Inhibitors of insulin release
-Alpha adrenergic drugs
-Beta blockers
-Sympathetic nerves
Insulin absorption and storage
-Absorbs glucose from blood into liver, skeletal muscles, and adipocytes.
-Stores glucose as glycogen in liver and skeletal muscles AND as triglycerides in fat cells.
Synthesis of insulin
Pro-insulin formed by rough endoplasmic reticulum in pancreatic Beta cells then it is cleaved to form insulin and C-peptide. It is then stored in secretory granules and released in response to Ca2+
Function of insulin
-secreted
Function of insulin
-Secreted in response to hyperglycaemia
-Glucose utilization and glycogen synthesis
-Inhibits lipolysis
-Reduces muscle protein loss
Alveolar ventilation
- Minute ventilation = tidal volume x respiratory rate.
- Alveolar ventilation = minute ventilation x dead space volume.
It is the volume of fresh air entering the alveoli per minute. - Anatomical dead space: 150mls. Gas Volume in respiratory tree not involved in gaseous exchange. Measured by Fowlers method. Increased by person size, increased lung volume and bronchodilators.
- Physiological dead space: 150mls. Volume of gas in anatomical dead space and alveoli NOT involved in gaseous exchange. Increased by increases in V/Q mismatch like PE, COPD, Hypotension.
Respiratory acidosis
Elevated CO2 usually as a result of alveolar hypo ventilation.
Causes: COPD, decompensation in other respiratory conditions(life-threatening asthma, pulmonary oedema), sedative drugs(benzodiazepines, opiate overdose)
Bile production
-Between 500mls and 1500mls produced a day.
-Composer of bile salts, bicarbonate , cholesterol, steroids, and water.
-Factors regulating flow: hepatic secretion, gall bladder contraction, and sphincter of Oddi resistance.
-90% of bile salts recycled by absorption at the terminal ileum then recycled to liver(entero hepatic circulation).
-Total pool of bile salts is recycled up to 6x a day.
Parathyroid hormone
-Secreted by chief cells of parathyroid glands. Increases Ca2+ serum by stimulating PTH receptor in kidney and bone. Half life = 4mins.
-Bone: Binds to Osteoblasts to signal osteoclasts to cause bone resorption which releases calcium.
-Kidney: Active reabsorption of Ca2+ and Mg2+ from distal convoluted tubule. Decrease phosphate reabsorption.
-Intestine via kidney: Increases intestinal Ca2+ absorption by increasing activated Vitamin D.
Thyroid hormones
- Hormones: Triiodothyronine T3(major hormone active in target cells), Thyroxine T4(most prevalent form in plasma; less biologically active), Calcitonin(lowers plasma calcium).
- Thyroid gland concentrates iodide to 25x serum concentration.
- Iodide is oxidised by peroxidase in follicular cells to atomic iodine then iodinates tyrosine residues in thyroglobulin.
- Iodinated tyrosine residues undergo coupling to either T3 or T4.
- Thyroid hormone secretion is stimulated by TSH. Normal thyroid has about 3-month reserves of thyroid hormones.
Graves’ disease
Patients develop IgG antibodies to the TSH receptors on the thyroid gland resulting in chronic stimulation of the gland with release of thyroid hormones.
Typically shows raised thyroid hormones and low TSH.
Thyroid receptor autoantibodies should be checked in individual presenting with hyperthyroidism (as they are present in up to 85% of cases)
Proximal convoluted tubule
Responsible for reabsorbing up to 2/3 of filtered water.
May undergo necrosis in situations like compartment syndrome.
Secretory function is lost effective at low systolic blood pressures(<100mmHg)
Low systolic blood pressures are a risk factor acute tubular necrosis. (Renal autoregulatory range = 80-180 SBP).
The process of facilitated diffusion of glucose refers to its co-transport with sodium.(SGLTs and GLUT)
Glucose, amino acids, and phosphate are co-transported with sodium.
Loop of Henle
About 60 litres of water containing 9000mmol of Na+ enters the descending limb in 24 hours.
Loops of the juxtamedullary nephrons run deep into the medulla.
The thick ascending loop is impermeable to water but highly permeable to Na+ and Cl-(both facilitated and passive reabsorption)
The energy dependent reabsorption of Na+ and Cl- helps to maintain the osmotic gradient. (Surrounding vasa recta with similar solute composition preventing diffusion and removal of this hypertonic fluid)
Adrenaline
-Catecholamine(phenylalanine & tyrosine).
-Neurotransmitter and hormone released by the adrenal gland.
-Effects on alpha 1&2 and beta 1&2 receptors.
-B1: increased heart rate, contractililty, cardiac output, vasoconstriction in skin &kidneys to stimulate renin and increase SVR.
-B2: bronchodilation, vasodilation of skeletal muscles, glucagon secretion in pancreas, and ACTH.
B3: stimulates lipolysis by adipose tissue.
Alpha: Inhibits insulin secretion by pancreas, stimulates glucogenolysis in liver and muscle, glycolysis in muscle.
ECG effects in hypokalaemia
-U waves
-Small or absent T waves(occasional inversion)
-Prolonged PR interval
-ST depression
-Long QT
Hypomagnesaemia
Causes: diuretics, diarrhoea, TPN, alcohol, hypokalaemia, hypocalcaemia.
Features: paraesthesia, tetany, seizures, arrhythmias, decreased PTH secretion(hypocalcaemia), ECG features of hypokalaemia, exacerbation of digoxin toxicity.
Causes of hyperuricaemia(mnemonic)
C-ciclosporin
A-alcohol
N-nicotinic acid
T-thiazides
L-loop diuretics
E-ethambutol
A-aspirin
P-pyrazinamide
Hyperuricaemia (Notes)
Increased uric acid levels secondary to either increased cell turnover or reduced renal excretion. It may be found in patients asymptomatic of gout.
Hyperuricaemia may be associated with hyperlipidaemia, hypertension, and metabolic syndrome.
INCREASED SYNTHESIS
-Lesch-Nyhan syndrome/disease
-Myeloproliferative disorders
-Diet rich in purines
-Exercise
-Psoriasis
-Cytotoxics
DECREASED EXCRETION
-Drugs (low dose aspirin, pyrazinamide)
-Pre-eclampsia
-Acidosis(DKA, starvation ketosis, salicylate toxicity)
-Alcohol
-Renal failure
-Lead
