AMK 2

Question 1

What are the parathyroid glands?- Action

Answer 1

4 glands on the posterior aspect of the thyroid gland.

• Release Parathyroid Hormone (Chief cells- CC) in response to Hypocalcaemia
• (LOW CA, CA SENSITIVE RECEPTOR ON CC STIMULATED LESS SO LESS INTRACELLULAR PATHWAYS INHIBIT PTH RELEASE. high CA detected by CSR and activated sending signals inside the cell to inhibit PTH release)
• Release Calcitonin (parafollicular cells )
  (OPPOSING EFFECT OF PTH- RELEASED IN RESPONSE TO HYPERCALCEMIA DETECTED BY CSR.)

Question 2

How does Parathyroid hormone work?

Answer 2

Increased activity of osteoclast - increased bone resorption (release CA , Pr etc from bone into blood)

  - PTH binds to PTH receptor on osteoblast. Osteoblast releases rank ligand which binds to rank receptor on osteoclast and increases its activity)

—(g protein coupled receptor activation by PTH , causes calcium channel proteins to be embedded in the DCT membrane - CA reabsorbed from filtrate)

-Absorption of CA From GI tract into bloodstream.
(Vitamin D binds to receptor inside enterocyte causing gene expression and production of CA CHANNELS - embedded into membrane)

Increases expression of 1- alpha hydroxylase in kidney

Question 3

Action of PTH?

Answer 3

• Increased activity of osteoclast - increased bone resorption
• `increased expression of 1 - alpha- hydroxylase in kidney involved in vitamin D synthesis.
• Increased absorption of CA from GI TRACT and DCT of kidney tubule

-

Question 4

What is Hypocalemia and causes?

Answer 4

Serum below 8.8mg/dl (2.2mmol/L)

-Alkalosis - COOH in albumin become ionised - lose H+. So Ca2+ binds with the h+ group (complexed no longer free ionised- FREE IONISED TAKES PART IN CELLULAR PROCESSES.)

• Hypoparathyroidism - (can be caused by surgery(PTH gland accidentally damage or removed) or Autoimmune destruction - Less PTH release less CA2+ released into the blood)
  - MAG Deficiency - Mg needed to produce PTH.
• Acute pancreatitis - Free Fatty acids released and complexes with CA2+ forming insoluble product.
• Kidney failure - too much CA2+excreted in the urine.
• Tissue injury - Burns,
  - Rhabdomyolysis -breakdown of muscle fibres - releases it’s products into bloodstream - myoglobin. Kidney breaks this down and its breakdown products damage kidney leading to kidney failure.
  - Tissue lysis syndrome - large cell death - release p043- which complexes wit CA2+ to form calcium phosphate which is insoluble.
• Vitamin D deficiency
• Too many blood transfusions

• Mild hypocalcemia may be asymptomatic or cause muscle cramps.

Question 5

Consequences of Hypocalcaemia ?

Answer 5

Tetany - involuntary muscle contraction
- Chvostek’s - involuntary twitching of facial muscles.

Trousseau’s signs - carpal spasm - blood supply reduced to hand when cuff inflated to 20mmhg. Ocuurs in alkalosis, HYPO - calcaemic, kalemia, magnesia.

muscle cramps.

• Severe hypocalcemia (serum calcium

Question 6

Treatment of hypocalcemia?

Answer 6

• Give IVcalcium gluconateto patients with tetany; treat others with oral calcium supplements. Vitamin D supplementation if needed.

(chronic hypocalcaemia - oral calcium supplements + vitamin D supplements if needed.)

If tetany occurs - do continuous potassium - calcium monitoring & ECG monitoring
0 if associated with hypomagnesia give magnesium gluconate.

Question 7

What is Hypercalcemia ?

Causes

Answer 7

serum calcium above 10.4 mg/DL (2.6 mmHG)

-Acidosis - COOH groups in Albumin. Lots of H+ so COOH in this form and positively charged so CA2+ is repelled. Less bound CA and more Free ionized CA.

-Too much PTH - Abnormally high activity of osteoclast - too much bone resorption
CA2+ released into blood.

