TSH
Consistent with thyrotoxicosis.
Thyrotoxicosis:
• Metabolic rate is increased: weight loss
• Cardiovascular: tachycardia, AF, palpitations
• Gastrointestinal: stimulates peristalsis, diarrhoea
• Respiratory: tachypnoea
• Skeletal: direct effect on osteoclasts causing osteopenia/osteoporosis
• Reproductive: dysmenorrhoea, infertility
Management:
Make diagnosis: low TSH, elevated T4 and T3
Technitium scan: high uptake vs low uptake
Thyroid autoantibodies (thyroid microsomal)
Aim of treatment is to keep patient safe! Give beta blocker
Think of other AI conditions (pernicious anaemia, coeliac, addisons)
ECG and DEXA scan
Radioactive Iodine: tag onto iodine, uptake into thyroid gland and slowly destroys thyoid gland, leading to hypothyroid over the following years.
• 131I RCP guidlines
• opthalmopathy/tracheal compression
• stop thionamide
• precipitation of thyroid storm: tachycardia, AF (give beta blocker)
• hypothyroidism: make patient underactive and then replace with thyroxine.
TSH 8.4, Free T4 11.7, Thyroid peroxidase (thyroid antibodies) positive
Normal ranges TSH 0.33-4.5mU/L Free T3 (3.2-6.5pmol/L) Free T4 (10.2-22.0pmol/L) Thyroglobulin
Consistent with sub-clinical hypothyroidism with risk of later clinical hypothyroidism.
Subclinical Hypothyroidism – “compensated hypothyroidism”
– Normal T4 levels, but TSH level is elevated
– TPO may be used to predict later thyroid disease
– Unlikely to be cause of symptoms
– Treating will not change the symptoms, unless they have elevated cholesterol levels. There is evidence of an association between subclinical hypothyroidism and hypercholestrolaemia, and these patients do benefit from treatment.
TSH 1.4, Free T4 12.1
Normal ranges TSH 0.33-4.5mU/L Free T3 (3.2-6.5pmol/L) Free T4 (10.2-22.0pmol/L) Thyroglobulin
Consistent with euthyroid status in a patient complaining of tiredness.
Sick Euthyroid Syndrome - alteration in pituitary thyroid axis in non-thyroidal illness, normal physiology, not ‘thyroid symptomatic’
• any severe illness (e.g. sepsis): thyroid tries to shut down to lower BMR
• low T4 when severe
• high normal TSH, later decreased
• low T3 and reduced T3 action
TSH 22. 4, Free T4 6.3.
Normal ranges TSH 0.33-4.5mU/L Free T3 (3.2-6.5pmol/L) Free T4 (10.2-22.0pmol/L) Thyroglobulin
Consistent with clinical primary hypothyroidism
- Majority of cases: it is a problem with the thyroid gland itself.
- Hashimoto’s disease (auto-immune condition affecting thyroid)
- Atrophic (congential or later in life)
- Post Graves’ disease (RAI, surgery, natural history or thionamides)
- Presentation: low BMR, CVS (bradycardic), GIT (slows down, constipation), Resp muscles have receptors and so breathing becomes more laboured, repro (irregular periods, infertility), may develop visual problems in pituitary tumour involved.
- Weight gain with decreased REE and poor appetite, cole hands and feet
- Hyponatraemia (thyroxine is involved in sodium transport and reabsorption in the kidneys)
- Normocytic or macrocytic anaemia (if pernicious anaemia)
- Myxoedema, goitre
Make diagnosis: low free T4, elevated TSH
Treatment: levothyroxine to a normal range TSH (around 100mcg/day), no EBM for excessive T4 treatment: excess treatment can cause osteopenia and atrial fibrillation. No evidence for using T3 instead of T4
Measure antibodies to thyroid peroxidase (suggestive of AI cause for thyroid disease)
Think of other AI conditions (pernicious anaemia, coeliac, addisions, - adrenal anti-bodies, early morning cortisol)
Must do an ECG before starting thyroid treatment as thyroxine increases cardiac contractility so cardiac patients would be at risk of ischaemia
Thyroglobulin 254
Normal ranges TSH 0.33-4.5mU/L Free T3 (3.2-6.5pmol/L) Free T4 (10.2-22.0pmol/L) Thyroglobulin
To screen for recurrence of differentiated thyroid carcinoma.
Thyroglobulin in the serum can be used to indicate if the thyroid cancer has come back – very sensitive. Measure thyrobulin when TSH is still elevated and later in life. Thyroglobulin indicates functioning thyroid tissue and therefore presence of the tumour cells.
Commonly associated with bradykinesia and rigidity
Pill rolling tremor Huntingtons Chorea Sydenhams chorea Benign essential tremor Intention tremor Spastic paraparesis
Pill rolling tremor: Parkinson’s disease is characterised by bradykinesia, rigidity and a pill rolling tremor of 4 – 7 Hz.
Lewy Bodies are found at postmortem, and dopamine levels are reduced in the substantia nigra.
Antiemetics and neuroleptics are dopamine antagonists, and as such cause a pill rolling tremor.
Lewy Bodies are found in post mortem brains in patients who have this movement disorder
Pill rolling tremor Huntingtons Chorea Sydenhams chorea Benign essential tremor Intention tremor Spastic paraparesis
Pill rolling tremor: Parkinson’s disease is characterised by bradykinesia, rigidity and a pill rolling tremor of 4 – 7 Hz.
Lewy Bodies are found at postmortem, and dopamine levels are reduced in the substantia nigra.
Antiemetics and neuroleptics are dopamine antagonists, and as such cause a pill rolling tremor.
Dominantly inherited
Pill rolling tremor Huntingtons Chorea Sydenhams chorea Benign essential tremor Intention tremor Spastic paraparesis
Huntingdon's Chorea: Huntington’s disease is dominantly inherited. Huntington disease (HD) is caused by expansion of the cytosine-adenine-guanine (CAG) trinucleotide repeats in the HTT gene (also known as the HD or IT15 gene) located on chromosome 4p16.3 that encodes the protein huntingtin. The disease is transmitted in an autosomal dominant manner. Individuals with early-onset HD tend to have a large number of CAG repeats, while those developing HD late in life typically have a low repeat number. The most common presenting symptom of HD in adults is chorea (hence the name Huntington chorea). Other usual findings at presentation include memory deficits, affective disturbances, personality changes, and other manifestations of motor dysfunction such as parkinsonism and dystonia. Patients with juvenile-onset HD have minimal or no chorea, but develop myoclonus and seizures as well as cognitive and behavioral problems. Children also have a more rapidly progressive disease.
Occurs following an infection
Pill rolling tremor Huntingtons Chorea Sydenhams chorea Benign essential tremor Intention tremor Spastic paraparesis
Sydenham’s Chorea: Rheumatic fever occurs about a month after a streptococcal sore throat.
Sydenham’s chorea (also known as St Vitus’ dance) is a major criterion of acute rheumatic fever, and is now known to be mediated by the immune system.
In which of the above is the Substantia Nigra affected?
Pill rolling tremor Huntingtons Chorea Sydenhams chorea Benign essential tremor Intention tremor Spastic paraparesis
Pill rolling tremor: Parkinson’s disease is characterised by bradykinesia, rigidity and a pill rolling tremor of 4 – 7 Hz.
Lewy Bodies are found at postmortem, and dopamine levels are reduced in the substantia nigra.
Antiemetics and neuroleptics are dopamine antagonists, and as such cause a pill rolling tremor.
Which of the above movement disorders is caused by antiemetics and neuroleptics?
Pill rolling tremor Huntingtons Chorea Sydenhams chorea Benign essential tremor Intention tremor Spastic paraparesis
Pill rolling tremor: Parkinson’s disease is characterised by bradykinesia, rigidity and a pill rolling tremor of 4 – 7 Hz.
Lewy Bodies are found at postmortem, and dopamine levels are reduced in the substantia nigra.
Antiemetics and neuroleptics are dopamine antagonists, and as such cause a pill rolling tremor.
The movement disorder that occurs in Rheumatic fever?
Pill rolling tremor Huntingtons Chorea Sydenhams chorea Benign essential tremor Intention tremor Spastic paraparesis
Sydenham’s Chorea: Rheumatic fever occurs about a month after a streptococcal sore throat.
Sydenham’s chorea (also known as St Vitus’ dance) is a major criterion of acute rheumatic fever, and is now known to be mediated by the immune system.
The movement disorder that occurs in Parkinson’s disease?
Pill rolling tremor Huntingtons Chorea Sydenhams chorea Benign essential tremor Intention tremor Spastic paraparesis
Pill rolling tremor: Parkinson’s disease is characterised by bradykinesia, rigidity and a pill rolling tremor of 4 – 7 Hz.
Lewy Bodies are found at postmortem, and dopamine levels are reduced in the substantia nigra.
Antiemetics and neuroleptics are dopamine antagonists, and as such cause a pill rolling tremor.
The movement disorder that is improved by alcohol?
Pill rolling tremor Huntingtons Chorea Sydenhams chorea Benign essential tremor Intention tremor Spastic paraparesis
A benign essential tremor is improved by alcohol.
The movement disorder that is caused by long term alcohol abuse?
Pill rolling tremor Huntingtons Chorea Sydenhams chorea Benign essential tremor Intention tremor Spastic paraparesis
Cerebellar atrophy occurs in long term alcohol abuse, resulting in an intention tremor.
The movement disorder mediated by the immune system?
Pill rolling tremor Huntingtons Chorea Sydenhams chorea Benign essential tremor Intention tremor Spastic paraparesis
Sydenham’s Chorea: Rheumatic fever occurs about a month after a streptococcal sore throat.
Sydenham’s chorea (also known as St Vitus’ dance) is a major criterion of acute rheumatic fever, and is now known to be mediated by the immune system.
Phagocytes:
Mediated by Toll like receptors which recognise PAMP
Oxidative killing
Pathogen recognition
Opsonsation
Non-oxidative killing
Pathogen recognition
Phagocytes:
May be mediated by anti-bodies, complement components or acute phase proteins and facilitates phagocytosis
Oxidative killing
Pathogen recognition
Opsonsation
Non-oxidative killing
Opsonisation
Phagocytes:
Describes killing mediated by ROS generated by the action of NADPH oxidase complex
Oxidative killing
Pathogen recognition
Opsonsation
Non-oxidative killing
Oxidative killing
Phagocytes:
May be mediated by bactericidal enzymes such as lysozyme
Oxidative killing
Pathogen recognition
Opsonsation
Non-oxidative killing
Non-oxidative killing
Innate Immune System:
Derived from monocytes and resident in peripheral tissues
Neutrophils
NK cells
Dendritic Cells
Macrophages
Macrophages
Innate Immune System:
Polymorphonuclear cells capable of phagocytosing pathogens and killing by oxidative and non-oxidative mechanisms
Neutrophils
NK cells
Dendritic Cells
Macrophages
Neutrophils
Innate Immune System: Lymphocytes that express inhibitory receptors, capable of recognising HLA class I molecules and have cytotoxic capacity
Neutrophils
NK cells
Dendritic Cells
Macrophages
Natural Killer Cells
Innate Immune System:
Immature cells are adapted for pathogen recognition and uptake whilst mature cells are adapted for antigen presentation to prime T cells
Neutrophils
NK cells
Dendritic Cells
Macrophages
Dendritic Cells
Adaptive Immune System: Express receptors that recognise peptides usually derived from intracellular proteins and expressed on HLA class I molecules
Th1 cells
CD8 T cells
T follicular helper (Tfh) cells
T regulatory cells
CD8 T cells
Adaptive Immune System:
Subset of lymphocytes that express Foxp3 and CD25
Th1 cells
CD8 T cells
T follicular helper (Tfh) cells
T regulatory cells
T regulatory cells
Adaptive Immune System:
Subset of cells that express CD4 and secrete IFN gamma and IL-2
Th1 cells
CD8 T cells
T follicular helper (Tfh) cells
T regulatory cells
Th1 cells
Adaptive Immune System:
Play an important role in promoting germinal centre reactions and differentiation of B cells into IgG and IgA secreting plasma cells
Th1 cells
CD8 T cells
T follicular helper (Tfh) cells
T regulatory cells
T follicular helper (Tfh) cells
Adaptive Immune System:
Exist with the bone marrow and develop from haematopoietic stem cells
Pre-B cells
IgA
IgG secreting plasma cells
IgM secreting plasma cells
Pre-B cells
Adaptive Immune System:
Cell dependent on the presence of CD4 T cell help for generation
Pre-B cells
IgA
IgG secreting plasma cells
IgM secreting plasma cells
IgG secreting plasma cells
Adaptive Immune System:
Are generated rapidly following antigen recognition and are not dependent on CD4 T cell help
Pre-B cells
IgA
IgG secreting plasma cells
IgM secreting plasma cells
IgM secreting plasma cells
Adaptive Immune System:
Divalent anti-body present within a mucous with helps to provide a constitutive barrier to infection
Pre-B cells
IgA
IgG secreting plasma cells
IgM secreting plasma cells
IgA
Area within secondary lymphoid tissue where B cells proliferate and undergo affinity maturation and isotope switching
Primary Lymphoid organs
Thoracic duct
Thymus
Germinal centre
Germinal centre
Include both the bone marrow and thymus; sites of B and T cell development
Primary Lymphoid organs
Thoracic duct
Thymus
Germinal centre
Primary Lymphoid organs
Carries lymphocytes from lymph nodes back to the blood circulation
Primary Lymphoid organs
Thoracic duct
Thymus
Germinal centre
Thoracic duct
Site of deletion of T cells with inappropriately high or low affinity for HLA molecules and of maturation of T cells into CD4+ or CD8+ cells
Primary Lymphoid organs
Thoracic duct
Thymus
Germinal centre
Thymus
What is the commonest form of prion disease?
Kuru Iatrogenic CJD Sporadic CJD Variant CJD Gerstmann-Straussler Scheinker syndrome
Sporadic CJD
Prion diseases are a protein-only infectious agent causing rapid neurodegeneration and are currently untreatable. Prion protein gene is on chr20 (codon 129 polymorphism, MM, MV, VV). Sporadic CJD = 80%
Acquired = <5% (kuru, vCJD, iatrogenic (blood, surgery, GH)
Genetic = 15% PRNP mutations (Gerstmann-Sträussler-Scheinker syndrome (GSS), fatal familial insomnia (FFI).
Sporadic CJD causes rapid dementia with myoclonus, cortical blindness, akinetic mutism & LMN signs. Mean onset 65 years, death with 6/12. Cause uncertain.
Diagnosis: EEG = periodic, triphasic complexes (nonspecific), MRI basal ganglia (increased signal cortical/striatal signal change on DWI MRI), CSF markers 14-3-3 protein (S100) may be elevated, Neurogenetics to rule out genetic cause, Tonsilar biopsy NOT useful
A 10-year-old boy is brought by his mother to your clinic. He is very thin, but has a distended abdomen. What is it that his diet does not contain enough of to cause this?
A. Folate B. Lipid C. Thiamine D. Carbohydrate E. Vitamin C F. Protein G. Vitamin A H. Vitamin D I. Niacin J. Fluoride K. Iron L. Zinc M. Copper N. Vitamin K O. Riboflavin P. Iodine
Protein
Kwashiorkor is characterized by marked muscle atrophy with normal or increased body fat and the presence of peripheral edema (anasarca). Edema is the defining characteristic for diagnosis. Inadequate protein and energy intake may contribute to the clinical features of kwashiorkor, but the pathogenesis is not fully understood. Anorexia is almost universal. Physical examination findings include:
●Normal or nearly normal weight and height for age
●Anasarca (severe generalized edema)
●Pitting edema in the lower extremities, presacral area, genitalia, and periorbitally
●Apathetic, listless affect
●Rounded prominence of the cheeks (“moon-face”)
●Pursed appearance of the mouth
●Dry, atrophic, peeling skin with confluent areas of hyperkeratosis and hyperpigmentation
●Dry, dull, hypopigmented hair that falls out or is easily plucked
●Hepatomegaly (from fatty liver infiltrates)
●Distended abdomen with dilated intestinal loops, but no ascites
●Hypothermia
Intermittent periods of adequate dietary intake restores hair color, resulting in alternating loss of hair color interspersed between bands of normal pigmentation (flag sign)
A 50-year-old homeless man walks into A and E. He is very thin, smells of alcohol and is vomiting. On neurological examination, you note he has nystagmus and walks with a broad based gait. You give him advice on how to stop drinking, what else would you give?
A. Folate B. Lipid C. Thiamine D. Carbohydrate E. Vitamin C F. Protein G. Vitamin A H. Vitamin D I. Niacin J. Fluoride K. Iron L. Zinc M. Copper N. Vitamin K O. Riboflavin P. Iodine
Thiamine (vitamin B1)
Thiamine deficiency has been associated with three disorders:
●Beriberi (infantile and adult)
●Wernicke-Korsakoff syndrome
●Leigh’s syndrome
Wernicke-Korsakoff syndrome is the best known neurologic complication of thiamine deficiency. Wernicke’s encephalopathy (WE) is an acute syndrome requiring emergent treatment to prevent death and neurologic morbidity. Korsakoff’s syndrome (KS) refers to a chronic neurologic condition that usually occurs as a consequence of WE. It is characterized by impaired short-term memory and confabulation with otherwise grossly normal cognition.
WE is a triad of nystagmus, ophthalmoplegia, and ataxia, along with confusion. This combination is almost exclusively described in chronic alcoholics with thiamine deficiency. The two entities are not separate diseases, but a spectrum of signs and symptoms. There may be a genetic predisposition for the development of WE since not all thiamine deficient patients are affected. Impairment in the synthesis of one of the important enzymes of the pentose phosphate pathway (erythrocyte transketolase) may explain such a predisposition. WE is treated with thiamine supplementation.It is common practice to delay giving dextrose to alcoholic patients until thiamine supplementation has been initiated to avoid precipitating Wernicke’s encephalopathy.
You see a young boy in your clinic. He complains of bone pain and he says he has felt unwell for a few weeks. On examination he is knock-kneed and walks with a waddling gait. What would you be most likely to treat him with?
A. Folate B. Lipid C. Thiamine D. Carbohydrate E. Vitamin C F. Protein G. Vitamin A H. Vitamin D I. Niacin J. Fluoride K. Iron L. Zinc M. Copper N. Vitamin K O. Riboflavin P. Iodine
Vitamin D
Rickets refers to deficient mineralization at the growth plate, as well as architectural disruption of this structure. Osteomalacia refers to impaired mineralization of the bone matrix. Rickets and osteomalacia usually occur together as long as the growth plates are open; only osteomalacia occurs after the growth plates have fused.
Calcipenic rickets usually is caused by dietary deficiency of vitamin D and/or calcium; this is the most common cause of rickets worldwide. Rarely, it is caused by genetic defects in vitamin D metabolism or action leading to vitamin D resistance.
Phosphopenic rickets in children and adolescents is almost always caused by renal phosphate wasting, which is usually an isolated phenomenon, but may be part of a generalized tubular disorder such as Fanconi syndrome, or may rarely result from inadequate dietary phosphorus or intestinal malabsorption.
The skeletal findings are similar for calcipenic and phosphopenic rickets, and may include delayed closure of the fontanelles, parietal and frontal bossing, enlargement of the costochondral junction (“rachitic rosary”), widening of the wrist, and lateral bowing of the femur and tibia (bow legs).
The concentration of serum alkaline phosphatase is elevated in both types of rickets, and it is a good marker of disease activity. Other biochemical findings include hypocalcemia and hypophosphatemia, but the pattern varies depending on the type and severity of the rickets (table 1). Serum concentration of parathyroid hormone (PTH) typically is elevated in calcipenic rickets, but not in phosphopenic rickets.
A 16-year-old girl presents with pain in her joints and her mother says that she has become increasingly forgetful over recent times. Last week she put a pan of water on the stove and forgot about it until it boiled dry and melted the pan. On examination you notice Kayser-Fleischer rings in the eyes. What substance is this girl most likely to handle abnormally?
A. Folate B. Lipid C. Thiamine D. Carbohydrate E. Vitamin C F. Protein G. Vitamin A H. Vitamin D I. Niacin J. Fluoride K. Iron L. Zinc M. Copper N. Vitamin K O. Riboflavin P. Iodine
Copper
Wilson disease (hepatolenticular degeneration) is due to a AR genetic abnormality that leads to impairment of cellular copper transport. Impaired biliary copper excretion leads to accumulation in several organs, (liver, brain, & cornea). Over time, the liver is progressively damaged and eventually becomes cirrhotic. The clinical manifestations of Wilson disease are predominantly hepatic, neurologic, and psychiatric, with many patients having a combination of symptoms. The majority of patients with Wilson disease are diagnosed between the ages of 5 and 35 years. Children most often initially present with liver disease, at an average age of 9 to 13 years, with Wilson disease accounting for 8 to 10 percent of chronic active hepatitis in children. Unlike children, who are more likely to present with hepatic manifestations, older patients (mid-teens and older) are more likely to present with neurologic manifestations. The mean age at presentation for patients with neurologic symptoms ranges between 15 and 21 years.
Signs and symptoms of Wilson disease may include:
●Kayser-Fleischer rings, visible in 50 percent of patients with hepatic disease (seen with all forms of liver involvement)
●Asymptomatic (steatosis, chronic hepatitis, compensated cirrhosis)
●Abdominal pain (acute hepatitis, acute liver failure)
●Jaundice (acute hepatitis, acute liver failure, cirrhosis)
●Hepatomegaly (acute and chronic hepatitis, acute liver failure)
●Splenomegaly (cirrhosis)
●Ascites (cirrhosis)
●Upper gastrointestinal bleeding (cirrhosis with varices or portal hypertensive gastropathy)
●Peripheral stigmata of chronic liver disease (cirrhosis)
●Mental status changes due to hepatic encephalopathy (acute liver failure, cirrhosis)
Laboratory test findings may include:
●Low level of serum ceruloplasmin (seen with all forms of liver involvement, though less likely with acute liver failure)
●Elevated aminotransferases (all forms of liver involvement)
●Thrombocytopenia (cirrhosis with splenomegaly)
●Coagulopathy (cirrhosis or acute liver failure)
●Coombs-negative hemolytic anemia (often seen in conjunction with acute liver failure)
Two main categories of cognitive impairment: a frontal syndrome and subcortical dementia, with some patients having features of both.
Cognitive impairment: the findings can be subtle and may only be recognized retrospectively.
Patients with a frontal syndrome may demonstrate impulsivity, promiscuity, impaired judgement, apathy, executive dysfunction (poor planning and decision making), decreased attention, and emotional lability. When severe, patients may have pseudobulbar features (sudden outbursts of inappropriate laughter or tearfulness).
Findings in subcortical dementia include slowed thinking, memory loss, and executive dysfunction. It lacks cortical signs such as aphasia, apraxia, or agnosia.
A 40-year-old woman is brought in by her husband. He explains that she has started getting up during the night and going for walks and then forgetting her way home. She says she has terrible diarrhoea day and night and she wakes to go to the toilet. On examination she has a tremor and you see red scaly patches on her skin. Which vitamin is she most likely to be deficient in?
A. Folate B. Lipid C. Thiamine D. Carbohydrate E. Vitamin C F. Protein G. Vitamin A H. Vitamin D I. Niacin J. Fluoride K. Iron L. Zinc M. Copper N. Vitamin K O. Riboflavin P. Iodine
Niacin
Pellagra is a rare but is still a common manifestation of niacin deficiency in poorer countries where the local diet consists of cereal, corn, or sorghum. In industrialized countries, pellagra tends to occur in alcoholics, and has been reported as a complication of bariatric surgery or anorexia nervosa.
The most characteristic finding is the presence of a symmetric hyperpigmented rash, similar in color to a sunburn, which is present in the exposed areas of skin. Other clinical findings are a red tongue and many non-specific symptoms, such as diarrhea and vomiting. Neurologic symptoms include insomnia, anxiety, disorientation, delusions, dementia, and encephalopathy.
Niacin deficiency can also be seen in three other settings:
●Carcinoid syndrome, in which metabolism of tryptophan is to 5-OH tryptophan and serotonin rather than to nicotinic acid. This leads to the deficiency of active forms of niacin and the development of pellagra.
●Prolonged use of isoniazid,(depletes stores of pyridoxal phosphate, which enhances the production of tryptophan, a precursor of niacin). Several other drugs induce niacin deficiency by inhibiting the conversion of tryptophan to niacin, including 5-fluorouracil, pyrazinamide, 6-mercaptopurine, hydantoin, ethionamide, phenobarbital, azathioprine, and chloramphenicol.
●Hartnup disease (MIM #234500), AR congenital disorder. Hartnup disease is associated with a defect of a membrane transport in the intestinal and renal cells normally responsible for the absorption of tryptophan (one of the precursors of nicotinamide-adenine dinucleotide). Through this pathway, around 50 percent of the daily niacin needs are synthesized. Due to the resulting niacin deficiency, all the symptoms of pellagra can be expected. The diagnosis is made by detecting a number of neutral amino acids in the urine, something that is not seen with dietary pellagra.
pH 6.9 bicarbonate 7.0
A. Metabolic alkalosis B. Respiratory alkalosis C. Compensated metabolic acidosis D. Compensated respiratory acidosis E. Respiratory acidosis F. Metabolic acidosis
Metabolic acidosis
Metabolic acidosis if unopposed, results in a reduction of the serum bicarbonate concentration (normal is 24 meq/L, with a normal range of 22 to 28 meq/L) and a low arterial pH (normal 7.4, with a normal range of 7.35 to 7.45). Acidemia (as opposed to acidosis) is defined as a low arterial pH (
pH 6.9 bicarbonate 26
A. Metabolic alkalosis B. Respiratory alkalosis C. Compensated metabolic acidosis D. Compensated respiratory acidosis E. Respiratory acidosis F. Metabolic acidosis
Respiratory acidosis - disorder that elevates the arterial PCO2 and reduces the pH.
No alteration to bicarb indicates no compensation has occurred
pH 7.6 bicarbonate 30
A. Metabolic alkalosis B. Respiratory alkalosis C. Compensated metabolic acidosis D. Compensated respiratory acidosis E. Respiratory acidosis F. Metabolic acidosis
Metabolic alkalosis: relatively common clinical problem that is most often induced by diuretic therapy or the loss of gastric secretions due to vomiting or nasogastric suction.
The development and subsequent maintenance of metabolic alkalosis requires two separate abnormalities:
1. An elevation in the plasma bicarbonate concentration due to excessive hydrogen loss in the urine or gastrointestinal tract, hydrogen movement into the cells, the administration of bicarbonate, or volume contraction around a relatively constant amount of extracellular bicarbonate (called a contraction alkalosis).
2. A decrease in net renal bicarbonate excretion (due to enhanced reabsorption and reduced secretion or markedly reduced renal function) since rapid excretion of the excess bicarbonate (primarily as sodium bicarbonate) would otherwise correct the alkalosis
Several factors are responsible for increased net renal bicarbonate reabsorption in metabolic alkalosis. In the absence of advanced renal failure, one or more of these factors must be present to sustain the high plasma bicarbonate concentration:
●A reduction in ECF volume or reduced effective arterial blood volume, which develops in many edematous states such as congestive heart failure and cirrhosis.
●Chloride depletion and hypochloremia.
●Hypokalemia.
●Increased distal tubule delivery and reabsorption of sodium in exchange for hydrogen ions and potassium.
pH 7.6 bicarbonate 14
A. Metabolic alkalosis B. Respiratory alkalosis C. Compensated metabolic acidosis D. Compensated respiratory acidosis E. Respiratory acidosis F. Metabolic acidosis
Respiratory alkalosis
The initial acute response is generated by a variety of pH buffering molecules present in all of the fluid compartments of the body (ie, total body buffering). Reactions with these molecules cause the serum HCO3 to increase (in respiratory acidosis) or decrease (in respiratory alkalosis) within minutes. The acute response is relatively modest.
pH7.1 bicarbonate 4.0
A. Metabolic alkalosis B. Respiratory alkalosis C. Compensated metabolic acidosis D. Compensated respiratory acidosis E. Respiratory acidosis F. Metabolic acidosis
Compensated metabolic acidosis
Compensation means improving the pH (towards 7.4) at the expense of worsening the bicarbonate or CO2.
The development of metabolic acidosis will normally generate a compensatory respiratory response. The reduction in the serum bicarbonate and pH caused by the metabolic acidosis results in hyperventilation and a reduction of the pCO2. The Henderson-Hasselbalch equation shows that the pH is determined by the ratio between the HCO3 concentration and pCO2. Thus, this fall in pCO2 will partially mitigate the fall in pH caused by a reduced HCO3.
pH 7.1 bicarbonate 45
A. Metabolic alkalosis B. Respiratory alkalosis C. Compensated metabolic acidosis D. Compensated respiratory acidosis E. Respiratory acidosis F. Metabolic acidosis
Compensated respiratory acidosis
Compensation means improving the pH (towards 7.4) at the expense of worsening the bicarbonate or CO2. By
Which is secreted by the zona glomerulosa?
A. Oestradiol B. Adrenaline C. Cortisol D. Renin E. Nor adrenaline F. Corticotrophin (ACTH) G. Aldosterone H. Histamine I. Testosterone J. Gastrin
Aldosterone: steroid hormone (mineralocorticoid family) produced by the outer section (zona glomerulosa) of the adrenal cortex in the adrenal gland.It plays a central role in the regulation of blood pressure mainly by acting on the distal tubules and collecting ducts of the nephron, increasing reabsorption of ions and water in the kidney, to cause the conservation of sodium, secretion of potassium, increase in water retention, and increase in blood pressure and blood volume. When dysregulated, aldosterone is pathogenic and contributes to the development and progression of cardiovascular and renal disease. Aldosterone has exactly the opposite function of the atrial natriuretic hormone secreted by the heart.
Drugs that interfere with the secretion or action of aldosterone are in use as antihypertensives, like lisinopril, which lowers blood pressure by blocking the angiotensin-converting enzyme (ACE), leading to lower aldosterone secretion. The net effect of these drugs is to reduce sodium and water retention but increase retention of potassium. Aldosterone is part of the renin-angiotensin system. Another example is spironolactone, a potassium-sparing diuretic, which decreases blood pressure by releasing fluid from the body while retaining potassium.
Which is secreted by the zona fasciculata?
A. Oestradiol B. Adrenaline C. Cortisol D. Renin E. Nor adrenaline F. Corticotrophin (ACTH) G. Aldosterone H. Histamine I. Testosterone J. Gastrin
Cortisol: steroid hormone, more specifically a glucocorticoid, which is produced by the zona fasciculata of the adrenal cortex. It is released in response to stress and a low level of blood glucose.
Its functions are to increase blood sugar through gluconeogenesis, to suppress the immune system, and to aid the metabolism of fat, protein, and carbohydrate. It also decreases bone formation.
High levels of which of the above is associated with hyper pigmentation?
A. Oestradiol B. Adrenaline C. Cortisol D. Renin E. Nor adrenaline F. Corticotrophin (ACTH) G. Aldosterone H. Histamine I. Testosterone J. Gastrin
Corticotrophin (ACTH): Adrenocorticotropic hormone is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the HPA and is often produced in response to biological stress (along with its precursor CRH from the hypothalamus). Its principal effects are increased production and release of corticosteroids. Primary adrenal insufficiency, also called Addison’s disease, occurs when adrenal gland production of cortisol is chronically deficient, resulting in chronically elevated ACTH levels; when a pituitary tumor is the cause of elevated ACTH (from the anterior pituitary) this is known as Cushing’s Disease and the constellation of signs and symptoms of the excess cortisol (hypercortisolism) is known as Cushing’s syndrome. A deficiency of ACTH is a cause of secondary adrenal insufficiency.
ACTH is synthesized from pre-pro-opiomelanocortin (pre-POMC) and undergoes cleavage, producing ACTH & MSH
Which binds to alpha, beta 1 and beta 2 adrenoreceptors?
A. Oestradiol B. Adrenaline C. Cortisol D. Renin E. Nor adrenaline F. Corticotrophin (ACTH) G. Aldosterone H. Histamine I. Testosterone J. Gastrin
Adrenaline: a hormone and neurotransmitter that acts on nearly all body tissues. Its actions vary by tissue type and tissue expression of adrenergic receptors. For example, high levels of epinephrine causes smooth muscle relaxation in the airways but causes contraction of the smooth muscle that lines most arterioles.
Epinephrine is a nonselective agonist of all adrenergic receptors, including the major subtypes α1, α2, β1, β2, and β3. Epinephrine’s binding to these receptors triggers a number of metabolic changes. Binding to α-adrenergic receptors inhibits insulin secretion by the pancreas, stimulates glycogenolysis in the liver and muscle, and stimulates glycolysis in muscle. β-Adrenergic receptor binding triggers glucagon secretion in the pancreas, increased adrenocorticotropic hormone (ACTH) secretion by the pituitary gland, and increased lipolysis by adipose tissue. Together, these effects lead to increased blood glucose and fatty acids, providing substrates for energy production within cells throughout the body.
The adult dose for refractory anaphylactic shock is usually 1 mg (1:10,000) IV/IO over 5 min and for cardiac arrest 1 mg (1:10,000) as an IV/IO push.
Reflects genetic abnormality affecting the innate immune system, often in a site-specific manner
Immunopathology Auto-Immune Disease Auto-Inflammatory Disease Familial Mediterranean Fever IPEX (Immune dysregulation, polyendocrinopathy, enteropathy, X-linked)
Auto-Inflammatory Disease: patients with autoinflammatory diseases do not produce autoantibodies or antigen-specific T or B cells. Instead, the autoinflammatory diseases are characterized by errors in the innate immune system.
The syndromes are diverse, but tend to cause episodes of fever, joint pains, skin rashes, abdominal pains and may lead to chronic complications such as amyloidosis.
Most autoinflammatory diseases are genetic and present during childhood. The most common genetic autoinflammatory syndrome is familial Mediterranean fever, which causes short episodes of fever, abdominal pain, serositis, lasting less than 72 hours. It is caused by mutations in the MEFV gene, which codes for the protein pyrin.
Single gene mutation involving MEFV and affecting the inflammasome complex, resulting in recurrent episodes of serositis
Immunopathology Auto-Immune Disease Auto-Inflammatory Disease Familial Mediterranean Fever IPEX (Immune dysregulation, polyendocrinopathy, enteropathy, X-linked)
Familial Mediterranean Fever: a disorder characterized by sporadic attacks of fever and serosal inflammation.
Most patients with FMF experience their first attack in early childhood; in 65 percent of cases, the initial attack occurs before the age of 10, and in 90 percent before the age of 20. The typical manifestations of the disease are recurrent attacks of severe pain (due to serositis at one or more sites) and fever, lasting one to three days, and then resolving spontaneously. In between attacks, patients feel entirely well. Acute attacks of FMF are accompanied by elevation in many of the serum markers of systemic inflammation (ESR, beta-2 microglobulin, CRP, SAA (serum amyloid protein), and fibrinogen). The diagnosis is usually made on clinical grounds and a response to colchicine. Genetic testing is also available but an appreciable proportion of patients with clinical FMF have only one or no MEFV mutations.
May describe damage resulting from the immune response to on-going infection
Immunopathology Auto-Immune Disease Auto-Inflammatory Disease Familial Mediterranean Fever IPEX (Immune dysregulation, polyendocrinopathy, enteropathy, X-linked)
Immunopathology
Reflects genetic abnormality affecting the adaptive immune system, and is often associated with the presence of auto-antibodies
Immunopathology Auto-Immune Disease Auto-Inflammatory Disease Familial Mediterranean Fever IPEX (Immune dysregulation, polyendocrinopathy, enteropathy, X-linked)
Auto-Immune Disease: pathologic condition caused by an adaptive autoimmune response, an immune response directed against an antigen within the body of the host, termed a self-antigen. The response may be induced by a foreign or self antigen. It usually involves a T-cell and B-cell response This may be restricted to certain organs (e.g. in autoimmune thyroiditis) or involve a particular tissue in different places (e.g. Goodpasture’s disease which may affect the basement membrane in both the lung and the kidney).
The treatment of autoimmune diseases is typically with immunosuppression—medication that decreases the immune response.
Diseases in which there is chronic inflammation but no evidence of autoreactive T cells or B cells, termed autoinflammatory diseases, are associated with the innate immune response.
