Hepatology, endocrinology, renal Flashcards
3 ways alcoholic liver disease affects liver
Hepatic steatosis (also obesity and DM) - alcohol metabolism prioritised, so fat not metabolised and accumulates in cytoplasm of liver cells
Alcoholic hepatitis - direct toxicity, collagen deposition, cirrhosis
Cirrhosis - final and irreversible. Hepatocytes regenerate with nodules and fibrous septa - blood flow disrupted and less efficient
Assoc of non alcoholic fatty liver diseae
Metaboic syndrome, insuin resistance
RF for NAFLD and sx
Obesity, diabetes, hyperlipidaemia
Asymptomatic of fatigue and malaise
Sx of alcoholic hepatitis
Anorexia, dv, tender hepatomegaly, ascites
Jaundice, bleeding, encephalopathy
Inv for alc hep
Raised MCV
Raised GGT
AST:ALT >2
Ascitic tap, abdo USS, portovenus duplex
Manage alc hep
Stop alcohol and drug withdrawal High dose vit B Optimise nutrition Daily weights LFT, UE, INR
Signs of chronic liver failure
Jaundice, oedema, ascites Bruising Encephalopathy - asterexis, constructional apraxia Fetor hepaticus Signs of cirrhosis
Manage chronic liver failure
ITU
Thiamine supplements
Prophylactic PPI for stress ulcers
Manage complications of chronc liver failure
Bleeding - Vit K, platelets, ffp, blood
Ascites - fluid and salt retention, spironolactone, furosemide, ascitic tap, daily weighing
Hypoglycaemia - regular BMs, IV glucose if <2
Sepsis - tazocin
Encephalopathy - avoid sedatives. Give lactulose/enemas, rifaximin
Seizures - lorazepam
Cerebral oedema - mannitol
Poor prognostic factors for chronic liver failure
Grade 3-4 hep encephalopathy
>40yo
Low albumin, raised INR
Drug induced
What is hepatic encephalopathy
Neuro disorder from 1) metabolic failure of hepatocytes and 2) blood shunting around liver - exposes brain to abn metabolites = oedema and astrocyte changes
Elimination of toxic nitrogenous products reduced and some act as false transmitters causing CNS disturbances
Sx of hep enceph
Disturbance of consciousness
Flapping tremor
Fluctuating neuro signs - muscular rigidly and hyperreflexia
Conditions where liver transplantation is used - 5
Acute and chronic liver disease Alcoholic liverdiseae PBC Chronic hep b/c with complications Primary metaoblic disease with endstage liver diseae eg Wilson’s, a1at
Absolute CI to liver transpant
Sepsis out]side hepbil tree, malignancy
Signs of rejection in liver transplant and manage
Early 5-10d = inflammatory reaction = pyrexia, general malaise, abdo tenderness from hepmeg
Give immunosuppression post transplant - Calcineurin inhibitor, steroids, azathioprine
Chronic - 6w-9m after - immunosuppression and retransplant
Manage ascites before liver transplant
Oral ciprofloxacin as prophylaxis against spontaneous bacterial peritonitis
Liver transplant criteria
King’s college hospital criteria
Paracettamol: pH <7.3 24h after ingestion, or INR >6.5 or creatinine raised, or grade 3-4 hep enceph
Non-paracetamol: INR>6.5 or 3 of: drug induced, <11 or >40yo, 1w between onset of jaundice and enceph, INR >3.5 or bilirubin very high
3 managements of alcohol withdrawal
Benzo for seizures
Disulfiram - makes very ill if drink as inhibition of acetaldehyde dehydrogenase
Acamprosate - reduces cravings as weak antagonist of NMDA receptors
Causes of budd-chiari and sx
Hepatic vein thrombosis, usually from procoagulable state - COCP, pregnancy, thrombophilia, polycythaemia rubra vera
= abdo pain (sudden onset and severe), ascites and tender hepatomegaly
Hereditary haemochromatosis - what is it and features and treatment
Abn iron metabolism, so increased iron abs and deposition in organs: MEALS
Myocardium - arrhythmias, dilated cardiomyopathy
Endocrine - diabetes, hypogonadism = amenorrhoea and infertility
Arthritis
Liver - chronic liver diseae = hepatocellular carcinoma
Skin - slate grey discolouration
Treat with venesection, low iron diet, transplant in cirrhosis
What is a1at deficiency and treatment
a1at inhibits neutrophil elastase in inflammatory cascade
Hepatitis in newborns, cirrhosis in adulthood, emphysema.
