Chemical Pathology Flashcards
Chemical Pathology 1 - Calcium handling and metabolic bone disease
What forms of Calium are present in the serum?
What are normal blood Calcium levels?
What is corrected Calcium? How do you calculate it?
Calcium in serum comes in 2 forms (and makes up 1% of all calcium):
- Free (ionised”) calcium - 50% biologically active
- Protein bound - 40% - albumin
- Complexed - 10% (citrate/phosphate)
Total serum Calcium is between 2.2 - 2.6 mmol/L.
Corrected calcium can be given, which is serum Calcium + 0.02 x (40-serum albumin in g/L). Because calcium binds to albumin and only the unbound (free or ionized) calcium is biologically active, the serum level must be adjusted for abnormal albumin levels.
Ionised calcium can also be given but not from a lab since the blood clots. With a low albumin, the bound calcium will show as low but the free will be normal. The corrected calcium refers to this.
Chemical Pathology 1 - Calcium handling and metabolic bone disease
Outline the homeostasis of calcium using a diagram
There should be a link from the PTH to the bone and the kidney. The Kidney produces
PTH released from parathyroid gland, which targets 3 sources of calcium. The bone, the gut (through increased absorption) and the kidney (reabsorption and 1 alpha hydroxylase activation). PTH is an 84 aa protein, only produced in the parathyroids. It can stimulate Calcium uptake, 1,25(OH)2 vit D synthesis (1 alpha hydroxylation) as well as Phosphate wasting.
Chemical Pathology 1 - Calcium handling and metabolic bone disease
What is the Homeostatic response to low calcium?
PTH released from parathyroid gland, which targets 3 sources of calcium. The bone, the gut (through increased absorption) and the kidney (reabsorption and 1 alpha hydroxylase activation). PTH is an 84 aa protein, only produced in the parathyroids. It can stimulate Calcium uptake, 1,25(OH)2 vit D synthesis (1 alpha hydroxylation) as well as Phosphate wasting.
Chemical Pathology 1 - Calcium handling and metabolic bone disease
Outline viatmin D synthesis
Vitamin D3 is made in the skin as cholecalciferol, which is converted into 25-hydroxycholecalciferol by 25 hydroxylase from the Liver. This is then converted into 1,25-dihydroxycholecalciferol 25-(OH)2 D3 by 1 hydroxylase from the kidney.
Chemical Pathology 1 - Calcium handling and metabolic bone disease
What are the roles of Vitamin D?
What is Vitamin D deficiency an what are its risk factors?
What are the symptoms of Osteomalacia and Rickets?
1,25-dihydroxycholecalciferol, Vitamin D roles:
- Intestinal Calcium absorption
- Intestinal Phosphate absorption
- Bone formation
- Cells have important Vit D receptors to control genes, cell proliferation, immune system and such
Vitamin D deficiency:
In children this is called rickets and in adults it is osteomalacia, which is the exact same thing just at different ages. In the UK ½ of adults are Vit D deficient and 16% have severe deficiency during winter.
Risk factors include:
- lack of sunlight exposure
- dark skin
- Dietary, Vitamin D deficient diet (chapatis)
- Malabsorption
- Kidney failure, since there would not be enough 1 alpha hydroxylase produced to convert 25-hydroxycholecalciferol into 1,25 dihydroxycholecalciferol
- Anticonvulsants stimulate vitamin d breakdown.
Osteomalacia: causes muscle and back pain, the biochemistry is Low Calcium and Phosphate, raised ALP
Rickets: causes bowed legs, costochondral swelling, widened epiphyses at the wrists and myopathy
Chemical Pathology 1 - Calcium handling and metabolic bone disease
What is Osteoporosis?
How is it diagnosed?
What are the risk factors?
What is the treatment?
Osteoporosis:
Normal biochemistry, a gradual reduction in bone density that will first present as a fracture. Diagnosed with a Dual energy X-ray absorptiometry (DEXA) scan. Of the hip and lumbar spine. The bone density is compared to the mean of a young healthy population. The standard deviations away from this is the T score. Z score is standard deviations away from age-matched control population. Definition of osteoporosis is a T score less than 2.5 standard deviations. Osteopenia is a T score between -1 and -2.5 standard deviations.
Risk factors:
- Childhood illness
- Early menopause (loss of oestrogen production)
- Lifestyle:
- sedentary, alcoholism, smoking, low BMI
- Steriods
- Endocrine: hyperthyroidism
Treatment:
- Lifestyle:
- Weight bearing exercises
- smoking cessation
- reduced alcohol intake
- Drugs:
- Vitamin D/Calcium
- Bisphosphonates, normally bone is made out of calcium and phosphate. These will synthetically put a nitrogen into the phosphate so that when an osteoblast lays down bone, there is calcium-bisphosphonate. This means that the osteoclast cannot break down the new bone since humans do not have an enzyme to break down carbon-nitrogen bonds. Making the bone permanent. Great but the side effects are tummy troubles, nauseas etc
- Strontium (less used since thought to be less strong bone)
- Oestrogens (also less used since increased risk of breast cancer)
- Selective Estrogen Receptor Modulators (SERMS) like Raloxifene and Tamoxifen. These are antagonists in bone and antagonists in the breast. Great, side effects are bad hot flushes.
Chemical Pathology 1 - Calcium handling and metabolic bone disease
What are the symptoms of Hypercalaemia?