Single gene mutation involving FOXp3 resulting in abnormality of T reg cells
Immunopathology Auto-Immune Disease Auto-Inflammatory Disease Familial Mediterranean Fever IPEX (Immune dysregulation, polyendocrinopathy, enteropathy, X-linked)
IPEX (Immune dysregulation, polyendocrinopathy, enteropathy, X-linked): is a rare and potentially fatal autoimmune lymphoproliferative disorder in which regulatory T cells (Tregs) are quantitatively or functionally deficient. These defects are caused by various mutations in FOXP3, a transcription factor fundamental to the functional differentiation of Treg cells. IPEX classically presents in male infants with a triad of enteropathy, dermatitis, and autoimmune endocrinopathy (usually type 1 diabetes or thyroiditis). Some patients have severe food allergy and/or immune-mediated cytopenias. IPEX is due to loss of function mutations in FOXP3. These mutations result in quantitative or functional deficiencies of Treg cells and thereby cause autoimmune disease and allergic inflammation. A large number of mutations have been described, many of which are familial, although sporadic cases have been reported
Polygenic Auto-inflammatory disease. Estimated 30% of patients have a mutation of CARD15 which may affect response of myeloid cells to bacteria
Crohn’s disease
Ankylosing spondylitis
Giant cell arteritis
Crohn’s Disease: disorder of uncertain etiology that is characterized by transmural inflammation of the gastrointestinal tract. CD may involve the entire gastrointestinal tract from mouth to the perianal area. Fatigue, prolonged diarrhea with abdominal pain, weight loss, and fever, with or without gross bleeding, are the hallmarks of CD. Patients can present with symptoms secondary to the transmural involvement of the bowel, including fistulas, phlegmon, abscess, perianal disease, and/or malabsorption. Extraintestinal manifestations, such as arthritis, eye and skin disorders, biliary tract involvement, and kidney stones may occur and tend to be more frequent with colonic involvement. The diagnosis of CD is established with endoscopic and imaging studies of the bowel in a patient with a compatible clinical history. Colonoscopy with intubation of the terminal ileum is used to establish the diagnosis of ileocolonic CD. We perform an MR enterography as the initial test to evaluate the small intestine. Wireless capsule endoscopy may also be useful for detecting small bowel involvement.
CARD15 or inflammatory bowel disease protein 1 (IBD1) is a protein that is encoded by the NOD2 gene located on chromosome 16. NOD2 plays an important role in the immune system. It recognizes bacterial molecules (peptidoglycans) and stimulates an immune reaction.
Mixed pattern auto-inflammatory disease/auto-immune disease with >90% heritability that results in inflammation, typically involving the sacra-iliac joints and responds to TNF alpha antagonists
Crohn’s disease
Ankylosing spondylitis
Giant cell arteritis
Ankylosing spondylitis: a form of spondyloarthritis (SpA - a family of disorders characterized by inflammation around the entheses (the sites of ligament insertion into bone) and an association with the human leukocyte antigen (HLA)-B27)), is a chronic inflammatory disease of the axial skeleton manifested by back pain and progressive stiffness of the spine; it can also involve the hips, shoulders, and peripheral joints.
The symptoms of AS include inflammatory back pain, buttock pain, limited spinal mobility, limited chest expansion, hip and shoulder pain, and enthesitis. Patients may have peripheral arthritis, dactylitis, and constitutional features. Inflammatory low back pain is characterized by age of onset
Polygenic auto-inflammatory disease resulting in a large vessel vasculitis and requiring immediate treatment with high dose corticosteroids
Crohn’s disease
Ankylosing spondylitis
Giant cell arteritis
Giant cell arteritis: chronic vasculitis of large- and medium-sized vessels. The mean age at diagnosis is approximately 72 years, and the disease essentially never occurs in individuals younger than 50. GCA is characteristically a systemic illness and although vascular involvement may be widespread, symptomatic blood vessel inflammation most frequently involves the cranial branches of the arteries that originate from the aortic arch. The most feared complication of GCA, visual loss, is one potential result of the cranial arteritis associated with this disease. Consider if: new headache, Abrupt onset of visual disturbances, Symptoms of PMR, Unexplained fever or anemia, Elevated ESR and/or serum CRP. Temporal artery biopsy is the gold standard for the diagnosis of GCA.
Tyrosine phosphatase expressed in lymphocytes associated with development of auto-immune disease, including rheumatoid arthritis
HLA DR4
PTPN22
HLA DR15
CTLA4
PTPN22: The protein tyrosine phosphatase N22 (PTPN22) gene helps regulate both T and B cells. The frequency of a single nucleotide polymorphism (SNP) in the gene was increased in RA patients
MHC class II molecule that is associated with development of auto-immune disease, including rheumatoid arthritis
HLA DR4
PTPN22
HLA DR15
CTLA4
HLA DR4: The DR4 “family” of alleles contains at least 22 members, only some of which are associated with RA.
Two alleles, DRB10401 and DRB10404, primarily account for the originally observed serological association of DR4 with rheumatoid arthritis (RA) in Caucasians. The most strongly associated RA alleles share a region of highly similar amino acid sequence, called the shared epitope, located at amino acids 67 to 74
Receptor for CD80/CD86, expressed on T cells, that influences T cell activation and is associated with auto-immune disease, including diabetes and thyroid disease
HLA DR4
PTPN22
HLA DR15
CTLA4
CTLA4 - also known as CD152, is a protein receptor that downregulates the immune system. CTLA4 is found on the surface of T cells, which lead the cellular immune attack on antigens. The T cell attack can be turned on by stimulating the CD28 receptor on the T cell. The T cell attack can be turned off by stimulating the CTLA4 receptor, which acts as an “off” switch.
The CTLA4 protein is encoded by the CTLA4 gene. CTLA4 is a member of the immunoglobulin superfamily, which is expressed on the surface of Helper T cells and transmits an inhibitory signal to T cells. CTLA4 is similar to the T-cell co-stimulatory protein, CD28, and both molecules bind to CD80 and CD86, also called B7-1 and B7-2 respectively, on antigen-presenting cells. CTLA4 transmits an inhibitory signal to T cells, whereas CD28 transmits a stimulatory signal. Intracellular CTLA4 is also found in regulatory T cells and may be important to their function.
Antigen presenting molecule that is strongly associated with the development of anti-GBM anti-bodies
HLA DR4
PTPN22
HLA DR15
CTLA4
HLA DR15: positively associated Goodpasture syndrome, early age onset multiple sclerosis, pernicious anaemia, sarcoidosis, hypocretin deficiency associated narcolepsy and a predisposition for postmenopausal osteoporosis.
T cell that expresses FoxP3 and CD25 and secretes cytokines IL-10 and TGF-beta to suppress activation of other T cells
Central tolerance of T cells
T reg cells
Central tolerance of B cells
T cell Anergy
T reg cells The dominant cytokines for Treg induction in humans are TGF-beta and IL-2. Induction of these cytokines leads to the activation of STAT5, which engages the transcription factor Foxp3. Treg secrete IL-10, TGF-beta, and IL-35. TGF-beta acts as the amplifying cytokine for Treg cells. T regulatory (Treg) cells represent a major subset of CD4+ T cells that may be involved in regulating and attenuating the activity of the three T helper subsets. T cells can be categorized based upon cell surface expression of CD4 or CD8. CD4+ cells recognize antigen presented in the context of class II major histocompatibility complex (MHC), while CD8+ cells recognize antigen presented in the context of class I MHC. CD4+ T helper subsets include T helper type 1 (Th1), T helper type 2 (Th2), and T helper type 17 (Th17) cells Th1 are pivotal in defense against intracellular microorganisms in general and mycobacteria in particular. Patients with mutations in the interferon-gamma (IFN-gamma) receptor or interleukin-12 (IL-12) receptor present with recurrent infections with mycobacteria and Salmonella. Th2 cells are integral in expelling parasitic infestations. Th17 seem to play a significant role in defense against extracellular bacteria and some fungi. Th1 and Th17 cells play major roles in autoimmunity, whereas Th2 cells are the hallmark of atopic disease.
Within the thymus cells that bind with low affinity to HLA molecules die by neglect and those that bind with a high affinity to HLA molecules are deleted
Central tolerance of T cells
T reg cells
Central tolerance of B cells
T cell Anergy
Central tolerance of T cells: T cells are selected for survival much more rigorously than B cells. They undergo both positive and negative selection to produce T cells that recognize self- major histocompatibility complex (MHC) molecules but do not recognize self-peptides. T cell tolerance is induced in the thymus.
Positive selection occurs in the thymic cortex. This process is primarily mediated by thymic epithelial cells, which are rich in surface MHC molecules. If a maturing T cell is able to bind to a surface MHC molecule in the thymus, it is saved from programmed cell death; those cells failing to recognize MHC on thymic epithelial cells will die.
T cells may also undergo negative selection in a process analogous to the induction of self-tolerance in B cells, this occurs in the cortex, at the cortico-medullary junction, and the medulla (mediated in the medulla predominately by medullary thymic epithelial cells (mTECs) and dendritic cells). mTEC display “self” antigens to developing T-cells and signal those “self-reactive” T-cells to die via programmed cell death (apoptosis) and thereby deleted from the T cell repertoire.
Regulatory T cells are another group of T cells maturing in the thymus, they are also involved with immune regulation but are not directly involved in central tolerance.
Genetic defects in central tolerance can lead to autoimmunity: Autoimmune Polyendocrinopathy Syndrome Type I (APECED) is caused by mutations in the human gene AIRE (chr21 - AR). This leads to a lack of expression of peripheral antigens in the thymus, and hence a lack of negative selection towards key peripheral proteins such as insulin. It is a mild immune deficiency, leading to persistent mucosal and cutaneous infections with candida yeasts. There is also decreased function of the spleen (hyposplenism).
Autoimmune dysfunction of the parathyroid gland (leading to hypocalcaemia) and the adrenal gland (Addison’s disease: hypoglycemia, hypotension and severe reactions in disease).
T cells that recognise HLA/peptide complexes on cells that do not express co-stimulatory molecules subsequently fail to respond to stimulation with antigen
Central tolerance of T cells
T reg cells
Central tolerance of B cells
T cell Anergy
T cell anergy. T-cell anergy can arise when the T-cell does not receive appropriate co-stimulation in the presence of specific antigen recognition. B-cell anergy can be induced by exposure to soluble circulating antigen, and is often marked by a downregulation of surface IgM expression and partial blockade of intracellular signaling pathways.
Cells that bind to polyvalent antigens in the bone marrow are deleted
Central tolerance of T cells
T reg cells
Central tolerance of B cells
T cell Anergy
Central tolerance of B cells: Tolerance is classified into central tolerance or peripheral tolerance depending on where the state is originally induced—in the thymus and bone marrow (central) or in other tissues and lymph nodes (peripheral). Central tolerance is the main way the immune system learns to discriminate self from non-self. Peripheral tolerance is key to preventing over-reactivity of the immune system to various environmental entities (allergens, gut microbes, etc.). Deficits in central or peripheral tolerance also cause autoimmune disease. Central tolerance refers to the tolerance established by deleting autoreactive lymphocyte clones before they develop into fully immunocompetent cells. It occurs during lymphocyte development in the thymus and bone marrow for T and B lymphocytes, respectively. In these tissues, maturing lymphocytes are exposed to self-antigens presented by medullary thymic epithelial cells and thymic dendritic cells, or bone marrow cells.
T cell mediated reaction to antigen
Type I hypersensitivity
Type II hypersensitivity
Type III hypersensitivity
Type IV hypersensitivity
Goodpasture Disease
Eczema
SLE
Multiple Sclerosis
Type IV hypersensitivity - Multiple sclerosis (oligodendrocyte proteins), diabetes (pancreatic beta cell antigens), allergic contact dermatitis (metals), RA (type II collagen), Hashimoto’s thyroiditis (thyroglobulin antigen)
Delayed hypersensitivity
Involves T cells and cytokines
Type IV reactions are not mediated by antibodies, in contrast to the other three types above. They involve the activation and expansion of T cells, which requires time (normally many hours or days after antigen exposure), hence the name delayed-type hypersensitivity (DTH). In some cases, other cell types (eg, macrophages, eosinophils, or neutrophils) are also involved. Type IV reactions can take many different forms, which vary in significance from inconvenient to life threatening.
CD4+ helper T cells recognize antigen in a complex with Class 2 major histocompatibility complex. The antigen-presenting cells in this case are macrophages that secrete IL-12, which stimulates the proliferation of further CD4+ Th1 cells. CD4+ T cells secrete IL-2 and interferon gamma, further inducing the release of other Th1 cytokines, thus mediating the immune response. Activated CD8+ T cells destroy target cells on contact, whereas activated macrophages produce hydrolytic enzymes and, on presentation with certain intracellular pathogens, transform into multinucleated giant cells.
Anti-bodies react with antigen form immune complexes that deposit, often causing vasculitic skin rash, glomerulonephritis and arthritis
Type I hypersensitivity
Type II hypersensitivity
Type III hypersensitivity
Type IV hypersensitivity
Goodpasture Disease
Eczema
SLE
Multiple Sclerosis
Type III hypersensitivity - SLE (nuclear antigens), serum sickness
Immune complex mediated hypersensitivity
Involves deposition of Ab/Ag complexes in tissue.
Occurs when there is an excess of antigen, leading to small immune complexes being formed that do not fix complement and are not cleared from the circulation. It involves soluble antigens that are not bound to cell surfaces (as opposed to those in type II hypersensitivity). When these antigens bind antibodies, immune complexes of different sizes form. Large complexes can be cleared by macrophages but macrophages have difficulty in the disposal of small immune complexes. These immune complexes insert themselves into small blood vessels, joints, and glomeruli, causing symptoms. Unlike the free variant, a small immune complex bound to sites of deposition (like blood vessel walls) are far more capable of interacting with complement; these medium-sized complexes, formed in the slight excess of antigen, are viewed as being highly pathogenic. Such depositions in tissues often induce an inflammatory response, and can cause damage wherever they precipitate. The cause of damage is as a result of the action of cleaved complement anaphylotoxins C3a and C5a, which, respectively, mediate the induction of granule release from mast cells (from which histamine can cause urticaria), and recruitment of inflammatory cells into the tissue (mainly those with lysosomal action, leading to tissue damage through frustrated phagocytosis by PMNs and macrophages)
Vasculitis, glomerulonephritis and arthritis are commonly associated conditions as a result of type III hypersensitivity responses.
Antibodies react with tissue antigens resulting in damage to the tissue
Type I hypersensitivity
Type II hypersensitivity
Type III hypersensitivity
Type IV hypersensitivity
Goodpasture Disease
Eczema
SLE
Multiple Sclerosis
Type II hypersensitivity - Goodpasture Disease, Graves Disease
Cytotoxic hypersensitivity
Involves anti-bodies binding to cells with complement mediated host cell destruction (or inhibition/activation or receptor signalling)
Often involves auto-immunity - the antibodies produced by the immune response bind to antigens on the patient’s own cell surfaces. The antigens recognized in this way may either be intrinsic (“self” antigen, innately part of the patient’s cells) or extrinsic (adsorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen). These cells are recognized by macrophages or dendritic cells, which act as antigen-presenting cells. This causes a B cell response, wherein antibodies are produced against the foreign antigen.
Examples include Red blood cells in Haemolytic Anaemia, Acetylcholine receptors in Myasthenia Gravis, and TSH receptors in Grave’s Disease. Another example of type II hypersensitivity reaction is Goodpasture’s syndrome where the basement membrane(containing collagen type IV) in the lung and kidney is attacked by one’s own antibodies
IgE mediated activation of mast cells leading to the release of substances including histamine, leukotrienes and prostaglandins. Reaction usually to foreign rather than self antigen
Type I hypersensitivity
Type II hypersensitivity
Type III hypersensitivity
Type IV hypersensitivity
Goodpasture Disease
Eczema
SLE
Multiple Sclerosis
Type I hypersensitivity - Eczema
Anaphylactic hypersensitivity - involves IgE and mast cells
Rarely auto-immunity
Anaphylaxis, atopic asthma
An allergic reaction provoked by reexposure to a specific type of antigen referred to as an allergen. In type 1 hypersensitivity, an antigen is presented to CD4+ Th2 cells specific to the antigen that stimulate B-cell production of IgE antibodies also specific to the antigen. The difference between a normal infectious immune response and a type 1 hypersensitivity response is that in type 1 hypersensitivity the antibody is IgE instead of IgA, IgG, or IgM. During sensitisation, the IgE antibodies bind to Fcε receptors on the surface of tissue mast cells and blood basophils. Mast cells and basophils coated by IgE antibodies are “sensitised.” Later exposure to the same allergen cross-links the bound IgE on sensitised cells, resulting in degranulation and the secretion of pharmacologically active mediators such as histamine, leukotriene (LTC4 and LTD4), and prostaglandin that act on the surrounding tissues. The principal effects of these products are vasodilation and smooth-muscle contraction.
Type 1 hypersensitivity can be further classified into an immediate and late-phase reaction. The immediate hypersensitivity reaction occurs minutes after exposure and includes release of vasoactive amines and lipid mediators, whereas the late-phase reaction occurs 2–4 hours after exposure and includes the release of cytokines
Binding of immune complexes to this protein triggers the classical pathway of complement activation
C3
C1
C9
MBL
C1 The classical pathway is triggered by activation of the C1-complex.
The following are the basic functions of complement:
Opsonization - enhancing phagocytosis of antigens
Chemotaxis - attracting macrophages and neutrophils
Cell Lysis - rupturing membranes of foreign cells
Agglutination- clustering and binding of pathogens together (sticking)
Cleavage of this protein may be triggered via the classical, MBL or alternative pathways
C3
C1
C9
MBL
C3 - It plays a central role in the complement system and contributes to innate immunity. In humans it is encoded on chromosome 19 by a gene called C3. Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are susceptible to bacterial infection.
In all three pathways, C3-convertase cleaves and activates component C3, creating C3a and C3b, and causing a cascade of further cleavage and activation events. C3b binds to the surface of pathogens, leading to greater internalization by phagocytic cells by opsonization. C5a is an important chemotactic protein, helping recruit inflammatory cells.
The following are the basic functions of complement:
Opsonization - enhancing phagocytosis of antigens
Chemotaxis - attracting macrophages and neutrophils
Cell Lysis - rupturing membranes of foreign cells
Agglutination- clustering and binding of pathogens together (sticking)
Binds to microbial surface carbohydrates to activate the complement cascade in an immune complex independent manner
C3
C1
C9
MBL
MBL: This pathway is activated by binding of MBL to mannose residues on the pathogen surface, which activates the MBL-associated serine proteases, MASP-1, and MASP-2 (very similar to C1r and C1s, respectively), which can then split C4 into C4a and C4b and C2 into C2a and C2b. C4b and C2a then bind together to form the classical C3-convertase, as in the classical pathway.
Part of the final common pathway resulting in the generation of the Membrane Attack Complex (MAC)
C3
C1
C9
MBL
C9 - protein involved in the complement system. It is a member of the Complement membrane attack complex (MAC) and induces pores on membranes.
Recurrent chest infections with high neutrophil count on FBC, but no abscess formation
IFN gamma receptor deficiency
Lymphocyte adhesion deficiency
Chronic granulomatous disease
Kostmann Syndrome
Lymphocyte adhesion deficiency: In each LAD syndromes, leukocytes (particularly neutrophils) cannot leave the vasculature to migrate normally into tissues under conditions of inflammation or infection.
LAD I: beta 2 integrin family (CD18) is deficient or defective, AR. Characterized clinically by recurrent bacterial infections, a persistent neutrophilia that increases markedly during infection, absent pus formation (a hallmark finding), and impaired wound healing (picture 2). A classic presenting infection is omphalitis, with delayed separation of the umbilical cord
LAD II: fucosylated carbohydrate ligands for selectins are absent, AR, results in defective rolling of hematopoietic cells
LAD III: activation of all beta integrins (1, 2, and 3) is defective, AR
Recurrent infections with hepatosplenomegaly and abnormal dihydrorhodamine test
IFN gamma receptor deficiency
Lymphocyte adhesion deficiency
Chronic granulomatous disease
Kostmann Syndrome
Chronic granulomatous disease: genetically heterogeneous group of immunodeficiencies. The core defect is a failure of phagocytic cells to kill organisms that they have engulfed because of defects in a system of enzymes that produce free radicals and other toxic small molecules.
Classically, patients with chronic granulomatous disease will suffer from recurrent bouts of infection due to the decreased capacity of their immune system to fight off disease-causing organisms. The recurrent infections they acquire are specific and are: pneumonia, abscesses of the skin, tissues and organs, suppurative arthritis, osteomyelitis, bacteremia/fungemia, superficial skin infections such as cellulitis or impetigo.
The nitroblue-tetrazolium (NBT) test is the original and most widely known test for chronic granulomatous disease. It is negative in CGD, meaning that it does not turn blue. A similar test uses dihydrorhodamine (DHR) where whole blood is stained with DHR, incubated, and stimulated to produce superoxide radicals which oxidize DHR to rhodamin in cells with normal function.
Recurrent infections with no neutrophils on FBC
IFN gamma receptor deficiency
Lymphocyte adhesion deficiency
Chronic granulomatous disease
Kostmann Syndrome
Kostmann Syndrome: group of diseases that affect myelopoiesis most prominently, causing severe congenital neutropenia (SCN), usually without other prominent overt physical malformations. SCN manifests in infancy with severe infections. Over 90% of SCN responds to treatment with granulocyte colony-stimulating factor (filgrastim), which has significantly improved survival. Postman Disease - Type 3 (SCN3) is a rare autosomal recessive condition in which severe chronic neutropenia is detected soon after birth, but the commonest subtype of Kostmann syndrome, SCN1, is autosomal dominant. Infants with SCN have frequent infections: 50% have a significant infection within 1 month, most others by 6 months
Infection with atypical mycobacterium. Normal FBC
IFN gamma receptor deficiency
Lymphocyte adhesion deficiency
Chronic granulomatous disease
Kostmann Syndrome
IFN gamma receptor deficiency: patients tend to develop severe disseminated mycobacterial disease in infancy or early childhood, requiring continuous antimycobacterial therapy.
Catheter associated BSI
MRSA C. difficile E. coli MSSA R Gram negs Yeasts / Candida
MRSA, MSSA, R Gram negs, Yeasts/Candida
BSI = blood stream infection
Urinary catheter associated UTI
MRSA C. difficile E. coli MSSA R Gram negs Yeasts / Candida
MRSA, E. coli, R Gram negs, Yeasts/Candida
Surgical site infection
MRSA C. difficile E. coli MSSA R Gram negs Yeasts / Candida
MRSA, MSSA, R Gram negs
Ventilator associated pneumonia
MRSA C. difficile E. coli MSSA R Gram negs Yeasts / Candida
E. coli
Antibiotic associated diarrhoea
MRSA C. difficile E. coli MSSA R Gram negs Yeasts / Candida
C. difficile
B Cell deficiencies
Adult with bronchiectasis, recurrent sinusitis and development of atypical SLE
IgA deficiency
Common Variable Immunodeficiency
Bruton’s X linked hypogammaglobulinaemia
X linked hyper IgM syndrome due to CD40 ligand mutation
Common Variable Immunodeficiency: the most common form of severe antibody deficiency affecting both children and adults. The characteristic immune defect in CVID is impaired B cell differentiation with defective production of immunoglobulin. CVID is defined by low total serum concentrations of immunoglobulin G (IgG), as well as low immunoglobulin A (IgA) and/or immunoglobulin M (IgM), poor or absent response to immunization, and the absence of any other defined immunodeficiency state.
Age of onset is variable. Most patients are diagnosed between the ages of 20 and 40 years. Bacterial infections of the sinopulmonary tract, particularly sinusitis and pneumonia, are experienced by most patients with CVID. In addition to recurrent infections, patients with CVID have evidence of immune dysregulation leading to autoimmunity, a variety of inflammatory disorders, and malignant disease. Patients may suffer from chronic lung disease, gastrointestinal and liver disorders, granulomatous infiltrations, lymphoid hyperplasia, splenomegaly, or malignancy.
The diagnosis of CVID requires a suggestive clinical history, a reduced total serum concentration of IgG, plus low IgA or IgM, and poor responses to both protein- and polysaccharide-based vaccines
B Cell deficiencies
Recurrent bacterial infections in a child, episode of pneumocystis pneumonia, high IgM, absent IgA and IgG
IgA deficiency
Common Variable Immunodeficiency
Bruton’s X linked hypogammaglobulinaemia
X linked hyper IgM syndrome due to CD40 ligand mutation
X linked hyper IgM syndrome due to CD40 ligand mutation: heterogeneous group of congenital and acquired conditions characterized by defective class-switch recombination (CSR), resulting in normal or increased levels of serum IgM associated with deficiency of IgG, IgA, and IgE and poor antibody function. CD40 ligand (CD40L) deficiency is the most common form of hyper-IgM syndrome. It is inherited as an X-linked trait. This disease affects the interaction between activated CD4+ T cells and cell types expressing CD40 (B cells, dendritic cells, monocyte/macrophages, platelets, activated endothelial and epithelial cells). The clinical phenotype of CD40L deficiency is marked not only by recurrent sinopulmonary infections, but also by opportunistic infections and liver disease
B Cell deficiencies
1 year old boy. Recurrent bacterial infections. CD4 and CD8 T cells present. B cells absent, IgG, IgA, IgM absent
IgA deficiency
Common Variable Immunodeficiency
Bruton’s X linked hypogammaglobulinaemia
X linked hyper IgM syndrome due to CD40 ligand mutation
Bruton’s X linked hypogammaglobulinaemia: primary humoral immunodeficiency characterized by severe hypogammaglobulinemia, antibody deficiency, and increased susceptibility to infection. Clinical symptoms (infections) are generally first noted between 3 and 18 months of age.
XLA is due to defects in a signal transduction molecule called Bruton tyrosine kinase (Btk). Patients who present because of clinical symptoms are usually initially identified by significant hypogammaglobulinemia/agammaglobulinemia and the near absence of CD19+ B cells. The diagnosis is then confirmed with molecular studies identifying a mutation in the BTK gene. The cornerstone of treatment for XLA is replacement therapy with immune globulin.
As a consequence of the failure of B cell development, patients affected by a mutation in BTK have significantly reduced levels of B lymphocytes in their blood and tissues, fail to generate plasma cells, and have severely-decreased production of all classes of immunoglobulins with markedly defective antibody responses.
As a result of their deficient humoral immune response, patients with XLA have an increased susceptibility to infection by encapsulated bacteria and certain blood-borne viruses, reflecting the important role of antibody in opsonization of encapsulated bacteria and neutralization of blood-borne enteroviruses.
B Cell deficiencies
Recurrent respiratory tract infections absent IgA, normal IgM and IgG
IgA deficiency
Common Variable Immunodeficiency
Bruton’s X linked hypogammaglobulinaemia
X linked hyper IgM syndrome due to CD40 ligand mutation
IgA deficiency: the selective deficiency of serum IgA (ie, serum levels of IgG and IgM are normal) in a patient older than four years of age, in whom other causes of hypogammaglobulinemia have been excluded.IgA is concentrated in mucosal secretions and is believed to be important in the immune functioning of the mucosal barrier. However, the vast majority of patients with sIgAD do not suffer from increased infections, possibly because there are redundant immune mechanisms that can compensate in most IgA-deficient individuals. Only a minority of IgA-deficient individuals are symptomatic. These patients may develop recurrent sinopulmonary infections, autoimmune disorders, gastrointestinal disorders, allergic diseases, and rare anaphylactic reactions to blood products.
T cell deficiency
Severe recurrent infections from 3 months, CD4 and CD8 T cells absent, B cells present, IgM present, IgA and IgG absent
Bare lymphocyte syndrome type II
X linked SCID
Di George’s Syndrome
IFN gamma receptor deficiency
X linked SCID: is the most common form of SCID. Patients usually present in the newborn period with recurrent severe infections, chronic diarrhea, and failure to thrive. X-linked SCID is due to defects in the common gamma chain (gamma-c, IL2RG). Peripheral T and NK cells are very low to absent and immunoglobulins are also very low to absent despite normal B cell numbers. Hematopoietic cell transplantation is curative.
T cell deficiency
Young adult with chronic infection with Mycobacterium marinum
Bare lymphocyte syndrome type II
X linked SCID
Di George’s Syndrome
IFN gamma receptor deficiency
IFN gamma receptor deficiency: patients tend to develop severe disseminated mycobacterial disease in infancy or early childhood, requiring continuous antimycobacterial therapy.
T cell deficiency
Recurrent infections in childhood, abnormal facial features, congenital heart disease, normal B cells, low T cells, low IgA and IgG
Bare lymphocyte syndrome type II
X linked SCID
Di George’s Syndrome
IFN gamma receptor deficiency
Di George’s Syndrome: classic triad of features on presentation is conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcemia, although the phenotype is variable. Palatal abnormalities and developmental delay are common.
●Immunodeficiency is common in patients with DGS and can range from recurrent sinopulmonary infections (partial DGS) to severe combined immunodeficiency (SCID) (complete DGS). The severity of the immunodeficiency is related to the degree of thymic hypoplasia.
●Other features of DGS that present outside of infancy and into adulthood include recurrent infections in patients with partial DGS, developmental delay, psychiatric abnormalities, and chronic inflammatory diseases
T cell deficiency
6 month baby with 2 recent severe bacterial infections. T cells present - but only CD8+ population. B cells present, IgM present but IgG absent
Bare lymphocyte syndrome type II
X linked SCID
Di George’s Syndrome
IFN gamma receptor deficiency
Bare lymphocyte syndrome type II: rare recessive genetic condition in which a group of genes called major histocompatibility complex class II (MHC class II) are not expressed. The result is that the immune system is severely compromised and cannot effectively fight infection. Clinically, this is known as a severe combined immunodeficiency (SCID).
Variant CJD True/False:
- The disease mainly effects elderly people
- vCJD is more rapidly progressive than sporadic CJD
- The initial symptoms are always neurological
- Tonsillar biopsy is often diagnostic
- EEG is usually abnormal
- The disease mainly effects elderly people - FALSE - disease mainly effects the younger population (mean age 26 years)
- vCJD is more rapidly progressive than sporadic CJD - FALSE - median survival time is 14 months (slightly longer than sporadic CJD)
- The initial symptoms are always neurological - FALSE - psychiatric onset of symptoms (dysphoria, anxiety, paranoia, hallucinations) followed by neurological (peripheral sensory symptoms, ataxia, myoclonus, chorea, dementia)
- Tonsillar biopsy is often diagnostic - TRUE - 100% sensitive and specific for vCJD (unlike sporadic where isn’t usefull) - often eliminates the need for further investigations (e.g. brain biopsy). MRI shows a positive pulvinar sign: a high signal in the thalamus, unlike in sporadic CJD where it is in the basal ganglia
- EEG is usually abnormal - FALSE - may show non-specific slow waves and not useful for diagnosis
Sporadic CJD True/False:
- Median survival time is less than 6 months
- Tonsillar biopsy is diagnostic
- EEG usually shows periodic complexes
- Median age of onset is 65 years old
- CSF marker (S100, 14-3-3) of neuronal damage may be elevated
- Median survival time is less than 6 months - TRUE (shorter than vCJD)
- Tonsillar biopsy is diagnostic - FALSE - not useful. Brain biopsy shows spongiform vacuolation (rarely carried out except confirming diagnosis at post mortem).
- EEG usually shows periodic complexes - TRUE - triphasic complexes, however these are non-specific, also seen in hepatic encephalopathy and lithium toxicity
- Median age of onset is 65 years old - TRUE - commonest form of CJD, cause unknown, thought to be a common cause of Alzheimers in elderly
- CSF marker (S100, 14-3-3) of neuronal damage may be elevated - TRUE - although not useful in vCJD
Complement Deficiency
Membranoproliferative nephritis and bacterial infections
C9 deficiency
C3 deficiency with the presence of nephritic factor
MBL deficiency
C1q deficiency
C3 deficiency with the presence of nephritic factor
Complement Deficiency
Meningococcus meningitis with a family history of sibling dying of the same condition aged 6
C9 deficiency
C3 deficiency with the presence of nephritic factor
MBL deficiency
C1q deficiency
C9 deficiency
Complement Deficiency
Severe childhood onset SLE with normal levels of C3 and C4
C9 deficiency
C3 deficiency with the presence of nephritic factor
MBL deficiency
C1q deficiency
C1q deficiency
Complement Deficiency
Recurrent infections when receiving chemotherapy but previously well
C9 deficiency
C3 deficiency with the presence of nephritic factor
MBL deficiency
C1q deficiency
MBL deficiency
Prion Genetics - True/False
- The vast majority of cases of vCJD have been found to be methionine homozygous (MM) at codon 129 of PRNP
- Familial prion disease does not cause ataxia
- In familial prion disease mutations are usually inherited recessively
- Familial CJD is more rapidly progressive than sporadic CJD
- The vast majority of cases of vCJD have been found to be methionine homozygous (MM) at codon 129 of PRNP - TRUE
- Familial prion disease does not cause ataxia - FALSE
- In familial prion disease mutations are usually inherited recessively - FALSE - – Specific PRNP mutations (~30 so far) – all dominant mutations
- Familial CJD is more rapidly progressive than sporadic CJD - FALSE
19 year old male presents to A&E with severe respiratory difficulty, light-headedness and a red itchy rash. On examination he has laryngeal oedema, bilateral wheezing across the lung fields and is hypotensive. He has recently been taking antibiotics for a chest infection.
A. Allergic bronchopulmonary Aspergillosis B. Food allergy C. Allergic Rhinitis D. Allergic asthma E. Acute Urticaria F. Angioedema G. Drug allergy H. Chronic Urticaria I. Anaphylaxis J. Contact dermatitis
Anaphylaxis
Strictly speaking you can only have a true anaphylactic reaction on 2nd exposure to an allergen (as the first time,
you get the IgE formation, without the cross-linking and mast cell degranulation), whereas anaphylactoid
reactions can occur on first exposure
A 3 year old girl is brought into A&E by her parents. She has had vomiting and diarrhoea since early yesterday evening when she was at a birthday party. On examination she has urticaria.
A. Allergic bronchopulmonary Aspergillosis B. Food allergy C. Allergic Rhinitis D. Allergic asthma E. Acute Urticaria F. Angioedema G. Drug allergy H. Chronic Urticaria I. Anaphylaxis J. Contact dermatitis
Food Allergy
A 40 year old man presents to his GP complaining of loss smell and nasal itching and discharge. On examination his nasal mucosa are swollen and have a bluish tinge. His symptoms improve with a corticosteroid spray
A. Allergic bronchopulmonary Aspergillosis B. Food allergy C. Allergic Rhinitis D. Allergic asthma E. Acute Urticaria F. Angioedema G. Drug allergy H. Chronic Urticaria I. Anaphylaxis J. Contact dermatitis
Allergic Rhinitis
A 25 year old woman presents to her GP complaining of itchy, red wheals on her torso which have been present for 7 weeks. She can not remember how they started but has noticed they are worse in the heat and when she exercises.
A. Allergic bronchopulmonary Aspergillosis B. Food allergy C. Allergic Rhinitis D. Allergic asthma E. Acute Urticaria F. Angioedema G. Drug allergy H. Chronic Urticaria I. Anaphylaxis J. Contact dermatitis
Chronic Urticaria
Acute urticaria is defined being present for less than 6 weeks, whereas chronic urticaria persists for more than 6 weeks. In both cases the urticarial rash is intermittent, comes and goes and normally persists in a single site for less than 24 hours.
Urticarial rashes that last more than 24 hours in a single site, resolve with bruising or skin depigmentation may raise the possibility of an underlying vasculitis. In this instance a skin biopsy of the urticarial lesion is useful to confirm/repute presence of a vasculitis.
A 30 year old women presents to her GP with a red, itchy, oozing rash around her neck and fingers
A. Allergic bronchopulmonary Aspergillosis B. Food allergy C. Allergic Rhinitis D. Allergic asthma E. Acute Urticaria F. Angioedema G. Drug allergy H. Chronic Urticaria I. Anaphylaxis J. Contact dermatitis
Contact Dermatitis
A 55 year old man with history of angina was advised to take a tablet before a long flight. After taking the pill, he suddenly finds that he has difficulty breathing, feels nauseous and is itching.