• Excess Vitamin D (from diet or supplements)
• Malignancy - tumour releases PTH related protein that mimics its action leading to increased activity of osteoclast and bon resorption.
• Medication - e.g. Thiazide diuretics - increase reabsorption - DCT

Question 8

Consequences/ symptoms of Hypercalcemia?

Answer 8

High CA - NA channels less likely to open —- harder to depolarize , less excitable.

Slower / absent reflexes

• Slower muscle contraction -
  - muscle weakness
  - constipation
• In the brain - hallucinations. confusion and Stupor ( altered consciousness only brought around by vigorous physical stimulation)
• Hypercalciuria (too much CA in urine )- draws water along with it - DEHYDRATION.
• Hypercalcemia + hypercalciuria cause kidney stones (calcium oxalate).

From capsule

The classic presentation of hypercalcaemia is ‘bones, stones, (abdominal) groans, and psychic moans’. Effects on the heart include arrhythmias and a short QT interval. Always consider hypercalcaemia in cancer patients with non specific symptoms.
Renal stones would be associated with a longstanding hypercalcaemia – so likely to be primary hyperparathyroidism rather than cancer

Question 9

Treatment of Hypercalcemia ?8

Answer 9

Mild Hypercal - confirm diagnosis before treatment

Moderate - Saline

             - Loop diuretic - makes the kidney past out more urine - CA excreted.  . 
             - Bisphosphonate - Zoledronate , Pamidronate (They prevent bone resorption (osteoclast)- same as calcitonin ) 

Severe - Oral phosphate (CA binds forms CA phosphate - insoluble )

or saline + loop diuretic

Emergency

Rehydration - saline 0.9%
Watch for fluid overload in elderly and renal impairment patients

Loop diuretic rarely used - usually only in fluid overload patients

2. Then intravenous biphosphonate (single dose)
   E.g zolendronic acid

2ND LINE TREATMENTS

Glucocorticoids (inhibit 1,25OHD production)
• In lymphoma, other granulomatous diseases or
25OHD poisoning
• Prednisolone 40mg daily
• Usually effective in 2 to 4 days

Calcitonin
• Can be considered if poor response to
bisphosphonates

Calcimimetics e.g cinacalet
• Licensed for hypercalcaemia due to primary
hyperparathyroidism, parathyroid carcinoma or renal
failure

Parathyroidectomy
• Can be considered in acute presentation of primary
hyperparathyroidism if severe hypercalcaemia and
poor response to other measurements

Question 10

Criteria to surgery for Primary Hyperparathyroidism?

Answer 10

SURGERY THE ONLY WAY TO Completely SOLVE PRIMARY HPTHism

Refer people with a confirmed diagnosis of primary hyperparathyroidism to a surgeon with expertise in parathyroid surgery if they have:

0 symptoms of hypercalcaemia such as thirst, frequent or excessive urination, or constipation or

0 end-organ disease (renal stones, fragility fractures or osteoporosis) or

0 an albumin-adjusted serum calcium level of 2.85 mmol/litre or above.

1.3.2Consider referral to a surgeon with expertise in parathyroid surgery for people with a confirmed diagnosis of primary hyperparathyroidism even if they do not have the features listed in recommendation 1.3.1.

Question 11

What is Hyperparathyroidism ?

Types?

Answer 11

Hyperparathyroidism - excessive secretion of PTH.

0 Primary - One or more PTH glands produces excess PTH

0 Secondary - PTH secretion in response to decreased CA. (caused by liver and bowel disease, Vitamin D deficiency . )

0 Tertiary - long-standing secondary hyperparathyroidism that starts to behave like primary hyperparathyroidism.

Question 12

What should be avoided when a person has hyperparathyroidism?

Answer 12

Thiazide diuretics - BP medication - can cause dehydration and raise serum CA2+.

Question 13

Non - surgical treatment of Pruimary Hyperparathyrodism ?

Answer 13

If surgery unsuccessful , , unsuitable or declined and albumin adjusted serum calcium is :
- >2.85mmol(with symptoms of hypercalcemia)
- > 3mmol/L (no symptoms)
- Cinacalcet (stimulates body to produce less PTH)
Indications :
secondary hyperparathyroidism- end stage renal disease.

