Chemical pathology Flashcards
How do you calculate osmolarity?
Osmolarity = charged ions + uncharged ions
= 2(cations) + Urea + Glucose mosmol/kg
How do you calculate anion gap?
Anion gap = cations - known anions (need HCO3- and Cl-)
What is the acid base equilibrium equation?
H+ + HCO3- = CO2 + H20
What acid-base disturbance is characterised by a low pH and a high PCO2?
Respiratory acidosis
What acid-base disturbance is characterised by a low pH and a low pCO2?
Metabolic acidosis
What acid-base disturbance is characterised by a high pH and a low pCO2?
Respiratory alkalosis
What acid-base disturbance is characterised by a high pH and a high pCO2?
Metabolic alkalosis
What acid-base disturbance is characterised by a high pH and a high pCO2?
Metabolic alkalosis
What metabolic bone disease would give you all normal parameters except raised ALP?
Paget’s disease
What are the primary defects in OP, OM/rickets, Paget’s bone disease and Renal bone disease?
OP: bone loss
OM: low vit D
Paget’s: Remodelling
PTH bone disease: high PTH
Renal bone disease: low 1a-hydroxylation, aluminium toxicity?
What is the commonest biological cause of primary hyperparathyroidism?
Parathyroid tumour/adenoma
What is the aetiology of familial hypocalciuric hypercalcaemia (FHH/FBH)?
A CaSR inactivating mutation which makes it less sensitive to high serum Ca2+ levels. The receptor therefor has a higher set point for PTH release causing permanent mild hypercalcaemia.
Define AKI
A rapid reduction in kidney function. This leads to an inability to maintain electrolyte, acid-base and fluid homeostasis.
What is AKI management?
Medical emergency
Refer to nephrologist for Dx and Tx
How is AKI classified?
3 stages of AKI
1) increase in creatinine of 1.5-1.9x reference range / >=26umol/L
2) increase in creatinine of 2-2.9x reference range
3) increase in creatinine of >3x reference range
Urine output should also be <0.5ml/kg/hr for 6 hrs
What are the hallmarks of each type of AKI?
Pre-renal - reduced renal perfusion
Post-renal - physical obstruction to urine flow
Intrinsic/renal - damage to any part of nephron
What are the 5 stages of CKD?
1) Kidney damage with normal GFR
2) Mild decrease in GFR
3) Moderate decrease in GFR
4) Severe decrease in GFR
5) End-stage kidney failure
What are the consequences of CKD?
1) Failure of homeostatic function -> hyperkalaemia, acidosis
2) Progressive failure of hormonal function -> decreased EPO, vit D, RAAS
3) CVD -> vascular calcification, uraemic myopathy (3 phases)
What is the normal range for bilirubin?
5-17
What is the condition characterised by all normal liver function tests except a high bilirubin level of 45 (5-17 normal range)?
Gilbert’s syndrome
A patient comes in and is jaundiced and complaining of a dull pain in their right epigastric region. Their stools have been a weird pale yellow colour since 2 days ago. You test their urine for the presence of urobilinogen and it is negative, what is the diagnosis?
Obstructive jaundice - blockage of the biliary tree
Which of these is the most representative of liver function?
a) Prothrombin time
b) Albumin
c) Bilirubin
d) Alanine amino transferase
e) Aspartate amino transferase
f) Alkaline phosphatase
g) Gamma GT
a) Prothrombin time
Clotting is the best indicator of hepatic function.
Albumin and bilirubin are okay
What is the normal range for prothrombin time?
12-14 seconds
What are the ddx for a hyperbilirubinaemia of 90?
Pre-hepatic: Gilbert’s syndrome, haemolytic anaemia
Hepatic: Viral hepatitis, alcoholic hepatitis, cirrhosis
Post-hepatic: Gallstones, pancreatic cancer
What do raised levels of AST, ALT and ALP mean respectively?
AST - hepatocyte damage (NR <50)
ALT - hepatocyte damage (NR <50)
ALP - Obstructive jaundice (NR <130)
In a patient with ALP of 200, ALT 1500 and AST 750, what is the likely pathology?
a) Pre-hepatic
b) Post-hepatic
c) Hepatic
c) Hepatic
What is a side effect of pabrinex?
Dark yellow urine
Which of these is causes by thiamine deficiency (B1)?
Rickets
Scurvy
Beri Beri
Pellagra
Pernicious anaemia
Neural tube defects
Beri beri
Rickets - vitamin D
Scurvy - vitamin C
Pellagra - Niacin deficiency (B3)
Pernicious anaemia - B12 (IF deficiency)
Neural tube - folate deficiency
On examination, a patient has multiple spider naevi, palmar erythema, dupuytren’s contracture and gynaecomastia, which one of the following is most likely?
Chronic stable liver disease
Portal hypertension
Jaundice
Hepatitis
Liver failure
Obstruction of bile ducts
Chronic stable liver disease
What is this and what does it signify?