A. Acute urticaria B. Urticarial vasculitis C. Allergic asthma D. Mast cell degranulation E. IgE mediated anaphylaxis F. Extrinsic allergic alveolitis G. Idiopathic angioedema H. Chronic urticaria I. C1 inhibitor deficiency J. Coeliac disease K. Panic attack
Mast cell degranulation (not IgE mediated)
Opioids, NSAIDs etc directly trigger mast cell degranulation.
A 24 year old medical student develops worsening swelling of the hands and feet and abdominal pain before her final year medical exams. She says that similar milder episodes have occurred preciously.
A. Acute urticaria B. Urticarial vasculitis C. Allergic asthma D. Mast cell degranulation E. IgE mediated anaphylaxis F. Extrinsic allergic alveolitis G. Idiopathic angioedema H. Chronic urticaria I. C1 inhibitor deficiency J. Coeliac disease K. Panic attack
C1 inhibitor deficiency
C1 inhibitor has a number of functions, in addition to inhibiting the activation of C1. For example, it also inhibits activation of the kinin pathway, the clotting pathway and the fibrinolytic pathway. It does this through inhibition of factor XII, activated factor XI, and kallikrein as well as C1.
It’s likely that activation of the kinin pathway and production of bradykinin mediates the angioedema associated with this condition.
A 50 year old Irish woman presents to her GP with episodes of diarrhoea, which is difficult to flush, abdominal pain, weight loss and fatigue. She also describes a blistering itchy rash on her knees.
A. Acute urticaria B. Urticarial vasculitis C. Allergic asthma D. Mast cell degranulation E. IgE mediated anaphylaxis F. Extrinsic allergic alveolitis G. Idiopathic angioedema H. Chronic urticaria I. C1 inhibitor deficiency J. Coeliac disease K. Panic attack
Coeliac disease
Coeliac disease is associated with a superficial, blistering skin rash ‘dermatitis herpetiformis’, which is intensely itchy!
A 26 year old male who has been suffering from ‘flu-like’ symptoms with fever presents to the GP after developing skin rash in the last few days.
A. Acute urticaria B. Urticarial vasculitis C. Allergic asthma D. Mast cell degranulation E. IgE mediated anaphylaxis F. Extrinsic allergic alveolitis G. Idiopathic angioedema H. Chronic urticaria I. C1 inhibitor deficiency J. Coeliac disease K. Panic attack
Acute Urticaria
Acute urticaria is defined being present for less than 6 weeks, whereas chronic urticaria persists for more than 6 weeks. In both cases the urticarial rash is intermittent, comes and goes and normally persists in a single site for less than 24 hours.
Urticarial rashes that last more than 24 hours in a single site, resolve with bruising or skin depigmentation may raise the possibility of an underlying vasculitis. In this instance a skin biopsy of the urticarial lesion is useful to confirm/repute presence of a vasculitis.
A 35 year old woman presents with persistent itchy wheels for the last 2 months. She noticed that when this is at its worst, she also has a fever and feels generally unwell. After an acute attack, she has bruising and post-inflammatory residual pigmentation at the site of the itching.
A. Acute urticaria B. Urticarial vasculitis C. Allergic asthma D. Mast cell degranulation E. IgE mediated anaphylaxis F. Extrinsic allergic alveolitis G. Idiopathic angioedema H. Chronic urticaria I. C1 inhibitor deficiency J. Coeliac disease K. Panic attack
Urticarial vasculitis (UV) is a clinicopathologic entity consisting of urticaria and evidence of leukocytoclastic vasculitis on skin biopsy. UV predominantly involves the skin but may affect other organs, particularly the lungs, kidney, and gastrointestinal tract. Hypocomplementemia, when present, may be associated with extensive vasculitis and systemic features.
Differentiating features:
Common urticaria is pruritic and not painful. By comparison, up to one-third of patients with UV report burning and tenderness as well as pruritus.
Individual lesions in UV last longer than those in chronic urticaria, persisting for more than 24 hours in two-thirds of patients, and sometimes for up to 72 hours. Resolution of these wheals may be associated with purpura and hyperpigmentation in up to 35 percent.
UV can present as angioedema when the vasculitis involves the capillary or postcapillary venules of the deeper layers of the dermis and submucosa
A 19 year old male presents to A&E with increasing breathlessness. On examination his blood pressure is 90/55 mmHg and his respiratory rate is 28/min. He shows you a generalised red itchy skin rash, and examination of his chest reveals bilateral inspiratory and expiratory wheezes throughout.
A. Allergic asthma B. Allergic rhinitis C. Acute angioedema D. Allergic bronchopulmonary aspergillosis E. Chronic urticaria F. Allergic conjunctivitis G. Contact hypersensitivity H. Anaphylaxis I. Acute urticaria J. Hereditary angioedema
Anaphylaxis
The combination of hypotension, respiratory distress, urticaria and bronchoconstriction is very suggestive of anaphylaxis
A 35 year old woman presents with a two day history of a red itchy skin rash which started soon after her first scuba-diving lesson. She is otherwise well.
A. Allergic asthma B. Allergic rhinitis C. Acute angioedema D. Allergic bronchopulmonary aspergillosis E. Chronic urticaria F. Allergic conjunctivitis G. Contact hypersensitivity H. Anaphylaxis I. Acute urticaria J. Hereditary angioedema
Acute Urticaria
This rash is very suggestive of acute urticaria. The temporal association with scuba diving may indicate an allergy to latex (in wet suits)
Acute urticaria is defined being present for less than 6 weeks, whereas chronic urticaria persists for more than 6 weeks. In both cases the urticarial rash is intermittent, comes and goes and normally persists in a single site for less than 24 hours.
Urticarial rashes that last more than 24 hours in a single site, resolve with bruising or skin depigmentation may raise the possibility of an underlying vasculitis. In this instance a skin biopsy of the urticarial lesion is useful to confirm/repute presence of a vasculitis. A
A 22 year old woman presents with an intermittently itchy and desquamating skin rash on her abdomen which is unresponsive to antihistamines
A. Allergic asthma B. Allergic rhinitis C. Acute angioedema D. Allergic bronchopulmonary aspergillosis E. Chronic urticaria F. Allergic conjunctivitis G. Contact hypersensitivity H. Anaphylaxis I. Acute urticaria J. Hereditary angioedema
Contact Hypersensitivity
This rash is typical of contact hypersensitivity. The distribution of the rash suggests that the specific agent is nickel, which used to be a component of the studs of jeans and is commonly found in the metal used in belts.
A 40 year old man complains of loss of smell with nasal itching and discharge over 4 weeks. He also describes morning sneezing. He is otherwise in good health. On examination his nasal mucosa are swollen and hyperaemic.
A. Allergic asthma B. Allergic rhinitis C. Acute angioedema D. Allergic bronchopulmonary aspergillosis E. Chronic urticaria F. Allergic conjunctivitis G. Contact hypersensitivity H. Anaphylaxis I. Acute urticaria J. Hereditary angioedema
Allergic Rhinitis
The combination of sneezing, rhinorrhea and loss of smell is very suggestive of allergic rhinitis
This 45 year old woman presents to A&E with tongue swelling and acute respiratory tract obstruction. She has longstanding hypertension and received a renal transplant two years previously. She has no history of allergic disease. On examination her blood pressure is stable, and examination of her lung fields reveal normal breath sounds. Her current medication includes cyclosporine, azathioprine, captopril and nifedipine.
A. Allergic asthma B. Allergic rhinitis C. Acute angioedema D. Allergic bronchopulmonary aspergillosis E. Chronic urticaria F. Allergic conjunctivitis G. Contact hypersensitivity H. Anaphylaxis I. Acute urticaria J. Hereditary angioedema
Acute Angioedema
This woman has angioedema of the tongue, without symptoms suggestive of a generalised allergic reaction. Isolated angioedema may be allergic in origin, but 94% of cases angioedema presenting to A&E are drug induced and the majority of these are associated with ACE inhibitors (eg captopril).
A 19 year old male presents to A&E with increasing breathlessness. On examination his blood pressure is 90/55 mmHg and his respiratory rate is 28/min. He shows you a generalised red itchy skin rash, and examination of his chest reveals bilateral inspiratory and expiratory wheezes throughout.
A. IM adrenaline 0.5 mL of 1:1000 B. IM adrenaline 1mL of 1:10000 C. Intraarticular corticosteroids D. IM adrenaline 1mL of 1:1000 E. Intranasal antihistamines F. PO antihistamines G. Intracardiac adrenaline H. IV antihistamines I. None of the above J. IV adrenaline 0.3mL of 1:1000 K. Inhaled corticosteroids L. Inhaled antihistamines M. Venom immunotherapy
IM adrenaline 1mL of 1:1000
The most important treatment of anaphylaxis is adrenaline, which should be given intramuscularly. (Note for final year pharm: 1:1000 means 1mg/mL; 1:10000 means 0.1mg/mL ; 1% means 1g/dL)
A 35 year old woman presents with a two day history of a red itchy skin rash which started soon after her first scuba-diving lesson. She is otherwise well.
A. IM adrenaline 0.5 mL of 1:1000 B. IM adrenaline 1mL of 1:10000 C. Intraarticular corticosteroids D. IM adrenaline 1mL of 1:1000 E. Intranasal antihistamines F. PO antihistamines G. Intracardiac adrenaline H. IV antihistamines I. None of the above J. IV adrenaline 0.3mL of 1:1000 K. Inhaled corticosteroids L. Inhaled antihistamines M. Venom immunotherapy
PO anti-histamines
Severe acute urticaria is effectively treated with a short course of oral anti-histamines
A 22 year old woman is presents with this intermittently itchy and desquamating skin rash which is unresponsive to antihistamines
A. IM adrenaline 0.5 mL of 1:1000 B. IM adrenaline 1mL of 1:10000 C. Intraarticular corticosteroids D. IM adrenaline 1mL of 1:1000 E. Intranasal antihistamines F. PO antihistamines G. Intracardiac adrenaline H. IV antihistamines I. None of the above J. IV adrenaline 0.3mL of 1:1000 K. Inhaled corticosteroids L. Inhaled antihistamines M. Venom immunotherapy
None of the above
Contact hypersensitivity should be treated by avoidance of the sensitising agent, in this case nickel
A 40 year old man complains of loss of smell with nasal itching and discharge over 4 weeks. He also describes morning sneezing. He is otherwise in good health. On examination his nasal mucosa are swollen and hyperaemic.
A. IM adrenaline 0.5 mL of 1:1000 B. IM adrenaline 1mL of 1:10000 C. Intraarticular corticosteroids D. IM adrenaline 1mL of 1:1000 E. Intranasal antihistamines F. PO antihistamines G. Intracardiac adrenaline H. IV antihistamines I. None of the above J. IV adrenaline 0.3mL of 1:1000 K. Inhaled corticosteroids L. Inhaled antihistamines M. Venom immunotherapy
PO anti-histamines
Oral antihistamines and intranasal corticosteroids are the mainstay of treatment of mild allergic rhinitis. (As intranasal corticosteroid is not an option available, the “single best” answer here is oral antihistamines.)
This 45 year old woman presents to A&E with tongue swelling and acute respiratory tract obstruction. She has longstanding hypertension and received a renal transplant two years previously. She has no history of allergic disease. On examination her blood pressure is stable, and examination of her lung fields reveal normal breath sounds. Her current medication includes cyclosporine, azathioprine, captopril and nifedipine.
A. IM adrenaline 0.5 mL of 1:1000 B. IM adrenaline 1mL of 1:10000 C. Intraarticular corticosteroids D. IM adrenaline 1mL of 1:1000 E. Intranasal antihistamines F. PO antihistamines G. Intracardiac adrenaline H. IV antihistamines I. None of the above J. IV adrenaline 0.3mL of 1:1000 K. Inhaled corticosteroids L. Inhaled antihistamines M. Venom immunotherapy
IM adrenaline 0.5 mL of 1:1000
Intramuscular adrenalin should be used in patients with severe local angioedema with secondary acute respiratory tract obstruction. However this is not always effective in ACE inhibitor-induced angioedema, and some patients will require intubation. Always stop the causative agent!
Cytokines exerting an anti-viral effect
A. Alternative complement pathway B. IgE C. IgG D. Major histocompatability complex class 2 E. Innate immune system F. CD8+ G. Major histocompatability complex class 1 H. IL6 I. Interferons J. IgA K. Natural Killer cells L. Classical complement pathway M. IgM
Interferons
Immunoglobulin dimer
A. Alternative complement pathway B. IgE C. IgG D. Major histocompatability complex class 2 E. Innate immune system F. CD8+ G. Major histocompatability complex class 1 H. IL6 I. Interferons J. IgA K. Natural Killer cells L. Classical complement pathway M. IgM
IgA
MHC associated with Th1 cells
A. Alternative complement pathway B. IgE C. IgG D. Major histocompatability complex class 2 E. Innate immune system F. CD8+ G. Major histocompatability complex class 1 H. IL6 I. Interferons J. IgA K. Natural Killer cells L. Classical complement pathway M. IgM
Major Histocompatibility complex class 2
Acts on hepatocytes to induce synthesis of acute phase proteins in response to bacterial infection
A. Alternative complement pathway B. IgE C. IgG D. Major histocompatability complex class 2 E. Innate immune system F. CD8+ G. Major histocompatability complex class 1 H. IL6 I. Interferons J. IgA K. Natural Killer cells L. Classical complement pathway M. IgM
IL-6
Arise in the first few days after infection and are important in defence against viruses and tumours
A. Alternative complement pathway B. IgE C. IgG D. Major histocompatability complex class 2 E. Innate immune system F. CD8+ G. Major histocompatability complex class 1 H. IL6 I. Interferons J. IgA K. Natural Killer cells L. Classical complement pathway M. IgM
Natural Killer cells
MHC associated with Th2 cells
A. Alternative complement pathway B. IgE C. IgG D. Major histocompatability complex class 2 E. Innate immune system F. CD8+ G. Major histocompatability complex class 1 H. IL6 I. Interferons J. IgA K. Natural Killer cells L. Classical complement pathway M. IgM
Major histocompatability complex class 2
MHC associated with cytotoxic T cells
A. Alternative complement pathway B. IgE C. IgG D. Major histocompatability complex class 2 E. Innate immune system F. CD8+ G. Major histocompatability complex class 1 H. IL6 I. Interferons J. IgA K. Natural Killer cells L. Classical complement pathway M. IgM
Major histocompatability complex class 1
Along with IgD, is one of the first immunoglobulins expressed on B cells before they undergo antibody class switching
A. Alternative complement pathway B. IgE C. IgG D. Major histocompatability complex class 2 E. Innate immune system F. CD8+ G. Major histocompatability complex class 1 H. IL6 I. Interferons J. IgA K. Natural Killer cells L. Classical complement pathway M. IgM
IgM
The most abundant (in terms of g/L) immunoglobulin in normal plasma
A. Alternative complement pathway B. IgE C. IgG D. Major histocompatability complex class 2 E. Innate immune system F. CD8+ G. Major histocompatability complex class 1 H. IL6 I. Interferons J. IgA K. Natural Killer cells L. Classical complement pathway M. IgM
IgG
Deficiencies in this predispose to SLE
A. Alternative complement pathway B. IgE C. IgG D. Major histocompatability complex class 2 E. Innate immune system F. CD8+ G. Major histocompatability complex class 1 H. IL6 I. Interferons J. IgA K. Natural Killer cells L. Classical complement pathway M. IgM
Classical complement pathway
Kostmanns syndrome is a congenital deficiency of which component of the immune system?
A. Bacterial B. B lymphocyte C. T lymphocyte D. Neutrophil E. Complement F. Mast cell G. Parasitic H. MHC Class I I. Fungal J. MHC Class II K. Viral
Neutrophil
Which component of the innate immune system is usually one of the first to respond to infection through a cut?
A. Bacterial B. B lymphocyte C. T lymphocyte D. Neutrophil E. Complement F. Mast cell G. Parasitic H. MHC Class I I. Fungal J. MHC Class II K. Viral
Neutrophil
Which infection is most common as a consequence of B cell deficiency?
A. Bacterial B. B lymphocyte C. T lymphocyte D. Neutrophil E. Complement F. Mast cell G. Parasitic H. MHC Class I I. Fungal J. MHC Class II K. Viral
Bacterial
Meningococcal infections are quite common as a result of which deficiency of the component of the immune system?
A. Bacterial B. B lymphocyte C. T lymphocyte D. Neutrophil E. Complement F. Mast cell G. Parasitic H. MHC Class I I. Fungal J. MHC Class II K. Viral
Complement
Produced by the liver, when triggered, enzymatically activate other proteins in a biological cascade and are important in innate and antibody mediated immune response?
A. Bacterial B. B lymphocyte C. T lymphocyte D. Neutrophil E. Complement F. Mast cell G. Parasitic H. MHC Class I I. Fungal J. MHC Class II K. Viral
Complement
A complete deficiency in this molecule is associated with recurrent respiratory and gastrointestinal infections.
A. Macrophages B. IgM C. C3b D. MAC E. AP50 F. IgG G. IgA H. CH50 I. Neutrophils J. C1 K. Myeloperoxidase L. C3a M. NADPH oxidoase
IgA
Leukocyte Adhesion Deficiency is characterised by a very high count in which of the above?
A. Macrophages B. IgM C. C3b D. MAC E. AP50 F. IgG G. IgA H. CH50 I. Neutrophils J. C1 K. Myeloperoxidase L. C3a M. NADPH oxidoase
Neutrophils
Which crucial enzyme is vital for the oxidative killing of intracellular micro-organisms?
A. Macrophages B. IgM C. C3b D. MAC E. AP50 F. IgG G. IgA H. CH50 I. Neutrophils J. C1 K. Myeloperoxidase L. C3a M. NADPH oxidoase
NADPH oxidase
Which complement factor is an important chemotaxic agent?
A. Macrophages B. IgM C. C3b D. MAC E. AP50 F. IgG G. IgA H. CH50 I. Neutrophils J. C1 K. Myeloperoxidase L. C3a M. NADPH oxidoase
C3a
What is the functional complement test used to investigate the classical pathway?
A. Macrophages B. IgM C. C3b D. MAC E. AP50 F. IgG G. IgA H. CH50 I. Neutrophils J. C1 K. Myeloperoxidase L. C3a M. NADPH oxidoase
CH50
Grave’s Disease
A. Type II – Antigen mediated B. Type II – Antibody mediated C. Type III – complement mediated D. Not an autoimmune disease E. Type III – Immune complex mediated F. Type III – T-cell mediated G. Type IV – T-cell mediated H. Type IV – Complement mediated
Type II – Antibody mediated
SLE
A. Type II – Antigen mediated B. Type II – Antibody mediated C. Type III – complement mediated D. Not an autoimmune disease E. Type III – Immune complex mediated F. Type III – T-cell mediated G. Type IV – T-cell mediated H. Type IV – Complement mediated
Type III – Immune complex mediated
Rheumatoid Arthritis
A. Type II – Antigen mediated B. Type II – Antibody mediated C. Type III – complement mediated D. Not an autoimmune disease E. Type III – Immune complex mediated F. Type III – T-cell mediated G. Type IV – T-cell mediated H. Type IV – Complement mediated
Type IV – T-cell mediated
Asthma
A. Type II – Antigen mediated B. Type II – Antibody mediated C. Type III – complement mediated D. Not an autoimmune disease E. Type III – Immune complex mediated F. Type III – T-cell mediated G. Type IV – T-cell mediated H. Type IV – Complement mediated
Not an autoimmune disease
Type 1 diabetes
A. Type II – Antigen mediated B. Type II – Antibody mediated C. Type III – complement mediated D. Not an autoimmune disease E. Type III – Immune complex mediated F. Type III – T-cell mediated G. Type IV – T-cell mediated H. Type IV – Complement mediated
Type IV – T-cell mediated
Immune thrombocytopaenic purpura
A. Type II – Antigen mediated B. Type II – Antibody mediated C. Type III – complement mediated D. Not an autoimmune disease E. Type III – Immune complex mediated F. Type III – T-cell mediated G. Type IV – T-cell mediated H. Type IV – Complement mediated
Type II – Antibody mediated
ABO hemolytic transfusion reaction
A. Type II – Antigen mediated B. Type II – Antibody mediated C. Type III – complement mediated D. Not an autoimmune disease E. Type III – Immune complex mediated F. Type III – T-cell mediated G. Type IV – T-cell mediated H. Type IV – Complement mediated
Type II – Antibody mediated
Hepatitis C associated membranoproliferative glomerulonephritis type I
A. Type II – Antigen mediated B. Type II – Antibody mediated C. Type III – complement mediated D. Not an autoimmune disease E. Type III – Immune complex mediated F. Type III – T-cell mediated G. Type IV – T-cell mediated H. Type IV – Complement mediated
Type III – Immune complex mediated
Goodpasture’s syndrome
A. Type II – Antigen mediated B. Type II – Antibody mediated C. Type III – complement mediated D. Not an autoimmune disease E. Type III – Immune complex mediated F. Type III – T-cell mediated G. Type IV – T-cell mediated H. Type IV – Complement mediated
Type II – Antibody mediated
Myaesthenia gravis
A. Type II – Antigen mediated B. Type II – Antibody mediated C. Type III – complement mediated D. Not an autoimmune disease E. Type III – Immune complex mediated F. Type III – T-cell mediated G. Type IV – T-cell mediated H. Type IV – Complement mediated
Type II – Antibody mediated
Systemic lupus erythematous
A. Anti-mitochondrial antibody B. Anti-centromere antibody C. Anti-GAD antibody D. Anti-cardiolipin antibody E. c-ANCA F. p-ANCA G. Anti-nuclear antibody H. Anti-CCP antibody I. Anti-DNA antibody J. Rheumatoid factor K. Coomb's test
Anti-DNA antibody
The rationale for the answer for SLE being anti-DNA antibody rather than ANA is that whilst ANA is very sensitive for SLE, it is not specific. Anti-DNA, in contrast, is highly specific to SLE (~95%).
Wegener’s granulomatosis
A. Anti-mitochondrial antibody B. Anti-centromere antibody C. Anti-GAD antibody D. Anti-cardiolipin antibody E. c-ANCA F. p-ANCA G. Anti-nuclear antibody H. Anti-CCP antibody I. Anti-DNA antibody J. Rheumatoid factor K. Coomb's test
c-ANCA
Remember that c-ANCA matches with Wegener’s Granulomatosis, whilst p-ANCA would match with polyarteritis nodosa
Rheumatoid arthritis
A. Anti-mitochondrial antibody B. Anti-centromere antibody C. Anti-GAD antibody D. Anti-cardiolipin antibody E. c-ANCA F. p-ANCA G. Anti-nuclear antibody H. Anti-CCP antibody I. Anti-DNA antibody J. Rheumatoid factor K. Coomb's test
Anti-CCP antibody
Rheumatoid factor is not specific or sensitive to rheumatoid arthritis and is common in the elderly. Anti-CCP is a more specific test for rheumatoid arthritis and a better predictor of an aggressive course.
Auto-immune haemolytic anaemia
A. Anti-mitochondrial antibody B. Anti-centromere antibody C. Anti-GAD antibody D. Anti-cardiolipin antibody E. c-ANCA F. p-ANCA G. Anti-nuclear antibody H. Anti-CCP antibody I. Anti-DNA antibody J. Rheumatoid factor K. Coomb's test
Coomb’s Test
Primary biliary cirrhosis
A. Anti-mitochondrial antibody B. Anti-centromere antibody C. Anti-GAD antibody D. Anti-cardiolipin antibody E. c-ANCA F. p-ANCA G. Anti-nuclear antibody H. Anti-CCP antibody I. Anti-DNA antibody J. Rheumatoid factor K. Coomb's test
Anti-mitochondrial antibody
Goodpastures: What is the specific auto-antigen that is the target of the immune system?
A. Skin B. Smooth linear pattern C. Type IV collagen D. Plasmapheresis E. Anti-neutrophil cytoplasmic antibodies F. Lung G. Blood vessels H. Lumpy-bumpy pattern I. Ciclosporin J. Prednisolone K. Glomerular basement membrane L. Mesangium M. Type II Hypersentivity N. Type II collagen
Type IV collagen
Goodpastures: The pattern of the antibody deposition in the glomerular basement membrane is typically described as what?
A. Skin B. Smooth linear pattern C. Type IV collagen D. Plasmapheresis E. Anti-neutrophil cytoplasmic antibodies F. Lung G. Blood vessels H. Lumpy-bumpy pattern I. Ciclosporin J. Prednisolone K. Glomerular basement membrane L. Mesangium M. Type II Hypersentivity N. Type II collagen
Smooth linear pattern
Goodpastures: Name the drug most likely to be used in the treatment of this disease.
A. Skin B. Smooth linear pattern C. Type IV collagen D. Plasmapheresis E. Anti-neutrophil cytoplasmic antibodies F. Lung G. Blood vessels H. Lumpy-bumpy pattern I. Ciclosporin J. Prednisolone K. Glomerular basement membrane L. Mesangium M. Type II Hypersentivity N. Type II collagen
Prednisolone
Goodpastures: Immune damage may be associated with the kidney and commonly which other tissue?
A. Skin B. Smooth linear pattern C. Type IV collagen D. Plasmapheresis E. Anti-neutrophil cytoplasmic antibodies F. Lung G. Blood vessels H. Lumpy-bumpy pattern I. Ciclosporin J. Prednisolone K. Glomerular basement membrane L. Mesangium M. Type II Hypersentivity N. Type II collagen
Lung
Which enzyme is defective in Von Gierkes disease?
A. Uricase
B. Glucose-6-phosphatase
C. Phospho Ribosyl Pyro Phosphate (PRPP) Synthase
D. Xanthine oxidase
E. Adenosine deaminase
F. Myophosphorylase
G. Hypoxanthine Guanosine Phospo Ribosyl Transferase (HGPRT)
Glucose-6-phosphatase
Severe combined immunodeficinecy (SCID) is due to deficiency of what enzyme?
A. Uricase
B. Glucose-6-phosphatase
C. Phospho Ribosyl Pyro Phosphate (PRPP) Synthase
D. Xanthine oxidase
E. Adenosine deaminase
F. Myophosphorylase
G. Hypoxanthine Guanosine Phospo Ribosyl Transferase (HGPRT)
Adenosine deaminase
Allopurinol inhibits what?
A. Uricase
B. Glucose-6-phosphatase
C. Phospho Ribosyl Pyro Phosphate (PRPP) Synthase
D. Xanthine oxidase
E. Adenosine deaminase
F. Myophosphorylase
G. Hypoxanthine Guanosine Phospo Ribosyl Transferase (HGPRT)
Xanthine oxidase
Lesch-Nyhan disease is due to the deficiency of which enzyme?
A. Uricase
B. Glucose-6-phosphatase
C. Phospho Ribosyl Pyro Phosphate (PRPP) Synthase
D. Xanthine oxidase
E. Adenosine deaminase
F. Myophosphorylase
G. Hypoxanthine Guanosine Phospo Ribosyl Transferase (HGPRT)
Hypoxanthine Guanosine Phospo Ribosyl Transferase (HGPRT)
Which enzyme is absent in mammals?
A. Uricase
B. Glucose-6-phosphatase
C. Phospho Ribosyl Pyro Phosphate (PRPP) Synthase
D. Xanthine oxidase
E. Adenosine deaminase
F. Myophosphorylase
G. Hypoxanthine Guanosine Phospo Ribosyl Transferase (HGPRT)
Uricase
Over-activity of which enzyme leads to gout?
A. Uricase
B. Glucose-6-phosphatase
C. Phospho Ribosyl Pyro Phosphate (PRPP) Synthase
D. Xanthine oxidase
E. Adenosine deaminase
F. Myophosphorylase
G. Hypoxanthine Guanosine Phospo Ribosyl Transferase (HGPRT)
Phospho Ribosyl Pyro Phosphate (PRPP) Synthase
A 16-year-old male has a past psychiatric history of self mutilation. He complains of pain in his first metatarso phalangeal joint, and polymorphs and needle shaped crystals are seen from an aspirate. When under polarised light, they appear yellow when parallel to the red compensator and blue when perpendicular to it. Name the syndrome that he has?
A. Klinefelters syndrome B. Pseudo-Gout C. Lesch-Nyhan syndrome D. Rheumatoid arthritis E. Gout F. Turners syndrome G. Osteoarthritis H. Septic arthritis
Lesch-Nyhan syndrome
A 28-year-old female has a painful inflamed swollen knee, and aspirate reveals polymorphs but no crystals?
A. Klinefelters syndrome B. Pseudo-Gout C. Lesch-Nyhan syndrome D. Rheumatoid arthritis E. Gout F. Turners syndrome G. Osteoarthritis H. Septic arthritis
Septic Arthritis
A 78-year-old female has a painful inflamed swollen knee, and aspirate reveals polymorphs and brick shaped crystals. When under polarised light, they appear blue when parallel to the red compensator and yellow when perpendicular to it?
A. Klinefelters syndrome B. Pseudo-Gout C. Lesch-Nyhan syndrome D. Rheumatoid arthritis E. Gout F. Turners syndrome G. Osteoarthritis H. Septic arthritis
Pseudo-Gout
A 52-year-old alcoholic male complains of pain in his proximal interphalangeal joint. Polymorphs and needle shaped crystals are seen from an aspirate. When under polarised light, they appear yellow when parallel to the red compensator and blue when perpendicular to it?
A. Klinefelters syndrome B. Pseudo-Gout C. Lesch-Nyhan syndrome D. Rheumatoid arthritis E. Gout F. Turners syndrome G. Osteoarthritis H. Septic arthritis
Gout
A 24-year-old female with renal failure complains of pain in her first metatarso phalangeal joint, and polymorphs and needle shaped crystals are seen from an aspirate. When under polarised light, they appear yellow when parallel to the red compensator and blue when perpendicular to it?
A. Klinefelters syndrome B. Pseudo-Gout C. Lesch-Nyhan syndrome D. Rheumatoid arthritis E. Gout F. Turners syndrome G. Osteoarthritis H. Septic arthritis
Gout
Which is the only pituitary hormone to be suppressed by a hypothalamic hormone?
A. Thyroid Stimulating Hormone (TSH or thyrotrophin) B. Oxytocin C. Insulin D. Corticotrophin E. Adrenaline F. Gonadotrophin Releasing Hormone (GnRH) G. Luteinising Hormone H. Thyrotrophin Releasing Hormone I. IGF-1 J. Prolactin K. Growth Hormone (somatotrophin) L. Follicle Stimulating Hormone M. Growth Hormone Releasing Hormone (GHRH) N. Leptin O. Dopamine P. Corticotrophin Releasing Hormone (CRH)
Prolactin
Prolactin is the only hormone that has an inhibiting factor. All the other anterior pituitary hormones are stimulated by releasing hormones.
Which hormone is most important in stimulating spermatogenesis?
A. Thyroid Stimulating Hormone (TSH or thyrotrophin) B. Oxytocin C. Insulin D. Corticotrophin E. Adrenaline F. Gonadotrophin Releasing Hormone (GnRH) G. Luteinising Hormone H. Thyrotrophin Releasing Hormone I. IGF-1 J. Prolactin K. Growth Hormone (somatotrophin) L. Follicle Stimulating Hormone M. Growth Hormone Releasing Hormone (GHRH) N. Leptin O. Dopamine P. Corticotrophin Releasing Hormone (CRH)
FSH
FSH stimulates follicle production in females and sperm production in males. Inhibin feeds back on FSH levels. LH causes ovulation in the female at the “LH surge”. In the male, it is responsible for the stimulation of the secretion of testosterone.
Which hormone is most important in stimulating the secretion of testosterone?
A. Thyroid Stimulating Hormone (TSH or thyrotrophin) B. Oxytocin C. Insulin D. Corticotrophin E. Adrenaline F. Gonadotrophin Releasing Hormone (GnRH) G. Luteinising Hormone H. Thyrotrophin Releasing Hormone I. IGF-1 J. Prolactin K. Growth Hormone (somatotrophin) L. Follicle Stimulating Hormone M. Growth Hormone Releasing Hormone (GHRH) N. Leptin O. Dopamine P. Corticotrophin Releasing Hormone (CRH)
LH
FSH stimulates follicle production in females and sperm production in males. Inhibin feeds back on FSH levels. LH causes ovulation in the female at the “LH surge”. In the male, it is responsible for the stimulation of the secretion of testosterone.
Which hormone is secreted by the liver?
A. Thyroid Stimulating Hormone (TSH or thyrotrophin) B. Oxytocin C. Insulin D. Corticotrophin E. Adrenaline F. Gonadotrophin Releasing Hormone (GnRH) G. Luteinising Hormone H. Thyrotrophin Releasing Hormone I. IGF-1 J. Prolactin K. Growth Hormone (somatotrophin) L. Follicle Stimulating Hormone M. Growth Hormone Releasing Hormone (GHRH) N. Leptin O. Dopamine P. Corticotrophin Releasing Hormone (CRH)
IGF-1
IGF-1 is produced by the liver in the presence of GH
Which hormone is secreted from the posterior pituitary?
A. Thyroid Stimulating Hormone (TSH or thyrotrophin) B. Oxytocin C. Insulin D. Corticotrophin E. Adrenaline F. Gonadotrophin Releasing Hormone (GnRH) G. Luteinising Hormone H. Thyrotrophin Releasing Hormone I. IGF-1 J. Prolactin K. Growth Hormone (somatotrophin) L. Follicle Stimulating Hormone M. Growth Hormone Releasing Hormone (GHRH) N. Leptin O. Dopamine P. Corticotrophin Releasing Hormone (CRH)
Oxytocin
Oxytocin comes from the posterior pituitary as does vasopressin.
Name the hypothalamic hormone that inhibits prolactin release?
A. Thyroid Stimulating Hormone (TSH or thyrotrophin) B. Oxytocin C. Insulin D. Corticotrophin E. Adrenaline F. Gonadotrophin Releasing Hormone (GnRH) G. Luteinising Hormone H. Thyrotrophin Releasing Hormone I. IGF-1 J. Prolactin K. Growth Hormone (somatotrophin) L. Follicle Stimulating Hormone M. Growth Hormone Releasing Hormone (GHRH) N. Leptin O. Dopamine P. Corticotrophin Releasing Hormone (CRH)
Dopamine
Name the hypothalamic hormone that stimulates prolactin release?
A. Thyroid Stimulating Hormone (TSH or thyrotrophin) B. Oxytocin C. Insulin D. Corticotrophin E. Adrenaline F. Gonadotrophin Releasing Hormone (GnRH) G. Luteinising Hormone H. Thyrotrophin Releasing Hormone I. IGF-1 J. Prolactin K. Growth Hormone (somatotrophin) L. Follicle Stimulating Hormone M. Growth Hormone Releasing Hormone (GHRH) N. Leptin O. Dopamine P. Corticotrophin Releasing Hormone (CRH)
Thyroid Stimulating Hormone (TSH or thyrotrophin)
An excess of which hormone produces amenorrhoea?
A. Thyroid Stimulating Hormone (TSH or thyrotrophin) B. Oxytocin C. Insulin D. Corticotrophin E. Adrenaline F. Gonadotrophin Releasing Hormone (GnRH) G. Luteinising Hormone H. Thyrotrophin Releasing Hormone I. IGF-1 J. Prolactin K. Growth Hormone (somatotrophin) L. Follicle Stimulating Hormone M. Growth Hormone Releasing Hormone (GHRH) N. Leptin O. Dopamine P. Corticotrophin Releasing Hormone (CRH)
Prolactin
When leptin levels are low, the hypothalamus stops making GnRH and as a consequence LH and FSH levels fall. Amenorrhoea results. Thus during starvation or anorexia, amenorrhoea results. A high level of prolactin has the same effect, and thus galactorrhoea and amenorrhoea result from high prolactin levels.
A deficiency of which hormone switches off the secretion of GnRH?
A. Thyroid Stimulating Hormone (TSH or thyrotrophin) B. Oxytocin C. Insulin D. Corticotrophin E. Adrenaline F. Gonadotrophin Releasing Hormone (GnRH) G. Luteinising Hormone H. Thyrotrophin Releasing Hormone I. IGF-1 J. Prolactin K. Growth Hormone (somatotrophin) L. Follicle Stimulating Hormone M. Growth Hormone Releasing Hormone (GHRH) N. Leptin O. Dopamine P. Corticotrophin Releasing Hormone (CRH)
Leptin
When leptin levels are low, the hypothalamus stops making GnRH and as a consequence LH and FSH levels fall. Amenorrhoea results. Thus during starvation or anorexia, amenorrhoea results. A high level of prolactin has the same effect, and thus galactorrhoea and amenorrhoea result from high prolactin levels.
