Endocrinology Flashcards
WHAT IS ACROMEGALY?
What is it caused by?
https://www.youtube.com/watch?v=54h3IUbvHDU
Too much growth hormone from the pituitary gland
Tumour
or hyperplasia
What does the hypothalamus release? What does this cause? In acromegaly
Release growth hormone releasing hormone
Stimulates pituitary to release growth hormone
Somatostatin (growth hormone inhibiting hormone)
Decrease growth hormone release from pituitary
What do gigantism and acromegaly involve?
Increase in growth hormone
What is the difference between gigantism and acromegaly?
Difference in when growth hormone is released
When does gigantism occur?
Before the closure of the epiphyseal plates
End up very tall
When does acromegaly occur?
After epiphyses fuse
Not tall
At what age does acromegaly start?
At 20-40
What are the symptoms of acromegaly?
Go through each topic RS etc
RS
Snoring
GI
“Wonky bite” (malocclusion)
Int
↑Sweating
Endo
↑Weight
UG
↓libido; amenorrhoea
MSK
Arthralgia; backache
Neuro
Acroparaesthesia; headache
What are the signs of acromegaly?
Skin darkening
Acanthosis nigricans
Face
Big supraorbital ridge
Interdental separation
Macroglossia
Prognathism
Laryngeal dyspnoea
Spade-like hands and feet
Tight rings
Carpal tunnel syndrome
What are the complications of acromegaly?
- *Impaired glucose tolerance** (40%)
- *Diabetes Mellitus** (15%)
Vascular
HTN
LVH
Cardiomyopathy
Arrhythmias
Colon cancer
How can you diagnose acromegaly?
IGF-1 (somatomedin) tells tissues to grow
Elevated
Glucose tolerance test
75g or glucose
Wait 90 mins measure growth hormone levels
Will stay elevated! Should decrease
Growth hormone levels
Not usually used becaue pulsatile
CT or MRI
Could be no tumour, could be ectopic source
What is the treatment of acromegaly?
Trans-sphenoidal Surgery
Radiation
Medications - suppress GH
Somatostatin anaologues
Octreotide
Recombinant GH receptor antagonist
Pegvisomant
WHAT IS PROLACTINOMA?
WHAT IS CUSHING SYNDROME?
https://www.youtube.com/watch?v=ea1sXgd5ui8
Endocrine disorder with elevated cortisol levels in the blood
What is the cause of cushings DISEASE?
Pituitary adenoma making excess ACTH
What does the hypothalamus secrete in cushing’s?
Corticotropin releasing hormone
What does CRH stimulate?
Pituitary gland to release adrenocorticotropin hormone (ACTH)
What does ACTH do?
Affects cells in the adrenal cortex of the adrenal glands
What is the outer layer of the adrenal glands split into?
Zona glomerulosa
Zona fasiculata
Zona reticularis
What is the zona festiculata?
Largest zone
Stimulate cells in this zone to secrete cortisol
Cortisol is a glucocorticoids
What are glucocorticoids not?
What are they bound to?
How much is free in the blood?
Soluble in water
Cortisol-binding globulin
Only 5% free in blood
Less than that is active
What happens to excess free cortisol?
Filtered in kidneys and put into urine
What is free cortisol involved in?
(Type of cycle)
Part of circadian rhythm
High in moring
Low at night
So if there is a problem with cortisol levels what would this lead to?
Problems with circadian rhythm
What happens to cortisol during stress?
What does it do?
(type of process)
Increaes
Increase gluconeogenesis
Increase lipolysis
Increase proteolysis
How does cortisol maintain blood pressure?
Increase sensitivity of peripheral blood vessels to catecholamines
Adrenaline and noradrenaline
This narrows the blood vessel lumen
What does cortisol do to the immune response?
Decereases the production and release of inflamatory medaitors
Prostaglandins and interleukins
Inhibiting T-lymphcytes
What is cortisol involved with in the brain?
Mood and memory
How does the body keep control of cortisol?
Negative feedback mechanisms
Decrease production of CRH and ACTH
Less CRH causes less ACTH too
What does excess cortisol lead to?
Overload of what it normally reacts with
Severe muscle, bone and skin breakdown
Hypertension
Inhibit gonadotropin releasing hormone from hypothalamus
Dampens inflammatory response
More susceptible to infections
Impair normal brain function
What does elevated breakdown of muscle, bone and skin cause?
(What does this produce)
Elevated blood glucose
High insulin levels
Targets adipocytes in center of body
Activates lipoprotein lipase
Accumulate more fat molecules
Cause
Moon face
Buffalo neck hump
How is hypertension caused by excess cortisol?
