Chemical Pathology Flashcards

Question

What are the biochemical features of osteoporosis? Clinical? What are the classic #s?

Answer 1

Bone loss but with normal Ca?` Asymptomatic until # Typical #= NOF, vertebral, wrist (Colle's)

Answer 2

Diagnsosed using a DEXA scan. Hop \* lumbar spine? Z score: SD from mean of age-matched control- useful to identify accelerated bone loss in younger patients T score: SD mean of young healthy population Osteoporosis: T score \<-2.5 Osteopenia: T score between -1 and -2.5

Answer 3

Osteoporosis

Answer 4

Osteopenia

Answer 5

Age related decline in bone mass Menopause (early menopause) Childhood illness (failure to attain peak bone mass) Lifestyle: sedentary, ETOH, smoking, low BMI.nutritional Endocrine: hyperprolactinaemia, thyrotoxicosis, Cushings Drugs: steroids Others e.g. genetic, prolonged intercurrent illness

Answer 6

Lifestyle: weight-bearing exercise, stop smoking, reduce ETOH Rx: Vitamin D/Ca Bisphosphonates (e.g. alendronate): decrease bone resorption Teriparatide (PTH) derivative: aanabolic Strontium: anabolic and anti-resoprtive Oestrogens SERMs e.g. raloxifene

Answer 7

Bisphosphonate used to decrease bone resorption PTH derivative " Selective oestrogen receptor modulator "

Answer 8

Polyuria/polydipsia Constipation Neuro: confusion/seizures/coma Overlap with HyperPTH \>3.0mmol/l

Answer 9

By PTH suppression

Answer 10

Inappropriate PTH response- primary problems with PTH regulation Priamry hyperparathyroidism (common) Familial hypocalcuric hypercalacemia (rare)

Answer 11

Appropriate PTh response- seek other causes Malignancy (common) Others (rare): sarcoid, vitamin D excess, thyrotoxicosis, milk alkali syndrome

Answer 12

Primary hyperparathyroidism 1. Adenoma (usually single, occasionally multiple): 80% 2. Hyperplasia (hyperplasia associated with MEN1) Primary "water clear" cell hyperplasia: 10% Primary chief cell hyperplasia: 8% 3. Carcinoma: 2%

Answer 13

Raised serum Ca, raised or inappropriately normal PTH, decreased serum Pi, raised urine Ca BONES: PTH bone disease STONE: renal calculi MOANS: abdominal moans: constipation, pancreatitis GROANS: confusion (psychiatric groans)

Answer 14

Parathyroids: regulates PTH release Renal: influences Ca resorption in a PTH independent fashion

Answer 15

CaSR mutation leading to a high set point for PTH release: mild hypercalcaemia ## Footnote **Reduced urine Ca**

Answer 16

1. Humoral hypercalcaemia of malignancy (e.g. SCLC): PTHrP 2. Bone metastases (e.g. Breast): local bone osteolysis 3. Haematological malignancy (e.g. myeloma): cytokines

Answer 17

Sarcoidosis: non-renal 1 alpha hydroxylation Thyrotoxicosis: thyroxine-\> bone resorption Hypoadrenalism: renal Ca transport Thiazide diuretics: renal Ca transport Excess Vit D e.g. sunbeds

Answer 18

FLUIDS +++ Bisphosphonates if known to be caused by cancer, otherwise aboid Treat underlying cause

Answer 19

Neuro-muscular excitability: Chvostek's sign Trousseau's sign Hyperreflexia Laryngeal spasm Convulsions Perioral paraesthesia ECG: prolonged QT Opthalmology: Choked disk

Answer 20

Ca and Vit D (usually activated forms i.e. 1 alpha hydroxylated except if simple vit D deficiency

Answer 21

Papilloedema Raised ICP, also hypocalcaemia

Answer 22

Is it a genuine result? repeat and adjust for albumin What is the PTH

Answer 23

PTH will be raised: secondary hyperparathyroidism: VitDD (dietary, malabsorption, lack of sunlight) Chronic kidney disease (1 alpha hydroxylation)- CAN PROGRESS TO TERTIARY PTH resistance: pseudohyoparathyroidsm

Answer 24

Sxal (post thyroidectomy) Auto immune hypoparathyroidism Congential absence of parathyroids (DiGeorge syndrome) Mg deficiency

Answer 25

Focal disorder of bone remodelling Focal pain, warmth, deformity, fracture, SC compression, malignancy, cardiac failure. Pelvis femur, skull and tibia **Elevated ALP**. Nuclear med scan/XR Bisphopshonates for pain

Answer 26

Englargement of head Deafness: 8th nerve Blindness: 2nd nerve Kyphosis Increased CO Bowing of the limbs Increased warmth and tenderness over bones

Answer 27

Great thickening of bones of skull with areas of demineralisation Bowing of tibia: fissure fractures, advancing edge.

Answer 28

Due to secondary hyperparathyroidism + retention of Al from dialysis fluid

Answer 29

Autonomous PTH secretion post renal transplant. Following long period of secondary hyperparathyroidism, reflects development of autonomous unregulated parathyroid function following a period of persistent parathyroid stimulation. Basis of treatment is prevention.

Answer 30

Surgical with removal of 3.5 parathyroid glands

Answer 31

Dehydration Cuffed

Answer 32

Hypoalbuminaemia

Answer 33

Osteomalacia Acute pancreatitis Overhydration respiratory alkalsosis (redcued ionised/active Ca)

Answer 34

Causes pancreatitis Caused by pancreatiits, release of pancreatic enzymes damages blood vessel walls causing interstitial leakage, TGs bind to Ca sequestering it and leading to reduced [serum]

Answer 35

Alkalosis causes decreased freely ionized serum Ca, causing membraine instability and subsequent vasoconstriction and paraesthesia

Answer 36

5% lifetime risk Renal colic/ asymptomatic

Answer 37

Dehydration-\> concentrated urine: encourage fluid intake Abnormal urine pH e.g. meat intake, renal tubular acidosis: acidify/alkalinise urine Increased excretion of stone constituents: adjust dietary intake, specfic treatments Urine infection: treat infection Antatomical abnormalities e.g. PUJ obstruction

Answer 38

Calcium: mixed (45%); radioopaque Calcium oxalate (45%): opaque Struvite (10%): opaque Uric acid (5%): lucent Calcium phosphate (1%): opaque Cysteine (1-2%): lucent Others e.g. xanthine

Answer 39

Calcium mixed Oxalate Phosphate Struvite (staghorn)

Answer 40

Uric acid Cysteine

Answer 41

Calcium mixed Calcium oxalate Struvite Uric acid Cysteine Calcium phosphate Xanthine

Answer 42

Hyperoxaluria (increased intake, absorption etc) Hypercalciuria (increased intake, renal leak) Most patients are normocalcaemic

Answer 43

General: avoid dehydration Reduce oxalate intake **Don't reduce Ca intake-\> increases bone resorption and increases oxalate excretion** Thiazides-\> hypocalciuric Citrate: alkalinise urine Treat underlying cause

Answer 44

Struvite: MgNH4P + CaP From when urine infection by urea splitting organisms: Klebsiella, proteus etc Lead to staghorn calculi General measures Treat/prevent infection

Answer 45

Hyperuricaemia (multiple causes)

Answer 46

Underlying genetic defect: cystinuria

Answer 47

Serum: creatinine, bicarbonate, Ca, P, urate, PTH (if hypercalcaemic) Urine: spot urine: pH, MC+S, amino acids, albumin 24 hour urine: volume (\>2.5l), Ca, oxalate, urate, citrate Stone analysis

Answer 48

Conservative: allow to pass spontaneously Lithotripsy Sx: cystoscopy, ureteroscopy

Answer 49

Metabolic alkalosis and respiratory acidosis

Answer 50

Metabolic acidosis and respiratory alkalosis

Answer 51

Acid/alkali? Does the pH fit? Does the bicarb fit with the pH Is there any compensation (partial/complete)

Answer 52

Bicarbonate: in ECF and glomerular filtrate Hb: HbH Phosphate: in renal tubular fluid and intracellularly-\> H2PO4 Also protein and bone

Answer 53

ECF buffering is at te expense of bicarbonate and is only effective in the ST To maintain normal homeostasis, the kidney needs to excrete H+ ions and regenerate bicarbonate1

Answer 54

Bicarbonate reabsorbed in the proximal tubule H+ excretion and bicarbonate regenration

Answer 55

Chemoreceptors in the hypothalamic respiratory centre. In health, any increase in CO2 stimulates respiration, to increase blow off

Answer 56

Carbon dioxidie is proportionate to H+ ions and bicarbonate

Answer 57

Decreased pH Decreased bicarbonate Normal/decrease (with compensation) Increased H production: DKA, lactic acidosis Decreased H excretion: renal tubular acidosis, renal failure Increased bicarbonate loss: intestinal fistula

Answer 58

Shift of equation to right Lungs try to blow off CO2 leading to reduction in pCO2

Answer 59

Metabolic acidosis with respiratory alkalosis

Answer 60

Whenever the PCO2 and [HCO3] are abnormal inopposite directions, ie, one above normal while the other is reduced, a mixed respiratory and metabolic acid-base disorder exists.

Answer 61

respiratory acidosis and metabolic acidosis coexist.

Answer 62

espiratory alkalosis and metabolic alkalosis coexist

Answer 63

Reduced pH N/raised bicarbonate if compensated Raised Co2 Decreased ventilation: COPD, scoliosis, pneumonia Poor lung perfusion: PE, COPD Impaired gas exchange

Answer 64

Over the course of a few days this leads to an increased renal excretion of H+ combined with generation of bicarbonate. H+ may return to near normal but pCO2 and bicarbonte remain elevated

Answer 65

Decrease in H+ ions with raised bicarbonate Compensation is through inhibition of respiratory centre leading to a rise in pCO2. Raised pH Raised bicarb N/Increased CO2 if compensated H loss: pyloric stenosis (vomiting of hydrochloric acid) Hypokalaemia: preferential excretion of H, antitransport with K out of cesss. Caused by e.g. diruetics Ingestion of bicarbonate

Answer 66

Raised pH N/low bicarbonate Reduced CO2 Voluntary, artificial ventilation or stimulation of respiratory centres

Answer 67

If prolonged this leads to decreased renal excretion of H+ and reduction in bicarbonate generation. H may return to normal but bicarb and pCO2 remain low

Answer 68

(Na+K)-(Cl+HCO3)

Answer 69

14-18mmmol

Answer 70

Difference between the total concentration of principle cations and principle anions= concnetration unmeasured anions in th eplasma

Answer 71

Ketoacdiosis (ETOCHic, DKA, starvation) Uraemia (renal failure) Lactic acidosis) Toxins (ethylene glycol, methanol, paraldehyde, salicylate)

Answer 72

Osmolality measured- osmolarity calculated

Answer 73

Provides indirect evidence for hte presence of an abnormal solute e.g. ethylene glycol, ethanol, methanol, mannitol. Useful in differentiating the cause of an elevated anion gap metabolic acidosis

Answer 74

Adrenergic: tremors, palpitations, sweating, hunger (appear first) Neuroglycopaenic: somnolence, confusion, incoordation, seizures, coma Asympptomatic: recurrent hypos cause adrenergic blunting

Answer 75

Can take 15-20 minutes to mobilise through glucagon. There is a risk of rebound hypoglycaemia as glucagon will cause insulin release

Answer 76

Extravasation can lead to irritation and phylebitis

Answer 77

On the basis of the aetiology, either in hte setting of hyper or hypoinsulinaemia and ketones

Answer 78

Iatrogenic insulin Sulfonylurea excess Insulinoma

Answer 79

Alcohol binge, no food Pituitary insufficeicy Addison's Liver failure

Answer 80

Non-pancreatic neoplasms- fibrosarcomata, fibromata

Answer 81

Reduced peripheral uptake Increased glycogenolysis Increased gluconeogenesis Increased lipolysis Increse in glucose and FFAs L

Answer 82

Detected in the hypothalamus: SNS activation as a later response. Increased ACTH and GH production

Answer 83

ECF Muscle gylcogen (local use only) Liver glycogen Ketone body production only occurs when insulin levels are low. Beta oxidaiton is very sensitive to circulating insulin levels

Answer 84

Grey top- fluoride oxalate.

Answer 85

Fasting or reactive Adult vs paediatric Critically unwell Organ failure Hyperinsulinaemia Post gastric bypass Extreme weight loss Factititous

Answer 86

Sulphonylurea

Answer 87

Beta-blockers Salicylates ETOH

Answer 88

C-peptide levels are a marker of beta-cell function

Answer 89

Insulin C peptide FFA Ketones Lactate Hepatomegaly

Answer 90

-ve sulphonylurea screen

Answer 91

Reduced glucose Reduced Insulin Reduced C-peptide Reduced FFA Reduced ketones Tumours that cause paraneoplastic syndrome, secreting big IGF-2 which binds ot IGF1 and insuline receptors

Answer 92

Infant of diabetic mother Beckwith Weidemann syndrome Nesidioblastosis

Answer 93

Beckwith–Wiedemann syndrome (/ˈbɛkˌwɪθ ˈviːdə.mən/; abbreviatedBWS) is an overgrowth disorder usually present at birth, characterized by an increased risk of childhood cancer and certain congenital features. Beckwith syndrome can also cause child behavior problems. Common features used to define BWS are:[1] macroglossia (large tongue), macrosomia (above average birth weight and length), midline abdominal wall defects (omphalocele/exomphalos, umbilical hernia, diastasis recti), ear creases or ear pits, neonatal hypoglycemia (low blood sugar after birth). Hepatoblastoma

Answer 94

Nesidioblastosis is a controversial medical term for hyperinsulinemic hypoglycemia attributed to excessive function of pancreatic beta cellswith an abnormal microscopic appearance. The term was coined in the first half of the 20th century. The abnormal histologic aspects of the tissue included the presence of islet cell enlargement, islet celldysplasia, beta cells budding from ductal epithelium, and islets in apposition to ducts. By the 1970s, nesidioblastosis was primarily used to describe the pancreatic dysfunction associated with persistent congenital hyperinsulinism and in most cases from the 1970s until the 1980s, it was used as a synonym for what is now referred to as congenital hyperinsulinism. Most congenital hyperinsulinism is caused by different mechanisms than excessive proliferation of beta cells in a fetal pattern and the term fell into disfavor after it was recognized in the late 1980s that the characteristic tissue features were sometimes seen in pancreatic tissue from normal infants and even adults, and is not consistently associated with hyperinsulinemic hypoglycemia.

Answer 95

Low glucose, personality cahgne, hungry

Answer 96

Endogenous insulin production

Answer 97

Low glucose, high insulin, low c-peptide

Answer 98

Mesenchymal tumours: mesothelioma, fibroblastoma Epithelial tumours: carcinoma

Answer 99

FFA metabolism defect

Answer 100

Rarely caused by Abs binding to insulin Rs. Bind and stimulate insulin release Low glucose, high insulin, low c-peptide Need to demonstrate IR-Ab to make diagnosis

Answer 101

Quinine stimulates insulin release

Answer 102

Treatment of trypanosomiasis, leishmaniasis, PCP Toxic to B cells, release pre-formed insulin

Answer 103

Ab directed to insulin, sudden dissociation may precipitate hypoglycaemia. Certain drugs are associated e.g. hydralazine, procainamide

Answer 104

Intermediary metabolism: glycolysis, glyocgen storage, glucose synthesis, amino acid synthesis, FA synthesis, lipoprotein metabolism. Xenobiotic: chemical modification: p450 enzyme system, acetylation, oxidation, reduction Conjugation: glucuorante, excretion. Hormone: Vit D hydroxylation, steroid hormone (conjugation and excretion), peptide hormone: catabolism

Answer 105

Bile Protein synthesis

Answer 106

Kuppfer cells: clearance of infection and LPS Antigen presentaiton Immune modulation Cytokines Erythropoeisis

Answer 107

Water Bile salts/ acids Bilirubin Phospholipids Cholesterol Proteins Drugs Metabolites

Answer 108

Cytoplasmic enzymes in hepatocytes involved in amino acid metabolism Levels become elevated whe hepatocytes die Present in low amounts in other organs

Answer 109

AST:ALT 2:1 "Second": little

Answer 110

AST:ALT 1:1

Answer 111

Toxins, virus or ischaemia

Answer 112

Found in hepatocytes and epithelium of small bowel ducts Found in liver, kidney, pancreas, spleen, heart, brain and seminal vesciles. Elevated in chronic alcohol use Also elevated in bile duct diesease and metastases. Used to confirm hepatic origin of bile ducts

Answer 113

From bile ducts liver isoenzyme located in sinusoidal and canalicular membranes Markedly elevated in obstructive jaundice or bile duct damage Less elevated in biral hepatitis or alcoholic liver disease NB other sources: bone, small intestine, kidney, WBCs, placenta Other cauess of rise include bone disease esp metastatic. And pregnancy

Answer 114

Major protein synthesised by the liver 8-14g/d Half life 20d therefore indicative of chronic liver problems Contributes to oncotic pressure and binds steroids/drugs/bilirubin/Ca

Answer 115

Chronic liver disease, malnutrition Loss: gut/kidney Sepsis (3rd spacing)

Answer 116

In foetal life made by yolk sac, GI epithelium and liver No known function in adults. Can be used in diagnosis of HCC: 80% secrete it but may not rise at all. Also raisd in hepatic damage/regeneration Raised in pregnancy and testicular cancer

