General Medicine Flashcards
What diseases does Raynaud’s present in?
SLE
Poly myosotis
Dermatologists
What diseases are associated with ankylosing spondylitis?
Crohn’s
Ulcerative colitis
What are the differentials for a monoarthritis?
Septic
Crystal
OA
Trauma
Which conditions can cause an asymmetrical arthritis?
Reactive
Psoriatic
When should you aspirate a joint?
Any monoarthritis
Apart from inflamed/potentially infected skin e.g. Psoriatic plaque
How does a diagnosis of RA affect lifespan?
Women - 7y decrease
Men - 4y decrease
Why is RA associated with a decreased lifespan?
Cardiovascular risk
Infections
Lymphoma
What is the genetic link of RA?
Increased incidence in 1st degree relatives
Polymorphism of HLA Class II genes
How does RA lead to inflammatory arthritis?
Immune response triggers inflammation
Local production of inflammatory cytokines (esp. TNF-alpha and IL-1) causes amplification of inflammation
Synovial tissue proliferates and erodes the joint causing pannus formation
Activated macrophages in pannus produce collagenases & proteinases
Cartilage is eroded and this leads to joint instability and deformity
In what order are joints commonly affected in RA?
Small joints first - hands and feet
Larger joints later
What does the presence of rheumatoid nodules indicate?
Severe arthritis and risk of extra-articulate disease
What are the X-Ray features of RA?
Symmetrical. Spares DIPJs
Early: soft tissue swelling and osteopenia
Strophic bone erosions - peri articulate bare areas
Later: joint space narrowing
What is the imaging method of choice in early arthritis?
Ultrasound or MRI
What is DAS in RA?
Disease Activity Score
Incorporates ESR/CRP, counts of swollen/tender joints, fatigue, radio graphic findings and limitation of function
What are the diagnostic criteria for RA?
Need at least 4 of... Morning stiffness Arthritis of 3 or more joints Arthritis of hand joints Symmetrical Rheumatoid nodules Serum Rheumatoid Factor Radiographic changes
What is Rheumatoid Factor?
Antibody directed against IgG
What is anti-CCP?
Antibody, binds to CCPs in synovial and has a pathogenic role
What are the principles of management of RA?
Symptomatic relief
Modification of underlying disease
Adjunctive therapy with steroids (flare-ups)
Biological agents
What are the indications for DMARD use?
Persistent/progressive disease despite regular NSAIDs
Erosive disease on X-Ray
How long do DMARDs take to work?
2-3 months
What is the range of doses of methotrexate?
7.5 - 25mg per week
What are the side effects of methotrexate?
Myelosuppression Pneumonitis Pulmonary fibrosis Mucositis Diarrhoea, nausea, vomiting Hepatotoxicicity Teratogenic
What is the diagnosis when TSH is raised but T4 is low?
Hypothyroidism
What is the differential when TSH and T4 are both raised?
Thyroid-secreting tumour
Thyroid hormone resistance
What is the diagnosis when TSH is low but T4 & T3 are both normal?
Sub clinical hyperthyroidism
What is sick euthyroidism?
Thyroid tests may be abnormal
What monitoring is required with methotrexate?
Regular FBC, LFT, UEs and creatinine
Baseline CXR
What are the effects of sulfasalazine on T cells?
Inhibits proliferation
Inhibits IL-2 production
What are the effects of sulfasalazine on neutrophils?
Reduced chemotaxis and degranulation
What are the side effects of sulfasalazine?
Nausea Headache Dizziness Rash Infrequent: myelosuppression and heptatoxicity
Which DMARDs are safe in pregnancy?
Sulfasalazine
Hydroxychloroquine
What conditions is hydroxychloroquine used to treat?
RA and SLE
What is hydroxychloroquine?
Anti-malarial
Inhibits toll-like receptors to reduce inflammation
What are the side effects of azathioprine?
Myelosuppression
Infrequent hepatotoxicity
Flu-like illness at onset of therapy
Name 2 anti-TNF agents
Infliximab
Etanercept
Name an anti B cell agent
Rituximab
Which patients are currently eligible for treatment with biological agents?
Clinically active RA
Failure of standard therapy with at least 2 DMARDs
Withdrawn if ADR or no response at 6 months
How does psoriatic arthritis present?
Asymmetrical large joint oligoarthritis
Skin lesions/psoriatic nail changes
Dactylitis
How is the Achilles affected in psoriatic arthritis?
Enthesitis seen on USS or MRI
How is psoriatic arthritis managed?
NSAIDs
Physio/OT
Dermatologists - methotrexate may be helpful when skin is badly affected
Anti-TNF
What is the epidemiology of ankylosing spondylitis?
Typically
How does ankylosing spondylitis present?
Low back pain & stiffness, improved with exercise and not relieved by rest
SIJ tenderness
Fatigue, weight loss & low grade fever
What are the key investigations for ankylosing spondylitis?
CRP/ESR - raised in half of patients
HLA B27 - Not a screening test as 8% all British makes carry it. Only 20% of those with B27 have ank spond
MRI, CT or x-Ray affected area
How is ankylosing spondylitis managed?
Exercise and physio
NSAIDs
DMARDs if peripheral synovitis
What are the types of diabetic retinopathy?
Macular
Pre-proliferation
Proliferative
What is a reactive arthritis?
An aseptic inflammatory arthritis
Precipitated by a distant infection
What infections commonly cause reactive arthritis?
Non-bonobo cal urethritis/cervicitis Acute diarrhoea Chlamydia trachomatis Campylobacter Salmonella
What is Reiter’s syndrome?
Classic triad…
Urethritis
Conjunctivitis
Arthropathy
How do you manage reactive arthritis?
Bed rest
Intra-articulate steroids
NSAIDs
Define osteoporosis
Quantitative decrease in bone matrix components
I.e. Too little bone, but what there is is normal
What are the risk factors for osteoporosis?
Smoking Alcohol Steroid use Sedentary lifestyle Family history Lean body type
What endocrine disorders cause osteoporosis?
Gonadal insufficiency Hyperparathyroidism Hyperthyroidism T1DM Crushing's
What GI disease can cause osteoporosis?
IBD Chronic liver disease Eating disorders Coeliac disease Malabsorption
When is bone protection required with steroids?
Prednisolone >5mg daily for >3 months
& either over 65 or T score
What are the indications for DEXA scanning?
Predict fracture risk
Confirm diagnosis of osteoporosis where there is evidence of osteopenia on radiographs
Planned steroid use >5mg for >3 months and age >65
What is the T score?
Number of standard deviations away from the mean of a young person of the same gender and ethnicity
Measures risk of future fractures
How is the T score used to define osteoporosis?
What is the Z score?
Number of standard deviations away from an age, gender and weight-matched population
What is the FRAX tool?
Gives probability of hip/major osteoporotic fractures integrating clinical factors and Bone mineral density
What is the action of bisphosphonates?
Reduce osteoclasts function and ultimately cause their apoptosis
What is Fosamax?
Alendronate (bisphosphonate)
How can you pharmacologically stimulate bone formation?
Give synthetic PTH analogue e.g. Teriparatide
What is the most common cause of osteomalacia in the UK?
Calcium or Vitamin D deficiency
What are the causes of calcium and vitamin D deficiency?
Dietary
Poor sun exposure
Gastrectomy
Malabsorption
What are the biochemistry results like for someone with osteomalacia?
Low phosphate Low calcium Raised alk phos Low vit D High PTH
What is responsible for Gout?
Monosodium urate monohydrate crystals
How does urate affect gout?
Hyperuricaemia increases risk of attacks
Normal urate levels during an attack don’t exclude gout
What are the risk factors for gout?
Family history Excess alcohol Diuretics Renal disease Ciclosporin and tacrolimus Chemotherapy for malignancy Diet
What joints does gout commonly affect?
MTPJs Mid foot Ankles Knees Olecranon bursa
What are the diagnostic criteria for gout?
At least 2 of... Typical history Tophi Raised serum urate Crystals in joint during attack
What do urate crystals look like?
Needle-shaped
Strongly negatively birefringent
What are the X-Ray features of gout?
Soft tissue swelling
Opacities due to Tophi
How do you treat acute attacks of gout?