Amplifies effect of catecholamines on blood vessels
Cortisol cross reacts with mineralcorticoid recptors
Mineralcorticoids released from zona glomerulosa
Triggers mineralcorticoid effect which is increasing blood pressure by retaining fluid
ALDOSTERONE
What does the inhibition of gonadotropin releasing hormone do?
Messes up ovarian and testicualr function
What are the causes of Cushing’s?
Exogenous cortisol
Medications (steroids)
Endogenous
Pituitary adenoma
Cushing disease
Cells don’t invade other tissues
Small cell lung cancer
ACTH
Tumour of the adrenal glands
Adrenal carciomas
Adrenal adenoma
Why do steroids cause Cushing’s?
Structure very similar to cortisol
Mimics action on tissue
Negative feedback on hypothamus and pituitary
How do the steroids affect the zona fesiculata?
Causes it to shrink in size
Because of lack of stimulation
How does a pituitary adenoma cause a rise in cortisol?
Causes the pituitary gland to secrete more ACTH
This affects the zona fasiculata
Causing it to grow in size
Secrete excess cortisol
What does a tumour on one adrenal gland do?
Divide abnormally and secrete excess cortisol
Suppress CRH and ACTH production
Other gland shrinks
What are the symptoms of Cushing’s?
Muscle wasting and thin extemities
Easy brusing
Abdominal striae
Fractues - osteoporisis
Full moon shaped face
Buffalo hump
Truncal obesity
Hypergylcemia
Diabetes mellitius
Hypertension
Cardiovascular disease risk
Increase vulnerability to infections
Poor wound healing
Amenorrhea
Psychiatric
What is the diangosis of Cushing’s?
ENDOGENOUS
Dexamethasone suppresion test
Low dose of dexamethasone (steroid)
Supressess ACTH production
Should cuase decrease cortisol levels
24 urine sample
Measuring free cortisol
Blood or saliva tests
Normal daily rise and fall of cortisol
What is the next stage after dexamethosone supression test?
ACTH plasma levels checked
Low ACTH gives diagnosis of
Adrenal adenomas and carcinoma
High ACTH gives diagnosis of
Cushing disease and ectopic ACTH production
What is the next stage if there is a high ACTH?
Injection of high amount of dexamethasone
Ectopic sites won’t respond
What types of imaging can be used?
MRI of pituitary
CT of adrenals
CT of chest abdomen or pelvis for ectopic
What is the treatment for Cushing’s?
Exogenous
Drug is gradually stopped
Adrenal crisis if too fast
Adrenal glands might be atrophied
Endogenous
Surgery
Adrenal steroid inhibitors
Ketoconazole and metyrapone
Most useful ectopic
What are you at risk of if you have your adrenals removed?
Nelson’s syndrome
Skin pigmentation increase
WHAT IS SYNDROME OF INAPPROPRIATE SECRETION OF ADH?
(Start with what it results in)
https://www.youtube.com/watch?v=0NHT8ERUBo0
Hyponatremia and hypo-osmolality
From inappropriate, continued secretion of ADH
Despite normal or increased plasma volume
Which results in impaired water excretion
What hormone controls water retention in the body?
What is it also called?
What does it also do?
ADH (vasopressin)
Also contricts arteries
What happens with the different levels of ADH?
More gives more water retention
Less gives less water retention
Where does ADH have its action on the nephron?
Distal convoluted and the collecting duct
What are the channels called that move into the membranes in the nepheron?
Aquaporins
What happens to the plasma osmolality when water is drunk?
Drops
What part of the body controls water regualtion?
Hypothalamus
What does the hypothalamus signal?
Pituitary
What does the pituitary do?
Decrease ADH
Less water retention
Increase osmolality
What happens if ADH continues to be secreted even if the plasma osmolality is low?
Increase aquaporins and increased water retention
Dilutes blood
Which dilutes sodium and also takes up more space
What does this taking up of more space cause to happen(hormone)?
Decrease aldosterone
What does the decrease in aldosterone do?
Excretes more sodium
This makes water follows
However end up with a very low sodium osmolality
Leading to SIADH
What are the different types of SIADH?
Type A
Type B
Type C
Type D
What is type A SIADH?
Erratic
Independent of plasma osmolality
Massive increase of ADH
Massive increase of urine osmolality

What is type B SIADH?
Constant release of ADH

What is type C of SIADH?
Baseline concentration of sodium is low
But is stable

What is type D SIADH?
ADH normal
Massive increase in urine osmolality

What are the symptoms caused by in SIADH?
