which leaves her unable to excrete potassium.
The most important goal in this scenario is to manage the patient’s hyperkalaemia and prevent cardiac arrest. Calcium chloride is given to stabilise the heart’s rhythm; calcium gluconate can be given, but contains less calcium, and more frequently needs repeat doses to elicit an adequate response. 10 units of insulin dissolved in 25g glucose is given to open cell membrane channels that allow potassium to move out of the blood and into cells (drives K+ into cells). Nebulised salbutamol has a similar effect, and helps shift potassium out of the blood.
Once the acute emergency has been managed, then the patient’s AKI can be addressed, but if the hyperkalaemia is not made a priority, they will arrest.
NB:
Modern blood gas analysers can interpret the blood levels of electrolytes, which is much faster than sending samples to the lab. This is especially useful in emergency cases such as this one. VBGs cannot be used to assess oxygen or carbon dioxide content of arterial blood, but they give an accurate measure of electrolytes and pH (which differs by a mean of 0.03).
The European Resuscitation Council classifies hyperkalaemia as:
mild: 5.5 - 5.9 mmol/L
moderate: 6.0 - 6.4 mmol/L
severe: ≥ 6.5 mmol/L
(3.5 - 5 is normal!)
Which of the following features the lowest serum calcium?
A. Primary hyperparathyroidism B. Secondary hyperparathyroidism C. Osteoporosis D. Paget's disease of the bone E. Breast cancer
B. Secondary hyperparathyroidism
Secondary hyperparathyridism refers to PTH that is elevated in response to hypocalcaemia, so calcium must, by definition, be low. Calcium is normal in both Paget’s and osetoeporosis, and high in primary hyperparathyroidism. Breast cancer may feature elevated calcium levels, as cancer cells may release un-regulated PTHrp which has the same effect as PTH and raises serum calcium.
NB: The majority of cases of secondary hyperparathyroidism are caused by chronic kidney disease. The diseased kidneys fail to hydroxylate enough vitamin D to stimulate sufficient calcium absorption form the gut. Furthermore, the kidneys fail to excrete phosphate, which reacts with calcium in the blood to form a complex which is then excreted, further lowering calcium.
What is the storage form of vitamin D prior to activation?
A. Cholecalciferol B. 25 hydroxyvitamin D C. Alfacalcidol D. 1, 25 hydroxyvitamin D E. Ergocalciferol
B. 25 hydroxyvitamin D
Vitamin D synthesis begins with 7-dehydrocholesterol, which is converted to cholecalciferol in the skin using UV light. Cholecalciferol is then hydroxylated in the liver to form 25-hydroxycholecalciferol, which is also stored in the liver. The active metabolite of vitamin D is produced in the kidney by 1-hydroxylase which produces 1, 25-dihydroxycholecalciferol.
Which of the following DEXA scan results would indicate osteopenia?
A. -2.8 B. -1.0 C. -0.8 D. -1.8 E. 0.3
D. -1.8
Dual energy x-ray absroptiometry (DEXA) is used to evaluate bone density. A score of -1 to -2.5 indicates osteopenia, whereas a score of -2.5 indicates osteoporosis.
Which of the following is the most sensitive measure of acute liver fuction impairment?
A. AST B. ALT C. ALP D INR E. Albumin
D. INR
Liver function tests are poorly named as they do not reflect liver function, instead they should be considered markers of liver cell damage. Albumin and INR are both measures of liver function (i.e. synthetic function), but albumin usually only drops in chronic liver disease (also in inflammation), whereas INR is a good indicator of acute impairment. This is because the half-life of clotting factors is a few hours, so INR (or PT time) will begin to change very quickly after synthetic function is impaired, whereas the half-life of albumin is 3 weeks.
A patient’s set of LFTs read as follows:
Bilirubin - 15 (<17) AST - 250 (<40 U/L) ALT - 75 (<40 IU/L) ALP - 80 (35-51 U/L) GGT - 120 (11-42 U/L)
What is the most likely diagnosis?
