Chemical Pathology Flashcards
Osteoporosis
Loss of bone mass, normal calcium/biochemistry
Osteomalacia/rickets
Vitamin D deficiency cause:
1. Osteomalacia - low Ca AND phosphate, raised ALP!! Looser zones. An also be caused by renal failure due to no vitamin D.
2. Rockets - widened epiphyses at wrist, Costochondral swelling, myopathy. Can be caused by anticonvulsants which break vitamin D down.
*phytic acid can also cause vitamin D deficiency
Pagets
leg!
spine, hip, skull
Hypocalcemia/hypercalcemia
Equation for calculating corrected calcium?
Total serum calcium + (0.02 x (40 - serum albumin) )
Role of PTH in kidney?
Converts 25 to 1-25OH (calcitriol). Via 1-alpha hydroxylase
Note 25 is stored and measured form. It is made in liver by 25 hydroxyalse
Vitamin D2 vs D3
Ergocalciferol - plant
Cholecalciferol
Parathyroid bone disease
oteitis fibrosa cystica - seen in primary hyperparathyroidism
Renal osteodystrophy
Pthrp?
Made in pregnancy, mother sacrifices calcium to build fetus skeleton
Which hormone controls water balance?
ADH, acts on V2
Stimuli for ADH release?
Reduction in blood volume or pressure - sensed by baroreceptors
Increased osmolality sensed by osmoreceptors
first step in the clinical assessment of a patient with hyponatraemia?
Assess volume status
Hypovolemic hyponatremia signs?
Causes?
Management?
- Tachycardia
–Postural hypotension
–Dry mucous membranes
–Reduced skin turgor
–Confusion/drowsiness
–Reduced urine output
–Low urine Na+ (<20) = KEY!! - most reliable, send test
1. Diuretics
2. Diarrhea, vomiting
3. Salt losing nephropathy
0.9% saline
Euvolemic hyponatremia
causes?
Management?
Hypothyroidism - TFTs
•Adrenal insufficiency - short syncthathen test
•Syndrome of inappropriate ADH (SIADH) - plasma and urine osmolality
Fluid restriction, check underlying cause
Hypervolemic hyponatremia signs?
causes?
Management?
Raised JVP
–Bibasal crackles (on chest examination)
–Peripheral oedema
Cardiac failure
–Cirrhosis
–Renal failure eg nephrotic syndrome,
Fluid restriction
–Treat the underlying cause
Hyponatremia?
Pathogensis?
Serum sodium < 135 mmol/L
Excess water due to ADH
SIADH causes?
Diagnosis?
Management
CNS or lung pathology, Drugs (SSRI, TCA, opiates, PPIs, carbamazepine), surgery
•Reduced plasma osmolality AND
•Increased urine osmolality (>100) = KEY
Tests rule out other causes of hypothyroidism, adrenal insufficiency AND hyPOVolemic hyponatremia are important
Demeclocycline
Tolvaptan
Central pontine myelenosos symptoms? Cause?
quadriplegia, dysarthria, dysphgia, seizures, coma, death
Raising sodium too much
Hypernatremia
Causes?
Management?
Serum [Na+] > 145 mmol/L
GI losses, sweat, diabetes insipidus!!
Correct water deficit - 5% dextrose
•Correct extracellular fluid volume depletion - 0.9% saline
•Serial Na+ measurements - Every 4-6 hours
Severe hyponatremia
Low GCS, siezures
Treat with 3% hypertonic saline
Investigations in patient with diabetes insipidus?
Serum glucose (exclude diabetes mellitus)
–Serum potassium (exclude hypokalaemia)
–Serum calcium (exclude hypercalcaemia)
–Plasma & urine osmolality
–Water deprivation test
Are thiazide diuretics useful in patients with high bp and a history of CAD?
Yes
How many years of poor glucose control before symptoms
15 years
Benefits of SGLT2 inhibitors eg empagliflozin
Additionally Beneficial in HF and patients w nephropathy
Flozins also useful in CKD with patients w or without type 2 diabetes
GLP1- analogues
1. Exanatide
2. Liraglutide
3. Semaglutide
T2DM management
1. Metformin
If insufficient best to combine with SGLT2 or GLP1
Adrenal glands and what is made in each zone
GFR = salt (aldosterone), sugar (cortisol), sex (comes last)
in medulla = adrenaline and NA
Learn reference range for sodium potassium and urea
Hemoglobin wbc and platelets
Addison’s disease
Confirmatory test?