Derived from decreased sodium in the blood
What are the symptoms of SIADH?
Dehydration
Headaches
Nausea
Vomiting
Muscle cramps
Cerebral oedema, Confusion, Mood swings
Seizure, Coma, Death
What is the diagnosis of SIADH?
Symptoms and lab results
Blood
Low sodium and low osmolality
Urine
High urine osmolality and high sodium
What causes SIADH?
Infection
Strokes
Haemorrhage
MS
Drugs
Mood stabilizers
Anti-epileptics
Surgery
Increased ADH secretion
Ectopic ADH
Small cell lung cancer
What is the treatment for SIADH?
Treat underlying cause
Restrict daily intake of fluid
High salt and protein diet
Inhibit ADH secretion drugs
Tolvaptan
Hypertonic IV fluids
THYROID DISORDERS?
What are the hormones produced by the thyroid gland?
Triiodothyronine (T3)
Active version x5 more
Thyroxine (T4)
What do the thyroid hormones do?
Burn foods
Stimulates sympathetic nervous system
GI motility
Increase heart rate
Increase blood pressure
Temperature
What does the hypothalamus release?
TRH
What does the pituitary release?
TSH
WHAT IS HYPOTHYROIDISM?
Low production of thyroid hormones
What is primary and secondary hypothyroidism?
Primary is a reduction in thyroxin (T4)
Secondary is a reduction in TSH
What are the causes of primary hypothyroidism?
Primary atrophic hypothyroidism (No goitre)
Hashimoto’s thyroiditis (Goitre)
Iodine deficiency
Post-thyroidectomy / radioiodine / antithyroid drugs
Lithium / amiodarone
What are the causes of secondary hypothyroidism?
Hypopituitarism
WHAT IS HASHIMOTO’s THYROIDITIS?
(inside hypothyroidism)
Autoimmune disease
What are the antibodies in hashimoto’s thyroiditis?
TRAbs = TSH receptor antibodies
Anti-Tg = Thyroglobulilin antibodies
TPOAb = Thyroperoxidase antibodies
What is the epidemology of hashimoto’s thyroiditis?
Older Women
What are the symptoms of hypothyroidism?
RS
Hoarse voice
GI
Constipation
Int
Cold intolerance
Endo
Weight gain
UG
Menorrhagia
MSK
Myalgia, weakness
Neuro / Psych
Tired, low mood, dementia
What are the signs of hypothyroidism?
- *B**radycardic
- *R**eflexes relax slowly
- *A**taxia (cerebellar)
- *D**ry, thin hair / skin
- *Y**awning / drowsy / coma
- *C**old hands +/- ↓T°C
- *A**scites
- *R**ound puffy face
- *D**efeated demeanour
- *I**mmobile +/- Ileus
- *C**CF
What are the investigations for hypothyroidism?
TFT
TSH RAISED
Lipids/cholesterol
High
FBC
Macrocytosis
What are the associations of hypothyroidism?
AUTOIMMUNE
Type 1 Diabetes Mellitus
Addison’s disease
Pernicious anaemia
Primary biliary cirrhosis
INHERITED
Turner’s syndrome
Down’s syndrome
Cystic fibrosis
What is the treatment of hypothyroidism?
Levothyroxine (T4)
Higher doses in the young
WHAT IS HYPERTHYROIDISM?
Too much thyroid hormones
What are the causes of hyperthyroidism?
GRAVES’ DISEASE
TOXIC MULTINODULAR GOITRE
TOXIC ADENOMA
ECTOPIC THYROID TISSUE (mets / struma ovarii)
EXOGENOUS (Iodine / T4 excess)
DE QUERVAIN’S THYROIDITIS (post-viral)
What happens in graves disease?
What are the triggers?
Autoimmune
IgG autoantibodies bind to and stimulate TSH receptors
Infection, stress, childbirth
What are the classic symptoms of graves disease?
Eye disease, pretibial myxoedema, thyroid acropachy
Autoimmune (vitiligo, type 1 DM, Addison’s)
What are the symptoms of hyperthyroidism?
CVS
Palpitations
GI
Diarrhoea
Int
Heat intolerance
Endo
↓Weight, ↑appetite
UG
Oligomenorrhoea +/- infertility
Neuro / Psych
Tremor, irritability, labile emotions
What are the signs of hyperthyroidism?
HANDS
Palmar erythema; warm, moist skin; fine tremor
PULSE
Tachycardia; SVT; AF
FACE
Thin hair; lid lag / retraction
NECK
Goitre; nodules; bruit
What are the investigations for hyperthyroidism?
