Before the Exam Flashcards
describe what causes normal gap metabolic acidosis
- this is also called hyercloremic metabolic acidosis
- this is what happens when bicarbonate decreases but the anion gap remains the same due to the increase in chloride ions
- this is normally due to gut issues
- it is seen when there is loss of bicarbonate and reduced excretion of hydrogen ions in the kidney - if the kidneys cannot excrete acids effectively then more bicarbonate is needed to buffer them causing a drop in the bicarbonate
what are the causes of normal gap metabolic acidosis
- severe diarrhea
- chronic laxative abuse
- villous adenoma
- external drainage of pancreatic or biliary secretions (eg fistulas)
- losses via NG tubes
- administration of acidifying salts
- urinary diversions
what do alpha intercalated cells secrete and reabsorb
secrete
- these cells secrete acid (via an atypical proton and ATPase and H+/K+ exchanger in the form of hydrogen ions
reasborbs
- bicarbonate (via band 3, a basolateral CL-/HCO3- exchanger
what do beta intercalated cells secrete and reabsorb
- secretes bicarbonate (via pendirin a specialised apical CL-/HCO3-)
reabsorbs
- acid (via a basal H+ ATPase)
what are the acute consequences of acidosis
Negative inotropic effects
Confusion
Kussmaul’s breathing
Hyperkalaemia
What are the chronic consequences of acidosis
Bone reabsorption leading to increased calciuria and this leading to stones
Insulin resistance
Progressive renal impairment
what do growth hormones do in
- adipose tissue
- liver
- skeletal muscles
Adipose Tissue:
Increases lipolysis.
Reduces glucose uptake.
Reduces lipogenesis.
Skeletal Muscle:
Reduces glucose uptake.
Increases lipoprotein lipase activity.
Liver:
Increases VLDL secretion.
Increases production and uptake of HDL and LDLs.
what does GLP-1 do
- inhibits glucagon secretion and hepatic glucose production
- slows gastric emptying
- promotes satiety
- augments glucose-induced inulin secretion
- rests beta cell function
- increases insulin biosynthesis
- promotes B cell differentiation
name some examples of malabsorption procedures
e.g. biliopancreatic diversion and Roux-en-Y gastric
name some restrictive procedures
adjustable gastric banding,
vertical banded gastroplasty
sleeve gastroplasty
name some expamples of restrictive plus malabsorption procedures
duodenal switch,
Roux-en-Y gastric bypass,
intragastric balloon
what is syndromic monogenic obesity
Syndromic monogenic obesity is exceptionally rare and characterized by mental retardation, dysmorphic features and organ specific abnormalities, in addition to obesity
what are the intrinsic and extrinsic factors of obesity that can lead to insulin resistance
Intrinsic factors as obesity can increase these
- (mitochondrial dysfunction, oxidative stress, ER stress) – this eventually impairs the reaction of the insulin
Extrinsic
- Accumulation of lipids and their metabolites or increased concentrations of circulating free fatty acids
- Chronic inflammation
- Altered adipokine levels
how can pro-inflammatory cytokines, saturated free fatty acids and amino acids cause insulin resistant
Pro-inflammatory cytokines, saturated FFAs, amino acids can activate Serine/Threonine kinases that can phosphorylate IRS, reducing its Tyr phosphorylation and also increasing its degradation
Why do not all insulin resistance people have diabetes
- this is because insulin resistance can be overcome by increasing insulin secretion therefore glucose control can be maintained
this happens by
- new Beta cells being generated in response to insulin resistance associated with obesity or pregnancy
- islet of langerhans increase in size and number due to beta cell increase in size and number
- there is an increased beta cell function
what do alpha glucosidase inhibitors do and what are teh side effects
Block disaccharide breakdown.
Reduces intestinal glucose absorption.
Decreases postprandial hyperglycaemia.
- Diarrhoea.
- Flatulence.
- Abdominal pain.
what is the clinical presentation of diabetic nephorpathy
Clinical presentation:
- Hypertension.
- Proteinuria.
- Decreased renal function.
what are the symptoms of McCunae-albright syndrome
hyper-functioning endocrine organs (goitre),
- precocious puberty
- hyperthyroid gotire
- adrenal hyperplasia
- somatotroph hyperplasia
bone deformities
Café-
au-lait skin pigmentation.