Answer 117

HCC Hepatic damage Hepatic regeneration Pregnancy Testicular cancer

Answer 118

Ostructive jaundice

Answer 119

Prehpeatic: haemolysis Hepatic: genetics, hepaitisi, drug reaction

Answer 120

Post-hepatic e.g. bile duct obstruction, durgs Genetics hepatitis drug reaction

Answer 121

Indocyanine green, bromsulphalein: measure excretory capacity of liver Measure hepatic blood flow

Answer 122

Measure of residual funcitoning liver cell mass, prediciton of survival in ETOHic liver disease

Answer 123

Elevated in cholestasis 10-100x in cholestasis of pregnancy 25x in PBS and PSC

Answer 124

PBC, PSC, alcohol, drugs, viral, autoimmune, severe bacterial infeciton, pregnancy

Answer 125

Stones Cancer of bile duct Mets Biliary stricture Post operative damage Parasitic infection

Answer 126

Pre-hepatic Hepatic Post-hepatic

Answer 127

Raised bilirubin Preserved syntheic function Normally LFTs with raised bilirubin and normal USS

Answer 128

Non-fasting and fasting conjungated and nonconjugated bilirubin

Answer 129

Unconjugated bilirubinaemia The cause of this hyperbilirubinemia is the reduced activity of theenzyme glucuronyltransferase,[6][7] which conjugates bilirubin and a few other lipophilic

Answer 130

Augmentin Obstructive jaundice picture that resolves spontaneously

Answer 131

Raised bilirubin Raised ALP Slightly raised transaminases and GGT Preserved synthetic function Itch, jaundice, dark urine. No bile duct obstruction on USS

Answer 132

Itch, pale stool, dark urine, yellow sclera, weight loss Bilirubinuria: obstructed

Answer 133

Dilated common bile duct Pancreatic mass

Answer 134

In the presence of a painless, palpable gallbladder, jaundice is unlikely to be caused by gall stones

Answer 135

AST and ALT very high Then mixed picture Serum IgM anti-HAV (rather than IgG so acute infection can be compared to the vaccination)

Answer 136

Poor synthetic funciton, all rest slighlty raised Stigmata of chornic liver disease IVDU Confirm serology Mx with IFN and ribavirin

Answer 137

Low INR Very high AST and ALT Acidoitc N-acetyl cysteine, transplant

Answer 138

120ml/min At 70 years 80ml/min Decline of 1ml/year from mid 20s

Answer 139

The volume of plasma that can be completely cleared of a marker substance per unit time

Answer 140

If a marker is not bound to serum proteins, is freely filtered by the glomerulus and not secreted/reabsorbed by tubular cells C=GFR

Answer 141

C= UxV/ P Urinary conc= plasma conc

Answer 142

Insulin It is freely filtered and is not processed by tubular cells. A constant infusion is needed and it is only used for research purposes due to its impracticality

Answer 143

Varaibel reabsorption Depends on nutritional state, hepatic function, GI bleeding. Limited clinical value

Answer 144

Exogenous marker of renal celarance Direct celarnace calculated from urine collection Indirect from plasma regression curve concentration

Answer 145

Derived from muscle cells Freely filtered Actively secreted by tubular cells into urine Generation of creatine vaires between indivduals so is not an accurate measure of GFR in itself

Answer 146

Endogenous marker. Cystein protease inhibitor. Constitutively produced by all nucleated cells with a constant rate of generation. Freely filtered, almost completely reabsorbed and catabolised by tubular cells.

Answer 147

Used to estimate creatinine clearance eCCR= (1.23x (140-age) x weight/ serum creatinine Adjusted by 0.85 if female. Estimaes GFR, and may overestimate GFR when \<30ml/min

Answer 148

Used to estimate GFR eGFR= 186 x (creatininex0.0113)-1.154xage-0.203 Adjusted by 0.742 if female May underestimate GFR if above average weight and young

Answer 149

Creatinine is insensitive Cystatin C is better. Constant rate infusion used as a research tool Single injection GFR is reserved for specific situations. eGFR and eCCR are best compromise. Most robust is to measure change in renal function over time

Answer 150

Homeostatic function Urine examination Imaging Histology

Answer 151

pH Specific gravity Protein Blood Leucocyte esterase Nitrate

Answer 152

RBC WC Casts Bacteria

Answer 153

Proliferative glomerular nephritis

Answer 154

Acute tubular necrosis

Answer 155

Proteinuria quantification Measurement of creatinine corrects for urine concentration

Answer 156

Proteinuria quantification (superceded by PCR) Creatinine clearance estimation Electrolyte esimation Stone forming elements Catecholamines

Answer 157

Plain KUB films IV urogram KUB USS can differentiate betweem cysts and more complex stones Cross-sectional imaging: CT and MRI Functional imaging Radioisotope: used in paeds to estimate degree of renal scarring

Answer 158

Renal stones Can also diagnose renal vein thrombosis and PKD

Answer 159

Acute nephritic syndrome

Answer 160

1-10% bleeding rate 0.1-10% major bleeding rate

Answer 161

Abrupt decline in GFR, potentially reversible.

Answer 162

Pre-renal Renal Post renal

Answer 163

Hallmark is reduced renal perfusion without structural abnormality Responds immediately to restoration of circulating volume Prolonged insult leads to ischaemic injury

Answer 164

Hypovolaemia Reduced CO Vasodilation RAS

Answer 165

Activation of central baroreceptors Activation of RAAS Vasopression release and SNS activation Vasoconstriction Increased CO Renal Na retention Pre-renal AKI occurs when normal adaptive mechanisms fail to maintain renal perfusion

Answer 166

Svere or prolonged insult, pre-exisitng disease, pharmacological inhibition of adaptive mechanisms

Answer 167

NSAIDs, diuretics, ACEI Because they interfere with the normal physiological response

Answer 168

ATN doesn't respond to restoration of circulating volume

Answer 169

Pathophysiologically more diverse group. Abnormalitiy of the nephrons Can be classified as: Vacular Glomerular Tubular Interstitial Immune Infiltrative

Answer 170

Vasculitis TTP Scleroderma Thromboembolism

Answer 171

Glomerulonephritis (nephrotic or nephritic disease)

Answer 172

ATN, tumour lysis syndrome Mostly ischaemic causes: Endogenous toxin: myoglobin (rhabdomyolysis) Ig (myeloma) Exogenous toxins: Contrast drugs, aminoglycosides, amphotericin, acyclovir

Answer 173

Analgesic nephropathy

Answer 174

Causes renal inflammation: glomerulonephritis and vasculitis

Answer 175

Amyloidosis Lymphoma Myeloma related renal disease

Answer 176

Hallmark is physical obstruciton to urine flow, USS shows dilated renal pelvis Infrarenal obstruction: Ureteric obstruction Prostatic obstruction Blocked urinary catheter

Answer 177

GFR dependant on hydraulic pressure gradient Obstruction leads to increased tubular pressure which leads to an immediate decline in GFR There is a secondary decline in renal blood flow

Answer 178

Glomerular ischaemia, tubular damage and LT interstitial scarring-\> Chronic disease

Answer 179

Pre-renal and ATN

Answer 180

Classification of AKI

Answer 181

Based on Risk: GFR or UO Injury Failure Loss of function ESRD

Answer 182

GFR reduced to \<75% Serum creatinine x3 UO \<0.5ml/kg/h or anuria for 12h

Answer 183

40% get complete recovery of renal funciton 22% partial recovery 20% die

Answer 184

Acute wound heals via 4 phases: Haemostasis Inflammation Proliferation Remodelling NB replacement of renal tissue by scar tissue results in chronic disease

Answer 185

Longstanding, irreversible decline in GFR Treatments targeted to prevent cxs and limit progression

Answer 186

Increased risk Early damage Reduced GFR Renal Failure Death

Answer 187

DM Atherosclerotic renal disease HTN Chronic GN Infective or obstructive uropathy PKD

Answer 188

Progressive failure of homeostatic function Progressive failure of hormonal function Cardiovascular disease Uraemia and death

Answer 189

Acidosis Hyperkalaemia

Answer 190

Metabolic acidosis resulting from failure of renal excreiton of protons Results in muscle and protein degradation, osteopaenia due to mobilisation of bone calcium, cardiac dysfunction Rx: oral sodium bicarbonate

Answer 191

Potassium is an intracellular cation which causes membrane depolarisaiton, involved in cardiac and muscle function. ECG changes: loss of p wave, tall "tented" T wave, widened QRS with tall T wave

Answer 192

Tented t-waves: hyperkalaemia

Answer 193

Anaemia Renal bone disease

Answer 194

Progressive decline in EPO producing cells with loss of renal parenchyma Usually occurs when GFR is \<30ml.min Normorhomic, normocytic anaemia Rx: injectable EPO: EPO alpha, beta or darbopoeitin

Answer 195

Fe deficiency: aboslute (bleeding), relative (availability) Inflammation and infection: TB Malignancy B12 and folate deficiency HyperPTH

Answer 196

Reduced bone density Bone pain and #s Osteitis fibrosa Osteomalacia Adynamic bone disease Mixed osteodystrophy

Answer 197

Osteoclastic resorption of calcified bone, replacement by fibrous tisse: seen in hyperparathyroidsim

Answer 198

Excessive suppresion of PTH results in low bone turnover and reduced osteoid

Answer 199

Causes low levels of 1,25 (OH)D3 and phosphate retention This causes P retention and resistance of bone to PTH

Answer 200

Stage 1: kidney damage with normal GFR \>90ml Stage 2: mild reduction in GFR 60-89 Stage 3: Moderate 30-59 Stage 4: Severe 15-29 Stage 5: ESRF \<15 or dialysis

Answer 201

P control: dietary, P binder VitD R activators: 1 alpha calcidol, paricalcitol Direct PTH suppression: cincalet

Answer 202

Ca gluconate Insulin Dexamethasone

Answer 203

Vascular calcification Uraemic cardiomytopathy Most improtant complication Risk directly predicted by GFR

Answer 204

Renal vascular lesions are frequently calcified plques rather than lipid-rich atheromas

Answer 205

LV hypertrophy LV dilatation LV dysfunction

Answer 206

Haemodialysis Peritoneal dialysis Renal transplant

Answer 207

Nausea Vomiting Fatigue Anorexia Weight loss Muscle cramps Pruritus Mental status changes Visual disturbances Increased thirst

Answer 208

Associated with fluid retention, anaemia and acidaemia. May be msucle wasting. Muscle cramping. Cardiac arrythmias and change in mental status Skin:uraemic frost, may have sallow coloration of skin Eyes may become icteric or red Mouth: ginigval hyperplasia, enamel hyoplasia, gingival bleeding CV: uremic pericarditis: rub or effusion, hypertension, AS Lungs: fluid retnetion-\> pulmonary oedema

Answer 209

Methanol Uremia Diabetic Ketoacidosis (or other ketoacidosis, such as Alcoholic and Starvation) Paraldehyde Isoniazid or Iron Lactic Acidosis Ethylene Glycol Salicylates

Answer 210

By their activity rather than their mass 1 IU= 1 international unit of enzyme acitivty-\> quantity of enzyme that catalyses the reaction of one umol of substance per minute. Debendant on assay conditions

Answer 211

Bone, liver, placenta and intestines. Increased in bone disease, can also be increased in liver disease

Answer 212

GGT Electrophoretic separation Bone specific ALP immunoassay available

Answer 213

Pregnancy (placental in 3rd trimester) Childhood: especially during growth spurt

Answer 214

Bone: Pagets, Ostemolacia Liver: Cholestasis Cirrhosis

Answer 215

Bone: Tumours, #s, osteomyelitis Liver: infiltrative disease Hepatitis

Answer 216

Not raised unless complicated by fractures

Answer 217

High serum amylase activity in acute pancreatitis \> 10 x ULN There is a salivary isoenzyme Small increase can also be seen in acute abdominal states

Answer 218

Marker of muscle damage 3 forms, dimers containing different subunits CK-MM: skeletal muscle CK-MB: cardiac muscle CK-BB: brain, activity minimal even in severe brain injury

Answer 219

Afro-carribean. \<5 x ULN

Answer 220

Muscle damage due to any cause: e.g. CPR, big bruise, injury Myopathy: Duchenne MD \>10 x ULN MI: \> 10 x ULN Severe exercise Statin related myopathy

Answer 221

Spectrum from myalgia to rhabdomyolysis Risk factors: Polypharmacy- gemifibrosil, cyclosporin, other drugs metabolised by the CYP 3A4 system High dose Previous hx of myopathy with another statin

Answer 222

Baseline CK

Answer 223

Troponin, myoglobin, CK MB

Answer 224

Rise is seen 4-6h pst MI Peak at 12-24h Remains elevated for 3-10d

Answer 225

6h then 12h post onset of the chest pain

Answer 226

100% Se, 98% Sp at 12-24h

Answer 227

None of them rise quickly enough to aid in decision regarding thrombolysis

Answer 228

1. Typical rise and gradual fall of troponin or more rapid rise and fall CK-MB with at least one of: ischaemic symptoms pathological q wavs ECG changes indicative of ischaemia coronary artery intervention 2. Pathological findings of an acute MI

Answer 229

ALP Bone scan or plain XR

Answer 230

Contain N in them which once incorporated into bone, cannot be broken down by osteoclasts

Answer 231

Increased ALP due to increased OB activity trying to make new bone Lack of vitamin D Secondary hyperPTH

Answer 232

Troponin, CK-MB, AST, LDH AST: 3d later

Answer 233

Raised K Low Na Low Glucose Will also get a high calcium which will suppress the PTH

Answer 234

ALT\>AST ViraL

Answer 235

AST\>ALT CirrhoSis

Answer 236

Raised acid phosphatase PSA

Answer 237

High Ca, low Vit D, high ALP

Answer 238

urea (4-25) then Na Creatinine doesn't move in an acute episode

Answer 239

Creatinine rise due to GFR fall

Answer 240

Fructosamine

Answer 241

High sodium, polyuria and polydipsia

Answer 242

Positively birefringent

Answer 243

Malaise, lethargy, sponts on skin, spongy gums, bleeding from mucous membranes, pallor, depression, loss of teeth, jaundice, faver neuropathy and death Vitamin C deficiency, Vit C is involved in collagen synthesis

Answer 244

Diarrhoea, dermatitis, dementia and death Desquamation, erythema, scaling and keratosis of sun exposed areas Sensitivity to sunlight Aggression Alopecia Beefy red glossitis Caused by Niacin deficiency

Answer 245

Colour blindness

Answer 246

Exfoliation hepatitis

Answer 247

(Retinol) Serum

Answer 248

Osteomalacia/rickets

Answer 249

Tocopherol

Answer 250

Anaemia, neuropathy, malignancy, IHD

Answer 251

Tocopherol Serum

Answer 252

Phytomenadione

Answer 253

Defective clotting

Answer 254

Beri-beri neuropathy Wernicke

Answer 255

RBC transketolase

Answer 256

Riboflavin

Answer 257

Vit B2 RBC glutathione reductase

Answer 258

Pyridoxine

Answer 259

Dermatitis/anaemia

Answer 260

Neuropathy

Answer 261

RBC AST activation

Answer 262

Hypercalcaemia

Answer 263

Pernicious anaemia

Answer 264

Renal stonse

Answer 265

Megaloblastic anaemia, neural tube defect

Answer 266

RBC folalte

Answer 267

Hypocrhomic anaemia

Answer 268

Haemochromatosis

Answer 269

FBC Fe Ferritin

Answer 270

Goitre hypothyroid

Answer 271

Dermatitis

Answer 272

Cu caeroplasmin

Answer 273

Dental caries

Answer 274

Vit A D E K

Answer 275

B1 B2 B3 B6 B12 C Folate

Answer 276

Fe I Zn Cu F

Answer 277

Chest disease Malignancy DM + metabolic syndrome Gynaecological disease Psychological CVD

Answer 278

Increased risk \>94 men, \>80 women Major risk \>102 men, \>88 women

Answer 279

Polyunsaturated fats

Answer 280

Reduce cholesterol concentrations

Answer 281

Reduce saturated fat and increase mono or polyunsaturated fats

Answer 282

Exclude endocrine causes and complications of obesity Diet and exercise Medical therapy: orlistat, sibutramine, rimonabant Sx: gastroplasty, roux en Y, adjustable gastric banding

Answer 283

Psychological PCOS Oesophagitis CHD Osteoarthritis Liver function Pregnancy Mortality

Answer 284

severe undernourishment causing an infant's or child's weight to be significantly low for their age (e.g., below 60 percent of normal). Shirvelled, growth retarded, severe muscle wasting and no subcut fat

Answer 285

Kwashiorkor /kwɑːʃiˈɔːrkər/ is a form of severe protein–energy malnutrition characterized byedema, irritability, anorexia, ulcerating dermatoses, and an enlarged liver with fatty infiltrates. Sufficient calorie intake, but with insufficientprotein consumption, distinguishes it from marasmus. Kwashiorkor cases occur in areas of famine or poor food supply.[1] Cases in the developed world are rare.[2]