          Hypercalcemia in  parathyroid carcinoma. Primary hyperparathyroidism  - Consider Bisphosphonate - in patients who have increased fracture risk - short term . (don't offer for chronic hypercalcemia of Hyperparathyroidism )

Question 14

What is Hypoparathyroidism ? Consequences , treatements?

Answer 14

Too little production of PTH

Hypocalcaemia, Hypophosphatemia (< 2.5 mg/dL (0.81 mmol/L).)

Symptoms of hypocalcaemia etc.

TREATMENTS - Restore CA (calcium gluconate - IV (for severe- urgent management, us ) and phosphorus levels (Oral sodium phosphate or potassium phosphate)

0 Parenteral phosphate is usually given IV. It should be administered in any of the following circumstances:

When serum phosphate is < 1 mg/dL (< 0.32 mmol/L)
Rhabdomyolysis, hemolysis, or central nervous system symptoms are present
Oral replacement is not feasible due to underlying disorder

diet should be rich in CA and phosphorus

0 Vitamin should be given if needed.

Question 15

What is Addison’s Disease ( primary , chronic , adrenocortical disease)?

Answer 15

Hypoadrenalism /adrenal insuffcinecy
- Not enough cortisol and aldosterone , andogens (sex hormone) produced

• Can be caused by autoimmune attack on adrenal cells leading to atrophy.
• iatrogenic - removal of adrenal gland
• Maligancy
• Adrenal hemorrage
• infection
• cushing sydrome medication
• secondary - insufficient ATCH secretion.

Need to prevent adrenal crisis - medical emergency.

Decreased androgens affects females more than males as the testes produce most of androgens in males.

Question 16

Symptoms of Addison’s Disease?

Answer 16

0 lack of energy or motivation (fatigue)

0 muscle weakness

0 low mood - CORTISOL EFFECTS THE BRAIN

0 loss of appetite and unintentional weight loss - CORTISOL INCREASES GLUCOSE LEVELS (INCREAES INSULIN WHICH CAUSES ADIPOCYTES TO ACCUMULATE FAT)

0 increased thirst

0 Over time, these problems may become more severe and you may experience further symptoms, such as dizziness, fainting, cramps and exhaustion.

Addisonian pigmentation - hyper-pigmentation - You may also develop small areas of darkened skin, or darkened lips or gums ( low cortisol —-> increased MHC - melanocyte- stimulating hormone —–> Hyperpigmentation )

• reduced Blood pressure- ALDOSTERONE RETAIN NA (SALT) AND WATER WHICH INCREASES BP. Cortisol causes vasoconstriction increasing BP
• decreased Libido - Androgens

Find May last wait together By Lewisham high 
F,M,L,W,T, B
F-fatigue 
M- muscle weakness
L - low mood
W - weight loss/loss of appetite 
B - decreased BP
L - libido 
H - hyperpigmentation

• abdominal pain - sometimes it can be mistaken for pancreatitis

Question 17

Treatment of Addison’s Disease?

Answer 17

Glucocorticoid replacement therapy (cortisol - glucocorticoid )
e.g. Hydrocortisone
0Dexamethasone
0 Prednisolone
Last two can be used to avoid peaks and throughs of hydrocortisone) - but less used.

0 Aldosterone replacement- fludrocortisone - mineralocorticoid

Need both mineralocorticoid + glucocorticoid

Question 18

Treatment of Adrenal crisis ?

Answer 18

Medical emergency - IV /IM hydrocortisone (at the doses used hydrocortisone has mineralocorticoid action as well as glucocorticoid action)

Question 19

Symptoms of Adrenal crisis ?

Answer 19

• Fatigue
• Low BP
• confusion - loss of consciousness
• loss of appetite
• Rapid HR ( body trying to correct LOW BP)
• RAPID RR
• Slow sluggish movement
• Nausea and vomiting
• high fever
• headache

Question 20

What is Conn’s syndrome ?

Consequences?

Answer 20

primary hyperaldosteronism - adrenal gland produces too much aldosterone

• Decreased K+ (Hypokalaemia - can be caused)
• Increased NA+ (can cause hypernatremia so High BP)
• Increased BV and pressure.

