SUGER 🍦🍧🍨🍩🍪🎂🍭🍬🍫 Flashcards

Question

Outline hormonal regulation of glomerular filtration

Answer 1

Renin-Angiotensin-Aldosterone System (RAAS) Atrial Natriuretic Peptide (ANP)

Answer 2

Renin released from JGA Initiates cascade Aldosterone influences Na reabsorption at distal tubule which influences blood volume and pressure

Answer 3

Released by atria Stimulus of blood volume Vasodilation of AFFERENT arterioles

Answer 4

Negative feedback mechanism Stabilises RBF and GFR Minimises impact of changes in BP on Na excretion Without renal autoreg - increase in BP leads to increase GFR and losses

Answer 5

- Respond to changes in pressure in glomerulus - Influence diameter of AFFERENT arterioles

Answer 6

Changes in blood volume Resultant hydrostatic pressure

Answer 7

Oncotic pressure exerted by proteins

Answer 8

Local release of prostaglandins, nitric oxide, bradykinin, leukotrienes, histamine, cytokines, thromboxanes

Answer 9

Prostaglandins Nitric slide 50

Answer 10

Umbrella term Causes: infection (bacterial/viral), autoimmune disorders, systemic diseases Presentation: haematuria, proteinuria, hypertension, impaired kidney function

Answer 11

Umbrella term Increased permeability of glomerular filtration barrier Presentation: triad of oedema + proteinuria + low albumin

Answer 12

Deposition of IgA antibody in the glomerulus Resultant inflammation and damage Cause: immune-mediated Presentation: haematuria, potentially following resp/GI infection

Answer 13

Thickening of GBM Most common cause of nephrotic syndrome in adults Cause: primary or secondary Presentation: proteinuria (often leading to nephrotic syndrome)

Answer 14

Prolonged exposure to high blood glucose Presentation: initially asymptomatic then progresses to proteinuria, hypertension and reduced kidney function

Answer 15

Type of nephrotic syndrome, only in children Only visible under electron microscope

Answer 16

Genetic disorder affecting GBM (X linked or autosomal recessive) Progressive kidney damage Potentially includes hearing loss and eye abnormalities

Answer 17

Disorder tending to make blood more acid than normal

Answer 18

Disorder tending to make blood more alkaline than normal

Answer 19

Low blood pH

Answer 20

High blood pH

Answer 21

Metabolic component intrinsic acid extrinsic acid 1more resp CO2 component CO2 bicarbonate

Answer 22

Principle: pH and HCO3- are dependent variables governed by: pCO2 Concentration of weak acids (ATOT) ATOT = Pi + Pr + Alb Strong ion difference (SID) SID = Na+ + K+ + Mg2+ + Ca2+ – Cl- – other strong anions (eg lactate, ketoacids)

Answer 23

Strengths: Identifies the factors controlling pH Problems: Calculation can be very problematic Probably adds little in practice

Answer 24

Disorders can be divided into acidoses – disorders that tend to make the blood acid and alkaloses Disorders can be respiratory (ie driven by changes in CO2 excretion) or metabolic (ie driven by changes in acid load, acid excretion or bicarbonate recycling) Different disorders can co-exist (mixed patterns)

Answer 25

pH pO2 pCO2 Std HCO3- Std Base excess May include other measures (eg lactate, Na+, K+)

Answer 26

What it would be if CO2 was normal- allows you to ignore the resp component of acid base in the blood

Answer 27

Measures of metabolic component of any acid-base disturbance Absolute bicarbonate is affected by both respiratory and metabolic components Standard bicarbonate is the bicarbonate concentration standardised to pCO2 5.3kPa and temp 37 Bicarbonate and std bicarbonate are calculated not actually measured

Answer 28

Quantity of acid required to return pH to normal under standard conditions Standard base excess corrected to Hb 50g/L Can be used to calculate bicarbonate dose to correct acidosis 0.3xWtxBE (but not generally used in practice) Base excess is negative in acidosis, can be referred to as base deficit

Answer 29

2 major approaches: Henderson Stewart’s theory (strong ion difference)

Answer 30

long term- stunted growth and muscle wasting Clinical features: Sighing respirations (Kussmaul’s resps), tachypnoea Compensatory mechanism: Hyperventilation to increase CO2 excretion