NSAIDs
Colchicine - reduces neutrophil chemotaxis
Corticosteroids
What are the indications for prophylaxis of attacks in gout?
2-3 acute episodes per year
Tophi and erosions present
Renal impairment/stones
What is used as prophylaxis in gout?
Allopurinol
What is the mechanism of action of allopurinol?
Xanthippe oxidase inhibitor - prevents conversion of purine to uric acid
What is responsible for pseudogout?
Calcium pyrophosphate dehydrate
What areas are commonly affected in pseudogout?
Knees
Wrists
Shoulders
Hips
How do you manage pseudogout?
Aspiration Injection NSAIDs Colchicine No prophylaxis
What comprises mixed connective tissue disease?
Systemic sclerosis & SLE & vascular disease
What does systemic sclerosis consist of?
Scleroderma (skin fibrosis) & vascular disease
What is CREST syndrome?
Calcinosis Raynaud's oEsophageal & gut dysmotility Sclerodactyly Telangiectasia
What is diffuse cutaneous systemic sclerosis?
Whole body may be involved
Organ fibrosis occurs early
Lots of skin fibrosis
How do you manage systemic sclerosis?
No cure
Immunosuppression if there is organ involvement or progressive skin disease
Control BP
Monitor renal function
What is Sjögren’s syndrome?
Inflammation and fibrosis of exocrine glands
Affects tear production, salivation plus other systemic features
What are the systemic features of Sjögren’s syndrome?
Polyarthritis Raynaud's Lymphadenopathy Vasculitis Lung, liver and kidney involvement Peripheral neuropathy Myosotis Fatigue
What are the signs of dermatomyositis?
Macular rash Heliotrope rash Nail fold erythema Gottron's papules on knuckles and elbows Subcutaneous calcification
How does polymyositis present?
Progressive symmetrical proximal muscle weakness
Myalgia & arthralgia
Can lead to dysphagia, dysphonia or resp muscle weakness
How does SLE typically present?
Non-specific: malaise, fatigue, myalgia and fever
Can mimic other systemic diseases
What parameters are used to monitor SLE disease activity?
Anti-dsDNA titres
Decreased C3 and C4
ESR raised (CRP normal in SLE)
How do you diagnose fibromyalgia?
Pain >3 months, both left and right sides occurring above and below the waist
What are the symptoms of giant cell arteritis?
Headache Temporal artery and scalp tenderness Jaw claudication Amaurosis fugax Sudden blindness
What is the treatment for GCA?
Mostly steroids - start immediately if GCA suspected to prevent irreversible blindness
What is Wegener’s granulomatosis?
Granulomatosis with polyangitis
Vasculitis of small/medium sized vessels
In what disease are anti-Jo antibodies found?
Polymyositis
What disease is found in 50% of patients with GCA?
Polymyalgia rheumatica
What are the features of Polymyalgia rheumatica?
> 50y
Shoulders and proximal limb muscles: aching, tenderness, morning stiffness
NO weakness
Fever, weight loss, fatigue, anorexia and depression
What are the blood results like in PMR?
Raised CRP and ESR
CK levels normal
What are the 5Rs of IV fluid therapy?
Resuscitation Routine maintenance Replacement Redistribution Reassessment
What is fluid resuscitation?
Fluids given urgently to restore circulation in hypovolaemia or fluid and electrolyte loss
E.g. Bleeding, dehydration, sepsis
When if IV fluid used for routine maintenance?
When patients can’t take fluids orally or enterally but have no deficits or ongoing losses
When is fluid replacement needed?
Not urgent but required on top of routine maintenance to correct losses or meet abnormal ongoing losses
E.g. GI losses, fever, burns
When is IV fluid required for redistribution?
When there are marked internal distribution changes or abnormal fluid handling
E.g. Sepsis, post-op, cardiac, liver or renal comorbidity
What proportion of body weight is water?
60%
How is total body water affected by obesity?
Lower % of body weight is water as adipose contains less water than lean tissue
How is body fluid divided between intra- and extra cellular compartments?
One thirds extracellular
Two thirds intracellular
What ions are mainly responsible for ECF osmolality?
Sodium
Chloride
Bicarbonate
What proportion of the ECF is intravascular?
A quarter
What is the intravascular volume dependent on?
Plasma on comic pressure - mainly due to albumin
What is the normal range for plasma albumin?
35-52g/L
What is the starling effect?
Hydrostatic pressure in capillaries drives fluid out
Oncotic pressure of plasma proteins draws fluid back in
What is the internal fluid balance?
Constant flow of fluid and electrolytes between the ECF and the GI tract
How much water is required per kg per day?
25 ml / kg / day
What is the physiological osmolality of plasma?
280 - 290 mOsm/kg
What is the volume obligatoire?
The minimum amount of urine needed to excrete waste products
About 500ml
How much does ECF need to be expanded by before oedema becomes an issue?
2 - 3 L
What is the urine : plasma urea ratio?
Osmolality ratio
Measure of the concentrating capacity of the kidney, in the presence of a water deficit
What is the normal range for plasma potassium?
3.5 - 5.3 mmol/L
How does hypokalaemia lead to further electrolyte disturbances?
Renal H+ reabsorption impaired to increase K+
Causes alkalosis
Decreased ability to excrete Na+ causes hypernatraemia
How is ADH affected by disease?
Levels increased
Retention of water
How much sodium is in normal saline?
154mmol/L
By what proportion does normal saline expand blood volume?
A quarter to a third
What are glucose solutions useful for doing?
Providing free water as it is distributed throughout total body water
What is the risk with giving too much glucose solution?
Hyponatraemia if too much given too quickly
Name a commonly used synthetic colloid
Hydroxymethyl starch (HES)
How do you give fluid resuscitation?
Rapid infusion (in less than 15mins) of 500ml boluses
Repeat as necessary until markers of volume status improve
How much glucose is used for routine maintenance?
50-100g per day
Who should you prescribe 20-25ml/kg/day fluid to?
Elderly/frail
Renal impairment/cardiac failure
Malnourished - at risk of referring syndrome
How do you assess fluid status clinically?
Blood pressure Fluid balance chart Peripheral/pulmonary oedema CRT Skin turgor Heart rate Resp rate Mucous membranes UEs JVP Thirst EWS
What are the indications for fluid resuscitation?
Systolic 90
Cap refill >2s
RR >20
EWS >5
How should you calculate fluid requirements for an obese patient?
Based on their ideal weight not their actual weight
How should you aim to increase sodium in a hyponatraemic patient?
No more than 3-5mmol/day
What is the normal range for blood glucose?
3.3 - 6 mmol/L
What is melaena?
Passage of black, tarry, foul-smelling stools
What is haematochezia?
Blood in the stools
What are the causes of pale stools?
Hepatitis
Gallbladder disorders
Malabsorption conditions
What is steatorrhea?
Fatty stool
Sticky and difficult to flush
Malabsorption syndromes
How should you investigate iron deficiency anaemia?
1st colonoscopy - more sinister potential causes
Upper GI endoscopy next if nothing found
What are the indications for an abdominal X-ray?
Acute abdominal pain
Small or large bowel obstruction
Acute exacerbation of IBD
Renal colic
What diameters show bowel obstruction?
Small bowel >3cm
Large bowel >6cm
Caecum >9cm
What is the difference between Haustra and valvulae conniventes?
Haustra are in the large bowel and only go part way across the wall
VCs are small bowel and go all the way across the wall
What is the main cause of small bowel obstruction?
Adhesions
What is the main cause of large bowel obstruction?
Colorectal cancer
How do you tell if the ileocaecal valve is competent on AXR and why is it significant?
If there is gas in the small bowel as well when the large bowel is obstructed
Perforation more likely if valve is competent: pressure higher in the large bowel if gas can’t flow back into the small bowel too
What is the coffee bean sign on abdominal X-ray?
Sigmoid volvulus starting in left iliac fossa and extending towards the right upper quadrant
What is the main indication for AXR in inflammatory bowel disease?
Suspected toxic mega colon
What is lead-pipe colon?
Chronic ulcerative colitis leading to loss of normal architecture
What is thumb-printing on abdominal X-ray?
Really thick haustra
Can result from anything causing oedema of the colon, but is classic of IBD
What is the flaciform ligament sign?