Answer 286

Both marasmus and kwashiorkor are diseases that arise due to an inadequate diet and starvation. There are subtle differences between the two conditions. Let us take a look at what they are: Symptoms A kid who is suffering from marasmus can be identified at a glance. He will have dry and lose skin hanging over the glutei. The child loses adipose or fat tissue from normal areas of the body like the buttocks and the thighs. The child is usually irritable and has an exceptionally strong appetite. The child also has alternated layers of non pigmented or pigmented hair. A patient with kwashiorkor suffers from damaged absorption. He may also display abnormal burns, nephrosis or a chronic liver disease. The child may also suffer from loss of muscular mass, edema or other immunodeficiency symptoms. The child also suffers from vomiting, infections and diarrhea. Causes Marasmus is caused by a severe nutritional deficiency in general. It is usually found in very young infants and very young children. It can be prevented by breastfeeding. It is actually caused by the total or partial lack of nutritional elements in the food over a period of time. Kwashiorkor is actually the result of a lack of protein in the diet. It is different from marasmus, which is a total lack of nutrition in the diet. The term kwashiorkor is derived from an African term which means ‘first- second child’. This is because it usually affects children who are weaned away because of the birth of a second child. Read more: Difference Between Kwashiorkor and Marasmus | Difference Between | Kwashiorkor vs Marasmus http://www.differencebetween.net/science/health/difference-between-kwashiorkor-and-marasmus/#ixzz45nzfXP8D

Answer 287

\>3 of : Fasing glucose \>6 Waist circumference \>102 men, \>88 women Microablumin, insulin resistane HDL \<1 men, \<1.3 women HTN \>135/80

Answer 288

In infants of low birth weight \<100g= 200x more liekly to die

Answer 289

Respiratory distress syndrome Retinopathy of prematuiry Intraventricular haemorrhage PDA NEC

Answer 290

Common before 30/40. Caused by lack of surfactant Mx w surfactant, O2 and mechanical breathing. Surfactant really starts at 34/40

Answer 291

Abnormal growth of vessels in the eye that can lead to vision loss Occurs in 32/40 Most heal themselves with little or no vision loss Mx by opthalmologist with cryotherapy

Answer 292

Administration of high O2

Answer 293

In VLBW preterms. Usually in the first 3d of life. Diagnosed by USS Most haemorrhages are mild and resolve with no or few lasting problems Severe bleeds can cause raised ICP-\> brain damage Mx is shunt to drain the fluid or medical management to reduce the fluid build up

Answer 294

Bypasses foetal lungs PDA can lead to heart failure Dx on echo Mx medically or surgically

Answer 295

Develops 2-3w post birth, feeding difficulties, abdominal swelling, bloody stools Mx: antibiotics and IV nutrition whilst the intestines heal. Sx may be required to remove damaged portions of bowel,. Inflammation of the bowel wall progressing to necrosis and perforation. Abx \>10d

Answer 296

From 36/40 Not until 2 years of age

Answer 297

Low GFR for surface area: Slow excretion of solute load Limited amount of Na avaialble for H exchange-\> compromised buffering SA of baby compared to adult is much larger

Answer 298

Short-\> lower reabsorptive capacity Due to low GFR this doesn't have massive effect Threshold for bicarb reabsorption is high-\> difficulty buffering

Answer 299

Short and juxtaglomerular, gives reduced concentrating ability with a maximum urine osmolality of 700mmol/kg

Answer 300

RAS mature by 40/40 Relatively unresponsive to aldosterone-\> leads to persistent Na loss Need 1.2mmol/kg/d just for growth, renal loss of 1.8 Reduced potential for potassium excretion due to low Na

Answer 301

Prem: 85% Term: 75% Adult: 60%

Answer 302

After birth babies lose wieight, physiological response. 10% weight loss Diuresis from ANP release. Neonates in \<30/40 need higher Na de to persistent loss.

Answer 303

High insensible water loss: high surface area, skin blood flow, metabolic and RR, high transepidermal fluid loss (esp in an incubator)

Answer 304

Bicarbonate Antibiotic: most are sodium salts, hard to offload Caffeinie for apnoea: leads to increased renal Na loss Indomethacin for PDA: causes oliguria

Answer 305

Uncommon and usually associated with dehydration

Answer 306

Dehydration Salt posioning and osmoregulatory dysfunction are rare but should be considered in repeated cases of hypernatraemia without obvious cause Rotine measurement of urea, creatinine and U&Es on admission may help differentiate causes

Answer 307

Same causes as adults plus: CAH Caffeine/theophylline when treating apnoea

Answer 308

21 hydroxylase deficiency: most common leading to a deficiency of aldosterone and cortisol Hyponatreamia with hyperkalaemia and marked volume depletion= salt losing crisis. may also get hypoglycaemia but rare Ambigious genitalia in female neonates as 17OH progesterone is an androgen precursor. Boys fail to be recognised and die Growth acceleration in the child Mx is through replacemetn

Answer 309

Measure precursor of 17-OH progesterone

Answer 310

HbF haemlolysis Low rate of transfer of bilirubin into the liver. Enhanced enterohjepatic circulation. Hydrolysed to become unconjugated and reabsorbed

Answer 311

Occurs when free bilirubin crosses the BBB-\> irreversible brain damage

Answer 312

Phototherapy Exchange transfusion

Answer 313

d4 350 d1 200 for \>38/40 23/40: 120 Lower levels to lower levels of lbumin which binds to bilirbuin

Answer 314

d2 450 (38/40) 23/40: 230

Answer 315

Haemolytic disease: ABO, rhesus G6PDD Crigler-Najjar syndrome: bilirubin metabolism defect

Answer 316

\>14d in term \>21d in preterm

Answer 317

Prenatal infection/ sepsis/ hepatitis Hypothyroidism Breast milk jaundice

Answer 318

Unconjugated bilirubinaemia

Answer 319

Always pathological

Answer 320

Biliary atresia Choledocal cyst Ascending cholangitis in TPN; related to lipid content Inherited metabolic disorders

Answer 321

20% associated with cardiac malformations. Polysplenia Sinus inversus Early sx essential within 6w

Answer 322

Galactosaemia Alpha-anti-1-tyrypsin Tyrosinaemia Peroxisomal disease

Answer 323

There is a high intrauterine calcium level which supprseses the PTH glands. This causes an initial drop in Ca by d3 which ppicks up again at the end of the frst week

Answer 324

Fraying, splaying and cupping of long bones: inability to lay down minerals onto the osteoid at the end of bone Biochem: Ca within reference range, phosphate \<1mmol, ALP raised. Rx: phsophate/calcium supplementation, 1 alpha calcidol

Answer 325

Osteopenia due to deficient activity of Vitamin D Bow legs, abdominal distension, frontal bossing, muscular hypotonia or tetany, hypocalacemic seizures, hypocalcaemic cardiomyopathy

Answer 326

Benign, very high ALP, distinguishable from Rickets by electrophoreisis

Answer 327

Lack of sunlight exposure Pseudo Vit DD1: defective renal hydroxylation Pseudo Vit DD2: receptor defct Familial hypophosphataemias: low tubular maximum reabsroption of phosphate, raised urine phosphoethanolamine

Answer 328

End product of purine metabolism

Answer 329

Diet e.g. achovies, mackerel, liver, beer Degradation of endogenous nucleotides e.g. ATP, DNA, cAMP, adenosine, guanosine De novo synthesis by PRPS enzyme

Answer 330

Route through which body tries to reuse purines. HPRT: guanine salvage enzyme APRT: adenine salvage enzyme

Answer 331

Final step in degradation of purines, produces urate

Answer 332

1/3rd into the gut and degraded by bacterial uricase: coverted to CO2 and ammonia 2/3rds renal: net excretion is 10% of filtered load. 99% reabsorbed in PCT, secreted in DCT

Answer 333

Gout Renal calculi Tophi (urate in soft tissue) Nephropathy

Answer 334

Men 0.12-0.42 Women 0.12-0.36

Answer 335

Oestrogen encourgaes ecvretion of urate

Answer 336

At physiological pH, 98% of the uric acid is in the ionised form- urate. Urate predominantly exists as monosodium urate. When urate levels exceed 38mmol/l, there is an increased risk of monosodium urate crystal formation and precipitation.

Answer 337

Urate under excretion: Primary- idipathic hyperuricaemia Secondary- reduced renal funciton, inhibition of urate secretions (DKA, lactic acidosis), drugs (e.g. thiazides) Urate over production: Primary- PRPPS overactivity, HPRT and GPRT transferase deficiency Secondary: Excessive dietary purine intake, high nucleotide turnover (psoriasis, myeloproliferative and lymphoproliferative diseases), increased ATP degradation

Answer 338

Tendency to form monosodium urate crystals-\> gout Renal calculi Tophi- urate in soft tissues Acute urate nephropathy due to sudden increases in urate production-\> widespread crystallisation in the renal tubules e.g. tumour lysis syndrome

Answer 339

Monosodium urate

Answer 340

Monosodium urate crystals are proinflammatory

Answer 341

Acute gout

Answer 342

Chronic gout

Answer 343

Hyperuricaemia FHx Obesity ETOH consumption HTN Renal impairment Drugs

Answer 344

Abrupt onset Rapid build yp of pain and exquisitely tender, red, hot, swollen joint 1st MTP in 90% of cases 1/3rd have normal uric acid concentrations during an acute attack DDx= septic arthritis

Answer 345

Inflammations: NSAIDs, colchicine (inhibits neutrophil activity, to avoid comorbidties/contraindications in NSAIDs, but therre is SE of diarrhoea), GCs (short course prednisolone Hyperuricaemia: do not attempt to change levels during an acute flare up as lowering exacerbates clinical condition. Interval/non-acute gout: drink plenty of water, address risk factors Indications for treatment: recurrent gout, tophi, chronic arthropathy and gout with uric acid stones. Rx: reduce synthesis with allopurinol. Increase renal excretion with uricosuric

Answer 346

Xanthine oxidase inhibitor

Answer 347

Probenecid Losartan Benzbromarone Fenofibrate

Answer 348

Diuretics: combination of bolume depletion and decreased tubular secretino or uric acid Tacrolimus Cytotoxic CTx ETOH: increases ATP turnover, purines in beer during the fermentation process Salicylates (low dose): causes uric acid retnetion At high dose: it is uricosuric (increases excretion)

Answer 349

Clinical: monoarthritis Tap effusion: joint aspirate View underpolarised ligtht: yellow when parallel and blue when perpendicular: negatively birefringent

Answer 350

Calcium pyrophosphate crystals Blue when parallel, yellow when perpendicular Postiviely birefringent. Occurs in patients w/ OA Self-limiting

Answer 351

Normal at birth Developmental delay apparent at 6/12 Hyperuricaemic with gouty features HGPRT deficiency: deficiency of salvage enzymes leading to purine loss and increased urate

Answer 352

7 disorders caused by deficiency in enzymes involved in haem biosynthesis leading to a build up for toxic haem precurosrs

Answer 353

AIP VP HCP and ALA dehydratase Primarily attack the nervous system resulting in episodic crises known as acute attacks, the principle symptom of which is abdominal pain, often accompanied by vomiting, HTN and tachycardia. More severe dysfunction may see neurological cxs e.g. motor neuropathy

Answer 354

Neurovisceral only: abdo pain, seizures, psych disturbances, N+V, tachycardia, HTN, sensory loss, muscle weakness, constipation, urinary incontinence No cutaneous manifestations due to absence of porphyrinogens

Answer 355

ALA and PBG in urine (Port Wine urine)

Answer 356

Hydroxymethylbilane synthase deficiency

Answer 357

Because there are no porphyrinogens

Answer 358

Hereditary coproporphyria and variegate porphyria AD

Answer 359

Neurovisceral with skin lesions Raised porphyrins in faeces or urine

Answer 360

ALA synthase inducers e.g. steroids, ETOH, barbs Stress: infection, Sx Reduced caloric intake and endocrine factors e.g. premenstrual

Answer 361

Avoid precipitating facotrs Analgesia IV carbohydrate/haem arginate

Answer 362

Skin lesions only Congenital erythropoietic porphyria Erythropoietic protoporphyria Porphyria cutanea tarda

Answer 363

Photosensitivity, burning, itching, oedema Following sun exposure

Answer 364

Inherited/acquired Uroporphyrinogen decarboxylase deficiency Symptoms: vescles (crusting, pigmented, superficial scarring on sun exposed sites)

Answer 365

Increased urinary porphyrins and coproporphyrins and raised ferritin

Answer 366

Avoid precipitants Phlebotomy | (ETOH, hepatic compromise)

Answer 367

Acute: Plumboporphyria Acute intermittent porphyria Hereditary coproporphyria Variegate porphyria Non-acute Congenital erythropoeitic porphyria Porphyria cutanea tarda Erythropoietic protoporphyria

Answer 368

ALA synthase Therapeutic target

Answer 369

Gentamicin

Answer 370

Theopylline

Answer 371

Relapse of mania in BPAD

Answer 372

Uncontrolled infection

Answer 373

Zero effect on bronchial smooth muscle

Answer 374

At high levels liver becomes saturated Can lead to a surge in plasma [phenytoin]

Answer 375

Levels increased with hypokalaemia Reduce dose in renal failure and in elderly

Answer 376

Excretion impaired by hyponatraemia, impaired renal function and diuretics

Answer 377

Mostly use single daily dosing Monitor peak and trough level before next dose

Answer 378

Variable t1/2 e.g. 4hrs in smokers 8hrs in nonsmokers 30hrs in liver disease Levles increased by erythromycin, cimetidine and phenyotin

Answer 379

Omit/reduce dose

Answer 380

RF may need haemodialysis

Answer 381

Omit/reduce dose

Answer 382

Omit/reduce dose

Answer 383

Hydrocortisone Eumovate Betnovate Dermovate

Answer 384

Hypothyroidism

Answer 385

Treated hypothyroidism or subclinical hypothyroidism (look for assoiciated hypercholesterolaemia)

Answer 386

Look for TSH secreting tumour or thyroid hormone resistance

Answer 387

Hyperthyroidism

Answer 388

Subclinical hyperthyroidism

Answer 389

Central hypothyroidsim

Answer 390

Sick euthyroidsim (with any severe illness)

Answer 391

?Assay interference Changes in TBG Amiodarone

Answer 392

Controls I2 uptake Iodide converted to iodine Tyrosine residues are iodinated by thyroid peroxidase to iodotrosines These iodotyrosines joint to form thyroxine

Answer 393

Blocks Iodine uptake by TSH

Answer 394

Block iodniated by blocking thyroid peroxidase

Answer 395

TBG-T4 (75%) TBPA-T4 (20%) Albumin-T4 (5%) fT4: 0.03% T3 more biologically activated

Answer 396

It is peripherally converted to T3 by type 1 5' monodeiodinase

Answer 397

bHCG as some activity of TSH In pregnancy free T4 increases early on but TSH decreases slightlty

Answer 398

Symptomatic: beta blockers, NSAIDS for De Quervain's

Answer 399

Beta blocker and antithyroid therapy: carbimazole, propylthiouracil Can be used in block and replace or titrate to TSH Can also use radioiodine or surgery

Answer 400

Thyroid replacement therapy

Answer 401

Follicular

Answer 402

Thyroid lymphoma

Answer 403

Anaplastic

Answer 404

Surgery +/- radioidine Thyroxine (to reduce TSH)

Answer 405

Surgery + RI + thyroxine

Answer 406

Levothyroxine (T4)

Answer 407

Pancreas Parathyroid Pituitary

Answer 408

Medullary thyroid carcinoma Parathyoid Phaemochromocytoma

Answer 409

Phaeochromocytoma Medullary thyroid carcinoma Marfanoid habitus/mucosal neuroma

Answer 410

Metabolic rate Weight gain with decreased REE and poor appetite Myxoedema Goitre Hyponatraemia Normocytic anaemia unless pernicious anaemia

Answer 411

Hyponatraemic

Answer 412

Normocytic anaemia (unless pernicious anaemia)

Answer 413

Predicts later thyroid diseaes Unlikely to be cause of any symptoms Associated with hypercholesterolaemia

Answer 414

Graves\> TMG\> Toxic adenoma

Answer 415

Alteration in pituitary thyroid axis in any non-thyroidal illness Occurs in any severe illness

Answer 416

Grave's disease TMG Solitary toxic adenoma Thyroidits TSH induced Thyroid cancer induced Trohponlastic tumour and strum ovarii

Answer 417

Diffuse goitre Thyroid associated opthalmopathy, dermopathy, acropachy Symptoms of hyperthyroidism

Answer 418

Beta blockers if HR \>100 Radioactive iodine: 131I Sx Thionamides: block and replace or titration regime

Answer 419

Rarely cause agranulocytosis Check FBC

Answer 420

Carbimazole PTU

Answer 421

Toxic adenoma

Answer 422

De Querbains Thyroidits

Answer 423

Primary atrophic hypothyroidism

Answer 424

Hashimoto's

Answer 425

Antithyroid drugs Lithium Amiodarone

Answer 426

Hyperthyroid Then hypo

Answer 427

Calcitonin CEA

Answer 428

Chylomicron\< FFA\< VLDL\< IDL\< LDL \< HDL

Answer 429

Binds LDLR and promotes its degradation

Answer 430

Loss of function mutation in PCSK9 lowers LDL levels

Answer 431

Familial hypercholesterolaemia Polygenic hypercholesterolaemia Familial hypera-lipoporteinaemia Phytoserolaemia

Answer 432

AD: LDLR, apoB, PCSK9 AR: LDLRAP1

Answer 433

Several polymorphisms

Answer 434

CETP deficiency

Answer 435

ABC G5 and G8

Answer 436

Lipoprotein lipase or apoC II def

Answer 437

ApoA V deficiency

Answer 438

Increased TG synthesis

Answer 439

Combined hyperlipidaemia Familial dysbetalipoproteinaemia Familial hepatic lipase deficiency

Answer 440

Abeta-lipoproteinaemia Hypobeta-lipoproteinaemia Tangier disease Hypoa-lipoproteineimia

Answer 441

MTP deficiency

Answer 442

Truncated ApoB protein

Answer 443

HDL deficiency

Answer 444

ApoA-I mutations

Answer 445

Most of the fat in diet is TG Gets hydrolysed in small intesting into FFAs Absorbed ad converted into chylomicrons which enter plasma These are rapidly hydrolyesed by lipoprotein lipase to FFA FFA can be uptake by adipose tissue and converted back to TG or by the liver It is rescreted by liver as VLDL and converted to LDL

Answer 446

Inherited levels of high HDL regarded as benign and atheroprotective, can be due to CETP deficiency

Answer 447

Familial type IV

Answer 448

Excessive VLDL production Whole blood is homogenously lipaemic

Answer 449

ApoE mutations

Answer 450

Familial dysbeta lipoproteinaemia

Answer 451

E4 Homozygous

Answer 452

Hormonjal (e.g. hypothyroidism) Metabolic disorders Renal dysfunction Obstructive liver disease Toxins: ETOH and CFCs Iatrogenic: antihypertensives, immunosuppressants

Answer 453

Abeta-lipoproteinaemia

Answer 454

Tangier disease: complete HDL deficiency

Answer 455

High LDL \>4.1mmol/l Low HDL \<0.9mmol/l

Answer 456

Total to HDL ratio \>5= considerable risk

Answer 457

Nicotinic acid

Answer 458

Blocks cholesterol absorption

Answer 459

Statins act by competitively inhibiting HMG-CoA reductase, the first and key rate-limiting enzyme of the cholesterol biosynthetic pathway. Statins mimic the natural substrate molecule, HMG-CoA, and compete for binding to the HMGCR enzyme.

