Metabolism Flashcards
What is Wilson’s disease?
A disease that causes copper to build up in the body, can cause liver disease
What are some cholestatic symptoms?
Pruritis, pale stools, dark urine
What would the INR be in liver disease?
High as decreased production of coagulation factors
What fo ALT above 500 and above 1500 suggest?
above 500 - autoimmune condition, above 1500 suggests hepatitis, drugs and ischemia
Deficiency of what can lead to Werninke’s encephalopathy?
Thiamine (B1)
How do you treat oesophageal varices?
Resus patient, Terlipressen which dilates splanchnic vessels, antibiotics
What’s the difference between NASH and NAFLD?
NASH is a more serious form of NAFLD where liver has now become inflammed (Mallory-Denk bodies on histology slide)
How is NAD+ and NADH related to alcohol?
During ethanol oxidation mediated by ADH, NAD+ is converted to NADH and higher NADH levels tells the cells to make more fatty acids (less fatty acid oxidation)
What level does the coeliac trunk branch at?
T12
What level do superior and inferior mesenteric arteries branch from?
L1 and L3
What is a positive Murphy’s sign?
Indicative of cholecystitis - palpate under costal margin, ask patient to inhale and if gallbladder inflammed it will cause pain
Where do direct inguinal hernias occur in relation in inferior epigastric vessels?
Medially
What is patent in indirect hernias?
Processus vaginalis
What innervates the external anal sphincter?
Pudendal nerve
Why do you get refeeding syndrom?
Metabolism changes from FAs to carbs, causes insulin secretion and ions to return to cells at expense of plasma concentration
How does acidaemia effect potassium levels?
Leads to hyperkalaemia as tissues release K+ in exchange for H+ from the blood
What causes low gap acidosis?
Drop in albumin - as albumin is the major unmeasured anion
How does glucose enter beta cells?
Via GLUT2 transporter
What is glucagon inhibited by?
Hyperglycaemia, GLP1, somatostatin, insulin, zinc
What inhibits growth hormone release?
Somatostatin
What stimulates growth hormone release?
Ghrelin, androgens, leptin, nutrition, exercise
Options for treating severe hypoglycaemia?
IV dextrose and intramuscular glucagon
How do biguanides eg metformin work?
they decrease liver production of glucose (gluconeogenesis) and enhance insulin sensitivity
What is a side effect of biguanides that mean it is contraindicated in patients with HF, liver and renal disease?
Lactic acidosis
How do thiazolidinediones work? Eg pioglitazone
increases the activity of PPAR-y, which promotes triglyceride storage in adipose tissue
How do sulfonylureas work?
They stimulate insulin release from the pancreas by binding to sulfonylura receptor -therefore only work when some beta cell activity (They may induce hypoglycaemia)
What type of drug is exenatide and tirzepatide?
GLP-1 agonist. Promotes insulin secretion, inhibits glucagon prod and prolongs gastic emptying
What type of drugs are empagliflozin and dapagliflozin?
They are sodium-glucose cotransporter inhibitors for diabetes, increase urinary glucose excretion
When might you see Kussmaul respiration?
In diabetic ketoacidosis - deep laboured breathing - body trying to remove carbon dioxide (an acid)
What is diabetic nephropathy characterised by?
Proteinuria, glomerular hypertrophy, decreased glomerular filtration and renal fibrosis
What does glycation of apolipoprotin do?
Impairs cholesterol efflux from atherosclerotic plaques
Where is the vomiting centre located?
Within the lateral reticular formation of medulla oblongata
What class of drugs are cyclizine, dramaine and dimenhydrinate?
antihistamine - H1 antagonist
What class of drug is aprepitant? for sickness
NK-1 receptor antagonist
What class of drugs are often used for postop nausea?
5HT3 receptor antagonists
Where is cholecystokinin (CCK) synthesised?
L cells in duodenum in response to fat and protein
What does CCK do?
Slows gastric emptying, releases bile and pancreatic enzymes and induces satiety
How does leptin act as a satiety signal?
By inhibiting NPy/ AgRP neurones and activating POMC/CART neurones
How does oxyntomodulin impact appetite?
It decreases grelin
What does an increase in malonyl coA do?
It suppresses food intake. Acts on CPT1c receptors to stimulate POMC/CART neurones
What type of drug is orlistat?
