Met PBLs Flashcards
Main energy fuels used during starvation
Amino acids from muscle
TAGs from adipose tissue
Ketones from the liver
Main substrates for gluconeogenesis
Lactate
Glycerol
Amino acids
Oxaloacetate
Features of Kwashiorkor
Ascites and pitting oedema
Hepatosplenomegaly
Dermatitis
How does starvation lead to ketosis?
Decreased glucose available for the brain
Brain can only use glucose and ketones for energy production
Large amounts of lipolysis releasing FFAs to the liver for metabolism produced large amounts of acetyl CoA
Excess acetyl CoA cannot be put into the Krebs cycle as oxaloacetate supplies are depleted due to it being used in gluconeogenesis
Therefore acetyl CoA is used to make ketone bodies
Ketone body examples
Acetoacetate
b-hydroyxbutarate
Why does feeding syndrome occur?
Insulin release in referring stimulates glycogen, fat and protein synthesis. These processes require vitamins and minerals such as phosphate, magnesium thiamine. Therefore large amounts of these substances enter cells upon feeding to deplete the plasma levels.
Leads to features associated with refeeding syndrome.
How is referring syndrome avoided?
Vitamin and mineral replacements
Slow increases in caloric intake
Causes of oedema
Increased capillary hydrostatic pressure
Reduced capillary oncotic pressure
Increased capillary permeability
Lymphatic blockage
AST
Aspartate + a-ketoglutarate –> oxaloacetate + glutamate
Uses vitamin B6 as cofactor
Found in the liver, muscles, bone, heart, pancreas
ALT
Alanine + a-ketoglutarate –> a-pyruvate + glutamate
Vitamin B6 cofactor
Found mostly in the liver
Raised to a greater extent in liver disease
AST/ALT ratio
Usually below 1
>1/2 = alcoholic causes or muscle disease
ALP
Raised in liver disease
Also in biliary obstruction and bone disease
GGT
Raised in liver disease
Also in biliary obstruction but not in bone disease
Large increases in excessive alcohol consumption
INR
Modified PT
Intrinsic pathway
What is in pabrinex?
Thiamine, riboflavin, pyridoxine, nicotinamide, vitamin C, glucose
Why is terlipressin used?
Reduces bleeding from oesophageal varices
Actions of Lactulose
Increases water excretion due to osmotic effect
Acidifies gut contents so reduces ammonia absorption to prevent hepatic encephalopathy
Metabolic diseases causing cirrhosis
Haemochromatosis
Wilson’s disease
Alpha-1-antitrypsin deficiency
Why does he have high urea?
Increased protein intake due to bleeding from varices
Treatments of ascites
Diuretics
Paracentesis
TIPS
Albumin supplements
Humalog
Fast acting insulin analogue
Must eat immediately after
Glargine insulin
Long acting insulin with a peak less profile that mimics the tonic release from beta cells
DKA treatment
Fluid and electrolyte replacement
Short acting insulin
How does alcohol lead to ketoacidosis?
Ethanol metabolism leads to increased NADH/NAD ratio
Inhibits Krebs cycle, glyconeogenesis and fatty acid oxidation
Causes fatty acid synthesis and ketogenesis
Actions of GKRP
Controls location of GK
GK involved in glycolysis and glycogen synthesis as well as sensing of glucose levels
Actions of PPARG
Transcription factor for lipid metabolism
–> increased lipid uptake and lipogenesis
Decreases circulating lipid levels
How does metformin work?
Activation of AMPK
Inhibits hepatic gluconeogenesis
Increases GLP-1 secretion
Increases GLUT4 translocation
How does sitagliptin work?
Inhibits breakdown of GLP-1
Enhances insulin secretion
How does pioglitazone work?
Increases PPARG transcription
Increases lipid uptake to decrease circulating FFA levels
Define microalbuminaemia
Albumin excretion 30-300mg/day
ACR>3mg/mmol
Define proteinuria
Albumin excretion >300mg/day
ACR>30mg/mmol
How does the glomerular filtration barrier normally prevent passage of albumin into the urine?