TFT
Increase T4 and T4
FBC
Normocytic anaemia
ESR (↑)
Calcium (↑)
LFT (↑)
Thyroid autoantibodies
Visual fields, acuity, eye movements
What is the treatment for hyperthyroidism?
β-blockers
Propanolol(rapid control of symptoms)
Antithyroid medication
Carbimazole SE = AGRANULOCYTOSIS
Block and replace (carbimazole + thyroxine)
Radioiodine (131I)
Thyroidectomy
What are some causes of goitre?
Physiological
Graves’ disease
Hashimoto’s thyroiditis
De Quervain’s
What are the thyroid cancers?
Papillary (60%)
Follicular (≤25%)
Medullary (5%)
Lymphoma (5%)
Anaplastic
WHAT IS PRIMARY ADRENAL INSUFFIENCY?
https://www.youtube.com/watch?v=V6XcBp8EV7Q
The adrenal glands can’t produce enough hormones
Aldosterone and cortisol
Primary refers to the adrenal glands themselves
What can addison’s disease be?
Acute and chronic
What are the different layers of the adrenal glands?
Cortex
Zona glomerulosa
Zona fasiculata
Zona reticularis
Medulla
What does the zona glomerulosa produce?
Aldosterone
What does the renin, angiotensin aldosterone system do?
Decrease potassium
Increase sodium
Increase blood volume and pressure
What is aldosterone stimulate by?
Renin
What is aldosterones actions?
Bind to receptors on the distal convulted tubules
Sodium potassium ion pumps of principal cells
Work harder
Drive potassium into cell from blood
Flows down concentration gradient into urine
At same time sodium goes in the opposite direction
Water also moves into blood
Increasing blood pressure
Proton/ATP pumps in alpha-intercalated cells
More protons secreted into urine
Bicarbonate pumped into blood
Increases pH
What is produced in the zona fasiculata?
Cortisol and glucocorticoids
How is cortisol released?
Hypothalamus releasing corticotropin releasing hormone
Acts on pituitary
This releases adrenocorticotropin into blood
Acts on zona fasiculata
What is special about cortisol?
Lipid soluble and can act on many cells in the body
What is a function of cortisol?
Gluconeogensis
From muscle
and fat
What does insulin do?
Reduce glucose levels in blood
What does the zona reticularis do?
Make androgens
E.g. deyhydroepiandosterone
Precursor to testosterone
What does testosterone do in males?
Contributes to development of male reproductive tissue
Secondary sex characteristics e.g. facial hair and adams apple
What is testosterone do in females?
Growth spurt in development
Underarm and pubic hair during puberty
Increase sex drive in adulthood
What is the production of androgens stimulated by?
ACTH
What happens to the adrenal cortex in primary adrenal insufficiency?
Gets progressively damaged
What are the causes of primary adrenal insuffiency?
In developed countries
Autoimmune destruction
Unclear reason
Developing countries
Tuberculosis
Infection spreads from lungs to adrenal glands
Metastatic carcinoma
What does the adrenal cortex have which allows it to keep healthy?
High functional reserve
Allows it to keep up with small amount of cells present
What do the symptoms of primary adrenal insufficiency depend on?
Which part of the adrenal cortex has been destroyed
What happens if the zona glomerulosa is destroyed?
Aldosterone levels fall
Leads to high potassium levels in the blood
Low sodium - hyponatremia
Low sodium water moves out of the blood vessels
Hypovolemia
High protons in blood
Metabolic acidosis since it’s caused by the kidneys
What are the symptoms if the zona glomerulosa is affected?
Cravings for salty foods
Nausea and vomiting
Fatigue
Dizzyness
What happens if the zona fasiculata is destroyed?
Cortisol falls
Inadequate glucose levels in times of stress
Pituitary glands become overactive
Since usually cortisol has negative feedback on pituitary
Produces proopiomelinocortin
Precursor to ACTH and MSH
What are the symptoms if the zona fasiculata is destroyed?
Fatigue in times of stress
Hyperpigmentation on knuckles and joints
What happens if the zona reticularis is destroyed?
Men not affected
Testes major source of male androgens
Females
Loss of pubic hair
decreased sex drive
What does primary adrenal insuffiency usually need to cause symptoms?
Symptoms often slow,
Major stressor comes along
Injury, surgery or infection
Cause symptoms to appear
Sudden need for aldosterone and cortisol
What is it called when the body suddenly needs aldosterone or cortisol and the body can’t deliver?
