URGE - Phase 1 Flashcards
Functions of thyroid hormones
mnemonic: matte bikini body guide (MATBBG)
* overall effect is increased protein synthesis and Na/K ATPase activity*
Metabolic enzyme expression increases as a result of increased protein synthesis
ATPase (Na+/K+) activity increases
Thermogenesis increase
BMR increases
Beta receptors increase leading to cardiac changes
Growth and differentiation – increases GH synthesis and enhances its anabolic effects
Synthesis of thyroid hormones in the thyroid gland
- Thyroglobulin synthesised from tyrosine residues and moved into colloid
- Iodide (I-) absorbed from blood by Na+ cotransport and moved into colloid
- TPO oxidises iodide to form iodine (I2)
- Iodination by TPO of tyrosine residues to form MIT and DIT on the TG backbone
- Coupling of MIT with DIT to form T3 and T4 catalysed by TPO
- Endocytosis of TG back into follicular cell
- Enzymatic hydrolysis to release T3 and T4 which diffuse out of the cell
- Deiodinase recycles MIT and DIT back into iodine and tyrosine to be recycled
Common causes of thyroid disease
primary thyroid disease = pathology occurs at the level of the thyroid
secondary thyroid disease = pathology occurs at the level of the hypothalamus/pituitary
Hyperthyroidism
Grave’s disease: occurs due to presence of autoantibodies that stimulate the TSH receptor, resulting in overactive thyroid regardless of pituitary activity
toxic multinodular goitre: multiple autonomously functioning nodules usually due to mutations in the TSH receptor
solitary toxic nodule/adenoma: may be benign or malignant, singular nodules in the thyroid gland that produce thyroid hormones
TSHoma: TSH secreting pituitary hormone resulting in an overactive thyroid
hypothyroidism
Hashimoto’s thyroiditis: autoimmune reaction to thyroid proteins that results in destruction of the gland (anti-TG, anti-TPO etc.) often begins with a transient hashitoxicosis as the damaged follicles release thyroid hormone
iodine deficiency: lack of dietary iodine results in an inability to synthesis thyroid hormones, primarily occurs in developing countries
reduced TSH drive e.g. hypophysectomy
other
de Quervain’s thyroiditis: transient thyroid inflammation following other viral infection such as mumps or coxsackievirus, involves a period of thyrotoxicosis as damaged follicles release hormone followed by a hypothyroid phase due to low TSH
postpartum thyroiditis: any thyroid disease occurring within 12 months of parturition, often involves a hyperthyroid phase followed by a hypothyroid phase, thought to be associated with immune changes during pregnancy, more likely if autoantibodies already present
Signs and symptoms of hyperthyroidism vs. hypothyroidism
Types of amine hormones (origins, solubility)
Layers of the adrenal glands, hormones and their functions
zona glomerulosa – aldosterone (mineralocorticoids), key role in water and electrolyte balance by upregulating the Na+/K+ ATPase in the late distal tubule to retain Na+ and excrete K+
zona fasciculata – cortisol (glucocorticoids), primary hormone of the stress response which has metabolic and immunosuppressive effects
zona reticularis – DHEA (androgens), precursor for sex hormones testosterone and oestrogen which are synthesised in the gonads
adrenal medulla – adrenaline and noradrenaline (catecholamines), the adrenal medulla is equivalent to a postganglionic SNS neuron which releases adrenaline into circulation
Major enzymes of steroid hormone synthesis
Cholesterol side-chain cleavage enzyme: conversion of cholesterol → pregnenolone,
Aromatase: necessary for oestrogen, present in gonads
5α-reductase: catalyses DHT formation, found in sensitive tissues such as prostate, seminal vesicles, scalp, skin
Hormones of the pituitary gland
posterior pituitary
ADH – role in water balance, increases expression of aquaporins to retain more water in the nephron when osmolarity increases
oxytocin – important hormone for uterine contractions in parturition as well as lactation
anterior pituitary
ACTH – stimulated by CRH, stimulates release of cortisol from the adrenal gland as part of the stress response