Short Synacthen test
You inject them with it
Normal patients - rise in cortisol
Addison’s - No rise
Phaeochromocytoma management
Alpha blocker first
Beta blocker next
Surgery
Conns syndrome management? (Primary hyperaldosteronism)
Spirinolactone
Top causes of Cushing’s syndrome?
Top cause is being on steroids
Then Pituitary dependent cushings disease = 85%
Ectopic ACTH
Adrenal Adenoma
Cushing’s syndrome if low dose dexamethasone suppresses cortisol falls to LESs than 50, what is diagnosis?
Normal obese person
If a patients cortisol remains high after a low dose dex suppression, what is the next test you need to do?
ACTH
you need to know if it suppressed
If ACTH is suppressed = adrenal tumour causing cushings - then the next test would be adrenal ct
If a low dose dex fails to suppress, what test do you do?
Pituitary sampling
High dose dex test is now redundant
hypercalcemia
symptoms?
causes?
management?
Polyuria / polydipsia
Constipation
Neuro – confusion / seizures / coma
1. primary hyperparathyroidism - PTH high. parathyroid adenoma, associated with MEN1
2. Malignancy - pTH suppressed. bony mets, haematological malignancy, small cell lung cancer
3. other minor like sarcoidosis
management = fluids, bisphosphonate ONLY if malignant cause
Hypocalcemia
symptoms - neuromuscular excitability
causes
Non-PTH driven:
1. vitamin D deficiency – dietary, malabsorption,
2. chronic kidney disease (1α hydroxylation)**
3. PTH resistance (“pseudohypoparathyroidism”)
Due to low PTH:
1.Surgical (inc post thyroidectomy)
2. Auto-immune hypoparathyroidism
3.Congenital absence of parathyroids (eg DiGeorge syndrome)
4. Mg deficiency (PTH regulation)
Osteitis fibrosa is seen in?
Renal osteodystrophy is seen in?
1. primary hyperparathyroidism
2. secondary hyperparathyroidism
pagets disease
raised ALK PHOS
interpret arterial blood gas results
H+ ] 35-45 nmol/l in ECF
pH 7.35 -7.46
pH = log 1/ [H+ ]
acid buffers in the body?
bicarbonate - main
hemoglobin - main in rbcs
phosphate
metabolic acidosis presents as?
causes
H+ increased or HCO3- decreased
compensated = reduction in CO2
Increased H+ production e.g. diabetic ketoacidosis
2. Decreased H+ excretion e.g. Renal tubular acidosis
3. Bicarbonate loss e.g. intestinal fistula
respiratory acidosis presents as?
increased CO2 which causes high H+
poor ventilation - pulmonary emboli
impaired gas exchange - emphysema
compensated = kidney increasing bicarb
metabolic alkalosis presents as?
causes?
decreased H+, increased HCO3-
compensation = increased CO2
Increased H+ production e.g. diabetic ketoacidosis
2. Decreased H+ excretion e.g. Renal tubular acidosis
3. Bicarbonate loss e.g. intestinal fistula
respiratory alkalosis presents as?
low CO2, which causes low H+ and bicarb
hyperventilation
compensation = decreases H+ excretion
1. H+/pH tells us whether there is an overt acidosis or alkalosis - look at this first
2. then this - pCO2 tells us whether there is a respiratory disturbance (primary or secondary)
3. then pO2
4. then Bicarbonate
sensitivity of test?
people in who disease is present
true positive/total disease present
specificity of a test?
people in who disease is absent
True negative/total disease absent
positive predictive value?
negative predictive value?
true positive/all positive
true negative/total negative
metabolic diseases & newborn screening
PKU
homocystinuria - lens dislocation, thromboembolism, mental retardation
MCAD
urea cycle defect presentation
hyperammonemia = KEY finding!
when levels very high -> coma
long term psychiatric findings may occur
red flags =
1. vomiting without diarrhea
2. neurological encephalopathy
3. avoidance food/ change in diet
4. resp alkalosis, hyperammonemia
autosomal recessive except OTC which is
treatment = removal of ammonia eg with sodium benzoate, dialysis sometimes
low protein diet
organic acidurias findings?
hyperammonemia with metabolic ACIDOSIS (contrast to urea cycle disorder)
in neonates:
1. unusual odour, lethargy, truncal hypotonia + limb hypertonia
2. hyperammonemia with metabolic ACIDOSIS
3. hypocaclemia, neutropenia, thrombopenia
chronic intermittent form in older kids:
- ketoacidotic coma, reyes syndrome (child with reyes syndrome can be due to metabolic disease -> therefore run ammonia, amino acid, organic acid, glucose and lactate tests)
- involve metabolism of branch chained amino acids leucine, isoleucine, valine
3OH-isovaleric acid - excretion causes cheesy sweaty smell
MCAD findings?
