**Fibrosing alveolitis is the most common pulmonary manifestation of rheumatoid arthritis. **impairment in renal function in Hepatorenal syndrome The hallmark is oliguria and progressive decline in renal function. The urine is typically free of protein or any other sediment. **Long-term haemodialysis is associated with carpal tunnel syndrome. is the most common complication **the most likely cause of bacterial meningitis in adult patients with neutropenia : Listeria monocytogenes. **the most frequent cause of a nosocomial wound infection: Insufficient hand disinfection **Osteoporosis is the most common cause of fracture of neck of femur and is not associated with any specific abnormality in the standard bone biochemistry profile. **Tuberculous arthritis usually affects children aged 2–5 years. The hip is one of the most frequently affected joints. **Meningitis due to enterovirus and meningococcus (N. meningitidis) are the most likely in this age group(28 yrs0 **Tuberculous meningitis is rare in the UK and the CSF typically shows a markedly raised protein (> 1 g/l), a low glucose (< 50% serum) and a lymphocytosis. **Streptococcus meningitis is the commonest cause of meningitis in those over 40 years of age; very high neutrophil counts are often seen in the CSF, which has a high protein and low glucose level. **Factors predisposing to digitalis toxicity are advanced age, hypoxia, hypokalaemia, hypomagnesaemia, hypercalcaemia, hypothyroidism, amyloidosis and renal failure. The most common precipitating factor is hypokalaemia. ** In Hodgkin’s disease Lymphocyte depleted has the worst prognosis. It is the least common variant and typically occurs in older people. **The commonest mutation in patients with cystic fibrosis (CF) is the Delta-F508 mutation. **in systemic lupus erythematosus Recurrent pleurisy and pleural effusions are the most common manifestations and are often bilateral **Cryptosporidium infection in HIV-positive patients along with cytomegalovirus, is the commonest cause of HIV-related diarrhoea and tends to present when the CD4 count is less than 100. **Diarrhoea and flushing, occurring separately or together, are the most frequent presenting features of carcinoid syndrome (approximately half of all patients). **Focal necrotising glomerulonephritis is the characteristic renal lesion of generalised Wegener’s granulomatosis. Typically, it presents with deteriorating renal function that progresses to renal failure within 3 months, **Glomerulonephritis is a common occurrence in chronic Schistosoma mansoni infection in Brazil, especially in patients with hepatosplenic disease **Tremor in the legs is a useful sign as it is almost always associated with idiopathic Parkinson’s disease. The tremor is typically a rest tremor unlike benign essential tremor, where actions such as drinking a cup of tea make the tremor worse. **Pericardial effusions are more common in patients with rheumatoid arthritis than constrictive pericarditis and acute pericarditis. **The earliest lesions to be detected in diabetic retinopathy are usually dot haemorrhages (capillary microaneurysms) and venous dilatation. **Hypertrophic cardiomyopathy is the single, most common cause of sudden death in young athletes. **the most common cause of paranoid psychosis with visual hallucination :Alcohol withdrawal **Basal cell carcinomas are the most common malignant skin tumour and are related to excessive skin exposure. They are common later in life and may present as a slow-growing nodule or papule. **The most common type of thyroid cancer is papillary cancer, which accounts for approximately 70% of all thyroid cancers ***Open angle glaucoma is 100 times more common than angle closure glaucoma, and is asymptomatic until central visual loss appears at the end stage. **a high white cell count with smear cells and mature lymphocytes. This is characteristic of chronic lymphocytic leukaemia... **Chronic lymphocytic leukaemia · Constitutes 25% of all leukaemias. It is chiefly a disease of the elderly · It is characterised by an accumulation of mature lymphocytes in the peripheral