Manage pulmonary and hepatic complications, quit smoking, consider a1at from pooled donors
What is wilson’s Disease and presentation
Aut rec disorder Excess copper deposition in tissues, from increased abs from SI and decreased excretion from liver Children - liver diseae Adults - neuro disaee Presents 10-25yo
Sx of wilson’s disease
Liver - hepatitis, cirrhosis
Neuro - basal ganglia degeneration (asterexis, chorea), speech and behavioural problems, dementia
Cosmetic - blue nails, Keyser fleicher rings in eyes
Renal tubular acidosis, haemolysis
Diagnosis of wilson’s Disease and treatment
Caeruloplasmin and serum copper low (copper carried by caeuroloplasmin)
Urine copper 24h excretion high
Treat with copper chelalator penicillamine
What is AI hepatitis
Suppressor T cell defects
Autoantibodies against hepatocyte surface antigens
Young/middle aged women
Present with acute hep and signs of other AI disease - fever, malaise, urticaria, polyarthritis, pulmonary infiltration, glomerulonephritis. Secondary amenorrhoea
AI hepatitis bloods
All LFTs high - gamma GT, ALP, ALT, AST
Positive autoantibodies
Anaemia, low WCC, low platelets - hyperplenism
Manage AI hepatitis
Immunosuppressants, prednisolone
Transplant if decompesated cirrhosis, or failure to respond to medication
Associated conditions with AI hepatitis
UC PSC Glomerulonephritis AI thyroiditis AI haemolysis Pernicious anaemia DM
Viral hepatitis presentation
Prodrome (hep a and b) - flu-like, malaise, arthralgia, nausea
Icteral (esp hep a then b) = acute hepatitis - hepatomegaly, abdo pain, cholestasis; extrahepatic - urticaria, arthritis
Chronic (esp hep c then b) = cirrhosis, increased hepcell carcinoma risk
Hep b serology
HBsAg = acute disease. Present for >6m = chronic inf Anti-HBs = immunity - exposure or immunisation. Neg in chronic disease Anti-HBc = previous (or current) infection, IgM present for about 6m, IgG Anti-HBc persists HbeAg = breakdown of core antigen from liver cells, so indicates infectivity
Diabetes complications and glucose levels for diagnosis
CVS disease, renal disease - can give kidney and pancreas transplant if renal failure in T1DM
Retinopathy if >6.5% HbA1c
Fasting glucose >7 or >11.1 2h after 75g glucose
HbA1c 6.5% or 48mmol - 42-47 (6-6.4%) = prediabetic
Insulin.’s role and cause of diabetes
Fuels metabolism and glucose uptake Inhibits protein catabolism Fatty acid clearance Active transport of aa into cells Inhibits gluconeongenesis and liver glycogen breakdown
Diabetes = abnormality in molecule, receptor or signalling
Sx of diabetes
Urinating Thirsty Hungry Blurred vision Fatigue Slow healing Weight loss - T1 Tinging or numbness in hands/feet - T2
Type 1 dm pathophysiology
AI destruction of B cells at varying rates = absolute insulin deficiency
Insulin suppresses ketone production, so no insulin = ketones = emergency
Autoantibodies and HLA associations
T1 dm management incl 1st regime in newly diagnosed adults and sick day rules
Patient education (for exercise, illness, food), home glucose monitoring, DAFNE course, HbA1c regularly
Start basal-bolus with 2x/d insulin detemir = long acting and soluble/rapid acting insulin for meals and correct high BMs
Sick day rule - never stop basal insulin
- continue meal time insulin and add extra:
— minor = +- ketones in urine, increase total in day and take correction
— major = ++ ketones in urine, increase background by a lot and take correction. Get help if ketones don’t fall in 2-4h
Indications for insulin sc pump and use
HbA1c stays >8.5%
Regular hypos from trying to control HbA1c
Can adjust basal rate throughout day
DM2 cause
Insulin resistance (levels may be high)
- pancreas creates more - eventually exhaustion - hyperglycaemia
Obesity
Insulin after bariatric surgery - 4
Fasting blood glucose normalises within 7d
Liver fat content falls
Insulin sensitivity normalises, then insulin release goes back to normal in 8w
Decrease in pancreatic fat = B cell function normalises
DM2 management categories
Diet and exercise
Anti obesity drugs
Hypoglycaemics - metformin, sulphonylurea, thiazolinodione, GLP-1 receptor analogue, DPP4 inhibitor
Insulin
What does metformin do and ADRs
Metformin = decreases gluconeogenesis and action of glucagon. Increases glucagon uptake peripherally
ADR - GI, rare = lactic acidosis
Don’t give if liver/renal failure
What does sulphonylurea do and ADR
Gliclazide - stimulates release of endogenous insulin. Decrease microvascular risk
ADR - hypoglycaemia, weight gain
What does thiazolinodione do and ADR
Pioglitazone - increase PPAR-Y, stimulating transcription of GLUT-1 and 4 - insulin sensitiser = increase glucose uptake
ADR - oedema and weight gain. Not if HF or osteoporosis/bone fracture risk
What does GLP-1 receptor analogue do and associated drug
Exenatide - increase response to glucose in GI, so stimulating insulin annd suppressing glucagon secretion = glucose-dependent
Weight loss, slows gastric emptying, increases satiety
ADR - GI = nvd, headache and dizzy
DPP4 inhibitor sitagliptin prevents incretin hormones GLP1 and GIP breakdown
DM medication in surgery
Variable rate insulin infusion if will miss more than 1 consecutive meal or emergency surgery
Don’t take med in morning if NBM, except metformin and pioglitazone
Insulin storage and where to use
In fridge until opened, then room temp. Use within 30d of opening
Don’t use other people’s insulin
SC pen into abdo or outer thigh, hold pen in for 10s
Also pump or syringes
Different types of insulin
Rapid = novorapid, 15m onset, 30-60m peak, 4h duration
Short acting = actrapid, 30m - 2h - 6-8h
Intermediate = humulin I, 2h - 4-6h - 14h
Long = lantus, 2h - no peak - 24h duration
Glargine - high strength, once a day, flatter and prolonged conc
When to use insulin infusion, adv and disadvantages and risks
DKA, HONK/HOHG
Surgery, major vascular event (CVA)
Vomiting, metabolically unwell (sepsis)
Enterally fed
Adv - control with target to improve clinical outcomes, avoid metabolic decompensation
Disadvantages - invasive, requires regular BM monitoring, difficult to control if patient is eating, prolongs stay
Risks - rebound hyperglycaemia or DKA if stopped suddenly; hyper-o-glycaemia if inadequate rate or monitoring; fluid overload; hypokalaemia/natraemia; line infection
Practicality of setting up insulin infusion and stopping
50 units of actrapid, mix with 49.5ml saline in 50ml insulin syringe, set up IV insulin syringe driver