Which hormone is suppressed by an oral load of glucose during a glucose tolerance test?
A. Thyroid Stimulating Hormone (TSH or thyrotrophin) B. Oxytocin C. Insulin D. Corticotrophin E. Adrenaline F. Gonadotrophin Releasing Hormone (GnRH) G. Luteinising Hormone H. Thyrotrophin Releasing Hormone I. IGF-1 J. Prolactin K. Growth Hormone (somatotrophin) L. Follicle Stimulating Hormone M. Growth Hormone Releasing Hormone (GHRH) N. Leptin O. Dopamine P. Corticotrophin Releasing Hormone (CRH)
Growth hormone (somatotrophin)
X-Linked Agammaglobulinaemia
A. CD3 mutation B. MHC Class II C. Bruton’s tyrosine kinase (Btk) gene D. IFN Receptor 1 gene E. IL-2 receptor F. WASP gene G. CD40 Ligand gene H. Chromosome 22q11 I. IL12 gene
Bruton’s tyrosine kinase (Btk) gene
Bruton’s X linked hypogammaglobulinaemia
• Defective B cell tyrosine kinase gene
• Pre B cells cannot develop to mature B cells -> Absence of mature B cells
• No circulating Ig after ~ 3 months
• Recurrent infections during childhood, bacterial, enterovirus
DiGeorge’s Syndrome
A. CD3 mutation B. MHC Class II C. Bruton’s tyrosine kinase (Btk) gene D. IFN Receptor 1 gene E. IL-2 receptor F. WASP gene G. CD40 Ligand gene H. Chromosome 22q11 I. IL12 gene
Chromosome 22q11
Facial: High forehead, low set, abnormally folded ears, cleft palate, small mouth and jaw
Hypocalcaemia, oesphageal atresia, T cell lymphopenia
Complex congenital heart disease
Normal B cells numbers, reduced T cell numbers, homeostatic proliferation with age, immune function improves with age
Developmental defect of 3rd/4th pharyngeal pouch, 75% sporadic, probably involves TBX1
Severe Combined Immunodeficiency
A. CD3 mutation B. MHC Class II C. Bruton’s tyrosine kinase (Btk) gene D. IFN Receptor 1 gene E. IL-2 receptor F. WASP gene G. CD40 Ligand gene H. Chromosome 22q11 I. IL12 gene
IL-2 Receptor
• Clinical phenotype of severe combined immunodeficiency:
o Unwell by 3 months of age
o Infections of all types
o Failure to thrive
o Persistent diarrhoea
o Unusual skin disease
o Colonisation of infant’s empty bone marrow by maternal lymphocytes
o Graft versus host disease
o Family history of early infant death
• Causes of SCID:
o 20 possible pathways identified
o Deficiency of cytokine receptors
o Deficiency of signalling molecules
o Metabolic defects
o Effect on different lymphocyte subsets (T, B, NK) depend on exact mutation
• Commonest form of SCID:
o X-linked SCID:
o 45% of all severe combined immunodeficiency
o Mutation of gamma chain of IL2 receptor on chromosome Xq13.1
o Shared by receptor for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21
o Inability to respond to cytokines causes early arrest of T cell and NK cell development and production of immature B cells
o Phenotype:
o Very low or absent T cell numbers
o Normal or increased B cell numbers
o Poorly developed lymphoid tissue and thymus
Wiskott-Aldrich Syndrome
A. CD3 mutation B. MHC Class II C. Bruton’s tyrosine kinase (Btk) gene D. IFN Receptor 1 gene E. IL-2 receptor F. WASP gene G. CD40 Ligand gene H. Chromosome 22q11 I. IL12 gene
WASP gene
Wiskott-Aldrich syndrome is an X-linked recessive disease characterised by: thrombocytopenia lymphopenia and depressed cellular immunity immunosuppression eczema malignant lymphoma
Bare lymphocyte syndrome
A. CD3 mutation B. MHC Class II C. Bruton’s tyrosine kinase (Btk) gene D. IFN Receptor 1 gene E. IL-2 receptor F. WASP gene G. CD40 Ligand gene H. Chromosome 22q11 I. IL12 gene
MHC Class II
o Defect in one of the regulatory proteins involved in Class II gene expression
o Regulatory factor X
o Class II transactivator
o Absent expression of MHC Class II molecules
o Profound deficiency of CD4+ cells
o Usually have normal number of CD8+ cells
o Normal number of B cells
o Failure to make IgG or IgA antibody
o BLS type 1 also exists due to failure of expression of HLA class I (therefore lack CD8 T cells)
o Clinical Phenotype:
• Unwell by 3 months of age
• Infections of all types
• Failure to thrive
• May be associated with sclerosing cholangitis
• Family history of early infant death
This region encodes C2, C4 and factor B
A. WASP gene B. CD40 Ligand gene C. IL-2 receptor D. Bruton’s tyrosine kinase (Btk) gene E. IFN Receptor 1 gene F. MHC Class III G. Adenosine Deaminase (ADA) gene H. CD3 mutation I. IL12 gene J. Chromosome 22q11
MHC Class III
Hyper IgM Syndrome
A. WASP gene B. CD40 Ligand gene C. IL-2 receptor D. Bruton’s tyrosine kinase (Btk) gene E. IFN Receptor 1 gene F. MHC Class III G. Adenosine Deaminase (ADA) gene H. CD3 mutation I. IL12 gene J. Chromosome 22q11
CD40 Ligand gene
A 25 year old woman comes to her GP about family planning. She is worried because she had an older brother who died before she was born and her grandmother lost two children which she things were both boys. Her GP thinks there may be a genetic disorder in her family affecting the IL-2 receptor. If correct she has a 50% of inheriting the trait from her mother and being a carrier herself. And there would be a 50% chance of passing it to her children. If inherited, her daughters would be carriers and her sons would require treatment which is usually a bone marrow transplant but gene therapy is sometimes used.
A. Bruton's X linked hypogammaglobulinaemia B. Severe combined immunodeficiency (SCID) C. Common variable immune deficiency D. Reticular dysgenesis E. TAP deficiency F. Bare lymphocyte syndrome G. DiGeorge syndrome H. Selective IgA deficency I. Hyper IgM syndrome
Severe combined immunodeficiency (SCID)
A jaundiced 8 month old child presents with failure to thrive, and a history of recurrent infections (viral, bacterial and fungal). On examination there is hepatomegally and blood tests show a raised alk phos and low CD4 count. A defect is found in the proteins that regulate MHC Class II transcription.
A. Bruton's X linked hypogammaglobulinaemia B. Severe combined immunodeficiency (SCID) C. Common variable immune deficiency D. Reticular dysgenesis E. TAP deficiency F. Bare lymphocyte syndrome G. DiGeorge syndrome H. Selective IgA deficency I. Hyper IgM syndrome
Bare lymphocyte syndrome
Patient X’s GP writes inquiring about whether to vaccinate. The patient suffers from recurrent respiratory tract infections and has been diagnosed with one of the B-cell maturation defects. For which one is immunisation still effective?
A. Bruton's X linked hypogammaglobulinaemia B. Severe combined immunodeficiency (SCID) C. Common variable immune deficiency D. Reticular dysgenesis E. TAP deficiency F. Bare lymphocyte syndrome G. DiGeorge syndrome H. Selective IgA deficency I. Hyper IgM syndrome
Selective IgA deficency
For which disorder would a bone marrow transplant be unhelpful but a thymic transplant may provide a cure?
A. Bruton's X linked hypogammaglobulinaemia B. Severe combined immunodeficiency (SCID) C. Common variable immune deficiency D. Reticular dysgenesis E. TAP deficiency F. Bare lymphocyte syndrome G. DiGeorge syndrome H. Selective IgA deficency I. Hyper IgM syndrome
Di George syndrome.
The thymus is affected but not the bone marrow, where B cell production and maturation take place. Hence there is no reduction in B cell numbers. B cells require T cell help (CD4+ cells) for activation and production of normal quantities of immunoglobulins.
Without this help, B cell activity is reduced.
In acute rejection, release of this substance from CD8+ lymphocytes helps kill target cells
A. HLA DR > A > B B. CD4+ T cells C. CD8+ T cells D. Diuretics E. Antibiotics F. IV Immunoglobulins and Plasmapheresis G. Amino acids H. Diabetes I. HLA DR > B > A J. Hypertension K. Hyperacute L. Granzyme B M. CD17+ T cells N. HLA type O. Interferon gamma P. Hypotension Q. ABO blood type R. High dose corticosteroids S. HLA A > B > DR T. Free radicals
Granzyme B
In acute rejection, these are produced as a result of the activation of neutrophils and macrophages
A. HLA DR > A > B B. CD4+ T cells C. CD8+ T cells D. Diuretics E. Antibiotics F. IV Immunoglobulins and Plasmapheresis G. Amino acids H. Diabetes I. HLA DR > B > A J. Hypertension K. Hyperacute L. Granzyme B M. CD17+ T cells N. HLA type O. Interferon gamma P. Hypotension Q. ABO blood type R. High dose corticosteroids S. HLA A > B > DR T. Free radicals
Free radicals
A difference in this between host and recipient is the main cause of transplant rejection
A. HLA DR > A > B B. CD4+ T cells C. CD8+ T cells D. Diuretics E. Antibiotics F. IV Immunoglobulins and Plasmapheresis G. Amino acids H. Diabetes I. HLA DR > B > A J. Hypertension K. Hyperacute L. Granzyme B M. CD17+ T cells N. HLA type O. Interferon gamma P. Hypotension Q. ABO blood type R. High dose corticosteroids S. HLA A > B > DR T. Free radicals
HLA type
Along with anti-HLA antibodies, the most important screen to ensure a match before transplantation
A. HLA DR > A > B B. CD4+ T cells C. CD8+ T cells D. Diuretics E. Antibiotics F. IV Immunoglobulins and Plasmapheresis G. Amino acids H. Diabetes I. HLA DR > B > A J. Hypertension K. Hyperacute L. Granzyme B M. CD17+ T cells N. HLA type O. Interferon gamma P. Hypotension Q. ABO blood type R. High dose corticosteroids S. HLA A > B > DR T. Free radicals
ABO blood type
Risk factor for chronic allograft rejection
A. HLA DR > A > B B. CD4+ T cells C. CD8+ T cells D. Diuretics E. Antibiotics F. IV Immunoglobulins and Plasmapheresis G. Amino acids H. Diabetes I. HLA DR > B > A J. Hypertension K. Hyperacute L. Granzyme B M. CD17+ T cells N. HLA type O. Interferon gamma P. Hypotension Q. ABO blood type R. High dose corticosteroids S. HLA A > B > DR T. Free radicals
Hypertension
Transplanting an ABO incompatible kidney will result in ___ rejection
A. HLA DR > A > B B. CD4+ T cells C. CD8+ T cells D. Diuretics E. Antibiotics F. IV Immunoglobulins and Plasmapheresis G. Amino acids H. Diabetes I. HLA DR > B > A J. Hypertension K. Hyperacute L. Granzyme B M. CD17+ T cells N. HLA type O. Interferon gamma P. Hypotension Q. ABO blood type R. High dose corticosteroids S. HLA A > B > DR T. Free radicals
Hyperacute
Treatment of acute antibody mediated rejection
A. HLA DR > A > B B. CD4+ T cells C. CD8+ T cells D. Diuretics E. Antibiotics F. IV Immunoglobulins and Plasmapheresis G. Amino acids H. Diabetes I. HLA DR > B > A J. Hypertension K. Hyperacute L. Granzyme B M. CD17+ T cells N. HLA type O. Interferon gamma P. Hypotension Q. ABO blood type R. High dose corticosteroids S. HLA A > B > DR T. Free radicals
IV Immunoglobulins and Plasmapheresis
Treatment of acute cell mediated rejection
A. HLA DR > A > B B. CD4+ T cells C. CD8+ T cells D. Diuretics E. Antibiotics F. IV Immunoglobulins and Plasmapheresis G. Amino acids H. Diabetes I. HLA DR > B > A J. Hypertension K. Hyperacute L. Granzyme B M. CD17+ T cells N. HLA type O. Interferon gamma P. Hypotension Q. ABO blood type R. High dose corticosteroids S. HLA A > B > DR T. Free radicals
High dose corticosteroids
The 3 most important HLA types to screen for in renal transplantation when matching donor and recipient, in order of importance
A. HLA DR > A > B B. CD4+ T cells C. CD8+ T cells D. Diuretics E. Antibiotics F. IV Immunoglobulins and Plasmapheresis G. Amino acids H. Diabetes I. HLA DR > B > A J. Hypertension K. Hyperacute L. Granzyme B M. CD17+ T cells N. HLA type O. Interferon gamma P. Hypotension Q. ABO blood type R. High dose corticosteroids S. HLA A > B > DR T. Free radicals
HLA DR > B > A
Lymphocyte that responds to foreign HLA DR types
A. HLA DR > A > B B. CD4+ T cells C. CD8+ T cells D. Diuretics E. Antibiotics F. IV Immunoglobulins and Plasmapheresis G. Amino acids H. Diabetes I. HLA DR > B > A J. Hypertension K. Hyperacute L. Granzyme B M. CD17+ T cells N. HLA type O. Interferon gamma P. Hypotension Q. ABO blood type R. High dose corticosteroids S. HLA A > B > DR T. Free radicals
CD4+ T cells
Lymphocyte that responds to foreign HLA A types
A. HLA DR > A > B B. CD4+ T cells C. CD8+ T cells D. Diuretics E. Antibiotics F. IV Immunoglobulins and Plasmapheresis G. Amino acids H. Diabetes I. HLA DR > B > A J. Hypertension K. Hyperacute L. Granzyme B M. CD17+ T cells N. HLA type O. Interferon gamma P. Hypotension Q. ABO blood type R. High dose corticosteroids S. HLA A > B > DR T. Free radicals
CD8+ T cells
Prevents DNA replication especially of T cells
A. Metolazone B. Cyclophosamide C. Perindopril D. Prednisolone E. Dobutamine F. Ciclosporin G. Thyroxine H. Chloramphenicol I. Cyproterone acetate J. Ribavirin K. Infliximab L. Gentamicin M. Mycophenolate mofetil N. Immunoglobulins
Mycophenolate mofetil
Both mycophenolate mofetil and cyclophosphamide prevent lymphocyte proliferation by inhibiting DNA replication. However, mycophenolate mofetil is more selective for T cells, whereas cycophosphamide affects B cells more than T cells. Note that cyclophosphamide at high doses will affect all cells with a high turnover
Causes a transient increase in neutrophil count
A. Metolazone B. Cyclophosamide C. Perindopril D. Prednisolone E. Dobutamine F. Ciclosporin G. Thyroxine H. Chloramphenicol I. Cyproterone acetate J. Ribavirin K. Infliximab L. Gentamicin M. Mycophenolate mofetil N. Immunoglobulins
Prednisolone
Monoclonal antibodies inhibiting the actions of cytokines
A. Metolazone B. Cyclophosamide C. Perindopril D. Prednisolone E. Dobutamine F. Ciclosporin G. Thyroxine H. Chloramphenicol I. Cyproterone acetate J. Ribavirin K. Infliximab L. Gentamicin M. Mycophenolate mofetil N. Immunoglobulins
Infliximab
Can cause gingival hypertrophy as a side effect
A. Metolazone B. Cyclophosamide C. Perindopril D. Prednisolone E. Dobutamine F. Ciclosporin G. Thyroxine H. Chloramphenicol I. Cyproterone acetate J. Ribavirin K. Infliximab L. Gentamicin M. Mycophenolate mofetil N. Immunoglobulins
Ciclosporin
Administration of this may boost the immune system
A. Metolazone B. Cyclophosamide C. Perindopril D. Prednisolone E. Dobutamine F. Ciclosporin G. Thyroxine H. Chloramphenicol I. Cyproterone acetate J. Ribavirin K. Infliximab L. Gentamicin M. Mycophenolate mofetil N. Immunoglobulins
Immunoglobulins
Corticosteroids, as well as being directly lymphotoxic in high doses, inhibit T-cell function via which other mechanism?
A. Mycophenolate mofetil B. Inhibition of DNA synthesis C. Plasmapheresis D. Diptheria, Tetanus, Pertussis vaccine E. Influenza type B vaccine F. Tacrolimus G. Blocking cytokine synthesis H. Polio vaccine I. Bee/wasp venom allergy J. Atopic dermatitis K. Infliximab L. Bone marrow suppression M. Goodpasture’s syndrome
Blocking cytokine synthesis
The antiproliferative drug cyclophosphamide inhibits lymphocyte proliferation by which mechanism?
A. Mycophenolate mofetil B. Inhibition of DNA synthesis C. Plasmapheresis D. Diptheria, Tetanus, Pertussis vaccine E. Influenza type B vaccine F. Tacrolimus G. Blocking cytokine synthesis H. Polio vaccine I. Bee/wasp venom allergy J. Atopic dermatitis K. Infliximab L. Bone marrow suppression M. Goodpasture’s syndrome
Inhibition of DNA synthesis
Plasmapheresis may be indicated in which condition?
A. Mycophenolate mofetil B. Inhibition of DNA synthesis C. Plasmapheresis D. Diptheria, Tetanus, Pertussis vaccine E. Influenza type B vaccine F. Tacrolimus G. Blocking cytokine synthesis H. Polio vaccine I. Bee/wasp venom allergy J. Atopic dermatitis K. Infliximab L. Bone marrow suppression M. Goodpasture’s syndrome
Goodpasture’s syndrome
Example of a vaccine that should NOT be given to a severely immunocompromised patient.
A. Mycophenolate mofetil B. Inhibition of DNA synthesis C. Plasmapheresis D. Diptheria, Tetanus, Pertussis vaccine E. Influenza type B vaccine F. Tacrolimus G. Blocking cytokine synthesis H. Polio vaccine I. Bee/wasp venom allergy J. Atopic dermatitis K. Infliximab L. Bone marrow suppression M. Goodpasture’s syndrome
Polio vaccine
A condition where antigen desensitization therapy may be indicated.
A. Mycophenolate mofetil B. Inhibition of DNA synthesis C. Plasmapheresis D. Diptheria, Tetanus, Pertussis vaccine E. Influenza type B vaccine F. Tacrolimus G. Blocking cytokine synthesis H. Polio vaccine I. Bee/wasp venom allergy J. Atopic dermatitis K. Infliximab L. Bone marrow suppression M. Goodpasture’s syndrome
Bee/wasp venom allergy
Prednisolone
A. Pneumonitis, pulmonary fibrosis and cirrhosis B. Ototoxicity C. Hair loss D. Dysrhythmias E. Bone marrow depression F. Hypertension and reduced GFR G. Lethargy H. Hypertension I. Anaphylaxis J. Anorexia
Hypertension
Ciclosporin
A. Pneumonitis, pulmonary fibrosis and cirrhosis B. Ototoxicity C. Hair loss D. Dysrhythmias E. Bone marrow depression F. Hypertension and reduced GFR G. Lethargy H. Hypertension I. Anaphylaxis J. Anorexia
Hypertension and reduced GFR
Azathioprine
A. Pneumonitis, pulmonary fibrosis and cirrhosis B. Ototoxicity C. Hair loss D. Dysrhythmias E. Bone marrow depression F. Hypertension and reduced GFR G. Lethargy H. Hypertension I. Anaphylaxis J. Anorexia
Bone marrow suppression
Methotrexate
A. Pneumonitis, pulmonary fibrosis and cirrhosis B. Ototoxicity C. Hair loss D. Dysrhythmias E. Bone marrow depression F. Hypertension and reduced GFR G. Lethargy H. Hypertension I. Anaphylaxis J. Anorexia
Pneumonitis, pulmonary fibrosis and cirrhosis
For methotrexate (MTX) induced cirrhosis monitor serum procollagen III rather than doing liver biopsy. MTX is given once WEEKLY as maintenance therapy in autoimmune disease; more often and you’re looking at anti-tumour regimens. Remember to replace folate.
Immunoglobulin
A. Pneumonitis, pulmonary fibrosis and cirrhosis B. Ototoxicity C. Hair loss D. Dysrhythmias E. Bone marrow depression F. Hypertension and reduced GFR G. Lethargy H. Hypertension I. Anaphylaxis J. Anorexia
Anaphylaxis
The most important cell in the initiation of normal haemostasis.
A. Thromboxane A2 B. Tissue plasminogen-activator (t-PA) C. Fibrinogen D. Fibrin E. a2 macroglobulin F. Megakaryocyte G. Endothelial cell H. Cycloxygenase I. Plasmin J. Platelet K. Protein C L. Antithrombin III M. Erythrocyte
Endothelial cell
Damage to the endothelial cells causes the release of substances that INITIATE the process of haemostasis, including platelet activation
The main component involved in stabilising the primary haemostatic plug.
A. Thromboxane A2 B. Tissue plasminogen-activator (t-PA) C. Fibrinogen D. Fibrin E. a2 macroglobulin F. Megakaryocyte G. Endothelial cell H. Cycloxygenase I. Plasmin J. Platelet K. Protein C L. Antithrombin III M. Erythrocyte
Fibrin
A serine protease which assists in the break down of blood clots by binding to the clot and localising agents which break it down.
A. Thromboxane A2 B. Tissue plasminogen-activator (t-PA) C. Fibrinogen D. Fibrin E. a2 macroglobulin F. Megakaryocyte G. Endothelial cell H. Cycloxygenase I. Plasmin J. Platelet K. Protein C L. Antithrombin III M. Erythrocyte
Tissue plasminogen-activator (t-PA)
9am Cortisol: 650nM
After 0.5mg dexamethasone suppression test:
9am Cortisol: 500nM
What is the Diagnosis:
A. Pituitary dependent Cushing’s Disease
B. Adrenal tumour causing Cushing’s syndrome
C. Ectopic ACTH causing Cushing’s syndrome
D. Normal Obese person
E. Cushing’s syndrome of indeterminate cause
Cushing’s syndrome of indeterminate cause
9am Cortisol: 500nM
After 2mg dexamethasone suppression test:
9am Cortisol: 170nM
What is the Diagnosis:
A. Pituitary dependent Cushing’s Disease
B. Adrenal tumour causing Cushing’s syndrome
C. Ectopic ACTH causing Cushing’s syndrome
D. Normal Obese person
E. Cushing’s syndrome of indeterminate cause
Pituitary dependent Cushing’s Disease
Pituitary receptors still have a little bit of functionality
A 10 year old girl with a painful knee - Normal WCC, raised ESR and CRP, x-ray shows abnormality of the tibia
Septic Arthritis Haemophilia A Osteomyelitis Thrombocytopenia Haemophilia B
Osteomyelitis
Unlikely to be haemophilia (female and febrile!)
Septic and Osteomyelitis are both possibilities but the x-ray changes point towards osteomyelitis
Test for Addison’s
Low dose Dexamethosone suppression test
High dose Dexamethosone suppression test
SynACTHen test
Glucose tolerance test
SynACTHen test
A 34 year old obese woman with type 2 diabetes presents with hypertension and bruising.
Na 146, K 2.9, U 4.0, Glucose 14.0
Aldosterone s and suggests another hormone is causing the hypertension
True or false
True
Dynamic Test for Cushing’s?
Insulin Tolerance (Stress) Test Dexamethasone Suppression Test SynACTHen Test Glucose Tolerance Test TRH Stimulation Test
Dexamethasone Suppression Test
Inhibitor of RANK ligand
Ustekinumab/Etanercept
Infliximab
Denosumab
Adalimumab/Tocilizumab
Denosumab - Treatment of osteoporosis
Inhibits IL-12/23 or TNF alpha
Ustekinumab/Etanercept
Infliximab
Denosumab
Adalimumab/Tocilizumab
Ustekinumab/Etanercept - Treatment of psoriasis
Inhibits TNF alpha
Ustekinumab/Etanercept
Infliximab
Denosumab
Adalimumab/Tocilizumab
Infliximab - Treatment of Crohn’s disease
Inhibits IL-6 or TNF alpha
Ustekinumab/Etanercept
Infliximab
Denosumab
Adalimumab/Tocilizumab
Adalimumab/Tocilizumab - treatment of RA
IFN alpha
Boosting the Immune System:
Post-transplant lymphoproliferative disorder
Part of Treatment for HepC
X linked hyper IgM syndrome
X linked SCID
Chronic Granulomatous Disease
Immunosuppressed seronegative individual after chicken pox exposure
Part of treatment for HepC
Bone Marrow Transplantation
Boosting the Immune System:
Post-transplant lymphoproliferative disorder
Part of Treatment for HepC
X linked hyper IgM syndrome
X linked SCID
Chronic Granulomatous Disease
Immunosuppressed seronegative individual after chicken pox exposure
X linked SCID
IFN gamma
Boosting the Immune System:
Post-transplant lymphoproliferative disorder
Part of Treatment for HepC
X linked hyper IgM syndrome
X linked SCID
Chronic Granulomatous Disease
Immunosuppressed seronegative individual after chicken pox exposure
Chronic Granulomatous Disease
EBV-specific CD8 T cells
Boosting the Immune System:
Post-transplant lymphoproliferative disorder
Part of Treatment for HepC
X linked hyper IgM syndrome
X linked SCID
Chronic Granulomatous Disease
Immunosuppressed seronegative individual after chicken pox exposure
Post-transplant lymphoproliferative disorder
Human Normal Immunoglobulin
Boosting the Immune System:
Post-transplant lymphoproliferative disorder
Part of Treatment for HepC
X linked hyper IgM syndrome
X linked SCID
Chronic Granulomatous Disease
Immunosuppressed seronegative individual after chicken pox exposure
X linked hyper IgM syndrome
Varicella zoster immunoglobulin
Boosting the Immune System:
Post-transplant lymphoproliferative disorder
Part of Treatment for HepC
X linked hyper IgM syndrome
X linked SCID
Chronic Granulomatous Disease
Immunosuppressed seronegative individual after chicken pox exposure
Immunosuppressed seronegative individual after chicken pox exposure
Basiliximab - Anti-IL2 receptor
- Inhibits T cell migration but may only be used in highly active relapsing/remitting MS
- Inhibits T cell activation and is effective in RA
- Depletes B cells and is effective in treatment of B cell lymphoma and RA
- Inhibits function of lymphoid and myeloid cells and used in management of RA
- Antibody specific for CD25 which inhibits T cell activation and is used to prevent rejection
Antibody specific for CD25 which inhibits T cell activation and is used to prevent rejection
Abatacept (CTLA4-Ig fusion protein)
- Inhibits T cell migration but may only be used in highly active relapsing/remitting MS
- Inhibits T cell activation and is effective in RA
- Depletes B cells and is effective in treatment of B cell lymphoma and RA
- Inhibits function of lymphoid and myeloid cells and used in management of RA
- Antibody specific for CD25 which inhibits T cell activation and is used to prevent rejection
Inhibits T cell activation and is effective in RA
Rituximab (Anti-CD20)
- Inhibits T cell migration but may only be used in highly active relapsing/remitting MS
- Inhibits T cell activation and is effective in RA
- Depletes B cells and is effective in treatment of B cell lymphoma and RA
- Inhibits function of lymphoid and myeloid cells and used in management of RA
- Antibody specific for CD25 which inhibits T cell activation and is used to prevent rejection
Depletes B cells and is effective in treatment of B cell lymphoma and RA
Natalizumab (Anti-alpha4 integrin)
- Inhibits T cell migration but may only be used in highly active relapsing/remitting MS
- Inhibits T cell activation and is effective in RA
- Depletes B cells and is effective in treatment of B cell lymphoma and RA
- Inhibits function of lymphoid and myeloid cells and used in management of RA
- Antibody specific for CD25 which inhibits T cell activation and is used to prevent rejection
Inhibits T cell migration but may only be used in highly active relapsing/remitting MS
Tocilizumab (Anti-IL6 receptor)
- Inhibits T cell migration but may only be used in highly active relapsing/remitting MS
- Inhibits T cell activation and is effective in RA
- Depletes B cells and is effective in treatment of B cell lymphoma and RA
- Inhibits function of lymphoid and myeloid cells and used in management of RA
- Antibody specific for CD25 which inhibits T cell activation and is used to prevent rejection
Inhibits function of lymphoid and myeloid cells and used in management of RA
Cyclophosphamide
Side Effects: Osteoporosis Infertility Progressive Multifocal Leukoencephalopathy Neutropenia particularly if TPMT low Hypertension
Infertility
Prednisolone
Side Effects: Osteoporosis Infertility Progressive Multifocal Leukoencephalopathy Neutropenia particularly if TPMT low Hypertension
Osteoporosis
Azathioprine
Side Effects: Osteoporosis Infertility Progressive Multifocal Leukoencephalopathy Neutropenia particularly if TPMT low Hypertension
Neutropenia particularly if TPMT low
Cyclosporin
Side Effects: Osteoporosis Infertility Progressive Multifocal Leukoencephalopathy Neutropenia particularly if TPMT low Hypertension
Hypertension
Mycophenolate mofetil
Side Effects: Osteoporosis Infertility Progressive Multifocal Leukoencephalopathy Neutropenia particularly if TPMT low Hypertension
Progressive Multifocal Leukoencephalopathy
FBC of an 83 year old man with no abnormal physical findings shows lymphocytosis and smear cells
Acute Lymphoblastic Leukaemia Chronic Lymphocytic Leukaemia HIV Infection Infectious Mononucleosis Whooping Cough
Chronic Lymphocytic Leukaemia
FBC of a 67 year old woman with facial plethora shows high WCC, RBCs, Hb and Haematocrit, Neutrophils and Basophils
Chronic Myeloid Leukamia Polycythaemia vera Pseudo-polycythaemia Renal Artery Stenosis Smoking Induced Hypoxia
Polycythaemia vera
FBC from a 67 year old in ITU, WCC 37.5 - raised Neutrophils, reduced lymphocyte count, immature precursors. Film shows left shift, increased Rouleaux and toxic granulation of neutrophils
Chronic Myeloid Leukaemia Normal for age and gender Reactive Neutrophilia Laboratory Error Acute Myeloid Leukaemia
Reactive Neutrophilia
FBC of a 64 year old as symptomatic Spanish woman with splenomegaly shows raised WCC. Film shows increased basophils, eosinophils and neutrophils
Chronic Myeloid Leukaemia Normal for age and gender Reactive Neutrophilia Laboratory Error Acute Myeloid Leukaemia
Chronic Myeloid Leukaemia
FBC of a North African woman with an 18 month old baby shows microcytic anaemia, hypochromia, anisocytosis, some elongated RBCs.
Normal for a North African Beta thalassaemia major Lead Poisoning Beta thalassaemia trait IDA
IDA - commonest causes are diet, menorrhagia, blood loss
Beta thalassaemia major is unlikely if she’s just had a baby
Lead Poisoning - rare
Beta thalassaemia trait - Hb too low for this, Hb will often be normal but there will be significant microcytosis
A 1 year old boy presents with joint bleeding
Normal Hb, WCC, platelet count
APTT prolonged - corrected by mixing plasma with normal plasma
PT Normal
Haemophilia A Haemophilia B Von Willebrand Disease Thrombotic thrombocytopenic purpura Has taken mother's warfarin tablets
Haemophilia A (Coagulation defect in a baby boy) Results indicate something at the top of the intrinsic pathway has gone wrong - factors APTT = intrinsic pathway, used to monitor heparin treatment. Normal APTT requires factors I, II, V, VIII, IX, X, XI, & XII. Notably, deficiencies in factors VII or XIII will not be detected with the APTT test. Prolonged in: heparin use, anti-phospholipid syndrome (especially lupus anticoagulant - which paradoxically increases propensity to thrombosis), coagulation factor deficiency (Haemophilia), Sepsis (coag factor depletion), Presence of anti-bodies against coagulation factors PT = extrinsic pathway, measures factors I (fibrinogen), II (prothrombin), V, VII and X. It is used to measure the clotting tendency of the blood - warfarin dosage, liver damage and vitamin K status
FBC of a North African woman with an 18 month old baby shows microcytic anaemia, hypochromia, anisocytosis, some elongated RBCs.
Normal for a North African Beta thalassaemia major Lead Poisoning Beta thalassaemia trait IDA
IDA
Beta thalassaemia major is unlikely if she’s just had a baby
Lead Poisoning - rare
Beta thalassaemia trait - Hb too low for this, Hb will often be normal but there will be significant microcytosis
6 year old Afro-Caribbean boy presents with chest and abdominal pain.
Hb 63 g/L, MCV 85fl, blood film shows sickle cells.
Most likely diagnosis?
Sickle Cell trait
Sickle Cell Anaemia
Sickle Cell/Beta Thalassaemia
Sickle Cell Anaemia
Afro Caribbean boy with jaundice, anaemia and abnormal blood film - most likely diagnosis?
Hepatitis A
Hepatits B
Hereditary Spherocytosis
G6PD deficiency
G6PD deficiency
Why can G6PD levels be normal in G6PD deficiency? In an acute haemolytic crisis we would mount a reticulocyte response (young red cells) which have a high level of G6PD, therefore this may elevate the measured G6PD level. Therefore you would have to measure the G6PD level after the acute haemolytic episode has resolved, to see if the patient is truly G6PD deficient. ps polychromatic macrocytes = reticulocytes (polychromasia due to ribosomal RNA)
Siblings with sickle cell anaemia present simultaneously with severe anaemia and a low reticulocyte count - likely diagnosis?
Splenic Sequestration Parvovirus B19 infection Folic Acid Deficiency Haemolytic Crisis Vitamin B12 deficiency
Parvovirus B19 infection
Complications of a sickle cell anaemia that are MORE common in adults than children include
Hand-foot syndrome Hyposplenism Red cell aplasia Splenic Sequestration Stroke
Hyposplenism
If you suspect an acute porphyria, what is the most useful sample to send?
Blood CSF Urine Muscle Biopsy Stool Skin Biopsy
Urine to look for porphyrins
A single chain glycoprotein, synthesised by the liver and endothelium, which has strongly anticoagulant action and is important in the mode of action of heparin.
A. Thromboxane A2 B. Tissue plasminogen-activator (t-PA) C. Fibrinogen D. Fibrin E. a2 macroglobulin F. Megakaryocyte G. Endothelial cell H. Cycloxygenase I. Plasmin J. Platelet K. Protein C L. Antithrombin III M. Erythrocyte
Antithrombin III - substance in plasma that inactivates thrombin
Its activity is increased manyfold by the anticoagulant drug heparin, which enhances the binding of antithrombin to factor II and factor X.
A single chain glycoprotein, synthesised by the liver and endothelium, which has strongly anticoagulant action and is important in the mode of action of heparin.
A. Thromboxane A2 B. Tissue plasminogen-activator (t-PA) C. Fibrinogen D. Fibrin E. a2 macroglobulin F. Megakaryocyte G. Endothelial cell H. Cycloxygenase I. Plasmin J. Platelet K. Protein C L. Antithrombin III M. Erythrocyte
Antithrombin III
This product of the cyclic endoperoxides induces platelet aggregation
A. Sensitised platelet B. Haemophilia C. Christmas disease D. Thromboxane A2 E. Ehlers-Danlos syndrome F. Autoimmune thrombocytopenic purpura G. Vitamin K deficiency H. Megakaryocyte I. Factor VIII deficiency J. Prostacyclin PGI2 K. Factor XII deficiency L. von Willebrand deficiency M. Marfan syndrome
Thromboxane A2
A 62 year old overweight woman presents to the Emergency Department following a Road Traffic Accident. A full set of investigations is carried out – which shows an increased Activated Partial Thromboplastin Time (APTT) and Prothrombin Time (PT)
A. Sensitised platelet B. Haemophilia C. Christmas disease D. Thromboxane A2 E. Ehlers-Danlos syndrome F. Autoimmune thrombocytopenic purpura G. Vitamin K deficiency H. Megakaryocyte I. Factor VIII deficiency J. Prostacyclin PGI2 K. Factor XII deficiency L. von Willebrand deficiency M. Marfan syndrome
Vitamin K deficiency
If thrombin time is up there is a fibrinogen problem.
If APTT or PT is up there is a coagulation factor dysfunction or deficiency.
If bleeding time is up there is a platelet dysfunction or deficiency.
If D-dimers (fibrin split products) are zero you can rule out DVT.