blood, bone marrow, spleen, liver and lymph nodes · Clinical findings include painless, symmetrical lymphadenopathy, hepatosplenomegaly, pruritus and symptoms due to bone marrow failure · Blood film will show large numbers of mature lymphocytes and smear or smudge cells. Anaemia and thrombocytopenia are common · Hypogammaglobulinaemia is common and monoclonal paraproteins are occasionally seen · Staging is by the Binet or Rai systems and depends on number of areas involved and full blood count results · Median survival is 3–5 years and one-third die of causes other than the leukaemia · In early stages no treatment is required. In later stages and in rapidly progressive disease treatment is with oral or intravenous chemotherapy such as chlorambucil or fludarabine. Stem cell transplantation is an option in younger patients **IgG is the most common paraprotein in myeloma. **Myeloma · Median age of diagnosis is 70 years · Diagnosis is made in the presence of two of monoclonal protein in blood or urine, 10% plasma cells in bone marrow and lytic bone lesions · Other clinical features are bone disease, hypercalcaemia, renal failure, bone marrow failure and immune paresis · 5 year survival is only 25% · Treatment is supportive, chemotherapy (which can be oral or intravenous) and autologous or allogeneic stem cell transplantation · Thalidomide has recently been used in relapsed and refractory disease ***Adrenergic inhibitors used in hypertension: Peripheral neuronal inhibitors: Reserpine, Guanethedine Central adrenergic inhibitors: M-dopa, Clonidine, Guananbenz, Guanafacine Alpha-receptor blockers: o Alpha 1 and 2 receptor blockers: Phenoxybenzamine, phentolamine o Alpha 1 blockers: Doxazosin, Terazosin Beta blockers Alpha and beta blockers: Labetalol **Polycythaemia rubra vera: · Splenomegaly · Aquagenic pruritus · Bleeding · Gout · Peptic ulcer · Conversion to myelofibrosis or leukaemia in 10% **Causes of Chorea Neurodegenerative: Huntington’s disease Benign hereditary chorea Dentatorubropallidoluysian atrophy Inherited metabolic: Wilson’s disease Lesch-Nyhan disease Neuroacanthosis Hypoxic/ischaemic: Stroke Hypotension Vasculitis Sickle cell disease Polycythaemia Toxic: Copper Mercury Drug induced: Oral contraceptive pill L-Dopa Neuroleptics Anticholinergics Cocaine Amphetamines Infection: Sydenham’s chorea Meningitis Viral encephalitis Mycoplasma pneumoniae Legionella Toxoplasmosis Creutzfeld-Jacob disease Autoimmune: SLE Primary anti-phospholipid syndrome Vasculitis Behcet’s Hashimoto’s thyroiditis (unrelated to hyperthyroidism) Endocrine: Thyrotoxicosis Chorea gravidarum Addison’s disease Metabolic: Hypocalcaemia Hypomagnesaemia Hyper/hypoglycaemia Hyper/hyponatraemia **Causes of sudden cardiac death · Arrhythmia -Acute myocardial infarction -Long-QT syndromes -Hypertrophic cardiomyopathy -Commotio cardis -Coronary anomalies -Myocarditis · Obstruction -Atrial myxoma -Infective endocarditis -Dissection **In Hypertrohpic Cardiomyopathy · Combination of palpable LVS4 and then double systolic apical impulse due to the mid systolic outflow obstruction · It increases in phase II of the valsalva maneouver (the straining phase) and decreases in phase IV (post release phase) · Severe diastolic dysfunction · Children have a worse prognosis than affected adults because of greater incidence of SCD · As in severe AS (because of greater myocardial oxygen demand) **5 histological stages have been described (WHO Classification) and treatment depends on this. There is a lack of clear correlation between clinical manifestations and the severity of renal involvement. Biopsy findings guide the selection of immunosuppressive therapy. WHO Classification of Lupus Nephritis Stage I ¡V Lupus nephritis without histological changes Stage II ¡V Mesangial lupus nephritis Stage III ¡V Focal proliferative lupus nephritis Stage IV ¡V Diffuse proliferative lupus nephritis (commonest & most severe form) Stage V ¡V Membranous lupus nephritis Conditions that recur in the transplanted kidney Focal glomerulosclerosis Mesangiocapillary glomerulonephritis Rapidly progressive (Crescentic) glomerulonephritis IgA nephropathy Alport¡¦s syndrome Cystinosis Oxalosis Lupus nephritis Goodpastures syndrome Wegner¡¦s granulomatosis **The most common renal disease in HIV is collapsing FSGS in which there is focal sclerosis associated with collapse down of the glomerulus leaving a space in Bowman’s capsule. It has a poor prognosis and usually leads to ESRF. **The indications for a native nephrectomy prior to renal transplant are: 1. Uncontrolled hypertension where a differential renin study shows that one or the other kidney is significantly contributing to hypertension 2. Pyonephrosis 3. Recurrent attacks of clinically significant UTI **Budd Chiari classically results in a very high protein ascites but may cause a transudate. **Transudates (protein < 30gdl or 75% of the serum albumin) are due to: - Reduced intravascular oncotic pressure (hypoalbuminaemia) - Increased intravascular hydrostatic pressure (cirrhosis, portal hypertension, CCF) **Teaching Notes for Question 15 Theme: Pancreatic Secretion The roles of individual gut hormones are not completely defined, but cholecystokinin (duodenum & jejunum) increases gall bladder contraction, increases colonic motility. Gastrin (gastric antrum & duodenum) increases gastric acid secretion,increases GI mucosal growth. Secretin(duodenum & Jejunum) increases pancreatic bicarbonate production. VIP(enteric nerves)increased intestinal secretion, splanchnic vasodilation. Motilin(whole gut) increases small bowel motility. Bombesin (gut & Pancreas)stimulates pancreatic exocrine activity. Neuropeptide Y (enteric nerves)regulates intestinal blood flow. Somatostatin (stomach & pancreas) inhibits secretion and action of gut hormones. Glucagon(pancreas)reduces GI motility **In systemic lupus erythematosus (SLE). Joint involvement is the most common clinical feature (> 90%). **Prolactinoma is the commonest pituitary tumour, making up 30% of all adenomas. Microadenomas occur with increasing frequency in women, macroadenomas more commonly in men. **ASDs account for about 10-15% of all congenital cardiac anomalies and are the second commonest congenital heart disease seen in adults. **VSDs are the commonest adult congenital heart disease. **Frontal lobe dementia------>a failure to generate list rapidly is the test of frontal lobe+difficulties with task sequencing and executive skills. EXPRESSIVE aphasia, primitive reflexes, perseveration, anosmia and changes in personality. Parietal lobe--------------->Dyscalculia(inability to perform mentalarithmetic) is a manifestation of the dominant parietal lobe Sensory inattention, apraxia, neglect, astereognosis(unable to recognise an object by feeling it) and visual field defects( typically homonymous inferior quadrantanopia). Temporal lobe-----------> typical homonymous superior quadrantanopia), Wernike's (RECEPTIVE) aphasia, auditory agnosia, and memory impairment Occipital lobe---------->cortical blindness(blindness due to damage to the visual cortex and may present as Anton syndrome where there is blindness but the patient is unaware or denies blindness), homonymous hemianopia, and visual agnosia( seeing but not percieving objects - it is diffirent to neglect since in agnosia the objects are seen and followed but cannot be named). Homonymous hemianopia----------> occipital lobe superior quanranopia---------------->temporal lobe inferior quanrtanopia------------------->parietal lobe **AUTOIMMUNE ASSOCIATIONS Thyroid disease, IDDM, Addison disease, pernicious anaemia, alopecia, vitiligo. MULTIPLE ENDOCRINE NEOPLASIA Autosomal dominant. The association of a number of endocrine tumours. MEN I MEN IIa Parathyroid Adrenal (phaeochromocytoma, Cushing) Pituitary (prolactin or GH or ACTH) Thyroid (medullary carcinoma) Pancreas Parathyroid hyperplasia (Thyroid) (Adrenal) Fasting calcium level (??) Calcitonin level ? (medullary ca. thyroid) Look for phaeochromocytoma MEN IIb is the same as MEN IIa, with Marfanoid features and multiple neuromas. Prophylactic total thyroidectomy is performed if the child is known to carry the gene for MEN II. **Adrenergic inhibitors