Answer 31

Difference between measured anions and cations Anion gap = [Na+] + [K+] – [Cl-] – [HCO3-] Normal 10-16

Answer 32

Lactic acidosis, ketoacidosis, ingestion of acid, renal failure

Answer 33

GI HCO3- loss: diahorrea, fissure, renal tubular acidosis,

Answer 34

Alkali ingestion Gastrointestinal acid loss: Vomiting Renal acid loss: Hyperaldosteronism, hypokalaemia

Answer 35

Hypoventilation (but limited by hypoxic drive), renal bicarbonate excretion

Answer 36

CO2 retention, leading to increased carbonic acid dissociation Causes: Any cause of respiratory failure Compensatory mechanism: Increased renal H+ excretion and bicarbonate retention (but only if chronic)

Answer 37

CO2 depletion due to hyperventilation Causes: Type 1 respiratory failure, anxiety/panic Compensation: Increased renal bicarbonate loss (if chronic)

Answer 38

What is the pH? What is the respiratory component (ie pCO2)? What is the metabolic component (std HCO3-, base excess)? Which component is congruent with the pH?

Answer 39

Renal blood flow- 1250ml/min Renal plasma flow- 700ml/min Glomerular filtration rate- 120ml/min Urine flow rate- 1ml/min

Answer 40

Active reabsorption of multiple solutes Metabolically active cells – lots of mitochondria Sodium gradient generated by Na/K ATPases Vulnerable to hypoxia and toxicity

Answer 41

Reabsorbed solute Disorder Glucose Renal glycosuria AAs Aminoacidurias (eg cystinuria) Phosphate Hypophosphataemic rickets (eg XLH) Bicarbonate Proximal renal tubular acidosis Multiple Fanconi syndrome

Answer 42

Defect: Sodium glucose transporter 2 (SGLT2) Mechanism: Failure of glucose reabsorption Clinical features: Incidental finding on testing, benign SGLT2 inhibitors (eg empagliflozin) now established as treatments for type 2 diabetes Wider use in heart failure and CKD

Answer 43

Defect: Sodium glucose transporter 2 (SGLT2) Mechanism: Failure of glucose reabsorption Clinical features: Incidental finding on testing, benign SGLT2 inhibitors (eg empagliflozin) now established as treatments for type 2 diabetes Wider use in heart failure and CKD

Answer 44

High fluid intake: High urine flow, lower concentration Alkalinise urine: Increases solubility of cystine Chelation: Penicillamine, captopril Management of individual stones (percutaneous treatment, surgery etc)

Answer 45

Commonest form is X-linked hypophosphataemic rickets (XLH) Defect: PHEX – zinc dependent metalloprotease PHEX mutation results in increased FGF-23 levels, leading to decreased expression and activity of NaPi-II in proximal tubule

Answer 46

Clinical features: Bow legged deformity, impaired growth Treatment: Phosphate replacement

Answer 47

Defect: Na/H antiporter Mechanism: Failure of bicarbonate reabsorption Clinical features: Acidosis, impaired growth Treatment: Bicarbonate supplementation

Answer 48

Genetic defects in carbonic anhydrase produce a mixed proximal/distal renal tubular acidosis Inhibited by acetazolamide – mild diuretic effect and induces a metabolic acidosis Used to treat altitude sickness – allows more rapid compensation of respiratory alkalosis

Answer 49

- Mechanism: Generalised proximal tubular dysfunction, possibly due to failure to generate sodium gradient by Na/K ATPase - Clinical features: Glycosuria, aminoaciduria, phosphaturic rickets, renal tubular acidosis - Causes: Genetic (eg cystinosis, Wilson’s disease), myeloma, lead poisoning, cisplatin - Not to be confused with Fanconi anaemia

Answer 50

Generates medullary concentration gradient Active Na reabsorption in thick ascending limb

Answer 51

Defect: NKCC2, ROMK, ClCKa/b, Barrtin Mechanism: Failure of sodium, potassium and chloride cotransport in thick ascending limb. Salt wasting, hypokalaemic alkalosis due to volume contraction, failure of voltage dependent calcium & magnesium absorption

Answer 52

Clinical features: Antenatal: Polyhydramnios, prematurity, delayed growth, nephrocalcinosis Classical: Delayed growth, polyuria, polydipsia Similar to effects of loop diuretics (eg furosemide, bumetanide)