To diagnose DIC you need low platelets, low fibrinogen, raised APTT and PT, raised D-dimers, schistocytes on blood smear,
and a compatible clinical setting.
Common pathway - factors I, II, V, X
Extrinsic pathway - factor VII
Intrinsic pathway - factors VIII, IX, XI, XII
Raised PT - problem in common or extrinsic pathway
Raised APTT - problem in common or intrinisc pathway. A deficiency of any factor except VII and XIII can raise the APTT.
A 25 year old man presents to the Emergency Department a day after attending his dentist for a routine check-up. After treatment at the dentists the previous day, his gums had not stopped bleeding. On investigation, his APTT and bleeding time are prolonged but a normal PT.
A. Sensitised platelet B. Haemophilia C. Christmas disease D. Thromboxane A2 E. Ehlers-Danlos syndrome F. Autoimmune thrombocytopenic purpura G. Vitamin K deficiency H. Megakaryocyte I. Factor VIII deficiency J. Prostacyclin PGI2 K. Factor XII deficiency L. von Willebrand deficiency M. Marfan syndrome
von Willebrand deficiency
If thrombin time is up there is a fibrinogen problem.
If APTT or PT is up there is a coagulation factor dysfunction or deficiency.
If bleeding time is up there is a platelet dysfunction or deficiency.
If D-dimers (fibrin split products) are zero you can rule out DVT.
To diagnose DIC you need low platelets, low fibrinogen, raised APTT and PT, raised D-dimers, schistocytes on blood smear,
and a compatible clinical setting.
Common pathway - factors I, II, V, X
Extrinsic pathway - factor VII
Intrinsic pathway - factors VIII, IX, XI, XII
Raised PT - problem in common or extrinsic pathway
Raised APTT - problem in common or intrinisc pathway. A deficiency of any factor except VII and XIII can raise the APTT.
A 25 year old man presents to the Emergency Department a day after attending his dentist for a routine check-up. After treatment at the dentists the previous day, his gums had not stopped bleeding. On investigation, his APTT and bleeding time are prolonged but a normal PT.
A. Sensitised platelet B. Haemophilia C. Christmas disease D. Thromboxane A2 E. Ehlers-Danlos syndrome F. Autoimmune thrombocytopenic purpura G. Vitamin K deficiency H. Megakaryocyte I. Factor VIII deficiency J. Prostacyclin PGI2 K. Factor XII deficiency L. von Willebrand deficiency M. Marfan syndrome
von Willebrand deficiency
A 16 year old girl presents to the Haematology Outpatients clinic describing a fluctuating history of easy bruising, epistaxis and menorrhagia. On investigation there is a thrombocytopaenia with increased megakaryocytes on BM examination.
A. Sensitised platelet B. Haemophilia C. Christmas disease D. Thromboxane A2 E. Ehlers-Danlos syndrome F. Autoimmune thrombocytopenic purpura G. Vitamin K deficiency H. Megakaryocyte I. Factor VIII deficiency J. Prostacyclin PGI2 K. Factor XII deficiency L. von Willebrand deficiency M. Marfan syndrome
Autoimmune thrombocytopenic purpura
Which protein, important in haemostasis, is vitamin K dependent but is not a serine protease?
A. Tissue factor B. Vascular subendothelium C. Vascular endothelium D. Arichidonic acid E. Protein S F. Tissue factor pathway inhibitor G. Factor VII H. Activated factor X I. Platelets J. Thrombin K. Cyclooxygenase L. Protein C
Protein S
Which option is required as a cofactor for protein C activity?
A. Tissue factor B. Vascular subendothelium C. Vascular endothelium D. Arichidonic acid E. Protein S F. Tissue factor pathway inhibitor G. Factor VII H. Activated factor X I. Platelets J. Thrombin K. Cyclooxygenase L. Protein C
Protein S
Which option synthesises tissue factor, vWF, prostacyclin, plasminogen activator, antithrombin III and thrombomodulin?
A. Tissue factor B. Vascular subendothelium C. Vascular endothelium D. Arichidonic acid E. Protein S F. Tissue factor pathway inhibitor G. Factor VII H. Activated factor X I. Platelets J. Thrombin K. Cyclooxygenase L. Protein C
Vascular endothelium
Which enzyme, important for platelet aggregation, is irreversibly inhibited by aspirin?
A. Tissue factor B. Vascular subendothelium C. Vascular endothelium D. Arichidonic acid E. Protein S F. Tissue factor pathway inhibitor G. Factor VII H. Activated factor X I. Platelets J. Thrombin K. Cyclooxygenase L. Protein C
Cyclooxygenase
Which key clotting factor activates both factors V and VIII, and also activates protein C?
A. Tissue factor B. Vascular subendothelium C. Vascular endothelium D. Arichidonic acid E. Protein S F. Tissue factor pathway inhibitor G. Factor VII H. Activated factor X I. Platelets J. Thrombin K. Cyclooxygenase L. Protein C
Thrombin
A 37 year old mother of 4 children, presents to her GP because of recurrent nose bleeds and feeling tired all the time and heavy periods.
A. Bile acid malabsorption B. Warfarin overdose C. Antiphospholipid antibody syndrome D. Sickle cell anaemia E. Haemophilia A F. Malignancy G. Von Willebrand’s Disease H. Henoch – Schönlein Purpura I. Osler-Weber-Rendu Syndrome J. Vitamin K Deficiency K. Factor V Leiden L. Disseminated intravascular coagulation M. Christmas Disease N. B-Thalassaemia
Osler-Weber-Rendu Syndrome
A rare autosomal dominant disorder. Alternative name = hereditary haemorrhagic telangiectasia. There is a structural abnormality of the blood vessels, resulting in telangiectases, which are thin walled so are likely to bleed. This leads to haemorrhage and anaemia. It is more common in females, and may not present until later in life. Epistaxis is the commonest presenting symptom. This patient is feeling tired, not just because of her 4 children, but because she also has iron deficiency anaemia.
A 3 year old boy is brought to see his GP by his mother. A fortnight ago he had been brought along because of cold-like symptoms, unsurprising since it was the middle of winter and he attends nursery. He was therefore sent home with some Calpol, and as expected his symptoms soon resolved. However this morning his mother noticed a rash on his bottom, and he said his tummy ached.
A. Bile acid malabsorption B. Warfarin overdose C. Antiphospholipid antibody syndrome D. Sickle cell anaemia E. Haemophilia A F. Malignancy G. Von Willebrand’s Disease H. Henoch – Schönlein Purpura I. Osler-Weber-Rendu Syndrome J. Vitamin K Deficiency K. Factor V Leiden L. Disseminated intravascular coagulation M. Christmas Disease N. B-Thalassaemia
Henoch – Schönlein Purpura
Affects children between 2-8yrs old. More common in winter. Usually presents following an upper respiratory tract infection. Rapid onset, with a palpable purpuric rash over the buttocks and legs, as well as symmetrical urticarial plaques, and haemorrhagic bullae. Arthritis of the knee and ankle. Abdominal pain – perhaps due to mesenteric vasculitis. Can have renal involvement – with haematuria/proteinuria. (not idiopathic thrombocytopenic purpura – because it’s not an option here)
22 year old Saharawi refugee presents with anaemia, weight loss, loose stools and blood tests reveal an increased PT and slightly increased APTT, with normal thrombin time and platelet count.
A. Bile acid malabsorption B. Warfarin overdose C. Antiphospholipid antibody syndrome D. Sickle cell anaemia E. Haemophilia A F. Malignancy G. Von Willebrand’s Disease H. Henoch – Schönlein Purpura I. Osler-Weber-Rendu Syndrome J. Vitamin K Deficiency K. Factor V Leiden L. Disseminated intravascular coagulation M. Christmas Disease N. B-Thalassaemia
Vitamin K Deficiency
Prevalence of coeliac disease is highest in Saharawi refugees. This patient has coeliac disease, and as a result of malabsorption is losing weight and has loose stools (steatorrhoea), and vitamin K deficiency. The blood results related to vitamin K deficiency.
A 5 year old boy has the following blood results: normal PT, increased APTT, normal platelet count, decreased VIII:C and decreased vWF.
A. Bile acid malabsorption B. Warfarin overdose C. Antiphospholipid antibody syndrome D. Sickle cell anaemia E. Haemophilia A F. Malignancy G. Von Willebrand’s Disease H. Henoch – Schönlein Purpura I. Osler-Weber-Rendu Syndrome J. Vitamin K Deficiency K. Factor V Leiden L. Disseminated intravascular coagulation M. Christmas Disease N. B-Thalassaemia
Von Willebrand’s Disease
The most common hereditary bleeding disorder, affect 1% of the population. vWF is a carrier protein for factor VIII and stabilises it. Mutation is in chromosome 12.
Haemophilia A = low FVIII and Haemophilia B = low FIX - Haemophilia is X-linked (the qu is about a boy), Von Willebrand’s Disease is autosomal dominant. - Remember that Haemophilia causes prolonged APTT, normal PT and normal bleeding time, with normal VWF level whereas von willebrand’s disease (VWD) causes prolonged APTT AND prolonged bleeding time (very impt to remember!), with low VWF level (but normal level in VWD type 2, which is functionally abnormal) - Both Haemophilia and VWD have normal platelet count. - Remember that FVIII levels may also be low in von willebrand’s disease, as von willebrand’s factor (VWF) is the carrier molecule for FVIII, preventing its premature degredation in the circulation, so if VWF is low, FVIII is vulnerable to degredation and is therefore also low.
A 32 week pregnant lady who has gestational diabetes and is epileptic has a caesarean section while on holiday in rural China. Her newborn baby is suffering from bleeding from the umbilical stump, as well as nose and gums. What is wrong with the baby?
A. Bile acid malabsorption B. Warfarin overdose C. Antiphospholipid antibody syndrome D. Sickle cell anaemia E. Haemophilia A F. Malignancy G. Von Willebrand’s Disease H. Henoch – Schönlein Purpura I. Osler-Weber-Rendu Syndrome J. Vitamin K Deficiency K. Factor V Leiden L. Disseminated intravascular coagulation M. Christmas Disease N. B-Thalassaemia
Vitamin K Deficiency
Drugs, such as anticonvulsants, which the mother is likely to be taking as she suffers from epilepsy, as well as isoniazid, rifampicin and anticoagulants, are risk factors for haemorrhagic disease of the newborn – which is what this baby has. This is due to vitamin K deficiency – although rare now in the UK as prophylactic vitamin K is given to newborns.
A fit 48-year-old investment banker presents to A&E with a painful R arm that was present when he woke up that morning. He is otherwise well and there is no history of trauma or abnormalities of any system. On examination there is marked tenderness and mild erythema along the anterolateral aspect of the forearm and cubital fossa, with no abnormality of the upper arm or axilla.
A. Axillary vein thrombosis B. Deep vein thrombosis C. Inferior vena caval obstruction D. Superficial venous thrombosis E. Thrombophlebitis F. Pulmonary embolism G. DIC H. Postphlebitic syndrome I. Varicose veins J. Superior vena caval obstruction
Superficial venous thrombosis - what it says on the tin - thrombosis of a superficial vein.
A 45-year-old lady, known heavy smoker with chronic respiratory problems, presents to her GP with increasing dyspnoea and swelling of her R arm and face. On examination of her chest there is no asymmetry or tracheal deviation, but there are added sounds over the R upper lobe and on bending forward her face becomes congested.
A. Axillary vein thrombosis B. Deep vein thrombosis C. Inferior vena caval obstruction D. Superficial venous thrombosis E. Thrombophlebitis F. Pulmonary embolism G. DIC H. Postphlebitic syndrome I. Varicose veins J. Superior vena caval obstruction
Superior vena caval obstruction
A 56-year-old woman returns to the Vascular Clinic with recurrence of her L leg ulcer after the area has been knocked by a shopping trolley. On examination the ulcer is situated above the medial malleolus, its dimensions being 6cm x 5cm. The base is filled with yellowish slough and the surrounding area is erythematous, with prominent oedema.
A. Axillary vein thrombosis B. Deep vein thrombosis C. Inferior vena caval obstruction D. Superficial venous thrombosis E. Thrombophlebitis F. Pulmonary embolism G. DIC H. Postphlebitic syndrome I. Varicose veins J. Superior vena caval obstruction
Postphlebitic syndrome
A 48-year-old man develops R-sided pleuritic chest pain and coughs up a trace of bloodstained sputum 8 days after a R hemicolectomy. He has mild dyspnoea but chest examination and chest radiography are normal.
A. Axillary vein thrombosis B. Deep vein thrombosis C. Inferior vena caval obstruction D. Superficial venous thrombosis E. Thrombophlebitis F. Pulmonary embolism G. DIC H. Postphlebitic syndrome I. Varicose veins J. Superior vena caval obstruction
Pulmonary embolism
A 32-year-old lady develops acute swelling of her L leg 2 days post-partum. She had bilateral leg swelling during the pregnancy but the delivery was normal. On examination there is tense swelling of the leg and thigh and some deep tenderness over the calf and medial aspect of the thigh.
A. Axillary vein thrombosis B. Deep vein thrombosis C. Inferior vena caval obstruction D. Superficial venous thrombosis E. Thrombophlebitis F. Pulmonary embolism G. DIC H. Postphlebitic syndrome I. Varicose veins J. Superior vena caval obstruction
Deep vein thrombosis
A drug that is administered intravenously and has a rapid effect by potentiating the action of antithrombin. Action can be reversed quickly which is of relevance in myocardial infarction patients who may require early invasive treatment (ie PTCA).
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Unfractionated heparin (UFH)
Potentiates antithrombin III. Usually given subcutaneously. Can cause osteoporosis and hyperkalaemia.
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Dalteparin (LMWH)
Used to monitor patients undergoing warfarin therapy.
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Prothrombin time (PT)
Used to monitor patients undergoing unfractionated heparin therapy.
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
APTT
This anticoagulant drug is directly contraindicated in pregnancy, especially the first 16 and last 4 weeks of a 40 week gestation.
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Warfarin
Reflects the amount and activity of fibrinogen.
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Thrombin time (TT)
Antiplatelet action. Indicated for primary prophylaxis of stroke in a patient experiencing recurrent retinal TIAs (amaurosis fugax). Ineffective for DVT prophylaxis.
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Aspirin
Antiplatelet action. Licensed for secondary prophylaxis of stroke. More effective than aspirin alone. Cheap.
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Dipyridamole modified release (MR) and aspirin
Antiplatelet action. Licensed for primary prevention of stroke in aspirin allergic patients, secondary prevention of stroke (but expensive) and in acute myocardial infarction in addition to aspirin.
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Clopidogrel
Dangerous combination with no added efficacy and increased GI bleed.
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Clopidogrel and aspirin
New (recommended, Tait) model of starting warfarin
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days
In patients with metallic heart valves, this drug is the most effective anticoagulant
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Warfarin
In patients with cancer and acute venous thromboembolism, the most effective drug at reducing the risk of recurrent VTE is __?
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Dalteparin (LMWH)
This drug when given alone initially increases the clotting risk
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Warfarin alone initially increases the clotting risk because proteins C and S (the anticoagulant proteins) have shorter half lives and disappear from the blood faster than factors II, VII, IX, X (the procoagulant proteins). Since this is dangerous, warfarin is always started under heparin cover.
Side effects include cutaneous necrosis
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Warfarin
The drug most likely to cause thrombocytopaenia with paradoxical thrombosis
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Unfractionated heparin (UFH)
Heparin induced thrombocytopaenia (HIT).
Type I is a predictable dose related effect mediated by platelet aggregation.
Type II is an unpredictable immune response with antibodies directed against the heparin-platelet factor 4 complex.
The large aggregates cause thrombosis.
Treatment is to stop the heparin and start a direct thrombin inhibitor, e.g. hirudin.
HIT more commonly follows treatment with UFH than with LMWH.
Indicated as thrombotic prophylaxis in DIC
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Dalteparin (LMWH)
DIC is a systemic process with the potential for causing thrombosis and hemorrhage. The processes of coagulation and fibrinolysis become abnormally (and often massively) activated within the vasculature, leading to ongoing coagulation and fibrinolysis.
Procoagulant exposure – Blood is exposed to one or more procoagulants, such as tissue factor (TF), from which it is normally protected.
Coagulation – Activation of the coagulation cascade leads to the production of thrombi consisting of fibrin and platelets. These can occur in the microvasculature and/or larger vessels. Formation of thrombi in turn leads to consumption of endogenous coagulation factors, platelets, and anticoagulant factors (eg, protein S, protein C, antithrombin).
Fibrinolysis – Fibrinolysis is activated at sites of thrombus formation, with generation of fibrin degradation products (FDP) that, when present in significant amounts, interfere with both fibrin clot formation and platelet aggregation.
End organ damage – Tissue or organ damage may result from reduced perfusion, thrombosis, and/or bleeding. Often, contributions from DIC itself and the condition that precipitated it are intertwined. Organ failure may result in significant morbidity and mortality.
Common causes of DIC include the following:
●Sepsis from a variety of organisms (bacterial, fungal, viral, and parasitic)
●Malignancy, especially acute promyelocytic leukemia, mucinous tumors (eg, pancreatic, gastric, ovarian), and brain tumors
●Trauma, especially to the central nervous system
●Obstetrical complications, including preeclampsia, retained dead fetus, acute fatty liver of pregnancy
●Intravascular hemolysis, often due to acute hemolytic transfusion reaction (AHTR) in the setting of ABO incompatible transfusion, but also in other forms of hemolysis such as in severe malaria
Contra-indicated if recent sore throat, if ever used before, or in the presence of proliferative retinopathy.
A. Aspirin B. Prothrombin time (PT) C. Warfarin D. Thrombin time (TT) E. 5mg, 5mg, 5mg, 5mg, measure on 5th day, 8th day and then every 4 days F. Dipyridamole modified release (MR) and aspirin G. Clopidogrel and aspirin H. Streptokinase I. LMWH and aspirin J. Dalteparin (LMWH) K. 10mg, 10mg, 5mg, measure on 4th day then every 2 days L. Clopidogrel M. Unfractionated heparin (UFH) N. APTT O. Pentapolysaccharide P. Calciparone
Streptokinase: single chain polypeptide derived from beta-hemolytic streptococcus cultures. It binds to plasminogen, forming a complex that becomes an active enzyme that cleaves peptide bonds on other plasminogen molecules, leading to plasmin activation
A 65 year old patient presents with hepatosplenomegaly. He is mildly anaemic and thrombocytompenic. A blood monocyte count of 1.2 x 109/l is observed. Bone marrow aspirate reveals ring sideroblasts at 15% of total blasts. Auer rods are observed.
A. Myelodysplastic syndrome,unclassifiable
B. Refractory anaemia
C. Refractory Anaemia with excess of Blasts II
D. Aplastic Anaemia
E. Refractory Cytopaenia with Multilineage Dysplasia
F. Chronic Myelomonocytic Anaemia
G. Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality (5q syndrome)
H. Acute Myeloid Leukaemia
I. Secondary Sideroblastic Anaemia
J. Refractory Anaemia with Ring Sideroblasts
K. Refractory Anaemia with excess of Blasts I
Chronic Myelomonocytic Anaemia
By definition, this has to be CMML, because the patient has:
a) 1/0 x 10^9/L
The diagnosis of AML requires >20% blasts, so clearly this patient doesn’t meet the criteria.
Chronic myelomonocytic leukemia (CMML)
- not to be confused with chronic myelogenous leukemia or CML
- characterized by less than 20% myeloblasts in the bone marrow
and greater than 1000 * 109/uL monocytes circulating in the peripheral blood.
Also something that often comes up in exams:
- syndrome, typically seen in older women with normal or high platelet counts
and isolated deletions of the long arm of chromosome 5 in bone marrow cells.
An alcoholic presents to your clinic with anaemia. Sideroblasts are observed on morphological examination.
A. Myelodysplastic syndrome,unclassifiable
B. Refractory anaemia
C. Refractory Anaemia with excess of Blasts II
D. Aplastic Anaemia
E. Refractory Cytopaenia with Multilineage Dysplasia
F. Chronic Myelomonocytic Anaemia
G. Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality (5q syndrome)
H. Acute Myeloid Leukaemia
I. Secondary Sideroblastic Anaemia
J. Refractory Anaemia with Ring Sideroblasts
K. Refractory Anaemia with excess of Blasts I
Secondary Sideroblastic Anaemia
(Refractory anemia with ringed sideroblasts (RARS)
- also characterized by less than 5% myeloblasts in the bone marrow,
but distinguished by the presence of 15% or greater red cell precursors in the marrow
being abnormal iron-stuffed cells called ‘ringed sideroblasts’)
A 58 year old lady complains of lethargy and “easy bruising”. She presents with purpura. Her FBC reveals Hb 10.5g/dl; WBCs 2.3x109/l and platelets 8x109/l. Blood film reveals
Refractory Cytopaenia with Multilineage Dysplasia: To count as significant, dysplasia must involve at least 10% of cells in a lineage. To count as RCMD, at least 2 MYELOID lineages must be dysplastic, and there must be bi or pancytopenia in the peripheral blood. (This can include anaemia!)
Refractory cytopenia with multilineage dysplasia:
Diagnosis requires at least 2 of the following:
• low red blood cell count
• low white blood cell count
• low platelet count
With monocytes less than 1 x 109/L, no/few blast cells and no Auer rods.
Bone marrow shows dysplasia in 2 or more cell types, affecting at least 10% of the cells, and less than 5% blasts
It is a form of Myelodysplastic Syndromes (MDS) - a group of related disorders in which stem cells in the bone marrow malfunction. Stem cells develop into red blood cells, white blood cells, and platelets. In MDS, defective stem cells produce too many defective blood cells and too few normal blood cells.
A 78 year old male patient with recurring infections of the face and maxillary sinuses associated with neutropenia. His bloods are: Hb 9.8 g/dl; WBC 1.3x109/l; Neutrophils 0.3x109/l; platelets 38x109/l.The lab informs you that there are Blasts approximately compromise 17% of bone marrow aspirate.
A. Myelodysplastic syndrome,unclassifiable
B. Refractory anaemia
C. Refractory Anaemia with excess of Blasts II
D. Aplastic Anaemia
E. Refractory Cytopaenia with Multilineage Dysplasia
F. Chronic Myelomonocytic Anaemia
G. Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality (5q syndrome)
H. Acute Myeloid Leukaemia
I. Secondary Sideroblastic Anaemia
J. Refractory Anaemia with Ring Sideroblasts
K. Refractory Anaemia with excess of Blasts I
Refractory Anaemia with excess of Blasts II
- characterized by 5-19% myeloblasts in the marrow
Refractory anaemia with an excess of blasts can be categorised into 1 and 2.
Both involve have monocytes less than 1 x 109/L, bone marrow showing dysplasia in 1 or more cell types and at least 1 of the following:
• low red blood cell count
• low white blood cell count
• low platelet count
But in type 1: there are no Auer rods in the peripheral film or bone marrow, less than 5% blasts in peripheral film and 5-19% blasts in the bone marrow
Whereas type 2: shows Auer rods in the peripheral film and bone marrow, 5-19% blasts in peripheral film, 10-19% blasts in the bone marrow
Refractory anemia with excess blasts in transformation (RAEB-T) - characterized by 20-29% myeloblasts in the marrow
You are called to A&E to see a 65 year old man. He is complaining of fever, shortness of breath, and has lost 5Kg in the last few months. His notes say he was previously diagnosed with “Refractory Anaemia with excess Blasts in Transformation” (RAEB-t). His blast cell count is approximately 30% of all nucleated cells.
A. Myelodysplastic syndrome,unclassifiable
B. Refractory anaemia
C. Refractory Anaemia with excess of Blasts II
D. Aplastic Anaemia
E. Refractory Cytopaenia with Multilineage Dysplasia
F. Chronic Myelomonocytic Anaemia
G. Myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality (5q syndrome)
H. Acute Myeloid Leukaemia
I. Secondary Sideroblastic Anaemia
J. Refractory Anaemia with Ring Sideroblasts
K. Refractory Anaemia with excess of Blasts I
Acute Myeloid Leukaemia
Refractory anaemia with an excess of blasts only takes you upto 20% in the bone marrow, anything greater than that is AML…remember AML is an associated condition and can develop from MDS
Cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. Acute myeloid leukemia (AML) is the most common acute leukemia in adults
The symptoms of AML are caused by replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells, platelets, and normal white blood cells. These symptoms include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection.
Enlargement of the spleen may occur in AML, but it is typically mild and asymptomatic. Lymph node swelling is rare in AML, in contrast to acute lymphoblastic leukemia.
Down syndrome is associated with a 10- to 18-fold increase in the risk of AML.
A 34 year old man with peripheral cytopenia suffers from bleeding gums. Peripheral blood shows 5% blast cells and bone marrow 42% blast cells.
A. Refractory cytopenia with multilineage dysplasia B. Inherited aplastic anaemia C. Secondary aplastic anaemia D. Juvenile myelomonocytic leukaemia E. Acute myeloid leukaemia F. 5q syndrome G. Refractory anaemia with an excess of blasts H. Idiopathic aplastic anaemia I. Myelofibrosis J. Refractory anaemia
Acute myeloid leukaemia
Refractory anaemia with an excess of blasts only takes you upto 20% in the bone marrow, anything greater than that is AML…remember AML is an associated condition and can develop from MDS
Cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. Acute myeloid leukemia (AML) is the most common acute leukemia in adults
The symptoms of AML are caused by replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells, platelets, and normal white blood cells. These symptoms include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection.
Enlargement of the spleen may occur in AML, but it is typically mild and asymptomatic. Lymph node swelling is rare in AML, in contrast to acute lymphoblastic leukemia.
Down syndrome is associated with a 10- to 18-fold increase in the risk of AML.
A 74 year old woman with high-normal platelet count. Bone marrow aspirate shows hyperplasia of hypolobulated micromegakaryocytes. Responds well to lenalidomide.
A. Refractory cytopenia with multilineage dysplasia B. Inherited aplastic anaemia C. Secondary aplastic anaemia D. Juvenile myelomonocytic leukaemia E. Acute myeloid leukaemia F. 5q syndrome G. Refractory anaemia with an excess of blasts H. Idiopathic aplastic anaemia I. Myelofibrosis J. Refractory anaemia
5q Syndrome - myelodysplasia with the 5q- syndrome
The Clinical picture is usually:
- Female, 74 years with mild to moderate degrees of anemia and a low white blood cell count.
- Normal or increased platelet counts along with bone marrow hyperplasia of hypo-lobulated micro-megakaryocytes
- Less than 5% blasts and no Auer rods
Approximately 5 percent of patients with MDS present with “5q minus syndrome” characterized by severe anemia, preserved platelet counts, and del(5q) as the sole cytogenetic abnormality. Patients with 5q minus syndrome have high response rates to treatment with low-dose lenalidomide.
A 20 year old man with hepatitis C complains of fatigue and breathlessness and bruises very easily.
A. Refractory cytopenia with multilineage dysplasia B. Inherited aplastic anaemia C. Secondary aplastic anaemia D. Juvenile myelomonocytic leukaemia E. Acute myeloid leukaemia F. 5q syndrome G. Refractory anaemia with an excess of blasts H. Idiopathic aplastic anaemia I. Myelofibrosis J. Refractory anaemia
Secondary aplastic anaemia - fatigue and breathlessness (anaemia), bruises (thrombocytopenia)
Aplastic anemia (AA) is characterized by diminished or absent hematopoietic precursors in the bone marrow, most often due to injury to the pluripotent stem cell. The diagnosis of AA should be considered in every patient presenting with pancytopenia (simultaneous presence of anemia, thrombocytopenia, and neutropenia).
Examination of the peripheral blood smear reveals normocytic or macrocytic red cells with a marked reduction in polychromatophilia (reticulocytes). Neutrophils and platelets are decreased in number. Abnormal circulating white blood cells are not present. The bone marrow biopsy is profoundly hypocellular with a decrease in all elements; the marrow space is composed mostly of fat cells and marrow stroma. Residual hematopoietic cells are morphologically normal, and infiltration with malignant cells or fibrosis is not present.
Hepatitis viruses and HIV can cause severe aplasia. The mechanism may involve T cell activation with release of cytokines (see below), or activation of a cytotoxic T cell clone which recognizes similar target antigens on both liver and bone marrow cells. Hepatitis-associated disease most often affects boys and young men, with aplasia developing two to three months after an episode of acute hepatitis
This patients blood film shows classic Pelger-Huet neutrophils and bone marrow blasts make up 15% of cells.
A. Refractory cytopenia with multilineage dysplasia B. Inherited aplastic anaemia C. Secondary aplastic anaemia D. Juvenile myelomonocytic leukaemia E. Acute myeloid leukaemia F. 5q syndrome G. Refractory anaemia with an excess of blasts H. Idiopathic aplastic anaemia I. Myelofibrosis J. Refractory anaemia
Refractory anaemia with an excess of blasts
Pelger-Huet anomaly: can occur as an inherited disorder or can be acquired in patients with myelodysplastic syndromes. There is reduced lobulation of mature neutrophils. Such cells typically have a bilobed nucleus connected by a thin strand, giving a “pince-nez” appearance, often accompanied by reduced or absent granulation
Refractory anaemia with an excess of blasts can be categorised into 1 and 2.
Both involve have monocytes less than 1 x 109/L, bone marrow showing dysplasia in 1 or more cell types and at least 1 of the following:
• low red blood cell count
• low white blood cell count
• low platelet count
But in type 1: there are no Auer rods in the peripheral film or bone marrow, less than 5% blasts in peripheral film and 5-19% blasts in the bone marrow
Whereas type 2: shows Auer rods in the peripheral film and bone marrow, 5-19% blasts in peripheral film, 10-19% blasts in the bone marrow
In this case haemoglobin is normal but there is a reduction in platelets and neutrophils
A. Refractory cytopenia with multilineage dysplasia B. Inherited aplastic anaemia C. Secondary aplastic anaemia D. Juvenile myelomonocytic leukaemia E. Acute myeloid leukaemia F. 5q syndrome G. Refractory anaemia with an excess of blasts H. Idiopathic aplastic anaemia I. Myelofibrosis J. Refractory anaemia
Refractory cytopenia with multilineage dysplasia:
Diagnosis requires at least 2 of the following:
• low red blood cell count
• low white blood cell count
• low platelet count
With monocytes less than 1 x 109/L, no/few blast cells and no Auer rods.
Bone marrow shows dysplasia in 2 or more cell types, affecting at least 10% of the cells, and less than 5% blasts
It is a form of Myelodysplastic Syndromes (MDS) - a group of related disorders in which stem cells in the bone marrow malfunction. Stem cells develop into red blood cells, white blood cells, and platelets. In MDS, defective stem cells produce too many defective blood cells and too few normal blood cells.
A 64-year old woman receiving long-term chemotherapy for lymphoma presents with worsening bone pain, recurrent fever and night sweats. Blood film shows blast cells with Auer rods.
A. Vincristine poisoning B. DIC C. Chronic lymphocytic leukaemia D. Chronic myeloid leukaemia E. Tumour-lysis syndrome F. Bronchial carcinoma G. Septicaemia H. Hairy cell leukaemia I. Acute promyelocytic leukaemia J. Lung fibrosis K. Acute myeloid leukaemia L. Hypothyroidism M. Acute lymphoblastic leukaemia N. Richter's syndrome
Acute Myeloid Leukaemia
Cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. Acute myeloid leukemia (AML) is the most common acute leukemia in adults
The symptoms of AML are caused by replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells, platelets, and normal white blood cells. These symptoms include fatigue, shortness of breath, easy bruising and bleeding, and increased risk of infection.
Enlargement of the spleen may occur in AML, but it is typically mild and asymptomatic. Lymph node swelling is rare in AML, in contrast to acute lymphoblastic leukemia.
Down syndrome is associated with a 10- to 18-fold increase in the risk of AML.
A 61-year-old man with CLL presents with recurrent pneumonia and haemoptysis. On fibreoptic bronchoscopy, the patient is found to have an endobronchial mass. The biopsy shows anaplastic, large cell lymphoma.
A. Vincristine poisoning B. DIC C. Chronic lymphocytic leukaemia D. Chronic myeloid leukaemia E. Tumour-lysis syndrome F. Bronchial carcinoma G. Septicaemia H. Hairy cell leukaemia I. Acute promyelocytic leukaemia J. Lung fibrosis K. Acute myeloid leukaemia L. Hypothyroidism M. Acute lymphoblastic leukaemia N. Richter's syndrome
Richter’s Syndrome - development of an aggressive large-cell lymphoma in the setting of underlying chronic lymphocytic leukaemia.
The onset of RT is heralded by sudden clinical deterioration, characterized by a marked increase in lymphadenopathy at one or more sites (often abdominal), splenomegaly, and worsening “B” symptoms (ie, fever, night sweats, weight loss). The serum level of lactate dehydrogenase (LDH) is elevated in 50 to 80 percent of patients with RT compared with 8 percent of CLL patients.
Biopsy is required to confirm the diagnosis, and usually shows a histologic pattern consistent with diffuse large B cell lymphoma.
The prognosis and outcome are historically poor for RT and the disease is invariably fatal if left untreated
A newly diagnosed ALL patient complains of tiredness, polyuria, polydipsia, abdominal pain and vomiting on receiving chemotherapy. On examination, BP: 160/100mmHg, temp: 39ºC, and ECG shows tented T waves. Blood test shows serum K+: 6.9mmol/L and phosphate: 7.1 mmol/L. The patient later dies of cardiac arrest.
A. Vincristine poisoning B. DIC C. Chronic lymphocytic leukaemia D. Chronic myeloid leukaemia E. Tumour-lysis syndrome F. Bronchial carcinoma G. Septicaemia H. Hairy cell leukaemia I. Acute promyelocytic leukaemia J. Lung fibrosis K. Acute myeloid leukaemia L. Hypothyroidism M. Acute lymphoblastic leukaemia N. Richter's syndrome
Tumour Lysis Syndrome (TLS) is an oncologic emergency that is caused by massive tumor cell lysis with the release of large amounts of potassium, phosphate, and nucleic acids into the systemic circulation resulting in hyperkalemia, hyperphosphatemia, secondary hypocalcemia, hyperuricemia, and acute kidney injury. Catabolism of the nucleic acids to uric acid leads to hyperuricemia, and the marked increase in uric acid excretion can result in the precipitation of uric acid in the renal tubules and can also induce renal vasoconstriction, impaired autoregulation, decreased renal blood flow, and inflammation, resulting in acute kidney injury. Hyperphosphatemia with calcium phosphate deposition in the renal tubules can also cause acute kidney injury.
The symptoms associated with TLS largely reflect the associated metabolic abnormalities (hyperkalemia, hyperphosphatemia, and hypocalcemia). They include nausea, vomiting, diarrhea, anorexia, lethargy, hematuria, heart failure, cardiac dysrhythmias, seizures, muscle cramps, tetany, syncope, and possible sudden death
TLS most often occurs after the initiation of cytotoxic therapy in patients with high-grade lymphomas (particularly the Burkitt subtype) and acute lymphoblastic leukemia.
A routine medical of 33-year-old footballer reveals: Hb = 9.9g/dl and WCC = 130 x 109/L. His blood film shows whole spectrum of myeloid precursors, including a few blast cells. He admits to having frequent night sweats and blurred vision. There is a presence of Ph chromosome t(9;22) on cytogenetic analysis.
A. Vincristine poisoning B. DIC C. Chronic lymphocytic leukaemia D. Chronic myeloid leukaemia E. Tumour-lysis syndrome F. Bronchial carcinoma G. Septicaemia H. Hairy cell leukaemia I. Acute promyelocytic leukaemia J. Lung fibrosis K. Acute myeloid leukaemia L. Hypothyroidism M. Acute lymphoblastic leukaemia N. Richter's syndrome
Chronic Myeloid Leukaemia: a myeloproliferative neoplasm characterized by the dysregulated production and uncontrolled proliferation of mature and maturing granulocytes with fairly normal differentiation.
CML is associated with the fusion of two genes: BCR (on chromosome 22) and ABL1 (on chromosome 9) resulting in the BCR-ABL1 fusion gene. This abnormal fusion typically results from a reciprocal translocation between chromosomes 9 and 22, t(9;22)(q34;q11), that gives rise to an abnormal chromosome 22 called the Philadelphia (Ph) chromosome. It is this deregulated tyrosine kinase that is implicated in the pathogenesis of CML.
