Endocinology Flashcards
What is T1DM?
Hyperglycaemia due to insulin deficiency.
By autoimmune destruction of beta cells of the pancreas.
Cause of T1DM?
Autoimmune
Genetic: HLA-DR3-DQ2 or HLA-DR4-DQ8
Enterovirus
Risk factors of T1DM (5)
Northern European
Family history (HLA)
Autoimmune diseases (Coeliacs, Addisons)
Enteroviruses
Vit D deficiency
Pathophysiology of T1DM
Autoantibodies destroy insulin-secreting Beta cells
Causes insulin deficiency
Leads to hyperglycaemia
Makes you thirsty
Lots of urine containing glucose
Can lead to diabetic ketoacidosis if no insulin given
Insulin is required to move glucose from blood into cells.
GLUT 4 (insulin regulated glucose transporter)
Signs & Symptoms of T1DM
Lean
Glucose + ketones in urine
Glove and stocking
Reduced visual acuity
Diabetic foot
Thirsty
Lots of urine
Weight loss
Lethargy
What effect does ketoacidosis have on the body?
Ketone bodies are strong acids:
lower the pH of the blood
impairs Hb ability to bind O2
acute kidney injury
reduced glucose supply to cells due to lack of insulin THUS ketones formed
Investigations of T1DM (4)
1- Blood glucose ≥11mmol/L
2- Fasting blood glucose:≥7.0 mmol/L
Two abnormal values are required in asymptomatic individuals
3- Oral glucose tolerance test:>11mmol/L
(two hours after a 75g oral glucose load)
7.8-11mmol/L suggests pre-diabetes.
4- HbA1C (uncommon as type 1 diabetes has fast onset)
Other: C-Peptide, Autoantibodies
When should you suspect MODY?
(maturity onset diabetes of the young)
Patients who are:
Non obese
Young
Family history of diabetes
How do you differentiate MODY from T1DM?
C peptide will be present, autoantibodies will be absent
Management for T1DM?
1- lifestyle (weight, smoking, alcohol, carb counting)
2- Basal - bolus
Complications of insulin therapy? (4)
- Hypoglycaemia: (also caused by SULFONYLUREA - antidiabetic drug)
- Injection site - lipohypertrophy
- Insulin resistance
- Weight gain: insulin makes people feel hungry
How do you manage T1DM?
HbA1c:measure every 3-6 months with a target of≤48 mmol/mol
Self monitoring
Annually diabetic review: retinopathy, renal function, diabetic foot, cardiovascular (BP), thyroid disease
What is T2DM?
production of insulin becomes insufficient due to insulin resistance.
What causes T2DM?
Combination of environmental and genetic factors, poor diet, lack of exercise and obesity.
Risk factors for T2DM?
Family history
Obesity
Hypertension
Increasing age
Gestational Diabetes
Low (HDL) & High triglycerides
Polycystic ovary syndrome
Drugs: corticosteroids, thiazide diuretics
Ethnicity - Middle Eastern, South-east Asian and Western pacific
What is the Pathophysiology of T2DM?
Hint: Starlings Curve
Insulin binds normally to its receptor on the surface of cells in DMT2 just like in healthy people
Circulating insulin levels are typically higher than in non-diabetics following diagnosis and tend to rise further, only to decline again after months or years due to eventual secretory failure - phenomenon is known as the Starling curve of the pancreas.
Initial compensatory mechanism is hyperplasia and hypertrophy of beta cells to secrete more insulin. This is then exhausted and leads to hypoplasia and hypotrophy.
Hyperglycaemia and lipid excess are toxic to beta cells
Signs & Symptoms of T2DM?
Acanthosis nigricans
Glove and stocking
Reduced visual acuity
Diabetic retinopathy
Diabetic foot disease
Increased thirst and urine
Recurrent infections
Lethargy
Investigations for T2DM?
Hint: same as T1DM investigations
Blood glucose: ≥11mmol/L is diagnostic
Fasting blood glucose:≥7.0 mmol/L
Oral glucose tolerance test:>11mmol/L
HbA1C: ≥48 mmol/mol
How to diagnose Patients with impaired fasting glucose (IFG)
raised fasting glucose and normal OGTT
How to diagnose patients with impaired glucose tolerance (IGT)?
raised OGTT, and may or may not have a raised fasting glucose
How to manage T2DM?
Lifestyle (diet and exercise)
Metformin if HbA1c rises above 48 mmol/mol(6.5%)
second anti-diabetic drug should be commenced if HbA1Crises above58 mmol/mol(7.5%)
Insulin based therapy
What are the side effects of metformin? (4)
anorexia
diarrhoea
nausea
abdominal pain
What is diabetic ketoacidosis? (3)
medical emergency that is characterised by hyperglycaemia, acidosis and ketonaemia.