Lipase inhibitor
What type of drug is wegovy (semaglutide)
GLP1 agonist
What are features of metabolic syndrome?
Insulin resistance, abdominal obesity, dyslipdaemia, hypertension
What enzyme is inhibited by steroids so they inhibit inflammation?
Phospholipase A2
How can B12 and folate deficiency be linked to CVD?
Results in low methionine levels and high blood homocysteine. Homocysteine is converted to toxic thiolactone which damages endothelial cells
Which part of adrenals is neural and which part glandular?
Medulla is neural - secretes adrenaline and noradrenaline
Cortex is glandular
What zone secretes cortisol?
Zona fasiculata
What does zona reticularis secrete?
Androgens
Where does superior suprarenal arteries branch from?
Inferior phrenic
What is the venous drainage of the adrenals?
Right suprarenal drains directly into IVC
left suprarenal drains directly into left renal vein which eventually drains into IVC
What are the four infrahyoid muscles that depress the hyoid bone?
Omohyoid, sternohyoid, sternothyroid, thyrohyoid
What is venous drainage of thyroid gland?
Superior and middle thyroid vein drain into IJV
inferior thyroid vein drains into brachiocephalic vein
What does damage to one and two recurrent laryngeal nerves do?
1= hoarse voice
2=dysphonia
Whereabouts would a gallstone have to be to cause pancreatitis?
Ampulla of Vater
What happens to calcium during alkalosis?
Ionised calcium falls as more of it binds to albumin to replace the lack of H+ ions. This leads to symptoms like tingling of the lips
Can cause sudden cardiac death
What does hypocalcaemia do?
It increaes permeability of excitable membranes to sodium which causes tachyarrythmias and tetany
In cardiac action potential what causes the plateau phase?
Calcium ions enter via L-type channels. Electrically balanced through K+ efflux
What is hyperkalemia effect on action potentials?
More excitability. More K+ outside cell leads to increased positivity, easier for sodium ions to enter which leads to depolarisation and increased risk of tachycardia
What stimulates the release of PTH?
Low serum calcium (and drops in Mg)
What cells secrete PTH?
Chief cells
What suppresses release of PTH?
Calcium binding to CaSR
Activated Vit D (calcitrol) suppresses PTH transcription
Also Cinacalet (a calcimimetic drugs used to treat hyperparathyroidsim)
What are the actions of PTH?
Kidney - decreases calcium excretion and increases phosphate excretion (kidney exception)
Bone - increases calcium and phosphate resorption
Inttesitne - increases calcium and phosphate resorption
OVERALL increases calcium, decreases phosphate
What cells are useful for nuclear medicine scanning of parathyroids?
Oxyphil cells - take up technetium sestamibi
Where does most resorption of calcium take place?
Proximal tubule (but it is PTH independent)
What effect do loop diuretics have on calcium?
Hypocalciaemia
Whereabouts in the kidney does PTH upregulate TRPV channels, calcium ATPase and Na/ca exchanger to leads to less calcium excretion?
Distal tubule
What do loop diuretics act on?
The Na/K/Cl co-transporter where they compete with Cl for the binding site
What do thiazides work on?
Na+/Cl- symporter in distal convoluted tubule
What does renal PTH do for vit d?
It activates it - Stimulation of 25(OH) D3 to 1,25(OH)2 D3 by upregulating 1-alpha hydroxylase
What do PTH and calcitriol stimulate in bone?
RANKL production (and downregulates OPG)
What can be given intermittently for osteoporosis but id given continuously will cause increased bone resorption?
PTH
What might you see on xray of someone with primary hyperparathyroidism?
Terminal tuft erosion, rugger jersey spine, brown tumours (not tumours - sites of bone remodelling)
Why can Tb and granulomatous conditions lead to hypercalcemia?
Bc the macrophages within the granulatomas have a positive feedback loop on the VitD receptors. So someone sunbathes, produces a lot of Vit D which then feeds back to increase calcium levels
What gene mutation can lead to Autosomal dominant hypophosphataemic rickets?
FGF23
What is FGF23 secreted by and what does it do?
By osteocytes and it reduces serum phosphate by decreasing its resorption in the kidneys
What is difference between primary and secondary hyperparathyroidism?