A visible vein on the anterior abdominal wall/Caput medusae
Portal hypertension/increase in umbilical venous pressure
Given portal hypertension, what other feature are you most likely to see?
a) hepatomeglay
b) splenomegaly
c) palpable bladder
d) bilateral, palpable kidneys
e) enlarged prostate gland on PR
b) splenomegaly - presuure in the portal vein increases -> pressure in the splenic vein increases -> pressure in the spleen increases and it enlarges -> splenomegaly
A patient has visible veins on his anterior abdomen, shifting dullness and splenomegaly on examination. What is the diagnosis?
Chronic liver disease
Jaundice
Hepatitis
Liver failure
Portal hypertension
Obstruction of bile ducts
Portal hypertension
What does a tremorous flap of the hands suggest when asked to keep hands 90 degrees from extended arms (similar hypercapnic flap)?
Liver failure - may be due to ammonia (unknown)
What are the hallmarks of liver failure?
Failure of: synthetic functions, clotting factor, albumin, bilirubin clearance, ammonia clearance (hepatic encephalopathy)
What are the sites of porto-systemic anastamoses?
Sites where portal circulation meets systemic circulation
Oesophagus
Abdominal wall near umbilicus
Rectum
Near spleen
What do scratch marks on the skin with jaundice suggest?
Obstruction of the bile ducts - gall stones or pancreatic carcinoma (head of the pancreas)
What is Couarvoisier’s law?
If a patient is jaundiced and their gallbladder is palpable it is likely to be pancreatic cancer rather than gallstones as gallstones cause the gallbladder to shrink and become fibrotic.
What do stellate cells activate into when there is liver damage?
When there is liver damage, quiescent stellate cells within the space of disse become activated and differentiate into myelofibroblasts which produce collagen which deposits fibrous scar tissue within the liver.
What happens to the cells of the liver when the liver is damaged ?
Hepatocytes lose their microvilli
Stellate cells differentiate into myelofibroplasts
Endothelial cells become continous and joined together - loss of fenestrations
Kupffer cells also become activated
What is micronodular cirrhosis most associated with?
Alcohol abuse, alcoholic liver disease
What is macronodular cirrhosis most associated with?
Viral hepatitis
What are the complications of liver cirrhosis?
1) Portal hypertension
2) Hepatic encephalopathy
3) Liver cell cancer
What does this picture show?
Spotty necrosis in acute hepatitis
What is the difference between the left and right picture?
Left picture: normal
Right picture: increasing fibrosis - not just in portal triad/tract but towards central vein etc. This causes intrahepatic shunting, as blood cannot enter the hepatocytes.
What does this picture show?
Fatty liver
Hepatocytes containing fat
Alcoholic liver disease
What does this picture show?
Alcoholic hepatitis - ballooning of cells (collapsed cytoplasm), mallory denk bodies, pericellular fibrosis, fat
What does this picture show?
Granulomatous disease centred around a hepatic bile duct that is being destroyed and is chronically inflamed.
Primary biliary cholangitis.
This can progress to a cirrhosis of the bile duct if not trated.
What does this picture show?
Pink globules show accumuations of alpha 1 anti trypsin within hepatocytes.
Alpha-1 antitrypsin deficiency in the liver.
What does this picture show?
Liver cell adenoma
What does this picture show?
Intrahepatic cholangiocarcinoma
Which of these is the commonest liver carcinoma?
a) Liver cell carcinoma
b) Cholangiocarcinoma
c) Metastatic adenocarcinoma
c) Metastatic adenocarcinoma
Which of these is not associated with fatty change in the liver?
a) Hepatitis B
b) Hepatitis C
c) Alcohol
d) Diabetes
Hepatitis B and Hepatitis C are not associated with fatty change in the liver.
Which of these is not associated with genetic haemochromatosis?
a) Kaiser Fleischer rings
b) Diabetes
c) Myocardial damage
d) Cirrhosis
a) Kaiser Fleischer rings
A 76 year old patient with a previuos MI has a BP of 140/80 on atenolol.
His LDL is 3.0mmol on atorvostatin 80mg.
Is there evidence to lower his BP further?
Yes, the patient should be offered thiazide diuretics or calcium channel blockers as intensive treatment will lower the risk of further cardiovascular disease, CV death, MI, acute coronary syndrome or heart failure.
Explain absolute reduction
An absolute reduction of 2% with regards to an outcome means that if the intervention is followed by 100 people, 2 less people will encounter the outcome as opposed to a group of 100 people with no intervention.
What are some treatments for lipid and cholesterol control is a patient is statin intolerant?
Ezetemibe
Plasma exchange
Evolocumab (PCSK9 monoclonal Ab)
What is PCSK9?
Proprotein convertase subtilisin kexin 9 (PCSK9)
PCSK9 regulates levels of the LDL receptor. It forms a complex with LDL R, which is endocytosed and then digested by lysosomal enzymes.