Review unstable BMs, assess rate/12h and need for infusion and fluids /24h
Continue until eating and drinking and back on usual DM drugs for 30m, then BM every 4h for 24h for no rebound hyperglycaemia
Measure BM every 1h for 12h then change rate if no effect
Can be reduced if sensitive, intermediate or increased rate if insulin resistance
Manage hypoglycaemia
<4mmol - 75ml of 20% dextrose over 15m, repeat if still <4
ACS or stroke - keep above 6mmol
Renal/cardiac disease - may need 10% dextrose
Once >4mmol, restart infusion
5 types of diabetes - not T1 or T2
- MODY - Maturity Onset Diabetes of the Young - B cell defect, aut dom, defect in insulin action at receptor
- Gestational diabetes - normally 3rd trimester
- Pancreatic (exocrine) related diabetes - pancreatitis, trauma, pancreatectomy, carcinoma
- Drug-related diabetes - thiazides, b blockers, psychotropics, glucocorticoids
- Growth hormone causes insulin resistance - acromegaly, Cushing’s
Complications of dm - acute and chronic
Acute - DKA, HONK
Chronic - microvascular (retinopathy, neuropathy, nephropathy)
- macrovascular (cerebrovascular, peripheral vascular, cardiovascular)
DKA cause, presentation, diagnosis
Non-compliance, or increased insulin requirements for stress - infection, MI
1. BM >11mmol or known DM
2. Ketones >3mmol/l blood or >2+ urine
3. Venous pH <7.3 +- bicarbonate <15mmol/l
= abdo pain, vomit, drowsy, dehydration, ketotic breath, hyperventilation
DKA management incl inv
VBG - pH, ketones, glucose, bicarb U&E - Na, K FBC and cultures ECG, CXR, MSU Continuous cardiac and pulse ox monitoring
50u actrapid in 50ml NaCl 0.9%, infusion at 0.1u/kg/h
Continue long acting insulin
Check pH, bicarb, K and glucose at 1h, 2h and every 2h, for:
- ketones <0.5mmol/l/h OR
- bicarb up by 3mmol/l/h and glucose down by 3mmol/l/h
Increase by 1u/h until reaching targets
Consider catheter, aim for 0.5ml/kg/h
Start LMWH
When glucose <14mmol, start 10% dextrose at 125ml/h alongside saline
Continue fixed rate until: - ketones <0.3mmol/l - pH >7.3 - bicarb >18mmol/l Urinary ketones will stay positive until after resolution
Find and treat inf/cause
Complications of dka - 5
Cerebral oedema from fluid overload
Hypophosphataemia, hypokalaemia
Thromboembolism
Aspiration pneumonia
What is HONK and treatment
Generally elderly DM2
- Hyperglycaemia >30mmol/l
- Hyperosmolar
- Hypovolaemia - don’t appear dehydrated as preserved intravascular volume
- Ketones <3 and HCO3 >15, pH >7.3
Osmotic diuresis due to increased glucose - water losses greater than Na and K
Long standing - 1w plus - extreme dehydration and metabolic disturbances
Treatment aims to reduce osmolality, replace fluids and electrolytes and normalise blood glucose
Treat underlying cause and prevent VTE
Insulin needed if any ketonaemia
Diag of hypoglycaemia and causes
Whipple’s triad: BM<3, symptoms, relief of symptoms with glucose admin
Hypoglycaemia and unwell:
- drug induced - insulin or alcohol
- hormone def - Addison’s
- organ failure - liver, chronic renal failure
- tumour - non-Islet cell tumour
Hypoglycaemia and well:
- insulinoma
- non-islet cell tumour - adrenal carcinoma, hepatocellular carcinoma, lymphoma
- functional B cell disorder
- AI
Sx of hypoglycaemia and treatment
Autonomic/adrenergic when BM2.5-3: sweating, hunger, tingling, trembling, palpitations, anxiety
Neuroglycopoenic when BM<2.5: visual disturbance, personality change, confusion poor concentration, lethargy, coma when <2
Eat carbs, glucogel, 100mll 20% dextrose, IM/SC 1ml glucagon
DM in pregnancy - before and during, and risks
Optimise HbA1c - not recommended to get pregnant if >86 Lose weight, smoking, alcohol, high dose folic acid, assess other teratogens eg ACEi Screen for retinopathy and nephropathy Increased risk of: - hypo during first trimester esp - worsening retinopathy and nephropathy - check every trimester - pre eclampsia - thromboembolic disease - DKA (+ potential foetal loss) Foetal risks: - cardiac, neural tube and renal defects - preterm - macrosomia - foetal mortality and still birth - NNU
Paeds DM
Random blood glucose >11.1 = diabetic - inpatient for 3d and teach amount insulin, diet etc
Start on 0.5u/kg/d. Basal in morning if <5yo, evening when >5yo, then 2 doses when puberty. Increase to 2u/kg/d in puberty as hormones = insulin resistance
Stabilise around 20yo
Elderly DM
More likely to have hypos due to 5+ drugs, poor diet, chronic kidney problems, more susceptible to illnesses
Exercise and diet harder
Cognitive complicatiotns more likely
Pathogenesis of diabetic eye disease and stages
10y after onset, damage to small blood vessels, also cataracts more common
Microvascular disease - retinal ischaemia - increased VEGF - new vessel formation
1. Background retinopathy = dots (micro aneurysms) and blots (haemorrhages) and hard exudates (yellow lipid patches)
2. Pre-proliferative retinopathy = cotton wool spots (retinal infarcts), multiple blot haemorrhages, venous bleeding and microvascular abnormalities
3. Proliferative = new vessels on disc and elsewhere, fibrovascular proliferation and tractional retinal detachment. Pre-retinal or vitreous haemorrhage
4. Maculopathy - exudate within 1 disc diameter of centre of fovea, group of exudates in macula, retinal thickening
Inv diabetic eye disease and treatment
Fluorescein angiography, eye screening
Trt
- control: glycaemia, blood pressure, lipids
- antiplatelet therapy
- lifestyle - smoking, alcohol, exercise
- laser treatment, VEGF inhibitors
RF for worse diabetic retinopathy
Smoking in DM1, glucose control, systemic htn, blood lipids
Age, race, genetic predisposition, pregnancy, duration of diabetes
Renal disease in DM
Leading cause of end stage renal disease
Proteinuria + DM
Main RF is time with diabetes
Likely to also have renal impairment, retinopathy and hypertension
Neuropathy in DM
Distal axonal loss from focal demyelination = reduced nerve conduction velocity or loss of nerve function
Causes: neuropathic ulcers, erectile dysfunction (autonomic neuropathy), altered sensation (pain and incresed sensitivity), Charcot arthropathy
What is Charcot foot
Sympathetic nerve loss = increased blood flow to foot
= increased osteoclast activity and bone turnover,
so foot more susceptible to damage,
and any trauma = destructive changes
Mostly tarsal-metatarsal or metatarso-phalangeal joints.