What is the transcription factor PUOF1 responsive for
- development of TSH, GH, PRL
What receptors do PYY act on
Y1-5 receptors expressed peripheral/vagal/central
Y2 is specifically reported as primary receptor mediating effects
what can decrease ghrelin levels in the plasma
oxytonmodulin
what does deficiets in the anorexigenic pathway lead to
Defects lead to Hyperphagia and obesity.
Genetic deletion of MC4R in both humans and mice has been linked to severe,
hyperphagic obesity.
What adult structures does the ureteric bud develop into
- ureter
- renal pelvis
- major and minor calyces
- collecting tubules
what adult structures does the metanephric (blastema) bud develop into
- Renal glomerulus and capillaries
- Bowman’s capsule
- Proximal convoluted tubule
- Loop of Henle
- Distal convoluted tubule
What are the names of the two symptoms of hypoglycameia
- neuroglycopaenia
- sympathetic response
what are the neuroglycopaenia symptoms of hypoglycaemia
Dizziness, visual disturbance, hunger
Confusion, personality change, aggression, goes quiet
Coma
what is the sympathetic response symptoms of hypoglycaemia
sweat
tremors
pallor
nausea
What is metabolic syndrome
- A syndrome including an increased risk of cardiovascular disease consisting of:-
- Insulin resistance/ Type II diabetes
- Abdominal obesity
- Dyslipidaemia (particularly hypertriglyceridaemia)
- Hypertension
How does the metabolic syndrome work
cells take up fatty aids
- lipoproteins takes the fatty acids of blood lipids
- CD36 then carries the fatty acids into the cells
- these fatty acids are normally metabolised in the mitochondria
- but if there are too much fatty acid production this can make toxic byproducts such as ceramide
- the toxic by products block signalling from the insulin receptor
- this means that the cells cannot take up glucose from the GLUT4 transporter as it cannot go to the surface
where and when can you palate the kidneys
You can palpate them at the Renal Angle: Junction of 12th rib and lat border of erector spinae muscles
◦ In order to palate as them to inspirited this lowers the diaphragm and moves them down this allows you to palpate them
why would Morrisons pouch (hepatorenal recess) be filled with fluid
heamoperitoneum,
- ascites,
- pancreatitis
describe the renal artereis
- These split form segmental arteries
- Interlobar arteries
- Arcuate arteries
- Interlobular arteries in the cortex
- Will then go into the nephron area – afferent arteriole, glomuerlus, efferent arteriole, peritiubular capillaeis/vasa recta,
name the nerve supply that make up the renal plexus
- Sympathetic T10-L2
- thoracic and lumbar splanchics
- parasympathetic vagus
- visceral afferent fibres T10-L2
what cells secrete what in the medulla
.- 80% of the medulla cells secrete adrenaline
- 20% noradrenaline,
- a few dopaminergic cells
How does the renal system acts on aldosterone
- via the principal cell
- via the intercalated cell
What are principal cells
Principal cells are the main Na+ reabsorbing cells and the site of action of aldosterone, K+-sparing diuretics, and spironolactone.
How do you diagnose conns syndrome
Aldosterone:Renin Ratio
- measure the aldostoenre and renin ratio, if renin levels are 0 and aldosterone is high then conns syndrome
Saline suppression test
- the low fluid volume increases aldosterone production therefore if you give them a bag of saline which raises the fluid level and there aldosterone levels are still high then this is pathological
CT Adrenal
Adrenal venous sampling
- this is when you insert a catheter into the groin and measure the aldosterone level form each adrenal gland
Metomidate PET
How do you diagnose Cushing syndrome
Overnight dexamethasone suppression test
– give tablet of dexamethasone at bedtime and measure the next morning they should be 0 or less than 20 nano meteres, if there not then there is a cortisol problem
24 hour urine free cortisol
LDDST: 0.5mg dexamethasone every 6 hours for 48 hours
Cortisol day curve plus midnight sleeping cortisol – measures cortisol throughout the day, if you have cushings disease the levels of cortisol will stay up all long
Blood test – midnight should be low
What can differitate between a pituitary adenoma and a ectopic ACTH secreting tumour as the cause of Cushings syndrome
- Inferior petrosal sinus sampling distinguishes between a pituitary adenoma and an ectopic ACTH secreting tumour as the cause of Cushing’s syndrome
- Blood is drawn directly from the venous sinuses around the pituitary.