FSH – stimulated by GnRH, spermatogenesis in males and ovarian follicle activity in females
LH – stimulated by GnRH, release of oestrogen in females and testosterone in males
GH – stimulated by GHRH and inhibited by somatostatin (GHIH), important hormone for growth and differentiation particularly in children/adolescents
prolactin – negatively regulated by dopamine (PIH), stimulates milk production in the breast
TSH – stimulated by TRH, induces release of thyroid hormones from the thyroid gland for control of basal metabolism
Functions of growth hormone and regulation of its secretion
mnemonic: GIMPLE
- *Glucose** – increases insulin resistance
- *IGF release from liver** – promotes soft tissue and bone growth
- *Mitosis** and differentiation
- *Protein synthesis** – directs energy and amino acids towards protein building
- *Lipolysis** – increased release of FAs for glucose sparing effect
- *Electrolyte balance** – increases retention of Na+, K+ and Cl- as well as GIT Ca2+ absorption
Neural and endocrine responses to stress
Neural response:
increase SNS tone and decreased PNS tone, this involves both postganglionic SNS neurons as well as activity of the adrenal medulla
effects – increased HR, bronchodilation, increased BP, arousal, alertness
Endocrine response:
primary hormone involves is cortisol released from the adrenal cortex due to CRH and ACTH release
effects – glucose mobilisation from tissues, immunosuppression, increased BP
Functions of cortisol
mnemonic: AMFIB
- *A1 receptor expression** increases resulting in peripheral vasoconstriction
- *Metabolism** – glucose mobilisation (gluconeogenesis, proteolysis, lipolysis)
- *Fibroblast inhibition** – poor wound healing
- *Immunosuppression** – decreased release of IL-2, inhibition of phospholipase A2 limits arachidonic acid release and therefore synthesis of leukotrienes and prostaglandins
- *Bone metabolism** – decreases osteoblast activity, collagen synthesis and GIT Ca2+ absorption therefore decreases bone building
Examples of intersex syndromes
the male/female sexual binary is defined in three ways:
- genetic sex: based on presence/absence of Y chromosome
- gonadal sex: presence/absence of the SRY gene which determines testes or ovaries
- phenotype: levels of hormones that influence sexual organ development
Klinefelter’s Syndrome (47XXY): genetic male with small testes and gynaecomastia
Turner’s Syndrome (45X): genetic female with low oestrogen, no breasts, amenorrhea
Overview of glomerular filtration (layers of the filtration barrier, driving force)
Layers of the filtration barrier
- fenestrated endothelium – pore size excludes large molecules/cells, lined with anionic proteins to exclude other anions
- collagenous basement membrane – anionic glycoproteins exclude other anions
- filtration slits between podocyte foot processes – regulate SA available for filtration
Glomerular filtration is driven by Starling forces of the blood plasma and the filtrate already present within the tubules
- hydrostatic pressure of blood favours filtration, this can be regulated by afferent/efferent arteriole radius
- plasma oncotic pressure goes against filtration, drawing fluid back into the capillaries
- tubular hydrostatic pressure also counteracts filtration, increases in urinary obstruction
The overall driving force is normally ~10mmHg in favour of filtration
Intrinsic and extrinsic regulation of GFR
Intrinsic
Myogenic autoregulation:
smooth muscle reflex in the afferent arteriole that responds to increased stretch due to elevated blood pressure by constricting, protecting the glomerulus in HTN, this also applies in reverse however the afferent arteriole is normally almost fully dilated
Tubuloglomerular feedback:
macula densa cells in early distal tubule respond to Na/Cl flux as an indicator of GFR
- ↑ GFR = ↑Na/Cl flux = release of adenosine = afferent constriction and renin inhibition
- ↓ GFR = ↓Na/Cl flux = release of prostaglandin = afferent dilation and renin release
Mesangial cells:
interstitial cells of the glomerulus that can respond to changes in blood pressure and maintain GFR by contracting/relaxing to alter the surface area available for filtration
Extrinsic
Hormonal:
there are a number of circulating factors that influence the afferent/efferent arteriolar diameter and therefore the GFR:
- adrenaline – constricts both
- angiotensin II – constricts both but efferent is far more responsive
- ANP/BNP – dilates afferent, constricts efferent
- dopamine – dilation of both
- prostaglandin – dilation of both
Neural:
activity of SNS nerves that innervate the kidney leads to increased renin secretion, sodium reabsorption and arteriolar constriction that decreases GFR
Reabsorption and secretion along the length of the renal tubule
Description of the medullary interstitial gradient
Maximal water reabsorption can be maintained due to the presence of a medullary interstitial osmotic gradient which drives water reabsorption from the descending loop of Henle and collecting duct, this is established by:
- Countercurrent mechanism – absorption of solutes from ascending loop into descending vasa recta creates a hyperosmotic interstitium
- Urea recycling – ADH driven reabsorption of urea in the collecting duct which is secreted back into the tubule at the loop of Henle maintains a high medullary urea concentration
Regulation of acid-base balance in the nephron
Role of the kidney in acid-base balance relies on two functions which can be regulated:
- HCO3- reabsorption in the PCT via the Na+/H+ exchanger, HCO3- then enters blood via cotransport with Na+ or exchange with Cl-
- H+ excretion in the late distal tubule via K+/H+ exchange and H+ ATPase, these can be trapped in acidic urine by buffering with ammonia and phosphate
Types of RTA
Renal tubular acidosis involves an acidic imbalance resulting from tubular defects
Type 1: distal, reduced H+ excretion in intercalated cells
Type 2: proximal: impaired HCO3- reabsorption in PCT
Type 4: distal, aldosterone deficiency or resistance leads to hyperkalaemic acidosis
Actions of ADH and aldosterone in the nephron
ADH: increases surface expression of aquaporin channels (AQP2) on apical and basolateral surfaces to facilitate water reabsorption, also aids urea absorption in collecting duct
Aldosterone: increases activity of Na+/K+ pump in principal cells as well as the H+ ATPase in intercalated cells, drives sodium reabsorption and potassium excretion
Causes of UTI
Most commonly caused by normal bowel flora: (KEEPS)
- Klebsiella*
- E. coli*
- Enterococcus*
- Proteus*
- Staph. saprophyticus*
Pathophysiology of UTI
Factors contributing to bacterial colonisation:
- patient factors: immunocompromised state, urinary stasis, female sex, diabetes, hygiene
- bacterial factors: virulence factors such as fimbriae and pili that allow adhesion
- bacterial access: catheterisation, surgical inoculation, trauma, sepsis
Once the urinary tract has been colonised by bacteria the result is irritation and inflammation of the urothelium which leads to symptoms – dysuria, frequency, urgency, suprapubic pain, fever
Major types of renal calculi (cause, frequency, shape, imaging)
Pathophysiology of nephrolithiasis
- stones form as a result of urine supersaturation:
- increased solute: diet, high cell turnover, bone metabolism, genetics, infection
- decreased solvent: dehydration, kidney diseaseprecipitation of solutes results in formation of a nidus
- continued precipitation grows nidus into a stone which obstructs the urinary tract typically at constriction points – PUJ, pelvic brim, VUJ
- obstruction causes symptoms including haematuria, loin-groin pain, dysuria, nausea
Imaging signs of ureteric obstruction
- hydronephrosis
- hydroureter
- perinephric stranding
- nephromegaly
Overview of the RAAS including functions of ATII
Nephrotic vs. nephritic syndromes
Features of a urine dipstick test
Definition of anion gap
Anion gap = measured difference between the concentration of Na and the concentration of HCO3 + Cl in the plasma, estimates the amount of unmeasured anions e.g. anionic proteins
- anion gap increases in metabolic acidosis due to lactic acidosis, ketoacidosis etc.
