Pathology 2014 Flashcards
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