The clinical hallmark of CML is the uncontrolled production of mature and maturing granulocytes, predominantly neutrophils, but also basophils and eosinophils. In the absence of treatment, CML has a triphasic or biphasic clinical course as it progresses from a chronic phase to an accelerated phase and on to a terminal blast crisis.
The peripheral smear typically demonstrates a leukocytosis. Bone marrow aspiration and biopsy demonstrates granulocytic hyperplasia with a maturation pattern that reflects that seen in the peripheral smear
Treatment: tyrosine kinase inhibitor (imatinib)
A 5-year-old girl presents with failure to thrive, recurrent fever and bruising. Immunotyping reveals the presence of CD10.
A. Vincristine poisoning B. DIC C. Chronic lymphocytic leukaemia D. Chronic myeloid leukaemia E. Tumour-lysis syndrome F. Bronchial carcinoma G. Septicaemia H. Hairy cell leukaemia I. Acute promyelocytic leukaemia J. Lung fibrosis K. Acute myeloid leukaemia L. Hypothyroidism M. Acute lymphoblastic leukaemia N. Richter's syndrome
Acute Lymphoblastic Leukaemia, the most common form of cancer in children, comprises approximately 30 percent of all childhood malignancies. Not likely to be AML as AML accounts for less than 10 percent of acute leukemias in children less than 10 years of age.
The most common presenting symptoms of ALL are nonspecific (eg, fever, bleeding, bone pain, lymphadenopathy). Bone pain, particularly affecting the long bones, and caused by leukemic involvement of the periosteum, is a presenting symptom in 21 to 38 percent of cases of acute leukaemia.
Lymphadenopathy associated with malignancy usually is non-tender, firm, rubbery, and matted - Approximately 50 percent of children with ALL present with lymphadenopathy.
Most children with ALL have anemia and/or thrombocytopenia with either normal or depressed WBC counts and lymphoblasts on peripheral smear. Approximately one-half of children with ALL present with bleeding (including petechiae and purpura) and three-quarters have a platelet count
A 6-year-old boy presents with bone pain. On examination you notice he looks pale and has many bruises. What is his diagnosis?
A. Magnesium exposure B. Chronic myeloid leukaemia C. Lymphocytes D. Ionising radiation E. Thalassaemia F. Acute lymphocytic leukaemia G. Blast cells H. Chronic lymphocytic leukaemia I. Acute myeloid leukaemia J. Neutrophils K. Sickle cell disease L. Marfan’s syndrome M. Down’s syndrome
Acute Lymphoblastic Leukaemia, the most common form of cancer in children, comprises approximately 30 percent of all childhood malignancies. Not likely to be AML as AML accounts for less than 10 percent of acute leukemias in children less than 10 years of age.
The most common presenting symptoms of ALL are nonspecific (eg, fever, bleeding, bone pain, lymphadenopathy). Bone pain, particularly affecting the long bones, and caused by leukemic involvement of the periosteum, is a presenting symptom in 21 to 38 percent of cases of acute leukaemia.
Lymphadenopathy associated with malignancy usually is non-tender, firm, rubbery, and matted - Approximately 50 percent of children with ALL present with lymphadenopathy.
Most children with ALL have anemia and/or thrombocytopenia with either normal or depressed WBC counts and lymphoblasts on peripheral smear. Approximately one-half of children with ALL present with bleeding (including petechiae and purpura) and three-quarters have a platelet count
A patient has acute lymphoblastic leukaemia. A bone marrow biopsy will show infiltration by which cells?
A. Magnesium exposure B. Chronic myeloid leukaemia C. Lymphocytes D. Ionising radiation E. Thalassaemia F. Acute lymphocytic leukaemia G. Blast cells H. Chronic lymphocytic leukaemia I. Acute myeloid leukaemia J. Neutrophils K. Sickle cell disease L. Marfan’s syndrome M. Down’s syndrome
Blast Cells (>20%)
Acute leukemia, the most common form of cancer in children, comprises approximately 30 percent of all childhood malignancies, with acute lymphoblastic leukemia (ALL) being five times more common than acute myeloid leukemia (AML).
The most common presenting symptoms of ALL are nonspecific (eg, fever, bleeding, bone pain, lymphadenopathy). Bone pain, particularly affecting the long bones, and caused by leukemic involvement of the periosteum, is a presenting symptom in 21 to 38 percent of cases of acute leukaemia.
Lymphadenopathy associated with malignancy usually is non-tender, firm, rubbery, and matted - Approximately 50 percent of children with ALL present with lymphadenopathy.
Most children with ALL have anemia and/or thrombocytopenia with either normal or depressed WBC counts and lymphoblasts on peripheral smear. Approximately one-half of children with ALL present with bleeding (including petechiae and purpura) and three-quarters have a platelet count
Patients with this inherited disorder have an increased risk of developing acute leukaemia.
A. Magnesium exposure B. Chronic myeloid leukaemia C. Lymphocytes D. Ionising radiation E. Thalassaemia F. Acute lymphocytic leukaemia G. Blast cells H. Chronic lymphocytic leukaemia I. Acute myeloid leukaemia J. Neutrophils K. Sickle cell disease L. Marfan’s syndrome M. Down’s syndrome
Downs Syndrome
Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children. The peak incidence occurs between two and five years of age. Children with certain genetic and immunodeficiency syndromes are at increased risk. These include Down syndrome, Neurofibromatosis type 1, Bloom syndrome, and ataxia telangiectasia.
The most common presenting symptoms of ALL are nonspecific: fever, infection, bleeding, bone pain, or lymphadenopathy. Unexplained persistence of any of these common signs or symptoms should prompt consideration of malignancy as a possible cause
An environmental factor associated with acute leukaemia.
A. Magnesium exposure B. Chronic myeloid leukaemia C. Lymphocytes D. Ionising radiation E. Thalassaemia F. Acute lymphocytic leukaemia G. Blast cells H. Chronic lymphocytic leukaemia I. Acute myeloid leukaemia J. Neutrophils K. Sickle cell disease L. Marfan’s syndrome M. Down’s syndrome
Ionising Radiation
The commonest adult leukaemia.
A. Magnesium exposure B. Chronic myeloid leukaemia C. Lymphocytes D. Ionising radiation E. Thalassaemia F. Acute lymphocytic leukaemia G. Blast cells H. Chronic lymphocytic leukaemia I. Acute myeloid leukaemia J. Neutrophils K. Sickle cell disease L. Marfan’s syndrome M. Down’s syndrome
Chronic Lymphocytic Leukaemia is a chronic lymphoproliferative disorder (lymphoid neoplasm) characterized by a progressive accumulation of functionally incompetent lymphocytes, which are usually monoclonal in origin.
CLL is the most common leukemia in Western countries, accounting for approximately 30 percent of all leukemias in the United States. It has a male predominance and is more common in Caucasians. The median age at diagnosis is 70 years. There are no clearly discernible occupational or environmental risk factors.
The vast majority of patients are asymptomatic at diagnosis and only come to the physician’s attention based upon abnormalities found on routine blood counts. Alternatively, some patients may present with painless swelling of lymph nodes, often in the cervical area, which spontaneously wax and wane, but do not altogether disappear. Less common presentations include constitutional “B” symptoms of lymphoma, symptoms related to an acquired immunodeficiency, or autoimmune complications.
Most patients with CLL have a prominent lymphocytosis in the peripheral blood and bone marrow at diagnosis. Neutropenia, anemia, and thrombocytopenia may also be observed at the time of initial diagnosis, and are usually of relatively mild degree.
Immunophenotypic analysis reveals a clonal population (kappa or lambda light chain) of cells that express B cell associated antigens (CD19, CD20, and CD23), the T cell associated antigen CD5, and low levels of surface immunoglobulin
A 50yr old man presents to his GP complaining of weight loss, tiredness, easy bruising and a painful big toe. On examination his spleen is massively enlarged. Investigation shows a raised serum urate. The peripheral blood film is abnormal, showing proliferation of which type of cell?
A. Pelger-Huet cells B. Clonal B lymphocytes C. Chromosome 9;22 translocation D. Chromosome 11q23 deletion E. Neutrophils F. Eosinophils G. Blast cells H. Auer rods I. Reticulocytes J. Platelets K. Spherocytes
Neutrophils - CML. Increased mass of turning-over cells generates urate.
Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome t(9;22)(q34;q11) and/or the BCR-ABL fusion gene. This genetic abnormality results in the formation of a unique gene product (BCR-ABL), which results in a constitutively active tyrosine kinase. It is this deregulated tyrosine kinase that is implicated in the development of CML and is the target of current therapies - Imatinib.
The clinical hallmark of CML is the uncontrolled production of mature and maturing granulocytes, predominantly neutrophils, but also basophils and eosinophils.
Decreased efficiency of renal uric acid excretion is responsible for about 85 to 90 percent of primary or secondary hyperuricemia. The remaining 10 to 15 percent of patients with hyperuricemia ostensibly overproduce uric acid. These disorders are often due to inherited defects in regulation of purine nucleotide synthesis, disordered adenosine triphosphate (ATP) metabolism, or disorders resulting in increased rates of cell turnover.
A 65yr old lady is seen in the haematology clinic where she has been treated for 7 years with Imantinib for chronic myeloid leukaemia. Having been previously well, she is now complaining of shortness of breath and general weakness. Examination reveals splenomegally. Her peripheral blood film has changed from previous appointments and reflects the progression of her disease. Which type of cell is now proliferating?
A. Pelger-Huet cells B. Clonal B lymphocytes C. Chromosome 9;22 translocation D. Chromosome 11q23 deletion E. Neutrophils F. Eosinophils G. Blast cells H. Auer rods I. Reticulocytes J. Platelets K. Spherocytes
Blast Cells - CML, blast phase. Transformation tends to be into AML but in 20% is lymphoblastic (ALL).
Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome t(9;22)(q34;q11) and/or the BCR-ABL fusion gene. This genetic abnormality results in the formation of a unique gene product (BCR-ABL), which results in a constitutively active tyrosine kinase. It is this deregulated tyrosine kinase that is implicated in the development of CML and is the target of current therapies. CML has historically been a triphasic disease. Approximately 85 to 90 percent of patients present in a chronic stable phase. Without treatment, this inevitably progresses to a more aggressive, accelerated phase, and then culminates in a very difficult to treat blast crisis.
In approximately 30 percent of cases, blast crisis in CML is of the lymphoid (ie, acute lymphoblastic leukemia [ALL]), rather than the myeloid (ie, acute myeloid leukemia [AML]) phenotype. Transformation may be suggested clinically by the development of signs and symptoms more typical of acute leukemia (eg, night sweats, weight loss, fever, bone pain, symptoms of anemia).
A 70yr old man complains of a year’s history of fatigue, weight loss and recurrent sinusitis. His white cell count is raised with a lymphocytosis of 283x109 /L. Blood film shows features of haemolysis and Coomb’s test is positive. Further investigation show the bone marrow, blood and lymph nodes are infiltrated with which cell population?
A. Pelger-Huet cells B. Clonal B lymphocytes C. Chromosome 9;22 translocation D. Chromosome 11q23 deletion E. Neutrophils F. Eosinophils G. Blast cells H. Auer rods I. Reticulocytes J. Platelets K. Spherocytes
Clonal B lymphocytes: CLL.
On immunophenotyping only two chronic B cell leukaemia/lymphomas are CD5+(an antigen commonly expressed by T cells): CLL (CD5+ CD23+) and Mantle Cell Lymphoma (CD5+ CD23-). CLL may be assoc. with Coombs positive AIHA and ITP. The combination is called Evans syndrome.
CLL is the most common leukemia in adults in Western countries and is considered to be mainly a disease of older adults (median age at diagnosis of 70 years). Most patients feel entirely well with no symptoms when a routine blood count reveals an absolute lymphocytosis, leading to a diagnosis of CLL. The most common abnormal finding on physical examination of the patient with CLL is lymphadenopathy, the spleen is the second most frequently enlarged lymphoid organ. The peripheral blood smear of patients with CLL demonstrates a lymphocytosis. The leukemic cells are typically small, mature appearing lymphocytes with a dense nucleus, partially aggregated (clumped) chromatin, and without discernible nucleoli. Bone marrow aspirate and biopsy are not required for the diagnosis of CLL. If bone marrow biopsy and aspiration are performed at the time of initial diagnosis, they usually demonstrate normal to increased cellularity, with lymphocytes accounting for >30 percent of all nucleated cells
Patients with CLL have an increased incidence of autoimmune hemolytic anemia (AIHA)
A routine full blood count on a 62yr old gardener reveals a high white cell count of 154x109 /L, and the differential shows this to be a neutrophilia. The haemoglobin and platelet count are normal. Biopsy shows a hypercellular “packed” bone marrow, and cells show the presence of which chromosomal abnormality?
A. Pelger-Huet cells B. Clonal B lymphocytes C. Chromosome 9;22 translocation D. Chromosome 11q23 deletion E. Neutrophils F. Eosinophils G. Blast cells H. Auer rods I. Reticulocytes J. Platelets K. Spherocytes
Chromosome 9;22 translocation
CML is a myeloproliferative neoplasm characterized by the dysregulated production and uncontrolled proliferation of mature and maturing granulocytes with fairly normal differentiation.
CML is associated with the fusion of two genes: BCR (on chromosome 22) and ABL1 (on chromosome 9) resulting in the BCR-ABL1 fusion gene. This abnormal fusion typically results from a reciprocal translocation between chromosomes 9 and 22, t(9;22)(q34;q11), that gives rise to an abnormal chromosome 22 called the Philadelphia (Ph) chromosome. It is this deregulated tyrosine kinase that is implicated in the pathogenesis of CML.
The clinical hallmark of CML is the uncontrolled production of mature and maturing granulocytes, predominantly neutrophils, but also basophils and eosinophils. In the absence of treatment, CML has a triphasic or biphasic clinical course as it progresses from a chronic phase to an accelerated phase and on to a terminal blast crisis.
The peripheral smear typically demonstrates a leukocytosis. Bone marrow aspiration and biopsy demonstrates granulocytic hyperplasia with a maturation pattern that reflects that seen in the peripheral smear
Treatment: tyrosine kinase inhibitor (imatinib)
The following are contraindications to renal transplantation: True/False
- Aged above 65 years
- Active Sepsis
- HIV positive
- BMI > 30
- Aged above 65 years: FALSE - must have a predicted survival
- BMI>30: FALSE - obesity is only a relative contraindication
Contraindications are
Active malignancy is a contraindication for transplantation because immunosuppressive therapy may aggravate underlying malignancy
Active HIV disease is a contraindication for transplantation
A 40 year old female presents with a rash and AKI is diagnosed. What is the most likely cause of her renal failure from the following list?
NSAIDS Systemic Vasculitis Amyloidosis Tumour Lysis Syndrome following chemotherapy for lymphoma Myeloma
Systemic Vasculitis
AKI - abrupt or rapid decline in renal filtration function. This condition is usually marked by a rise in serum creatinine concentration
Can be divided into 3 categories:
- Prerenal - As an adaptive response to severe volume depletion and hypotension, with structurally intact nephrons
- Intrinsic - In response to cytotoxic, ischemic, or inflammatory insults to the kidney, with structural and functional damage
- Post-renal - From obstruction to the passage of urine
Systemic vasculitis includes all the large (Takayasu, giant cell), medium (Polyarteritis nodosa, Kawasaki disease) and small (Wegener’s granulomatosis, Churg-Strauss, microscopic polyarteritis, Henoch Schonlein purpura) vessel vasculitides
Regarding Hyperkalaemia, which of the following is true?
A. ECG changes are peaked p waves and flattened t waves
B. In those with CKD, dietary intake is a major cause and high potassium levels are found in foods such as milk, chocolate, dried fruits and tomatoes.
C. NSAIDs can lower potassium levels
D. Hyperaldosteronism is a common cause
E. All of the above
TRUE - In those with CKD, dietary intake is a major cause and high potassium levels are found in foods such as milk, chocolate, dried fruits and tomatoes.
ECG changes are tall tented t waves, loss of p waves and a broad QRS
Hypoaldosteronism is a cause
You patient with CKD has been started on an ESA but does not respond. What could be the cause?
Iron deficiency TB Malignancy B12 and folate deficiency Hyper-parathyroidism Any of the above
Any of the above
Anemia has been implicated as a contributing factor in many of the symptoms associated with reduced kidney function. The partial correction of anemia in chronic kidney disease (CKD) patients with end-stage renal disease (ESRD) and CKD improves physiologic and clinical parameters and quality of life, compared with the severely low hemoglobin (Hgb) levels that were common prior to the availability of erythropoiesis-stimulating agents (ESAs)
A 68 year old man with previously normal renal function is found to have a creatinine of 624umol/L. Renal ultrasound shows hydro-nephrosis in both kidneys. What is the likely cause of his AKI?
Right sided kidney stone Left ureteric transitional cell carcinoma Membranous glomerulonephropathy Benign prostatic hypertrophy Amyloid
Benign prostatic hypertrophy: something that is causing compression of both sides!
Why does each drug predispose to patients to developing pre-renal AKI?
NSAIDs
Calcineurin inhibitors
ACEI/ARBs
NSAIDs - decrease afferent arteriolar dilatation
Calcineurin inhibitors - decrease afferent arteriolar dilatation
ACEI/ARBs - decreases efferent arteriolar constriction
Diuretics
Which is the following is true regarding urine dipstick testing?
A. If the dipstick is negative for blood it reliably excludes haematuria
B. Haematuria is the only cause of a positive dipstick test for blood
C. You can reliably exclude bacteriuria if the urine dipstick is negative for nitrites
D. The urine dipstick detects Bence Jones proteins
E. Glycosuria detected by the dipstick means the patient has diabetes
If the dipstick is negative for blood it reliably excludes haematuria
Not all bacteria will convert nitrates in the urine to nitrites - so even if this test is negative bacteria may still be present
Bence Jones proteins are not detectable on dipstick but will show as a monoclonal band on electrophoresis
Which factor limits the use of a serum creatinine as a marker of GFR?
A. It is influenced by intake of fat B. It is lower in the black population C. It is reabsorbed by the renal tubules D. It is related to muscle mass E. All of the above
It is related to muscle mass
- It is influenced by the intake of protein, not fat
- Tends to be higher in the black population (associated with a higher muscle mass in these patients)
Which has the lowest calcium?
A. Primary Hyperparathyroidism B. Secondary Hyperparathyroidism C. Osteoporosis D. Paget's disease of the bone E. Breast Cancer
Secondary Hyperparathyroidism - increased PTH production in response to hypocalcaemia
Primary Hyperparathyroidism - excess PTH production by parathyroids - usually an adenoma
Osteoporosis doesn’t alter blood calcium levels.
Paget’s disease of the bone = increased calcium and ALP
A 65-year-old chronic alcoholic presents to the A&E Department with a minor head injury. On examination he is found to be pale. Blood tests show a high MCV. What is the likeliest result of MCV (fl) in a normal person?
A. 15 B. 2.2 C.130 D. 30 E. 4 F. 290 G. 90
90: The normal range (95 percent confidence) for the MCV in adults is 80 to 96 fL.
By definition, microcytosis is taken to mean the presence of red blood cells (RBCs) with a mean corpuscular volume (MCV) less than normal, while macrocytosis means the presence of RBCs with an MCV greater than normal. Since the MCV is an average value, a sample with an MCV in the normal range may still have a significant population of small and/or large red cells. This situation is best assessed by direct examination of the peripheral smear, although a clue to the presence of cells of varying sizes (ie, anisocytosis) can be obtained from a determination of the RBC distribution width.
CAUSES OF NORMOCYTIC ANEMIA — By definition, the mean red blood cell (RBC) volume is normal (MCV between 80 and 96 fL) in patients with normocytic anemia. This is an extremely large and amorphous category, which can be narrowed somewhat by examination of the blood smear to determine if there is a subpopulation of RBCs with distinctive size or shape abnormalities, which would place the patient in one of the categories listed below (ie, early microcytic or early macrocytic anemia), and by use of a kinetic approach to determine the mechanism(s) underlying the anemia.
CAUSES OF MACROCYTOSIS — Macrocytic anemias are characterized by a mean corpuscular volume (MCV) above 100 fL
Depending upon the population studied, the most common causes of an increased MCV are:
●The presence of an increased number of reticulocytes
●Macrocytosis associated with alcoholism
●Deficiency of folate or vitamin B12
●Antiviral treatment of HIV infection
●Use of chemotherapeutic agents, especially hydroxyurea
●Presence of one of the myelodysplastic disorders
A 40-year-old woman presents with a two month history of tiredness, intermittent pyrexia and abdominal pain. On examination she has an enlarged palpable spleen. Blood tests show anaemia with a raised white cell count. What is the likeliest result of a white cell count (x 109 per l) in a normal person?
A. 15 B. 2.2 C.130 D. 30 E. 4 F. 290 G. 90
4: The normal white cell count is usually between 4 and 11 x 109/L.
Neutrophils are the most abundant white blood cell, constituting 60-70% of the circulating leukocytes. They defend against bacterial or fungal infection. They are usually first responders to microbial infection; their activity and death in large numbers forms pus. They are commonly referred to as polymorphonuclear (PMN) leukocytes, although, in the technical sense, PMN refers to all granulocytes. They have a multi-lobed nucleus, which consists of three to five lobes connected by slender strands.The cytoplasm may look transparent because of fine granules that are pale lilac when stained. Neutrophils are active in phagocytosing bacteria and are present in large amount in the pus of wounds. These cells are not able to renew their lysosomes (used in digesting microbes) and die after having phagocytosed a few pathogens. Neutrophils are the most common cell type seen in the early stages of acute inflammation.
Eosinophils compose about 2-4% of the WBC total. This count fluctuates throughout the day, seasonally, and during menstruation. It rises in response to allergies, parasitic infections, collagen diseases, and disease of the spleen and central nervous system. They are rare in the blood, but numerous in the mucous membranes of the respiratory, digestive, and lower urinary tracts.
They primarily deal with parasitic infections. Eosinophils are also the predominant inflammatory cells in allergic reactions. The most important causes of eosinophilia include allergies such as asthma, hay fever, and hives; and also parasitic infections. They secrete chemicals that destroy these large parasites, such as hook worms and tapeworms, that are too big for any one WBC to phagocytize. In general, their nucleus is bi-lobed. The lobes are connected by a thin strand. The cytoplasm is full of granules that assume a characteristic pink-orange color with eosin staining.
Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine causing the dilation of blood vessels. Because they are the rarest of the white blood cells (less than 0.5% of the total count) and share physicochemical properties with other blood cells, they are difficult to study.[11] They can be recognized by several coarse, dark violet granules, giving them a blue hue. The nucleus is bi- or tri-lobed, but it is hard to see because of the number of coarse granules that hide it.
They excrete two chemicals that aid in the body’s defenses: histamine and heparin. Histamine is responsible for widening blood vessels and increasing the flow of blood to injured tissue. It also makes blood vessels more permeable so neutrophils and clotting proteins can get into connective tissue more easily. Heparin is an anticoagulant that inhibits blood clotting and promotes the movement of white blood cells into an area. Basophils can also release chemical signals that attract eosinophils and neutrophils to an infection site
A 5-year-old boy presents with a purpuric rash and petechiae following a recent viral infection. Blood tests showed thrombocytopenia. What is the likeliest result of a platelet count (x109/l) in a normal adult?
A. 15 B. 2.2 C.130 D. 30 E. 4 F. 290 G. 90
290
Thrombocytopenia (ie, platelet count
A 35-year-old man presents with hypertension. Blood tests show normal sodium, urea and glucose and a raised potassium. What is the likeliest result of potassium (mmol/l) in a normal person?
A. 15 B. 2.2 C.130 D. 30 E. 4 F. 290 G. 90
4
Hyperkalemia is most often due to impaired urinary potassium excretion due to acute or chronic kidney disease and/or disorders or drugs that inhibit the renin-angiotensin-aldosterone axis. Less commonly, redistributive hyperkalemia results from the movement of potassium out of the cells, even though the total body potassium may be reduced. The main cause of redistributive hyperkalemia is uncontrolled hyperglycemia.
- Mild - 5.5-5.9 mmol/L
- Moderate - 6.0-6.4 mmol/L
- Severe - >6.5 mmol/L
The most serious manifestations of hyperkalemia are muscle weakness or paralysis, cardiac conduction abnormalities, and cardiac arrhythmias. These manifestations usually occur when the serum potassium concentration is ≥7.0 meq/L with chronic hyperkalemia or possibly at lower levels with an acute rise in serum potassium. Patients with skeletal muscle or cardiac manifestations typically have one or more of the characteristic ECG abnormalities associated with hyperkalemia (tall tented T-waves, shortened QT–> lengthening PR interval & QRS duration, P-wave may disppear & ultimately QRS widens to a sine wave pattern –> flat line).
Stop further potassium accumulation:
•Stop any potassium supplements or drugs that conserve potassium.
•Consider stopping digoxin and beta-blockers, as these may prevent buffering of intracellular potassium and reduce effectiveness of insulin-glucose.
•Decrease high intake of potassium in the diet.
Protect cardiac membrane:•
Give 10 ml 10% calcium gluconate (calcium chloride is an alternative ideally given via central access) which will improve ECG changes within 1-3 minutes, but this effect only has a transient effect of 30-60 minutes.
•If there is no improvement then give 10 ml every 10 minutes until ECG normalises (may need up to 50 ml).
•In patients who are taking digoxin, give calcium gluconate in an infusion (add to 100 ml glucose 5%) and run over 20 minutes (otherwise, can precipitate myocardial digoxin toxicity).
Shift potassium into cells:
•Insulin-glucose IV - usually 10 units of Actrapid® are added to 50 ml of glucose 50% and infused over 30 minutes.
•Capillary blood glucose needs to be checked before, during and after.
•Potassium will decrease (0.6-1.0 mmol/L) in 15 minutes and the reduction lasts for 60 minutes.
•Check potassium 30 minutes afterwards and if there is a good response check U&E 1-2 hours later.
•Also give 10-20 mg nebulised salbutamol - this reduces potassium (0.5-1.0 mmol/L) in 15-30 minutes and lasts for two hours.
Remove potassium from the body:
•Calcium polystyrene sulfonate resin (Calcium Resonium®) with regular lactulose will remove potassium via the gastrointestinal tract.
•Each gram removes 1 mmol/L of potassium but onset is slow, taking over two hours.
•Haemodialysis will also remove potassium from the body
A 70-year-old woman presents in a coma with a long history of polyuria and polydipsia. Investigations show that her plasma osmolarity is raised. What is the likeliest result of plasma osmolarity (mmol/l) in a normal person?
A. 15 B. 2.2 C.130 D. 30 E. 4 F. 290 G. 90
290
Normal human reference range of osmolality in plasma is about 285-295 milli-osmoles per kilogram
Calculated osmolarity = 2 Na + Glucose + Urea ( all in mmol/L).
Osmolality of blood increases with dehydration and decreases with overhydration. In normal people, increased osmolarity in the blood will stimulate secretion of antidiuretic hormone (ADH). This will result in increased water reabsorption, more concentrated urine, and less concentrated blood plasma. A low serum osmolality will suppress the release of ADH, resulting in decreased water reabsorption and more concentrated plasma.
A 14-year-old boy presents with symptoms of chronic liver failure. LFTs display abnormally high levels of transaminases with normal alk phos & bilirubin levels. There’s marked accumulation of copper-associated protein in hepatocytes obtained from a biopsy. His serum copper levels and caeruloplasmin are abnormally low.
A. Chronic hepatitis B B. Chronic hepatitis C C.Crigler Najjar syndrome D. Budd-Chiari syndrome E. Hepatitis A F. Primary hepatocellular carcinoma G. Primary biliary cirrhosis H. Wilson's disease
Wilson disease (hepatolenticular degeneration) is due to a genetic abnormality inherited in an autosomal recessive manner that leads to impairment of cellular copper transport. It is found worldwide, with a prevalence of approximately 1 case in 30,000 live births in most populations. Impaired biliary copper excretion leads to accumulation of copper in several organs, most notably the liver, brain, and cornea. Over time, the liver is progressively damaged and eventually becomes cirrhotic. A small percent of patients develop acute liver failure, most often in the setting of advanced fibrosis of the liver. In addition, patients may develop neurologic complications, which can be severe. The clinical manifestations of Wilson disease are predominantly hepatic, neurologic, and psychiatric, with many patients having a combination of symptoms [1]. Hemolysis is also a common finding in patients with acute liver failure due to Wilson disease.
Signs and symptoms of hepatic Wilson disease may include:
●Kayser-Fleischer rings, visible in 50 percent of patients with hepatic disease (seen with all forms of liver involvement)
●Asymptomatic (steatosis, chronic hepatitis, compensated cirrhosis)
●Abdominal pain (acute hepatitis, acute liver failure)
●Jaundice (acute hepatitis, acute liver failure, cirrhosis)
●Hepatomegaly (acute and chronic hepatitis, acute liver failure)
●Splenomegaly (cirrhosis)
●Ascites (cirrhosis)
●Upper gastrointestinal bleeding (cirrhosis with varices or portal hypertensive gastropathy)
●Peripheral stigmata of chronic liver disease (cirrhosis)
●Mental status changes due to hepatic encephalopathy (acute liver failure, cirrhosis)
A 30-year-old Thai male presents to a day surgery unit for a cholecystectomy. His LFTs reveal very elevated transaminases with normal bilirubin & alk phos levels. Microscopy of a liver biopsy identifies antigens from a dsDNA virus in the cytosol of hepatocytes.
A. Chronic hepatitis B B. Chronic hepatitis C C.Crigler Najjar syndrome D. Budd-Chiari syndrome E. Hepatitis A F. Primary hepatocellular carcinoma G. Primary biliary cirrhosis H. Wilson's disease
Chronic hepatitis B
Many patients with chronic hepatitis B are asymptomatic (unless they progress to decompensated cirrhosis or have extrahepatic manifestations), while others have nonspecific symptoms such as fatigue. Some patients experience exacerbations of the infection which may be asymptomatic, mimic acute hepatitis, or manifest as hepatic failure.
Physical examination may be normal, or there may be stigmata of chronic liver disease. Jaundice, splenomegaly, ascites, peripheral edema, and encephalopathy may be present in patients with decompensated cirrhosis. Laboratory tests may be normal, but most patients have a mild to moderate elevation in serum AST and ALT. During exacerbations, the serum ALT concentration may be as high as 50 times the upper limit of normal, and alfa-fetoprotein (AFP) concentrations as high as 1000 ng/mL may be seen [14]. A progression to cirrhosis is suspected when there is evidence of hypersplenism (decreased white blood cell and platelet counts) or impaired hepatic synthetic function (hypoalbuminemia, prolonged prothrombin time, hyperbilirubinemia).
This type of infection dramatically increases the incidence of hepatocellular carcinoma (liver cancer). Across Europe hepatitis B and C cause approximately 50% of hepatocellular carcinomas. A persistent elevation of serum ALT for more than six months indicates a progression to chronic hepatitis.
Chronic carriers are encouraged to avoid consuming alcohol as it increases their risk for cirrhosis and liver cancer. Hepatitis B virus has been linked to the development of membranous glomerulonephritis (MGN).
Hepatitis D (HDV) can occur only with a concomitant hepatitis B infection, because HDV uses the HBV surface antigen to form a capsid. Co-infection with hepatitis D increases the risk of liver cirrhosis and liver cancer.
A 58-year-old woman presents with recent onset of Jaundice. LFTs reveal increased bilirubin & markedly elevated alk phos & normal transaminases. Further investigations uncovered raised IgM and serum cholesterol. Anti mitochondrial antibodies are also detected. A liver biopsy shows enlargement of the portal tracts by white blood cells and granulomas. Bile ducts are also less than normal.
A. Chronic hepatitis B B. Chronic hepatitis C C.Crigler Najjar syndrome D. Budd-Chiari syndrome E. Hepatitis A F. Primary hepatocellular carcinoma G. Primary biliary cirrhosis H. Wilson's disease
Primary biliary cirrhosis
Characterized by a T-lymphocyte-mediated attack on small intralobular bile ducts. A continuous assault on the bile duct epithelial cells leads to their gradual destruction and eventual disappearance. The sustained loss of intralobular bile ducts causes the signs and symptoms of cholestasis and eventually results in cirrhosis and liver failure The diagnosis should be considered in the patient, particularly a woman, who complains of unexplained itching, fatigue, jaundice, or unexplained weight loss with right-upper-quadrant discomfort, and/or whose serum alkaline phosphatase is unaccountably elevated. Such patients should be questioned about symptoms of diseases frequently associated with PBC, such as Sjögren’s syndrome (dry eyes and mouth), arthritis, and Raynaud phenomenon.
Primary biliary cirrhosis is probably present if the serum alkaline phosphatase and IgM concentrations are both elevated and the antimitochondrial antibody test is positive.
A 48-year-old male returning from a 6mths round the world trip presents with a recent Hx of nausea, anorexia & distaste for cigarettes. He developed jaundice; his urine became dark and his stools pale. His spleen was palpable. Investigations showed bilirubinuria, increased urinary urobilinogen & a raised serum AST & ALT. Within 4 weeks his symptoms had completely subsided.
A. Chronic hepatitis B B. Chronic hepatitis C C.Crigler Najjar syndrome D. Budd-Chiari syndrome E. Hepatitis A F. Primary hepatocellular carcinoma G. Primary biliary cirrhosis H. Wilson's disease
Hepatitis A: 27 nm, nonenveloped, icosahedral, positive-stranded RNA virus classified in the Heparnavirus genus of the Picornaviridae family.
HAV is spread via the fecal-oral route and is more prevalent in low socioeconomic areas where a lack of adequate sanitation and poor hygienic practices facilitate spread of the infection.
Hepatitis A virus (HAV) infection usually results in an acute, self-limited illness and only rarely leads to fulminant hepatic failure. Fulminant hepatic failure occurs more commonly in patients with underlying liver disease, particularly chronic hepatitis C virus (HCV) infection.
The incubation period averages 30 days (range 15 to 49 days), after which the illness begins with the abrupt onset of prodromal symptoms including fatigue, malaise, nausea, vomiting, anorexia, fever, and right upper quadrant pain. Within a few days to one week, patients note dark urine, acholic stool (light-colored stools lacking bilirubin pigment), jaundice, and pruritus. The prodromal symptoms usually diminish when jaundice appears; jaundice typically peaks within two weeks.
The diagnosis of acute hepatitis A virus (HAV) infection is made by the detection of anti-HAV antibodies in a patient with the typical clinical presentation. Serum IgM anti-HAV is the gold standard for the detection of acute illness.
Because the disease is usually self-limited, the treatment is supportive.
A 55-year-old woman presents with a short Hx of nausea and abdominal pain; tender hepatomegaly and ascities. LFTs show mildly raised transaminases, bilirubin and normal alk phos. The woman also had polycythaemia rubra vera. Liver biopsy suggests venous outflow obstruction.
A. Chronic hepatitis B B. Chronic hepatitis C C.Crigler Najjar syndrome D. Budd-Chiari syndrome E. Hepatitis A F. Primary hepatocellular carcinoma G. Primary biliary cirrhosis H. Wilson's disease
Budd-Chiari syndrome: hepatic venous outflow tract obstruction, independent of the level or mechanism of obstruction, provided the obstruction is not due to cardiac disease, pericardial disease, or sinusoidal obstruction syndrome (veno-occlusive disease). Primary Budd-Chiari syndrome is present when there is obstruction due to a primarily venous process (thrombosis or phlebitis), whereas secondary Budd-Chiari is present when there is compression or invasion of the hepatic veins and/or the inferior vena cava by a lesion that originates outside of the vein.
Symptoms in patients with Budd-Chiari syndrome may include fever, abdominal pain, abdominal distension (from ascites), lower extremity edema, jaundice, gastrointestinal bleeding, and/or hepatic encephalopathy. Patients with subacute or chronic Budd-Chiari syndrome may be asymptomatic. In such patients, the hepatic venous outflow obstruction is often discovered as part of the evaluation of abnormal liver blood tests or when imaging is obtained for other reasons.
A liver enzyme raised after a myocardial infarction
A. Aspartate transaminase B. Gamma globulin C. Alanine transaminase D. Direct bilirubin E. Activated partial thromboplastin time F. Gamma glutamyl transpeptidase G. Alkaline phosphatase H. Total bilirubin I. Prothrombin time J. Albumin
Aspartate transaminase
Large increases in mitochondrial AST occur in serum after extensive tissue necrosis and assay of mitochondrial AST has been advocated as an accurate test for the detection of myocardial infarction [10]. However, other serum tests, such as troponins, are considered the standard for the diagnosis of myocardial infarction.