Indicates perforation - you only ever see the flaciform ligament when there’s gas either side of it
How many calories are there in 1g of protein?
4kcal
How many calories are there in 1g of carbohydrate?
4kcal
How many calories are there in 1g of fat?
9kcal
What is the daily calorie requirement per kg?
25kcal per kg
What does vitamin A deficiency lead to?
Blindness - vit A needed for retina
What is vitamin C needed for?
Immune system
Collagen synthesis
What is vitamin D needed for?
Calcium absorption
Bones
How does starvation cause malnutrition?
Hormone levels drop and lipase levels rise
Burn fat for energy - so lose fat
How does illness cause weight loss?
No time to adjust and increase lipase levels
All glucose and glycogen used first
Muscle broken down to provide glucose
So you lose muscles
What are the daily fluid requirements for an average person?
25 ml/kg/day
What does TPN provide?
Macro and micronutrients
Minerals
Fluid
How many calories does 1unit of alcohol provide?
56kcal
What are the causes of scurvy?
Vitamin C deficiency
Poor, pregnancy or strange diet
What are the signs of scurvy?
Anorexia & cachexia Gingivitis Loose teeth Smelly breath Bleeding from gums, nose, hair follicles Muscle pain and weakness Oedema
What is Beriberi disease?
Vitamin B1 / thiamine deficiency
How do you treat beriberi?
Give thiamine urgently
May lead to wernicke’s encephalopathy
What is pellagra disease?
Lack of nicotinic acid
Triad: diarrhoea, dementia, dermatitis
What is xerophthalmia?
Vitamin A deficiency
Dry conjunctivae
Corneas cloudy and soft
How does malabsorption present?
Diarrhoea Weight loss Lethargy Steatorrhea Bloating
What are the main causes of malabsorption in the UK?
Coeliac disease
Chronic pancreatitis
Crohn’s disease
What is the prevalence of coeliac disease?
1 in 300-1500
What is the pathophysiology of coeliac disease?
T-cell mediated autoimmune
Affects small bowel
Prolamin intolerance
Causes villous atrophy and malabsorption
When are the peaks in incidence of coeliac disease?
Infancy
50-60y
How do you diagnose coeliac disease?
Low Hb, B12 and ferritin
Antibodies: alpha-gliadin, transglutaminase, anti-endomysial
Duodenal biopsy
What are the complications of coeliac disease?
Anaemia Lactose intolerance GI T-cell lymphoma Increased risk of malignancy Myopathies/neuropathies Hyposplenism Osteoporosis
What are the causes of chronic pancreatitis?
Alcohol Haemochromatosis Pancreatic duct obstruction Hyperparathyroidism Congenital
How does chronic pancreatitis present?
Epigastric pain radiating to back Relieved by sitting forward or hot water bottles Bloating Steatorrhea Weight loss
What is the medical management of chronic pancreatitis?
Analgesia Lipase Creon (enzymes) Fat-soluble vitamins ? Insulin requirements
Diet: no alcohol and low fat
When is surgery indicated for chronic pancreatitis?
Unremitting pain
Narcotic abuse
Weight loss
What are the complications of chronic pancreatitis?
Pseudocyst Diabetes Biliary obstruction Aneurysm Splenic vein thrombosis Gastric varices Pancreatic carcinoma
What is the most common cause of upper GI bleeding?
Peptic ulcer disease
What are the common causes of upper GI bleeding?
Peptic ulcer disease Gastroduodenal erosions Oesophagitis M-W tear Varices Malignancy
How can you tell if a patient is shocked following upper GI bleed?
Cool/clammy with decreased capillary refill
Pulse over 100
Systolic BP lower than 100
Urine output less than 30ml/h
What is the mortality rate from upper GI re bleeding?
40%
What are the alarm symptoms related to dyspepsia?
Anaemia Loss of weight Anorexia Rapid onset Melaena/haematemesis Swallowing difficulty
What are the risk factors for developing a duodenal ulcer?
H.pylori infection
Drugs e.g. NSAIDs, steroids, SSRIs
When is pain from a duodenal ulcer worst?
Before meals or at night, i.e. When the stomach is empty
How do you manage peptic ulcers?
- Lifestyle - reduce smoking, alcohol and aggravating foods
- H.pylori eradication (triple therapy)
- Drugs to reduce acid secretion: PPIs or H2 antagonist
- Surgery
What are the potential complications of peptic ulcers?
Bleeding
Perforation
Malignancy
Gastric outflow obstruction
Define GORD
Reflux of stomach contents causing symptoms of heartburn, with more than 2 episodes per week
Give some causes of GORD
Hiatus hernia Abdo obesity Smoking or alcohol Overeating H.pylori Gastric acid hypersecretion Pregnancy
What are the potential complications of GORD?
Oesophagitis Ulcers Benign stricture Iron deficiency Barrett's oesophagus
What can cause oesophagitis?
Corrosives NSAIDs Herpes Candida Duodenal or gastric ulcer Cardiac disease
What are the conservative management measures for GORD?
Raise whole bed Weight loss Smoking cessation Small, regular meals Avoid hot/fizzy drinks, spicy food Don't eat within 3hours of going to bed
What is a sliding hiatus hernia?
Gastro-oesophageal junction slides up into chest
Acid reflux may accompany
What is a rolling hiatus hernia?
Junction remains in abdomen
Bulge of stomach herniated into chest alongside oesophagus
Acid reflux uncommon (junction remains competent)
What type of hiatus hernia should be surgically repaired?
Rolling
This can strangulate so repair prophylactically
What is the treatment for C.difficile colitis?
Metronidazole 400mg/8h
Stop causative antibiotics
When is colectomy required for c.diff colitis?
Toxic megacolon
Raised LDH
Rapidly deteriorating
Define extensive UC
Extending beyond the splenic flexure
How does smoking affect ulcerative colitis?
Decreases incidence
May induce remission
How does smoking affect Crohn’s?
Increases incidence
What are the cardinal symptoms of ulcerative colitis?
Bloody diarrhoea
Urgency
Tenesmus
Define mild ulcerative colitis
Fewer than 4 stools per day
No systemic features
Define severe ulcerative colitis
More than 6 stools per day
+ blood
+ systemic features
What are the extra-intestinal features of UC that are related to the disease activity?
Erythema nodosum
Aphthous ulcers
Episcleritis
Acute Arthropathy
What are the extra-intestinal features of UC that are unrelated to the disease activity?
Sacroileitis
Ank spond
PSC
What are the aims of treatment in ulcerative colitis?
Induce remission in acute disease
Maintain remission
Improve quality of life
Decrease risk of colorectal cancer
Why do UC patients get heparin?
IBD flares cause a prothrombotic state which can be severe
How are steroids used in UC?
Induce remission
No role in long term therapy due to side effects
Why is important to slowly weane off steroids in UC?
Doing it too quickly can cause flare up
How is azathioprine used in UC?
Steroid-sparing
Maintenance of remission
Takes at least 6 weeks to work
What are the side-effects of azathioprine?
Flu-like GI upset Leukopenia Hepatitis Pancreatitis Rash Infections
How is ciclosporin used in UC? What is its mechanism of action?
Salvage therapy in severe refractory colitis
Calcineurin inhibitors
When are laxatives used in UC?
Proximal constipation
Relieving this can induce remission in left-sided disease
What are the indications for surgery in UC?
Perforation
Massive haemorrhage
Toxic dilatation
Failed medical therapy
How are platelet measurements useful in IBD?
High platelets indicates severity of disease
What is the prevalence of Crohn’s disease?
0.5-1 per 1000
When is the peak age for Crohn’s to present?
20 - 40y and 60 - 70y
What are the symptoms of Crohn’s?
Diarrhoea and urgency Abdo pain Weight loss Fever Malaise Anorexia
What are the examination signs of Crohn’s?
Apthous ulcers Abdo tenderness Perinatal abscess, fistulae Clubbing Skin, joint and eye problems
Why is albumin low in Crohn’s?
The liver switches protein synthesis to favour inflammatory proteins eg CRP
What are the indications for surgery in Crohn’s?
Failure of medical management Perforation Obstruction by stricture Fistula Abscess
What is the incidence of IBS?
10-20% population
What symptoms should make you think of something other than IBS?