Negative charge of endothelial cells repeals anions like albumin
Large diameter too large to pass through the pores of the filtration barrier
Prevents passage of molecules with molecular weight >60,000Daltons
Pathological changes seen in the glomerular filtration barrier in diabetes?
BM thickening
Glomerulosclerosis
Mesangial cell hypertrophy and increased matrix secretion
How does kidney disease lead to hypertension?
Reduced GFR –> increased RAAS activation
Increased water and electrolyte retention
Increases SNS activity
BP aim for diabetics
135/85
First line BP lowering drug in diabetics
ACEI or ARB
Causes of goitre
Follicular cell hypertrophy and hyperplasia due to increased TSH levels
Increased colloid accumulation in follicles
Inflammatory processes
Neoplastic processes
Main cell type in Hashimoto’s
Lymphocytes
Effects of thyroid hormones sytsemically
Increased BMR and non-shivering thermogenesis
Increased mitochondria number
Increased cardiac myocyte activity
Effects of thyroid hormones on the liver
Antagonise insulin
Increase gluconeogenesis and glycogen breakdown
Effects of thyroid hormones on muscle
Act alongside insulin
Increase uptake by increasing GLUT4 translocation
Effects of thyroid hormones on adipose tissue?
Activate LPL
Increased removal of TAGs from lipoproteins
When is ACTH released?
Begins at 3am
Peaks upon waking
Decreases throughout the day
When is GH released?
In pulses
Mostly at night
What inhibits PRL secretion?
Dopamine
What are high PRL levels seen?
Pregnancy
Exercise
Stress
Antipsychotic drugs
What does high PRL inhibit?
Kisspeptin
–> low oestrogen
Symptoms of low ACTH
Fatigue Weakness Vomiting Abdominal pain Low blood sugar Low BP Weight loss Hyper pigmentation
Symptoms of low TSH
Tiredness Cold intolerance Dry skin Brittle hair Paleness Mental slowness
Symptoms of low GH
Reduced strength and stamina
Reduced ability to exercise
Impaired lipid profile
Symptoms of low FSH/LH
Loss of periods
Symptoms of low oestrogen
Low libido
Symptoms of tumour mass
Headaches
Visual disturbance
Metabolic actions of GH
Stimulates protein synthesis
Increases gluconeognesis
Increases lipolysis
Increases ketogenesis
IGFs
Types 1 and 2
Produced mainly by the liver
Some auto/paracrine release in peripheral tissues
Resemble proinsulin in structure
Counteract the diabetogenic effects of GH
Responsible for non-suppressible insulin like activity
Metabolic actions of cortisol
Stimulate gluconeogensis
Stimulate muscle proteolysis
Stimulate lipolysis
Inhibition of glucose uptake by muscle and adipose tissue
Insulin stress test
Measures functioning of HPA axis and GH axis
Blood taken
Fast acting insulin given
Blood taken again at 30 minute intervals
Treatment
TSS Hydrocortisone Thyroxine Sex hormone replacement GH replacement
Sympathetic detrusor innervation
Hypogastric nerve
Inhibitory
Beta 3 receptors
Parasympathetic detrusor innervation
Pelvic nerves
Excitatory
M3 receptors
Internal urethral sphincter innervation
Sympathetic
Hypogastric nevre
Alpha 1 receptor
External urethral sphincter innervation
Somatic
Pudendal nerve
S2-4
Tamsulosin
Alpha 1 blocker
Relaxes bladder neck and IUS
Eases urination
Finasteride
5a reductase inhibitor
Reduces testosterone –> DHT
Reduces prostate size
Surgical options for BPH
TURP
TUIP
Urolift
Indications for prostate biopsy
High PSA
Abnormal digital rectal exam –> uneven texture