A. Viral hepatitis B. Alcoholic liver disease C. Ischaemic hepatitis D. Hepatocellular carcinoma E. Gallstones
B. Alcoholic liver disease
If both AST and ALT are elevated, the ratio between them is important. A ratio of AST:ALT >2 is classically associated with alcoholic liver disease
HCC marker is a-FP (AFP) not ALP
A patient’s set of LFTs read as follows:
Bilirubin - 236 (<17) AST - 55 (<40 U/L) ALT - 65 (<40 IU/L) ALP - 1024 (35-51 U/L) GGT - 59 (11-42 U/L)
What is the most likely diagnosis?
A. Viral hepatitis B. Alcoholic liver disease C. Ischaemic hepatitis D. Hepatocellular carcinoma E. Gallstones
E. Gallstones
The very high ALP in conjunction with other raised markers of liver damage imply a cholestatic picture (note that isolated raised ALP does not suggest cholestasis). This points to gallstones blocking the bile duct.
A patient’s set of LFTs read as follows:
Bilirubin - 168 (<17) AST - 2380 (<40 U/L) ALT - 2500 (<40 IU/L) ALP - 190 (35-51 U/L) GGT - 39 (11-42 U/L)
Toxin screens are negative, as is hepatitis serology
What is the most likely diagnosis?
A. Autoimmune hepatitis B. Alcoholic liver disease C. Ischaemic hepatitis D. Hepatocellular carcinoma E. Gallstones
C. Ischaemic hepatitis
There are three things that can elevate AST and ALT into the thousands and they are: toxic hepatitis, ischaemic damage (rare as liver blood supply is v good), and viral hepatitis.
Which of the following is not a sign of liver failure?
A. Spider naevi B. Dupuytren's contracture C. Palmar erythema D. Kolionychia E. Gynaecomastia
D. Kolionychia
(side note- remember difference between compensated and decompensated cirrhosis and their signs. decompensated when liver can’t copy anymore- jaundice, ascites, encephalopathy, peripheral oedema, variceal bleeding. Spider naevi, gynaecomastia, dupuytren’s etc. all compensated).
Blood tests provide the following results: Na: 145 K 5.0 Urea: 10 pH: 6.85 Glucose: 25
What is this patient’s osmolality?
335 osm/L
Osmolality = 2(Na + K) + U + G Osmolality = 2(145 + 5) + 10 + 25 Osmolality = 335 osm/L
Blood tests provide the following results: Na: 145 K 5.0 Urea: 10 pH: 6.85 Glucose: 25 Chloride: 102 HCO3: 24
What is the anion gap?
24 mM
Anion Gap = Na + K - Cl - HCO3
Anion Gap = 145 + 5 - 102 - 24
Anion Gap = 24mM
The normal range for an anion gap varies depending on how it is measured, but with modern selective electrode measuring is 3/4-11/12mmol/L
Blood tests provide the following results: Na: 160 K: 6.0 Urea: 50 pH: 7.30 Glucose: 60
What is the osmolality?
442 osm/L
Osmolality = 2(Na + K) + Urea + Glucose Osmolality = 2(160 + 6) + 50 + 60 Osmolality = 442 osm/L
normal is 275-295 mOsm/kg
(osmolarity /L, osmolality/kg)
Blood tests provide the following results: Na: 140 K: 4.0 Urea: 4.0 pH: 7.10 Glucose: 4.0
What is the osmolality?
296 osm/L
Osmolality = 2(Na + K) + Urea + Glucose Osmolality = 2(140 + 4) + 4 + 4 Osmolality = 296
Blood tests provide the following results: Na: 140 K: 4.0 Urea: 4.0 pH: 7.10 Glucose: 4.0 Chloride: 90 HCO3: 4.0
What is the anion gap?
50 mM
Anion Gap = Na + K - Cl - HCO3
Anion Gap = 140 + 4 - 90 - 4
Anion Gap = 50mM
The normal range for an anion gap varies depending on how it is measured, but with modern selective electrode measuring is 3/4-11/12mmol/L
A patient presents with the following blood test results:
Na: 125 K: 6.5 U: 10 Glucose: 2.9 FT4: <5 TSH: >50
What is the most likely diagnosis?