Primary caused by hyperplasia, adenomas, carcinomas of thyroid whereas secondary is a physiological compensation for hypocalcemia or vit D deficiency
What causes tertiary hyperparathyroidism?
happens after long-term secondary hyperparathyroidism when the parathyroid glands have been producing high levels of parathyroid hormone for such a long time that they become overgrown and permanently overactive
In familial hypocalciuric hypercalcemia what do the mutations affect?
Inactivating mutations of Calcium sensing receptor
What is the most potent stimulator of aldosterone?
Serum potassium levels
What effects does aldosterone have in kidney?
It increases Na+ and water reabsorption and decreases K+ secretion
What is Conn’s syndrome?
Primary hyperaldoesteronism
What are three mainstays of Conn’s
hypertension, hypokalemia, metabolic alkaosis
How would you treat bilateral Conn’s disease?
Mineralcorticoid receptor antagonists or potassium sparing diuretics
What is Liddle syndrome?
It is an autosomal dominant mutation in the ENaC sodium channel which leads to a high level of expression - hypertension, hypokalemia, metabolic alkalosis
What does the binding of ACTH to MC2R on receptor of ZF cells do?
It upregulates the enzymes involved in converting cholestrol to cortisol
What is Cushings an excess of?
Glucocorticoid - cortisol
What could an ectopic ACTH secreting neuroendocrine tumour cause?
Cushings syndrome
What can a high overnight dexamethasone suppression test be a sign of?
Cushing’s. Dexameth is a glucocortiod med and should provide neg feedback to pituatary to suppress ACTH production and in turn suppress cortisol
What is Addison’s disease?
Adrenal insufficiency - low cortisol and aldosterone
Why do you get hyperpigmentation in Addison’s disease?
ACTH stimulates the MC1R in the skin
What would you find in Addison’s disease?
Low BP, Low glucose, low Na, High K
How do you treat Addison’s disease?
Replacement steroids - hydrocortisone to replace glucocorticoid and fludrocortisone to replace mineralcorticoid
How do you diagnose Addison’s?
Low 9am cortisol
High ACTH
Short synACTHen Test
What are phaeochromocytomas?
Tumours of chromaffin cells in medulla
What is phenoxybenzamine?
An alpha blocker - given pre-operatively with beta blocker.
alpha blocker to stop the hypertension, beta blocker to stop the associated tachycarida
What does the 11 betaHSD-2 enzyme do?
Oxidises cortisol to the inactive cortisone to prevent activation of MCR
Name two mineralcorticoid receptor antagonists?
Spironolactone and eplerenone
Where does the thyroid descend from in development?
Foramen Cecum
Where is TRH secreted?
Paraventricular nucleus of the hypothalamus
Where is TSH secreted?
By the thyrotropes in the anterior pituitary gland
What form is 80% of thyroid hormone?
T4
What is the inactive form of thyroid hormone?
T4
What transports thyroid hormones around the blood?
Thyroxine binding globlin
What happens to thyroid during pregnancy?
Increase of oestrogen causes sialyation of TBG which means it is cleared slower from plasma. Binds to more T4 which means less T4 is free for uptake by cells
What are the functions of the three thyroid deiodinases?
D1 = plasma T3 production
D2= local t3 production
D3 = T3 degradation
Which of the thyroid deiodinases are present in brain, placenta and foetus?
D3
What thyroid deiodinases are upregulated in hypothyroidism
D2 (opposite for hyper)
What heart problems common in hyperthyroidism?
Tachycardic and AF
What effect does hyperthyroidism have on insulin?
Reduced insulin secretion and increased insulin turnover, leads to hyperglycaemia
What disease do you get lid lag and lid retraction?
Hyperthyroidism/Graves
Name a skin problem you get in hyperthyroidism?
Pretibial myoxedema
What is Grave’s disease?
Autoantibodies that bind to THSR and cause over-expression of thyroid hormone
Why do you get Grave’s eye disease?
Bc retrooribital fibrocytes express TSH receptor
Bind to this, T cells, lymphocytes release IFNy and fibroblasts secrete GAGS
How would you treat a toxic adenoma?
Treat with I-131 radioactive iodine
What drug can cause thyrotoxicosis?
Amiodarone - drug to treat arrythmias
What is a struma ovarii?
a benign cystic teratoma containing majority thyroid tissue which can cause hyper thyroidism
What are the two drugs for managing hyperthyroidism?