Older than 40 Less than 6 month history Anorexia and weight loss Waking at night with pain or diarrhoea Mouth ulcers Abnormal CRP, ESR, Hb or coeliac serology
Why is ispaghula better than lactulose to relieve constipation in IBS?
Lactulose ferments so can exacerbate bloating
How do you treat bloating?
Mebeverine 135mg QDS
This is an antispasmodic
At what point does hyperbilirubinaemia cause visible jaundice?
> 60umol/L
Why do you get dark urine and pale faeces alongside jaundice?
Conjugated bilirubin enters urine, darkening it
Less conjugated bilirubin reaches the gut, so there is less in faeces and they are pale
What do pale stools and dark urine commonly indicate?
Chile stasis
How does drug-induced jaundice present?
DRESS:
Drug Rash with Eosinophilia and Systemic Symptoms
What does decompensated liver disease mean?
Signs and symptoms present and patient generally unwell
What are the 2 main pathological processes leading to the clinical features of chronic liver disease?
Reduced hepatocyte mass
Portal hypertension
What clinical features are caused by reduced hepatocyte mass?
Encephalopathy
Loss of lean body mass
Coagulopathy
What clinical features are caused by portal hypertension?
Varices
Ascites
Splenomegaly
What are the features of hepatic encephalopathy?
Reduced attention span Reversed sleep pattern Metabolic flap Constructional dyspraxia Coma
What does cirrhosis mean?
Irreversible liver damage
Loss of normal architecture plus modular regeneration
What are the causes of cirrhosis?
Chronic alcohol abuse HBV or HCV infection Genetic disorders Non-alcoholic fatty liver Autoimmune eg PBC Drugs
How does cirrhosis lead to kidney problems?
Reduced hepatic clearance of immune complexes
Means they become trapped in the kidney
Commonly IgA nephropathy
What are the signs of chronic liver disease found in the hands?
Clubbing
Palmar erythema
Leuconychia
What are the causes of decompensation of chronic liver disease?
Drugs (eg alcohol) Electrolyte disturbance Sepsis GI bleed Hepatoma
How is encephalopathy graded?
I altered mood
II drowsy
III stupor
IV coma
What is fulminant hepatic failure?
Massive necrosis of liver cells
Leads to severe liver function impairment
What is the most common cause of fulminant hepatic failure?
Paracetamol
What emergencies should you look out for in hepatic failure?
Sepsis
Hypoglycaemia
GI bleeds/varices
Encephalopathy
How do you treat cerebral oedema?
20% mannitol IV
How do you treat Ascites?
Fluid restriction
Low salt diet
Diuretics
What drugs should be avoided in hepatic failure?
Constipation drugs
Oral hypoglycaemics
Saline IV
All drugs with hepatic metabolism
NB warfarin’s effects are enhanced in hepatic failure
Name 5 hepatotoxic drugs
Paracetamol Isoniazid Methotrexate Azathioprine Oestrogen Salicylates Tetracycline 6-MP
How does ammonia cause cerebral oedema?
Ammonia builds up as liver fails
Passes into brain - taken up by astrocytes
Convert glutamate to glutamine to clear ammonia
Glutamine has osmotic effect and draws water into astrocytes
Leads to cerebral oedema
Define hepatorenal syndrome
Cirrhosis + Ascites + Renal Failure
Name a screening tool for alcoholism
CAGE
What is the prognosis for an alcoholic with cirrhosis who keeps drinking?
48% 5yr survival
What type of anaemia is seen in alcoholism and why?
Macrocytic
Marrow depression, GI bleeds, folate deficiency and haemolysis
What are the CVS complications of alcoholism?
Arrhythmias
Hypertension
Cardiomyopathy
Sudden death due to binges
What are the symptoms of alcohol withdrawal?
Tachycardia Hypotension Tremor Convulsions Fits Hallucinations
How do you manage alcohol withdrawal?
Beware of hypotension
Chlordiazepoxide 10-50mg QDS PO for 3 days & gradually wean over 7-10days
Vitamin supplements eg pabrinex
What is the effect of disulfiram?
Causes acetaldehyde build-up and unpleasant effects when alcohol is consumed
Used to treat chronic alcohol dependence
What is Charcot’s triad?
Fever, pain and jaundice
Cholangitis
Describe the typical pain of biliary colic
Central, severe and constant
Radiates to back
Lasts for as long as the stone is stuck
Doesn’t have to be everyday, can be any frequency
NB no abdominal tenderness
What are the alarm symptoms related to dyspepsia?
Anaemia Loss of weight Anorexia Rapid onset Melaena/haematemesis Swallowing difficulty
What are the risk factors for developing a duodenal ulcer?
H.pylori infection
Drugs e.g. NSAIDs, steroids, SSRIs
When is pain from a duodenal ulcer worst?
Before meals or at night, i.e. When the stomach is empty
How do you manage peptic ulcers?
- Lifestyle - reduce smoking, alcohol and aggravating foods
- H.pylori eradication (triple therapy)
- Drugs to reduce acid secretion: PPIs or H2 antagonist
- Surgery
What are the potential complications of peptic ulcers?
Bleeding
Perforation
Malignancy
Gastric outflow obstruction
Define GORD
Reflux of stomach contents causing symptoms of heartburn, with more than 2 episodes per week
Give some causes of GORD
Hiatus hernia Abdo obesity Smoking or alcohol Overeating H.pylori Gastric acid hypersecretion Pregnancy
What are the potential complications of GORD?
Oesophagitis Ulcers Benign stricture Iron deficiency Barrett's oesophagus
What can cause oesophagitis?
Corrosives NSAIDs Herpes Candida Duodenal or gastric ulcer Cardiac disease
What are the conservative management measures for GORD?
Raise whole bed Weight loss Smoking cessation Small, regular meals Avoid hot/fizzy drinks, spicy food Don't eat within 3hours of going to bed
What is a sliding hiatus hernia?
Gastro-oesophageal junction slides up into chest
Acid reflux may accompany
What is a rolling hiatus hernia?
Junction remains in abdomen
Bulge of stomach herniated into chest alongside oesophagus
Acid reflux uncommon (junction remains competent)
What type of hiatus hernia should be surgically repaired?
Rolling
This can strangulate so repair prophylactically
What is the treatment for C.difficile colitis?
Metronidazole 400mg/8h
Stop causative antibiotics
When is colectomy required for c.diff colitis?
Toxic megacolon
Raised LDH
Rapidly deteriorating
Define extensive UC
Extending beyond the splenic flexure
How does smoking affect ulcerative colitis?
Decreases incidence
May induce remission
How does smoking affect Crohn’s?
Increases incidence
What are the cardinal symptoms of ulcerative colitis?
Bloody diarrhoea
Urgency
Tenesmus
Define mild ulcerative colitis
Fewer than 4 stools per day
No systemic features
Define severe ulcerative colitis
More than 6 stools per day
+ blood
+ systemic features
What are the extra-intestinal features of UC that are related to the disease activity?
Erythema nodosum
Aphthous ulcers
Episcleritis
Acute Arthropathy
What are the extra-intestinal features of UC that are unrelated to the disease activity?
Sacroileitis
Ank spond
PSC
What are the aims of treatment in ulcerative colitis?
Induce remission in acute disease
Maintain remission
Improve quality of life
Decrease risk of colorectal cancer
Why do UC patients get heparin?
IBD flares cause a prothrombotic state which can be severe
What is the normal range for blood glucose?
3.3 - 6 mmol/L
What are the symptoms of hyperglycaemia?
Polyuria Polydipsia Weight loss Visual blurring Genital thrush
What are the normal actions of insulin on glucose metabolism?
Inhibits liver glycogen breakdown
Enhances glucose uptake by liver
Enhances glucose uptake by muscle and adipose
What is the pathophysiology of type 1 diabetes?
Autoimmune destruction of beta cells
Causes absolute insulin deficiency
What proportion of all diabetes is type 1?
5-10%
Why are ketones produced?
Ketone production normally suppressed by insulin
In starvation or insulin deficiency, ketone production is activated
What hormones antagonise the action of insulin?
Cortisol
Growth hormone
Glucagon
Adrenaline
How do you manage cardiovascular risk in diabetics?