Answer 460

For ever decrease of 1mmol/l Total moratlity decreases by 12% Coronary mortality decreases by 19% Major vascular events decrease by 25%

Answer 461

MTP inhibitor Useful for homozygous type 2 who have no LDLR to upregulate with a statin

Answer 462

LDL particle with ApoA bound around it Acts like plasminogen and competes for plasminogen activating factor Atherogenic and thrombotic

Answer 463

Phase 1: oxidation- cytochorme P450 Phase 2: conjugation with glucuronide or sulphate

Answer 464

May lead to bone marrow toxicity when treated with azathioprine, 6-mercaptopurine or 6-thioguanine

Answer 465

Theophylline Carbamazepine Phenytoin Mycophenylate

Answer 466

Measure of the difference between toxic and therapeutic doses High TI= good Low Ti= bad

Answer 467

Gentamicin Amikacin Tobramycin Vancomycin

Answer 468

Phenytoin Lamotrigine

Answer 469

Ciclosporin Mycophenolate

Answer 470

Drug levels monitored

Answer 471

Non linear or saturation kinetics e.g. Phenytoin

Answer 472

6-12h post dose to avoid peak

Answer 473

12 hours post dose

Answer 474

Loading dose Maintenace dosing

Answer 475

Measure trough levels and renal function

Answer 476

PKU Congenital hypothyroidism CF Sickle Cell MCADD

Answer 477

Phenylalanine hydroxylase deficiency

Answer 478

Dysgenesis/agenesis of the thyroid gland

Answer 479

Fatty acid oxidation disorder

Answer 480

Well deifned disorder Associated with signifcant morbidity and mortality Period before onset where intervention improves outcome Known incidence Robust screening test with acceptable sensitvity and specificity that can be applied in a an ethical and safe manner

Answer 481

Phenylalanine hydroxylase deficiency Phenyalanine is an essential amino acid, metabolised by hydroxylation to tyrosine PKU results in phenylalanine accumulation in the blood. Phenylpyruvate and phenylacetic acid result

Answer 482

Mental retardation Blonder/lighter hair (tyrosine is a precuros to melanin) Physically well

Answer 483

Blood phenylalanine

Answer 484

Implement phenylalanine free diet and institute as early as possible

Answer 485

True positive/total disease present

Answer 486

True negative/total disease absence

Answer 487

True positives/total positives

Answer 488

True negatives/total negatives

Answer 489

Carnitine shuttles fatty acids into mitochondria for metabolism MCADD results in build up of fatty acids that cannot be broken down. They escape cell and can be detected in the blood: c6-10 acylcarnitines

Answer 490

Unable to metabolise fats When fasted beyond glyocgen stores, no further energy can be mobilised Child cannot break down fat Classic cause of cot death

Answer 491

Defect of methionine remethylation Commonly due to cystathionone beta-synthae enzyme Leads to homocystine accumulation

Answer 492

Deposition in lens leading to discoloration Mental retardation Thromboembolism

Answer 493

Very large doses of vitmanin B6 which will increase the activity of cystathionone beta-synthase

Answer 494

Respiratory alkalosis and hyperammonaemia Vomiting without diarrhoea- cyclical Neurological encephalopathy Avoidance- change in diet

Answer 495

All lead to hyperammonaemia

Answer 496

X-linked defect in urea cycle

Answer 497

Measure plasma amino acids and urine orotic acid

Answer 498

\<30 Slightly higher for smokers \<100 in terminal hepatic disease

Answer 499

Urea cycle disorders

Answer 500

Attempt to excrete excess ammonia by converting it to glutamine

Answer 501

If there is an early defect in cycle Orotic acid produced and excreted in urine

Answer 502

Remove ammonia Reduce ammonia production

Answer 503

Can occur in other metabolic disorders, not just urea cycle disorders

Answer 504

Organic acidurias

Answer 505

Group of meatbolic disorders that disrupt amino acid metabolism, particulalrly branched chain amino acids (leucine, isoleucine, valine)

Answer 506

Transamination: get rid of ammonia Dehydrogenate Results in compoun with a CoA group, CoA is conjugated to carnitine to allow it to be moved out of the cell Excreted by a further dehydrogenase reaction These abnormal metabolites have a strange smell

Answer 507

?Organic aciduria

Answer 508

Organic aciduria

Answer 509

Recurrent episodes of ketoacidotic coma, cerebral abnormalities Can't diagnose until you have excluded metabolic disorders

Answer 510

Reye Syndrome

Answer 511

Collect samples during acute episode Ammonia- plasma and urine Amino acids: plasma and urine Urine organic acids Plasma glucose and lactate Blood spot carnitine profile (abnormal all the time, even in remission)

Answer 512

Unusual not to have ketones in urine if hypoglycamic Occurs if you can't break down fat

Answer 513

Unable to break down galactose Most common carbohydrate disorders

Answer 514

Galactose-1-phosphate uridylyltransferase deficiency is the most severe and most common

Answer 515

Hepatomegaly, avoid eating, jaundice (conjugated hyperbilirubinaemia), vomiting, diarrhoea, sepsis

Answer 516

Metabolite of galactose Causes liver and kidney disease

Answer 517

Galactosaemia

Answer 518

Urine reducing substances Red cell gal-1-PUT

Answer 519

Abnormal metabolite made from gal-1-phosphate Converting enzyme located in lens of eye Therefore, opthalmological opinion

Answer 520

A result of defects in glycogen synthesis or breakdown. Commonly have muscular, liver and other consequences.

Answer 521

GSD Type 1 Glucose-6-phosphate deficiency

Answer 522

Leads not only to excessive glycogen storage but also prevents glucose export from gluconeogenetic organs

Answer 523

Glucose 6 phosphaase defect

Answer 524

Intraorganelle substrate accumulation leading to organomegaly and consequent dysmorphia and regression

Answer 525

Exogenous administration of enzymes Bone marrow transplant

Answer 526

Urine mucopolysaccharides and oligosaccharides Leucocyte enzyme activity

Answer 527

Disorder in the metabolism of very long chain fatty acids and biosynthesis of complex phospholipids

Answer 528

Peroxisomal disorders

Answer 529

Peroxisomal disorders

Answer 530

Very long chain fatty acids

Answer 531

Defective ATP production leads to multisystem disease especially affecting the organs with a high energy requirement e.g. brain, muscle, kidney, retina, endocrine organs

Answer 532

Clinical manifestation becomes evident at a certain threshold of mutant DNA

Answer 533

Mitochondrial DNA is maternally inherited although nuclear genome also plays a role in function Mitochondrial disorders can appear in any organ at any age with any inheritance pattern due to mutant DNA threshold and the interaction with nuclear DNA

Answer 534

Barth Syndrome

Answer 535

Mitochondrial encephalopathy, lactic acids and stroke like epsidoes

Answer 536

Kearns-Sayre

Answer 537

Eleveated lactate after periods of fasting CSF lactate-pyruvate ratio: deproteinised as bedside CSF protein rasied in KS syndrome CK: cardiomyopathy Muscle biopsy Mitochondrial DNA analysis

Answer 538

Defect of post-translational protein glycosylation Multisystem disorders associated with cardiomyopathy, osteopenia, hepatomegaly and dysmoprhic facial features in some cases

Answer 539

Congenital disorders of glycosylation

Answer 540

Congenital disorders of glycosylation

Answer 541

Total number of particles in solution mmol/kg

Answer 542

Calculated= mmol/l

Answer 543

Na + K + Cl + HCO3 + urea + glucose

Answer 544

Endogenous e.g. glucose Endogenous e.g. ethanol, mnannitol

Answer 545

2(Na+K)+urea+glucose

Answer 546

Termed the osmolar gap and can be used in metabolic acidosis

Answer 547

70% freely exchangeable, rest complexed in bone Preodminantly an extracellular cation maintained by active transport Principle determinant of ECF volume

Answer 548

Treat the underlying cause not the hyponatraemia (unless severe)

Answer 549

Nausea and vomiting (\<136) Confusion (\<131) Seizures, non-cardiogenic pulmonary oedema \<125 Coma \<117 eventually death

Answer 550

Serum osmolality

Answer 551

Glucose/mannitol infusion

Answer 552

Spurious Drip arm sample Pseudohyponatraemia (hyperlipidaemia, paraproteinaemia)

Answer 553

True hyponatraemia

Answer 554

Hyponatraemia from water reabsorbed from damaged prostate

Answer 555

Hydration status Urine Na

Answer 556

=RENAL Diuretics Addison's Salt losing nephropathies

Answer 557

=NONRENAL Vomiting DIarrhoea Excess sweating Third space losses (ascites, burns) Depend on fluid replacement

Answer 558

SIADH Primary polydipsia Severe hypothyroidism

Answer 559

=RENAL Acute/chronic renal failure

Answer 560

Cardiac failure Cirrhosis Inappropriate IV fluid

Answer 561

Central pontine myelinolysis

Answer 562

Central pontine myelinolysis

Answer 563

Over hydration with hypotonic IV fluids Transient ADH increase due to stress of surgery

Answer 564

True hyponatraemia Clinically euvolaemic Inappropriately high urine osmolality and increased renal sodium excretion \>20mmol Normal renal, adrenal, thyroid and cardiac function **Diagnosis of exclusion**

Answer 565

Malignancy: SCLC (most common) Pancreas, prostate, lymhpoma CNS disorders: meningoencephalitis, haemorrhage, abscess Respriatory: TB, pneumonia, abscess Drugs: opiates, SSRIs, Carbamezapine

Answer 566

Iatrogenic

Answer 567

Hypernatraemia

Answer 568

Rapid correction can lead to cerebral oedema

Answer 569

Cranial Nephrogenic

Answer 570

Fluid deprivation test

Answer 571

Lack or no ADH

Answer 572

Head trauma Surgery Tumour

Answer 573

Receptor defect- insensitivity to ADH

Answer 574

Inherited Lithium CRF

Answer 575

8 hour fluid deprivation test

Answer 576

Primary polydipsia

Answer 577

Cranial DI

Answer 578

Nephrogenic DI

Answer 579

Tachycardia Postural hypotension Dry mucous membranes Reduced skin turgor Confusion/drowsiness Reduced urine output

Answer 580

\<30ml/hour abnormal

Answer 581

Fluid replacement with 0.9% saline

Answer 582

Fluid restriction Treat underlying cause

Answer 583

Fluid restriction Treat the underlying cause

Answer 584

Look for cause of SIADH CXR CT head

Answer 585

Fluid restriction and treat underlying cause If fluid restriction is insufficeint: Demeclocylcine Tolvaptan

Answer 586

Reduces respsoniveness of CD cells to ADH

Answer 587

Monitor U&Es due to risk of nephrotoxicity

Answer 588

V2R antgonist

Answer 589

Seek expert help Hypertonic saline: slow and controlled manner Do not correct serum Na \>12mmol/l in the first 24h

Answer 590

Serum glucose Serum K Serum Ca: raised Ca and low K causes nephrogenic DI through increasing resistance to ADH PLasma and urine osmolality Water deprivation test

Answer 591

2 lines: one with 0.9% saline Other 5% dextrose Measure Na every 4-6 hours

Answer 592

Rate of correction = 10mmol in 24 hours  In this case the lady needs to be corrected for 28 mmol = (168-140)  This needs to be corrected for over 67.2 hours = 28/10 x 24 hours  Need to give her 4.8L over 67.2 hours = 71ml per hour.  Obligatory water losses from stool and skin is about 40ml/hour = 111mL/hour.  Measure the serum sodium every 4-6 hours for at least the first 12-24 hours.

Answer 593

Variable effect Hyperglycaemia will draw water out of the cells leading to a dilutional hyponatraemia Osmotic diruesis leads to loss of water and hypernatraemia

Answer 594

Osmotic diuresis is the increase of urination rate caused by the presence of certain substances in the small tubes of the kidneys.[2] The excretion occurs when substances such as glucose enter the kidney tubules and cannot be reabsorbed (due to a pathological state or the normal nature of the substance). The substances cause an increase in the osmotic pressure within the tubule, causing retention of water within the lumen, and thus reduces the reabsorption of water, increasing urine output (i.e. diuresis). The same effect can be seen in therapeutics such as mannitol, which is used to increase urine output and decrease extracellular fluid volume. Substances in the circulation can also increase the amount of circulating fluid by increasing the osmolarity of the blood. This has the effect of pulling water from the interstitial space, making more water available in the blood and causing the kidney to compensate by removing it as urine. In hypotension, often colloids are used intravenously to increase circulating volume in themselves, but as they exert a certain amount of osmotic pressure, water is therefore also moved, further increasing circulating volume. As blood pressure increases, the kidney removes the excess fluid as urine. Sodium, chloride, potassium are excreted in Osmotic diuresis, originating from Diabetes Mellitus (DM). Osmotic diuresis results in dehydration from polyuria and the classic polydipsia (excessive thirst) associated with DM.

Answer 595

Predominant intracellular cation, only 2% is extracellular Maintained by active tranpslant 90% freely exchangeable, the rest is bound in RBCs, bone and rain tissue

Answer 596

Caused by depltion or shift into to cells, very rarely due to decreased intake

Answer 597

1. GI loss 2. Renal loss: Hyperaldosteronism Increased Na delivery to distal nephron Osmotic diuresis 3. Redistribution into cells Insulin Beta agonists Alkalosis 4. Rare causes Rare tubular acidosis type 1 and 2 Hypomagnesia

Answer 598

Intimately link As one moves into cells, one moves out For every drop in pH of 0.1 theres is an increase in K of 0.7

Answer 599

Angiotensin II cause aldosterone release from adrenals Aldosterone promotes Na reabsroption in exchange for K

Answer 600

Hyperkalaemia

Answer 601

10ml 10% calcium gluconate over 20 mins with cardiac monitoring 50ml 50% dextrose and 10 units of insulin Nebulised salbutaoml Treat underlying cause

Answer 602

Renal impairment? Drugs that affect the RAAS Adrenal insufficiency? Release from cells?

Answer 603

Sodium reabsorption: in the ascending limb of the loop of Henle and in the distal convoluted tubule. If inhibit Na reabsorption in loop of henle e.g. loop diuretics and Bartter syndrome, it will increase distal Na delivery reabsorb and excrete K.