Propylthiouracil and carbimazole (both inhibit TPO)
What waves are present on ECG in hypothermia
J waves (looks like a camel hump)
Why might you find mild hyponatraemia in hypothyroidism?
Bc you have a reduced GFR
How do you treat hypothyroidism?
Levothyroxine (T4)
How can corticosteroids help with treatment of Hashimoto’s?
They decrease TBG (thyroxine binding globulin) which means more free T4
In Hashimoto’s what are there antibodies against?
TPO which leads to follicular cell apoptosis
How does Acetazolamide work?
It is a carbonic anhydrase inhibitor - blocks resorption of bicarbonate (in proximal convoluted tubule). Promotes bicarbb, sodium and chloride excretion
What type of drugs are frusemide and bumetanide?
Loop diuretics
What do loop diuretics act om?
Binds with chloride binding site on Na+/K+/2Cl- transporter
What’s a side effect of loop diuretics?
Kidney stones bc more calcium in the urine
What drugs are benfroflumethiazide and hydrochorothiazide?
Thiazide diuretics
Where do thiazide diuretics work?
On the distal convoluted tubule. They block the sodium chloride co transporter
What imbalance can thiazides cause?
Hypercalcaemia
Hyponatraemia
Hypokalemia
What are the two classes of potassium sparing diuretics?
Epithelial Na channel antagonists and aldosterone antagonists
When are aldosterone antagonists used?
Hyperaldosteronism, HF, hypokalaemia (from other diuretics)
What stimulates IGF-1 production and where is it produced?
Growth Hormone and in the liver
What inhibits growth hormone release?
somatostatin
What effect does arginine vasopressin have on cortisol?
It stimulates ACTH which stimulates cortisol release
What does ghrelin do to growth hormone?
Stimulates the release of it
What mutation causes McCune-Albright syndrome?
GNAS gene
Not inherited (mosaic)
What problems might you find with McCune-Albright?
Fibrous dysplasia
Cafe au lait spots
endocrine dysfunction - precocoious puberty
What mutation can cause pituatary tumours?
AIP
What gene can cause gigantism?
duplication or upregulation of GPR101
Giant
People
Rise
101
What mutation causes red hair and fair skin?
MC1-R
(melanocortin 1 receptor)
Cushing’s disease vs syndrome?
disease = when there is a pitutary tumour causing it
syndrome = group of symptoms you get when you have excess cortisol
What does inhibin do?
Inhibits secretion of LH and FSH
When might GnRH agonists be given?
In breast or prostate cancer. Continuous pituatary stimulation - receptor desensitisation stops from producing androgens
What does kisspeptin stimulate?
Secretion of GnRH
What is Kallmann syndrome
failure of correct production of GnRH - reproductive problems along with no sense of small. Comes from failure of development of olfactory neurons
What is diabetes insipidus a deficiency of?
AVP (No insertion of aquaporins into membrane)
How can you treat diabetes insipidus?
DDAVP = desmopressin
Ratio of what carry a better diagnostic value of lipid associated CV risk that total cholestrol of HDL?
ApoB/ApoA ratio
Apo B carries Bad LDL
Apo A is ACE carries Good
What does eGFR look at?
Creatine clearance from plasma
What breast cancer antigens are used to monitor treatment?
CA15-3 and CA27-29
What can be used to help diagnose liver cancer?
Alpha-fetoprotein
What happens to mesonephric duct and paramesonephric in females?
Mesonephric duct degenerates and paramesonephric (Mullerian) forms oviduct
What happens to mesonephric and paramesonephric duct in males?
Mesonephric forms male reproductive tract
paramesonephric degenerates
What might you find in a pregnancy with a foetus with bilateral agenesis?
Oligohydramnios as in the uterus fetal kidney is important for generation of amniotic fluid
What does a horse shoe kidney get stuck on
Inferior mesenteric artery
What causes autosomal dominant and autosomal recessive polycystic kidney?
Autosomal dominant = problem with polycystin PKD-1 and PKD-2
Autosomal recessive: problem with fibrocystin
What subunit do HCG, FSH, LH and TSH all share?
Alpha
What substance is freely filtered by glomerulus and can be used to estimate GFR?
Creatinine
Why does creatinine overestimate GFR?