HYPOKETOTIC (cant break down fat) HYPOGLYCEMIA -> key finding
Galactosemia (carb disorder)
presentation?
Conjugated hyperbilirunemia!!!
vomiting, diarrhea
hypoglycemia
sepsis
bilateral cataracts -> due to galctitiol buildiup in kids if not picked up earlier
galactose-1-phoshate uridyl transferase (Gal-1-PUT) is the most severe and the most common
diagnosis = Red cell Gal-1-PUT
galactose free diet
Glycogen storage disease type 1 (von gierke)
a carb disorder
Hypoglycemia!!!
lactic acidosis!!!
hepatomegaly
nephromegaly
neutropenia
mitochondrial disorders examples?
Tests?
Barth (cardiomyopathy, neutropenia, myopathy)
MELAS (mitochondrial encephalopathy, lactic acids and stroke-like episodes)
Kearns-Sayre (Chronic progressive external ophthalmoplegia, retinopathy, deafness, ataxia)
lactate - elevated fasting lactate is a clue
CK
CSF protein
muscle biopsy
peroxisomal disorders?
presentation?
impaired metabolism of very long chain fatty acids
neonates = severe hypotonia
infants = retinopathy often leading to early blindness, sensorineural deafness, hepatic dysfunction, osteopenia and enlarged fontanelle
lysosomal storage disease?
intraorganelle substrate accumulation leading to organomegaly -> connective tissue, solid organs, bone, cartilage -> dysmorphia, regression
common problems in LBW babies?
respiratory distress syndrome, retinopathy of prematurity
intraventricular hemorrhage
patent ductus arteriosus
necrotising enterocolitis - necrosis of bowel wall = abdominal distension (AXR Shows intramural air), bloody stools
differences in a nephron in a baby
short proximal tubule -> reduced resorptive capacity
short loops of henle and dct -> reduced urine concentrating ability
distal tubule quite unresponsive to aldosterone -> persistent loss of sodium
drugs given to babies
bicarbonate for acidosis
caffeine/theophiline for apneoa of prematurity
indomethacin for pda
Hypernatremia in newborns?
common in first days of life
Hyponatremia in newborns?
congenital adrenal hyperplasia
treatment for hyperbilirubenemia
in a term baby:
340 = phototherapy
450 = exchange transfusion
causes of hyperbilrubinemia in first few days of life?
Haemolytic disease (ABO, rhesus etc)
G-6-PD deficiency
Crigler-Najjar syndrome
causes of prolonged jaundice?jaundice that lasts for more than 14 days in term babies and more than 21 days in preterm babies
Prenatal infection/sepsis/hepatitis
Hypothyroidism
Breast milk jaundice
conjugated!!! hyperbilirubinemia is always pathological. causes include?
- biliary atresia
- choledocal cyst
- ascending cholangitis in total parenteral nutrition in premature babies due to lipid content
-inherited metabolic disorders eg galactosemia
the lower limit for hypocalcemia is much lower in in infants than in adults.
Osteopenia of prematurity presents as?
treatment?
fraying, splaying, cuffing of long bones
low phosphate -> suggest calcium depletion even though calcium may be normal
Alk Phos 10x upper limit of normal
calcium and phosphate supplements
rickets present as?
osteopenia due to vitamin D deficiency
frontal bossing, bow legs
hypocalcemic seizure/ cardiomyopathy
what is porphyria?
deficiencies in heam synthesis pathway
Neurovisceral symptoms - due to 5 ALA
blistering cutaneous symptoms. - due to porphoryins
non blistering cutaneous symptoms - due to porphoryins
most common porphyria?
1. Porphyria cutanea tarda - uroporphyrinogen decarboxylase deficient. skin affected only, non acute. sun avoidance is treatment. typically caused by liver disease eg hep b
2. Acute intermittent Porphyria
3. Erythorpoietic protoporphyria - most common in children. skin affected only, non acute. sun avoidance
ALA synthase deficiency causes?
x-linked sideroblastic anemia
not a porphyria
PBG synthase/ALA dehydratase deficiency signs?