Blood glucose > 11 mmol/L
Ketosis > 3 mmol/L
Acidosis pH < 7.3
Causes/ Risk factors for DKA?
Infection
Diabetes
Heart attack
Hypothyroidism & pancreatitis
Corticosteroids, diuretics, salbutamol
Sings and symptoms of DKA?
Smell of acetone (‘fruity’ breath)
Vomiting
Dehydration
Abdominal pain
Hyperventilation (Kussmaul; deep sighing)
Hypovolaemic shock
Drowsiness
Coma
What is the pathophysiology of DKA?
Lack of insulin = body unable to utilise glucose
More glycogenolysis + gluconeogenesis + lipolysis
Lipolysis —> FA’s —> ketogenesis)
Ketones = weak acids
Leads to dehydration and electrolyte imbalances (K+) + hyperglycaemia
How to diagnose DKA? (3)
Ketonaemia: 3mmol/L and over
Blood glucose over 11mmol/L
Bicarbonate below 15mmol/L or venous pH less than 7.3
How to manage DKA?
Mild = rehydrate + subcutaneous insulin injection
Moderate = IV fluids + insulin and glucose infusion + potassium replacement
Severe = ABCDE approach for emergency resuscitation
Cerebral oedema = Major Complication !!!
What is Hyperosmolar Hyperglycaemic State (HHS)?
occurs in people with type 2 diabetes who experience very high blood glucose levels
- absence of significant ketoacidosis
Causes of HHS? (4)
Infection
Medications that cause fluid loss or lower glucose tolerance
Surgery
Impaired renal function
Pathophysiology of HHS?
lack of insulin is coupled with a rise in counter-regulatory hormones (e.g. cortisol, growth hormone, glucagon) that leads to a profound rise in glucose.
Enough insulin, which prevents the development of ketosis that epitomises DKA
excessive glucose (kidneys at max capacity) —> osmotic diuresis within the kidneys —> loss of electrolytes —> dehydration
Blood becomes thick and viscous
Diagnostic criteria for HHS? (3)
- severe hyperglycaemia (>=30mmol/L)
- hypotension
- hyperosmolality (usually >320 mosmol/kg).
No significant acidosis
Main difference between DKA and HHS?
DKA presents with acidosis and ketosis whereas HHS does not.
DKA in T1DM
HHS in T2DM
What are the signs and symptoms of HHS?
Nausea and vomiting
Lethargy
Weakness
Confusion
Dehydration
Coma
Seizure
Management of HHS? (4)
IV fluids
Insulin (if glucose doesn’t fall)
K+ replacement
Anticoagulants (VTE prophylaxis)
What are the Primary Causes of Hyperthyroidism?
(Caused by thyroid disfunction)
Graves disease
Toxic thyroid adenoma
Multinodular goitre
Silent thyroiditis
De Quervain’s thyroiditis (painful goitre)
Radiation
What are the Secondary Causes of Hyperthyroidism?
TSH producing Pituitary adenoma
Ectopic tumour
Gestational
Hypothalamic tumour
Lithium
Presentation of Hyperthyroidism?
Fine tremor
Finger clubbing
Sweating
Swollen arms and legs with plaques
Goitre (depending on cause)
Thyroid bruit
Protruding eyes & lid retraction
Atrial fibrillation
Diarrhoea
Muscle wasting
Tachycardia
How does Graves’ disease cause hyperthyroidism?
Anti TSH receptor antibodies which over stimulate thyroid gland
How does toxic adenoma / toxic multinodular goitre cause hyperthyroidism?
Iodine deficiency leads to compensatory TSH secretion
The excess TSH can cause the thyroid to enlarge and create a multinodular goiter.
Nodules can become TSH independent and secrete thyroid hormone
Toxic adenoma = 1 nodule
What causes Secondary Hyperthyroidism?
Benign Tumours
Pituitary - TSH secreting
Hypothalamic - TRH secreting
Ectopic - hCG secreting
How to diagnose hyperthyroidism?
Thyroid function test
Antibodies test (anti TSH receptor)
Ultrasound if palpable nodule
What are the TSH and T4 levels in someone with Primary Hyperthyroidism?
Low TSH
High T4
What are the TSH and T4 levels in someone with Secondary Hyperthyroidism?
