Chemical Pathology Flashcards
What are the characteristics of Uric Acids?
Weak acid
pH of blood pH>pKa urate anions predominate and binds to Na
the pH of urine pH<pKa Uric acid predominates
Exist as Uric acid, Urate ion, and Na Urate
Much less soluble
Decreased further in low pH hence increase precipitation–> kidney stones
Describe the characteristics of sodium urate.
more soluble than uric acid
solubility decreases at lower temperatures hence more precipitation.
How do the kidneys handle uric acid?
Excretes 75%
100% G filtration
90-99% Actice Reabsorption in PCT
Simultaneously secretion
10% filtered
Describe the role of uric acids in humans.
lack uricase- retention of uric acid
Anti-oxidant
anti-natriuretic
innate immune enhancer
Describe purine metabolism
PPRP undergoes de novo synthesis
this produces nucleotides (inosine monophosphate), then this catabolized into nucleosides (inosine), nucleobases hypoxanthine
requires HGPRT to undergo savage to produce a Nucleotide again, not present and produces uric acid only from hypoxanthine and guanine
Discuss what tumor lysis syndrome is.
Metabolic complications
rapid lysing of malignant cells
release of breakdown products and intracellular contents of dying cells
results in AKI, and reduce renal excretion of solutes.
48-72 hrs after
Describe the signs/diagnosis and give the pathogenesis of tumour lysing.
Uric acid-
induces AKI intrarenal crystalization, hypoxia,
pro-inflammatory agent, release cytokines- systemic immune response, WBC further damage
scavenged nitric oxide causing vasoconstriction
Hyperkalaemia-
cardiac dysrhythmias
Hyperphosphataemia-
lead to hypocalcemia
and inhibits alpha-1 hydroxylase, Vit D activation decrease absorption of calcium in GIT.
deposits of calcium and phosphates in soft tissues (metastatic calcification)
Hypocalcaemia-
Secondary to HyperPh
neuromuscular irritability
dysrhythmia
seizures
What are the prevention strategies for TLS?
Suspect and anticipate
Adequate IV hydration
Reduce: UA- allopurinol and Rasburicase
Explain how rasburicase works.
Uric acid to water-soluble allantoin
expensive
Explain Mutliple myeloma.
malignant proliferation of a clone of plasma cells in the bone marrow, often caused by genetic alterations
What is polyclonal?
The N-terminal end of each antibody is extremely variable, thus there are millions of antibodies with different antigen binding sites, each produced by a different “clone” of plasma cells. Polyclonal.
How does MM become monoclonal?
Uncontrolled proliferation of these plasma cells and the secretion of high levels of abnormal and non-functional immunoglobulins. The expansion of the malignant clone suppresses the formation of other clones, thus leading to the over-production of a single, monoclonal, antibody. Secretes only one type of light chain.
How does hypocalcemia affect the ECG?
Prolonged QT interval, longer to repolarize the ventricles, hence can lead to ventricular arrhythmias.
What are the complications of TLS?
Cardiac Arrhythmias
Acute Renal Failure- Oliguric
Metabolic Acidosis-consumption of HCO3 due to ARF
How do you treat Hyperkalaemia?
Acute situation- Calcium Gluconate 4, stabilizes cardiac muscle
limit k intake
Removal from body
loop diuretics
kayexalate- cation ion exchanger
dialysis
into cells
insulin and glucose
NaHCO3
B2 adrenergic agonist
What is the cause for URIC ACID increase?
Increase in nucleic acid degradation- cell lysis
increase purine breakdown
How can you prevent Hyperuricemia?
Allopurinol
Alkalinisation of urine and proper hydration, increases solubility.
Describe the Hematological findings in MM.
Pancytopenia
ESR raised due to increased sedimentation due t increased production of immunoglobulins.
Describe the total protein and albumin levels in MM.
Large globin gap
albumin can either decrease or remain normal, however total protein increases despite this, hence another protein component is being overproduced that is not albumin.
How does albumin decrease?
Chronic inflammation
liver production decreases
increase renal lost
Besides biochemical testing, what are other tests than can be done in a MM?
Serum protein electrophoresis- separates plasma proteins in a buffer of particular pH with a small voltage
separation in 5 groups, albumin net negative to anode and immunoglobulin with net positive to the cathode.
then stained and can visibly be seen
immunofixation/subtraction
serum free light chains
Urine Bence Jones Proteins- Detects monoclonal proteins in urine, normal renal function this would be undetectable in serum.
What is the pathogenesis of hypercalcemia in MM?
Plasma cells secrete cytokines
stimulate osteoblast to express RANK-L
Plasma cells also express proteoglycan syndecan-1 that mops up osteoprotegerin (decoy RANK-L)
Activates Osteoclast.
What is the diagnostic procedure for gout?
Joint aspiration with polarizing the light to see crystals,
How does alcohol affect urate excretion?
Ethanol decreases uric acid secretion by affecting the urate tubular secretion.
What is another complication of uric acid in a patient with gout?
Tophaceous gout-crystals
