MET2 OVERVIEW Flashcards
Precursors to insulin - insulin production
Preproinsulin (110 amino acids) to proinsulin (86 amino acids) to insulin (51 amino acids)
Function of glucokinase enzyme
Senses the level of glucose in the beta cell of the pancreatic island - conversion of the glucose to glucose-6-phosphate for release of insulin
Location of GLUT1
Beta cell of pancreatic island
Location of GLUT4
Muscle cells and adipocytes
Function of insulin at the muscle and the adipocytes
Increased glycogesis
Reduced glucogenolysis
Increased lipogenesis
Reduced glygenolysis
Function of insulin at the liver
Increased mRNA translation for increased protein production
Reduced breakdown of proteins
Enzyme causing lipolysis
Lipase
Ketone bodies are produced from
Acetyl CoA
Equation to denote acid being added to water
HA –> H+ + A- (conjugate base)
Normal pH for human blood
7.35-7.45
pH of human blood leading to death
<6.8
>8
Three systems to maintain the blood pH and how long does each one take
Chemical system - immediate action
Respiratory system - 1 to 3 minutes
Renal system - hours to days
Three chemical buffer systems
Phosphate
Bicarbonate
Proteins e.g. Hb and albumin
Definition of anion gap
The difference between the measure anions and the measured cations
Cation
Ion with a positive charge
Anion
Ion with a negative charge
What is excluded when calculating the anion gap and why?
Generally exclude potassium K+ because this value is generally negligible
Normal range for anion gap
8-16
Significance of increased anion gap
Increased anion gap - metabolic acidosis
Significance of decreased anion gap
Decreased anion gap - metabolic alkalosis
General cations measured for the anion gap
Na+
Sometimes K+
General anions measured for the anion gap
HCO3-
Cl-
Why are veins more acidic than arteries?
Veins contain more CO2 - acidic
Enzyme involved in the reabsorption of HCO3- in the proximal convoluted tubule
Carbonic anhydrase
Three common causes for metabolic acidosis
Diarrhoea
Ketoacidosis
Lactic acidosis
Three common causes for metabolic alkalosis
Vomiting
Hypokalaemia
Ingestion of HCO3-
What is the blood supply to the liver?
25% - coeliac trunk
75% - hepatic portal system of veins
What is portal hypertension - how does this occur?
Due to cirrhosis of the liver - fibrosis of the parenchyma - blood cannot perfuse to the whole of the liver - builds up and there is a state of hypertension
How can you calculate the portal pressure gradient?
Difference between the normal portal pressure and the pressure of the IVC - if this is greater than 10: portal hypertension
Normal portal pressure - 9
IVC pressure - 2-6
What is the consequence of cirrhosis on a patient and why?
Splenomegaly - increased portal hypertension - increased blood flow to the spleen - causes it to swell
Causes of cirrhosis
Alcoholism
Hepatitis B/C
Why does cirrhosis result in ascites?
Damage to the liver - cannot produce enough albumin - reduced plasma proteins in the blood - blood has an increased water potential - increased movement of water out of the blood into the extra cellular tissues of the peritoneum - swelling in the abdomen - ascites
Anastomoses of which veins result in oesophageal varices?
LEFT gastric vein and oesophageal vein
Cause of caput medusae
Blood attempts to leave the portal system due to the increased pressure - formation of this from mass blood movement
Blood supply to the gallbladder
Cystic artery
What is contained within the ducts of the biliary tree?
Bile
Will a gallstone in the cystic duct cause jaundice?
No
Will a gallstone in the common bile duct cause jaundice?
Yes
Will a gallstone in the hepatopancreatic ampulla cause jaundice?
Yes
What is an adipokine?
Cytokine released by adipose tissue
Does insulin resistance mean that diabetes will occur? Why?
No - because there is islet compensation to allow for the generation of new beta cells which can also be larger and secrete even more insulin
Metformin - how does this drug act and what is it used for?
Drug used for the treatment of diabetes
Increases sensitivity to insulin at the muscle cells and at the adipocytes
Also acts to decrease the levels of gluconeogenesis
Other forms of diabetes, not T1DM or T2DM
Gestational
MODY - mature onset diabetes of the young
LADA - late autoimmune diabetes of adults
What is the most common sign of diabetic nephropathy? in a test?
Proteinuria i.e. presence of protein in the urine due to insufficient filtration by the glomerulus
What is the significance of raised protein kinase C levels?