Target other risk factors e.g. Hypertension Smoking Obesity Hyperlipidaemia
What is DAFNE?
Dose adjustment for normal eating
Course to educate diabetics on insulin doses
What is the most effective time for lifestyle intervention in type 2 diabetes?
Phase of impaired glucose tolerance
What does HbA1c measure?
Average glucose levels over the past 8 weeks
What are the microvascular complications of diabetes?
Nephropathy
Neuropathy
Retinopathy
What are the macrovascular complications of diabetes?
Cerebrovascular
Peripheral vascular
Cardiovascular
What is the mechanism of action of metformin?
Decreases hepatic gluconeogenesis
Increases muscle glucose metabolism
Mild anorexic
What are the side effects of Metformin?
GI upset
Rarely lactic acidosis
What are the contraindications for Metformin?
Renal failure
Hepatic impairment
Give an example of a sulfonylurea
Gliclazide
What is the mechanism of action of sulfonylureas?
Increased insulin release from beta cells
Binds and closes K+ channels to depolarise the cell
What are the side effects of sulfonylureas?
Weight gain
Hypoglycaemia
Give an example of a thiazolidinedione
Pioglitazone
What is the mechanism of action of Pioglitazone?
Activates PPAR-alpha to stimulate transcription of glut-1 and -4
What is the mechanism of action of acarbose?
Inhibits carbohydrate digestion to reduce glucose absorption
What are the side effects or acarbose?
Bloating
diarrhoea
What is exenatide?
GLP-1 receptor analogue
Stimulates insulin release
Inhibits glucagon release
What is the mechanism of action of dapagliflozin?
Inhibits SGLT2 to inhibit renal glucose reabsorption
What are the side effects of dapagliflozin?
UTI
Genital thrush
Hypoglycaemia
Increased urination
Give 2 examples of ultra-fast insulin
Humalog
Novorapid
Give an example of a mixed insulin preparation and its content
NovoMix
30% short acting
70% long acting
Give 2 examples of long-acting insulin
Glargine
Insulin detemir
When is glargine taken?
Bedtime
What is a QDS insulin regime?
Before meals: ultrafast
Bedtime long-acting
What is a good starter regime for T2 diabetics switching from tablets to insulin?
Once-daily long-acting insulin at bedtime
Can retain Metformin
How are insulin requirements affected by illness?
Insulin requirement increases despite eating less
What is the target blood pressure for diabetics?
Less than 140/80mmHg
What is the target BP for diabetics with CKD?
Less than 125/75 mmHg
What is the pathophysiology of diabetic retinopathy?
Capillary basement membrane thickening leads to leaky vessels, occluded vessels and macular oedema
Why are diabetics screened for retinopathy?
Allows laser photo coagulation to be used
Stops production of angiogenesis factors from is ischaemic retina
Blindness is preventable!
How does pre-proliferative retinopathy look?
Cotton-wool spots
Haemorrhages
Venous bleeding
How does proliferative retinopathy look?
New vessels have formed (they are likely to bleed)
Haemorrhages
How do you treat macular oedema?
Intra-vitreal steroids
Prompt laser treatment
Why do diabetics get cataracts?
Acute hyperglycaemia induces osmotic changes in the lens
Reversed when blood glucose returns to normal
What is the increased cardiovascular risk for diabetics?
MI 4 times more likely
Stroke twice as likely
What is the pathophysiology of diabetic foot disease?
Peripheral vascular disease
Peripheral neuropathy
Increased susceptibility to infection
What are the consequences of diabetic foot?
Ulceration
Infection
Gangrene
Charcot’s foot
What are the features of diabetic ketoacidosis?
Gradual drowsiness Vomiting Dehydration Abdo pain Polyuria/polydipsia/weight loss Ketotic breath Coma Deep breathing
How do you diagnose DKA?
Blood pH
What are the potential complications of DKA?
Cerebral oedema
Aspiration pneumonia
Hypokalaemia/magnaesemia/phosphataemia
Thromboembolism
How do you treat DKA?
50units actrapid insulin in 50ml 0.9% saline
Continue their long-acting insulin
What is the target decrease in blood ketones in DKA?
0.5mmol/L/h
What are the common triggers of DKA?
Infection Surgery MI Pancreatitis Chemotherapy Antipsychotics Poor insulin dosing or non-compliance
What is HONK?
Hyperosmolar non-ketotic syndrome
Dehydration + blood glucose >35mmol/L
How do you treat HONK?
Slow rehydration: 110-220mmol/Kg deficit
Use 0.9% NaCl
Why should blood glucose be maintained between 10 and 15 mmol/L for the first 24h in HONK?
To avoid cerebral oedema
How do you treat hypoglycaemic coma?
20-30g glucose IV
(Eg 200-300ml 10% dextrose)
Give sugary drinks and meal once conscious
Define hypoglycaemia
Plasma glucose
What are the autonomic symptoms of hypoglycaemia?
Sweating Anxiety Hunger Tremor Palpitations Dizziness
What are the neuroglycopenic symptoms of hypoglycaemia?
Confusion Drowsiness Visual disturbance Seizures Coma
What is the main cause of fasting hypoglycaemia?
Insulin or sulfonylurea treatment
Increased activity, missed meal or an overdose
What are the causes of hypoglycaemia in non-diabetics?
EXPLAIN: EXogenous drugs Pituitary insufficiency Liver failure Addison's disease Islet cell tumours Non-pancreatic neoplasms
How do you manage hypoglycaemia?
Oral sugary drink and long-acting starch (eg sandwich)
If can’t swallow: IV 25-50ml 50% glucose
If no IV access: 1mg IM glucagon
What are the risks of gestational diabetes?
Miscarriage Pre-term labour Pre-eclampsia Congenital malformations Macrosomia
What are the risk factors for gestational diabetes?
Older than 25 Family history Overweight Non-Caucasian HIV Previous GDM
What proportion of patients with gestational diabetes go on to develop T2DM later in life?
50%
What % of pregnancies are complicated by gestational diabetes?
3.5%
What blood glucose level should be maintained in the peri operative period?
6-11mmol/L
How long should VRII be maintain postop?
Until eating and drinking normally
How is blood glucose affected by being acutely ill?
Blood glucose higher due to:
Cortisol, adrenaline and growth hormone release
Physical inactivity
Alteration in diet
What is the initial management for Hyperlipidaemia?
Diet modification
Address other CVS risk factors: smoking, hypertension, excess weight
What are the target levels for cholesterol?
Total
What drugs are used to treat hypercholesterolaemia?
Statins
Ezetimibe/fibrates
Bile acid-binding resins
What drugs are used to treat hypertriglyceridaemia?
Fibrates
Nicotinic acid
Fish oil capsules
What are the indications for starting statin therapy?
Diabetes mellitus and over 40y
Total cardiovascular disease risk >20% over 10y
2 of: family history, albuminuria, hypertension and smoking
Men with LDL>6.5 despite dietary change
Familial hypercholesterolaemia
When are statins indicated for secondary prevention?
Coronary artery disease
TIA or strike
Peripheral artery disease
What is low dose dexamethasone suppression test used for?
Screening for cushing’s
What is the high dose dexamethasone suppression test used for?
Determining pituitary vs adrenal cause of Cushing’s syndrome
What is the synacthen test?
Normal response is to cause cortisol release form the adrenals
Test of primary adrenal failure
What is the insulin stress test?
Should cause cortisol release to >600
Insulin-induced hypoglycaemia
Good test for hypopitutarism as it tests ACTH and GH reserve
What are the contraindications for the insulin stress test?
Epilepsy
Ischaemic heart disease
What is the glucose tolerance test?
Should suppress growth hormone
Test for acromegaly
Bonus of glucose will suppress GH in normal people, failure to suppress in acromegaly
What are the effects of pituitary tumours?
Excess hormone production
Physical effects of lump on surrounding structures
What are the features of acromegaly?
Growth of hands and feet Coarse features Headache Sweating Carpal tunnel syndrome
Which hormones are affected by something blocking the pituitary stalk?
Increase in all pituitary hormones
EXCEPT prolactin as this is mainly under inhibitory control by dopamine
What is IGF-1?
Released from the liver in response to growth hormone
This is the main way growth hormone takes its effect
What is the treatment for acromegaly?