Addisonian crisis (acute primary adrenal insufficiency)
What are the symptoms of addisonian crisis?
Pain in back abdomen or legs
Vomiting and diarrhoea leading to dehydration
Low blood pressure leading to loss of consciousness
Death
What syndrome can cause an addisonian crisis?
Waterhouse-friderichsen syndrome
Causes blood vessels in adrenal glands to rupture
How can you diagnose addison’s disease?
ACTH hormone test
Small amount of synthetic ACTH injected
Measure cortisol and aldosterone produced
Both will be low
Bloods
FBC(anaemia, eosinophilia)
U&E(↓Na+, ↑K+, ↑Ca2+, ↑Urea)
BM(↓)
What is the treatment for addison’s disease?
Homones
Cortisol
Aldosterone
Androgens
Take for life
Stopping can lead to crisis
WHAT IS SECONDARY ADRENAL INSUFFICIENCY?
Lack of ACTH
and therefore cortisol
What are the causes for secondary adrenal insufficiency?
Medications
Glucocorticoids
Pituitary mass or infection
Why is aldosterone unaffected in secondary adrenal insufficiency?
Aldosterone secretion independent of ACTH
What is the diagnosis of secondary adrenal insufficiency?
Bloods
Low cortisol
What is the treatment for secondary adrenal insufficiency?
Glucocorticoid analogues
WHAT IS CONN’S SYNDROME?
https://www.youtube.com/watch?v=JBfkGNr01V8&t=1s
Hyperaldosteronism
Adenoma of the glandular epithelial cells
Secrete too much aldosterone
If there is high aldosterone levels, what will the ion levels be in the blood?
Potassium low
Sodium high
Less protons
What do the ions in the blood in conn’s syndrome cause?
Hypertension
Metabolic alkolosis
What are the symptoms of Conn’s syndrome?
Headaches and flushing
Constipation
Weakness
Heart rhythm changes
What is the diagnosis of Conn’s syndrome?
Bloods
High levels of aldosterone
Low levels of renin
What is the treatment for Conn’s syndrome?
Potassium sparing diuretic
Spirinolactone
Surgery
Remove tumour
WHAT DIABETES MELLITUS?
Trouble moving glucose from blood into cells
High level in blood
Not alot in cells
How does the body control movement of glucose in and out of cells?
Insulin
Decrease glucose
Glucagon
Increase glucose
Where are the hormones released from to monitor blood glucose?
Islets of langerhans
Beta cells in the middle release insulin
Alpha cells on the periphery release glucagon
What happens in a cell when insulin is released into the blood?
Insulin in the blood binds to receptors on muscle cells or adipose tissue
Causes vesicles containing glucose transporters to fuse with membrane
Allows glucose to enter
What does glucagon do?
Causes the liver to make glucose from other sources
Breaks down glycogen into glucose
Put into blood
What happens in diabetes mellitus?
Too much glucose in blood
How much of the population has diabetes mellitus?
10%
What are the different types of diabetes?
Type 1
10%
Type 2
90%
What is type 1 diabetes mellitus?
Body doesn’t produce enough insulin
What does the immune system do in type 1 diabetes and what type of hypersensitivity is it?
Bodies own cells attack the pancreas
Type 4 hypersensitivty reaction
Cell-mediated response
What are antigens made up of?
Peptides
Polysaccarides
Lipids
What is the process that gets rid of T cells which attack our own cells called?
Self tolerance
What happens with type 1 diabetes which loses self tolerance?
Genetic abnormality
Loses self tolerance of T cells attacking beta cells
T cells attract other T cells
What happens if beta cells are destoryed?
Glucose accumilates in blood
What genes encode the MHCs?
What chromosome are they on?
HLA system
Chromosome 6
Which genetic genes are affected in type 1 diabetes?
HLA-DR3
HLA-DR4
No everyone develops diabetes
What are the symptoms of type 1 diabetes?
Polyphagia
Glycosuria
Polyuria
Polydipsia
How does polyphagia happen?
Glucose can’t get into cells
Starved of glucose
Adipose tissue breaks down fat
Muscles break down protein
Causes weight loss and hunger
How does glycosurina and polyuria happen?
Lots of glucose in blood goes into urine
Since glucose is osmotically active it draws water into it leading to polyuria
How does polydipsia happens?
Since there is so much urination it leads to move drinking
What are some complications of diabetics with bad control?
Vascular disease
Nephropathy
Neuropathy
Diabetic foot
Retinopathy
What is the treatment for type 1 diabetes?
Lifelong insulin injections
Education
What is a big complcation of type 1 diabetes?