Answer 53

Distal tubule and cortical collecting duct allow “fine tuning” of sodium reabsorption, potassium and acid-base balance Collecting duct mediates water reabsorption and urine concentration

Answer 54

Gitelman’s syndrome Distal (type 1) renal tubular acidosis Disorders resembling hyperaldosteronism Type 4 renal tubular acidosis Nephrogenic diabetes insipidus

Answer 55

Gitelman’s syndrome Distal (type 1) renal tubular acidosis Disorders resembling hyperaldosteronism Type 4 renal tubular acidosis Nephrogenic diabetes insipidus

Answer 56

Steroid hormone – predominantly acts on transcription Increase expression of ENaC, Na/K ATP-ase Mineralocorticoid receptor also activated by cortisol Cortisol entry to renal tubular cells prevented by 11-beta hydroxysteroid dehydrogenase

Answer 57

Defect: ? Luminal H+ ATPase or H+/K+ ATPase Mechanism: Failure of H+ excretion and urinary acidification Can be genetic or acquired (eg Sjogren’s syndrome, chronic pyelonephritis, drugs – amphotericin)

Answer 58

Excessive aldosterone activity produces sodium retention, hypertension and hypokalaemic alkalosis Excessive aldosterone production may be primary (eg Conn’s syndrome) or secondary (eg renal artery stenosis) Several disorders can produce a “hyperaldosteronism” phenotype with high blood pressure, hypokalaemia and alkalosis

Answer 59

Defect: Chimeric gene – 11beta hydroxylase and aldosterone synthetase Mechanism: Aldosterone is produced in the adrenal in response to ACTH, so levels inappropriately high Treatment: Suppress ACTH using glucocorticoids

Answer 60

Defect: Activating mutation of ENaC Mechanism: Sodium channel always open so constant aldosterone like effect Treatment: Amiloride (blocks ENaC)

Answer 61

Defect: 11-beta hydroxysteroid dehydrogenase Mechanism: Cortisol not broken down in the renal tubules, therefore activates mineralocorticoid receptor. Treatment: Spironolactone (mineralocorticoid receptor antagonist)

Answer 62

Defect: Low aldosterone levels Mechanism: Reduced generation of electrochemical gradient, resulting in failure of H+ and K+ excretion Common in elderly patients with diabetes Treatment: Diuretics or fludrocortisone

Answer 63

Defect: Vasopressin V2 receptor or aquaporin 2 water channel Mechanism: Failure of water reabsorption in the collecting duct, resulting in inability to concentrate urine Clinical features: Polyuria, polydipsia, hypernatraemia

Answer 64

- Formed of small clusters of glandular epithelial cells - 98-99% of cells are clusters called acini

Answer 65

Exocrine activity performed by acinar cells Manufacture and secrete fluid and digestive enzymes, called pancreatic juice, which is released into the gut

Answer 66

- Endocrine activity performed by islet cells - Manufacture and release several peptide hormones into portal vein

Answer 67

60-70% beta cells- insulin rest alpha cells which secrete glucagon and delta cells which secrete somatostatin

Answer 68

Paracrine 'crosstalk' between alpha and betacells is physiological, i.e., local insulinrelease inhibits glucagon

Answer 69

Insulin Glucagon Somatostatin Pancreatic polypeptide Ghrelin

Answer 70

polypeptide, 51 amino acids Reduces glucose output by liver, increases storage of glucose, fatty acids, amino acids

Answer 71

29 amino acid peptide Mobilises glucose, fatty acids and amino acids from stores

Answer 72

Somatostatin secreted from d cells – inhibitor

Answer 73

Pancreatic Polypeptide – inhibit gastric emptying

Answer 74

Ghrelin – stimulates release of glucagon

Answer 75

Suppresses hepatic glucose output - Decreases Glycogenolysis - Decreases Gluconeogenesis Increases glucose uptake into insulin sensitive tissues - Muscle – glycogen, and protein synthesis - Fat – fatty acid synthesis Suppresses - Lipolysis - Breakdown of muscle (decreased ketogenesis)

Answer 76

Counterregulatory Increases hepatic glucose output - Increases Glycogenolysis - Increases Gluconeogenesis Reduces peripheral glucose uptake Stimulates peripheral release of gluconeogenic precursors (glycerol, AAs) - Lipolysis -Muscle glycogenolysis and breakdown