Somatostatin analogues eg ocreotide
Growth hormone receptor blockers eg pegvisomant
How do you distinguish between active and inactive acromegaly?
Active: headaches, sweating
Inactive means they have already had treatment, but may still have big features
What are the features of Cushing’s syndrome?
Moon fancies Thinning of skin Easy bruising Buffalo hump Central obesity Abdominal striae Hypertension/diabetes
How do you do a low dose dexamethasone suppression test?
0.5mg dexamethasone QDS for 48h
If cortisol decreases to less than 30nmol/L, it is not true Cushing’s syndrome
What are the physical effects of a pituitary tumour?
Hypopitutarism
Visual field disturbance (bitemporal hemianopia)
Headache
What effect does compression of the pituitary stalk have on prolactin?
Causes hyperprolactinaemia
What are the features of primary adrenal insufficiency?
Hyponatraemia
Hyperkalaemia
Postural hypotension
Increased pigmentation
What are the causes of primary adrenal insufficiency?
Autoimmune TB Iatrogenic Sepsis Infiltrative disease
What is the management of a hypo adrenal crisis?
Fluid resuscitation Glucose Steroids Treat sepsis Find cause
What can Addison’s disease mimic clinically?
Depression
Often not diagnosed until they have a crisis
What are the symptoms of hypothyroidism?
Bradycardia Slow reflexes Goitre Carpal tunnel Weight gain Depression Fatigue Cold intolerance Constipation
What are the symptoms of hyperthyroidism?
Weight loss despite good appetite Tremor Palpitations Heat intolerance Diarrhoea Irritability Tachycardia Proptosis Hyperreflexia Lid lag Goitre
In what order are hormones affected by hypopituitarism?
Growth hormone Gonadotrophins Prolactin TSH ACTH
What are the usual causes of panhypopituitarism?
Irradiation
Surgery
Pituitary tumour
What is the most common type of pituitary tumour?
Benign adenoma
What cranial nerves are affected by pituitary tumours?
CN III, IV and VI
What is the management of a prolactinoma?
Medical therapy with dopamine agonist
What is pituitary apoplexy?
Rapid bleed into a pituitary tumour
Causes rapid expansion
Why does hyperprolactinaemia present earlier in females than males?
Causes menstrual disturbance in females
Erectile dysfunction in males
Why does hyperprolactinaemia cause hypogonadism, infertility and osteoporosis?
Inhibits secretion of gonadotrophin releasing hormone
Where is dopamine released from?
Hypothalamus
What are the causes of hyperprolactinaemia?
Excess pituitary production eg prolactinoma
Disinhibition eg compression of pituitary stalk causes reduced local dopamine levels
Dopamine antagonist use
What drugs can cause hyperprolactinaemia?
Metoclopramide
Haloperidol
Antipsychotics
(Dopamine antagonists)
Name a dopamine agonist
Bromocriptine
Why are free T3 and T4 levels a more useful test than total hormone levels?
Total levels are affected by TBG levels, which are increased in pregnancy or HRT
What are thyroid function tests like in hyperthyroidism?
Raised T4
Low TSH
At what time of day are TSH levels lowest and highest?
Lowest about 2pm
Highest in the dark
What is ‘sick euthyroidism’?
Thyroid function tests may be deranged with any systemic illness
Typically all results are low
Retest when recovered
Name the thyroid autoantibodies implicated in grave’s and hashimoto’s disease
Anti thyroid peroxidase
Antithyroglobulin
Which patients should be screened for thyroid abnormalities?
AF Hyperlipidaemia DM Gestational diabetes Those on lithium and amiodarone Down's/turner's syndrome Addison's disease
What proportion of thyrotoxicosis is due to Grave’s disease?
Two thirds
What is the male:female ratio for hyperthyroidism?
1:9
What is the pathophysiology of Grave’s disease?
Circulating IgG antibodies bind to TRH receptors and cause thyroid enlargement and increased hormone production
What proportion of patients with Grave’s disease get thyroid eye disease?
25-50%
Define proptosis
Eyes protruding beyond the orbit
Have to look from above to see this
How do you treat symptoms of hyperthyroidism?
Beta blockers
How do you prescribe carbimazole?
- Titration: start with 20-40mg/day PO for 4 weeks. Reduce depending on TFTs every 1-2 weeks
- Block-replace: give carbimazole and thyroxine together
What are the side effects of carbimazole?
Agranulocytosis: see GP if they get an infection, need FBC
What are the contraindications of radio-iodine treatment?
Pregnancy
Lactation
What structures may be damaged during thyroidectomy?
Recurrent laryngeal nerve
Parathyroid glands
What are the potential complications of thyrotoxicosis?
Heart failure Angina AF Osteoporosis Ophthalmopathy Gynaecomastia
What is myxoedema?
Hypothyroidism
What are the causes of hypothyroidism?
Primary atrophic hypothyroidism (common)
Hashimoto’s thyroiditis
Iodine deficiency
What is primary atrophic hypothyroidism?
Lymphocytic infiltration of thyroid leads to atrophy
No goitre
What diseases is hashimoto’s disease related to?
Type 1 diabetes
Addison’s disease
Pernicious anaemia
What problems can hypothyroidism cause in pregnancy?
Eclampsia Anaemia Premature birth Low birthweight Stillbirth Post-Partum haemorrhage
What is the treatment for hypothyroidism?
Levothyroxine 50-100ug/day
What is sub clinical hypothyroidism?
TSH raised but T3 and T4 are normal
Asymptomatic
What is the effect of amiodarone on the thyroid and why?
Can cause hyper or hypothyroidism
Amiodarone is structurally similar to T4 (contains lots of iodine)
What types of hormone does the adrenal cortex produce?
Steroids:
Mineralocorticoids
Glucocorticoids
Androgens
How is cortisol excreted?
Urinary free cortisol
What is the most common cause of Cushing’s syndrome?
Oral steroids
What is the most common endogenous cause of Cushing’s syndrome?
80% due to increased ACTH
Pituitary adenoma (Cushing’s disease) is the most common cause of this
What is the normal range for blood glucose?
3.3 - 6 mmol/L
What are the symptoms of hyperglycaemia?
Polyuria Polydipsia Weight loss Visual blurring Genital thrush
What are the normal actions of insulin on glucose metabolism?
Inhibits liver glycogen breakdown
Enhances glucose uptake by liver
Enhances glucose uptake by muscle and adipose
What is the pathophysiology of type 1 diabetes?
Autoimmune destruction of beta cells
Causes absolute insulin deficiency
What proportion of all diabetes is type 1?
5-10%
Why are ketones produced?
Ketone production normally suppressed by insulin
In starvation or insulin deficiency, ketone production is activated
What hormones antagonise the action of insulin?
Cortisol
Growth hormone
Glucagon
Adrenaline
How do you manage cardiovascular risk in diabetics?
Target other risk factors e.g. Hypertension Smoking Obesity Hyperlipidaemia
What is DAFNE?
Dose adjustment for normal eating
Course to educate diabetics on insulin doses
What is the most effective time for lifestyle intervention in type 2 diabetes?
Phase of impaired glucose tolerance
What does HbA1c measure?
Average glucose levels over the past 8 weeks
What are the microvascular complications of diabetes?
Nephropathy
Neuropathy
Retinopathy
What are the macrovascular complications of diabetes?
Cerebrovascular
Peripheral vascular
Cardiovascular
What are the causes of decreased ACTH levels?
Adrenal adenoma/cancer
Adrenal modular hyperplasia
Oral steroids
What are the symptoms of Cushing’s?
Weight gain Depression, lethargy, irritability Psychosis Proximal weakness Gonadal dysfunction Acne Recurrent Achilles rupture
What are the signs of Cushing’s?
Central obesity Moon face Buffalo hump neck Supraclavicular fat distribution Skin and muscle atrophy Bruises, purple abdo striae Osteoporosis Hypertension Hyperglycaemia Increased infection risk and poor healing
Why are random cortisol levels not reliable?
Cortisol is a stress hormone so can be increased due to the situation eg illness
What are incidentalomas?
Non-functioning masses found on imaging
Not the actual cause of Cushing’s
5% have adrenal incidentalomas
10% have pituitary incidentalomas
What are the causes of pseudo-Cushing’s?