- decreased PBG
- ALA accumulation = neurovisceral symptoms = coma, motor neuropathy, abdominal pain
HMB synthase/PBG deaminase deficiency signs?
causes Acute intermittent prophyria
-increased PBG and, ALA = neurovisceral symptoms - siezures, quadraparesis.
SIADH
no cutaneous syndromes as no increase in prophoryins
90% people have no symptoms only which precipitating factors eg ALA synthase inducers/drugs
diagnosis = increased urinary PBG/ALA
treatment = IV heam arginate, IV carbs, avoid precipitants
name the acute porphyrias with skin lesions and the deficient enzymes
Hereditary coproporphyria - coproporphyrinogen oxidase
Variegate porphyria - protoporphyrinogen oxidase
neurovisceral symptoms due to accumulated products which inhibit HMB synthase by negative feedback
blistering skin lesions
how to differentiate acute porphyrias
AIP – no skin lesions
HCP & VP – skin lesions
Urine PBG – raised in all three
Urine and faeces for porphyrins
Raised HCP or VP, but not AIP
how to test for porphyrias
neurovisceral symptoms:
1. Urine PBG
-normal = excludes attack
- raised = enzyme activity, urine/faecal porphyrins, DNA
Skin features:
- urine/faecal porphyrins
photosensitivity (cutaneous syndrome without blisters):
- red cell protoporphyrins to rule out EPP
Urine samples taken during an acute attack for diagnosis of porphyrias should be?
protected from light
primary hypercholesterolemia causes
familial hypercholesterolemia type 2 - homozygous may have atheroma of aortic root, heterozygote = corneal arcus, xanthelasma, tendon xanthoma
polygenic hypercholesterolemia
familal hyperalipoproteinemia
phytosterolemia
Most common mutation in Familial hypercholesterolemia (type 1 familial dyslipidemia)
1. Mutation of LDL gene
2. mutation of APOB
least common = gain of function mutation in PCSK9
primary hypertryglyceridemia causes ?
presentations?
type 1 familial dyslipidemia (hyperchylomicronemia) = lipoprotein lipase or apoC 2 deficiency. creamy layer on top of plasma sample which indicates chylomicrons. eruptive xanthomas.
type 4 familial dyslipedemia (hypertriglyceridemia) = increased synthesis of TG. Vldl particles which dont float
type 5 familial dyslipedemia =apoA 5 deficiency. vldl + layer of floating chylomicrons
name a cause of primary mixed hyperlipedemia and its cause
familial dysbetalipoproteinemia type 3 = ApoE 2 polymorphism = palmar straie (yellow palmar crease), eruptive xanthomas on elbow
state 3 secondary causes of hyperlipedemia
metabolic - obesity, gout, diabetes - could present with eruptive xanthomas
renal dysfunction
obstructive liver disease - eg primary billiary cirrhosis - may cause gross xanthelasma
hormonal factors - hypothyroidism
hypolipidemia causes
AB - lipoprotenemia = MTP deficiency
Hypo - B -lipoprotenemia = truncated ApoB
Tangier disease - HDL deficiency
Obesity treatment?
diet and execise
orlistat
Bariatric surgery if BMI > 40 kg/m2 - with gastric band being least invasive
which enzyme controls uptake of idoide into thyroid gland?
TSH
once taken in, idoide converted to iodine (by thyroid peroxidase)
iodine taken up by thyroglobulin
Tyrosine residues iodinated (blocked by thionamides)
iodotyrosines join to form thyroxine
what is T4 mostly bound to?
1. TBG - 75% thyroglobulin binding globulin
2. TBPA
3. Albumin
3 most common causes of hypothyroidism?
1. hashimotos disease
2. Atrophic thyroid - congenital or acquired
3. Post Graves disease - eg radioiodine treatment
others less common
if thyroid peroxidase antibodies present, this suggests autoimmune cause of hypothyroidism
hypothyrodism is linked to other autoimmune processes so measure adrenal antibodies, early morning cortisol
effect of giving too much levothyroxine?
osteopenia, atrial fibrillation
what is subclinical hypothyroidism? learn!
T4 levels are normal
pituitary gland senses this as too low, thus TSH levels are elevated
+TPO antibodies predicts later thyroid disease!!
only treat if cholesterol levels are elevated
what happens in early pregnancy?
hcg produced binds to TSH receptor, causes increased T4. and lower TSH
later on in pregnancy when hcg decreased, T4 decreases and TSH increases
normal pregnancy physiology
what is sick euthyroid syndrome? learn!
low T4 level
TSH normal or slightly high
T3 low
individual sick eg sepsis, thyroid shuts down to reduce metabolic rate
- can be mistaken for hypothyroidsim or subclinical hypothyroidism -> to differentiate these patients wont have clinical signs of hypothyroidism - bradycardia, hyporeflexia, weight gain
3 main causes of hyperthyroidism?