High TSH and High T4
How to manage hyperthyroidism? (4)
Beta blocker (Propanol) for symptomatic relief
And carbimazole/ propylthiouracil to stop thyroid making hormones
Radio- iodine for goitres and adenomas
Thyroidectomy for recurrent goitres
How to manage a Thyroid storm? (4)
IV beta blocker (propanol)
IV Dijoxin (increases cardiac output but decreases HR)
Anti thyroid medication
Steroids
What is De Quervain’s thyroiditis?
Hyperthyroidism from acute inflammation of the thyroid gland, due to viral infection
Most common cause of hypothyroidism in the developed world?
Hashimoto’s thyroiditis
What is Hashimoto’s thyroiditis?
Autoimmune process associated withHLA-DR5andanti-TPO antibodies
Thyroid gland feels smooth but larger than normal
How does thyroiditis causes hypothyroidism?
Thyroiditis can also cause symptoms of hypothyroidism, or underactive thyroid. In some cases, after your thyroid is overactive for a period of time, it may become underactive.
What are the causes of hypothyroidism? (7)
Hashimoto’s
Autoimmune
Goitre (fibrous tissue)
Iodine deficiency
Postpartum
Viral (De Quervain’s)
Drugs (lithium)
How to diagnose Hypothyroidism?
Thyroid function test
- high TSH and low T4 = primary
- low TSH and low T4 = secondary
Test for antibodies
Management for Hypothyroidism?
Levothyroxine (manufactured thyroid hormone)
Risks include osteoporosis and cardiac arrythmias.
How to investigate a thyroid cancer? (4)
1- Ultrasound (malignant or benign)
2- Fine needle biopsy (malignant or benign)
3- Thyroid function tests (manage hypo/Hyperthyroidism first)
4- Laryngoscopy (paralysed vocal cord is highly suggestive of malignancy)
Papillary cancer is derived from which cells?
And what do these cells do?
Follicular cells
They secrete thyroglobulin and take up radioiodine
Follicular cancer is derived from which cells?
And what do these cells do?
Follicular cells
secretes thyroglobulin and takes up radioiodine
How does follicular cancer spread?
Early metastasis
vascular invasion
Distal spread more common
How to manage follicular cancer?
Lobectomy (with lymph removal)
Radioiodine
TSH suppression and Levothyroxine
Medullary cancer is derived from which cells?
And what do these cells do?
para-follicular cells
(aka C-Cells responsible for calcitonin production)
Very aggressive cancer
How to manage Medullary cancer?
Lobectomy
Thyroid hormone replacement for normal TSH (no TSH suppression)
What is the most aggressive thyroid cancer?
Anaplastic
Poor differentiation and Very aggressive
infiltrative to local structures, soft tissue of neck, widespread metastases, early mortality
How to manage Anaplastic cancer
- Does not respond to radioactive iodine
- If possible a total thyroidectomy is done
- Combined chemotherapy and radiation - may be palliative
What is Cushing’s Syndrome
Hypercortisolism (excess glucocorticoids )
What causes Cushing’s syndrome? (4)
ACTH INDEPENDENT
Excess steroid use
adrenal adenoma or adrenal hyperplasia - secreting excess cortisol
ATCH DEPENDENT
pituitary adenoma secreting excess ACTH (Cushing’s disease )
Ectopic ACTH e.g. from small cell lung cancer
Signs and symptoms of Cushing’s syndrome?
- Hypertension
- Moon face
- Buffalo hump
- Central adiposity
- Violaceous striae
- Muscle wasting and proximal myopathy
- Acne
- Bloating and weight gain
- Mood change & Tiredness
- Menstrual irregularity & Reduced libido
How to investigate Cushing’s syndrome?
(Gold standard)
Overnight Dexamethasone suppression test (shows failure of cortisol suppression) GOLD
Plasma cortisol levels (could be unreliable)
Exclude excess steroid use
24-hour urinary free cortisol
How does a dexamethasone suppression test distinguish between Cushing’s disease and an ectopic ACTH source?
Dexamethasone suppress ACTH production from the pituitary gland.
(Low dose DST = cortisol not suppressed)
After High dose DST: cortisol should be suppressed if its Cushing’s disease.
Cortisol will remain High if its an ectopic cause.
Other investigations to localise the cause of Cushing’s syndrome?
MRI pituitary (pituitary adenoma)
CT chest, abdomen, pelvis (ectopic)
What is the Cortisol pathway from the hypothalamus?
Hypothalamus secrets CRH
CRH causes the pituitary to secrete ACTH
ACTH causes adrenal cortex (Zona fassicularis) to secrete cortisol
When does cortisol levels peak and what are its effects?