A. Grave's disease B. A toxic thyroid nodule C. Schmidt's syndrome D. Primary hypothyroidism E. Addison's disease
C. Schmidt’s syndrome
Schmidt’s syndrome refers to occurrence of primary hypothyroidism along with Addison’s disease, as they occur together more often than they should by sheer chance.
schmidt’s syndrome also known as a autoimmune polyglandular syndrome- are endocrine disorder defined by the combined occurrence of primary adrenal insufficiency with autoimmune thyroid disease and/or type 1 diabetes (also autoimmune)
A 33 year-old with previously recorded hypertension has the following blood test results:
Na: 147 K: 2.8 U: 4.0 Glucose: 4.0 Plasma aldosterone high Plasma renin low
What is the most likely diagnosis?
A. Essential hypertension B. Conn's syndrome C. Phaeochromocytoma D. Cushing's syndrome E. Cushing's disease
B. Conn’s syndrome
Conn’s syndrome is caused by excess aldosterone secretion from the adrenal glands, due to hyperplasia or tumours. This causes suppression of renin release from the juxtaglomerular apparatus.
(also pt is young for HTN- think phaeo, Conn’s)
A 33 year-old with previously recorded hypertension has the following blood test results:
Na: 146 K: 2.9 U: 4.0 Glucose: 14.0 Plasma aldosterone low Plasma renin low High dose dexamethasone test fails to suppress cortisol
What is the most likely diagnosis?
A. Essential hypertension B. Conn's syndrome C. Phaeochromocytoma D. Cushing's syndrome E. Cushing's disease
Which test has superseded the high-dose dexamethasone suppression test?
D. Cushing’s syndrome
Cushing’s syndrome refers to excess cortisol release, whereas Cushing’s disease specifically refers to high cortisol as a result of an ACTH-releasing pituitary adenoma.
Inferior petrosal sinus sampling has superseded high-dose dexamethasone tests as it is more reliable, though the technology to perform sampling is not always available.
Which of the following is not a direct effect of PTH?
A. Excretion of phosphate in the kidney B. Activation of 1-alpha hydroxylase C. Resorption of calcium in the kidney D. Absorption of calcium in the gut E. Resorption of calcium from bone
D. Absorption of calcium in the gut
This is a tricky one, but PTH does not directly act on the gut, it exerts an effect by activating 1-alpha hydroxylase which increases 1,25-OH vitamin D levels, which acts on the gut.
PTH increases blood Ca2+ by any means
Which of the following is the inactive storage form of vitamin D, and is the form that is usually measured?
A. 1,25-dihydroxycholecalciferol B. 25-hydroxycholecalciferol C. Cholecalciferol D. 7-dehydrocholesterol E. Cholesterol
B. 25-hydroxycholecalciferol
In which organ is 25-hydroxylase found?
A. Liver B. Kidney C. Skin D. Parathyroid E. Bone
A. Liver
25 hydroxylase converts cholecalciferol into 25-hydroxycholecalciferol - the main storage form of vitamin D. It is this form that is measured by a vitamin D test.
Which of the following commonly presents with depression?
A. Hyperkalaemia B. Hypokalaemia C. Hypercalcaemia D. Hypocalcaemia E. Uraemia
C. Hypercalcaemia
‘Stones, abdominal moans, and psychic groans’ is the way to remember the effects of hypercalcaemia:
Stones - renal stones
Abdominal moans - constipation and abdominal pain
Psychic groans - depression
A 28 year-old woman presents to hospital with jaundice, pruritis, and dark urine. Her only PMHx is a visit to her GP for antibiotics to treat a UTI (Augmentin). Her LFTs reveal a cholestatic picture, but USS shows no bile duct obstruction.
What is the most likely diagnosis?
A. Cholestasis of pregnancy B. Gallstones C. Primary sclerosing cholangitis D. Drug-induced cholestasis E. Pancreatic cancer
D. Drug-induced cholestasis
Drug induced cholestasis may present as an acute illness that promptly subsides with the withdrawal of the offending agent. It may present with or without jaundice.