It is actively secreted by peritubular capillaries
What condition is characterised by a defect in the apical NaCl cotransporter at DCT lead to?
Gitelman’s. (Mimics effects of thiazides - hypokalaemia, hypomagnesia, hypercalcaemia)
What does Bartter type 1 mimic the effects of?
Loop diuretics (Furosemide)
What classes of diuretic act on proximal tubule?
Carbonic anhydrase inhibitors
What diuretic is used in volume overload from CKD?
Loop diuretic
What nerve inhibits sympathetic efferents to allow micturition to occur?
Hypogastric nerve
What part of loop is impermeable to water?
Thick ascending loop, it is where active transport of sodium takes place
In the presence of ADH what happens to aquaporins?
They become permeable to water allowing passage of water from collecting tubule to interstitium down a conc gradient
What are Councilman bodies?
hepatocytes undergoing apoptosis
What acts as a glucose sensor?
glucokinase
What ratio leads to insulin secretion?
Increased ATP to ADP ratio, closes potassium channel = depolarisation. Opens calcium channel, triggering insulin secretion
What stimulates insulin release besides glucose?
leucine and arginine (amino acids)
other things like glp1 and cck can potentiate but require glucose
What are the catecholamines synthesised from and where?
phenylalanine and tyrosine in chromaffin cells of medulla
What receptor do the catecholamines signal through?
G-protein coupled receptor
Where is glucagon like peptide synthesised?
primarily in ileo-colonic (L) enteroendocrine cells
What is a congenital problem of the foregut?
oesphageal atresia - oesophagus seals itself off
What are three problems of mid gut?
1) duodenal atresia
2)meckel’s diverticulum - when yolk sak remnant persists
3) malrotation / volvulus
What is Hirschprung disease?
a congenital megacolon due to lack of enteric neurones in distal part of gut
What muscle supports the external anal spinchter and assists in creating anorectal angle?
Puborectalis
What supplies motor supply to external anal spinchter?
inferior rectal nerve ( via pudendal )
What is innervation of internal anal spinchter?
autonomic -
sympathetic from L5 segment via hypogastric plexus
parasympathetic from S2 to S4 via pelvic plexus
what causes passive incontinence vs urge incontinence?
passive - problem with internal sphincter
urge - problem with external
What creates the inguinal ligament?
inferior border of external oblique
What abdominal muscle is absent in the inguinal canal?
transversus abdominis
Nerve roots of genitofemoral reflex?
L1 L2
Cremaster cremaster L1 L2 pulls your balls up faster
Where do you find the deep inguinal ring?
Mid point of inguinal ligament
Which is raised more in liver damage due to alcohol?
AST>ALT
What is the name of the pouch between the liver and the kidney?
Morrison’s pouch - hepato renal recess
What are the oesophageal porto-systemic shunts between?
Left gastric vein, azygous
What veins are involved in caput medusa?
enlarged epigastric veins and intercostal veins from recanalising of ligamentum teres
What enzyme catalyses the breakdown of triglycerides into free fatty acids and glycerol?
Hormone sensitive lipase
What happens to glucagon in diabetes?
excess circulating glucagon levels (as although there is a lot of glucose in blood, cant get into cells so they are still starving)
How does pancreas initially respond to insulin resistance?
new beta cells are initially generated so islets increase in both size and number
What is MODY and what is it caused by?
Maturity Onset diabetes of the young
Monogenic diabetes - mutation in one gene in autosomal dominant way
What is the most common autoantibody in latent autoimmune diabetes of adults?
Gluatamic acid decarboxylase antibody
What is Teplizumab for T1D a monoclonal antibody for?
Anti-CD3 antibody
What are DPP-4 inhibitors/ when are they given?
DPP-4 degrades GLP1 so given with GLP1 agonists, by inhibiting GLP will stay for longer
What part of the kidney do SGLT2 inhibitors work on?
The SGLT2 in renal proximal convoluted tubule
What are flavonoids?
pigmented polyphenol plant compounds, found in fruit veg, tea and coffee. Beneficial for stroke and MI
What can high levels of IGF-1 in the blood be a sign of?
acromegaly or growth hormone excess
What does HbA1c measure?
glycated haemoglobin
What requires peripheral de-iodination to achieve its maximal effect?