Answer 604

Taking a loop diuretic all the time

Answer 605

Gitelman syndrome is an autosomal recessive kidney disorder characterized by hypokalemic metabolic alkalosis with hypocalciuria, and hypomagnesemia. It is caused by loss of function mutations of the thiazide sensitive sodium-chloride symporter (also known as NCC, NCCT, or TSC) located in the distal convoluted tubule.[1] Gitelman syndrome was formerly considered a subset of Bartter syndrome until the distinct genetic and molecular bases of these disorders were identified. Bartter syndrome is also an autosomal recessive hypokalemic metabolic alkalosis, but it derives from a mutation to the NKCC2 found in the thick ascending limb of the loop of Henle

Answer 606

Hypokalaemia NB hypokalaemia causes nephrogenic DI

Answer 607

Screen with an aldosterone:renin ratio Adrenal tumour= excess alodsterone, rening will be suppressed therefore the ratio will be increased

Answer 608

IV KCL Maximum rate of 10mmol/hr Rates \>20mmol/hr are highly irritating to peripheral veins- would have to put in a central vein

Answer 609

Oral KCL, two tablets TDS for 48hrs Recheck potassium on day 3

Answer 610

* Aldosterone number of open Na+ channels in the luminal membrane * Sodium reabsorption * makes the lumen electronegative & creates an electrical gradient * Potassium is secreted into the lumen

Answer 611

Ascending loop of Henle

Answer 612

Gitelman syndrome

Answer 613

Furosemide

Answer 614

Diuretics Mx with 0.9% saline

Answer 615

Cardiac failure Mx fluid restriction Treat underlying cause

Answer 616

Cirrhosis Fluid restriction Treat underlying cause

Answer 617

Hypothyroidism TFTs Mx: thyroxine replacement

Answer 618

Addison's Short synACTHen test Treat underlying cause: hydrocortisone, fludrocortisone

Answer 619

SIADH OPlasma and urine osmolality CXR

Answer 620

Cranial DI

Answer 621

•Aldosterone: Renin ratio ?Adrenal tumour

Answer 622

Stone Bones Groans Moans Polyuria Muscle weakness

Answer 623

Correct dehydration Bisphosphonates Correct cause

Answer 624

Perioral paraesthesia Carpopedal spasm Neuromuscular excitability (Trousseau's, Chvostek's)

Answer 625

Mild: give calcium CKD: alfacalcidol Severe: 10% Ca gluconate IV

Answer 626

Metabolic acidosis

Answer 627

Na + K - Cl- bicarb

Answer 628

Presence of additional anions e.g. ketones

Answer 629

Respiratory alkalosis

Answer 630

Anion gap is normal

Answer 631

442m/osm because the brain is VERY dehydrated. Osmotic diuresis

Answer 632

Metabolic acidosis o Osmolality: 296 mosm/kg o Anion Gap: 50 excess of anions. o Metformin: works by blocking the Cori cycle. In an OD/ renal failure can cause a lactic acidosis  Glucose  lactate: when used by muscles and released into circulation. Anaerobic glycolysis  Lactate  liver  Liver : lactate  glucose: this step is slighlty inhibited by Metformin. Gluconeogeneisis o Unconscious: due to severe acidosis.

Answer 633

Ketones Methaonl Ethanol Lactate

Answer 634

Can cause a lactic acidosis Inhibits the cori cycle and the metabolism of lactate to glucose by the liver

Answer 635

Fasting glucose \> 7.0 mM Glucose tolerance test (75 grams glucose given at time 0) Plasma glucose \> 11.1 mM at 2 hours (2h value 7.8 – 11.1 = impaired glucose tolerance).

Answer 636

2h value after GGT 7.8-11.1

Answer 637

H loss e.g. vomiting Hypokalaemia Ingestion of bicarboate

Answer 638

Cell: Low K means lesss travels into cell but Na still needs to be pumped out, this will be performed by the Na/H exchanger which causes H to moveinto the cells. Renal level: hypokalaemia stimulates the secretion of acid

Answer 639

Low H leads to a K shift into cells Alkalosis leads to increased K secretion by the distal part of the kidney

Answer 640

Pituitary in nature

Answer 641

Ectopic ACTH

Answer 642

High levels of cortisol that can also bind to aldosterone receptor

Answer 643

Aspirin GTN Beta blocker Pain relief Thrombolysis or angioplasty

Answer 644

Albumin CRP Ig A1AT Transferrin Caerulopasmin Tumour markers

Answer 645

Haptoglobins Careuloplasmin

Answer 646

Transferrin LDL Complement

Answer 647

Bind to free Hb with high affinity, thereby inhibitng its oxidative activity

Answer 648

Oncotic pressure Source of amino acids Buffer Ligand binding

Answer 649

Almost always low, incresae only seen in severe dehydration Acts as a negative acute phase protein Reduced levels are primarily due to increased capilllary permeability Renal and gut losses common

Answer 650

Disease of low albumin Decreased synthesis-\> gross ascites Fluid shift to extravascular space due to loss of oncotic pressure

Answer 651

Increases 6-8 hours after tissue damage i.e trauma, infection and inflammaiton Peaks after 24-48h Stays elevated if there is a continuing stimulus

Answer 652

Antagnoist of serine proteases

Answer 653

Positive acute phase reactant

Answer 654

Urine microablumin

Answer 655

\<25g/l Usually due to low albumin

Answer 656

Congestive heart failure: dilutional effect on albumin Liver cirrhosis: decreased synthesis Hypoalbuminaemia Peritoneal dialysis: lose albumin

Answer 657

Parapneumonic effusion Malignancy PE

Answer 658

Pancreatitis RA SLE TB Haemothorax

Answer 659

Gilberts Recessive inheritance

Answer 660

The van den Bergh reaction measures serum bilirubin via fractionation. A direct reaction measures conjugated bilirubin. The addition of methanol causes a complete reaction, which measures total bilirubin (conjugated plus unconjugated); the difference measures unconjugated bilirubin (an indirect reaction).

Answer 661

Albumin Clotting factors (PT, PTTK) Bilirubin

Answer 662

Alcoholic hepatitis

Answer 663

Signs of chronic stable liver disease

Answer 664

Splenomegaly

Answer 665

List the possible sites Oesophageal varices Rectal varices Umbilical vein recanalising Spleno-renal shunt

Answer 666

Will have ab vs surface NOT core or E

Answer 667

If jaundiced and gall bladder is palpablle , not gallstones as the gall bladder in gallstones tends to become thin and fibrotic

Answer 668

Pneumococcal

Answer 669

Has hyalorunidase whereas Staph doesn't

Answer 670

Caused by fibrodysplasia of the renal artery in the intima, perimedia or adventitia usually narrowing the mid portion of the main renal artery. There is usually a Hx of paediatric HTN

Answer 671

ACT as a consequence of myoglobinuria

Answer 672

Radiolucent therefore AUSS

Answer 673

Calcium on the front of your eye

Answer 674

0.9% saline Frusemide

Answer 675

Bone lesion caused by HPTH Multinucleated giant cells in bone

Answer 676

High dose prednisolone

Answer 677

Fructosamine

Answer 678

Lesch–Nyhan syndrome (LNS), also known as Nyhan's syndrome and juvenile gout,[1] is a rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), produced by mutations in the HPRT gene located on the X chromosome. LNS affects about one in 380,000 live births.[2] The disorder was first recognized and clinically characterized by medical student Michael Lesch and his mentor, pediatrician William Nyhan, who published their findings in 1964.[3] The HGPRT deficiency causes a build-up of uric acid in all body fluids. This results in both hyperuricemia and hyperuricosuria, associated with severe gout and kidney problems. Neurological signs include poor muscle control and moderate intellectual disability. These complications usually appear in the first year of life. Beginning in the second year of life, a particularly striking feature of LNS is self-mutilating behaviors, characterized by lip and finger biting. Neurological symptoms include facial grimacing, involuntary writhing, and repetitive movements of the arms and legs similar to those seen in Huntington's disease. The etiology of the neurological abnormalities remains unknown. Because a lack of HGPRT causes the body to poorly utilize vitamin B12, some boys may develop megaloblastic anemia.

Answer 679

GHRH GnRH TRH Dopamine CRH

Answer 680

Stimulates GH

Answer 681

Stimulates LH/FSH

Answer 682

Stimulates TSH Stimulates Prolactin

Answer 683

Inhibits prolactin

Answer 684

Stimulates ACTH

Answer 685

Assessment of all components of anterior pituitary function used particularly in pituitary tumours or following tumour treatment

Answer 686

Ischaemic heart disease Epilepsy Untreated hypothyroidism (impairs the GH and cortisol response)

Answer 687

Sweating, palpitations, LOC Rarely: convulsions with hypoglycaemia Pateintsshould be warned that with the TRH injection they may experience transient symptoms of metallic taste in mouth, flushing and nausea

Answer 688

Insulin tolerance test TRH test GnRH test

Answer 689

Rises greater than 170 to above 500nmol/l

Answer 690

Rise to greater than 6mcg/l

Answer 691

TSH rise to \>5mU/l (30 min value \>60 minute value) If the 60 min sample \> 30 min value then there is primary hypothalamic disease

Answer 692

TSH remains suppressed

Answer 693

Exagerrated response

Answer 694

30 or 60 minutes

Answer 695

LH \>10 and FSH \>2

Answer 696

Possible early indication of hypopituitarism

Answer 697

On te bassal levels rather than the dynamic response

Answer 698

Low testosterone in the absence of raised basal gonadotrophins

Answer 699

Low oestradiol without elevated basal gonadotrophions and no response to clomiphene

Answer 700

Should have no response If sex steroids are present i.e. precocious puberty, the pituitary will be primed and will therefore respond to LHRH. Priming with steroids must not occur before this test

Answer 701

\<10mm Usually benign

Answer 702

\>10mm Usually aggressive

Answer 703

Lung: paraneoplasias, SCC and small cell, pneumoniae Brain: TBI, meningitis Iatrogenic: SSRIs, amitryptiline Effect is euvolaemic hyponatraemia i.e. SIADH

Answer 704

Failure/damage to hypothalamus and thirst drive Hypernatraemia without increased thirst response

Answer 705

Drugs anti-emetics, antipschotics (i.e. dopamine antaongists) Non-functioning piutitary adneoma

Answer 706

Unlikely to be non-functioning pituitary adenoma = prolactinoma If 4000 then could be either small prolactinoma or pituitary failure

Answer 707

Fast overnight Give insulin until glucose \<2.2mM Montior BM regularly to ensure hypoglycaemia

Answer 708

50ml 20% dextrose as 50% is too thick

Answer 709

Urgent: hydrocortisone replacement Nonurgent- thyorixne, oestrogen, replacement, GH

Answer 710

Dopamine agonist: Cabergoline, bromocriptine

Answer 711

GTT Should suppress GH

Answer 712

Hydrocortisone RTx Cabergoline Octreotide

Answer 713

Deficiency of MC i.e. aldosterone

Answer 714

Deficeincy of GC i.e. cortisol

Answer 715

Addison's disease and Primary hypothyoridism Polyglandular autoimmune syndorme II

Answer 716

Pituitary tumour

Answer 717

Low dose: suppresses cortisol in individuals with no pathology in endogenous cortisol production High dose exerts negative feedback on ACTH producing cells but not ectopic ACT-producing cells or adrenal adenoma

Answer 718

Autoimmune TB Tumour deposits Adrenal haemorrhage Amyloidosis

Answer 719

Short SynACTHen test

Answer 720

Hydorcortisone and fludrocortisone Saline to reydrate

Answer 721

Measure cortisol and ACTH at start of test (9AM) No adrenal funciton- low cortisol (\<10nm), high ACTH Inject 250mgrams of synthetic ACTH Funcitoning adrenal makes excess of cortisol immediately In Addison's won't see a rise in cortisol If funcitonal adrenals, will see a rise

Answer 722

Cushing's syndrome: cortisol Phaeochromocytoma: adrenaline Conn's snydorme: aldosterone

Answer 723

Aldosterone:Renin ratio

Answer 724

Aldosterone antaongists/K sparing diuretics Spironolactone Eplerenone Amiloride

Answer 725

Adrenal medullary tumour that secretes adrenaline and can cause severe HTN, arrythmias, death

Answer 726

Plasma and 24h urinary metadrenaline measuraement/catecholamine and VMA

Answer 727

Urgent: alpha blockade with phenoxybenzamine- inhibits synthesis and is long lasting Beta blockade Curative: bilateral adrenalectomy

Answer 728

Suppressable: Cushing's disease-\> MRI pit Fail to suppress: ectopic ACTH or adrenal adneoma-\> measure ACTH if high= cancer, low= adrenal

Answer 729

Myriad Can be cotricotrophic, somatotrophic Catecholaminergic Secondary to increased insulin resistance or absolute defieicncy

Answer 730

Symptoms + 1 of fasting glucose/OGTT or Without symptoms + fasting glucose + OGTT HbA1c \>48 should also be used

Answer 731

\>6,1 but \<7.0

Answer 732

Hydralazine

Answer 733

Cryoglobulinaemic vasculitis IgA vasculitis (HSP) Hypocomplementaemic urticarial vasculitis (antiC1q) Anti-GBM

Answer 734

SLE kidney

Answer 735

Scleroderma Onion skin

Answer 736

Non-necrotizing granulomas: histiocytes (epithelioid cells), multinucleated giant cells of Langhans (peripheral nuclei) and lymphocytes. Sarcoid

Answer 737

Thyrotoxicosis Infiltrative opthalmoapthy with exopathlmos Infiltrative dermopathy- pretibial myxoedema

Answer 738

Papillary 75-85% Follicular 10-20% Medullary 5% Anaplastic \<5%

Answer 739

Thyroid adenoma

Answer 740

Thyorid papillary carcinoma

Answer 741

Follicular carcinoma

Answer 742

Medullary carcinoma

Answer 743

G F R Medulla

Answer 744

Aldosterone

Answer 745

Glucocorticoids

Answer 746

Androgens and glucocorticoids

Answer 747

Cushgin's Disease

Answer 748

80% aldosterone secreting adenomas- Conns 20% bilateral adrenal hyperplasia

Answer 749

Aspartate transaminase

Answer 750

Ham's test

Answer 751

Heparin- unfractionated

Answer 752

EME = ecgonine methyl ester BE = benzoylecgonine They are the two degredation products of cocaine produced by pseudocholinesterases and hydrolysis respectively.

Answer 753

cyanide, iron, ethanol, lithium, acid or alkali, pesticides

Answer 754

Hyperreflexia and widened QRS

Answer 755

Immunoassay

Answer 756

Blood sample

Answer 757

Liquid chromatogrpahy

Answer 758

Thin layer chromatography

Answer 759

if the cause is glycosuria, the glucose has to be above 10mM to hit the renal threshold. Thus a glucose of 5.6 or 6.1 cannot cause polyuria if the 2h value is also 5.5mM.

Answer 760

Griseofulvin Phenytoin Phenobarbitone and other barbiturates Alcohol- chronic use Rifampicin, rifambutin, rifapentine Carbamezapine, OCP Sulfonylurea Smoking St John's Wort NNRTis: nevirapine, efavrinez, PI ritonaivr

Answer 761

Lamotrigine, pregabalin, levetriacetam BZDs (not barbs) Azithromycin (not other macrolides) Tetracylcien Quinolones (not ciprofloxacin)

Answer 762

Depressed: MAOIs, duloxetine, fluoexteine, sertraline, paroxetine, not citalopram Grapefuit juice Protease inhibotr: Ritonavir Diltiazem Amiodarone Verapamil e to visit Sodium Valproate Isoniazid Cimetidine not ranitidine Ketoconazole Alcohol (binge drinking) Chloramphenicol Erythromycin and other macrolides, not azithromycine Synercid Dot: Disulfiram Ciprofloxain Omeprazole not lansoprazole Metronidazole Allpurinol Sulfipnpyrazone Atorvastatin Phenylbutazone

Answer 763

Protease inhibitor In terms of CP450 it is a triple: substrate, inducer, inhibitor

Answer 764

Within 1 hr of overdose

Answer 765

Diuretic use

Answer 766

Renal tubular acidosis Renal stone is the giveaway

Answer 767

Addison's NB TB is the most common cause of Addison's worldwide

Answer 768

Haemolysis

Answer 769

Cranial DI

Answer 770

Causes nonosmotic release of ADH The commonest cause of SIADH in cancer patients is not brain intherapy, it is nausea from CTx

Answer 771

Addisonian crisis

Answer 772

Nelson's syndrome

Answer 773

Nelson's syndrome is a potentially life-threatening condition which occurs when an adrenocorticotrophic hormone (ACTH) secreting tumour develops following therapeutic total bilateral adrenalectomy (TBA) for Cushing's disease

Answer 774

Adrenal carcinoma

Answer 775

21-Hydroxylase Deficiency

Answer 776

17-Hydroxyprogesterone

Answer 777

Pregnanetriol

Answer 778

Hyponatreamia with Hyperkalaemia

Answer 779

Normal ACTH levels

Answer 780

Acute diffuse proliferative GN

Answer 781

Clear cell carcinoma

Answer 782

Von Hippel-Lindau (VHL) disease is an inherited disorder causing multiple tumours, both benign and malignant, in the central nervous system (CNS) and viscera. The most common tumours are retinal and CNS haemangioblastomas, renal cell carcinoma (RCC), renal cysts and phaeochromocytoma

Answer 783

Risk of phaeo is low but can develop all other tpyes

Answer 784

Have phaeos with: 2a: low risk of RCC 2B: high risk of RCC 2C: no other neoplasms

Answer 785

Acute tubular necrosis

Answer 786

Acute interstitial nephritis

Answer 787

IgA nephropathy

Answer 788

(creatinine urine concentration x vol)/ (plasma creatinine concentration) Units have to match

Answer 789

20 mls/min

Answer 790

35 mls/min

Answer 791

In general= diarrhoea

Answer 792

The exact mechanism is complicated. However in the absence of adequate thyroxine (and also cortisol), the renal tubules do not clear free water at a normal rate. Thus if you drink some water, the kidneys are slow to clear the free water, and thus hyponatraemia ensues. The GFR is NOT altered. The hyponatraemia occurs because the tubules do not clear free water and behave as if they are being stimulated by ADH, even when none is present. If a normal person drinks a litre of water, they start to increase their urine output within 20 minutes. If an Addisonian or severely hypothyroid patient drinks a litre of water, they only start increasing urine output an hour later, and this goes on for 24 hours. Thus they complain of nocturia (not polyuria).