used in hypertension: Peripheral neuronal inhibitors: Reserpine, Guanethedine Central adrenergic inhibitors: M-dopa, Clonidine, Guananbenz, Guanafacine Alpha-receptor blockers: o Alpha 1 and 2 receptor blockers: Phenoxybenzamine, phentolamine o Alpha 1 blockers: Doxazosin, Terazosin Beta blockers Alpha and beta blockers: Labetalol **Mixed connective tissue disease (MCTD) is an overlap connective tissue disease with features of SLE, polymyositis and progressive systemic sclerosis. The characteristic auto-antibody pattern is of high titre anti-RNP and speckled pattern ANA. **The antiphospholipid syndrome is one of the commoner causes of hypoadrenalism and may precipitate adrenal infarction and haemorrage through adrenal vein thrombosis. **Biphasic high amplitude sharp waves are characteristic of ceutzfeld-jacob disease. **Causes of dilated pupils: Holme's adie(myotonic pupils) Third nerve palsy drug poisons(atropine, CO, Ethylene glycol) Causes of small pupils : horner;s syndrome old age pontine haemorrhage Argyl Robertson pupil Drug poisons(opiate, organophosphate) **Optic neuropathy------------->central scotoma. Optic tract lesion--------------->incongrous homontmous hemianopia. Chiasmal lesion---------------->bitemporal hemianopia. optic radiation and occipital lobe---------------->congrous hemianopia. **Listeria meningitis is typically associated with brain stem signs. CSF shows neutrophilic pleocytosis, low glucose and high protein. **Nystagmus is defind as involuntary oscillations of the eyes. THis may be 1-Pendular: when the oscillations are equal in rate and amplitude. 2-Jerking: when there are quick and slow phases(the quick phase is used to define the direction). pendular nystagmus is usually duee to loss of macular vision, but maybe seen in diffuse brain stem lesions. jerking nustagmus which is of constant direction regardless of the direction of gaze, suggests a labyrinthine or cerebellar lesion. Nystagmus which changes with the direction of gaze suggests a widspread central involvement of vestibular nuclei. Jerking nystagmus present only on lateral gaze, and who's fast component is in the direction of gaze, indicates a lesion of brain stem or cerebellum. Nystagmus confined to one eye suggests a peripheral lesion of the nerve or mucsle, or a lesion of the mediallongitudinal bundle. Nystagmus restricted to the abducting eye on lateral gaze(ataxic nystagmus) is due to a lesion of the medial longitudinal bundle between the ponds and midbrain as in MS. Nystagmus occuring on upward gaze with the fast component upwards( upbeat nystagmus) maybe due to a lesion in the mid-brain at the level of the superior colliculus. Downbeat nystagmus(fast phase downward) suggests a lesion in the lower part of the medulla. It's therefore, typical of the Arnold Chiari malformation. **Causes of absent ankle reflexes and extensor plantars: subacute combined degeneration of the cord syphilitic taboparesis friedreich's ataxia motor neuron disease **Bicuspid aortic valve is perhaps the most common form of congenital heart disease in adults(1-2% of population). **hyporeflexia is a common clinical sign in patients with hypercalceamia. Biphosphanates inhibit bone resorption and are the first line pharmacological treatment of hypercalceamia of malignancy. **Premature epiphysial closure is a classical finding of CAH. **Flecainide is the drug most likely to restore sinus rhythm in atrial fibrillation. **Lithium can produce Diabetes Insipidus and hypercalceamia. **Constrictive pericarditis produces an elevated JVP, with prominent x & y descent.Pulsus paradoxus occurs less frequently than in tamponade. **Streptococcus bovis is a normal commensal of the GI tract. However, S.bovis bactereamia and endocarditis has a strong association with GI malignancy. **Neisseria meningitidis( Gram negative diplococci) Streptocuccus pneumonia(gram positive diplococci) Rx: gram stain unavailable: cefotaxime+- ampicillin g +ve cocci: Cefotaxime +vancomycin( S.pneumonia) G +ve bacilli:Ampicillin +gentamicin.(listeria) G -ve cocci: Benzyl penicillin.