1. Graves disease
2. Toxic multinodular goitre
3. single Toxic adenoma
these 3 have high uptake on technetium scan
others: postpartum thyroiditis, subacute thyroiditis (these 2 have low uptake on scan)
thyrotoxicosis/ hyperthyroidism management
- B block if pulse >100
think of other autoimmune conditions might have
- ECG - to rule out a fib
- DEXA scan - rule out osteopenia
- radioactive iodine -> release radiation to destroy thyroid gland -> may precipitate thyroid storm. AVOID in patient with Graves eye disease
- carbimazole/propylthiouracil (thionamides, prevent iodide to iodine)
presence of thyroid autoantibodies can help with diagnosis
treatment for viral or portpartum thyroiditis?
thyroxine replacement
contrast to other causes of hyperthyroidism
Thyroid cancer types?
treatment?
1. papillary thyroid cancer
2. follicular thyroid cancer
3. medullary thyroid cancer
thyroidectomy, then radioiodine treatment to remove any remaining thyroid cells, then excess thyroxine to lower TSH levels to prevent thyroid cells growth
measure thyroglobulin in plasma to check if functioning thyroid tissue still present
how to screen for medullary thyroid carcinoma?
measure calcitonin and CEA
(mtc is associated with MEN2)
if a patient presents with elevated thyroglobulin? what does this mean@
you need to screen for recurrence of differentiated thyroid carcinoma
pituitary driven thyrotoxicosis presents as?
elevated TSH and T4
Map out the purine catabolism pathway
Purine -> hypoxanthine
Hypoxanthine -> xanthine
Via xanthine oxidase
Xanthine -> urate
Via xanthine oxidase
Urate -> allantoin
Via uricase
Uricase is inactive in humans, so urate must be excreted. And it is insoluble. Men have higher urate plasma concs.
Learn
-> de Novo purine synthesis
-> Purine salvage pathway - more efficient, dominates, except in bone marrow
What is the rate limiting step in de novo purine synthesis?
PRPS -> PPRP
catalysed by PAT
Inhibited by feedback inhibition by the products AMP and GMP
Importance of HGPRT?
Transfers guanine back up to GMP
And hypoxanthine back up to ionosinic acid
Lesch Nyhan syndrome cause?
Symptoms?
HGPRT deficiency. No GMP and IMP being made through salvage pathway, decreased negative feedback on PAT, so increased de novo purine synthesis which is catabolised to urate
X linked
Normal at birth
Developmental delay apparent by 6 months
Hyperuricemia!! -> gouty arthritis in child
Choreiform movements
Mental retardation
Self mutilation - > bite lips, digits
Secondary causes of increased urate production?
Lesch nyhan is a primary cause
Conditions with increased cell turnover:
-> myeloproliferative disorders
-> lymphoproliferative disorders
Causes of decreased urate excretion?
Primary = FJHN
Secondary = CRF, lead poisoning, diuretics!! barters syndrome
Acute gout is called?
Chronic gout is called?
Podagra
Tophaceous
Hyperuricemia management?
Acute gout attack - NSAIDs, colchicine
Non acute/ interval - water, reduce synthesis with allopurinol, probenacid
Side effects of allopurinol?
Interacts with azathioprine
Causes levels of mercaptopurine to build up. Mercaptopuribe metabolises azathiprine this u are doubling/increasing azathioprine dose to toxic amount which can break down bone Marrow -neutropenia
Allopurinol mechanism of action?
Lowers urate levels by inhibiting xanthine oxidase
Gout mono sodium urate crystal shape
Needle shaped and Negatively birrefringente
(It is blue at 90 degrees to axis/ compensator)
Pseudo gout
Caused by pyrosphosphate crystals
Positively birrefringent so they are blue parallel to axis/compensator
Commonly affects people with osteoarthritis, commonly affects knee
vitamin A deficiency and excess?
vision problems
skin problems, hepatitis
Vitamin E deficiency?
anemia
neuropathy
vitamin K deficiency?
defective clotting
PTT test
vitamin B1/thiamine deficiency?
test?
beri beri
neuropathy
wernicke syndrome
RBC transketolase
Vitamin B2/ riboflavin Deficiency?
test?