What are the casues of hypercalcaemia?
Symptoms:
- Polyuria
- Polydypsia
- Constipation
- Neuro- confusion/ seizures/ coma
Important questions to ask following a hypercalcemia result:
- firstly , DOUBLE CHECK THE RESULTS
- Secondly, is the PTH SUPPRESSED (like it should be in normal physiology)?
Chemical Pathology 1 - Calcium handling and metabolic bone disease
What are the causes of Hypercalaemia with innapropriate PTH production?
Causes of Hypercalaemia with PTH suppression?
Hypercalcaemia causes with inappropriate PTH production:
Primary hyperparathyroidism: parathyroid adenoma, hyperplasia is associated with MEN1 genetic mutation. Due to increased serum Calcium you get BONES (PTH bone disease) STONES (renal calculi) abdominal MOANS (constipation, pancreatitis) and psychiatric GROANS (confusion).
Familial hypocalciuric hypercalcemia: PTH is abnormally released by the parathyroid gland due to Calcium sensing receptor (CaSR relseass) mutation. Qute rare but you distinguish from primary hyperparathyroidism by looking at the urine Calcium, if it is low it’s FHH high means it is primary hyperparathyroidism.
Hypercalcemia with PHT suppression:
How does malignancy cause hyperparathyroidism?:
- Lung and kidney cancer can make PTH related Peptide (PTHrP). In normal adults the PTHrP is always 0. This is the gene that is turned on before you are born allows you to make a skeleton. PTHrP is very important since this can also make cells invade by activating osteoclasts.
- Bone metastases
- Haematological malignancy e.g.myeloma
Other hypercalcaemia causes:
- Sarcoidosis, produces non-renal 1 alpha hydroxylase (converting 1 hydroxycalciferol into 1,25 dihydroxycalciferol)
- Thyrotoxicosis, thyroxine causes increased bone resorption
- Hypoadrenalism, affecting renal calcium transport
- Thiazide diuretics, also affecting renal calcium transport
- Sunbeds causing excess Vitamin D
Treatment:
Fluids, lots of normal saline, they will start to pee out lots of calcium. Bisphosphonates can be given if the known cause is cancer, as well as treat the underlying cause (e.g. chemotherapy).
Chemical Pathology 4 - Sodium and fluid balance
What is the physiological basis of Hyponatremia?
Excess water = ADH/Vasopressin acts as the hormone that regulates water reabsorption by acting on V2 receptors in the collecting ducts of the kidneys. These have their effect by inserting aquaporin-2 into the membranes of the collecting duct cells.
ADH also acts as a vasoconstrictor by acting on V1 receptors in:
- Vascular smooth muscle, causing vasoconstriction and therefore a higher concentration
Chemical Pathology 4 - Sodium and fluid balance
What are the two main stimuli for ADh secretion?
Serum osmolality = detected by osmoreceptors in the hypothalamus, when osmolality increased more ADH is released
Blood volume/pressure = detected by baroreceptors in the carotid arteries, atria and aorta. Low blood volume/pressure causes a stimulation of the hypothalamus to release more ADH
Chemical Pathology 4 - Sodium and fluid balance
How do you assess a patient as Hypovolaemic?
Little water, dry mucous membranes, low skin turgor, tachycardia, confused / drowsiness.
LOW URINE SODIUM. Kidneys are better than Nephrologists at telling how much sodium a patient needs. If it is less that 20. It’s low. Of course, if that patient is on diuretic, you cannot tell. So stop the diuretics and do the urine sodium test 24 hours later.
Chemical Pathology 4 - Sodium and fluid balance
What are the common causes of Hypovolaemic Hyponatraemia?
What is the treatment of Hypovolaemic Hyponatraemia?
- Can be Renal (Diuretics)
- or Extra renal (Diarrhoea, Vomiting)
Treatment:
- Volume replacement with 0.9% Saline
Chemical Pathology 4 - Sodium and fluid balance
What does a euvolaermic patient look like?
Common Euvolemic causes
Normal water balance
Common Euvolemic causes:
- Hypothyroidism
- Adrenal insufficiency
- Syndrome of Inappropriate ADH secretion:
- Causes of SIADH:
- CNS pathology
- Lung pathology
- Drugs
- Tumours
- Surgery
Chemical Pathology 4 - Sodium and fluid balance
Investigations for Euvolemic Hyponatremia?
Treatment for euvolemic hyponatremia?
Investigations for Euvolemic Hyponatremia:
- TFTs
- Short synacthen test
- Plasma and urine osmolality = Diagnosis needs to show a reduced plasma osmolality and increased urine osmolality (>100). Need to be sure about your diagnosis because SIADH treatment is fluid restriction. If you misdiagnose this as hypovolaemic and treat them with saline then you’ll kill them.
Treatment for euvolemic hyponatremia:
- Fluid restriction
- Treat the underlying cause
Chemical Pathology 4 - Sodium and fluid balance
What does a Hypervolaemic patient look like?
Common Hypovolemic causes?
Signs: raised JVP, bibasal crackles, peripheral oedema
Common Hypovolemic causes:
- Cardiac failure (too much water>too much ADH> something is stimulating this ADH release, in HF, it’s a reduced cardiac output).
- Cirrhosis ( too much water> too much ADH > made because patients with cirrhosis usually are vasodilated)
- Nephrotic syndrome