(N.meningitidis) G -ve bacilli: Cefotaxime + gentamicin(heamophilus influenza) **Anaplastic carcinoma carries the worst prognosis in thyroid cancer followed by thyroid medullary carcinoma in MEN 2B.\ **ANCA ab are of 2 types: 1- C-ANCA which correlates with antiproteinase 3 antibodies--->most specific for wegener's granulomatosis. 2- P-ANCA which correlates with anti myeloperoxidase ab. P-ANCA/MPO ab. are highly sensitive and specific for rapidly progressive glomerulonephritis and haemorrhagic alveolar capillaritis. AMA ab--------> PBC Anticentromere ab.--------> CREST/scleroderma syndrome ANA and anticardiolipin ab.----------->SLE. **Clozapine is associated with agranulocytosis in app.1-2% of patients **Acute pancreatitis with worse prognosis: Age>55 WCC>16,000 LDH>600 AST>120 Glu>10 **Pendred's syndrome Pendred's syndrome is a rare autosomal recessive condition characterised by incomplete oxidation of trapped iodide prior to organification. It may be confirmed by a positive perchlorate discharge test. **Anti 21 hydroxylase ab. found in about 80% of cases of addison's disease. **SSRIs are a recognised cause of SIADH. **Astimulatory mutation of thr Gs protein alpha subunit has been noted in approx.30% of GH secreting pituitary tumours. **Carcinoid tumours of the foregut unlike tumours of the midgut are not associated with carcinoid syndrome but may secret CRF/ACTH resulting in ectopic cushing's syndrome.Other associated conditions include somatostatinoma, Zollinger -Ellison syndrome and Acromegaly. **The antiphospholipid syn. is one of the commoner causes of hypoadrenalism and may precipitate adrenal infarction and haemorrhage through adrenal vein thrombosis. **Osteopenia is defined as a T score of between -1 and -2.5 standard deviation below the bone mineral density of a young female.Osteoporosis is defined as <2.5 SD. **bcl-2 is an inhibitor of apoptosis. fas and caspases promote apoptosis but are nottumour supressor genes p53 is a tumour supressor gene that inhibits mitosis and promotes apoptosis. ras is oncogene. **Congenital adrenal hyperplasia is autosomal recessive disorder. **beta blockers are the mainstay of treatment in long QT interval. The most commonly used drugs are propranolol and nadolol. **pulmonary complications of reumatoid arthritis" Fibrosing alveolitis pleural effusions empyema cryptogenic organising pneumonia bronchiectasis pulmonary ndules **Fetal alcohol syn., Down's syn., and congenital rubella syn. are ass. with an ASD(Loud 2nd sound plus fixed splitting. **VIP Achlorhydria profuse diarrhea hypokalaemic acidosis hyperglycaemia **Cavitations on pulmonary x ray: squamous cell carcinoma abscess(staph. aureus, Klebsiella, and pseudomonas aeruginosa0 lymphoma rheumatoid nodule pulmonary infarction wegener's granolumatosis **p-ANCA is present in approx. 70% with UC and less than 20% of Crohn. 85% of untreated subjects with wegener's will have c-ANCA **prerenal failure: urinary Na<20 urine osmolality> 500 urine/plasma ratio>8and urine/plasma creatinine >40\ Renal failure: Na>40 osmolality urine<350 U/P ratio<3 U/P creat.<20 **Vitamin D resistant rickets is x linked dominant. **infection is the commonest cause of death in multiple myeloma. **Antimicrosomal antibodies------>Hashimoto's thyroiditis **Behchet's disease is associated with HLA B5 **Venous beading, loops and soft exudates(cotton wool spots) are ccharacteristic of preproliferative retinopathy. Microaneurysms, Hard exudates and Macular edema suggests background diabetic retinopathy New vessels suggests proliferative retinopathy. **Hexosaminidase A deficiency is ass. Tay-Sachs disease Sphingomyelinase deficiency ->Nieman-Pick disease Arylsulphatase-A Def. ass. with metachromic leucodystrophy Iduronidase def. ass. with Hurler's syn. B-glucosidase def.--->Gaucher's disease. **Methotrexate is a well known cause of acute pneumonitisand interstitial lung disease. **Clopidegrol prevent platelet aggregation through antagonism of the ADP receptor. **Patients with painful, isolated third nerve palsy with pupillary involvement are assumed to have posterior communicating artery aneurysm until proven otherwise.