glossitis
RBC glutathione reductase
Vitamin B6/pyridoxine deficiency?
test?
dermatitis/anemia
excess = neuropathy
RBC AST activation test
B12 Cobalamin deficiency?
test?
pernicious anemia
serum B12
niacin deficiency?
pellagra - diarrhea, dermatitis, dementia
iodine deficiency can cause?
goitre
hypothyroidsm
zinc deficiency can cause?
dermatitis
copper deficiency can cause?
excess?
anemia
wilsons disease
fluoride deficiency can cause?
dental caries
leptin vs ghrelin?
ghrelin - hunger hormone
leptin - anti hunger hormone
PYY - satiety hormone
interpreting BMI
25 - 30 is overweight
> 30 is obese
> 40 is morbidly
what waist circumference increases risk of CV disease?
men >94
women > 80 cm
waist circumference important in measuring degreeof adiposity and CVR risk
polyunsaturated fat is good because it lowers?
LDL
treatment for obesity?
exclude endocrine cause
exclude complications of obesity
educate
diet and exercise
medical therapy - orlistat, GLP-1 agonist
surgical therapy
what surgery is the best for obesity
gastric bypass - you loose the most weight with this specific type as well
benefits of bariatric surgery?
improvement in T2DM
improvement in HTN
improved lipid profile
resolution of PCOS and improved fertility
marasmus vs kwashiokor
kwashiokor patients lack protein only and they are edematous
marasmus low carbs and lipids as well, muscle wasting
best predictor of MI risk and benefit of statins?
measurement of total plasma cholesterol and lipoprotein levels
alcohol intoxication treatment?
thaimine pabrinex
what type of autoimmune disease is primary billiary cirrhosis?
organ specific but no organ specific antibodies
SLE symptoms
skin - butterfly rash, photosensitivity, discoid lupus
oral ulcers
joints
neurological - psychosis, depression
serositis - pleuritic chest pain
renal - lupus nephritis - 6 classes - 1 presentation is wire looping = thick walled capillaries in GBM = KEY!!
hematological - pancytopenia
immunological - ANA, anti-dsDNA, antiSmith (most specific but not specific), antiHistone(drug related lupus eg hydralazine)
non infective endocarditis -> libman-sacks
scleroderma/ systemic sclerosis
diffuse vs limited form
excess collagen
diffuse= antibodies to DNA topoisomerase Scl70. truncal skin involvement
Limited = CREST anticentromere antibody
Calcinosis
raynauds
esophageal dysmotility
sclerodactyly
Telangiectasia
nucleolar pattern of immunofluorescence may be seen
nail fold capillary dilatation may be seen
microstomia
Histology; Intimal proliferation, leading to renal hypertensive crisis - KEY
mixed connective tissue disease presents as ?
features of:
SLE
Scleroderma
Polymyositis - elevated CK
Dermatomyositis - gottrons papules
Speckled pattern of ANA seen
anti-RNP
Sarcoidosis presentation?
joint
skin - lupus pernio, erythema nodosum
lungs - BHL, fibrosis, lymphocytosis
lymphadenopathy
heart
eyes -uveitis, keratoconjuctivitis
neuro - meningitis, cranial nerve lesions
liver - hepatitis, cholestasis, cirrhosis
bilateral enlargement of parotids
hypercalcemia
Hypergammaglobinemia
Raised ACE
state 2 large vessel vasculitis
Giant cell arteritis - steroids, ESR bloods, biopsy
Takayasu arteritis
State 2 medium vessel vasculitis
polyarteritis nodosa - renal and mesenteric vessels - gut ischemia, renal impairment, angiogram shows beading of vessels due to aneurysms, associated with hep B. necrotising arteritis
kawasaki disease - fever, erythema and desquamation of palms and soles, lymphadenopathy, self limiting although coronary arteries may be affected
state 2 small vessel vasculitis
describe their presentations?
Wegners - granulomatosis with polyangiitis:
1. ENT - nosebleeds, sinusitis, ear problems
2. Lungs - breathlessness, cavities in lungs
3. Kidneys - blood/protein in urine
- C ANCA +ve <- request this. antibody binds to proteinase 3 in CYTOPLASM
Churg strauss - eosinophilic granulomatosis with polyangitis
1. Asthma
2. Eosinophilia
3. Vasculitis
- P ANCA against myleoperoxidase, binds Perinuclear. <- request this test
a palpable purpural rash is due to?