Thyroxine
What is the name for t3?
triiodothyronine
What does TPO do?
catalyzes the oxidation of the iodide to its active form, I2, and the binding of this active form to the tyrosine in thyroglobulin to form mono- or diiodotyrosine
What is oxybutinin used for?
overactive bladder - it is an antimuscarinic blocking actions of acetyl choline
What part of the kidney secretes aldosterone?
zona glomerulosa (it is a mineralcorticoid)
What vitamin should be given to alcoholic cirrhosis patients to prevent wernike-korsakoff encephalopthy?
b1 - thiamine
What lipoprotein main role is reverse cholestrol transport?
HDL
what immune cells are involved in atherosclerosis and release cholestrol when they die?
macrophages
What are the two substances secreted by posterior lobe?
ADH and oxytocin
What are the endocrine functions of pancreas?
releases insulin and glucagon into blood stream
What recieves sensory inputs for control of vomiting?
nucleus tractus solitarius
What type of drugs are hyoscine / scolpalamine?
alkaloid and anticholinergic drugs on m3/m5
What type of drugs are metoclopramide and domperidone? (nausea)
dopamine D2 receptor antagonists
Why do chemo drugs cause sickness?
bc they liberate 5HT from enterochromaffin cells within mucosa of upper GI
What do the 5Ht3 anti cancer sickness all end in?
-setron
What atypical anytipsyhotic can be used in breakthrough vomiting?
Olanzapine
What is the equation to work on pH?
pH = -log10 [H+]
Where does the majority of bicarbonate reabsorption take place?
proximal tubule
Why do you get normal anion gap acidosis ?
occurs due to a primary loss in bicarbonate but you get a compensatory rise in chloride
What accounts for greater than 90% of ases of hypercalcemia?
PHPT and malignancy
What is the inactive form of cortisol?
cortisone
What is saline suppression test?
test for Conn’s, give infusion of saline, see if aldosterone falls
What receptor does ACTH bind to to cause the release of glucocorticoids?
MC2R (melanocortin receptor 2) / ACTH receptor
What is glucocorticoid remediable aldosteronism?
is a heriditary form of primary hyperaldosteronism where aldosteron synthase becomes ACTH sensitive
Where is CRH released?
hypothalamus, causes release of ACTH
What are paragangliomas?
extra-adrenal chromaffin cell tumours
What might you on see on ECG for hypothyroidism?
J waves of hypothermia
bradycardia
If peripheral oedema up to sacrum how much weight do you need to take off to work out dry weight?
10kg
5kg if up to knee
1kg if just around ankle
Where is ghrelin sectreted?
gastric fundus
Where is glucose-dependent insulinotrophic polypeptide released?
by k cells in small intestine (anorexigenic hormone)
why is leptin not a target for obesity?
Bc obese individuals have high leptin anyway and are said to have leptin resistance similar to db/db mouse
Whereabouts in hypothalamus is food intake controlled?
arcuate nucleus
What do AGRP/NPY neurones release which activates Y1 receptors to increase food intake?
NPY
How do POMC/CART neurones decrease food intake?
By releasing melanocortins
what are caveats about using creatinine for GFR ?
muscular people have high creatinine, malnourished low and some drugs inhibit secretion of creatinine
What stimulates the release of ACTH?
Coritcotroph releasing hormone and arginine vasopressin
What does oestrogen and testosterone feed back on on gonadal axis?
Feed back on KNDY cells which release kisspeptin triggering GnRH release
What does metanephric kidney develop from?
mesonephric duct
where do carbonic anhydrase inhibitors work?
proximal convulted tubule
what acid base balance does acetazolamide cause?
metabolic acidosis (counteracts resp alkalosis)
What do 5-alpha reductase inhibitors lead to less of in the blood?
DHT
what type of drug is mirabegron? (urge incontinence)
Beta 3 adrenergic
What cells are renin producing?
juxtaglomerular
How can you distinguish the distal tubule from the proximal tubule?
a lack brush border and rich in mitochondria to provide energy for ion pumps
What cells are regulators of acid base balance in the collecting ducts?
intercalated cells
what do cortical vs medullary fibroblasts produce?
cortical produce erythropoietin
medullary produce gylcosamingolycans and prostaglandin E2
What gene is involved in the majority of clear cell carcinomas?
VHL gene - Von Hippel Lindau disease