A test of the integrity of the extrinsic pathway
A. Aspartate transaminase B. Gamma globulin C. Alanine transaminase D. Direct bilirubin E. Activated partial thromboplastin time F. Gamma glutamyl transpeptidase G. Alkaline phosphatase H. Total bilirubin I. Prothrombin time J. Albumin
Prothrombin time
The intrinsic pathway is initiated by the activation of the ‘contact factor’ of plasma and can be measured by the aPTT test (heparin - antithrombin III & factor 10 if unfract). The extrinsic pathway is initiated by the release of tissue factor and can be measured by the PT test (warfarin - vitamin K - F2,7,9,10).
An enzyme markedly raised in obstructive jaundice along with direct bilirubin
A. Aspartate transaminase B. Gamma globulin C. Alanine transaminase D. Direct bilirubin E. Activated partial thromboplastin time F. Gamma glutamyl transpeptidase G. Alkaline phosphatase H. Total bilirubin I. Prothrombin time J. Albumin
Alkaline phosphatase
Cholestasis may develop in the setting of extrahepatic or intrahepatic biliary obstruction (table 6). In patients with cholestasis, the alkaline phosphatase is typically elevated to at least four times the upper limit of normal. The magnitude of the serum alkaline phosphatase level does not distinguish extrahepatic cholestasis from intrahepatic cholestasis. Lesser degrees of elevation are nonspecific and may be seen in many other types of liver disease, such as viral hepatitis, infiltrative diseases of the liver, and congestive hepatopathy. The gamma-glutamyl transpeptidase (GGT) may also be elevated in the setting of cholestasis.
To confirm an isolated elevation in the alkaline phosphatase is coming from the liver, a GGT level or serum 5’-nucleotidase level should be obtained. These tests are usually elevated in parallel with the alkaline phosphatase in liver disorders, but are not increased in bone disorders. An elevated serum alkaline phosphatase with a normal GGT or 5’-nucleotidase should prompt an evaluation for bone diseases.
Raised in alcohol abuse
A. Aspartate transaminase B. Gamma globulin C. Alanine transaminase D. Direct bilirubin E. Activated partial thromboplastin time F. Gamma glutamyl transpeptidase G. Alkaline phosphatase H. Total bilirubin I. Prothrombin time J. Albumin
Gamma-glutamyl transpeptidase (GGT) catalyzes the transfer of the gamma-glutamyl group from gamma-glutamyl peptides such as glutathione to other peptides and to L-amino acids. GGT is present in cell membranes in many tissues, including the kidneys, pancreas, liver, spleen, heart, brain, and seminal vesicles [50]. It is thought to play a role in amino acid transport.
The normal range is 0 to 30 IU/L (0 to 0.5 mkat/L)
An isolated elevation in serum GGT or a GGT elevation out of proportion to that of other enzymes (such as the alkaline phosphatase and alanine aminotransferase) may be an indicator of alcohol abuse or alcoholic liver disease
Levels can be affected by diet
A. Aspartate transaminase B. Gamma globulin C. Alanine transaminase D. Direct bilirubin E. Activated partial thromboplastin time F. Gamma glutamyl transpeptidase G. Alkaline phosphatase H. Total bilirubin I. Prothrombin time J. Albumin
Albumin: is the most abundant protein in human blood plasma. It is produced in the liver. Albumin constitutes about half of the blood serum protein. It is soluble and monomeric.
Albumin transports hormones, fatty acids, and other compounds, buffers pH, and maintains osmotic pressure, among other functions.
Albumin is synthesized in the liver as preproalbumin, which has an N-terminal peptide that is removed before the nascent protein is released from the rough endoplasmic reticulum. The product, proalbumin, is in turn cleaved in the Golgi vesicles to produce the secreted albumin.
The reference range for albumin concentrations in serum is approximately 35 - 50 g/L. It has a serum half-life of approximately 20 days.
Maintains oncotic pressure
Transports thyroid hormones
Transports other hormones, in particular, ones that are fat-soluble
Transports fatty acids (“free” fatty acids) to the liver and to myocytes for utilization of energy
Transports unconjugated bilirubin
Transports many drugs; serum albumin levels can affect the half-life of drugs
Competitively binds calcium ions (Ca2+)
Buffers pH
Serum albumin, as a negative acute-phase protein, is down-regulated in inflammatory states. As such, it is not a valid marker of nutritional status; rather, it is a marker of an inflammatory state
Prevents photodegradation of folic acid
Low blood albumin levels (hypoalbuminemia) can be caused by: This condition is a sign of chronic dehydration:
Liver disease; cirrhosis of the liver is most common
Excess excretion by the kidneys (as in nephrotic syndrome)
Excess loss in bowel (protein-losing enteropathy, e.g., Ménétrier’s disease)
Burns (plasma loss in the absence of skin barrier)
Redistribution (hemodilution [as in pregnancy], increased vascular permeability or decreased lymphatic clearance)
Acute disease states (referred to as a negative acute-phase protein)
Malnutrition and wasting[3]
Mutation causing analbuminemia (very rare)
A 26-year-old receptionist presents to her GP with a history steatorrhoea, abdominal pain and weight loss, as well as feeling tired all the time. Initial blood tests reveal a microcytic anaemia.
A. Ham's test B. p-ANCA C. ANA D. Anti-acetylcholine receptor antibody E. Anti-gastric parietal cell antibodies F. c-ANCA G. Anti-DsDNA H. Anti-endomysial antibodies I. Anti-GAD J. Anti-smooth muscle antibody K. Osmotic fragility test L. Anti-scl70 M. Anti-mitochondrial antibody
Anti-endomysial antibodies or Tissue-transglutaminase antibodies - coeliac disease: close association with the HLA-DQ2 and/or DQ8 gene loci
ELISA for IgA antibodies to gliadin and the immunofluorescence test for IgA antibodies to endomysium, a structure of the smooth muscle connective tissue, is virtually pathognomonic for celiac disease
The classic definition of celiac disease or gluten-sensitive enteropathy includes the following three features: villous atrophy; symptoms of malabsorption such as steatorrhea, weight loss, or other signs of nutrient or vitamin deficiency [7]; and resolution of the mucosal lesions and symptoms upon withdrawal of gluten-containing foods, usually within a few weeks to months. Patients with classic disease present with diarrhea, weight loss, or malabsorption, and possess antibodies against gliadin and especially tissue transglutaminase.
The histologic severity ranges from a mild alteration characterized by increased intraepithelial lymphocytes (type 0 lesion) to a flat mucosa with total mucosal atrophy, complete loss of villi, enhanced epithelial apoptosis and crypt hyperplasia (type 3 lesion)
Patients may present with classic signs, including diarrhea with bulky, foul-smelling, floating stools due to steatorrhea and flatulence. These symptoms are paralleled by the consequences of malabsorption, such as growth failure in children, weight loss, severe anemia, neurologic disorders from deficiencies of B vitamins, and osteopenia from deficiency of vitamin D and calcium.
Celiac disease is frequently associated with dermatitis herpetiformis, Down syndrome, selective IgA deficiency, and other conditions which have autoimmune features such as type 1 diabetes mellitus, thyroid disease, and liver disease. Patients with celiac disease (and their families) may also be more likely to have atopic dermatitis
A 60-year-old woman with hypothyroidism presents with progressive dyspnoea and tiredness. FBC reveals macrocytic anaemia.
A. Ham's test B. p-ANCA C. ANA D. Anti-acetylcholine receptor antibody E. Anti-gastric parietal cell antibodies F. c-ANCA G. Anti-DsDNA H. Anti-endomysial antibodies I. Anti-GAD J. Anti-smooth muscle antibody K. Osmotic fragility test L. Anti-scl70 M. Anti-mitochondrial antibody
Anti-gastric parietal cell antibodies Pernicious anemia (PA; B12 deficiency caused by lack of intrinsic factor) is a common cause of Cbl deficiency. It is usually under-diagnosed, and is not an uncommon problem in older adult subjects. The underlying pathogenesis of PA is thought to be autoimmune and may be part of a more general autoimmune disorder called polyglandular autoimmune syndrome type 2 (PAS 2), which can include such disorders as autoimmune thyroid disease, Addison's disease, type 1 diabetes mellitus, and vitiligo. Autoantibody formation against intrinsic factor – Cbl deficiency in PA is thought to result directly from an autoimmune attack on gastric intrinsic factor (IF) [1,6]. Anti-intrinsic factor antibodies are detectable in the serum in 50 to 70 percent of patients with PA, providing a highly specific (>95 percent) but relatively insensitive (50 to 84 percent) test [1,11]. There are two types of anti-IF antibodies: one that blocks the attachment of Cbl to IF; and one that blocks attachment of the Cbl-IF complex to ileal receptors [12]. The net result of these anti-IF antibodies is to prevent absorption of dietary Cbl, leading to Cbl deficiency and its various sequelae. The chronic atrophic gastritis in PA is associated with an increased risk of intestinal-type gastric cancer and of gastric carcinoid tumors. Gastrectomy and gastritis are other gastric abnormalities that can produce Cbl deficiency
A 40-year-old plumber presents to his GP with a history of wheezing and lethargy, along with recurrent nose bleeds. On examination he has crackles in his upper left lung field. Urine dipstick is positive for blood and protein.
A. Ham's test B. p-ANCA C. ANA D. Anti-acetylcholine receptor antibody E. Anti-gastric parietal cell antibodies F. c-ANCA G. Anti-DsDNA H. Anti-endomysial antibodies I. Anti-GAD J. Anti-smooth muscle antibody K. Osmotic fragility test L. Anti-scl70 M. Anti-mitochondrial antibody
Wegener’s : Antibody to Proteinase-3 : 3 is the 3rd letter of the alphabet; c-ANCA.
Granulomatosis with polyangiitis - GPA.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), the Churg-Strauss syndrome (CSS) and renal-limited vasculitis.
MPA is distinguished from GPA and CSS by the absence of granuloma formation and the presence of a necrotizing vasculitis.
systemic disorder that involves both granulomatosis and polyangiitis. It is a form of vasculitis (inflammation of blood vessels) that affects small- and medium-size vessels in many organs. Damage to the lungs and kidneys can be fatal. It requires long-term immunosuppression.
Kidney: rapidly progressive glomerulonephritis (75%), leading to chronic kidney failure
Upper airway, eye and ear disease:
Nose: pain, stuffiness, nosebleeds, rhinitis, crusting, saddle-nose deformity due to a perforated septum
Ears: conductive hearing loss due to auditory tube dysfunction, sensorineural hearing loss (unclear mechanism)
Oral cavity: strawberry gingivitis, underlying bone destruction with loosening of teeth, non-specific ulcerations throughout oral mucosa
Eyes: pseudotumours, scleritis, conjunctivitis, uveitis, episcleritis
Trachea: subglottal stenosis
Lungs: pulmonary nodules (referred to as “coin lesions”), infiltrates (often interpreted as pneumonia), cavitary lesions, pulmonary haemorrhage causing haemoptysis, and rarely bronchial stenosis.
Arthritis: Pain or swelling (60%), often initially diagnosed as rheumatoid arthritis
Skin: nodules on the elbow, purpura, various others
The standard treatment for GPA is cyclophosphamide and high dose corticosteroids for remission induction and less toxic immunosuppressants like azathioprine, leflunomide, methotrexate or mycophenolate mofetil.
A 30-year-old market trader presents with tiredness and jaundice, and further history reveals he suffered from a chest infection one week previously. On examination mild splenomegaly is noted, and blood tests show reticulocytosis, hyperbilirubinaemia, and spherocytosis.
A. Ham's test B. p-ANCA C. ANA D. Anti-acetylcholine receptor antibody E. Anti-gastric parietal cell antibodies F. c-ANCA G. Anti-DsDNA H. Anti-endomysial antibodies I. Anti-GAD J. Anti-smooth muscle antibody K. Osmotic fragility test L. Anti-scl70 M. Anti-mitochondrial antibody
Spherocytosis: Osmotic fragility test.
Causes of hemolysis are subdivided into two groups: those that are intrinsic (intracorpuscular) and those extrinsic to the red blood cell (RBC) (table 2). With few exceptions (eg, paroxysmal nocturnal hemoglobinuria and the rare condition of acquired alpha thalassemia), the causes of intrinsic RBC defects are hereditary. Extracorpuscular causes are almost always acquired conditions leading to increased destruction of otherwise normal RBCs.
An 80-year-old retired clerk presents with a 2-month history of skin itching and lethargy. Examination is normal. LFTs are: bilirubin 6umol/l (reference range 0-17umol/l); ALT 24U/l (reference range 0-31U/l); Alk Phos 500U/l (reference range 30-130U/l).
A. Ham's test B. p-ANCA C. ANA D. Anti-acetylcholine receptor antibody E. Anti-gastric parietal cell antibodies F. c-ANCA G. Anti-DsDNA H. Anti-endomysial antibodies I. Anti-GAD J. Anti-smooth muscle antibody K. Osmotic fragility test L. Anti-scl70 M. Anti-mitochondrial antibody
PBC - AMA E2 subtype of pyruvate dehydrogenase complex
Primary biliary cirrhosis
Characterized by a T-lymphocyte-mediated attack on small intralobular bile ducts. A continuous assault on the bile duct epithelial cells leads to their gradual destruction and eventual disappearance. The sustained loss of intralobular bile ducts causes the signs and symptoms of cholestasis and eventually results in cirrhosis and liver failure The diagnosis should be considered in the patient, particularly a woman, who complains of unexplained itching, fatigue, jaundice, or unexplained weight loss with right-upper-quadrant discomfort, and/or whose serum alkaline phosphatase is unaccountably elevated. Such patients should be questioned about symptoms of diseases frequently associated with PBC, such as Sjögren’s syndrome (dry eyes and mouth), arthritis, and Raynaud phenomenon.
Primary biliary cirrhosis is probably present if the serum alkaline phosphatase and IgM concentrations are both elevated and the antimitochondrial antibody test is positive.
A 10-year-old girl presents with weight loss, polyuria, tachypnoea, vomiting. Looks very dehydrated. Beta hydroxybutyrate is raised in the blood.
A. Ham's test B. p-ANCA C. ANA D. Anti-acetylcholine receptor antibody E. Anti-gastric parietal cell antibodies F. c-ANCA G. Anti-DsDNA H. Anti-endomysial antibodies I. Anti-GAD J. Anti-smooth muscle antibody K. Osmotic fragility test L. Anti-scl70 M. Anti-mitochondrial antibody
Type 1 diabetes: Anti-Glutamic acid decarboxylase antibodies (Anti-GAD).
Type 1A diabetes mellitus results from autoimmune destruction of the insulin-producing beta cells in the islets of Langerhans
The pathogenesis of type 1A diabetes is quite different from that of type 2 diabetes mellitus, in which both decreased insulin release (not on an autoimmune basis) and insulin resistance play an important role.
Polymorphisms of multiple genes are reported to influence the risk of type 1A diabetes (including, HLA-DQalpha, HLA-DQbeta, HLA-DR, preproinsulin, the PTPN22 gene, CTLA-4, interferon-induced helicase, IL2 receptor (CD25)
Antibodies to GAD (a 65-kD protein) are found in about 70 percent of patients with type 1 diabetes at the time of diagnosis.
A 55-year-old woman is warned of future risk of AML given her recent diagnosis of PNH following a spontaneous cerebral venous sinus thrombosis.
A. Ham's test B. p-ANCA C. ANA D. Anti-acetylcholine receptor antibody E. Anti-gastric parietal cell antibodies F. c-ANCA G. Anti-DsDNA H. Anti-endomysial antibodies I. Anti-GAD J. Anti-smooth muscle antibody K. Osmotic fragility test L. Anti-scl70 M. Anti-mitochondrial antibody
Ham’s test
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder. Clinical findings include unexplained hemolytic anemia, thrombosis in an atypical location, or nonspecific symptoms attributable to consequences of hemolysis.
Hemolysis may cause symptoms directly attributable to anemia and/or red blood cell (RBC) lysis, as well as findings caused indirectly by hemoglobin release, such as smooth muscle dystonia, pulmonary hypertension, and renal insufficiency.
Laboratory findings in PNH include typical findings of hemolytic anemia, loss of glycosylphosphatidylinositol (GPI)-anchored proteins, and findings associated with organ damage from hemolysis and/or thrombosis.
Screening for PNH is appropriate in patients with a direct antiglobulin (Coombs) negative hemolytic anemia, aplastic anemia, refractory anemia, or unexplained thrombosis in conjunction with cytopenias or hemolysis.
Some patients with PNH develop acute leukemia [60-68]. The lifetime risk is 5 percent or less. The leukemia may evolve from either the PNH clone or a non-PNH clone. Acute myeloid leukemia (AML) is most common
A 40-year-old woman presents with polyuria and polydipsia. She has a fasting glucose 5.1mmol/L and an oral glucose tolerance test value of 5.0mmol/L. She has a corrected calcium of 2.80mmol/L and a PTH of 7.2pmol/L.
A. Diabetes mellitus type 2 B. Psychogenic polydipsia C. Sarcoidosis D. Lung cancer E. Gestational diabetes F. Impaired fasting glucose G. Hypocalcaemia H. Primary hyperparathyroidism I. Crohn’s disease J. Tuberculosis K. Impaired glucose tolerance L. Vitamin D deficiency M. Secondary hyperthyroidism N. Malignancy O. Diabetes mellitus type 1
Primary hyperparathyroidism
If someone is complaining of polyuria, if the cause is glycosuria, the
glucose has to be above 10mM to hit the renal threshold. Thus a glucose of 5.6 or 6.1 cannot cause polyuria!!!
Normal Ca: 2.12 to 2.62 mmol/L
Hypercalcaemia is an uncommon problem. Primary hyperparathyroidism is the most common cause of raised calcium levels
3.5mmol/l: All above plus abdo pain, vomiting, dehydration, lethargy, cardiac arrhythmias, shortened QT interval, coma, pancreatitis
Non-PTH-mediated hypercalcaemia:
Malignancy - the most common cause of non-PTH-mediated hypercalcaemia.
Granulomatous conditions - eg, sarcoidosis and tuberculosis.
Endocrine conditions - eg, thyrotoxicosis, phaeochromocytoma and primary adrenal insufficiency.
Drugs - eg, thiazide diuretics, vitamin D and vitamin A supplements.[7]
Familial - eg, familial hypocalciuric hypercalcaemia.[5]
Other - eg, prolonged immobilisation, calcium-alkali syndrome, AIDS.
A raised albumin level in the presence of a raised urea indicates dehydration.
A raised albumin level in the presence of a normal urea suggests a cuffed specimen.
A normal alkaline phosphatase is indicative of myeloma (raised plasma protein), calcium-alkali syndrome (formerly milk-alkali syndrome),[9] thyrotoxicosis or sarcoidosis.
A raised alkaline phosphatase suggests bony metastases, sarcoidosis or thyrotoxicosis.
A raised calcitonin level is suggestive of B-cell lymphoma.
Raised PTH levels are suggestive of primary, secondary or tertiary hyperparathyroidism, or familial hypocalciuric hypercalcaemia.
Low PTH levels are seen in granulomatous disease, iatrogenic causes (eg, renal dialysis), adrenal insufficiency, thyrotoxicosis,and vitamin D intoxication.
The levels in malignancy may be low, normal or high.
A 35-year-old Afro-Caribbean woman presents with polyuria and polydipsia. She also complains of a dry cough. She has a fasting glucose of 5.8mmol/L and an oral glucose tolerance test value of 6.5mmol/L. She has a corrected calcium of 2.7mmol/L and a PTH of
Sarcoidosis
Normal Ca: 2.12 to 2.62 mmol/L
Hypercalcaemia, low PTH, afro-carib, dry cough
Sarcoidosis is a multisystem granulomatous disorder of unknown etiology that affects individuals worldwide and is characterized pathologically by the presence of noncaseating granulomas in involved organs. It typically affects young adults, and initially presents with one or more of the following abnormalities:
●Bilateral hilar adenopathy
●Pulmonary reticular opacities
●Skin, joint, and/or eye lesions
Sarcoidosis most frequently involves the lung, but up to 30 percent of patients present with extrathoracic manifestations of sarcoidosis (table 1) [11-13]. Diffuse interstitial lung disease is the classic type of lung involvement; other less common pulmonary manifestations include pneumothorax, pleural thickening, chylothorax, and pulmonary hypertension.
Common presenting respiratory symptoms include cough, dyspnea, and chest pain; these are frequently accompanied by fatigue, malaise, fever, and weight loss
he serum angiotensin converting enzyme (ACE) level is elevated in 75 percent of untreated patients with sarcoidosis
The Kveim test uses a suspension of heat-sterilized splenic cells from patients with sarcoidosis (the Kveim-Siltzbach reagent) in an intradermal skin test (similar to a tuberculin skin test) to evoke a sarcoid granulomatous response over approximately three weeks [32]. The Kveim test is essentially a research tool due to limited availability of the reagent and concerns about disease transmission with testing.
Biopsy should be performed in most cases of suspected sarcoidosis.
The characteristic morphologic feature of sarcoidosis is the noncaseating granuloma.
The sarcoid granuloma is a focal, chronic inflammatory reaction formed by the accumulation of epithelial cells, monocytes, lymphocytes, macrophages, and fibroblasts
A 15-year-old girl presents with weight loss, polyuria and polydipsia. Over the last few months she reports feeling increasingly tired and complains of perianal itching. On examination you notice a small perianal abscess. Her fasting glucose is 22.3mmol/L. Her corrected calcium is 2.5mmol/L and his PTH is 7.0pmol/L.
A. Diabetes mellitus type 2 B. Psychogenic polydipsia C. Sarcoidosis D. Lung cancer E. Gestational diabetes F. Impaired fasting glucose G. Hypocalcaemia H. Primary hyperparathyroidism I. Crohn’s disease J. Tuberculosis K. Impaired glucose tolerance L. Vitamin D deficiency M. Secondary hyperthyroidism N. Malignancy O. Diabetes mellitus type 1
Diabetes mellitus type 1
Type 1A diabetes mellitus results from autoimmune destruction of the insulin-producing beta cells in the islets of Langerhans [1]. This process occurs in genetically susceptible subjects, is probably triggered by one or more environmental agents, and usually progresses over many months or years during which the subject is asymptomatic and euglycemic. This long latent period is a reflection of the large number of functioning beta cells that must be lost before hyperglycemia occurs
Polymorphisms of multiple genes are known to influence the risk of type 1A diabetes (HLA-Dqalpha; HLA-Dqbeta; HLA-DR, preproinsulin, the PTPN22 gene, and CTLA-4),
There are a number of autoantigens within the pancreatic beta cells that may play important roles in the initiation or progression of autoimmune islet injury including glutamic acid decarboxylase (GAD), insulin, insulinoma-associated protein 2 (IA-2), and zinc transporter ZnT8.
A 56-year-old obese woman presents with polyuria and polydipsia. She complains of tiredness and depression. Her fasting glucose is 4.9mmol/L and her OGTT is 4.5mmol/L. She has a corrected calcium of 2.4mmol/L and a PTH of 7.1mmol/L
A. Diabetes mellitus type 2 B. Psychogenic polydipsia C. Sarcoidosis D. Lung cancer E. Gestational diabetes F. Impaired fasting glucose G. Hypocalcaemia H. Primary hyperparathyroidism I. Crohn’s disease J. Tuberculosis K. Impaired glucose tolerance L. Vitamin D deficiency M. Secondary hyperthyroidism N. Malignancy O. Diabetes mellitus type 1
Psychogenic polydipsia - nothing wrong with her biochem!!!!
A 58-year-old Afro-Caribbean gentleman presents with polyuria, polydipsia and weight loss. He has an oral glucose tolerance test of 10.1mmol/L. His corrected calcium is 2.5mmol/L and his PTH is 7.0pmol/L.
A. Diabetes mellitus type 2 B. Psychogenic polydipsia C. Sarcoidosis D. Lung cancer E. Gestational diabetes F. Impaired fasting glucose G. Hypocalcaemia H. Primary hyperparathyroidism I. Crohn’s disease J. Tuberculosis K. Impaired glucose tolerance L. Vitamin D deficiency M. Secondary hyperthyroidism N. Malignancy O. Diabetes mellitus type 1
Impaired glucose tolerance
A normal fasting blood glucose level is less than 6 mmol/L.
Diabetes : a fasting blood glucose > 7 mmol/L , OR
a blood glucose > 11.1 mmol/L after a two-hour oral glucose tolerance test (GTT)
Impaired glucose tolerance: a fasting blood glucose 7.8 mmol/L but
Varies with posture when sample is taken.
A. Potassium B. Creatinine Kinase C. Triglycerides D. Urea E. Albumin F. ALP G. Glucose H. ALT I. Cortisol
Albumin
Plasma renin activity also varies with posture - it rises in the upright position. Some people have so-called benign postural and/or exercise-induced albuminuria.
Varies with exercise
A. Potassium B. Creatinine Kinase C. Triglycerides D. Urea E. Albumin F. ALP G. Glucose H. ALT I. Cortisol
Creatinine Kinase
There are 3 main iso-forms of CK.
CK-MM: present in muscles.
CK-BB: Present in Brain.
CK-MB: Present in cardiac muscle.
Increases during pregnancy
A. Potassium B. Creatinine Kinase C. Triglycerides D. Urea E. Albumin F. ALP G. Glucose H. ALT I. Cortisol
ALP
Varies with race
A. Potassium B. Creatinine Kinase C. Triglycerides D. Urea E. Albumin F. ALP G. Glucose H. ALT I. Cortisol
Creatinine Kinase
There are 3 main iso-forms of CK.
CK-MM: present in muscles.
CK-BB: Present in Brain.
CK-MB: Present in cardiac muscle.
Most likely to vary with time of sampling
A. Potassium B. Creatinine Kinase C. Triglycerides D. Urea E. Albumin F. ALP G. Glucose H. ALT I. Cortisol
Cortisol
A 19-year-old woman admitted to hospital with acute asthma suffered a cardiac arrest after treatment. She was already taking several medications for her respiratory condition. What drug excess is likely to have caused this problem?
A. Kidneys B. Low therapeutic index C. Liver D. Warfarin E. Digoxin F. Oxidation by cytochrome P450 G. Gentamicin H. GI system I. Rosiglitazone J. Poor compliance K. Conjugation by sulphate/gluconaride L. High therapeutic index M. Theophylline N. Lungs
Theophylline has bronchodilatory, antiinflammatory, immunomodulating, and bronchoprotective effects. Theophylline remains a potentially useful and inexpensive medication for patients with chronic asthma whose symptoms are not controlled with conventional doses of inhaled glucocorticoids, and patients who cannot take or are poorly compliant with inhaled medications.
Theophylline is not routinely indicated for the treatment of acute severe asthma in the intensive care unit. Intravenous theophylline (as theophylline or aminophylline) may be added when patients with severe acute asthma fail to respond to vigorous use of inhaled albuterol and ipratropium with systemic glucocorticoids, although evidence for this is lacking.
Failure to respond to drug therapy is commonly caused by what?
A. Kidneys B. Low therapeutic index C. Liver D. Warfarin E. Digoxin F. Oxidation by cytochrome P450 G. Gentamicin H. GI system I. Rosiglitazone J. Poor compliance K. Conjugation by sulphate/gluconaride L. High therapeutic index M. Theophylline N. Lungs
Poor compliance
Lipid soluble drugs require metabolism by the liver in two phases. What is Phase I?
A. Kidneys B. Low therapeutic index C. Liver D. Warfarin E. Digoxin F. Oxidation by cytochrome P450 G. Gentamicin H. GI system I. Rosiglitazone J. Poor compliance K. Conjugation by sulphate/gluconaride L. High therapeutic index M. Theophylline N. Lungs
Oxidation by cytochrome P450
Drugs are mainly excreted by which organ?
A. Kidneys B. Low therapeutic index C. Liver D. Warfarin E. Digoxin F. Oxidation by cytochrome P450 G. Gentamicin H. GI system I. Rosiglitazone J. Poor compliance K. Conjugation by sulphate/gluconaride L. High therapeutic index M. Theophylline N. Lungs
Kidneys
The effect of which drug can be measured by the surrogate marker HbA1C
A. Kidneys B. Low therapeutic index C. Liver D. Warfarin E. Digoxin F. Oxidation by cytochrome P450 G. Gentamicin H. GI system I. Rosiglitazone J. Poor compliance K. Conjugation by sulphate/gluconaride L. High therapeutic index M. Theophylline N. Lungs
Rosiglitazone
Rosiglitazone and pioglitazone are used as monotherapy or with a sulfonylurea, metformin, or insulin. However, there are concerns with combined thiazolidinedione and insulin therapy because of an increased incidence of heart failure (HF).
The thiazolidinediones increase insulin sensitivity by acting on adipose, muscle, and liver to increase glucose utilization and decrease glucose production.
hey bind to and activate one or more peroxisome proliferator-activated receptors (PPARs), which regulate gene expression in response to ligand binding
A 58-year-old man presents to your A&E complaining of chest pain and palpitations. He says he takes several drugs for his ‘heart problems’ and admits to being diabetic. What drug could be causing his problems?
A. Kidneys B. Low therapeutic index C. Liver D. Warfarin E. Digoxin F. Oxidation by cytochrome P450 G. Gentamicin H. GI system I. Rosiglitazone J. Poor compliance K. Conjugation by sulphate/gluconaride L. High therapeutic index M. Theophylline N. Lungs
Possible features of DIGOXIN TOXICITY include:
arrhythmia: the most common arrhythmias are ventricular extrasystoles, ventricular bigeminy / trigeminy and atrial tachycardia with complete heart block
anorexia, nausea and vomiting and occasionally, diarrhoea
confusion especially in the elderly
yellow vision (xanthopsia), blurred vision and photophobia
Peak and trough levels of this drug should be taken
A. Lithium B. Phenytoin C. Phenobarbitone D. Theophylline E. Clonazepam F. Carbamazepine G. Heparin - unfractionated H. Digoxin I. Warfarin J. Gentamicin K. Heparin - Low molecular weight L. Ethosuximide M. Ciclosporin N. Aspirin
Gentamicin is a bactericidal antibiotic that works by irreversibly binding the 30S subunit of the bacterial ribosome, interrupting protein synthesis. This mechanism of action is similar to other Aminoglycosides
Active against a wide range of human bacterial infections, mostly Gram-negative bacteria including Pseudomonas, Proteus, Serratia, and the Gram-positive Staphylococcus.[4] Gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila bacterial infections (because of the risk of the patient going into shock from lipid A endotoxin found in certain Gram-negative organisms).
Aminoglycosides are toxic to the sensory cells of the ear, but they vary greatly in their relative effects on hearing versus balance.
Prevention of nephrotoxicity includes judicouss use of IV fluids to correct and avoid volume depletion, correction of hypokalemia and hypomagnesemia. Once daily dosing has been shown to be less toxic than multiple daily doses. Gentamicin is usually dosed by ideal body weight. Various formulae exist for calculating gentamicin dosage. Trough and peak serum levels of gentamicin are monitored during treatment to individualize therapy and prevent excess exposure.[9]
Gentamicin, like other aminoglycosides, causes nephrotoxicity by inhibiting protein synthesis in renal cells. This mechanism specifically causes necrosis of cells in the proximal tubule, resulting in acute tubular necrosis which can lead to acute renal failure
Symptoms of under-treatment and toxicity may be similar
A. Lithium B. Phenytoin C. Phenobarbitone D. Theophylline E. Clonazepam F. Carbamazepine G. Heparin - unfractionated H. Digoxin I. Warfarin J. Gentamicin K. Heparin - Low molecular weight L. Ethosuximide M. Ciclosporin N. Aspirin
Digoxin
Possible features of DIGOXIN TOXICITY include:
arrhythmia: the most common arrhythmias are ventricular extrasystoles, ventricular bigeminy / trigeminy and atrial tachycardia with complete heart block
anorexia, nausea and vomiting and occasionally, diarrhoea
confusion especially in the elderly
yellow vision (xanthopsia), blurred vision and photophobia
Decreased excretion, increased plasma concentration and increased risk of toxicity may occur when this taken in conjunction with thiazide diuretics
A. Lithium B. Phenytoin C. Phenobarbitone D. Theophylline E. Clonazepam F. Carbamazepine G. Heparin - unfractionated H. Digoxin I. Warfarin J. Gentamicin K. Heparin - Low molecular weight L. Ethosuximide M. Ciclosporin N. Aspirin
Lithium is used primarily for bipolar disorder. Those who use lithium should receive regular serum level tests and should monitor thyroid and kidney function for abnormalities, as it interferes with the regulation of sodium and water levels in the body, and can cause dehydration. Dehydration, which is compounded by heat, can result in increasing lithium levels. The dehydration is due to lithium inhibition of the action of antidiuretic hormone, which normally enables the kidney to reabsorb water from urine. This causes an inability to concentrate urine, leading to consequent loss of body water and thirst.
Hyponatremia can cause lithium retention and thus increased lithium levels.
Lithium concentrations are known to be increased with concurrent use of diuretics — especially loop diuretics (such as furosemide) and thiazides — and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and aspirin.[1] Lithium concentrations can also be increased with concurrent use of ACE inhibitors such as captopril, enalapril, and lisinopril.[43]
Lithium is mainly removed from the body through glomerular function, but some are then reabsorbed together with sodium through the proximal tubule. Its levels are therefore sensitive to water and electrolyte balance.[44] Diuretics act by lowering water and sodium levels. This causes more reabsorption of lithium in the proximal tubules so that the removal of lithium from the body is less, leading to increased levels of lithium.[44][45] ACE inhibitors have also been shown in a retrospective case-control study to increase lithium concentrations. A possible mechanism is that ACE inhibitors can lead to a decrease in sodium and water. This will increase lithium reabsorption and its concentrations in the body.[44]
There are also drugs that can increase the clearance of lithium from the body, which can result in decreased lithium levels in the blood. These drugs include theophylline, caffeine, and acetazolamide. Additionally, increasing dietary sodium intake may also reduce lithium levels by prompting the kidneys to excrete more lithium.[46]
Lithium is also known to be a potential precipitant of serotonin syndrome in people concurrently on serotonergic medications such as antidepressants, buspirone and certain opioids such as pethidine (meperidine), tramadol, oxycodone, fentanyl and others.[1][47] Lithium co-treatment is also a risk factor for neuroleptic malignant syndrome in people on antipsychotics and other antidopaminergic medications.
ENZYME INDUCERS: GPPARCS SSS NN
Griseofulvin
Phenytoin
Phenobarbitone and other barbiturates (Phenobarbital, meprobamate, primidone)
Alcohol (chronic use) - CYP 2E1
Rifampicin, Rifabutin, Rifapentine
Carbamazepine > Oxcarbazepine, Topiramate (induces the Oral Contraceptive Pill)
Sulfonylureas
Smoking
St John’s Wort (Hypericum perforatum)
NNRTIs: Nevirapine (substrate and inducer), Efavirenz (substrate, inducer, inhibitor = the ‘triple’)
and the PI Ritonavir (substrate, inducer, inhibitor = the ‘triple’)
ENZYME NEUTRAL Lamotrigine, Pregabalin, Levetiracetam Benzodiazepines (not barbiturates) Azithromycin (Not other macrolides) Tetracycline Quinolones (Not Ciprofloxacin)
ENZYME INHIBITORS: Depressed GP DAVe to visit SICKFACES.COM ASAP
Depressed: MAO-Is, Duloxetine (SNRI), Fluoxetine, Fluvoxamine, Sertraline, Paroxetine, Not Citalopram
Grapefruit juice Protease Inhibitors (Ritonavir is the only 'triple', the rest are straight inhibitors)
Diltiazem
Amiodarone
Verapamil
e
to visit
Sodium Valproate
Isoniazid especially in SLOW acetylators
Cimetidine not ranitidine
Ketoconazole (most potent inhibitor) > Itraconazole > Fluconazole (mildest)
(Fluconazole)
Alcohol (binge drinking)
Chloramphenicol
Erythromycin, Clarithromycin, Telithromycin, not Azithromycin
Synercid (Quinupristin-Dalfopristin)
Dot : Disulfiram
Ciprofloxacin (inhibits 1A2.. yay warfarin and theophylline toxicity)
Omeprazole not lansoprazole
Metronidazole (remember metro has a disulfiram like effect)
Allopurinol
Sulfinpyrazone
(Atorvastatin)
Phenylbutazone
Is ototoxic and nephrotoxic
A. Lithium B. Phenytoin C. Phenobarbitone D. Theophylline E. Clonazepam F. Carbamazepine G. Heparin - unfractionated H. Digoxin I. Warfarin J. Gentamicin K. Heparin - Low molecular weight L. Ethosuximide M. Ciclosporin N. Aspirin
Gentamicin is a bactericidal antibiotic that works by irreversibly binding the 30S subunit of the bacterial ribosome, interrupting protein synthesis. This mechanism of action is similar to other Aminoglycosides
Active against a wide range of human bacterial infections, mostly Gram-negative bacteria including Pseudomonas, Proteus, Serratia, and the Gram-positive Staphylococcus.[4] Gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila bacterial infections (because of the risk of the patient going into shock from lipid A endotoxin found in certain Gram-negative organisms).