Answer 793

Renal Tubular Acidosis (RTA) is a syndrome due to either a defect in proximal tubule bicarbonate reabsorption, or a defect in distal tubule hydrogen ion secretion, or both. This results in a hyperchloraemic metabolic acidosis with normal to moderately decreased GFR. Anion gap is normal. A typical situation where RTA would be suspected is if urine pH is greater than 7.0 despite the presence of a metabolic acidosis. In contrast, the acidosis that occurs with acute, chronic, or acute on chronic renal failure is a high anion gap metabolic acidosis.

Answer 794

redominantly tubular damage ---\> Normal anion gap acidosis (Renal tubular acidosis - RTA) Distal (or type 1) RTA Proximal (or type 2) RTA Type 4 RTA Predominantly glomerular damage ---\> High anion gap acidosis Acidosis of acute renal failure Uraemic acidosis

Answer 795

This is also referred to as classic RTA or distal RTA. The problem here is an inability to maximally acidify the urine. Typically urine pH remains \> 5.5 despite severe acidaemia ([HCO3] \< 15 mmol/l). Some patients with less severe acidosis require acid loading tests (eg with NH4Cl) to assist in the diagnosis. If the acid load drops the plasma [HCO3] but the urine pH remains \> 5.5, this establishes the diagnosis.

Answer 796

Hereditary (genetic) 3,4 Autoimminue diseases (eg Sjogren’s syndrome, SLE, thyroiditis) Disorders which cause nephrocalcinosis (eg primary hyperparathyroidism, vitamin D intoxication) Drugs or toxins (eg amphotericin B, toluene inhalation) Miscellaneous - other renal disorders (eg obstructive uropathy)

Answer 797

Type 1 RTA

Answer 798

Renal tubular acidosis

Answer 799

Type 2 RTA is also called proximal RTA because the main problem is greatly impaired reabsorption of bicarbonate in the proximal tubule. he increased distal Na+ delivery results in hyperaldosteronism with consequent renal K+ wasting. The hypokalaemia may be severe in some cases but as hypokalaemia inhibits adrenal aldosterone secretion, this often limits the severity of the hypokalaemia. Hypercalciuria does not occur and this type of RTA is not associated with renal stones. During the NH4Cl loading test, urine pH will drop below 5.5. Note that the acidosis in proximal RTA is usually not as severe as in distal RTA and the plasma [HCO3] is typically greater than 15 mmol/l.

Answer 800

Salivation Lacrimation Urination Defectation GI disturbance Emesis

Answer 801

Acid phosphatase

Answer 802

Cardiac troponin

Answer 803

Plasma cholinesterase

Answer 804

Cardiac troponin

Answer 805

Adenosine deaminase

Answer 806

Mycophosphorylase

Answer 807

In Wilson's Disease, the level of copper carrying protein in the blood is low, the total plasma copper level is low (if you measure it). Thus one could argue that the patient is deficient in copper. The plasma free copper is high, but this is only a tiny proportion of the total copper. Thus the excess free copper is the bit that does the damage. Because the free copper is high, the urinary (free) copper is also high. This is because bound copper cannot get into the urine.

Answer 808

Subacute granulomatous thryroiditis

Answer 809

Hashimoto's Askanazy cells are associated with hypothyroidism, as is lymphocytic infiltration in the thyroid gland. And right again about hashitoxicosis (initially resembling hyperthyroidism). Hashimoto's thyroiditis (autoimmune hypothyroidism): At presentation, 75% of patients are euthyroid, 20% are hypothyroid, and 5% are hyperthyroid - a disease known as hashitoxicosis. About 50% eventually become hypothyroid because of destruction of the thyroid gland. ps Remember association with hashimoto's and lymphoma. Ashkenazy cells. See attached file for more info.

Answer 810

Giant cell thyroiditis

Answer 811

Haem arginate

Answer 812

Co-trimoxazole

Answer 813

Acute intermittent porphyria

Answer 814

5-aminolevulinic acid

Answer 815

Porphyria cutanea tarda

Answer 816

ALA synthase

Answer 817

Activated porphyrins and oxygen free radicals

Answer 818

De Quervain's

Answer 819

early Hashitoxicosis

Answer 820

subacute granulomatous thyroiditis

Answer 821

Subacute lymphocytic thyroiditis

Answer 822

struma ovarii

Answer 823

exogenous iodine increases thyroid hormone stores

Answer 824

Very idodine rich, cuauses hyper and hypothyroidism

Answer 825

The Wolff–Chaikoff effect is an autoregulatory phenomenon that inhibits organification in the thyroid gland, the formation of thyroid hormones inside the thyroid follicle, and the release of thyroid hormones into the bloodstream.[6] This becomes evident secondary to elevated levels of circulating iodide. The Wolff–Chaikoff effect is an effective means of rejecting a large quantity of imbibed iodide, and therefore preventing the thyroid from synthesizing large quantities of thyroid hormone.[7] Excess iodide transiently inhibits thyroid iodide organification. In individuals with a normal thyroid, the gland eventually escapes from this inhibitory effect and iodide organification resumes; however, in patients with underlying autoimmune thyroid disease, the suppressive action of high iodide may persist.[8] The Wolff–Chaikoff effect lasts several days (around 10 days), after which it is followed by an "escape phenomenon,"[9] which is described by resumption of normal organification of iodine and normal thyroid peroxidase function. norganic iodine concentration secondary to down-regulation of sodium-iodide symporter (NIS) on the basolateral membrane of the thyroid follicular cell. The Wolff–Chaikoff effect can be used as a treatment principle against hyperthyroidism (especially thyroid storm) by infusion of a large amount of iodine to suppress the thyroid gland. Iodide was used to treat hyperthyroidism before antithyroid drugs such as propylthiouracil and methimazole were developed. Hyperthyroid subjects given iodide may experience a decrease in basal metabolic rate that is comparable to that seen after thyroidectomy.[6] The Wolff–Chaikoff effect also explains the hypothyroidism produced in some patients by several iodine-containing drugs, including amiodarone. The Wolff–Chaikoff effect is also part of the mechanism for the use of potassium iodide in nuclear emergencies.

Answer 826

Askenazi cells (otherwise known as Hurthle Cells or oncocytes) are thyroid cells with granular eosinophilic cytoplasm due to proliferating mitochondria. They are not strictly limited to Hashimotos as there is a rare tumour called a Hurthle cell adenoma that can be invasive locally or metastasize. Is usually put into the classification of follicular thyroid cancer although apparently it has slightly different treatment although it behaves similarly

Answer 827

Riedel's thyroiditis, also called Riedel's struma is a chronic form of thyroiditis. It is now believed that Riedel's thyroiditis is one manifestation of a systemic disease that can affect many organ systems called IgG4-related disease. It is often a multi-organ disease affecting pancreas, liver, kidney, salivary and orbital tissues and retroperitoneum. The hallmarks of the disease are fibrosis and infiltration by IgG4 secreting plasma cells

Answer 828

Lesc-Nyhan

Answer 829

Low dose aspirin

Answer 830

alcohol metabolism to lactate contributes to urate retention - port, some red wines and stouts contain purines or oxypurines, which lead to an increased purine load - alcohol may contribute to obesity which is associated with underexcretion of uric acid.

Answer 831

Aspirin decreases the kidneys ability to excrete uric acid.

Answer 832

hiazides are secreted by the organic acid transporter in the proximal tubule. They compete for this transporter with uric acid, so raising serum urate.

Answer 833

lassically we think that eating stimulates gastric acid production and causes pain with gastric ulcers, within 15-30 mins of eating. Although duodenal ulcers are relieved by eating / drinking milk, pain does occur 2-3 hours after eating. Nocturnal pain is very common with a duodenal ulcer and patients may put on weight as a result of increased intake of food and milk, whereas patients with gastric ulcers are often to afraid to eat and therefore lose weight. NB - tip: remember that duodenal ulcers are almost never malignant, but gastric ulcers may be benign/malignant, and therefore need a biopsy.

Answer 834

Tertiary Hyperparathyroidism

Answer 835

Papillary Carcinoma

Answer 836

Pseudohypoparathyroidism

Answer 837

Tertiart hyperparathyroidism

Answer 838

Primary hyperparathyroidism

Answer 839

PTHrP related (80%) Osteolytic metastases Tumour production of calcitriol

Answer 840

Breast Lung, lymphoma Thyroid Kidney Prostate Multiple myeloma

Answer 841

Biochemical: An ISOLATED elevated ALP should make you think of Paget's. The question tells you that blood tests reveal a LONE increase in ALP. Remember that osteomalacia can cause raised ALP, but other abnormalites include low Vitamin D!, low calcium, low phosphate and high PTH (secondary hyperparathyroidism). Clinically: Both can cause musculoskeletal pain (ostemalacia can cause aches and pains everywhere including the back). Remember that rickets is vit d deficency in children and osteomalacia in adults. Bowing of the legs usually found in rickets, ie growing children. Bowing of the long bones occurs in Paget's (tibia sabre). NB In Paget's sites most commonly affected are the pelvis, lumbar spine, femur and thoracic spine. This disease rarely affects the appendicular bones e.g. bones of the hand and feet.

Answer 842

Mixed respiratory and metabolic acidosis

Answer 843

Acute respiratory alkalosis with co-existent metabolic acidosis

Answer 844

Compensated respiratory alkalosis

Answer 845

Metabolic alkalosis with compensatory hypoventilation

Answer 846

Respiratory acidosis

Answer 847

\> 6 times adult requirements

Answer 848

Nectrotising enterocolitis

Answer 849

ALP is typically normal

Answer 850

Defect in renal hydroxylation

Answer 851

Renal osteodystrophy causes osteomalacia resulting from a def of 1,25(OH)Vit D (defective 1-hydroxylation due to the renal failure). Renal osteodystrophy ALSO leads to an increase in phosphate which reduces ionised Ca in the blood therefore inducing hyperparathyroidism. This then increases bone resorption by releasing Ca from bone stores. This is secondary hyperparathyroidism. If this becomes autonomous then it is termed tertiary hyperparathyroidism, which is biochemically no different to primary other than it is as a result of renal failure. The patient who has renal failure for a long time, will have failure of 1 alpha hydroxylation, and hence secondary hyperparathyroidism. This goes on for years, and the parathyroids can become very hyperactive, but the calcium remains low because there still is no 1 alpha. Then he suddenly has a kidney transplant, and the 1 alpha reactivates. The overactive hypertrophic parathyroid glands are now autonomous, and now primary hyperparathyroidism results. When this occurs after secondary hyperparathyroidism, it is called tertiary. Biochemically primary and tertiary are the same.

Answer 852

This is Albright's hereditary osteodystrophy (pseudohypoparathyroidism) - which causes hypocalcaemia because of a receptor insensitivity to PTH, i.e. end organ resistance to PTH - therefore the parathyroid glands produce loads of PTH to try and increase blood calcium levels but to no avail because the receptors are non-functional.

Answer 853

[H+]= constant x [pCO2/HCO3-] the constant is always 180. so you can always work out the bicarb and decide if a compensation has occurred or not. helps me loads!

Answer 854

Respiratory alkalosis with metabolic acidotitc compensation

Answer 855

The metabolic acidosis occurs because salicylates in overdose uncouple oxidative phosphorylation so aerobic metabolism fails and anaerobic metabolism takes over. This leads to a metabolic (lactic) acidosis. Salicylates also stimulate the respiratory centre in overdose, which is how they cause hyperventilation and respiratory alkalosis.

Answer 856

Pseudohypoparathyroidism (PHP) is a rare disorder characterised by failure of target cells to respond to parathyroid hormone (PTH). Inheritance is autosomal dominant. The gene involved, GNAS1, encodes Gs-alpha, the G-protein subunit that acts as an adenyly cyclase activator in its active, GTP-bound form. Gs-alpha function is required for target organ responses to PTH, TSH and FSH/LH. Loss of function mutations of the MATERNAL allele of Gs-alpha causes PHP. Loss of function mutations of the PATERNAL allele of Gs-alpha causes pseudo-PHP. Gain of function mutations of Gs-alpha causes McCune Albright syndrome (Polyostotic fibrous dysplasia, cafe au lait macules, precocious puberty).

Answer 857

Pseudohypoparathyroidism

Answer 858

is hypercalcaemia in a patient with a malignant neoplasm in the absence of skeletal metastases or primary hyperparathyroidism; believed to be due to formation of parathyroid-like hormone by nonparathyroid tumour tissue

Answer 859

Pseudopseudohypoparathyroidism (pseudoPHP) is an inherited disorder, named for its similarity to pseudohypoparathyroidism in presentation. The term pseudopseudohypoparathyroidism is used to describe a condition where the individual has the phenotypic appearance of pseudohypoparathyroidism type 1a, but is biochemically normal. It is sometimes considered a variant of Albright hereditary osteodystrophy.[1] It was characterized in 1952 by Fuller Albright as "pseudo-pseudohypoparathyroidism" (with hyphen)

Answer 860

Pseudohypoparathyroidism

Answer 861

Cortisol replacement

Answer 862

Androgen insufficiency

Answer 863

Corticotrophin insufficiency

Answer 864

Metabolic syndrome

Answer 865

Lipoprotein lipase

Answer 866

Alcohol abuse

Answer 867

Chylomicron Lipoprotein lipase High density lipoprotein (HDL) Chylomicron Intermediate density lipoprotein

Answer 868

Crigler-Najjar syndrome

Answer 869

Glucose-6-phosphate dehydrogenase deficiency HS may present at birth but it is very uncommon an adolescent/adult presentation is more usual. The key here is haemoglobinuria which tells you it is intravascular haemolysis (HS is extra vascular)

Answer 870

21 hydroxylase deficiency

Answer 871

Lesch-Nyhan syndrome

Answer 872

Amino acids (urine and plasma) Plasma and urine amino acids would be in first line metabolic screen. The Canadian hint is trying to point towards Type 1 tyrosinaemia which is more common in Quebec. (plus, the overlap between jaundice and sepsis suggest either tyrosinaemia or galactosaemia, and it doesn't fit with the latter in other ways)

Answer 873

Tachypnoea with neuro signs suggests respiratory alkalosis and encephalopathy, characteristic of urea cycle defects - ie. ammonia would be raised.

Answer 874

Very long chain fatty acids Of the inborn errors, the 2 that produce dysmorphic signs are peroxisomal and congenital disorders of glycosylation. Of these, only the first is associated with jaundice.

Answer 875

Galactase-1-phosphate uridyl transferase jaundice suggests galactosaemia or tyrosinaemia - In this case, cataracts occur because of accumulation of galacitol, and jaundice because of excess galactose-1-phosphate in liver.

Answer 876

Even modest renal impairment predisposes to upper GI bleed.

Answer 877

Pioglitazone (Thiazolidinedione)

Answer 878

Fasting plasma glucose 6.9 mmol/l. 2hrs post OGGT plasma glucose 10.5 mmol/l

Answer 879

Plasma glucose 14 mmol/l; pH 7.2; pCO2 3.0 kPa. Urine positive for ketones

Answer 880

Fasting whole blood glucose 6.0 mmol/l. Osmolarity 352 mOsm/kg.

Answer 881

Plasma glucose 1.45 mmol/l; pH 7.58; pCO2 2.4 kPa. This patient has most likely taken excess insulin (or missed a meal after insulin), and has become hypoglycaemic. This leasd to anxiety/hyperventilation leads to respiratory alkalosis (high pH/ low pCO2)

Answer 882

Biguanine Metformin normalizes post prandial hyperglycaemia and reduces fasting hyperglycaemia. Proposed mechanisms of action: - stimulation of glycolysis in tissues, with increased glucose removal from blood - reduced hepatic and renal gluconeogenesis. - slowed glucose absorption from the gut with increased glucose-to-lactate conversion in enterocytes - reduced plasma glucagon levels

Answer 883

- are PPAR gamma ligands - reduce insulin resistance by altering expression of genes involved in glucose and lipid metabolism - clinical role uncertain since rosiglitazone was associated with increase in myocardial infarction in a case control study of 42 trials (the odds ratio for myocardial infarction was 1.43 (95% confidence interval [CI], 1.03 to 1.98; P=0.03), and the odds ratio for death from cardiovascular causes was 1.64 (95% CI, 0.98 to 2.74; P=0.06). NEJM 2007;356:2457-71 - Karim Meeran "Rosiglitazone almost got withdrawn, and there was lots in the press, but it survived. However it is less popular than previously. It is likely to be used less and less because it causes osteoporosis, as well as the possible cardiac failure (actually unproven)."

Answer 884

Increase insuline release

Answer 885

Divide by 1.12 to 1.15

Answer 886

ALT usually \> AST in hepatic disease AST to ALT switch may indicate cirrhosis AST:ALT 2:1 indicates alcoholic liver disease \<1 suggests other cause

Answer 887

Renal tubular acidosis (D) occurs when there is a defect in hydrogen ion secretion into the renal tubules. Potassium secretion into the renal tubules therefore increases to balance sodium reabsorption. This results in hypokalaemia with acidosis. Renal tubular acidosis is classified according to the location of the defect: type 1 (distal tubule), type 2 (proximal tubule), type 3 (both distal and proximal tubules). Type 4 results from a defect in the adrenal glands and is included in the classification as it results in a metabolic acidosis and hyperkalaemia.