Diabetic ketoacidosis
What happens when the body breaks down fat?
Turns fat into fatty acids
What does the liver turn the fatty acids into?
Ketone bodies
Acetoacitic acid
Ketoacid
Beta-hydroxybutyric acid
Reduced ketone
What are ketone bodies used for?
Energy by cells
What can ketones do to the blood?
Make the blood acidic
What does making the blood acidic do to the body to compensate?
Kussmaul respiration
Deep/labored breathing
To reduce CO2
Reduce acidity
What transporter to cells have on their surface?
Proton potassium transporter
When there is no insulin what problem does this cause for cells?
Insulin also activates a potassium sodium pump
If there is none like in diabetes pump doesn’t work
More potassium stays outside of the cell
Gets into blood and causes hyperkalaemia
What does the body do with all the potassium in the blood with diabetes?
Excretes it
But levels of potassium in cells stays low
What is the high anion gap in diabetes?
Large measured difference in negative and positive ions
This is from ketoacid build up
How can a diabetic ketoacidosis happen in somebody who already has insulin treatment?
A stress e.g. infection
Release of epinephrine
Release of glucagon
More glucose in blood
Loss of glucose in urine
Loss of water
Dehydration
Need for alternative energy
Generation of ketone bodies
What do the ketone bodies break down into? What does this cause to the breath?
Acetone
Fruity smell
What does ketoacidosis cause?
Nausea
Vomiting
Mental status changes
Cerebral oedema
What is the treatment for diabetic ketoacidosis?
Fluids for dehydration
Insulin to lower blood glucose
Electrolytes (K+)
What is type 2 diabetes mellitus?
Body makes insulin but the cells don’t respond
Not fully understood
What happens when insulin gets to the cell?
Cells don’t respond
Transporters don’t go to the membrane
Insulin resistance
What are the risk factors for type 2 diabetes?
Obesity
Lack of exercise
Hypertension
What is thought to be a cause of diabetes type 2?
Excess of adipose tissue releases free fatty acids and adipokines
These two molecules can cause inflammation
This is related to insulin resistance
What genetic factors show genetic link with diabetes type 2?
Having a twin with type 2 diabetes dramitically increases the risk of having diabetes in the twin
What happens to the glands in the pancreas as a result of the cells not responding to insulin?
Secrete more insulin leading to beta cell hyperplasia and hypertrophy
What is normoglycemia?
Insulin levels high when cells don’t respond to insulin
Blood glucose levels remain normal
What other protein do the beta cells release?
Islet amyloid polypeptide (amylin)
What happens in the beta cells of the pancreas after a while when they are trying to compensate?
Hypotrophy and hypoplasia
What happens when the beta cells of the pancreas decrease?
Less insulin leading to hyperglycemia leading to polyuria etc etc
What is different from type 1 diabetic ketoacidosis from type 2 diabetic ketoacidosis?
Insulin and glucagon balance is okay
so diabetic ketoacidosis doesn’t occur
What is the state that is much more common in type 2 diabetes?
Hyperosmolar, hyperglycemic state
What does hyperosmolar, hyperglycemic state cause?
Plasma osmolarity from dehydration
Increase concentration in glucose in blood
Sometimes mild ketoemia and acidosis
What happens to the cells in HHS?
They shrivel up as water leaves them to go into the blood
What does increased water in blood vessels do?
Lead to increased urination
and total body dehydration
What does total body dehydration lead to?
Mental status changes
What does HHS overlap with?
Diabetic ketoacidosis
What are the test for diabetes?
Fasting glucose
No food or drink for 8 hours
7 mmol/l or over indicates diabetes
Non-fasting or random glucose
Over 11.1 mmol/l
Oral glucose tolerance
Over 11.1 mmol/l at 2 hours
HbA1C
Percentage or red blood cells with glucose on
48 or higher
What is a complication of diabetes in blood vessels?
Cause damage to microvasculature
Hyalinearteriscleorsis
In capillaries basement membrane thickens
Makes hard to oxygen transfer
Hypoxia
Medium and large wall damage
Athersclerosis
What systemic problems can diabetes cause?
Retinopathy
Kidneys
Nephrotic syndrome
Nerves
Decrease in sensation
Stocking-glove distribution
WHAT IS CARCINOID SYNDROME?
What three symptoms are under the syndrome?
Specific type of tumour
Causes neuroendocrine cells to secrete hormones
Syndrome
Diarrhoea
SOB
Flushing
Where are neuroendocrine cells found?
Epithelial layer of GI organs and lungs
How are neuroendocrine cells activated and what can they release?