Some common drugs associated with cholestatic injury include chlorpromazine, ciprofloxacin, ofloxacin, cimetidine, phenytoin, naproxen, captopril, erythromycin, azithromycin, and dicloxacillin. Amoxicillin-clavulanic (augmentin) acid is also an important cause of cholestatic jaundice.
A 74 year-old retired publican with a significant alcohol history presents with a 3-week history of itchiness, pale stools, dark urine, and yellow sclera. He has experienced 7kg weight loss over the past month. O/E you note epigastric fullness but no tenderness.
What is the most likely diagnosis?
A. Liver cirrhosis B. Gallstones C. Pancreatic cancer D. Primary sclerosing cholangitis E. Hepatocellular carcinoma
C. Pancreatic cancer
Remember Courvoisier’s rule: jaundice with a painless palpable gallbladder is unlikely to be due to gallstones. The alcohol history (questions may just say they are a publican and let you connect the dots) particularly indicates pancreatic cancer, liver cancer, and cirrhosis. The weight loss and epigastric fullness most suggest pancreatic cancer, and the itchiness, pale stools, and dark urine imply an obstructive picture i.e. the tumour is obstructing the bile duct.
likely to be cancer of the head of the pancreas
What are the three main buffers in the body?
Extracellular fluid - Bicarbonate
Intracellular fluid - Phosphate
Red blood cells - Haemoglobin (Haldane effect)
ie acid/base buffers
Assess the nature of the acid-base disturbance described by this ABG: pH - 6.9 pCO2 - 3.0 pO2 - 24 Bicarbonate - 6
Severe metabolic acidosis
Respiratory acidosis is caused by retaining CO2, and respiratory alkalosis is caused by over-ventilation causing depletion of CO2. Whilst this is simple to remember, the causes of metabolic acidosis and alkalosis are far more diverse.
Raised anion gap acidosis:
M - methanol
U - uraemia (renal failure-retains H+, not the uraemia itself)
D - diabetic ketoacidosis
P - paracetamol
I - iron, isoniazid, inborn error of metabolism
L - lactic acidosis
E - ethylene glycol (antifreeze) (ethanol is also included, but only causes acidosis through increased lactic acid in the blood, as does metformin in overdose)
S - salicylatyes (aspirin)
side note- A key concept for the exam is to understand that salicylate overdose leads to a mixed respiratory alkalosis and metabolic acidosis. Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis. In children metabolic acidosis tends to predominate. + tinnitus
Normal gap acidosis:USED CAR Park U - ureteric-intestinal diversion S - sigmoid fistula E - excess saline D - diarrhoea C - carbonic anhydrase inhibitors A - Addison's R - renal tubular acidosis P - pancreatic fistula
Assess the nature of the acid-base disturbance described by this ABG: pH - 7.55 pCO2 - 8.2 pO2 - 10.0 Bicarbonate - 51
***Metabolic alkalosis
NB: due to the equilibrium of the reactions involving carbonic acid and bicarbonate, CO2 and bicarbonate will usually mimic each other
The three main causes of metabolic aklaosis that are taught to us are:
H+ loss (e.g. vomiting)
Long-standing hypokalaemia: If K+ plasma concentration is low, then the Na+/K+ co-transporter can’t work to pump Na+ out of cells. Instead, the Na+/H+ co-transporter moves Na+ out of the cell, but moves H+ into the cell, lowering the plasma pH. This may be caused by long-term diuretic use (which causes hypokalaemia). Furthermore in hypokalaemia, H+ ions will be lost in the kidney as K+/H+ transporters attempt to retain potassium.