Answer 888

ETOH Enzyme inducing drugs e.g. phenytoin, carbamazepine, phenobarbitone.

Answer 889

AR disorder resulting in riased conjugated bilirubin due to reduced secretion of conjugated bilirubin into the bile. AST and ALT levels are normal.

Answer 890

Hereditary disease resulting in either complete or partial reduciton in UDP glucornosyl transferase causing an unconjugated hyperbilirubinaemia

Answer 891

Addison’s disease (C) is caused by primary adrenal insufficiency resulting in a reduced production of cortisol and aldosterone. It is diagnosed using the synACTHen test. In the short synACTHen test, baseline plasma cortisol is measured at 0 minutes, the patient is given 250 μg of synthetic ACTH at 30 minutes and plasma cortisol is rechecked at 60 minutes; if the final plasma cortisol is \<550 nmol/L, a defect in cortisol production exists. The long synACTHen test distinguishes between primary and secondary adrenal insufficiency. A 1 mg dose of synthetic ACTH is administered; after 24 hours, a cortisol level of \<900 nmol/L signifies a primary defect. Due to reduced mineralocorticoid production, blood tests will also reveal a hyponatraemia and hyperkalaemia

Answer 892

``` Vitamin C (F) is a water soluble vitamin, essential for the hydroxylation of collagen. When deficiency of vitamin C is present, collagen is unable to form a helical structure and hence cannot produce cross-links. As a consequence, damaged vessels and wounds are slow to heal. Vitamin C deficiency results in scurvy, which describes both bleeding (gums, skin and joints) and bone weakness (microfractures and brittle bones) tendencies. Gum disease is also a characteristic feature. ```

Answer 893

Vitamin E (tocopherol; H) is an important anti-oxidant which acts to scavenge free radicals in the blood stream. Deficiency leads to haemolytic anaemia as red blood cells encounter oxidative damage and are consequently broken down in the spleen. Spino-cerebellar neuropathy is also a manifestation, which is characterized by ataxia and areflexia. Vitamin E deficiency has also been suggested to increase the risk of ischaemic heart disease in later life, as low-density lipoproteins become oxidized perpetuating the atherosclerotic process.

Answer 894

Homocystinuria (H) is an amino acid disorder in which there is a deficiency in the enzyme cystathionine synthetase. This metabolic disorder presents in childhood with characteristic features such as very fair skin and brittle hair. The condition will usually lead to developmental delay or progressive learning difficulties. Convulsions, skeletal abnormalities and thrombotic episodes have also been reported. Management options include supplementing with vitamin B6 (pyridoxine) or maintaining the child on a low-methionine diet.

Answer 895

Phenylketonuria (PKU; A) is also an amino acid disorder. Children classically lack the enzyme phenylalanine hydroxylase, but other co-factors may be aberrant. Since the 1960s PKU has been diagnosed at birth using the Guthrie test but in some countries the test may not be available. The child will be fair-haired and present with developmental delay between 6 and 12 months of age. Later in life, the child’s IQ will be severely impaired. Eczema and seizures have also been implicated in the disease process.

Answer 896

Von Gierke’s disease (E) is one of nine glycogen storage disorders, in which a defect in the enzyme glucose-6-phosphate results in a failure of mobilization of glucose from glycogen. The metabolic disease presents in infancy with hypoglycaemia. The liver is usually significantly enlarged and kidney enlargement can also occur. Other glycogen storage disorders (and enzyme defects) include Pompe’s (lysosomal α-glucosidase), Cori’s (amylo-1,6-glucosidase) and McArdle’s (phosphorylase); each disorder presents with varying degrees of liver and muscle dysfunction.

Answer 897

Maple syrup urine disease (C) is an organic aciduria, a group of disorders that represent impaired metabolism of leucine, isoleucine and valine. As a result, toxic compounds accumulate causing toxic encephalopathy which manifests as lethargy, poor feeding, hypotonia and/or seizures. Characteristic of maple syrup urine disease are a sweet odour and sweaty feet. The gold standard diagnostic test is gas chromatography with mass spectrometry. Management involves the avoidance of the causative amino acids.

Answer 898

Fabry’s disease (F) is a lysosomal storage disorder in which there is deficiency in α-galactosidase. Presentation is almost always a child with developmental delay together with dysmorphia. Other findings may involve movement abnormalities, seizures, deafness and/or blindness. On examination, hepatosplenomegaly, pulmonary and cardiac problems may be noted. The pathognomonic feature of lysosomal storage disorders is the presence of a ‘cherry-red spot’.

Answer 899

``` Peroxisomal disorders (A) result in disordered β-oxidation of verylong- chain fatty acids (VLCFA); these accumulate in the blood stream. ```

Answer 900

Short-chain acyl-coenzyme A dehydrogenase (SCAD) deficiency (D) is one of the four fatty acid oxidation disorders

Answer 901

Urea cycle disorders (G) arise due to deficiency in one of the six enzymes in the urea cycle, resulting in hyperammonaemia. Enzyme deficiency occurs in an autosomal recessive fashion.

Answer 902

Galactosaemia (I) results from the deficiency in the enzyme galactose- 1-phosphate uridyl transferase (Gal-1-PUT).

Answer 903

Phenytoin (H) is a commonly used anti-epileptic agent. Serum levels of phenytoin must be monitored due to its narrow therapeutic range (10–20 μg/mL). Phenytoin also exhibits saturation kinetics; a small rise in dose may lead to saturation of metabolism by CYP enzymes in the liver, hence producing a large increase in drug concentration in the blood as well as associated toxic effects. Phenytoin toxicity can lead to hypotension, heart block, ventricular arrhythmias and ataxia.

Answer 904

Lithium (B) is a therapeutic agent used in the treatment of bipolar disorder. Drug monitoring is essential (12 hours post dose) due to its low therapeutic index as well as the potential life-threatening effects of toxicity. Lithium is excreted via the kidneys and therefore serum drug levels may increase (with potential toxicity) in states of low glomerular filtration rate, sodium depletion and diuretic use. Features of lithium toxicity include diarrhoea, vomiting, dysarthria and coarse tremor. Severe toxicity may cause convulsions, renal failure and possibly death.

Answer 905

Theophylline (D) is a drug used in the treatment of asthma and COPD. A low therapeutic index and wide variation in metabolism between patients lead to requirement for drug monitoring. Toxicity may manifest in a number of ways including nausea, diarrhoea, tachycardia, arrhythmias and headaches. Severe toxicity may lead to seizures. The toxic effects of theophylline are potentiated by erythromycin and ciprofloxacin. Without monitoring, many patients would be under-treated.

Answer 906

Procainamide (A) is an anti-arrhythmic agent.

Answer 907

Methotrexate (C) is an anti-folate drug used in the treatment of cancers and autoimmune conditions.

Answer 908

Carbamazepine (F) is an anti-convulsant medication.

Answer 909

Toxicity is associated with acute renal failure. Calcium channel antagonists and certain antibiotics such as erythromycin predispose to nephrotoxicity, whereas anticonvulsants such as phenytoin reduce blood levels of the drug.

Answer 910

This is a difficult question but the answer can be deduced with a basic knowledge of electrolyte physiology. This patient suffers from bulimia nervosa as characterized by the use of characteristic purging after meals to keep her weight under control. The main abnormalities in the investigations reveal a hypokalaemia with arterial alkalosis and paradoxical aciduria. The alkalosis is likely to be due to excessive purging leading to a loss of hydrogen ions. The hypokalaemia is secondary to the metabolic alkalosis as potassium and hydrogen are transported across cell membranes by the same transporter. The reduction of plasma hydrogen ions leads to increased potassium uptake leading to hypokalaemia. As part of a normal homeostatic mechanism, potassium is exchanged forhydrogen ions in the distal convoluted tubule of the nephron, resulting in an apparent paradoxical aciduria. Acute renal failure (A) tends to give hyperkalaemia and metabolic acidosis. This is due to the failure of homeostatic mechanism, the causes of which are classically defined as pre-renal, renal or postrenal. Pre-renal failure is caused by a reduction in glomerular filtration rate. This may be due to reduced blood flow or reduced perfusion pressure. Common causes include hypovolaemia or hypotension from shock. Intrinsic renal failure has a wide aetiology including drugs, inflammation and infection. Post-renal failure is caused by obstruction anywhere from the collecting ducts distally. This classically presents in elderly men with prostatic disease with urinary retention relieved by catheterization. Citalopram (C) is a selective serotonin reuptake inhibitor (SSRI) used in the treatment of depression. Some SSRIs cause hyponatraemia, but not usually hypokalaemia. Renal tubular acidosis (B) generally causes a lack of ability to acidify urine and hyperkalaemia. The exception is type II renal tubular acidosis with a bicarbonate leak in the proximal convoluted tubule where hypokalaemia is common but the urine is only acidified during systemic metabolic acidosis. This is not the case in this patient. Finally anaemia (D) does not usually cause electrolyte abnormalities.

Answer 911

This patient’s hyponatraemia is most likely secondary to Carbamezepine therapy (B), a well documented side effect of this antiepileptic medication. Carbamezepine stimulates the production of vasopressin, the mechanism of action of which will be discussed shortly. It is also one of the ‘terrible 3 Cs’ which cause aplastic anaemia, the other two being carbimazole and chloramphenicol. Any patient with signs of infection or bleeding must be taken very seriously as fulminant sepsis may ensue without prompt treatment. This patient, however, has mounted a white cell response with a normal platelet count therefore making aplastic anaemia unlikely. Pneumonia (A) does not normally cause a sodium abnormality on its own. Less commonly, Legionnaire’s disease caused by the bacterium Legionella pneumophilia can have extrapulmonary features including hyponatraemia, deranged liver function tests and lymphopenia. This is unlikely to be the case as this organism often colonizes water tanks in places with air conditioning and has a prodromal phase of dry cough with flu-like symptoms. The alternative indirect pulmonary cause of hyponatraemia is lung cancer producing a SIADH; the tumour predisposes the patient to pneumonia by obstructing the normal ciliary4clearance of the bronchi. It is unlikely in this patient given the lack of smoking history or cachexia. Risperidone (C) is an atypical antipsychotic and only very rarely causes hyponatraemia. More common side effects include gastrointestinal disturbance and dry mouth. SIADH (D) is the excessive production of antidiuretic hormone (also called vasopressin) from the posterior pituitary. Its release is stimulated physiologically by osmoreceptors responding to an increased plasma osmolality, as well as baroreceptors responding to decreased intravascular volume. Vasopressin activates vasopressin 2 receptors in the renal collecting duct principal cells, which in turn activate adenylate cyclase to increase intracellular cyclic AMP levels. This is turn increases aquaporin 2 gene transcription and the protein inserts into the apical membrane of the cells allowing free water influx to normalize increased plasma osmolality. SIADH occurs when there is excessive production of vasopressin leading to a euvolaemic hyponatraemia. It is a diagnosis of exclusion and requires two criteria in the blood, two criteria in the urine and three exclusion criteria and can be remembered as ‘two low in the blood, two high in the urine, three exclusions everywhere else’. 1 Two low in the blood – hyponatraemia and hypo-osmolality 2 Two high in the urine – high urinary sodium \>20 mmol/L and high urinary osmolality 3 Three exclusions – NO renal/adrenal/thyroid/cardiac disease, NO hypovolaemia, NO contributing drugs. Cerebral salt wasting (CSW) syndrome (E) occurs after head injury or neurosurgical procedures where a natriuretic substance produced in the brain leads to sodium and chloride loss in the kidneys, reducing intravascular volume and leading to water retention. There is therefore a baroreceptor-mediated stimulus to vasopressin production. It resembles SIADH in that both are hyponatraemic disorders seen after head injury with high urinary sodium, urinary osmalility and vasopressin levels. The difference is the primary event in CSW is high renal sodium chloride loss, not high vasopressin release.

Answer 912

Hyponatraemia and hypo-osmolality High urinary sodium (\>20) and high urinary osmolality No renal/adrenal/thyroid/cardiac disease. No hypovolaemia, no contributing drugs!! SIADH

Answer 913

This patient has tertiary hyperparathyroidism (C) given the presence of elevated calcium levels with high parathyroid levels in the presence of chronic renal failure. Plasma calcium levels are controlled via parathyroid hormone (PTH) which is produced in the parathyroid glands situated within the thyroid gland. Reduced ionized calcium concentration is detected by the parathyroid glands leading to a release of PTH which circulates in the blood stream. PTH increases calcium resorption from the kidneys whilst increasing phosphate excretion. PTH also stimulates 1-alpha hydroxylation of 25-vitamin D to make 1,25-vitamin D. Finally, PTH increases bone resorption of calcium via osteoclast activation. The sum effects of increased PTH levels are to increase plasma calcium concentration and to reduce phosphate concentration. PTH has an indirect, but very important, mechanism via 1,25-vitamin D which acts to increase gut absorption of calcium. Tertiary hyperparathyroidism (C) is seen in the setting of chronic renal failure and chronic secondary hyperparathyroidism leads to hyperplastic or adenomatous change in the parathyroid glands resulting in autonomous PTH secretion. The causes of calcium homeostasis dysregulation are multifactorial including tubular dysfunction leading to calcium leak, inability to excrete phosphate leading to increased PTH levels and parenchymal loss resulting in lower activated vitamin D levels. As a result tertiary hyperparathyroidism gives a raised calcium with a very raised PTH, with normal or low phosphate. Serum alkaline phosphatase is also raised due to the osteoblast and osteoclast activity (note, osteoblasts produce alkaline phosphatase. This is why there is a normal alkaline phosphatase in myeloma, as it directly stimulates the osteoclasts). Treatment of tertiary hyperparathyroidism is subtotal parathyroidectomy. Tertiary hyperparathyroidism is differentiated from primary hyperparathyroidism (A) by the presence of chronic renal failure but is otherwise difficult to distinguish biochemically. Primary hyperparathyroidism is most commonly caused by a solitary adenoma in the parathyroid gland. Surgeons sometimes use sestamibi technetium scintigraphy to locate the offending adenoma prior to surgical removal. Secondary hyperparathyroidism (B) occurs where there is an appropriately increased PTH level responding to low calcium levels. This is commonly due to chronic renal failure or vitamin D deficiency but can be seen in any pathology resulting in reduced calcium or vitamin D absorption or hyperphosphataemia. Pseudohypoparathyroidism (also known as Albright’s osteodystrophy) results from a PTH receptor insensitivity in the proximal convoluted tubule of the nephron. As a result, calcium resorption and phosphate excretion fail despite high PTH levels. Furthermore, other physical signs associated with this condition include short height, short 4th and 5th metacarpals, reduced intelligence, basal ganglia calcification, and endocrinopathies including diabetes mellitus, obesity, hypogonadism and hypothyroidism. Type 1 pseudohypoparathyroidism is inherited in an autosomal dominant manner where the renal adenylate cyclase G protein S alpha subunit is deficient, thus halting the intracellular messaging system activated by PTH. Patients with pseudopseudohypoparathyroidism (E) have similar physical features to pseudohypoparathyroidism but with no biochemical abnormalities of calcium present. This condition is a result of genetic imprinting where the phenotype expressed is dependent on not just what mutation is inherited but also from whom. In other words, inheriting the pseudohypoparathyroidism mutation from one’s mother leads to pseudohypoparathyroidism, but inheriting it from one’s father leads to pseudopseudohypoparathyroidism. At the molecular level, this is signalled by differential methylation of genes thus providing a molecular off switch controlling its expression. Another example of genetic imprinting occurs in Prade–Willi syndrome and Angelman’s syndrome, caused by a microdeletion on chromosome 15.

Answer 914

pyridoxine

Answer 915

To prevent hyperkalaemia due to the well known side effect of tissue injury postoperatively.