Peaks in the morning (circadian rhythm )
Cortisol
- ↑gluconeogenesis, proteolysis, lipolysis
- ↑ insulin levels
- ↑ sensitivity to catecholamines = vasoconstriction
- ↑ BP & fluid retention
- ↓gonadotrophin releasing hormone
- ↓ dampens immune response
How to manage Cushing’s syndrome?
ACTH-dependent causes
ACTH-dependent causes
Cushing’s disease: trans-sphenoidal resectionof the pituitary tumour
Ectopic: Treat cancer
(glucocorticoid antagonists or radiotherapy)
How to manage Cushing’s syndrome?
ACTH-INdependent causes
ACTH-INdependent causes
Review medications
Adrenal tumour:tumour resection
(replacement of glucocorticoids and mineralocorticoids)
Excessive growth hormone secretion causes which condition?
Acromegaly
What are the 3 main causes of acromegaly?
Pituitary adenomas (> 90% cases)
Hypothalamic tumour (excess GHRH)
Ectopic (GH/GHRH)
What effects does Growth Hormone have?
Liver releases more glucose
Muscles retain Nitrogen for growth
Osteoblasts stimulated
More insulin resistance = ↑Blood glucose
Stimulates insulin like growth factor 1 production!
What should growth hormone be suppressed by?
Somatostatin
How does acromegaly cause type 2 diabetes and inappropriate growth?
Excess GH causes insulin resistance
Excess GH causes excessive IGF-1
Signs and symptoms of acromegaly?
Large hands and feet
Outward growth of the jaw and head with increased inter dental spacing and macroglossia
Headaches
Erectile dysfunction
Voice change
Increased sweating
Mood disturbances
Polyuria
How to investigate acromegaly?
Test to see if Serum insulin-like growth factor 1 (IGF-1) is raised.
Oral glucose tolerance test.
(Glucose load should suppress GH)
Pituitary MRI
How to manage acromegaly?
trans-sphenoidal surgery - remove pituitary tumour
Somatostatin receptor ligands
GH analogue
Dopamine agonist
What are some of the complications of acromegaly?
T2DM (insulin resistance from excess GH)
Cardiomyopathy
Carpel tunnel syndrome
Organomegaly
Arthritis
Difference between acromegaly and gigantism?
Gigantism = Excess GH secretion in children (before fusion of the growth plates)
What is Conns syndrome
Primary hyperaldosterone
Which cells produce aldosterone, and what does it do?
Zona glomerulosa
↓K+
↑ Na+
↑BP
Aldosterone binds to DCT
Principal cells: ↑ Na/K pumps (more Na+ in blood)
Intercalated cells: ↑ ATPase pumps (more protons in urine = ↑pH)
Causes of hyperaldosterone?
Primary:
Adrenal adenoma (Conns Syndrome)
Adrenal hyperplasia or carcinoma
Secondary (inappropriate activation of RAAS):
Renal artery stenosis
Heart failure
Signs and symptoms of Hyperaldosterone?
Classically, the disease presents as refractory hypertension, hypokalaemia, and metabolic alkalosis. Hypernatraemia may or may not be seen.
- Lethargy
- Mood disturbance
- Paresthesia and muscle cramps
- Polyuria and nocturia
How to investigate hyperaldosteronism?
Aldosterone/renin ratio
high aldosterone, with LOW renin in cases of primary hyperaldosteronism (Do CT after)
high aldosterone and HIGH renin in cases of secondary hyperaldosteronism.
Serum U+E
Blood gas
Adrenal venous sampling (measure corticosteroids secreted from each adrenal gland to see if uni or bilateral problem)
How to manage Hyperaldosteroism?
Aldosterone antagonists
Adrenalectomy for unilateral adrenal adenoma/ hyperplasia
Potassium sparing diuretics (promotes Na+ excretion) for bilateral (Spironolactone)
For Secondary hyperaldosteronism - renal artery angioplasty to resolve renal artery stenosis
What happens if a pituitary adenoma affects the mammotrophs?
hyperprolactinaemia caused by a prolactinoma.
(Prolactin causes breasts to grow and develop and causes milk to be made after a baby is born)
What happens if a pituitary adenoma affects the somatotroph cells?
Acromegaly due to excess growth hormone.
What happens if a pituitary adenoma affects the Corticotroph cells?
excess cortisol (Cushing’s syndrome) through excess production ofACTH.
What is Addisons Disease?
primary adrenal insufficiency caused by destruction or dysfunction of the adrenal cortex.