Alcohol excess
Obesity
Depression
What is the treatment for Cushing’s disease?
Transphenoidal removal of adenoma
When can adrenal insufficiency suddenly develop?
In those on long-term steroids
Septic individuals
Malignancy
What is the main cause of adrenocortical insufficiency?
Autoimmune
What are the symptoms of Addison’s disease?
Tearful Tired, weakness Abdo pain Vomiting Anorexia Dizziness, faints Flu-like arthralgias/myalgias Postural hypotension Pigmented palmar creases
How does an Addisonian crisis present?
Shock: hypotensive and tachycardic
Fever
Coma
What are the electrolyte abnormalities found in Addison’s disease?
Hyponatraemia
Hyperkalaemia
Hypoglycaemia
Uraemia
Hypercalcaemia
What is the short synacthen test?
Do plasma cortisol before and after 250ug IM synacthen
Not Addison’s if cortisol is less than 550nmol/L at 30min
What is the treatment for Addison’s disease?
Steroids: 15-25mg hydrocortisone daily
Give early in the day to avoid insomnia
Fludrocortisone for postural hypotension and to decrease sodium and increase potassium
What are patients with Addison’s given for emergencies?
Syringes of IM hydrocortisone
Inject 100mg if vomiting prevents oral intake
What is primary hyperaldosteronism?
Excess production of aldosterone with no increase in RAAS activity
Leads to increased sodium and water retention and decreased renin release
What are the features of primary hyperaldosteronism?
Hypertension
Hypokalaemia
Alkalosis
Sodium slightly raised or normal
What is Conn’s syndrome?
Single aldosterone-producing adenoma
Causes primary hyperaldosteronism
How are renin and aldosterone levels affected by primary hyperaldosteronism?
Suppressed renin
Raised aldosterone
When should the adrenals be MRId?
After hyperaldosteronism confirmed
Due to high incidence of incidentalomas
What is used to medically manage hyperaldosteronism?
Spironolactone
What is secondary hyperaldosteronism?
High renin levels caused by reduced renal perfusion
What is a phaeochromocytoma?
Rare tumour usually found in adrenal medulla
Produces catecholamines
What is the triad of features found in phaeochromocytoma?
Episodic headache
Sweating
Tachycardia
Name an alpha blocker and a use
Phenoxybenzamine
Preop medical management of phaeochromocytoma
What are the actions of parathyroid hormone?
Increased osteoclast activity
Increased calcium/decreased phosphate resorption in kidney
Increased production of 1,25-dihydroxyvitamin D
What is the overall effect of parathyroid hormone?
Increased serum calcium
Decreased serum phosphate
What is the main cause of primary hyperparathyroidism?
Single adenoma
What are the features of hypercalcaemia?
Weak Tired Depression Thirsty Renal stones Abdo pain Pancreatitis Ulcers
Why is alk phos raised in hyperparathyroidism?
Increased bone resorption
What is the treatment for mild hyperparathyroidism?
Increase fluid intake to avoid stones
Avoid thiazides and high calcium/vit D intake
What are the complications of removing a parathyroid adenoma?
Hypoparathyroidism
Recurrent laryngeal nerve damage
Symptomatic hypocalcaemia
How does Cinacalcet work?
Increases sensitivity of parathyroid cells to Ca2+
Increases negative feedback effect
Decreases PTH secretion
What are the causes of secondary hyperparathyroidism?
Reduced Vit D intake
Chronic renal failure
What is PTHrP commonly produced by?
Squamous cell lung cancers
Breast cancer
Renal cell carcinoma
What is the acute management of hypercalcaemia?
Correct dehydration with 0.9% saline
Bisphosphonate (max dose 90mg)
Diagnose and treat underlying cause
What is primary hypoparathyroidism?
Primary gland failure causing decreased PTH secretion and hence hypocalcaemia
What are the causes of secondary hypoparathyroidism?
Surgery
Radiation
Hypomagnesaemia (needed for PTH production)
What are the features of hypocalcaemia?
Spasms Anxious, irritable, irrational Seizures Hypertonic smooth muscle (colic, wheeze, dysphagia) Dermatitis Impaired orientation & confusion
What is the treatment of mild hypocalcaemia?
Calcium 5mmol/6h PO
What is the treatment of severe hypocalcaemia?
10ml 10% calcium gluconate IV over 30mins
What are the causes of hypocalcaemia with increased phosphate levels?
CKD Hypoparathyroidism Acute rhabdomyolysis Vit d deficiency Hypomagnaesemia
What are the causes of hypocalcaemia with normal or decreased phosphate levels?
Osteomalacia
Acute pancreatitis
Over hydration
Respiratory alkalosis
What are the levels of FSH and LH like in primary Hypogonadism?
High
What are the levels of FSH and LH like in secondary hypogonadism?
Normal or low
What chromosomal abnormalities cause hypogonadism?
Klinefelter
Turner
What are the causes of primary hypogonadism?
Klinefelter/Turner syndrome Autoimmune eg Addison's Infection Haemochromatosis Surgery on gonads
What are the causes of secondary hypogonadism?
Hypothalamic or pituitary defect:
Hypothalamic eg kallmann syndrome
Pituitary eg hypopituitarism
PCOS
What is the treatment for secondary hypogonadism?
Men: testosterone replacement therapy
Women: oestrogen and progesterone replacement
How can morbid obesity be managed medically?
Orlistat - prevents absorption of fats by inhibiting lipase
What are the indications for bariatric surgery?
BMI over 40kg/m2
Non-surgical measures failed for at least 6 months
Intensive specialist management
Fit for surgery
Patient commits to need for long-term follow-up
When is surgery the 1st line treatment for obesity?
Adults with BMI > 50
What is MEN?
Multiple endocrine neoplasia
Functioning hormone-producing tumours in multiple organs
Autosomal dominant inheritance
What are the features of MEN-1?
Parathyroid hyperplasia or adenoma
Pancreas endocrine tumours
Pituitary prolactinoma
What are the features of MEN-2a?
Thyroid carcinoma
Adrenal eg phaeochromocytoma
Parathyroid hyperplasia
How is genetic testing used in MEN?
MEN-2 gene is a proto-oncogene
Test for it and do prophylactic thyroidectomy before 3 years of age
What is the normal range for GFR?
70-140ml/min
How much of the cardiac output do the kidneys receive?
20%
How much urine do the kidneys normally produce?
50-100ml per hour
Where is the urine made acidic?
Collecting ducts: whatever sodium resorption that occurs is accompanied by an equivalent excretion of H+ and K+
Where does sodium resorption occur?
60-70% proximal tubule
20-30% loop
5-8% distal tubule
Why is GFR better than creatinine at measuring renal impairment?
Creatinine also dependent on muscle mass - so if muscle mass is low, creatinine can be normal despite GFR being reduced
What is the MDRD equation?
Estimates GFR from 4 parameters: Serum creatinine Age Gender Race
What is the normal range for pCO2?
4.7 - 6 kPa
What is the normal range for HCO3-?
22-28mmol/L
What is the equation for anion gap?
(Na+ + K+) - (Cl- + HCO3-)
What is the normal range for the anion gap?
10-18mmol/L
What is the anion gap useful for?
Determining the cause of metabolic acidosis
What are the causes of metabolic acidosis with an increased anion gap?
Lactic acid eg shock, infection, ischaemia
Urate ie renal failure
Ketones (DKA, alcohol)
Drugs/toxins
What are the causes of metabolic acidosis with a normal anion gap?
Renal tubular acidosis Diarrhoea Drugs Addison's disease Pancreatic fistula Ammonium chloride ingestion
Why does the anion gap increase in some metabolic acidosis?
Increased production or reduced excretion of organic acids
Causes HCO3- to fall
Other organic anions rise
What are the causes of metabolic alkalosis?
Vomiting
Potassium depletion eg diuretics
Burns
Ingesting base
What causes respiratory acidosis?
Type 2 respiratory failure of any cause
Most commonly COPD
What causes respiratory alkalosis?
Hyperventilation
Eg stroke, asthma, anxiety, pregnancy, PE, drugs
Give 2 examples of loop diuretics
Furosemide
Bumetanide
What is the mechanism of action of loop diuretics?