Nerves
Serotonin
Histamine
Bradykinin
Prostaglandins
Where is somatostatin released from and what does it act on?
What does it inhibit?
Hypothalamus + GI tract
Acts on surface of neuroendocrine cells
Serotonin
What happens to serotonin?
What is it metabolised to?
What happens to the reamining serotonin?
Goes to the liver through the portal vein where it is metabolised
5-hydroxyindoleacetic acid
Goes into blood stream
What are the actions of serotonin?
GI
Increased motility and peristalsis
Blood vessels
Taken by platelets and constrict blood vessels
Heart
Stimulates fibroblasts to make collagen
Where is the most common place for a cacinoid tumour and what do they also produce more of?
GI tract
Somatostatin receptors
Where is the most common site for a neuroendocrine tumour to metastisize?
Liver
What is often neccesary for carcinoid syndrome?
Why?
Metastatisis to the liver
Liver normally metabolises the hormones released from the tumours so they build up
Causing symptoms
What does the increase in histamine and bradykinin do?
Dilates blood vessels causing flushing
What does the increase in serotonin cause?
Fibrosis of heart
Tricuspid valve regugitation
Pulmonary stenosis
Bronchoconstriction
Asthma
Shortness of breath
**_Reduces tryptophan_** Reduces niacin (vit b3) Pellagra
What are the symptoms of carcinoid syndrome?
Diarrhoea
SOB
Flushing
Itching
What are symptoms of carcinoid syndrome worsened by?
Alcohol
Emotional stress
What is the diagnosis for carcinoid syndrome?
CT scan
Octreoscan
Inject radioactive labelled octreotide
Binds to increase number of somatostatin
Urinalysis
5-hydroxyindoleacetic acid
Blood tests
Niacin deficiency
What is the treatment for cacinoid syndrome?
Somatostatin analogues
Octreotide
Decrease
Emotional stress
Alcohol
Carcinoid tumour
Surgery
Chemo
WHAT IS HYPOCALCEMIA?
Low calcium in the blood
<8.5mg/dl
What detects a change in calcium?
Parathyroid cells called calcium sensing receptor
What does parathyroid hormone do?
More
Increases release of calcium from bones
Kidneys to absorb more calcium
Kidneys to synthesie more calcitriol
Calcitriol makes the GI tract absorb more calcium
Keep extracellualr calcium in range
8.5-10mg/dl
What happens if there is a high ph or alkolosis?
Very few protons around
COO- form of albumin
More negative
Calcium attracts more to albumin
Less free ionized calcium
Symptoms of hypocalcemia
What are the causes for hypocalcaemia?
Vit D deficiency
Diet
Lack of sunlight
Malabsoption
Magnesium deficiency
Hypoparathyroidism
What are the other sings and symptoms of low calcium?
Chvostek’s sign
Trousseau’s sign
Muscle cramps
Abdominal pain
Perioral tingling
Seizures
How do you diagnose hypocalcemia?
Low calcium in blood <8.5mg/dl
ECG
Prolonged QT interval
Prolonged ST segments
Arrythmias
Lab tests
Parathyroid hormone
Vitamin D
Albumin
Phosporus
Magnesium
What is the treatment of hypocalcemia?
Normalize calcium levels
Calcium gluconate
Vitamin D supplementation
WHAT IS HYPERCALEMIA?
Higher than normal calcium levels in the blood >10.5mg/dl
What happens when there is a low ph or acidosis?
Lots of protons
COO- pick up a proton
Become COOH
More COOH becomes more positive
Calcium and albumin repel eachother
Increase in ionized calcium in blood
Whatare some causes of hypercalcemia?
Increased osteoclast activity
Increased parathyroid
Too much vitamin D
Diet or from supplements
Medications
Thiazide diuretics
Increased reabsorption
What do the kidneys do when there is hypercalcemia?
Dump more calcium in urine
Hypercalciuria
Loss of fluid
Dehydration
Leads to calcium oxalte stones
How is hypercalcemia diagnosed?
High levels of calcium in blood >10.5mg/dl
ECG
Bradycardia
AV block
Short QT interval
Osbourne wave
Lab tests
Parathyroid
Vitamin D
Albumin
Phosphorus
Magnesium
What is the treatment of hypercalcemia?
HYDRATION
DIURETICS
GLUCOCORTICOIDS (EXCRETION)
BISPHOSPHONATES
WHAT IS DIABETES INSIPIDUS?
Lack of ADH
What happens from a lack of ADH?
Water not sufficiently reabsorbed from collecting duct
Large amounts of undiluteurine
What are the symptoms of diabetes insipidus?