Increased permeability of blood vessels
Increased occlusion of blood vessels and vasoconstriction
Increased mitochondrial dysfunction
What is the hypothalamo-hypophyseal portal system?
System of blood vessels connecting the hypothalamus to the anterior pituitary
What are the vascular connections of the hypothalamus and the pituitary gland?
Superior hypophyseal artery from hypothalamus to the APG
Secondary capillary plexus between anterior and posterior PGs
Drainage into the hypophyseal portal vein from the APG
Which nerve runs anteriorly to the thyroid gland?
Recurrent laryngeal nerve
What is the blood supply to the pancreas?
Coeliac trunk - splenic artery - transverse pancreatic branch
SMA - inferior pancreato-duodenal artery
Blood supply to the adrenal glands
Superior adrenal artery from the inferior phrenic
Middle adrenal artery from the abdominal aorta
Inferior adrenal artery from the renal artery
Functions of the kidney
Excrete waste products of metabolism
Maintain water and electrolyte balance
Maintain acid/base balance
Which kidney is more superiorly located and why?
The left kidney is located more superiorly
The right kidney has the liver directly superior to it and this pushes down
What is situated on top of each kidney?
Adrenal glands
What is the hepatorenal recess and where is this?
Subhepatic recess/Morrison’s pouch
Separates the live from the right kidney
This is where fluid collects if a patient is lying supine
When might fluid collect in the hepatorenal recess?
Ascites
Pancreatitis
Which organ lies anterior to both and stretches across from the right to the left kidney?
Pancreas - head of the pancreas at the right kidney and tail of the pancreas at the left kidney
Is the pancreas retro or intraperitoneal?
Pancreas is intraperitoneal apart from the tail which is retroperitoneal
What is the shape of the right adrenal gland?
Pyramidal/triangular
What is the shape of the left adrenal gland?
Crescent shaped
Are the kidneys retroperitoneal or intraperitoneal?
Kidneys are retroperitoneal
What is Gerota’s fascia?
This is the renal fascia - the kidneys are encapsulated in their own layer of fat
Arcuate line
Aka. the douglas line
Horizontal line along the rectus abdominis where the inferior epigastric vessels perforate the abdominal rectus sheath
Superiorly to the arcuate line, they are outside of the sheath and inferiorly, they are inside the sheath
‘Arcuate nucleus’
Main control centre of hunger located in the hypothalamus
How does hypothalamus control satiety and hunger?
Via usage of neurotransmitters
Orexigenic vs. anorexigenic
Orexigenic - appetite stimulating
Anorexigenic - appetite suppressing
Orexigenic neurotransmitters
Neuropeptide Y (NPY)
Agouti related peptide (AgRP)
MHC
Anorexigenic neurotransmitters
POMC
CART
Effect of serotonin on the neurotransmitters and on appetite
Reduce NPY and increase POMC
Appetite suppressant
Effect of ghrelin on the neurotransmitters and on appetite
Decrease NPY
Appetite stimulant
Which cells and what organ release GLP-1?
L-cells of the small intestine
What organ releases ghrelin and which cells?
Stomach
Parietal cells
What is ghrelin otherwise known as?
‘Hunger hormone’
Effect of GLP-1 on the neurotransmitters and on appetite?
Decrease NPY and increase POMC
Appetite suppressant
To what receptor does GLP-1 bind to?
Y2R
What other hormone does GLP-1 have the same effect as?
Serotonin
Where is the hormone cholecystokinin secreted from - what organs and which cells?
Duodenum and large intestine
Enterendocrine cells
Effect of cholecystokinin on appetite?
Suppress appetite
Effect of PYY on neurotransmitters and on appetite
Suppress appetite
Reduces NPY and increase POMC
When is PYY released?
When there is something in the gut
Effect of leptin on neurotransmitters and appetite
Reduces the level of AGRP
Appetite suppressant
Where are leptin receptors located and which are the most important?
Throughout range of tissues
Most important are in the hypothalamus
Cells that secrete leptin
Adipocytes
NB. white adipose tissue
Who secretes more leptin and why?
Those with a greater level of body fat - have more adipocytes
What is leptin resistance?
The idea that people can learn to ignore the feeling of satiety given by leptin release and continue to eat anyway
Results in increased levels of obesity
Effect of insulin on neurotransmitters and on appetite
Decrease the levels of AGRP
Appetite suppressant
Effect of malonyl co-A on neurotransmitters and on appetite
Increase POMC
Appetite suppressant
What controls malonyl coA levels?