(Aldosterone acts on DCT and stimulates increased NA+/K+ PUMP. - K+ pump out of cell into filtrate and into urine. NA+ is pump into cells and into blood - water follows NA+ increased Blood volume and pressure.

• note secondary hyperaldosteronism can be cuased by hyper activity of RAAS.

Question 21

Treatment of Conn’s syndrome ?

Answer 21

Spirolactone - Potassium sparing Diuretic
(prevents binding of aldosterone - so potassium not lost)

Adrenalectomy - removal of tumor

Question 22

Causes of Conn’s syndrome ?

Answer 22

Adrenal adenoma

- Adrenal hyperplasia (congenital ) - group of conditions that result in the adrenal gland being bigger than normal.

Question 23

What is acromegaly, causes ?

Answer 23

Too much Growth hormone secreted by Anterior pituitary gland.

Causes

0 Pituitary adenoma - hypersecretion of GH.

• ( note - hyper-secretion of GH before puberty will cause Gigantism (extensive growth of bones , after puberty - acromegaly )

0 cancer ectopic (out of place) growth - release of etopic GH or etopic Growth hormone releasing hormone (GHRH from Hypothalamus )

0Ectopic acromegaly is a rare syndrome (less than 1% of acromegalic patients) caused by ectopic growth hormone-releasing hormone (GHRH) or growth hormone(GH)-producing tumours.

Question 24

Consequences of Acromegaly?

Answer 24

Bitemporal Hemianopia - loss of vision of the outer halves of the eye.

   If pitiuitary ademona is significantly sized  it can can compress the optic chiasm( where optic nerves cross)

• Headaches
• overgrowth of tissues
  - Frontal Bossing - prominent brow and forehead.
  - Large nose
  - Macroglossia - large tounge
  - large hands and feet
  - Prognathism - protruding jaw

Organ dysfunction

- Hypertrophic heart 
- Hypertension 
- Diabetes
- linked to colorectal cancer

Question 25

Treatment of Acromegaly ?

Answer 25

Doctors will discuss best option 1st - surgery - Transsphenodial selective adenomectomy - removal of adenoma or cancerous growth (in this case (hypophysectomy - removal of pituitary gland ) - if surgery not possible - give medications - 0 moderate to severe - give Somatostatin- receptor ligand (SRL) or Pegivosomant 0 mild - give Dopamine agonist -usually cabergoline. (i think SRL are used first ) Pegvisomant (GH antagonist)- daily injection subcataneous - octreotide, lanreotide , pasireotide - Somatostatin analogues - Block GH * Bromocriptine, Cabergoline tablets - Dopamine angonist. - reduced GH secretion. -

Question 26

GH - IGF axis

Answer 26

GH - Growth Hormone IGF - insulin like growth factor. GHRH (growth hormone releasing hormone ) REALSE --------.

Question 27

GH - IGF axis

Answer 27

GH - Growth Hormone IGF - insulin like growth factor. 2 pathways 1. GHRH released from Hypothamulus ---------> GHRH acts on anterior pituray --------> release of GH into bloodstream ------> acts on target organs 2. GHRH (growth hormone releasing hormone ) Released from hypothalamus --------> acts on Anterior pituary gland ------> releases GH -------> GH binds to receptor on liver -------> Actication of JAK - STAT pathway. (phosporylation of tyrosine kinase receptor ----> phosphorylation of JAK , phosphorylation of STAT) --------> production of mRNA by transcription ------- > production of IGF protein. ------> IGF released.

Question 28

Action of GH ( and IGF -1 ) ?