Warm, swollen and painful foot
X-ray = osteolytic changes, fractures and joint reorganisation
Subluxation of metotarsophalangeal and dislocation of large joints
Identify early and immobile to prevent joint destruction
Macrovascular risk in DM and factors to control
2-4x increased risk of MI
Peripheral vascular disease in 10%
75% will die of macrovascular disease
Prevent with BM, lipid and bp control, smoking and weight loss
First line = always ACEi and target 140/80
Hypertension in DM
Insulin resistance, hyperinsulinanemia
Assoc with earlier microalbuminuria and nephropathy
What is lipid disease and who gets it
Combination of genetic and envirnemental factors. Primary = normally genetic, Secondary = obesity and DM2 are biggest factors. RF:
- premature CHD
- atherosclerosis
- diabetes or insulin resistance
- post-menopausal females not on HRT
- alcohol
- family hx of hyperlipidaemia, early CHD or atherosclerotic disease
Manage lipid disease
Lower cholesterol - 10% loss = 25% reduction in CVS risk
Statin - HMG-CoA reductase inhibitor decreases rate limiting step in cholesterol synthesis in liver = increases LDL receptors to increase clearance.
- CYP3A4 metabolism, avoid grapefruit juice, can interact with ciclosporin
- 1st line if LDL or mixed high
Fibrate - better for increasing HDL and reducing triglycerides by increasing lipoprotein lipase activity and LDL receptor mediated LDL clearance
- ADR nausea, anorexia, diarrhoea, gallstones, myopathy (esp with statin)
- 1st line if LDL high, 2nd line with statin if TAG or mixed
Bile acid sequestration - safe in pregnancy, ADR = GI sx
Cholesterol absorpation blocker ezetimibe - with or instead of statin, inhibits dietary and biliary LDL absorption
- use 2nd line to statins if LDL only high
Where is the pituitary and what does it release
Sella turca in base of brain
[FLAGToPa]
Ant pit - FSH, LH, ACTH, GH, TSH, PTH
Post pit - oxytocin, ADH
Disorders of the hypothalamus - causes and effect
Decreased production of all hormones except prolactin as hypothalamus suppresses this
- from trauma/surgery, radiotherapy, SIADH (excess)
Hyperpituitarism and treatment
Prolactinoma adenoma - excess prolactin production, reduced production of other hormones
- more in women - oligo, amenorrhoea, infertility (interfere with GnRH)
- Galactorrhoea, erectile dysfunction, visua field defects and headache
Suppression test, treat with dopamine agonist bromocriptine
Hypopituitarism cause and sx
Non-functioning adenoma, suppresses pituitary functions by compression in order of GH, LH, FSH, ACTH, TSH, prolactin
Sx - depression, tiredness, hypogonadism
- headache, vomiting, papilloedema
- visual disturbance, CN palsy
- oligo/amenorrhoea, reduced libido, infertility in men
Surrounding tumours - craniopharyngioma, glioma, meninioma, mets (bronchus, breast)
Pit infarction from sheehan’s = panhypopituitiarism - no lactate, amenorrhoea, death
Inv hypopituitarism and treat
Basal hormone level and stimulating hormone
Inhibition eg synACTHen
Visual field test
MRI, CT
Treat with all hormone replacement except prolactin
Post pituitary diseases - 2
Diabetes insipidus - defective ADH production = plasma osmolality very high, urine osmolality low, clinical features.
- Can cause fatal dehydration
SIADH - from inf, neuro, endocrine, malignancy diseases = plasma osmolality very low, hyponatraemia, urine osmolality very high with high sodium in urine
- malaise, weakness, confusion, coma
What are T3 and T4 bound to in blood
Albumin
TBG, TTR
Hyperthyroidism symptoms, exam and treatment
Sx - sweating, palpitations, irritability, overheating, hyperactivity, insomnia, pruritis, increased stool frequency, thirst and polyuria, oligomenorrhoea
Exam - sinus tachycardia, AF, palmar erythema, fine tremor, hyperkinesia, hyperreflexia, wam and moist, hair loss, muscle wasting
Grave’s - diffuse goitre, exophthalmos, optic neuropathy, periorbital oedema, gritty eye, retrobulbar pressure pain - from grave’s antibodies
Treat
- carbimazole for 1y, usually only works once, then monitor once off treatment. ADR = GI upset, agranulocytosis
- surgery - risk of RLN damage
- radioiodine
ADR of thyroidectomy
Local haemorrhage causing laryngeal oedema Wound infection Thyroid storm Hypoparathyroid RLN damage
What happen when someone with hyperthyroid gets infection
Thyroid storm:
Altered mental status, tachycardia, fever, vomiting, diarrhoea and jaundice
Treat in ITU and monitor cardiac, fluid and cooling
- digoxin for arrhythmia once hypokalaemia corrected
Secondary hyperthyroid?
From TSH secreting adenoma or reistance to thyroid hormone
Hypothyroid cause and sx
Inflammation in thyroid, normally from Hashimoto’s. Causes transient hyperthyroid then hypothyroid. Thyroid is lymphocitic and fibrotic - painless, variably sized goitre
Sx - fatigue, lethargy, constipation, menorrhagia then oligo/amenorrhoea, cold intolerance, muscle stiffness, cramps, dry skin and hair loss, deep hoarse voice, OSA, decreased visual acuity
Treat with levothryoxine, increasing dose slowly. May need increase 25-50% during pregnancy, abs reduced in coeliac or atrophic gastritis
Hypothyroidism and infection?