Results in mineralocorticoid (aldosterone), glucocorticoid (cortisol) and gonadocorticoid (androgens) deficiency
What causes Addisons Disease? (5)
Autoimmune
Infection (TB,HIV)
Infarction
Congenital
Medication
What does a reduction in glucocorticoids, mineralocorticoids, and androgens have?
↓glucocorticoids = ↓cortisol, weight loss, fatigue,
(No -ve feedback so more CRH & ACTH = more prolactin)
↓mineralocorticoids = ↓Na+, ↓H2O, ↓BP, tachycardia
↓androgens = ↓ libido
Signs and symptoms of Addison’s disease?
Hypotension and tachycardia
Fatigue and weakness
Nausea and vomiting
Syncope
Pigmentation (due to an increase in ACTH pre-cursors)
How to investigate Addison’s disease?
Morning Cortisol levels (less than 100nmol/L = highly suggestive)
ACTH stimulation test (Synacthen): failure of adequate rise = highly suggestive
Check for adrenal antibodies, U+E’s
CT adrenals
How to manage Addison’s disease?
Corticosteroid replacement:
(Hydrocortisone & Flurocortisone)
Androgen replacement for women
1- What is Addisons crisis?
2- Signs and symptoms?
3- Management?
1- Adrenal crisis due to a a drop in corticosteroids
Severe Metabolic acidosis, hyperkalaemia, hyponatraemia.
2- Hypotension, hypovolemic shock, confusion, nausea, abdo pain, Trigger (e.g infection)
3- IV fluids and Hydrocortisone, treat underlying cause
What is Secondary Adrenal Insufficiency?
Adrenal insufficiency due to insufficient pituitary or hypothalamic action on the adrenal glands. (lack of ACTH)
Causes of Secondary Adrenal Insufficiency?
Long term steroid use
Hypothalamic pituitary disease - resulting in reduced ACTH production
Removal of pituitary tumour - remaining ACTH-secreting cells in the pituitary gland may be sluggish in their recovery
Difference between clinical manifestation of primary and secondary adrenal insufficiency?
Similar presentation to Addison’s disease.
However in Secondary = no hyperpigmentation as there is no excess ACTH
Primary = High ACTH
Secondary = Low ACTH
Note: In Secondary Mineralocorticoid production remains intact.
What will a patient with Secondary Adrenal Insufficiency levels be like for:
1- Cortisol,
2- ACTH
3- Mineralocorticoids
Cortisol = low
ACTH = low
Mineralocorticoids = normal
How to manage Secondary Adrenal Insufficiency? (2)
Adrenals will recover if long-term steroids are slowly weaned off
Oral hydrocortisone
Where is ADH produced?
Where is ADH stored?
When is ADH released?
What does ADH do?
magnocellular neurons in the paraventricular and supraoptic nuclei of the hypothalamus
Stored and released by the posterior pituitary
In response to rising plasma osmolality
ADH acts on the DCT and collecting duct to increase water reabsorption independent of sodium. Insertion of aquaporin-2 channels allowing the free entry of water.
What is SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion)?
ADH excess
Reduced diuresis
Increased total body water
Hyponatremia
Pathophysiology of SIADH?
Increased ADH release
water retention by increased insertion of aquaporin 2, butnotthe reabsorption of solutes. This increases blood volume and decreases serum osmolarity.
Increase in blood volume leads to stretching of heart muscle and release of ANP and BNP (natriuretic peptide). This inhibits renin release and activity. This promotes natriuresis (excretion of sodium). This leads to sodium and water excretion
euvolaemic state rather than a hypervolaemic state, coupled with hyponatraemia.
Overall, patients will have high urine Na+ levels and low serum Na+ levels. They will be euvolaemic due to compensatory mechanisms.
Causes of SIADH?
Neurological - meningitis, cranial haemorrhage, stroke
Malignancy
Infections - TB, HIV, Pneumonia
Endocrine - Hypothyroidism, Hypopituitarism
Drugs - CARDISH - chemo, antidepressants, recreational drugs, diuretics, inhibitors e.g. ACEI & SSRIs, sulfonylurea, hormones e.g. desmopressin)
Signs and symptoms of SIADH?
Hyponatraemic and euvolaemic
Mild(130-135 mmol/L):
- Nausea, vomiting, headache, lethargy, anorexia
Moderate (125-129 mmol/L):
- Weakness, muscle aches, confusion, ataxia, asterixis
Severe(< 125 mmol/L):
- Reduced consciousness, seizures, myoclonus, respiratory arrest
How to investigate SIADH? (2)
Blood test (low plasma osmolary)
Urine test (high osmolarity and Na+)
Clinical euvolaemia
How to manage SIADH? (3)
Fluid restriction (up to 750ml/day) and treat underlying cause
ADH antagonists (e.g. tolvaptan, deomeclocycline)
Oral sodium and furosemide (diuretic)
Treat acute fast and chronic slow
Rapid correction = central pontine myelinolysis (brain shrinks)
How does insulin, adrenaline, and aldosterone affect K+ homeostasis?