Gain-of-function mutations in PCSK9 reduce LDL receptor levels in the liver, resulting in high levels of LDL cholesterol in the plasma.
Loss-of function mutations in PCSK9 increase LDL receptor levels in the liver, resulting in lower LDL cholesterol levels and conferring protection from coronary heart disease.
What is an example of a monoclonal Ab for PCSK9?
Evolocumab
What is the effect on number needed to treat, if your risk reduction is extremely small?
High number needed to treat
Likely to have little/no effect on mortality
What condition is PCSK9 inhibitors approved for?
Familial Hypercholesterolaemia
How many years does good glucose control take to make a difference to a patient’s health (UK prospective diabetes study i.e. newly diagnosed diabetes patients)?
It takes a long time i.e. 12-15 years after diagnosis, to make a real difference in terms of outcomes.
After a patient stops intensive glucose control, they have 10 years of long-term health benefits compared to lax glucose control. This is called the legacy effect.
What are the landmark studies done into blood glucose control?
DCCT - T1DM - good control = improved outcomes
UKPDS - intensive control improves outcomes after around 15 years, 10 years worth of legacy effects - long-term benefits to health after intensive control ceases
ACCORD - Old people with coronary artery disease + intensive control = death
ADVANCE - Not much difference between intensive and conventional control in diabetes vascular patients - perhaps a reduction
What was presumed the culprit drug of the ACCORD study?
Rosaglitazone - now banned as increases mortality
What is an SGL2 inhibitor example?
Empagliflozin, used for diabetes
What effects do SGL2 inhibitors have?
HbA1c reduction, weight loss, systolic BP reduction, Waist circumference reduction, early reduction in diastolic BP, treatment of heart failure, protect the kidneys (sustain eGFR)
Which study on glucose control suggested that tight control increases mortality?
a) ACCORD
b) ADVANCE
c) DCCT
d) UKPDS
e) No study
a) ACCORD
What does SGLT2 and GLP-1 stand for?
XXXX
What is the inheritance pattern of familial hypercholesterolaemia?
Autosomal dominant
Rare types can be inherited via an autosomally recessive pattern
What is the most common electrolyte abnormality in hospitalised patients?
Hyponatraemia
A serum sodium level of less than 135 mmol/L
1/4 patients have hyponatraemia
What is the underlying pathogenesis of hyponatraemia?
Increased extracellular water - ‘dilution’
Which hormone controls water balance?
Anti-diuretic hormone (vasopressin)
How does anti-diuretic hormone/vasopressin work?
Acts on V2 receptors in the collecting duct, upregulates insertion of aquaporin-2 in the collecting duct wall which leads to more water reabsorption into the blood.
Also acts on V1 receptors in vascular smooth mucle, causing vasoconstriction typically at higher concentrations.
What are the 2 main stimuli for ADH secretion?
1) Increased serum osmolality - this is mediated by hypothalamic osmoreceptors
2) Low blood volume/pressure - this is mediated by baroreceptors in the carotids, atria and aorta
What makes you feel thirsty?
An increase in osmolality detected by the hypothalamic osmoreceptors
What is the first step in the clinical assessment of a patient with hyponatraemia?
Clinical assessment of volume status
When vomiting, why do we become hyponatraemic?
Because we lose blood volume when we vomit through loss of fluid. This is detected by the baroreceptors at the carotids, atria and aorta. This leads to increased water retention as more ADH is secreted by the posterior pituitary. This leads to increased extracellular water compared to sodium concentration.
What is the most reliable indicactor of hypovolaemia?
Low urine Na+
What are the causes of a hyponatraemic hypovolaemia?
Diarrhoea
Vomiting
Diuretics
Salt losing nephropathy
What are the causes of a hyponatraemic euvolaemia?
Hypothyroidism
Adrenal insufficiency
SIADH
What are the causes of hyponatraemia in a hypervolaemic patient?
Cardiac failure
Cirrhosis
Nephrotic syndrome
Why do you get a low urine Na+ in hyponatraemic hypervolaemia?
Cardiac failure leads to a secondary hyperaldosteronism which leads to reabsorption of Na+. This means less Na+ is excreted in the urine.
How would you manage a hypovolaemic patient with hyponatraemia?
Volume replacement with 0.9% saline
How would you manage a hypervolaemic or euvolaemic patient with hyponatraemia?
Fluid restriction and treat the underlying cause
What does fluid restriction mean practically?
0.5-1L in 24 hours
What is the most important point to remember when correcting hyponatraemia?
Serum Na must not be corrected >8-10mmol/L in the first 24 hours. Risk of osmotic demyelination increases (central pontine myelionlysis) due to rapid shift in fluids within brain cells. This is a disruption of the blood brain barrier. Signs of central pontine myelionlysis include quadriplegia, dysarthria, dysphagia, seizures, coma and death.
What are the causes of hypernatraemia?
1) Unexplained water loss (GI loss, renal loss, sweat loss)
2) Patient cannot control water intake i.e. Alzheimer’s, baby, child