Myxoedema coma
Treat in ICU with external warming (0.5degree/h). Monitor for arrhythmia, hypoglycaemia, hyponatraemia. Treat illness - abx
Thyroid cancer
Biggest risk is radiation <20yo
Solitary nodule or increasing goitre size
80% papillary thyroid carcinoma - 20-30yo, treat with surgery, adjuvant radioiodine
Follicular thyroid carcinoma - 50yo, mets haematogenous spread to lung and bones
Lifelong follow up as can recurr
What is sick euthyroid
TSH in normal range, T3 and 4 low
Causes of primary hyperaldosteronism - 3
Biateral adrenal hyperplasia
Conn’s syndrome
Adrenal carcinoma
Main features of bilateral adrenal hyperplasia and treatment
Aldosterone = inhibit renin secretion, increase sodium reabsorption and potassium and hydrogen secretion = hypokalaemia alkalosis
- most common cause of secondary hypertension (10% of htn)
- resistant to conventional treatment
- LV hypertrophy
Treat with mineralocorticoid receptor antagonist spironolactone if not fit for surgery
Surgery - laparoscopic adrenalectomy
Sx of Cushing’s syndrome and diagnosis of cause
Excess cortisol - ACTH dependent (from pituitary adenoma = Cushing’s disease, suppressed with high dose dexamethasone, or ectopic tumour) or ACTH independent (adrenal tumour)
Round face, skin thin, striae on breasts, abdo and thigh, acne and hirsuitism
Weight gain - buffalo hump, truncal obesity, prox muscle weakness
Mood disturbance, insomnia, depression, psychosis
Menstrual disturbance, low libido
High VTE risk
Hypokalaemia metabolic alkalosis
Assoc features with Cushing’s syndrome
Hypertension Impaired glucose tolerance, DM2 Osteopoenia/osteoporosis Vascular disease from metabolic syndrome Infection susceptibility
Treat cushing’s
Transphenoidal surgery if Cushing’s disease, or pituitary radiotherapy
Adrenalectomy
Adrenal insufficiency causes and inv
Lack of mineralocorticoids and glucocorticoids
Primary - mostly AI (addison’s), or TB
- no response to synACTHen test
Secondary - hypopituitarism or hypothalamus disorder
- responds to synACTHen, no pigmentation as no ACTH
Adrenal incidentaloma - found on imaging for something else, determine if functional +- malignant
Follow up for 3y then discharge if benign and non functioning
Remove if >4cm, malignant or functioning
Addison’s sx
Depression and lethargy
Weight loss, abdo pain, anorexia, nvd/constipation
Hypoglycaemia
Postural hypotension
Pigmentation from lack of cortisol neg feedback ACTH and POMC secretion = stimulates melatonin receptor
Vitiligo
Addisonian crisis
Treat addisons
Hydrocortisone and fludrocortisone, wear med alert bracelet and steroid card, increase if ill
Wean off slowly
Addisonian crisis sx, cause and treat
Increased heart rate, postural drop
Oliguria, confusion, hypoglycaemia
From trauma, inf, surgery and stopping long term steroids
Hydrocortisone IV, crystalloid (glucose)
Causes of hypercalcaemia
Main are malignancy (bone mets, myeloma) or primary hyperparathyroidism
Less common = Addison’s, Sarcoidosis
Drugs - lithium, thiazides
Renal failure
Sx of hypercalcaemia
Stones, polyuria, polydipsia Anorexia, constipation, abdo pain, vomiting Confusion, lethargy, depression Pruritis, sore eyes Eventually - renal failure, hypertension
Primary hyperparathyroidism and sx and presentations
From parathyroid adenoma or hyperplasia
Asymptomatic or features of hypercalcaemia
Stones - renal stones, polyuria
Moans - depression
Bones - osteopororis, pathological fractures
Groans - abdo pain, nv, constipation, pancreatitis
Inv hyperparathyroidism
Calcium high
PTH normal or high
ALP high
Phosphate low
Treat hyperparathyroidism and complications
Remove
Observe if mild
Complications of surgery - vocal cord paresis from RLN palsy, tracheal compression from haematoma, hypocalcaemia
Inv and treat hypercalcaemia of malignancy
High calcium, low PTH
Aggressive rehydration and zolidronic acid
Causes of hypocalcaemia and sx
With high phosphate: from hypoparathyroid dysfunction - infiltration, radiation, surgery. Or CKD
With normal or low phosophate: impaired bone release - osteomalacia. Or acute pancreatitis or DiGeorge syndrome
Sx from increased muscle excitability = SPASMODIC:
Spasms - carbopedal (Troussea’s sign)
Periorbital paraesthesia
Anxious, irritable, irrational
Seizures
Muscle tone increased in smooth muscle - wheeze, colic, dysphagia
Orientation impaired - confusion
Dermatitis
Impetigo herpetiformis (very serious in pregnancy if low Ca and pustules)
Chvostek’s sign: 3Cs: choreoathetosis, cataracts, cardiomyopathy (long qt)
Inv and treat hypocalcaemia
Inv - low calcium, high, low or normal phosphate, high PTH, normal ALP
Treat - calcium supplements, calcitriol
Calcium gluconate if acute tetany and seizures
Vit d deficiency causes and treatment
Sunlight, diet, secondary hypoparathyroid - malabsorpation gastrectomy
Calciferol, correct biochem abn, heal bone abn
What is pseudohypoparathyroid, inv and treat
Target organs don’t respond to PTH
Short stature, short 4th and 5th metacarpals
Inv - low calcium, high PTH
Give calcium and calcitriol
What is premature ovarian insufficiency
3: 1. Amenorrhoea, 2. oestrogen def and 3. elevated gonadotrophins
<40yo
Due to ovarian follicular failure and accelerated depletion of ovarian germ cells
Sx - amenorrhoea, sx of oestrogen def, other AI conditions, FSH >40 x2 and low oestradiol levels
What is Turner’s syndrome and management
45XO
Short, wide spaced nipples, webbed neck
Gonadal dysgenesis, amenorrhoea, no SSC
Aortic dissection, coeliac disease, congenital renal abnormalities
Give sex hormone replacement and managecomlicatiotns
HRT advantages and disadvantages
Adv
- reduce risks of CVD and osteoporosis
- reduce flushes, vaginal atrophy, urinary sx
Disadv
- breast tenderness, mood changes, irregular bleeding
- risk of breast cancer, endometrial cancer, gall stones, migraines, endometriosis and uterine fibroids, liver disease
What is primary hypogonadism and sx
Testicular failure with normal hypothalamus and pituitary