Excess bicarbonate intake
Thiazide diuretics reduce potassium concentration in blood through two indirect mechanisms: inhibition of sodium-chloride symporter at distal convoluted tubule of a nephron and stimulation of aldosterone that activates Na+/K+-ATPase at collecting duct. Inhibition of sodium-chloride symporter increases availability of sodium and chloride in urine. When the urine reaches the collecting duct, the increase in sodium and chloride availability activates Na+/K+-ATPase, which increases the absorption of sodium and excretion of potassium into the urine. Long term administration of thiazide diuretics reduces total body blood volume. This activates the renin–angiotensin system, stimulates the secretion of aldosterone, thus activating Na+/K+-ATPase. Often ACEis given alongside TDs to prevent hypoK+
Assess the nature of the acid-base disturbance described by this ABG: pH - 7.41 pCO2 - 10.4 pO2 - 7.8 Bicarbonate - 47
Either:
Mixed respiratory acidosis and metabolic alkalosis
Or a fully compensated respiratory acidosis/ metabolic alkalosis
This case was a 72 y/o man with COPD causing CO2 retention, but was also taking furosemide for heart failure, which had lead to hypokalaemia and metabolic alkalosis. However without the clinical background, it is equally plausible to say this could be a fully compensated abnormality rather then a mixed picture.
furosemide-Hypokalemia is caused by the increased distal delivery of potassium and secondary mineralocorticoid excess
A man is brought to hospital 8 hours after taking an aspirin overdose.
Assess the nature of the acid-base disturbance described by this ABG:
pH - 7.46
pCO2 - 2.0
pO2 - 17.8
Bicarbonate - 10
Mixed respiratory alkalosis and metabolic acidosis
This picture is classic of aspirin overdose which produces mixed acidosis and alkalosis. There is a suggestion that this could be a partially compensated respiratory alkalosis, however this is very unlikely because respiratory alkalosis is caused by hyperventilation. The kidneys take much longer to compensate than the lungs, and so this person would have to be hyperventilating for weeks to produce this picture.
initially salicylic acid OD- resp alkalosis (as stims resp centres- hyperventilation) then metabolic acidosis (as it’s an acid)- mixed picture- remember this by lungs change pH much faster than kidneys
Which of the following would confirm a diagnosis of diabetes mellitus type 2?
A. Fasting plasma glucose over 6.5mM
B. A 2 hour plasma glucose in a GGT of 9.0nM
C. A 2 hour plasma glucose in a GGT of 10.0nM
D. A 2 hour plasma glucose in a GGT of 11.0nM
E. HbA1c > 6.5% (48mmol/mol)
E. HbA1c > 6.5% (48mmol/mol)
T2DM diagnosis used to require either a fasting plasma glucose measurement of 7.0mM or greater, or a 2h GGT plasma glucose of 11.1mM or greater. These are both still in use, but an additional criterion has been added: an HbA1c > 6.5% can be used to diagnose diabetes.
https://www.diabetes.org.uk/for-professionals/improving-care/clinical-recommendations-for-professionals/diagnosis-ongoing-management-monitoring/new_diagnostic_criteria_for_diabetes
Which of the following is a measure of glucose control over the last 3 weeks?
A. Fasting plasma glucose B. Random plasma glucose C. OGTT D. HbA1c E. Fructosamine
E. Fructosamine
HbA1c gives a picture of control over the last 3 months, and is used to monitor control in diabetics. However in cases where the doctor needs a snapshot of control over the last few weeks, fructosamine is useful.
Give the three main functions of purines
Energy source (ATP, GTP)
Secondary messenger in cell membrane signalling (cAMP, cGMP)
Components of DNA
pyrimidines have ‘Y’ in them + uracil
Which of the following is a crucial enzyme for the salvage pathway of purine manufacture
A. HGPRT B. PAT C. Xanthine oxidase D. PPRP E. GTPase
A. HGPRT
HGPRT (also known just as HPRT) salvages purine metabolites to regenerate purines. The salvage pathway is far more efficient and predominates over the de novo pathway in most tissues.
Absolute deficiency of HGPRT leads to Lesch-Nyan syndrome, which usually presents as developmental delay around the 6 month mark though they appear normal at birth. Patients will also feature gout, classic self-mutilating behaviour (biting lips and digits), mental retardation, spasticity, and choreiform movements.
PAT is the general rate-limiting enzyme for purine metabolism.
Porphyria cutanea tarda and acute intermittent porphyria are the two most common porphyrias: which enzymes are deficient in each?
Porphyria cutanea tarda - Uroporphyrinogen decarboxylase
Acute intermittent porphyria - HMB synthase (a.k.a. Porphobilinogen deaminase)
remember HMB with AIP and A (AIP) then B (HMB)