Polydipsia
Polyuria
Dehydration
Hypernatremia
What is central and nephrotic diabetes insipidus?
Central problem with hypothamus and pituitary
ADH low
Nephrotic problem with kidneys
ADH high
What are the causes of central diabetes insipidus?
Tumour
Lack of blood supply (incSheehan’s)
Impact/fracture
Surgical
Autoimmune
What are the nephrogenic causes of diabetes insipidus?
Lithium toxicity
Release of obstruction
Hypercalcemia
Hypokalaemia
How can you determine the cause of diabetes insipidus?
Give desmopressin
If urine output falls, osmolality increases
Suggests central
What is the treatment of diabetes insipidus?
Central
Desomopressin
Diuretics
Hydrocholorothiazide
Why do you give a patients diuretics with nephrotic diabetes insipidus?
Promote water AND SALT LOSS
Activate RAAS!!
WHAT IS HYPERKALAEMIA?
High amount of potassium in the blood
> 5.5mmol/L
What are the causes of hyperkalaemia?
External
Beta blocker
ACEi
Internal
Diabetes mellitus
Acidosis (H+ for K+ that are inside cells)
Rhabdomyolysis
Oliguric renal failure
Addison’s
Burns
What can hyperkalaemia lead to?
Myocardial excitability → VF and cardiac arrest
How can you diagnose hyperkalaemia?
ECG
Tall tented T waves
Small P waves
Wide QRS (eventually becoming sinusoidal)
VF
What is the treatment for hyperkalaemia?
Insulin
Drive K+ into cells
Treat underlying cause
Polystyrene sulfonate resin (binds K+ in gut)
Calcium gluconate (Stabilize membrane potential)
WHAT IS HYPOKALAEMIA?
Low potassium in blood
< 3.5mmol/L
What are the causes of hypokalaemia?
External
Diuretics; V/D
Internal
Excess Insulin
Alkolosis
Cushing’s
Conn’s (Increased aldosterone)
What are the symptoms of hypokalaemia?
Smooth muscle
Constipation
Skeletal muscle
Weakness
Cramps
How is hypokalaemia diagnosed?
Low potassium in blood
ECG
Prolonged QT interval
Prolonged PR interval
U wave
Arrthymias
What is the treatment for hypokalaemia?
Treat underlying cause
Supplements
Potassium sparing diuretics
WHAT DOES THE PARATHYROID DO?
What does this hormone do?
Release parathyroid hormone
Increases bone resorption
Increases calcium absorption in kidneys
Increases Vit D synthesis in kidney
Vit D increases GI absorption
What does the thyroid release in high levels of calcium?
What does this do?
Calcitoin
Increase bone deposition
Decrease kidney absorption of calcium
WHAT IS HYPERPARATHYROIDISM?
Increase in parathyroid hormone
What are the different causes of hyperparathyroidism?
Primary
Adenoma
Secondary
PTH is high to attempt to correct persistently low calcium levels
Tertiary
After many years of uncorrected secondary hyperparathyroidism
What are the symptoms of hyperparathyroidsm?
STONES, BONES and GROANS
Increased Ca2+
Weak, tired, depressed, thirsty, renal stones, abdopain.
Bone resorption
Pain, fractures, osteopenia/porosis.
Increased BP
Check Ca2+ in hypertension.
What are the tests for primary hyperparathyroidism?
PTH
High
Calcium
High
Phosphate
Low
Phosphatase
High
What is the treatment for primary hyperparathyroidism?
Treat underlying cause
What are the causes of secondary hyperparathyroidism?
CKD
vit D deficiency
GI disease such as bypass and Crohn’sare also possible
What are the symptoms for hyperparathyroidism?
Bony
Osteomalacia
What are the tests for secondary hyperparathyroidism?
PTH
High
Calcium
Low
Phosphate
High
Phosphatase
High
What is the treatment for secondary hyperparathyroidism?
Treat underlying cause
Bisphosphonates
WHAT IS HYPOPARATHYROIDISM?
Low levels of parathyroid hormone
What are the causes of hypoparathyroidism?
Primary
AI, congenital (Di George syndrome)
Secondary
Radiation, surgery, hypomagnesaemia
What are the signs of hypoparathyroidism?
Hypocalcaemia
SPASMODIC
Spasms
Trousseau’s on inflation of cuff
anxious
seixures
Chvostek’s – tap facial nerve over parotid – corner of mouth twitches.
What is the treatment of hypoparathyroidism?
Ca2+ supplements
Calcitriol (prevents hypercalciuria)