Answer 28

GH stimulates production of IGF - 1 0 Increase muscle size , thus muscle function- IGF - 1 causes muscle to take up animo acids from bloodstream and produce proteins (link animo acids up -- protein synthesis e.g actin, myosin) 0 IGF - 1 - bone growth- regulate activity of osteoblast , osteoclast - increase both of their activity - bone deposition , bone resorption - 1. enhance endochrondial ossification - increase in bone mass. 2. protein synthesis - collagen Type 1 & proteoglycans production ``` iGF - 1 - Cartilage - increases interstitial growth ( growth of cartilage and its replacement with bone tissue) - IGF - 1 stimulated by GH acts on epiphyseal plate - causes chondrocytes to proliferate. ``` * Chondrocytes produce and maintain the cartilaginous matrix - consisting of collagen and proteoglycans. GH - stimulates gluconeogenesis (e.g. adipose tissue - binds to receptor on adipose cell -----> activates hormone sensitive ligase ------> break down triglycerides into glycerol and fatty acids. ) Summary ``` 0 IGF - 0 Muscle - increased 1. Animo acid uptake 2. protein synthesis. 0 Bone - 1. increase and regulate activity of osteoclast , osteoblast ``` 2. enhance endochondrial ossification 3. increase collagen & Proteoglycans Cartilage - 1. increased interstitial growth - production of chondrocytes (proliferation ) GH acts directly on : liver 0 increased gluconeogenesis 0 IDF - 1 production Adipose 0 Lipolysis Muscles animo acids.

Question 29

What is Prolactin ?

Answer 29

Normal levels - male - < 15 ng / ml Female - < 25 ng / dl non -pregnant women - 24 to 386 ng /ml after birth of child - during breast feeding - prolactin released in slightly larger consquences - for milk production and inhibition of preganacy during this time. - inhibits GnRH production thus LH and FSH

Question 30

What is prolactinoma

Answer 30

prolactinoma - non cancerous tumor of pituitary gland - secretes too much prolactin - hyperprolactemia ``` 0 infertility 0 loss of libido 0 galactorrhea 0 amenorrhoea 0 osteoporosis 0 erectile sydunction. ``` can push on nerves whch released dopamine (inhibitor of prolactin ) dopamine never reaches prolactin. can compress optic chiasm - bitemporal heminopia.

Question 31

Treatment of prolactinoma ?

Answer 31

dopamine receptor agonist - bromocriptine , cabergoline Surgery

Question 32

What are Paragangliomas ?

Answer 32

chromaffin cell origins - situated along entire sympathetic chain

Question 33

What are the different severity of hypercalcaemia?

Answer 33

> 3 mmol /L - most likely to be asymptomatic 3 - 3.5 - may be tolerated if rise is slow . But can be become symptomatic- prompt treatment usually indicated > 3.5 mmol/L - severe - needs emergency treatment- risk of dysrithmia and coma * note - on a ecg - hypercalcaemia will show shortened QT interval due to dysrthymia.

Question 34

What is Glucocorticoid induced osteoporosis ?

Answer 34

Risk increases with ; 0 Age 0 Dose 0 duration - have previous fragility fracture. GC - negative feedback on pituary galnd ------------------> reduction in FSH (less androgens & estrogen) , less ATCH (androgens ) LOW ANDROGENS & ESROGENS - INCREASED RISK OF OSTEOPOROSIS. GC - increased RANK ligand production (more osteoclast activity 7 bone resorption) - inhibit production osteoprotergerin - (Function - binds to rank ligand preventing osteoclast activity. ) INCREASE RISK OF FRACTURES HYPOCALCEMIA TRIGGERS -----------------------------> PTH STIMULATION -------------------------------> ACTIVATION OF RANK LIGAND ------------------> CYCLE STARTS AGAIN (reason why hypocalemia is caused is ------------------> increased resorption by osteoclasts ------------------> high CA & PH in blood -----------------> consquence - body reduces intestinal absorption of CA (more urine )----------------> causes hypocalcemia. SIGNS FRACTURES e.g Veterbral (most common) (often asymptomatic and found by chace on imaging)

Question 35

What do you have to be careful with when on Denosumab?

Answer 35

Cant stop suddenly have to work way to stopping by transferring safety to bisphosphonates instead. if you don't risk of veterbral fractures.

Question 36

passmedicine - lowest doses to start glucocorticoid induced osteoporosis prophylaxis ?