Block Na/K/Cl cotransporter in thick ascending limb
Prevent reabsorption of sodium, chloride and potassium
Increases amount of solute in filtrate
Reduces water reabsorption
What are the uses of loop diuretics?
Acute pulmonary oedema Peripheral oedema Ascites Heart failure Severe hypercalcaemia
What are the side effects of loop diuretics?
Hypokalaemic metabolic alkalosis (because they cause H+ and K+ excretion)
Hypovolaemia
Ototoxicity
Allergies
Give 2 examples of thiazides
Bendroflumethiazide
Metolazone
What is the mechanism of action of thiazides?
Inhibit NaCl transporter in distal tubule
Decrease NaCl reabsorption to increase water loss
How do thiazides affect serum potassium?
Cause hypokalaemia
Due to excessive potassium loss
What are the uses of thiazides?
Hypertension
Long-term oedema eg heart failure
Reduce renal stone formation in hypercalcuria
What are the side effects of thiazides?
Hypokalaemia Hyponatraemia Hypomagnaesemia Metabolic alkalosis Hyperglycaemia Increased serum lipid Increased uric acid level
Name 2 aldosterone antagonists
Spironolactone
Eplerenone
Name 4 potassium sparing diuretics
Spironolactone and Eplerenone
Amiloride and triameterene
What is the mechanism of action of amiloride?
Block ENaC in distal tubule to prevent sodium reabsorption
What potassium abnormality is common with potassium-sparing diuretics?
Hyperkalaemia
They reduce potassium excretion
Which works more quickly, Spironolactone or amiloride?
Amiloride works in hours
Spironolactone takes days for full effect
How can you prevent hyperkalaemia when using potassium sparing diuretics?
Use in combination with loop or thiazides diuretic
What are the side effects of Spironolactone?
Gynaecomastia
GI upset
Hyperkalaemia
Name an osmotic diuretic and its mechanism of action
Mannitol
Freely filtered but not reabsorbed - stays in lumen and causes less water to be reabsorbed from the proximal tubule
What are the uses of mannitol?
Reduce brain volume/ICP
Haemolysis
Rhabdomyolysis
Reduce intraocular pressure
What are the side effects of mannitol?
Headache
Nausea
Vomiting
Hypernatraemia
Define hypokalaemia
K+
What is the most common cause of hypokalaemia?
Diuretic therapy
What ECG changes appear in hypokalaemia?
Flat T wave U waves Long PR Depressed ST Tachyarrhythmias
What are the symptoms of hypokalaemia?
Weakness Intestinal ileus Hypotonia and hyporeflexia Cramps Tetany Palpitations Light-headedness Cardiac arrest
How do you manage mild hypokalaemia?
Oral K+ supplement
Consider changing to potassium-sparing diuretic
How do you treat severe hypokalaemia?
IV KCl cautiously
No more than 20mmol/h
Not more concentrated than 40mmol/L
What is the maximum rate and concentration of potassium that it is safe to give?
20mmol per hour
40mmol/L
What potassium concentration is an emergency?
Above 6.5 mmol/L
What are the causes of hyperkalaemia?
Oliguric renal failure Potassium-sparing diuretics Rhabdomyolysis Metabolic acidosis Excess K+ therapy Addison's disease Massive blood transfusion Burns Drugs eg ACEi Artefactual result
Why do you get artefactual results stating hyperkalaemia?
Commonly from primary care causing delayed analysis
Difficult venue puncture causing haemolysis
Contamination with EDTA in FBC bottle - do UEs first
What are the concerning signs in hyperkalaemia?
Fast irregular pulse Chest pain Weakness Palpitations Light-headedness
What are the ECG changes in hyperkalaemia?
Tall tented T waves
Small P waves
Wide QRS
VF
How do you manage non-urgent hyperkalaemia?
Treat underlying cause
Stop precipitating medications
Calcium resonium: binds to K+ in gut to prevent its absorption
How do you treat severe hyperkalaemia?
> 6.5mmol/L get senior help
IV calcium gluconate 10ml 10% over 2min
Insulin + dextrose IV
Dialysis
What is the pathophysiology of rhabdomyolysis?
Skeletal muscle breakdown
Release of contents into circulation (myoglobin, potassium, urate, CK)
What are the consequences of rhabdomyolysis?
Hyperkalaemia
AKI as myoglobin is filtered at glomerulus then obstructs renal tubules
What are the causes of rhabdomyolysis?
Post-ischaemia Prolonged immobilisation Burns Crash injury Excessive exercise Uncontrolled seizures Myosotis Infections Drugs
What is plasma CK like in rhabdomyolysis?
Very raised, over 1000iU/L
How do you distinguish between rhabdomyolysis and MI?
Troponin negative in rhabdomyolysis
How do you treat rhabdomyolysis?
Treat hyperkalaemia urgently
IV fluids to prevent AKI
Maintain urine output of 300ml/h until myoglobinuria has stopped
What is the normal range for plasma sodium?
135-145 mmol/L
What are the features of hyponatraemia?
Anorexia, nausea, malaise Headache Irritability Confusion Weakness Reduced GCS and seizures Cardiac failure/oedema
What are the causes of hyponatraemia with hypovolaemia?
Renal loss of sodium : diuretics, Addison’s
Extra renal loss: vomiting, diarrhoea, burns, sweat
What are the causes of hyponatraemia with normovolaemia?
Inappropriate IV fluid (eg 5% dextrose) Hypothyroidism SIADH Sickle cell Drugs eg carbamazepine
What are the causes of hyponatraemia with Hypervolaemia?
Renal failure Cardiac failure Hepatic failure Nephrotic syndrome Inappropriate IV fluid eg excess 0.9% saline
How should sodium be replaced in hyponatraemia?
Replace sodium and water at the same rate they were lost
How do you manage Asymptomatic, chronic hyponatraemia?
Restrict fluid intake
Demeclocycline (ADH antagonist) may be needed
What are the dangers of correcting hyponatraemia too quickly?
Central pontine myelinolysis
What is the maximum rate of increase in acute hyponatraemia?
1 mmol/h
What is the action of vasopressor receptor antagonists?
Cause water excretion without losing electrolytes
Effective for hyper/euvolaemic hyponatraemia
Define clinical criteria for SIADH
Concentration of urine >20mmol/L Na+
Hyponatraemia
Low plasma osmolality
What are the causes of SIADH?
Malignancy CNS disorders Chest disease eg TB or pneumonia Endocrine disease eg hypothyroid Drugs Porphyria Trauma Major abdo/thoracic surgery
How do you treat SIADH?
Restrict fluid intake and treat cause
If severe, may require salt and loop diuretic
Define hypernatraemia
Plasma sodium > 145mmol/L
What are the features of hypernatraemia?
Lethargy Thirst Weakness Irritability Confusion Coma Fits Signs of dehydration
What is the mechanism of action of cyclizine?
H2 receptor antagonist
Used to treat GI causes of vomiting
What is the action of metoclopramide?
D2 receptor antagonist
What is the mechanism of action of ondansetron?
5HT3 receptor antagonist
How do bulking agents work? Give an example
Increase faecal mass to stimulate peristalsis
Ispaghula husk eg fybogel
How do stimulant laxatives work? Give an example
Increase intestinal motility
Senna
How do osmotic laxatives work?
Retain fluid in the bowel
Also retain ammonia so used in hepatic encephalopathy
Give two examples of osmotic laxatives
Lactulose
Macrogol (movicol)
What dose of codeine phosphate is used to treat diarrhoea?
30mg TDS PO
What is the dose of loperamide?
2mg PO after each loose stool
Max 16mg per day
Define AKI
Rapid reduction in renal function over a period of hours to days
How is AKI measured?
Serum urea and creatinine
What are the risk factors for AKI?
Age over 75 CKD Heart failure PVD Chronic liver disease Diabetes Drugs Sepsis Low fluid intake/increased losses History of urinary symptoms
How is urine output used to diagnose AKI?
Less than 0.5ml/kg/h for 6h - stage 1
12h - stage 2
24h - stage 3
How is serum creatinine used to define AKI?
Stage 1 - >26umol/L increase or 1.5x baseline
What are the common causes of pre-renal AKI?
Hypo perfusion
Hypotension
Renal artery stenosis
ACE inhibitors