Before puberty: penis <5cm, testes volume <5ml, no rugae or pigmentation, gynaecomastia, high voice, central fat distribution, delayed bone age
After puberty: osteoporosis, central fat distribution, gynaecomastia, anaemia
What is secondary hypogonadism
By hypothalamic/pituitary dysfunction eg Kallman’s - failure of GnRH producing neurones to migrate to hypothalamus - and anosmia
What is Klinefelter’s - sx, inv and treatment
47XXY
Small testes, gynaecomastia, tall, features of hypogonad, cognitive dysfunction
Less facial hair, reduced libido and ED, infertility, obesity
Low T, raised LH and FSH
Risk DM2, VTE, osteoporosis, malignancies
Treat - lifelong androgen replacements
Androgen replacement therapy
For libido, mood, muscle mass, sexual function
Prevent osteoporosis
Will need gonadotrophins to initiate and stimulate spermatogenesis if want fertility
Risks - prostate cancer, acne CVS disease, polycythaemia, gynaecomastia, fluid retention, hepatotoxicity, OSA
What is obesity and its staging and consequences
Excess of body fat sufficient to adversely affect health
0 - no risk factors, no physical sx or functional limitations
1 - sx of physical limitation (exertional SOB) and subclinical conditions (borderline htn, impaired fasting glucose, elevated liver enz)
2 - chronic conditions - DM2, htn, OSA, GORD, PCOS
3 - end organ damage - MI, HF, DM complications, significant impairment to wellbeing
4 - disabilities from obesity related chronic disease
Consequences - dyslipidaemia, stroke, asthma, htn, DM2
Treat obesity
Orlistat - pancreatic lipase inhibitor, reducing fat absorption from GI
Bariatric surgery - gastric bypass, sleeve gastrectomy, adjustable gastric banding
What is carcinoid syndrome and sx
10% part of MEN
Neuroendocrine tumours of enterochromaffin cell which produces 5HT
Sx: FIVE-HT; presents with GI signs
Flushing, Intestinal (abdo pain, appendicitis, intussusception, obstuction, diarrhoea), Valve fibrosis (pulmonary stenosis, tricuspid regurg), whEEze, Hepatic involvement (bypassed first metabolism), Tryptophan def
Crisis = tumour outgrows blood supply or handled too much = mediator release
- vasodilation, hypotension, bronchoconstriction, hyperglycaemia
What is MEN
Multiple Endocrine Neoplasia: PAP, FPP, FPMM 1 - aut dom, aggressive, high mortality, 2/3 of: Parathyroid tumour/hyperplasia; Ant pit adenoma; Pancreatic neuroendocrine tumour 2a - Familial medullary thyroid carcinoma Phaechromocytoma Parathyroid 2b - Familial medullary thyroid carcinoma Phaechromocytoma Mucosal neuromas Marfanoid habittus
Acromegaly causes
Pituitary tumour - 99%
Ectopic GH releasing tumour
Assoc with Men1
Sx of acromegaly
Acroparaesthesia, arthralgia, back ache
Amenorrhoea, redued libido
Headache, sweating, snoring
Signs - hands, supra orbital ridge, wide nose, coarse facial features, macroglossia
Acanthosis nigricans
OSA, carpal tunnnel
Pit mass effect - hypopituitarism, vision, hemianopia, fits
Complications of acromegaly
CCF or ketoacidosis
Impaired glucose tolerance
Vascular - raised BP, LV hypertrophy, cardiomyopathy, arrhythmia, IHD, stroke
Colon cancer risk
Tests for acromegaly
Increased glucose, phosphate and calcium
Don’t trust GH test as pulsatile - increase in sleep and stress
If high, or IGF1 high = OGTT
- GH normally suppressed by glucose so hardly detectable in normal person - not suppressed in acromegaly
MRI pituitary fossa
Hypopituitarism inv and visual fields and acuity
ECG and echo
Treat acromegaly
Transphenoidal surgery
If that doesn’t reduce GH and IGF1 = somatostatin analogue
If doesn’t work = GH antagonist
Phaeochromocytoma what is it
Tumour of sympathetic paraganglia cells in adrenal cortex, secretes catecholamines
Can be bilateral, extra-adrenal, linked to Men2
Classic triad: episodic headache, sweating, tachycardia
Sx of phaeochromocytoma
Psych - anxiety, panic, hyperactive, psychosis
CNS - visual disturbance, headache, dizzy, fits, Horner’s
Heart - arrhythmia, VT, angina, MI, SOB, faint, cardiomyopathy
GI - dv, abdo pain over site, mass
Others - sweating, heat intolerance, temp, haemoptysis, pallor
Tests for phaeochromocytoma
WCC raised
Urine metadrenaline 3 x 24h and plasma
Clonidine suppression test
Treat phaeochromocytoma
A and b blockade pre-op - a first to avoid unopposed a-adrenergic stimulation
Key substances controlled by kidney
Na, K, Ca, PO4
Epo, renin
25,hydroxyvitD to 125,dihydroxyvitD
RAAS mechanism
From JGA in response to reduced flow or sympathetic stimulation
- convert angiotensinogen to angiotensin 1, which is then converted to angiotensin 2 by ACE. Angiotensin 2:
— constricts efferent arteriol and peripheral vasoconstriction
— stimulates adrenal cortex to release aldosterone which activates NaK pump - for Na and H20 absorpation with K and H loss
Cause, sx and treatment of hypernatraemia
Due to water loss in excess of sodium: diabetes insipidus, hyperaldosteronism, fluid loss, osmotic diuresis, incorrect fluid replacement
Sx - weakness, lethargy, irritability, thirst, coma and fits
Give water, or 5% dextrose, or saline if hypovolaemia
Sx and treatment of hyponatraemia
Sx - nausea and anorexia, malaise, headache, irritability, confusion, weakness, seizures
Asymptomatic chronic hyponatraemia - fluid restriction, +- ADH antagonist demeclocycline
Acute/symptomatic hyponatraemia - cautious rehydration with saline, - slowly to avoid fatal pontine demyelination - furosemide if not hypovolaemic to avoid fluid overloaded
Cause of hyponatraemia and oedema
Nephrotic syndrome
Cardiac failure
Liver cirrhosis
Renal failure
Hyponatraemia with normal urine osmolality
Water overload
Glucocorticoid insufficiency
Hyponatraemia with increase urine osmolality
SIADH
Hyponatraemia, dehydration and high urine sodium
Addison’s
Renal failure
Diuretics
Osmolar diuresis
Hyponatraemia, dehydration and low urine sodium
Water and sodium loss other than kidneys: Diarrhoea, vomiting, burns Small bowel obstruction, CF Trauma Heat exposure