High ACTH in the petrosal veins in a patient with confirmed Cushing’s compared to the periphery =
Pituitary Source of ACTH
ACTH in the petrosal veins equal to the periphery with confirmed Cushing’s = Peripheral source of ACTH
How do you diagnose Addison disease
Low 9am cortisol
High ACTH
Short Synacthen Test – synthetic ACTH – if adrenal glands are working expect to increase the amount of cortisol that is being produced
what are the two types of tumours from chromaffin cells
phaeochromocytoma
paraganglioma
how do you make a diagnosis of PPGL
• 24 hour urine metanephrines • Plasma metanephrines • CT/MRI adrenals and abdomen • 123I-MIBG scintigraphy - MIBG – tracer taken up ny neuroendocrine cells and localise din the granules where they caetcholamines are made
What is the treatments of PPGL
• Surgical resection
• Pre-operative alpha and beta-blockade – because the symptoms of these tumours are due to too much alpha and beta cell stimulus, can lead to anaesthetic bad reaction without these
– Phenoxybenzamine 10mg bd and titrate
– Propranolol 10mg qds and titrate
• Acute crisis: IV phentolamine or nicardipine
• Avoid opiates – adrenal cells have opiate receptors on them
• 131I-MIBG therapy for malignant disease
describe the embryo development of the thyroid
- develops over 24 days
- made from 2 pharyngeal pouches and 1 groove, more over following days
- then we develop additional grooves and pouches over the following days.
- Pouch 3 - inferior parathyroid and thymus
- Pouch 4 - superior parathyroid and ultimobranchial body
Ultimobranchial body - C-cells - Thyroid diverticulum starts at foramen cecum and descends Non duct closure - thyroglossal cyst
what inhibits TBG binding
Binding inhibited by phenytoin, salicylate, furosemide
what are the transports that regulate thyroid hormone uptake
MCT8
MCT10
OATP1C1
how do you treat hyperthyroidism
Thionamide drugs
- Propylthiouracil
- Carbimazole
Radioactive Iodine I-131
Thyroidectomy
name the three things that the globular filtration barrier is made out of
- Fenestrated capillary endothelium
- Basement membrane
- Podocyte layer of Bowman’s capsule – end feet that stick down on the basement membrane, between the podocyte process they have membranes and proteins that can regulate and charge
what epithelium is int he collecting ducts
columnar
- everywhere else in the renal tubular has cuboidal epithelium
define the glomerular filtration rate
- this is the total amount of fluid filtered through all the glomeruli in both kidneys
- usually 120-125 ml/min
what is clearance
it is the effective volume of plasma completely cleared of a substance per minute
what happens if there is a defect with the apical Na/Cl/K in the thick ascending loop
• Bartter’s type 1
mimic of the effects of furosemide.
causes
- Hypokalaemia,
- metabolic alkalosis,
- hypocalcaemia,
- hypomagnasaemia
what happens if there is a defect in the apical sodium chloride con transporter in the distal tubule
• Gitelman’s:
- Mimic of thiazide use.
causes
- Hypokalaemia,
- metabolic alkalosis,
- hypomagnasaemia,
- hypercalcaemia
what are the types of lower urinary tract symptoms
- Storage irritative symptoms – frequency, nocutria, urgency, urgency incontinence
- Voiding (obstructive) symptoms – hesitancy, straining, poor flow, intermittency, incomplete emptying – also terminal dribbling, dysuria, haematuria (blood in urine)
- Overactive bladder (to do with storage symptoms)– urgency with or without incontinence usually with frequency and nocutira
what factors make up the international prostate symptom score
- incomplete emptying
- frequency
- incontinency
- urgency
- weak stream
- straining
- nocturia
name some disorders of
- anatomical
- functional
- medical
- Anatomical disorders – obstructive, incontinence
- Functional disorders – stroke, spinal cord injury, neurologic disease, idiopathy
- Medical disorders – cardiac, hepatic and renal failure
name some - storage - voiding - both or neither symptoms
storage
- incomplete emptying
- frequency
- urgency
voiding
- intermittency
- weak stream
- straining
both or niether
- nocturia
Which of the following are released in response to food intake and is proportional to calorie intake?
pancreatic polypeptide
hyperkalemia is associated with …
DKA