Answer 36

The risk of osteoporosis is thought to rise significantly once a patient is taking the equivalent of prednisolone 7.5mg a day for 3 or more months. It is important to note that we should manage patients in an anticipatory, i.e. if it likely that the patient will have to take steroids for at least 3 months then we should start bone protection straight away, rather than waiting until 3 months has elapsed. A good example is a patient with newly diagnosed polymyalgia rheumatica. As it is very likely they will be on a significant dose of prednisolone for greater than 3 months bone protection should be commenced immediately. Management of patients at risk of corticosteroid-induced osteoporosis The RCP guidelines essentially divide patients into two groups. 1. Patients over the age of 65 years or those who've previously had a fragility fracture should be offered bone protection. 2. Patients under the age of 65 years should be offered a bone density scan, with further management dependent: T score Management 0 Greater than 0 Reassure 0 Between 0 and -1.5 Repeat bone density scan in 1-3 years 0 Less than -1.5 Offer bone protection The first-line treatment is alendronate. Patients should also be calcium and vitamin D replete.

Question 37

Causes of hypokalemia / low potassium ? - Capsule symptoms treatment -

Answer 37

0 reduced ingestion (illness, eating disorder, problematic diet) 0 increased excretion (diarrhoea, vomiting, osmotic diuresis) 0 transcellar shifts (alkalosis) 0 Mg deficiency - need to correct this first before hypokalaemia - mg needed to allow na/ k channel to work and to inhibit ROMK channel in DCT of nephron which excrete k into urine. 0 drugs (loop or thiazide diuretics, insulin, proton pump , corticosteriods , beta agonists e.g terabuline , salbutamol , aminoglycosides - gentamcin. etc.) Low extracellular potassium reduces cell excitability and thus impedes muscle fibre conduction (smooth and skeletal): - Absent reflexes - Constipation - Cramps - Weakness - Tiredness * if have symptomatic diarrhoea - hypokalemia - give 0.9 % sodium chloride with Potassium (Chloride )(maximum of 10mmol/hr - 40mmol over 4 hours etc) - any higher risk phlebitis (inflammation of vein - a lot of other parental drugs do this if no symptoms - (and mild - moderate ) - oral KCL i n 0.9 NACL. Give IV if cant tolerate oral , severe or has symptoms.

Question 38

SEvere hypokalemia vs mild .

Answer 38

Severe - below 2.5 mild - below 3.5 moderate - 2.5 - 3mmol /L if you see ECG changes - indicates more serious case - e.g if there are arrythmias , - but can happen in mild if there is history of ischaemic heart disease, heart failure or left v hypertrophy.

Question 39

what is secondary aldosteronism ?

Answer 39

Reduced blood flow to kidney causes activation of RAAS ----------------. hypersecretion of aldosterone. Causes of reduced blood flow 0 obstructive renal artery - atheroma , stenosis 0 renal vasoconstriction 0Edematus disorder- heart failure , nephrotic sundrome , cirrhosis with acites Aldsterone is trying to raise BP -----------> does this by retaining sodium but loses K as a result, attracts water , increases BV -------------------> so increased BP , but hypokalemia .

Question 40

What is kerticterus ?

Answer 40

Brain damage & seizures cause by build up of bilirubin in babies (new born jaundice ) * jaundice is normal in babies -usually get better on its own within 24 hrs. treatment - 1. phototherapy - blue light polymerises bilirubin more easy to pass out. or 2. Exchange transfusion - blood of baby removed and transfused with donor blood. pathological hyperbilirubinaemia: unconjugated - medical emergency 1ST LINE immediate exchange transfusion + phototherapy (Started while preparing for transfusion and continued after) + hydration pathological hyperbilirubinaemia: conjugated 1ST LINE treatment of underlying cause. If above 95 percentile for bilirubin level for their age group ( on graph for exchange transfusion) 1ST LINE ET + PHOTOTHERAPY + HYDRATION If above 95 percentile for bilirubin level for their age group ( on graph for phototherapy) 1ST LINE Phototherapy + hydration

Question 41

Causes of spider navei ?

Answer 41

Hormones e.g oestroegn increase during pregnancy or oral contraceptive pill - liver or thyroid disease. * usually a cosmetic concern - treating underlying cause usually fixes it.

Question 42

What is Hamman's sign ?

Answer 42

Hamman's sign (a.k.a. Hamman's crunch) is a “mediastinal crunch” heard upon auscultation in the setting of mediastinal emphysema (air in the mediastinum). With each heartbeat, the air is displaced creating this auscultatory finding. ( indicative of surgical emphysema) crepitus on swollen areas in a sign of surgical emphysema - air in the tissues