Hyperkalaemia level, cause, sx and treatment
> 6.5mmol/l = emergency
From: K sparing diuretics, metabolic acidosis, rhabdomyolysis, oliguric renal failure, ACEi, Addison’s
Sx: fast irregular pulse, palpitations, chest pain, weakness, lightheaded
ECG: tall tented T, wide qrs, small p, VF
Treat: calcium resonium binds K in GI, preventing reabsorption, over a few days
Emergency: calcium gluconate to stabilise heart membrane) 10ml 10% calcium gluconate) and 10u actrapid in 50ml 20% glucose to drive K into cells
Causes of hypokalaemia and main drug effect
Diuretics
Vomiting and diarrhoea
Cushing’s, Conn’s
Renal tubular failure, alkalosis
Exacerbates digoxin toxicity
Signs of hypokalaemia
Muscle weakness,hypotonia, hyporeflexia
Cramps, tetany
Palpiations, light headed
Treat hypokalaemia
Oral K if mild
IV K cautiously, no more than 20mmol/h, if severe <2.5 - never stat bolus
Continuous ecg
Symptoms of acidosis
Kussmaul breathing Decreased myocardial contractility, arteriodilatation, venoconstriction Resistant arrhythmias (VF)
Anion gap formula
(Na + K) - (Cl + HCO3)
Causes of increased anion gap acidosis
KUSMAL Ketones Uraemia Salicylate Methanol Aldehydes Lactic acidosis
Treat acidosis
Sodium bicarb if pH <7 and impaired cardiac performance
Don’t give bicarb in DKA as delays removal of ketone bodies
Causes of metaoblic alkalosis including drugs
Vomiting, burns
Diuretics
CF
Laxatives, bicarb, penicillins, massive transfusion
Sx of metabolic alkalosis
Most sx from hypovolaemia or hypokalaemia
From decreased cerebral and cardiac perfusion - headache, confusion, seizures, angina, arrhythmias
Compensatory hypoventilation or hypocapnoea
Manage metabolic alkalosis
Treat cause
- KCl if low K, stop drugs causing it
Electrolytes in Hartmann’s
Na, Cl, K, HCO3, Ca, lactate
Distribution of saline and 5% dextrose
Saline - same Na concentration as plasma (150mmol/l), extracellular compartment, takes time to reach intracellular
5% dextrose - liver metabolises dextrose quickly so the water rapidly equilibrates across all compartments - useless in resusc as 1/9 stays in intravascular space
5 causes of transient haematuria
Exercise Sex Viral illness Trauma Menstruation
Glomerular causes of haematuria
IgA nephropathy
Alport’s
Focal GN
Upper urinary tract causes of haematuria
Stones, pyelonephritis
<40yo - trauma, polycystic kidney disease, ureteral structure
>40yo - renal cell carcinoma, transitional cell tumour, renal TB
Lower urinary tract causes of haematuuria
Cystitis, prostatitis, bladder cancer, prostate cancer
<40yo - urethral stricture
>40yo - BPH
RF for malignancy with haematuria
> 40yo, gross haematuria
Pelvic irradiation, occupational exposure
Smoking, alcohol, analgesia abuse
Signs suggestive of glomerular lesion
Proteinuria
Dysmorphic red cells and red cell casts
Renal impairment, high blood pressure
Inv for macroscopic haematuria
Urine cytology and MC&S
Cystoscopy, CT with and without contrast
FBC, U&E, G&S, clotting, PSA, Hb
Inv for microscopic haematuria
Repeat dipstick after 1w Urine MCS and PCR and cytology x3 eGFR CT, USS Nephrology workup
Diagnostic criteria for AKI - 3
Urine = <0.5ml/kg/h for 6h
Serum creatinine >26.5micromol/l within 48h
Serum creatinine >1.5x baseline
3 stages of AKI
KDIGO staging: Urine output: 1 - <0.5ml/kg/h for 6h 2 - <0.5ml/kg/h for 12h 3 - <0.3ml/kg/h for 24h or anuria for 12h Serum creatinine rise above baseline: 1 - >1.5x 2 - 2-2.9x 3 - >3x
3 categories of AKI and causes
Prerenal - hypovolaemia, sepsis (vasodilation and reduced CO)
Intrinsic renal - renal parenchyma = ATN, glomerular apparatus or interstitial damage
Postrenal - obstuction causing backflow - must have both blocked, or only 1 kidney to get AKI
RF for AKI
Age
CKD, diabetes, cardiac disease (LV dysfunction), myeloma
Volume depletion
Surgery
Drugs causing renal vasomotor changes - ACEi, ARB, NSAIDs
Presenting features of AKI
Non-specifically unwell, deteriorating Hypovolaemia, or fluid overload causing pulmonary oedema Decreased urine output Increasing urea and creatinine Hyperkalaemia
Imaging for AKI
Renal USS
CXR - sepsis?
Complications of AKI - 4
Pulmonary oedema
Uraemia
Acidaemia
Hyperkalaemia
Manage AKI
Fluid resusc until improved signs of volume depletion:
Reduced tachycardia, rising BP, visible JVP, improved urine output
Assess volume status
Remove nephrotoxic drugs
Indications for renal replacement therpay in AKI
K >6.5 Fluid overload (pulmonary oedema) refractory to medical treatment
Relative indications: Acidosis pH<7.2 Critically unwell Hyperthermia Toxin removal Uraemic complications Diuretic resistance in cardiac failure
CKD classification
Ideally should be 2 readings 3 months apart
1 - GFR >90 WITH evidence of kidney damage
2 - GFR 60-89 WITH evidence of kidney damage
3a - GFR 45-59 (+- evidence of kidney damage)
3b - GFR 30-44 (+- evidence of kidney damage)
4 - GFR 15-29
5 - GFR <15 = end stage, or approaching end stage
5D - GFR <15, on dialysis
Evidence of kidney damage =
- proteinuria, haematuria,
- or abnormal renal imaging,
- or genetic or histologically established disease
Causes of CKD
Diabetes
Hypertension, atherosclerotic disease
Cystic, congenital disease, glomerulonephritis
Infective or obstructive
Inv for CKD
FBC, U&E, ESR, glucose
Calcium low, phosphate and ALP high
PTH high if CKD stage 3+
Urine - MCS, cytology, ACR. Proteinuria = chronic kidney damage
Renal USS - small unless infiltration disease, look at anatomy
Biopsy and histology if rapidly progressive disease
Anaemia in CKD and treatment and why
Increase in severity with stage of CKD, higher risk if black or diabetic
Normocytic normochromic with normal level of WCC and platelets, from reduced EPO production
Treat with human recombinant epo, or erythropoeisis stimulating agents in dialysis or early CKD - improve exercise capacity, reduce fatigue, improve QoL cognitive function and sleep quality
Iron in late stages of CKD
Cause of falling phosphate in late stage CKD?