Insulin & Adrenaline: causes an intracellular shift of K+
Aldosterone: promotes K+ excretion
At what serum concentration is a patient considered hyperkalemic?
A serum level >5.5 mmol/L is considered to be hyperkalaemia
A serum level > 6.5mmol/L = MEDICAL EMERGENCY!
Drugs which can cause Hyperkalaemia? (6)
- Potassium-sparing diuretics e.g. spironolactone - COMMON
- ACE inhibitors (interfere with RAAS) e.g. ramipril - COMMON
- NSAIDs - COMMON
- Heparin
- Beta-antagonists: inhibit cellular entry of potassium
- Digoxin: inhibitor of Na+/K+ ATPase causing reduced cellular entry of potassium
Causes of Hyperkalaemia?
IMPAIRED EXCRETION
Kidney injury
Addison’s disease (reduced aldosterone causes K+ excretion)
Hypoaldosteronism
Drugs
INCREASED K+ RELEASE FROM CELLS
Lactic acidosis (acidosis swap H+ from blood with K+ in cells)
Insulin deficiency (insulin activates Na/K pumps)
Haemolysis
How does high levels of K+ affect action potential?
- When K+ levels in the blood rise - this reduces the difference in electrical potential between cardiac myocytes and outside of the cells meaning the threshold for action potential is significantly decreased resulting in increased abnormal action potential and thus abnormal heart rhythms that can result in ventricular fibrillation and cardiac arrest
- In smooth muscle it can cause cramping - due to depolarisation and contraction
- In skeletal muscle it can cause weakness and flaccid paralysis - resting potential is too high, which means muscle can’t repolarise and then contract again
What are the Signs and Symptoms of Hyperkalaemia?
Tachycardia (arrhythmia)
ECG differences - tall tented T waves, small P waves, wide QRS
Muscle weakness
Lightheadedness
Muscle cramps
Paresthesia (tingling in skin)
Palpitations
Chest pain
How to investigate Hyperkalaemia?
ECG ( flat P waves, short QT interval, broad QRS, ST depression, and tented T waves)
U&E’s
Lithium heparin sample: rule out pseudohyperkalaemia. This is where thrombus formation and haemolysis causes falsely elevated potassium concentration
VBG: check for acidosis which may be causing the hyperkalaemia
How to manage Hyperkalaemia?
Calcium gluconate (calcium protects cardiac membranes)
Insulin
Salbutamol
At what plasma concentration is a Pattie to described as Hypokalaemic?
plasma K+ concentration < 3.5 mmol/L.
Severe: < 2.5 mmol/L
Causes of Hypokalaemia?
Inadequate intake
Increased excretion (diuretics, excess mineralcorticoids, Cushing’s, Conns, Nephrotic syndrome, steroid use, diarrhoea)
Shift from extracellular to intracellular (alkalosis, excess insulin, Activation of beta-adrenergic receptors)
How does low K+ affect Cardiac, Smooth, Skeletal, and Respiratory muscles?
Diminished contraction.
- Cardiac - arrhythmias and cardiac arrest
- Smooth muscle - constipation
- Skeletal muscle - weakness, cramps and flaccid paralysis
- Respiratory muscles - respiratory depression
Signs and Symptoms of Hypokalaemia?
Arrhythmias
Muscle paralysis
Hypotonia
Hypoflexia
Fatigue
Generalised weakness
Light headedness
Muscle cramps and pain
Tetany
Palpitations
Constipation
How to diagnose and manage Hypokalaemia?
Measure plasma K+ conc (<3.5mmol/L)
ECG (Prolonged PR, ST segment depression, flattening of T wave, U wave present)
Treat underlying cause
Review meds
K+ replacement (orally or K+ sparing diuretics)
What is Diabetes Insipidus?
The patient is unable to make ADH or respond to ADH.
Resulting in the production of large quantities of dilute urine.
Inability to concentrate urine.
Causes of Diabetes Insipidus?
NEPHROGENIC:
Drugs (lithium)
Genetic
Electrolyte imbalances
Renal disease
CRANIAL:
Head trauma
Meningitis
Inflammation (sarcoidosis)
Vascular (sickle cell)
Difference between central and nephrogenic DI?