Answer 916

Can cause solute washout in the renal medulla reducing the action of ADH

Answer 917

Lithium Demeclocycline

Answer 918

Dilute urine for the first 8 hours Concentrated urine after the desmopressin administration

Answer 919

PBG deaminase deficiency (A) causes acute intermittent porphyria, which this patient suffers from. The porphyrias are a group of seven disorders caused by enzyme activity reduction in the haem biosynthetic pathway. Haem is manufactured in both the liver and bone marrow where branched chain amino acids together with succinyl CoA and glycine are needed. The first step involves 5 aminolevulinic acid (ALA) synthesis by ALA synthase. This is the rate limiting step which is under negative feedback from haem itself. A simplified schema of haem production is provided with the products depicted on the left, and the enzyme responsible along with the type of porphyria caused if it was deficient on the right. The features of porphyria can be generally classified into neurological, cutaneous and microcytic anaemia. The exact combination of symptoms depends on where in the haem pathway the deficiency occurs. Neurological symptoms, including peripheral neuropathy, autonomic neuropathy and psychiatric features, are caused by the increase of porphyrin precursors 5 ALA and prophobilinogen (PBG). Cutaneous symptoms are due to photosensitive porphyrins which are produced later on in the sequence. Finally microcytic anaemia occurs due to the deficiency of haem production. Acute intermittent porphyria (AIP) presents without cutaneous symptoms, this is because the enzyme deficiency is further upstream from the photosensitive porphyrins which cause the cutaneous symptoms. Instead neurological symptoms of the peripheral, autonomic and psychiatric systems predominate, as in this patient. The symptoms cluster in attacks if toxins induce ALA synthase or PBG deaminase activity. These include alcohol, the oral contraceptive pill and certain antibiotics including rifampicin and pyrazinamide (two commonly used anti-tuberculosis drugs). Other common precipitants include surgery, infection and starvation. Investigations classically show urine which becomes brown or black upon standing in light as well as reduced erythrocyte PBG deaminase levels. Note there is no increase of faecal porphyrins in AIP. Treatment is to avoid precipitants as well as dextrose infusion and haem arginate intravenously which both inhibit ALA synthase activity. Uroporphyrinogen synthase (B) results in congenital erythropoeitic porphyria which is one of the rarest inborn errors of metabolism. It is caused by a mutation on chromosome 10q26 and is inherited in an autosomal recessive fashion. Symptoms include vesicles, bullae and excessive lanugo hair as well as mutilating deformities of the limbs and face. Urine is classically burgundy red as well as patients having erythrodontia – red stained teeth. Treatment is to avoid sunlight and symptomatically treat the anaemia. Coproporphyrinogen oxidase (C) causes hereditary coproporphyria and is another rare type of porphyria. The symptoms are predominantly neuro-visceral. Diagnosis is confirmed with increased faecal and urinary coproporphyrinogen. Protoporphyrinogen oxidase deficiency (D) causes variegate porphyria which is caused by an autosomal dominant mutation of chromosome 14. It is relatively rare in the world except in South Africa where its incidence is as high as one in 300 (most probably due to the founder effect from early settlers). Attacks feature neuro-cutaneous features, although not necessarily together at the same time. It is almost always precipitated by drugs making it difficult to distinguish from AIP. In variegate porphyria, however, there is increased faecal protoporphyria as well as positive plasma fluorescence scanning. Uroporphyrinogen decarboxylase (E) causes porphyria cutanea tarda and can be inherited in an autosomal dominant manner. It is characterized by cutaneous features including bullous reactions to light, hyperpigmentation, as well as liver disease. Non-inherited causes include alcohol, iron, infections (hepatitis C and HIV) and systemic lupus erythematosus (SLE). Investigations reveal abnormal liver function tests, raised ferritin (always) and increased urinary uroporphyrinogen. This gives a characteristic pink red fluorescence when illuminated with a Wood’s lamp. Treatment is to avoid precipitants as well as chloroquine which complexes with porphyrins and promotes uroporphyrin release from the liver.

Answer 920

Although all of these factors can contribute to hyperuricaeamia, well controlled psoriasis (D) in this patient is unlikely to contribute to this attack of gout. Gout may be acute or chronic and is caused by hyperuricaemia. Hyperuricaemia is caused either by increased urate production or decreased urate excretion. Uric acid is a product of purine metabolism and is produced in three main ways – metabolism of endogenous purines, exogenous dietary nucleic acid and de novo production. De novo production involves metabolizing purines to eventually produce hypoxanthine and xanthine. The rate limiting enzyme in this pathway is called phosphoribosyl pyrophosphate aminotransferase (PAT) which is under negative feedback by guanine and adenlyl monophosphate. The metabolism of exogenous and endogenous purines, however, is the predominant pathway for uric acid production. The serum concentration of urate is dependent on sex, temperature and pH. A patient with acute gout does not necessarily have an increased urate concentration, therefore making serum urate levels an inaccurate method of diagnosis. The diagnosis of acute gout, which most commonly affects the first metatarsophalangeal joint (‘podagra’) is best made by observing weakly negatively birefringent crystals in an aspirate of the affected joint. This test is performed with polarized light – urate crystals are rhomboid and illuminate weakly when polarized light is shone perpendicular to the orientation of the crystal (hence negative birefringence). This is in contrast with pseudogout which has positively birefringent, spindly crystals – these illuminate best when the polarized light is aligned with the crystals. X-ray of the affected joint shows soft tissue inflammation early on, but as the disease progresses, well defined ‘punched out’ lesions in the juxta-articular bone appear with a late loss of joint space. There is no sclerotic reaction. Treatment is with a non-steroidal anti-iflammatory (e.g. diclofenac) in the acute phase or colchicine. Aspirin (E) is avoided because it directly competes for urate acid excretion in the nephron therefore worsening hyperuricaemia. After the acute attack settles, long term xanthine oxidase inhibitors (the enzyme responsible for the final production of urate) can be inhibited by allopurinol. Alternatively, but less commonly, uricosuric drugs such as probenecid may be used (e.g. prevention of cidofovir nephropathy). Finally rasburicase, recombinant urate oxidase, is a newer pharmacological treatment in the setting of chemotherapy to prevent hyperuricaeamia. Thiazide diuretics such as bendroflumethiazide (A) act by inhibiting NaCl transport in the distal convoluted tubule. They are contraindicated in gout as they increase uric acid concentration and are a well known precipitant of gout. Other diuretics do not have this property and therefore this patient should have his antihypertensive medication reviewed. Other side effects of thiazides include hyperglyacaemia, hypercalcaemia and increased serum lipid concentrations. Alcohol (C) increases urate levels in two ways – first it increases adenosine triphosphate turnover thus activating the salvage pathway producing more urate. It also decreases urate excretion in the kidney as it increases organic acids which compete for urate excretion in the nephron (much like aspirin). Chemotherapy (B) involves the destruction of malignant cells, which release all of their intracellular contents into the blood stream including purines. Widespread malignancy treated with chemotherapy can dramatically increase urate concentration. Therefore some patients undergoing chemotherapy are given prophylactic allopurinal to prevent this side effect as well as being encouraged to drink plenty of fluid to essentially dilute the urate produced. Psoriasis (D) is a dermatological condition characterized by discrete patches of epithelial hyperproliferation. There are different types including flexural, extensor, guttate, erythrodermic and pustulopalmar. Some special clinical signs associated with this condition often asked about include Koebner’s phenomenon (appearance of psoriatic plaques at sites of injury) and Auspitz’s sign (dots of bleeding when a plaque is scratched off representing reticular dermis clubbing with capillary dilatation). Severe psoriasis results in T-cell mediated hyperproliferation and eventual breakdown of cells releasing their intracellular contents resulting in hyperuricaemia in much the same mechanism as chemotherapy. The treatment for psoriasis includes phototherapy with ultraviolet light, topical agents including tar and oral tablets including antiproliferatives.

Answer 921

Type A is the most commonly associated with shock. Hypoperfusion of the tissues reduces the capacity of cells to continue aerobic respiration which leads to the formation of lactate via anaerobic respiration. Physiologically lactate concentration is around 1 mM but can rise up to 10 mM in extreme situations. It can also be falsely raised when replacing fluids which contain lactate (e.g. Hartmann’s solution – a common surgical fluid used to treat hypovolaemia). This is particularly important when dealing with suspected bowel ischaemia where fluid resuscitation is a vital initial management step. Lactate is often used to distinguish the presence of ischaemia which could be falsely elevated if using this fluid!.

Answer 922

Type B lactic acidosis occurs in the absence of significant oxygen delivery problems and usually occurs secondary to drugs. Common culprits include metformin in a patient with renal failure, paracetamol overdose, ethanol or methanol poisoning or acute liver failure. A useful and often quoted mnemonic to remember the causes of metabolic acidosis with a raised anion gap is MUDPILES: Methanol, Uraemia, Diabetic ketoacidosis, Propylene glycol, Isoniazid, Lactic acidosis, Ethylene glycol, Salicylates.

Answer 923

Metabolic acidosis with a normal anion gap implies the loss of bicarbonate or ingestion of hydrogen ions. The loss of bicarbonate is compensated for by chloride thus normalizing the anion gap. This is why this type of acidosis is sometimes called hyperchloraemic acidosis. Alternatively excessive chloride load (e.g. ammonium chloride ingestion) can cause acidosis where bicarbonate concentration reduces to compensate. The causes of this type of acidosis are generally due to problems either in the kidneys, GI tract or secondary to drugs. In the kidneys, failure of acid secretion is the main problem. This may be due to an intrinsic problem in the tubules (called renal tubular acidosis (RTA)) or secondary to drugs manipulating the acid transport systems.

Answer 924

Gastrointestinal loss of bicarbonate is the other main cause of metabolic acidosis with a normal anion gap. Diarrhoea caused by any pathology can lead to this problem. It is particularly associated in the setting of VIPoma (vasoactive intestinal peptide–oma). Also known as Verner Morrison syndrome, this rare disease is due to a non-beta islet cell tumour, usually in the pancreas. It causes profound diarrhoea, hypokalaemia, achlorhydia and flushing. Note vomiting causes hypochloraemic alkalosis due to the loss of hydrogen chloride in the stomach. Other gastrointestinal causes include pancreatic or biliary fistulae, ileostomy or ureterosigmoidostomy.

Answer 925

Urinary aniong gap Na + K - Cl- The UAG is a rough estimate of the bicarbonate concentration in the urine – the more negative the number, the higher the ammonium concentration and vice versa. This therefore helps distinguish the cause of the normal gap metabolic acidosis. If the bowel is responsible through bicarbonate loss, it would be sensible to assume the kidneys will try to compensate by increasing the ammonium excretion which is exchanged for hydrogen ions. The opposite is true for a loss of acid through the kidneys. A useful aide memoire is the word ‘neGUTive’. The negative urinary anion gap implies the gut is the culprit of the acidosis.

Answer 926

The negative urinary anion gap implies the gut is the culprit of the acidosis

Answer 927

Additional soilutes May also be seen in patients with hyperlipidaemia or hyperproteinaemia

Answer 928

Patients with chronic renal failure normally suffer from hyperphosphataemia, not hypophosphataemia (E). This is due to renal impairment of calcium metabolism which is under the control of parathyroid hormone (PTH) and vitamin D. In the evolving stages of chronic renal failure, a secondary hyperparathyroidism exists to compensate for the inability of the kidney to retain calcium and excrete phosphate. Therefore hypocalcaemia (D) is associated with chronic renal failure. This stimulates a physiological secretion of PTH by the parathyroid glands in an attempt to retain calcium. PTH is also responsible for excreting phosphate in the kidney, which is impaired due to the failure. Hyperphosphataemia also increases PTH levels as part of a negative feedback loop designed to maintain its homeostasis. Patients with chronic renal failure usually take phosphate binders (e.g. Sevelamer) which act to reduce phosphate absorption. This reduces PTH production which also reduces bone resorption thus improving renal osteodystrophy, a complex metabolic bone pathology associated with chronic renal failure. It is also important to reduce phosphate concentration to reduce ectopic calcification – if this precipitates in the tubules, this may reduce what little function there is left.

Answer 929

Resistant severe hyperkalaemia (\>7) Refractory pulmonary oedema Severe metabolica cidosis \<7.2 or BE \<10 Uraemic encephalopahty Uraemic pericarditis

Answer 930

Seen commonly in sick euthyroid syndrome Important to exclude secondary hypothyroidism as the assoicated hypoadrenalism could be fatal Another explanation is recently treated hyperthyroidism in which there is sometimes residual suppression of TSH following hyperthyroid treatment

Answer 931

Rare abnormality of albumin which results in increased binding affinity of albumin for T4, this interferes with te assay and shows a normal TSH and T3 with apparently increasd T4

Answer 932

Osteoblasts produce ALP In myeloma bone resorption occurst in an osteoclast dependant fashion with no osteoblastic activation, hence there is no raise in ALP

Answer 933

Ca x P Diagnostically \<2.4 whereas the normal value is 3

Answer 934

Seen in Paget's disease which reflects osteoclastic activity

Answer 935

Due to the highly vascular nature of pagetic bone

Answer 936

B This neonate, born with cataracts, poor feeding, lethargy, conjugated hyperbilirubinaemia with hepatomegaly and reducing sugars in the urine after starting milk, is likely to have galactosaemia (B). This is a rare autosomal recessive inherited condition most commonly due to a mutation in the galactose-1-phosphate uridyltransferase gene on chromosome 9p13. It results in excessive galactose concentrations when milk, which contains glucose and galactose, is introduced into the baby’s diet.

Answer 937

Galacitol produced by aldolase on galactose-1-P

Answer 938

Galactosaemia Because galactose is a reducing sugar, need to exclude glucose using glucose specific sticks

Answer 939

Galactose-1-P uridyltransferase level

Answer 940

Galactokinase (C) deficiency is another cause of galactosaemia but much less common. It is due to a defective galactokinase gene on 17q24

Answer 941

Fructose intolerance (A) is caused by fructose-1-phosphate aldolase deficiency which normally converts fructose-1-phosphate to dihydroacetone phosphate and glyceraldehyde. These products are further metabolized and can enter either glycolytic or gluconeogenesis pathways depending on the energy state of the cell. The explanation is made more complicated by the fact that there are three isoenzymes of fructose-1-phosphate aldolase (A, B and C) of which B is expressed exclusively in the liver, kidney and intestine as well as metabolizing three different reactions. Aldolase B can produce triose phosphate compounds which are central to the glycolytic pathway, but this can also be reversed making it important in gluconeogenesis. A deficiency therefore explains the hypoglycaemia experienced by these patients. Furthermore, the reduced fructose metabolism increases its blood levels which consequently changes the ATP:ADP ratio. This increases purine metabolism resulting in excess uric acid production which competes for excretion in the kidney with lactic acid.

Answer 942

Tyrosinaemia (E) is another autosomal recessive inherited disorder of metabolism which has three subtypes – types I, II and III. Type I is the hereditary form which has a specifically high incidence in Quebec, Canada and is characterized by a defect in fumarylacetoacetate hydrolase. The investigation of choice is urinary succinylacetone and treatment is to restrict dietary tyrosine and phenylalanine and to treat the liver failure, sometimes with a transplant.

Answer 943

Urea cycle disorders (D)

Answer 944

Crigler–Najar syndrome (D) is caused by a genetic defect in glucoronyl transferase which is responsible for transporting bilirubin into the hepatocyte.

Answer 945

Crigler najar caused by a genetic defect in glucoronyl-transferase Gilberts caused by defect in bilirubin uridinediphosphate-glucuornyltransferase Gilberts doesn't cause liver damage, relatively benign Unconjugated jaundice in the absence of haemolysis and normal plasma bile acids. No bilirubinuria and no increase in urobilinogen either

Answer 946

Only used in type 2, which is characterised by a partial reduciton in glucuronyl-transferase

Answer 947

because the pancreas is responsible for emulsification and digestion of fats which facilitate fat soluble vitamin absorption including vitamins A, D, E and K.

Answer 948

Prostate carcinoma also classically causes a sclerotic bone picutre but raises Ca levels whereas in Pagets, raised ALP is the principle biochemical abnormality

Answer 949

Hepatic: cholestasis, hepatitis, fatty liver, tumour Drugs: phenytoin, erythromycine, carbamezapine, verapamil 3. Bones: Bone disease: Paget's, renal osteodystrophy, fracture Non-bone disese: VitDD, malignancy, secondary hyperparathyroidism 4 Nonmetastatic malignant disease

Answer 950

Demetnia Diarrhoea Dermatitis Death

Answer 951

Because tryptophotan can also be converted into niacin Coexistence of kwashiorkor i.e. nutritional deficiency thus contributes

Answer 952

Primary: poor nutrition Secondary: malabsroptive problems Iatrogenic: isoniazid, zathioprine

Answer 953

Tocopherol (A) is also known as vitamin E,

Answer 954

Riboflavin deficiency (B), also known as vitamin B2,

Answer 955

Assaying erythrocyte levels Assayiong the activity of erythrocyte glutathione reductase which requires flavin adenin dinculeotide for its activity

Answer 956

Develop oin the conjunctiva and represent an accumulation of keratine Seen in Retnol (Vit A) deficiency

Answer 957

Vit A deficiency

Answer 958

Usually, drugs take between 4 and 5 half lives to reach a steady state. The half life is the time it takes for the plasma concentration of the drug to halve. Drugs such as phenytoin are monitored because underdosing will lead to no effect but overdosing will lead to toxicity. Most drugs have a wide therapeutic window – that is the difference between the minimum effective concentration and minimum toxic concentration. Drugs with narrow therapeutic windows may be suitable for drug monitoring to optimize treatment.

Answer 959

Antibiotics: gentamicin, vancomycin Anticonvulsants: phenytoin, lamotrigine Immunosuppressants: methotrexate, mycophenolate, tacrolimus Lithium Digoxin

Answer 960

Galstones Ethanol Trauma Steroids Mumps Autoimmune (polyarteritis nodosa) Scorpion venom (Trinidadian) Hypercalcaemia, hypertriglyceridaemia, gypothermia ERCP Drugs: thiazides, azathioprine, valproate, oestrogens

Answer 961

PaO2: \<8kPa Age \>55 Neutrophilia \>15 Calcium \<2 Renal function urea \>16 Enzymes: LDH \>600 or AST \>200 Albumin \<32 Sugar \>10mmol \>3= early ICU referral

Answer 962

Calcium Gluconate: stabilises myocardium, doesn't lower K Calcium resonium can be used to lower K over hours Insulin + Dextrose is mainstay, driving K into cells along with glucose. Nebulised salbutamol Sodium bicarbonate indirectly lowers K levels by neutralising acid int he blood, if H ion concentration decreases, K enters the cell. Lowering the K levels

Answer 963

Rises in 6-12h post infarction and rapidly normalises

Answer 964

Rises after 12h and takes 72h to normalise

Chemical Pathology Flashcards

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