Vasculitis
secondary causes of vasculitis
infective endocarditis
Rheumatoid arthritis
SLE
ethylene glycol poisoning signs
alcoholic
calcium oxalate stones
imaging choice for 28 year old with suspected renal stones
CT over ultrasound KUB
causes of pre renal AKI
True volume depletion
Hypotension
Oedematous states
Selective renal ischaemia
Drugs affecting glomerular blood flow
Intrinsic/Renal AKI
Vascular Disease e.g. vasculitis
Glomerular Disease e.g. glomerulonephritis
Tubular Disease e.g. ATN
Interstitial Disease e.g. analgesic nephropathy
contrasts, drugs, endogenous toxins
infiltration - amyloidosis, lymphoma
immune dysfunction - vasculitis
dilated bilateral kidneys on ultrasound may be caused by?
BPH
Post Renal AKI causes
Hallmark is physical obstruction to urine flow
(Intra-renal obstruction)
Ureteric obstruction (bilateral)
Prostatic / Urethral obstruction
Blocked urinary catheter
most common causes of AKI?
decreased renal perfusion
medication
contrast media
postoperative
sepsis
causes of CKD?
Diabetes
Atherosclerotic renal disease
Hypertension
Chronic Glomerulonephritis
Infective or obstructive uropathy
Polycystic kidney disease
consequences of CKD?
Progressive failure of homeostatic function
-Acidosis
-Hyperkalaemia
2]Progressive failure of hormonal function
-Anaemia
-Renal Bone Disease - Osteitis fibrosa, Osteomalacia, Adynamic bone disease, Mixed osteodystrophy
3]Cardiovascular disease - MOST IMPORTANT consequence of CKD main cause of death. risk directly predicted by EGFR
-Vascular calcification
-Uraemic cardiomyopathy -Left ventricle (LV) hypertrophy, LV dilatation, LV dysfunction
4]Uraemia and Death
What two measures do we use to define severity of acute kidney injury?
1. serum creatinine
2. urine output
contraindications to renal transplantation?
active sepsis
any malignant disease
osteitis fibrosa
Osteoclastic resorption of calcified bone and replacement by fibrous tissue
what is adynamic bone disease?
Excessive suppression of PTH results in low turnover and reduced osteoid
treatment for renal bone disease?
Phosphate control
Dietary
Phosphate binders
Vit D receptor activators
1-alpha calcidol
Paricalcitol
Direct PTH suppression
Cinacalcet
heroin abuse main risks?
respiratory depression, aspiration pneumonitis
cocaine abuse main risks?
cardiac dysarrhythmias, MI, acute HF, sudden death
amphetamines main risks?
hyperthermia, rhabdomyolysis, renal failure
methadone main risks?
respiratory depression
pregabalin/gabapentin main risks?
euphoria
how to calculate osmolality?
osmolality = charged molecules + uncharged
= cations + anions + urea + glucose
= Na, K. + Cl, HCO3. + urea + glucose
since charged molecules = uncharged, what is the simplified formula
2 (Na+ K+) + urea + glucose
you double sodium and potassium because cations = anions (cl- and hco3-)
very high osmolality can cause someone to be unconsious due to dehydration
in diabetes would be due to hyperosmolar hyperglycemic syndrome
how to calculate anion gap?
(cations - anions )
what is a normal anion gap?
Na + K - Cl - bicarb
4-12?
if high anion gap eg 50, it means cl and bicarb are low and thus other anions making up their space - may be ketones, alcohol, lactate (metformin overdose can cause lactic acidosis)
learn normal ph and C02 range so you can tell if something is acidosis or alkalosis in exam and metabolic vs repsiratory
definition of type 2 diabetes
fasting glucose > 7
if fasting glucose is below 7 but
GTT shows plasma glucose >11.1 at 2 hours
2 hour value 7.8 - 11.1 = impaired glucose tolerance
causes of mixed alkalosis and acidosis?
aspirin overdose
Potts fracture vs Colles fracture
Potts -> ankle
Colles -> wrist
single investigation to distinguish cause of hypercalcemia between cancer, primary hyperparathyroidism and sarcoidosis
PTH
in primary hyperparathyroidism, PTH is raised or inappropriately normal
in sarcoidosis, PTH is suppressed. sarcoidosis is treated with steroids
hypercalcemia symptoms?
psychic moans (depression), bones (fractured - cystic lesions, brown tumour on histology), groans(abdo pain, pancreatitis), stones(renal)
nephrogenic DI -> polydipsia, polyuria
renal stones(pain, hematuria), pancreatitis, Peptic ulcer disease
band keratopathy
**hypercalcemia commonly presents with depression
emergency management of hypercalcemia?