Central DI results from any condition that impairs the production, transportation, or release of ADH.
Nephrogenic DI results from conditions that impair the renal collecting ducts’ ability to respond to ADH.
Signs and symptoms of DI?
Postural hypotension
Hypernatraemia
Lots of urine
Thirsty
Dehydration
How to investigate DI?
Water deprivation test (desmopressin)
- cranial: after desmopressin urine osmolarity increases
- nephrogenic: after desmopressin, no effect to urine osmolarity
U&E’s (high Na+)
Serum glucose (exclude DM)
Urine osmolarity (low)
Serum osmolarity (high)
MRI for cranial DI
How to manage DI?
Cranial DI = Desmopressin.
Sodium should be monitored routinely due to the risk of hyponatraemia.
Nephrogenic DI= Thiazade diuretics
correct any metabolic abnormality and stopping any offending drugs.
At what plasma concentration are patients referred as Hypercalcemic?
> 10.5mg/dL
How is calcium homeostasis maintained?
The parathyroid glands, specifically the chief cells in the glands, produce parathyroid hormone in response to low calcium.
The parathyroid hormone causes:
The bones to release calcium
The kidneys to reabsorb more calcium so it’s not lost in the urine (as well as excrete more phosphate)
The kidneys to synthesise calcitriol/ active Vitamin D. Active Vitamin D then goes on to cause the gastrointestinal tract to increase calcium absorption.
What causes Hypercalcemia?
Acidosis- promotes less binding between albumin and calcium. This causes less bound calcium and more free ionised calcium
Hyperparathyroidism
Malignant Tumours (secrete PTHrP)
Excess Vit D
Sarcoidosis
Milk-alkali syndrome
Drugs - thiazides diuretics, lithium
How does High levels of Calcium affect neurones?
High levels of extracellular Ca, voltage-gated sodium channels are less likely to open up, which makes it harder to reach depolarisation, and makes the neuron less excitable.
Slower or absent reflexes, muscle contraction
Signs and symptoms of Hypercalcemia?
Abdominal pain
Vomiting
Constipation
Dehydration
Polydipsia and polyuria
Muscle weakness
Confusion + hallucinations
Pyrexia
How to investigate Hypercalcemia?
Blood test (Ca, PTH, Vit D, Albumin, Phosphorus, Mg)
Urine test (High Ca)
ECG + imaging
How to manage Hypercalcaemia?
Rehydration
Loop diuretics (inhibit calcium reabsorption in the loop of Henle)
Glucocorticoids (Decrease calcium absorption from GI tract)
Calcitonin + Biphophonates (reduce bone resorption)
Chemo for malignancy
At what plasma concentration is a patient described as Hypocalcaemic?
Ca < 8.5mg/dL or 2.1mmol/L
Causes of Hypocalcaemia?
(1) With increased phosphate
(2) with normal/ low phosphate
Chronic kidney diseases (lack of reabsorption)
Hypoparathyroidism
Acute rhabdomyolysis: large numbers of cells die and release phosphate. The phosphate binds to the ionised calcium and forms calcium phosphate, making it insoluble
Vit D deficiency (osteomalacia)
Acute pancreatitis: free fatty acids end up binding to ionised calcium, which is insoluble
Respiratory alkalosis: high pH (alkalosis) causes more binding between albumin and calcium
How does low Calcium affect neurones?
Low levels of calcium, voltage-gated sodium channels are more likely to open up, which allows the cell to depolarise more easily, and makes the neurone more excitable. This can trigger tetany.
Signs and Symptoms of Hypocalcaemia?
SPASMODIC
S – Spasms (Trousseau’s sign)
P – Perioral parasthaesia
A – Anxiety/Irritability
S – Seizures
M – Muscle tone increase (colic, dysphagia)
O– Orientation impairment (i.e. confusion)
D – Dermatitis
I – Impetigo herpetiformis
C – Chvostek’s sign
How to investigate Hypocalcaemia?
Blood test: (Ca, PTH, Vit D, albumin, phosphorus, Mg)
ECG (prolonged QT, prolonged ST segment, and arrhythmias)
X-ray (suspected osteomalacia)
How to manage Hypocalcaemia?
Calcium and Vit D supplements
Calcium gluconate (spasms/ ECG changes)
Correct alkalosis if present
How is Primary Hyperparathyroidism caused?
Uncontrolled PTH produced directly by a tumour of the parathyroid glands. Can lead to Hypercalcemia
How is Secondary Hyperparathyroidism caused?