AMPK - AMP kinase
Calcium levels - controlled by ghrelin so controlled by gut hormones
Effect of gut microbes on appetite
Believed to have a role - being researched
Different gut microbes in lean and overweight people
Drug which acts to increase appetite
Cannabinoids
How do you calculate BMI?
Weight (kg) / height (m) squared
‘Syndromic monogenic obesity’
Single gene mutation causing obesity associated with a range of other features e.g. mental retardation and dysmorphic features
30 potential gene mutations
‘Non-syndromic monogenic obesity’
Single gene mutation causing obesity and no other features
12 potenital gene mutations
Apple shape vs. pear shape - which is most dangerous and why?
Apple shape - more visceral fat - increased risk of health related issues
Blood supply to anterior pituitary gland
Supra hypophyseal artery
Blood supply to posterior pituitary gland
Inferior hypophyseal artery
Vascular connection of anterior and posterior pituitary glands
Secondary capillary plexus
Venous drainage from the anterior pituitary gland
Hypophyseal portal vein
What structure does the pituitary gland sit in and why is this important to be aware of with a pituitary tumour?
Sella turcica - has bone anteriorly and posteriorly but no bone laterally
Tumour will grow out laterally
What are the first structures that a pituitary adenoma will cause damage to?
CNs III, IV and V1, V2, V3
Optic chiasm
Carotid artery
What visual field defect will pituitary adenoma commonly result in?
Bitemporal hemianopia
What is meant by primary underactivity of a hormone?
a
What is meant by secondary underactivity of a hormone?
a
What affects the thyroid hormone levels in the thyroid axis?
a
What affects the GH hormone levels in the GH axis?
a
When in life would you have greater secretion of GH?
a
What is the condition where there are elevated levels of cortisol?
a
What is the conidtion where there is too little levels of cortisol?
a
Independent of cortisol hormone production, how might one develop Cushing’s syndrome?
a
Function of oxytocin
a
Function of ADH
a
Hormone released from thyroid gland - name
a
Active form of thyroid gland
a
Enzyme responsible for conversion of T4 to T3
a
Site of conversion of T4 to T3
a
Isoforms of enzyme that convert T4 to T3
a
Isoform of enzyme that inactivates T4 (and T3)
a
Isoform of deiodinase enzyme expressed in the periphery
a
Isoform of deiodinase enzyme expressed in the brain and pituitary gland
a
What happens to the levels of T4 and D2 during hypothyroidism?
IMPORTANT FOR EXAM
During hypothyroidism, T4 levels go down
D2 gets upregulated SO more T4 is converted into T3
What happens to the levels of T4 and D2 during hyperthyroidism?
IMPORTANT FOR EXAMS
In hyperthyroidism, there are very high levels of T4
D2 gets down regulated so the brain converts less T4 to T3
‘Thyroid binding globulin’ and when does this increase?
a
Three layers of the adrenal cortex of the adrenal gland and what they release
Glomerulosa - Mineralocorticoids e.g. aldosterone
Fasciculata - Glucocorticoids e.g. cortisol
Reticulosa - Androgens e.g. testosterone
Three types of hormones
Peptide
Steroid
Amine
Conn’s syndrome and effect
Hyperaldosterone
Effect of glucocorticoids on the immune system
Inhibition of the immune system
‘Cushing’s syndrome’
Elevated levels of cortisol
‘Addison’s disease’
Primary adrenal cortex failure
‘Adrenal hyperplasia’
Comes up in exams
Adrenal hyperplasia - causes various enzymes to not work congenitally SO lack of production of hormones from adrenal cortex
Example of enzyme deficiency in adrenal hyperplasia
21-hydroxylase
Two signs of adrenal hyperplasia
Adrenal insufficiency
Virrilisation - female babies born with male genitalia
Hormones released from adrenal medulla
Catecholamines e.g. adrenaline and noradrenaline
Cells that release catecholamines
Chromaffin cells
Effect of alpha 1 adrenoreceptor activation
Bronchial smooth muscle contraction i.e. vasoconstriction
Effect of beta 1 adrenoreceptor activation
Positive ionotrophic and chronotrophic effect on the heart
Increased renin
Effect of beta 2 adrenoreceptor activation
Bronchial, vascular, uterine smooth muscle relaxation
Glycogenolysis
Effect of Cohn’s syndrome
Increased aldosterone
Reduced plasma renin
Hypertension