Aminoglycosides are toxic to the sensory cells of the ear, but they vary greatly in their relative effects on hearing versus balance.
Prevention of nephrotoxicity includes judicouss use of IV fluids to correct and avoid volume depletion, correction of hypokalemia and hypomagnesemia. Once daily dosing has been shown to be less toxic than multiple daily doses. Gentamicin is usually dosed by ideal body weight. Various formulae exist for calculating gentamicin dosage. Trough and peak serum levels of gentamicin are monitored during treatment to individualize therapy and prevent excess exposure.[9]
Gentamicin, like other aminoglycosides, causes nephrotoxicity by inhibiting protein synthesis in renal cells. This mechanism specifically causes necrosis of cells in the proximal tubule, resulting in acute tubular necrosis which can lead to acute renal failure
Requires regular monitoring of APTT
A. Lithium B. Phenytoin C. Phenobarbitone D. Theophylline E. Clonazepam F. Carbamazepine G. Heparin - unfractionated H. Digoxin I. Warfarin J. Gentamicin K. Heparin - Low molecular weight L. Ethosuximide M. Ciclosporin N. Aspirin
Heparin - unfractionated
highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule
Antidote to heparin overdose[edit] Protamine sulfate (1 mg per 100 units of heparin that had been given over the past four hours) has been given to counteract the anticoagulant effect of heparin.
Heparin binds to the enzyme inhibitor antithrombin III (AT), causing a conformational change that results in its activation through an increase in the flexibility of its reactive site loop.[13] The activated AT then inactivates thrombin and other proteases involved in blood clotting, most notably factor Xa. The rate of inactivation of these proteases by AT can increase by up to 1000-fold due to the binding of heparin.
The effects of heparin are measured in the lab by the partial thromboplastin time (aPTT)
A man was put into custody after driving under the influence of drugs. On arrest he was reported as acting extremely aggressive and paranoid. He also claimed his heart was racing. One hour later he was found dead. There was suspicion of police brutality.
A. Cyanide B. Cannabis C. Heroin D. Paracetamol E. Ethanol F. Carbon monoxide G. Police brutality H. Aspirin I. Strychnine J. Cocaine K. Amphetamines L. Ecstasy M. Methadone N. Methanol O. Organophosphate P. Benzodiazepines
Cocaine: EME = ecgonine methyl ester and BE = benzoylecgonine are the two degredation products of cocaine produced by pseudocholinesterases and hydrolysis respectively.
It is a stimulant, an appetite suppressant, and a nonspecific voltage gated sodium channel blocker, which in turn causes it to produce anaesthesia at low doses. Biologically, cocaine acts as a serotonin–norepinephrine–dopamine reuptake inhibitor, also known as a triple reuptake inhibitor (TRI). It is addictive due to its effect on the mesolimbic reward pathway.[6] At high doses, it is markedly more dangerous than other CNS stimulants, including the entire amphetamine drug class,[7] due to its effect on sodium channels, since blockade of Nav1.5 can cause sudden cardiac death.
With excessive or prolonged use, the drug can cause itching, tachycardia, hallucinations, and paranoid delusions.[15] Overdoses cause hyperthermia and a marked elevation of blood pressure, which can be life-threatening,[15] arrhythmias,[8] and death.
A 24-year-old woman goes to a party where she has some pills. She subsequently becomes feverish and confused. She was found to be hyperthermic and blood results showed a raised urea and creatinine, her myoglobin was also found to be high.
A. Cyanide B. Cannabis C. Heroin D. Paracetamol E. Ethanol F. Carbon monoxide G. Police brutality H. Aspirin I. Strychnine J. Cocaine K. Amphetamines L. Ecstasy M. Methadone N. Methanol O. Organophosphate P. Benzodiazepines
Ecstacy
Peak effects of MDMA toxicity occur within two hours of ingestion and typically last four to six hours. Concentrations of MDMA contained in illicitly produced pills vary widely.
MDMA intoxication can cause a myriad of dangerous effects including severe hypertension, hyperthermia, delirium, psychomotor agitation, and profound hyponatremia. Potential life-threatening complications of these effects include intracranial hemorrhage, myocardial infarction, aortic dissection, disseminated intravascular coagulation, rhabdomyolysis, seizure, and serotonin syndrome.
We recommend severe hypertension and psychomotor agitation be treated with benzodiazepines (eg, lorazepam, 1 to 2 mg IV push; may repeat until hypertension is controlled or patient is sedated) (Grade 1C). Refractory hypertension may be treated with nitroprusside or phentolamine. We avoid beta-blocking agents, including labetalol, in the treatment of sympathomimetic poisoning because they may lead to unopposed alpha-adrenergic stimulation and a paradoxical increase in blood pressure. (See ‘Psychomotor agitation’ above.)
●For a recent ingestion (ie, less than one hour) of MDMA, we suggest a single dose of activated charcoal (1 g/kg; maximum dose 50 g) be administered (Grade 2C). Charcoal should be withheld in patients who are sedated and may not be able to protect their airway, unless endotracheal intubation is performed first. However, endotracheal intubation should not be performed solely for the purpose of giving charcoal.
James Pond comes to A&E claiming he’s been poisoned. Minutes later he dies. His skin was brick red and there was a faint odour of almonds.
A. Cyanide B. Cannabis C. Heroin D. Paracetamol E. Ethanol F. Carbon monoxide G. Police brutality H. Aspirin I. Strychnine J. Cocaine K. Amphetamines L. Ecstasy M. Methadone N. Methanol O. Organophosphate P. Benzodiazepines
Cyanide: Because of the decreased utilization of oxygen by tissues, venous oxyhemoglobin concentration will be high, making venous blood appear bright red. Therefore, despite hypotension, apnea, and/or bradycardia, the patient does not appear cyanotic in the setting of cyanide poisoning.
Antidotal treatment of cyanide poisoning involves three strategies: binding of cyanide, induction of methemoglobinemia, and use of sulfur donors.
Following a death in the family, a young woman is brought into the hospital with confusion. On inspection she appears jaundiced. Her friend reports that she had been vomiting earlier and that she had found an empty medicine bottle in her room.
A. Cyanide B. Cannabis C. Heroin D. Paracetamol E. Ethanol F. Carbon monoxide G. Police brutality H. Aspirin I. Strychnine J. Cocaine K. Amphetamines L. Ecstasy M. Methadone N. Methanol O. Organophosphate P. Benzodiazepines
Paracetamol: Appropriate acetaminophen doses produce a small amount of NAPQI which is rapidly conjugated with hepatic glutathione, forming nontoxic cysteine and mercaptate compounds that are excreted in the urine [26,31]. However, with toxic doses of a acetaminophen the sulfation and glucuronidation pathways are saturated, and more acetaminophen is metabolized to NAPQI via the cytochrome P450 enzymes [32]. When hepatic glutathione stores are depleted by approximately 70 to 80 percent, NAPQI begins to react with hepatocytes, and injury ensues. NAPQI arylates and binds covalently to the cysteine groups on hepatic macromolecules, forming NAPQI-protein adducts [35-37]. This process is irreversible and leads to oxidative injury and hepatocellular centrilobular necrosis
In the first 24 hours after overdose, patients often manifest nausea, vomiting, diaphoresis, pallor, lethargy, and malaise. Some patients remain asymptomatic.
From 24 to 72 hours after ingestion, the clinical and laboratory evidence of hepatotoxicity and, occasionally, nephrotoxicity become evident.
Liver function abnormalities peak from 72 to 96 hours after ingestion. The systemic symptoms of stage I reappear in conjunction with jaundice, confusion (hepatic encephalopathy), a marked elevation in hepatic enzymes, hyperammonemia, and a bleeding diathesis
Signs of severe hepatotoxicity include plasma ALT and AST levels that often exceed 10,000 IU/L, prolongation of the PT or INR, hypoglycemia, lactic acidosis, and a total bilirubin concentration above 4.0 mg/dL
A man was found collapsed on the floor of his room and his breathing was found to be severely depressed. A urine test was found to be positive for 6-MAM.
A. Cyanide B. Cannabis C. Heroin D. Paracetamol E. Ethanol F. Carbon monoxide G. Police brutality H. Aspirin I. Strychnine J. Cocaine K. Amphetamines L. Ecstasy M. Methadone N. Methanol O. Organophosphate P. Benzodiazepines
Heroin
The classic signs of opioid intoxication include: depressed mental status, decreased respiratory rate, decreased tidal volume, decreased bowel sounds, and miotic pupils. The best predictor of opioid poisoning is a respiratory rate
A 30-year-old farmer presents to casualty complaining of diarrhoea and painful mouth ulcers. On questioning he admitted accidentally ingesting liquid paraquat
A. N-acetylcysteine B. Haemodialysis C. Dicobalt edentate D. Naloxone E. Symptomatic and Supportive treatment F. Glucagon G. Atropine H. Hyperbaric oxygen I. Activated charcoal J. Gastric lavage K. Desferrioxamine
Activated charcoal
Paraquat is used in agriculture, and when ingested oxidative stress created by the production of free radicals and the depletion of NADPH directly causes cell damage (via lipid peroxidation, mitochondrial dysfunction, necrosis and apoptosis) and triggers a pronounced secondary inflammatory response.
Over a period of hours to days these processes lead to multi-organ failure. The organs most affected are those with high blood flow, oxygen tension, and energy requirements, in particular the lungs, heart, kidneys, and liver. The brain is uncommonly affected as paraquat does not readily cross the blood-brain barrier, although paraquat has been detected in the CSF
Oral and gastrointestinal symptoms are common. Patients usually have a painful mouth and pain with swallowing. Nausea, vomiting, and abdominal pain occur in most patients. Activated charcoal (1 g/kg in water; maximum dose 50 g) or Fuller’s Earth (2 g/kg in water; maximum 150 g in water) should be given as soon as possible per oral or via a nasogastric tube to patients who present within approximately two hours of ingestion.
A 15-year-old girl presents with sweats and hyperventilation indicative of a severe metabolic acidosis; after taking a large number of salicylate tablets
A. N-acetylcysteine B. Haemodialysis C. Dicobalt edentate D. Naloxone E. Symptomatic and Supportive treatment F. Glucagon G. Atropine H. Hyperbaric oxygen I. Activated charcoal J. Gastric lavage K. Desferrioxamine
Haemodialysis
There are 2 reasons why haemodialysis is a better answer than activated charcoal. One, because
you have no direct information about when she took the overdose - most guidelines only advise giving activated charcoal if the patient presents within 1 hour of taking the tablets. Having said that, the fact that she is severely acidotic with hyperventilation suggests some time has elapsed since the tablets were taken, as a metabolic acidosis and partial respiratory compensation don’t develop instantaneously. This leads into the second reason why haemodialysis is a better answer - this girl
is really sick! Lots of body functions, including much enzyme activity, is pH dependent, so she needs treatment for her acid-base and electrolyte imbalance. Sodium bicarbonate can be used to correct acidosis, but haemodialysis is the treatment of choice for severe poisoning and those with high salicylate levels.
Early symptoms of acute aspirin toxicity include tinnitus, vertigo, nausea, vomiting, and diarrhea; subsequent symptoms portending a more severe intoxication include altered mental status (ranging from agitation to lethargy), hyperpyrexia, noncardiac pulmonary edema, and coma. Early symptoms are typically present within one to two hours after a single acute ingestion. Hyperpnea is often observed in salicylate overdose. Salicylates stimulate the respiratory center directly, resulting in an early fall in the PCO2 and respiratory alkalosis. An anion-gap metabolic acidosis then follows, due primarily to the accumulation of organic acids, including lactic acid and ketoacids.
Treatment of salicylate intoxication is directed toward decreasing the fraction of uncharged (protonated) molecules, which is accomplished by increasing the systemic pH (ie, lowering the H+ ion concentration). This is referred to as “alkalinization” and is most easily accomplished by administering sodium bicarbonate. Increasing the systemic pH reduces the diffusion of salicylate anions into the central nervous system, as charged molecules do not easily diffuse across the blood-brain barrier. Alkalinization also “traps” salicylate anions within the renal tubule, preventing back-diffusion across the renal epithelium into the systemic circulation.
Indications for hemodialysis include the following:
●Altered mental status
●Pulmonary or cerebral edema
●Renal insufficiency that interferes with salicylate excretion
●Fluid overload that prevents the administration of sodium bicarbonate
●A serum salicylate concentration >100 mg/dL (7.2 mmol/L) in acute overdose
●Clinical deterioration despite aggressive and appropriate supportive care
Aspirin intoxication may decrease cerebral glucose concentrations despite a normal serum glucose. Therefore, we suggest that adults with salicylate poisoning who are hypoglycemic or manifest alterations in mental status, regardless of their serum glucose concentration, be treated with supplemental glucose
A 26-year-old woman collapses after a massive overdose of atenolol. She remains in cardogenic shock despite initial treatment with IV atropine
A. N-acetylcysteine B. Haemodialysis C. Dicobalt edentate D. Naloxone E. Symptomatic and Supportive treatment F. Glucagon G. Atropine H. Hyperbaric oxygen I. Activated charcoal J. Gastric lavage K. Desferrioxamine
Glucagon in beta-blocker overdose is to counteract hypoglycaemia secondary to beta-
block of glycogenolysis. However, it can also have an effect on bradycardia and subsequent cardiogenic shock because glucagon
receptors are G-protein coupled receptors that lead to an increase in adenyl cyclase activity and increased intra-cellular cAMP.
This bypasses the need for B1-receptor activity to increase cAMP.
Complications following beta blocker overdose are related to excessive beta adrenergic blockade, and occasionally the proarrhythmic (membrane-stabilizing) activity of these agents on cardiac conduction [2]. Ingestion of other cardioactive agents in association with beta blockers increases mortality following overdose [2,3]. Common and potentially dangerous coingestions include calcium channel blockers, cyclic antidepressants, and neuroleptics
●Beta 1, which are found primarily in heart muscle. Activation of these receptors results in an increase in heart rate, contractility, atrioventricular (AV) conduction, and a decrease in AV node refractoriness.
●Beta 2, which are present in heart muscle but are more prominent in bronchial and peripheral vascular smooth muscle. Activation of these receptors results in vasodilation and bronchodilation.
●Beta 3, which are found in adipose tissue and the heart. Activation of these receptors may mediate catecholamine-induced thermogenesis and may reduce cardiac contractility.
Bradycardia and hypotension are the most common effects, and in severe overdoses can result in profound myocardial depression and cardiogenic shock. Ventricular dysrhythmias are seen more frequently following propranolol and acebutolol exposures
Beta blockers decrease conduction velocity across the atrioventricular (AV) node, resulting in PR prolongation; they also slow automaticity within the sinoatrial (SA) node, causing bradycardia
- Stabilization of the airway as necessary (avoid induction agents that exacerbate hypotension)
- Additional IV boluses of isotonic crystalloid
- IV glucagon
- IV calcium salts
- Vasopressor (eg, epinephrine)
- IV high-dose insulin and glucose
- IV lipid emulsion therapy
A pregnant 30-year-old woman is found drowsy in her rented flat. She complains of severe nausea for the last 3 hours. Her carboxyhaemoglobin level is 41%.
A. N-acetylcysteine B. Haemodialysis C. Dicobalt edentate D. Naloxone E. Symptomatic and Supportive treatment F. Glucagon G. Atropine H. Hyperbaric oxygen I. Activated charcoal J. Gastric lavage K. Desferrioxamine
Hyperbaric oxygen
CO poisoning is most common during winter in cold climates, but it may occur in all seasons and environments. Smoke inhalation is responsible for most unintentional cases. Other potential sources of CO include poorly functioning heating systems, improperly vented fuel-burning devices (eg, kerosene heaters, charcoal grills, camping stoves, gasoline-powered electrical generators), and motor vehicles operating in poorly ventilated areas.
CO diffuses rapidly across the pulmonary capillary membrane and binds to the iron moiety of heme with approximately 240 times the affinity of oxygen. The degree of carboxyhemoglobinemia (COHb) is a function of the relative amounts of CO and oxygen in the environment, duration of exposure, and minute ventilation.
The clinical findings of CO poisoning are highly variable and largely nonspecific. Mild to moderate CO-intoxicated patients often present with constitutional symptoms, including headache (most common), malaise, nausea, and dizziness, and may be misdiagnosed with acute viral syndromes. In the absence of concurrent trauma or burns, physical findings in CO poisoning are usually confined to alterations in mental status, ranging from mild confusion to seizures and coma. A careful neurologic examination is crucial.
The diagnosis of CO poisoning is based upon a compatible history and physical examination in conjunction with an elevated carboxyhemoglobin level. Diagnosis requires quantification by cooximetry of a blood gas sample; standard pulse oximetry (SP02) is unable to distinguish between oxyhemoglobin and COHb. Blood PO2 measurements tend to be normal because PO2 reflects O2 dissolved in blood, and this process is not affected by CO
Hyperbaric oxygen therapy (HBO): to decrease the incidence and severity of delayed neurocognitive deficits following CO poisoning
A 25-year-old man is delirious and hyperpyrexial after taking a pill in a club. He is hyperreflexic and is hyponatraemic
A. N-acetylcysteine B. Haemodialysis C. Dicobalt edentate D. Naloxone E. Symptomatic and Supportive treatment F. Glucagon G. Atropine H. Hyperbaric oxygen I. Activated charcoal J. Gastric lavage K. Desferrioxamine
Symptomatic and Supportive treatment
MDMA-associated hyponatremia frequently produces obtundation to a degree that necessitates endotracheal intubation. No induction or paralytic agent commonly used for rapid sequence intubation (RSI) is contraindicated in the setting of MDMA intoxication.
We recommend severe hypertension and psychomotor agitation be treated with benzodiazepines (eg, lorazepam, 1 to 2 mg IV push; may repeat until hypertension is controlled or patient is sedated). Refractory hypertension may be treated with nitroprusside or phentolamine. We avoid beta-blocking agents, including labetalol, in the treatment of sympathomimetic poisoning because they may lead to unopposed alpha-adrenergic stimulation and a paradoxical increase in blood pressure.
For a recent ingestion (ie, less than one hour) of MDMA, we suggest a single dose of activated charcoal (1 g/kg; maximum dose 50 g) be administered. Charcoal should be withheld in patients who are sedated and may not be able to protect their airway, unless endotracheal intubation is performed first. However, endotracheal intubation should not be performed solely for the purpose of giving charcoal.
Butyrophenones (such as haloperidol and droperidol) interfere with heat dissipation, may prolong the QTc, and may reduce the seizure threshold. We suggest butyrophenones NOT be used to sedate patients with MDMA toxicity
Seizures, hyperthermia, and serotonin syndrome should be treated in standard fashion
An 18 year old female is brought in to A&E from a rave in the early hours of the morning. On initial examination she is agitated with a heart rate of 120 bpm. She is very sweaty and has wide dilated pupils
A. Lithium B. Tricyclic antidepressants C. Carbon Monoxide D. Ecstasy E. Naloxone F. Paracetamol G. Desferrioxamine H. Methanol I. Acetylcysteine J. Salicylates K. Organophosphates
Ecstacy
MDMA-associated hyponatremia frequently produces obtundation to a degree that necessitates endotracheal intubation. No induction or paralytic agent commonly used for rapid sequence intubation (RSI) is contraindicated in the setting of MDMA intoxication.
We recommend severe hypertension and psychomotor agitation be treated with benzodiazepines (eg, lorazepam, 1 to 2 mg IV push; may repeat until hypertension is controlled or patient is sedated). Refractory hypertension may be treated with nitroprusside or phentolamine. We avoid beta-blocking agents, including labetalol, in the treatment of sympathomimetic poisoning because they may lead to unopposed alpha-adrenergic stimulation and a paradoxical increase in blood pressure.
For a recent ingestion (ie, less than one hour) of MDMA, we suggest a single dose of activated charcoal (1 g/kg; maximum dose 50 g) be administered. Charcoal should be withheld in patients who are sedated and may not be able to protect their airway, unless endotracheal intubation is performed first. However, endotracheal intubation should not be performed solely for the purpose of giving charcoal.
Butyrophenones (such as haloperidol and droperidol) interfere with heat dissipation, may prolong the QTc, and may reduce the seizure threshold. We suggest butyrophenones NOT be used to sedate patients with MDMA toxicity
Seizures, hyperthermia, and serotonin syndrome should be treated in standard fashion
A 25 year old male is admitted with hyperventilation. He is sweating and appears nauseous. He says that he has ringing in his ears. Blood gases show that he has mixed acid-base disturbance
A. Lithium B. Tricyclic antidepressants C. Carbon Monoxide D. Ecstasy E. Naloxone F. Paracetamol G. Desferrioxamine H. Methanol I. Acetylcysteine J. Salicylates K. Organophosphates
Salicylates
Sodium bicarbonate can be used to correct acidosis, but haemodialysis is the treatment of choice for severe poisoning and those with high salicylate levels.
Early symptoms of acute aspirin toxicity include tinnitus, vertigo, nausea, vomiting, and diarrhea; subsequent symptoms portending a more severe intoxication include altered mental status (ranging from agitation to lethargy), hyperpyrexia, noncardiac pulmonary edema, and coma. Early symptoms are typically present within one to two hours after a single acute ingestion. Hyperpnea is often observed in salicylate overdose. Salicylates stimulate the respiratory center directly, resulting in an early fall in the PCO2 and respiratory alkalosis. An anion-gap metabolic acidosis then follows, due primarily to the accumulation of organic acids, including lactic acid and ketoacids.
Treatment of salicylate intoxication is directed toward decreasing the fraction of uncharged (protonated) molecules, which is accomplished by increasing the systemic pH (ie, lowering the H+ ion concentration). This is referred to as “alkalinization” and is most easily accomplished by administering sodium bicarbonate. Increasing the systemic pH reduces the diffusion of salicylate anions into the central nervous system, as charged molecules do not easily diffuse across the blood-brain barrier. Alkalinization also “traps” salicylate anions within the renal tubule, preventing back-diffusion across the renal epithelium into the systemic circulation.
Indications for hemodialysis include the following:
●Altered mental status
●Pulmonary or cerebral edema
●Renal insufficiency that interferes with salicylate excretion
●Fluid overload that prevents the administration of sodium bicarbonate
●A serum salicylate concentration >100 mg/dL (7.2 mmol/L) in acute overdose
●Clinical deterioration despite aggressive and appropriate supportive care
Aspirin intoxication may decrease cerebral glucose concentrations despite a normal serum glucose. Therefore, we suggest that adults with salicylate poisoning who are hypoglycemic or manifest alterations in mental status, regardless of their serum glucose concentration, be treated with supplemental glucose
An 80 year old man and his 79 year old wife were brought in after a neighbour found them collapsed in their home. On questioning the neighbour it was found that the couple had not been feeling well for a few weeks and had been complaining of nausea, headaches and dizziness
A. Lithium B. Tricyclic antidepressants C. Carbon Monoxide D. Ecstasy E. Naloxone F. Paracetamol G. Desferrioxamine H. Methanol I. Acetylcysteine J. Salicylates K. Organophosphates
Carbon Monoxide
CO poisoning is most common during winter in cold climates, but it may occur in all seasons and environments. Smoke inhalation is responsible for most unintentional cases. Other potential sources of CO include poorly functioning heating systems, improperly vented fuel-burning devices (eg, kerosene heaters, charcoal grills, camping stoves, gasoline-powered electrical generators), and motor vehicles operating in poorly ventilated areas.
CO diffuses rapidly across the pulmonary capillary membrane and binds to the iron moiety of heme with approximately 240 times the affinity of oxygen. The degree of carboxyhemoglobinemia (COHb) is a function of the relative amounts of CO and oxygen in the environment, duration of exposure, and minute ventilation.
The clinical findings of CO poisoning are highly variable and largely nonspecific. Mild to moderate CO-intoxicated patients often present with constitutional symptoms, including headache (most common), malaise, nausea, and dizziness, and may be misdiagnosed with acute viral syndromes. In the absence of concurrent trauma or burns, physical findings in CO poisoning are usually confined to alterations in mental status, ranging from mild confusion to seizures and coma. A careful neurologic examination is crucial.
The diagnosis of CO poisoning is based upon a compatible history and physical examination in conjunction with an elevated carboxyhemoglobin level. Diagnosis requires quantification by cooximetry of a blood gas sample; standard pulse oximetry (SP02) is unable to distinguish between oxyhemoglobin and COHb. Blood PO2 measurements tend to be normal because PO2 reflects O2 dissolved in blood, and this process is not affected by CO
Hyperbaric oxygen therapy (HBO): to decrease the incidence and severity of delayed neurocognitive deficits following CO poisoning
A depressed 30 year old woman was brought into A&E after being found by a friend. On examination she appears very drowsy with sinus tachycardia and wide dilated pupils. She has marked reflexes and extensor plantar responses. ECG shows a wide QRS interval
A. Lithium B. Tricyclic antidepressants C. Carbon Monoxide D. Ecstasy E. Naloxone F. Paracetamol G. Desferrioxamine H. Methanol I. Acetylcysteine J. Salicylates K. Organophosphates
Tricylic Anti-Depressants
Both TCA od’s and ecstasy od’s can cause wide dilated pupils. Ecstasy is more likely to lead to agitation and TCA drowsiness.This points very clearly to TCA overdose (reflexes and widened QRS complexes). Also….remember that ecstasy may induce vasopressin secretion and an SIADH, with hyponatraemia
Symptoms and signs of TCA intoxication generally consist of vital sign abnormalities, mental status changes, seizures, and anticholinergic toxicity. Sinus tachycardia and hypotension are common. Sedation is the most typical alteration in mental status, but confusion, delirium, or hallucinations may occur. Anticholinergic toxicity commonly manifests as hyperthermia, flushing, dilated pupils that respond poorly to light, delirium, intestinal ileus, and urinary retention.
Cardiac conduction abnormalities are common in patients with TCA poisoning. These abnormalities can degenerate into ventricular tachycardia and ventricular fibrillation (VT and VF), which occur in approximately 4 percent of TCA overdose cases. The electrocardiogram (ECG) is a most valuable tool in determining the extent of TCA poisoning. The following signs suggest cardiotoxicity:
•Prolongation of the QRS >100 msec
•Abnormal morphology of the QRS (eg, deep, slurred S wave in leads I and AVL)
A 45 year old farm worker is admitted complaining primarily of nausea and vomiting. On further questioning it is revealed that he also has a headache, hypersalivation and he is finding it hard to breathe. On examination the patient appears sweaty and has flaccid paresis of his limb muscles
A. Lithium B. Tricyclic antidepressants C. Carbon Monoxide D. Ecstasy E. Naloxone F. Paracetamol G. Desferrioxamine H. Methanol I. Acetylcysteine J. Salicylates K. Organophosphates
Organophosphates
Acute toxicity from organophosphorus agents presents with manifestations of cholinergic excess. The dominant clinical features of acute cholinergic toxicity include bradycardia, miosis, lacrimation, salivation, bronchorrhea, bronchospasm, urination, emesis, and diarrhea.
Moderately to severely poisoned patients with markedly depressed mental status require 100 percent oxygen and immediate tracheal intubation. In addition, patients who appear mildly poisoned may rapidly develop respiratory failure. Succinylcholine should be avoided when performing rapid sequence intubation in patients with OP poisoning. Bradycardia and hypotension are usually present in moderate to severe poisonings. Adequate volume resuscitation with isotonic crystalloid should be performed concomitantly with other resuscitative and diagnostic efforts.
We recommend atropine therapy for all patients with moderate to severe cholinergic toxicity from OP or carbamate poisoning. Atropine is started at a dose of 2 to 5 mg IV for adults
We suggest that oxime therapy (eg, pralidoxime) be given to all patients with evidence of cholinergic toxicity, patients with neuromuscular dysfunction, or patients with exposures to organophosphorus agents known to cause delayed neurotoxicity
Which of the above techniques can be used to test for all classes of drugs of abuse (DOA)?
A. Thin layer chromotography B. Barbituates C. Immunoassay D. Benzodiazepines E. Blood sample F. Liquid chromotography G. Urine sample H. Drugs of abuse (DOA) I. Stool sample J. Paracetamol K. Liver sample
Immunoassays are by far the most widely used method of initial testing for DOA in the clinical setting. Typically providing a result within minutes after sample application, immunoassays are able to detect low concentrations of a substance with a high degree of specificity. They are technically easy to perform and relatively inexpensive.
Immunoassays use antibodies that recognize a drug or metabolite. There are two general types of immunoassay techniques: noncompetitive and competitive. Noncompetitive assays recognize an analyte that is sandwiched between two antibodies, each of which recognizes a different site (or epitope) of the molecule. In a competitive immunoassay, non-labeled analyte in the patient’s serum or urine competes for a limited number of binding sites with a labeled version of the analyte that is provided with the immunoassay; displacement of the labeled analyte is the signal that suggests the presence of the drug.
The immunoassays most widely used for routine DOA testing are microparticle capture assays. These use a substance, often latex, that can collect in high concentration in a particular location, forming a colored band that can be visually read. The simplest such design uses an antidrug antibody with colored micro-particles and a capture zone consisting of the immobilized drug. Similar technology is used in other widely available point-of-care (POC) testing kits, such as those for urine pregnancy or streptococcal antigen. These are all typically conducted in a cassette containing the strip or matrix to which the biologic sample (and sometimes reagent) is added. After a period of minutes, the presence or absence of a colored band is interpreted as a positive or negative result.
What sample is required for use with gas chromatography mass spectroscopy?
A. Thin layer chromotography B. Barbituates C. Immunoassay D. Benzodiazepines E. Blood sample F. Liquid chromotography G. Urine sample H. Drugs of abuse (DOA) I. Stool sample J. Paracetamol K. Liver sample
Blood sample
Chromatography refers to several related techniques whose common approach involves physical separation of substances. The multiple methods (such as liquid chromatography, thin layer chromatography, and gas chromatography) all include a combination of a mobile phase and a stationary phase. The stationary phase usually consists of fine particles, and the mobile phase is usually liquid or gas. The time required to traverse the length of the chromatography column or the distance traveled in a media during a set time (in thin layer chromatography) is consistent and highly reproducible.
Colorimetric can be used to test for which drug commonly taken in overdose?
A. Thin layer chromotography B. Barbituates C. Immunoassay D. Benzodiazepines E. Blood sample F. Liquid chromotography G. Urine sample H. Drugs of abuse (DOA) I. Stool sample J. Paracetamol K. Liver sample
Paracetamol
Which of the above techniques can be used to test for benzodiazepines and various antipsychotic drugs?
A. Thin layer chromotography B. Barbituates C. Immunoassay D. Benzodiazepines E. Blood sample F. Liquid chromotography G. Urine sample H. Drugs of abuse (DOA) I. Stool sample J. Paracetamol K. Liver sample
Liquid Chromatography
Chromatography offers a highly sensitive and specific technique for detecting drugs or metabolites. However, it requires highly trained laboratory staff, instruments, and commonly takes many hours to provide results, and thus it is usually not a methodology used for initial DOA testing. A notable exception is when an extended, comprehensive toxicology screening, which may detect hundreds of medications and drugs, is performed as an initial investigation.
Which of the above techniques can be used to analyse samples of stool, liver and also urine?
A. Thin layer chromotography B. Barbituates C. Immunoassay D. Benzodiazepines E. Blood sample F. Liquid chromotography G. Urine sample H. Drugs of abuse (DOA) I. Stool sample J. Paracetamol K. Liver sample
Thin layer chromotography
Which option is the best specimen for assessing long-term drug use?
A. MDMA B. Saliva C. Cocaine D. THC E. Blood F. Urine G. Morphine H. Hair I. Paracetamol J. Forensics K. Toxicology
Hair
Hair drug testing is a method that can detect drug use over a much longer period of time, and is often used for highly safety-critical positions where there is zero tolerance of illegal drug use. Standard hair follicle screen covers a period of 30 to 90 days. The growth of hair is usually at the rate of 0.5 inches per month. The hair sample is cut close to the scalp and 80 to 120 strands of hair are needed for the test. In the absence of hair on the head, body hair can be used as an acceptable substitute.[29] This includes facial hair, the underarms, arms, and legs or even pubic hair. Because body hair grows at a different rate than head hair, the timeframe changes, with scientists estimating that drug use can be detected in body hair for up to 12 months.
Which drug is found in the most addict related deaths?
A. MDMA B. Saliva C. Cocaine D. THC E. Blood F. Urine G. Morphine H. Hair I. Paracetamol J. Forensics K. Toxicology
Morphine
The classic signs of opioid intoxication include: depressed mental status, decreased respiratory rate, decreased tidal volume, decreased bowel sounds, and miotic pupils. The best predictor of opioid poisoning is a respiratory rate <12.
Although suppression of respiratory drive is most prominent, opioid intoxication can also be complicated by hypothermia, coma, seizure, head trauma, aspiration pneumonia, and rhabdomyolysis.
In cases of suspected opioid overdose, we recommend the short-acting opioid antagonist naloxone be given (Grade 1B). While the intravenous (IV) route is preferred, naloxone may be given subcutaneously or intramuscularly if IV access is unavailable.
Activated charcoal and gastric emptying are almost never indicated in opioid poisoning. The large volume of distribution of the opioids precludes removal of a significant quantity of drug by hemodialysis.
Which option is responsible for the analysis of samples for drugs and poisons?
A. MDMA B. Saliva C. Cocaine D. THC E. Blood F. Urine G. Morphine H. Hair I. Paracetamol J. Forensics K. Toxicology
Toxicology
Which option is the best example of a quick, cheap, easy and non-invasive specimen which is likely to be adulterated for forensic drug analysis? Disadvantages include a small window of detection.
A. MDMA B. Saliva C. Cocaine D. THC E. Blood F. Urine G. Morphine H. Hair I. Paracetamol J. Forensics K. Toxicology
Saliva
Saliva / oral fluid-based drug tests can generally detect use during the previous few days. Is better at detecting very recent use of a substance.
Detection in saliva tests begins almost immediately upon use of the following substances, and lasts for approximately the following times:
Alcohol: 6-12 h
Marijuana: 1-24h
Auto-Antibody against:
Cardiolipin, Apoplipoprotein H, anti-β2 glycoprotein
Anti-Phospholipid Syndrome
Auto-Antibody against:
Smooth Muscle, Liver Kidney Microsomal, Soluble liver Antigen, Actin
Autoimmune Hepatitis
Auto-Antibody against Rhesus
AIHA
Auto-Antibody against cANCA / proteinase-3 (Cytoplasmic)
Wegeners/ Granulomatous Polyangitis
Auto-Antibody against pANCA / MPO (Perinuclear)
Churg Strauss
Microscopic polyangiitis
Primary sclerosing cholangitis
Auto-Antibody against platelet (GPIIb/IIIa)
ITP
Auto-Antibody against:
Jo-1 (t-RNA synthetase) (Cytoplasmic
speckled)
Dermatomyositis
Polymyositis
Auto-Antibody against:
SCL-70 (Topoisomerase) (Nucleolar), RNA Pol 1,2,3 (Nucleolar), Fibrillarin (Nucleolar)
Diffuse Systemic sclerosis
Auto-Antibody against centromere
CREST
Auto-Antibody against:
GBM (NC α3 COL4)
Goodpastures, HLA-DR2
Auto-Antibody against:
Desmosomes (cadherins)
Pemphigus
Auto-Antibody against:
Hemidesmosomes (collagen XVII)
Pemphigoid
HLA-B8
PSC