There is increased secretion of PTH in response to low calcium because of kidney, liver, or bowel disease.
The glands become more bulky.
The serum calcium level will be low or normal but the parathyroid hormone will be high.
How is Tertiary Hyperparathyroidism caused?
Autonomous secretion of PTH, usually because of chronic kidney disease (CKD).
when the cause of the secondary hyperparathyroidism is treated the parathyroid hormone level remains inappropriately high. hypercalcaemia.
Signs and Symptoms of Hyperparathyroidism?
Moans, Stones, Groans and Psychiatric Moans
Painful Bones
Renal Stones
Abdominal Groans - GI symptoms: Nausea, Vomiting, Constipation, Indigestion
Psychiatric Moans – Effects on nervous system: lethargy, fatigue, memory loss, psychosis, depression
Causes of Hyperparathyroidism?
Primary, secondary and tertiary
Adenomas
Vit D deficiency
Pancreatitis, rhabdomyolysis
Calcium malabsorption/ deficiency
CKD
Prolonged secondary hyperparathyroidism
The glands become autonomous, producing excessive PTH even after the cause of hypocalcaemia has been corrected.
How to investigate Hyperparathyroidism?
Blood test (PTH, Ca, Vit D, Phosphate)
Primary and tertiary (High PTH and Ca)
Secondary (High PTH and LOW Ca)
Urine test (raised Ca)
How to manage Hyperparathyroidism?
Primary: remove tumour, reduce Ca intake, Calcimimetics (mimics Ca and binds to receptors on parathyroid cells)
Secondary: Vit D, phosphate binders, Renal transplant if renal failure.
Tertiary: Surgical removal of parathyroid tissue
What cause Primary and Secondary Hypoparathyroidism?
Autoimmune
DiGeorge syndrome
Autosomal dominant hypoparathyroidism (mutation in the parathyroid cell’s calcium-sensing receptor.)
Removal of parathyroid glands during surgery
Low Mg - Mg needed for PTH secretion
Signs and symptoms of Hyperparathyroidism?
Chvostek’s sign: facial muscles twitch after the facial nerve is lightly tapped.
Trousseau’s sign: muscle spasm that makes the wrist and metacarpophalangeal joints flex.
Arrhythmias
Tetany
Pins and needles
Seizures
How to investigate Hyperparathyroidism?
Blood test: (Low PTH, low Ca, Low Vit D, High Phosphate)
ECG: prolonged QT, prolonged ST segment, and arrhythmias
How to manage Hyperparathyroidim?
Calcium and vitamin D supplements
Recombinant human parathyroid hormone
What is a carcinoid tumour?
tumour of the neuroendocrine cells, resulting in excessive release of certain hormones.
Neuroendocrine cells release….
amines: serotonin and histamine
polypeptides: bradykinin and prostaglandins = Vasodilators
What is carcinoid syndrome?
Carcinoid syndrome occurs when there is a buildup of hormones produced by the neuroendocrine cells as the liver is no longer able to metabolise them.
Increased histamine and bradykinin: can cause vasodilation leading to flushing
Increased histamine: can cause itching
Increased serotonin: can cause thickening of fibrosis, particularly in the heart valves leading to heart dysfunction
Signs and symptoms of a carcinoid tumour?
Abdominal pain
Diarrhoea
Flushing
Wheeze
Pulmonary stenosis
- effects of excess serotonin
How to investigate a carcinoid tumour?
24 hr urine 5-hydroxyindoleacetic acid (high levels)
X ray/ MRI/ CT to identify location
Plasma chromogranin A (marker for the tumour)
Ostreoscan (binds to somatostatin receptor on tumour)
How to manage Carcinoid Tumours?
Decreasing emotional stress and alcohol consumption
Somatostatin analogues (Octreotide)
Surgical resection
Radiofrequency ablation of hepatic metastases
What is a Pheochromocytoma?
tumour (usually benign) arising from chromaffin cells in the adrenal medulla resulting in the overproduction of catecholamines
Catecholamines ie adrenaline
Sign and symptoms of pheochromocytoma?
Hypertension
Tachycardia
Palpitations
Anxiety
Sweating
Hypersensitive retinopathy
How to investigate Pheochromocytoma?
Plasma metanephrines and urinary metenephrines
(Metenephrines = breakdown product of catecholamines)
Adrenal imaging
PET scan
How to manage Pheochromocytoma?
Alpha blockade - BP and heart rate to normalise
Beta blockade - for BP control and expand Blood volume
Remove the tumour
How to diagnose Pre-Diabetes?
HbA1c between 42-47 mmol/mol