Renal osteodystrophy - altered bone morphology, in CKD 4 and 5 - check these
See fall in phosphate, calcium, vit D, and increase in PTH
CVS risks with CKD - 4
Coronary disease
CCF
Stroke
Peripheral vascular disease
CVS risk factors unique to CKD and manage
Valvular calcification, myocardial fibrosis Volume overload Anaemia Vit D def, hyperparathyroidism Insulin resistance
Offer statin to everyone with CKD +- antiplatelet
Factors affecting CKD progression
AKI, urine outflow obstruction (BPH) or structural/calculi (stones)
CVD, hypertension, diabetes
Multisystem disease with potential kidney involvement eg SLE
Smoking
Chronic use of NSAIDs, nephrotoxins
Estimation of eGFR - 4 inputs
Sex, race, age, creatinine
= MDRD equation
Manage hypertension in CKD and targets
Not diabetic, urine ACR <30mg/mmol - treat as normal
Urine ACR >30 - lisinopril or losartan (reduce intraglomerular pressure and proteinuria even if no htn)
- ACR <70mg/mmol, target BP 140/90
- ACR >70, target BP 130/80
Role of proteinuria in CKD - 3
Marker for progression
Causes progression itself
Independent RF for CVS
When to refer to nephrology with proteinuria
Very high ACR, +- haematuria
A bit high ACR + haematuria
When to assess nephrotoxicc drugs and when to start dialysiss - 8 indications
EGFR <60
Dialysis: GFR <15 and sx of advanced CKD - persistent nv, anorexia, malnutrition, volume overload GFR <5-7 regardless of sx Refractory hyperkalaemia, acidosis Pulmonary oedema Pericarditis, encephalopathy, neuropathy
Definition of diabetic nephropathy, and bp/HbA1c target
Dipstick proteinuria in someone with diabetes
Aim for HbA1c <7% and bp <130/80 to prevent
If proteinuria, target bp <125/75
Role of dialysis and what it can’t do compared to kidney
Remove excess salt, water and acid
Remove/regulate electrolytes - K, Ca, Mg, PO4
Remove waste products of metabolism
Can’t make epo or activate vit d
How does haemodialysis work
Hydrostatic pressure of blood, through semi permeable membrane to dialysate on countercurrent through dialyser, to clear solutes by diffusion. Both on high pressure, doesn’t clear large molecules well
- 4h 3x/w
What is haemofiltration and adv
No dialysate - clear solutes by convection, through transmembrane pressure across membrane. Need large volumes for adequate clearance, but clears large molecules better than haemodialysis. Greater haemodynamic stability so favoured in critical care
Dialysis access?
AV fistula - connection between artery and vein, takes 6-8w to mature before using. Synthetic graft is second best - risk of infection and operation, but can use within days.
Care for AV fistula:
- preserve arm veins in pre-dialysis patients - no cannula between elbow and wrist
- don’t bleed AV fistula
- dont do tourniquet or BP on that arm
Temporary haemodialysis catheter for immediate use eg AKI - higher infection rate and catheter malfunction
Complication of AV fistula
Infection of graft - normally needs surgical removal
Aneurysm/pseudoaneurysm at needle sites if not rotated
Distal ischaemia - flow through fistula compromising distal flow
Extravasation causing rapid limb swelling, haemodynamic compromise, compartment syndrome, secondary infection
Adv of peritoneal dialysis
Residual renal function preserved
Can be at home - patient independence, mobility, patient engagement
No vascular access needed
Cheaper
Use peritoneum (cap endothelium, matrix and peritoneal mesothelium) as semipermeable membrane, has 3 different sized pores for large, small solutes and water. 1 bag of dialysate in, 1 drains from peritoneal space into other bag
CI to peritoneal dialysis
Absolute = colostomy/ileostomy, hernia, abdo wall infection
Relative CI = gastroparesis, adhesions, morbid obesity, very big polycystic kidney
Complication of peritoneal dialysis, its sx, consequences and risk factors and treatment
Peritonitis - can relapse, abx failure, acute and chronic ultrafiltration failure, malnutrition
Sx - abdo pain, nausea, vomiting, cloudy dialysate. Then fever and sepsis, ileus, peritonism
RF - DM2, catheter type and implantation technique
Treat with IV antibiotics - vancomycin and cephalosporin
Advantages of renal transplant and measurement of outcomes
Patient survival, quality of life better
Physiological corrections of uraemia and anaemia better
Better sexual function and fertility
Better for health economy
Measure outcomes by 1) patient survival, 2) graft survival, 3) graft outcome
Kidney transplant contraindications - 3
Uncontrolled infection
Uncontrolled malignancy
Life expectancy <5y
Kidney transplant complications
Early - bleeding, wound infection, vascular thrombus/embolism, urinary leak, lymphocoele, early obstruction
Late - renal artery stenosis, ureteric stenosis, bladder dysfunction, skin cancer
Immunosuppression for kidney transplant
Induction = intense, at time of transplant, then maintenance for life
Triple therapy including steroid
Causes of mono arthritis and inv
Septic
Crystal arthropathy
Haemarthrosis
- aspirate, WCC, gram stain and culture, polarised light microscopy
Chronic = OA, psoriatic, meniscal tear, TB, foreign body
Causes of oligo and polyarthritis
Oligo - crystal arthritis, psoriatic, relative, OA, ankylosing spondylitis
Poly
- symm - RA, OA, viruses
- asymm - reactive, psoriatic
Systemic disease - SLE