Ca2+ >3.0 mmol/L = emergency management:
0.9% saline:
furosemide
IV pamidronate
non emergency:
hydration
avoid thiazides
surgery - parathyroidectomy
aldosterone effect in kidney?
stimulates sodium reabsorption and increases urinary potassium excretion
state 3 main causes of hyperkalemia
1. renal impairment (reduction in GFR)
2. drugs: ACE inhibitor, angiotensin 2 receptor blocker, spironolactone, NSAIDS
3. low aldosterone: Addisons, Type 4 RTA which has low renin and low aldosterone
4. release from cells: rhabdomyolysis, acidosis
management for hyperkalemia?
10 ml 10% calcium gluconate
50 ml 50% dextrose + 10 units of insulin
Nebulized salbutamol
Treat the underlying cause
causes of hypokalemia
GI loss
Renal loss
Hyperaldosteronism, (Excess cortisol)
Increased sodium delivery to distal nephron
Osmotic diuresis - thiazide and loop diuretic
Redistribution into the cells
Insulin, beta-agonists, alkalosis
Rare causes: Renal tubular acidosis type 1& 2 (barterr in ascending loop and gietlemann syndromes in dct), hypomagnesaemia
hypokalemia symptoms?
Muscle Weakness
Cardiac arrhythmia
Polyuria & polydipsia (nephrogenic DI)
hypokalemia management?
Serum potassium 3.0-3.5 mmol/L
Oral potassium chloride (two SandoK tablets tds for 48 hrs)
Recheck serum potassium
Serum potassium < 3.0 mmol/L
IV potassium chloride
Maximum rate 10 mmol per hour
What screening test would you order in a patient with hypokalaemia and hypertension?
aldosterone:renin ratio
normal potassium levels?
3 -5 mmol/L
gold standard way of demonstrating hypoglycemia?
venous blood glucose
c peptide is a cleavage product of what
proinsulin
hypoglycemia from injected insulin causes what c peptide levels
low cpeptide
high insulin
name a cause of hypoinsulineamic hyperglycemia
(low insulin
low c peptide)
anorexia (low liver gylcogen stores)
critically unwell
fasting
endocrinopathies - addisons disease, pahypopituitarism
name a cause of hyperinsulineamic hyperglycemia
(high insulin
high cpeptide)
pancreatic causes - insulinoma, sulphunylureas
hypoglycemia, low cpeptide low insulin BUT also negative ketones and FFA in
1. 60 year old man
2. newborn
typically due to?
60 year old - non-islet cell tumour hypoglycemia
newborn - errors of fatty acid metabolism
define Km
1/2vmax
causes of raised ALP?
intrahepatic and extrahepatic bile ducts
bone causes - fracture, pagets disease, cancer etc
placenta - pregnancy in last trimester, germ cell tumours
Intestine
- check LFTS - GGT ALT, if normal check vitamin D
patient presents with polydipsia, polyuria, glycosuria. diabetes suspected. very dehydrated. BP 80/40 patient unconcious - what is the most likely reason?
patients anion gap is 12, is diabetic ketoacidosis likely?
hyperosmolar non ketotic coma
not DKA due to low anion gap
ectopic acth -> lung cancer -> resp exam shows reduced sounds on right, dullness to percussion, increased vocal resonance
most likely cause?
collapse and consolidation
how to distinguish acute renal failure from chronic renal failure?
renal biopsy
pituitary failure causes hypotension. true or false?
False!!
- pituitary gland does not control aldosterone! it controls cortisol!
- renin controls aldosterone
what investigation is done next when someone is found to have prolactinoma on pituitary mri??
combined pituitary function test!! -ACTH, GH
(make sure pituitary can respond to stress)
done by administering insulin to cause hypoglycemia
severe hypoglycemia occurs? -> 20% dextrose
In pituitary failure, what hormone is most important to replace first?
in addition to various hormones replaced hydrocortison, thyroxine, estrogen GH, what other treatment is needed for prolactinoma?
hydrocortisone
fludrocortisone is given in addisons disese! = adrenal!! failure (aldosterone replacement)
cabergoline or bromocriptine!! (dopamine agonist)
pituitary tumour, prolactin <3000
other hormones low
most likely diagnosis?
non functioning pituitary adenoma
28 year old with visual field defect
GH quite high other hormones low. most likely diagnosis?
acromegaly!
