Chemical Pathology

Question 1

What are the characteristics of Uric Acids?

Answer 1

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

Question 2

Describe the characteristics of sodium urate.

Answer 2

more soluble than uric acid
solubility decreases at lower temperatures hence more precipitation.

Question 3

How do the kidneys handle uric acid?

Answer 3

Excretes 75%
100% G filtration
90-99% Actice Reabsorption in PCT
Simultaneously secretion

10% filtered

Question 4

Describe the role of uric acids in humans.

Answer 4

lack uricase- retention of uric acid
Anti-oxidant
anti-natriuretic
innate immune enhancer

Question 5

Describe purine metabolism

Answer 5

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

Question 6

Discuss what tumor lysis syndrome is.

Answer 6

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

Question 7

Describe the signs/diagnosis and give the pathogenesis of tumour lysing.

Answer 7

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

Question 8

What are the prevention strategies for TLS?

Answer 8

Suspect and anticipate
Adequate IV hydration
Reduce: UA- allopurinol and Rasburicase

Question 9

Explain how rasburicase works.

Answer 9

Uric acid to water-soluble allantoin
expensive

Question 10

Explain Mutliple myeloma.

Answer 10

malignant proliferation of a clone of plasma cells in the bone marrow, often caused by genetic alterations

Question 11

What is polyclonal?

Answer 11

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.

Question 12

How does MM become monoclonal?

Answer 12

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.

Question 13

How does hypocalcemia affect the ECG?

Answer 13

Prolonged QT interval, longer to repolarize the ventricles, hence can lead to ventricular arrhythmias.

Question 14

What are the complications of TLS?

Answer 14

Cardiac Arrhythmias
Acute Renal Failure- Oliguric
Metabolic Acidosis-consumption of HCO3 due to ARF

Question 15

How do you treat Hyperkalaemia?

Answer 15

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

Question 16

What is the cause for URIC ACID increase?

Answer 16

Increase in nucleic acid degradation- cell lysis
increase purine breakdown

Question 17

How can you prevent Hyperuricemia?

Answer 17

Allopurinol
Alkalinisation of urine and proper hydration, increases solubility.

Question 18

Describe the Hematological findings in MM.

Answer 18

Pancytopenia
ESR raised due to increased sedimentation due t increased production of immunoglobulins.

Question 19

Describe the total protein and albumin levels in MM.

Answer 19

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.

Question 20

How does albumin decrease?

Answer 20

Chronic inflammation
liver production decreases
increase renal lost

Question 21

Besides biochemical testing, what are other tests than can be done in a MM?

Answer 21

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.

Question 22

What is the pathogenesis of hypercalcemia in MM?

Answer 22

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.

Question 23

What is the diagnostic procedure for gout?

Answer 23

Joint aspiration with polarizing the light to see crystals,

Question 24

How does alcohol affect urate excretion?

Answer 24

Ethanol decreases uric acid secretion by affecting the urate tubular secretion.

Question 25

What is another complication of uric acid in a patient with gout?

Answer 25

Tophaceous gout-crystals