- diarrhoea or RTA leads to loss of bicarbonate but does not alter anion gap due to HCO3/Cl exchange in the nephron
there are many other causes of anion gap increases
Types of diuretics (examples, MOA, potency)
Triple whammy drug interaction
- diuretic: reduces overall blood volume
- ARB/ACE inhibitor: inhibiting ATII effects = efferent vasodilation
- NSAID: ↓ PG synthesis = afferent vasoconstriction
Embryological development of the genitourinary systems
renal system
- urogenital ridge and nephrogenic cord form from the intermediate mesoderm
- nephrogenic cord forms a pronephros, mesonephros (early urine formation) and metanephros which will persist as the functional kidney
- ureteric bud in the mesonephros induces development of the kidney and vice versa
- ascension of the kidney from pelvis to their final position with blood flow from arterial branches that develop from the aorta
- initially urinary outflow is into the cloaca however the UT becomes separated from the GIT by the urorectal septum
reproductive
- initial development of the reproductive system is common from the genital ridge
- primordial germ cells form around yolk sac and migrate into the embryo and settle on the genital ridge to form an undifferentiated gonad
- formation of male/female structures depends on presence of SRY gene which causes a testis to form and produce hormones – anti-Mullerian (Sertoli) and testosterone (Leydig)
- initial genital ducts in nephrogenic cords
- Wolffian – male structures, persist with testosterone present
- Mullerian – female structures, degenerates with anti-Mullerian hormone present
- external sex organs are also initially the same but differentiate as a result of the presence or absence of testosterone
Classification of acute kidney injury
Prerenal – decrease in renal perfusion
e.g. haemorrhage, dehydration, shock, heart failure, renal artery stenosis
Intrarenal – intrinsic disease within the kidney, typically
e.g. acute tubular necrosis, nephrotoxins, glomerulonephritis, acute interstitial nephritis
Postrenal – obstruction of the urinary tract leading to increase in tubular hydrostatic pressure
e.g. renal calculi, malignancy, BPH
Diagnosis of chronic kidney disease and major causes
CKD is diagnosed based on one of the two following criteria:
- GFR <60mL/min
- >3-month history of kidney disease signs such as proteinuria or haematuria
most common causes are diabetes and hypertension as well as PCKD, SLE, obstruction and glomerulonephritis
Types of dialysis
Haemodialysis – blood passes through a dialyser machine which filters the blood, requires an AV fistula or other blood access
- typically done at an outpatient clinic, for 4-6 hours per day, 3 days per week
- can be performed at home with extensive training
Peritoneal dialysis – filtration occurs across the peritoneal membrane with the peritoneal cavity filled with dialysate via a catheter
- exchange takes about 40 minutes and must be done 3-5 times per day
Pathophysiology of T1DM
Autoimmune disease characterised by absolute insulin deficiency due to a type IV hypersensitivity reaction that destroys β cells, symptoms appear when 90% of cells are destroyed
Aetiology involves a combination of genetic/environmental/immune factors:
- identified gene loci associated with immune pathways such as the HLA system
- environmental factors suggested including viral infection, diet and vitamin D deficiency
- association with other autoimmune diseases
Complications of diabetes
Main pharmacological treatment for diabetes patients
Neurological control of micturition
Embryological development of the scrotum
Male sex hormone regulation
Examples of oncogenic viruses
Overview of the menstrual cycle
- late luteal/early follicular: low oestrogen and progesterone reduces negative feedback allowing FSH and LH to increase, initiating follicle recruitment (LH – stimulates thecal androgen production, FSH – stimulates granulosa cell growth and oestrogen production)
- late follicular: oestrogen secretion peaks as the granulosa continues to grow, once a critical time and concentration is reached the HPG axis switches to positive feedback causing an LH surge
- ovulation: LH surge triggers increase in antral fluid and size of the dominant follicle, after 16-24 hours the follicle ruptures and the remaining theca/granulosa become luteal cells
- early luteal: corpus luteum produces oestrogen, progesterone and inhibin
- late luteal/menses: without pregnancy, the corpus luteum will die after 12 days and oestrogen/progesterone levels will decrease initiating menses and increase in FSH/LH
Major placental abnormalities
Overview of foetal/maternal circulation
Common psychological conditions in the perinatal period
Pathophysiology of common STIs that cause discharge in Australia
Pathophysiology of common STIs that cause ulceration in Australia
Pathophysiology of common STIs that cause lumps/bumps in Australia
Barrier forms of contraception Types, MOA, Advantages and Disadvantages
Hormonal/devices forms of contraception Types, MOA, Advantages and Disadvantages
Surgical and Misc other forms of contraception Types, MOA, Advantages and Disadvantages
Common neoplasms of endocrine organs
Physiological changes that occur during pregnancy
Major types of genetic inheritance and examples of disorders
Causes of male and female infertility
Progesterone and Oestrogen effects