Answer 77

Other counterregulatory hormones (adrenaline, cortisol, growth hormone have similareffects to glucagon and become relevant in certain disease states, including diabetes

Answer 78

Glucose entry via GLUT2 glucosetransporter Glucokinase does glucose metabolism which produces ATP which stimulates the ----> look at it again- slide 12

Answer 79

- Proinsulin contains the A and B chains of insulin (21 and 30 amino acid residues respectively), joined by the C peptide. - Disulfide bridges link a and B chains - Presence of C peptide implies endogenous insulin production

Answer 80

- B-cells sense rising glucose and aim to metabolise it - First phase response is rapid release of stored product - Second phase response is slower and as it is the release of newly synthesised hormone

Answer 81

Insulin receptors on plasma membrane-n high affinity Signalling cascade stimulates GLUT4 vesicles which mobo 15

Answer 82

Glucose levels should remain constant Liver glycogen is a short-term glucose buffer

Answer 83

>6 is too high SHort term response- Make glycogen (glucose to glycogen= glycogenesis) Long term response- Make triglyceride lipogenesis slide 16

Answer 84

- Primary glucose sensors are in the pancreatic islets - Also in medulla, hypothalamus and carotid bodies - Inputs from eyes, nose, taste buds, gut all involved in regulating food - Sensory cells in gut wall also stimulate insulin release from pancreas - incretins

Answer 85

- Primary glucose sensors are in the pancreatic islets Also in medulla, hypothalamus and carotid bodies - Inputs from eyes, nose, taste buds, gut all involved in regulating food Sensory cells in gut wall also stimulate insulin release from pancreas - incretins

Answer 86

K and L cells in gut secrete glp 1 and gip

Answer 87

Increase of insulin-> rising plasma glucose stimulates beta cells to secrete incuijn

Answer 88

dipeptidyl peptidase IV cleaves GLP-1 Half life is 1-2 mins DPPIV prevents hypoglycaemia

Answer 89

- In the fasting state, all glucose comes from liver - Breakdown of glycogen - Gluconeogenesis (utilises 3 carbon precursors to synthesise glucose including lactate, alanine and glycerol) - Glucose is delivered to insulin independent tissues, brain and red blood cells - Insulin levels are low - Muscle uses FFA for fuel - Some processes are very sensitive to insulin, even low insulin levels prevent unrestrained breakdown of fat

Answer 90

- After feeding (post prandial) - physiological need to dispose of a nutrient load - Rising glucose (5-10 min after eating) stimulates 5-10 fold increase in insulin secretion and suppresses glucagon - 40% of ingested glucose goes to liver and 60% to periphery, mostly muscle - Ingested glucose helps to replenish glycogen stores both in liver and muscle - Excess glucose is converted into fats - High insulin and glucose levels suppress lipolysis and levels of non-esterified fatty acids (NEFA or FFA) fall

Answer 91

A disorder of carbohydrate metabolism characterised by hyperglycaemia

Answer 92

Mutations to Kir 6.2 Sulphonylureas

Answer 93

-The process by which gametes are produced in the reproductive organs (gonads) of an organism. -Gametes are fundamental for sexual reproduction and genetic diversity.

Answer 94

follicule 1 oocyte

Answer 95

Primordial follicle-> Primary follicle -> Developing follicles -> Mature (graafian) follicle + secondary ovum -> ruptured follicle + liberated ovum -> early corpus luteum -> corpus luteum -> corpus albicans

Answer 96

Oogenesis Begins in fetal life, with significant milestones at puberty and ceasing at menopause

Answer 97

Oogonium (diploid) divides by mitosis to form 2 daughter oogonium These then grow and form primary oocytes

Answer 98

Primary oocyte (diploid) undergoes meiosis I to form the first polar body and a secondary oocyte (haploid)

Answer 99

Oocyte initially covered in cumulus cells then when that is gone it is covered in a layer of proteins called the zona pellucida

Answer 100

FSH- stimulates maturation of the oocyte LH- stimulates the release of an oocyte

Answer 101

Around 28 days

Answer 102

FSH goes to ovary and stimulates production of follicles and stimulates oestrogen production

Answer 103

Oestrogen stimulates proliferates endometrium cells so the endometrium gets thicker

Answer 104

Proliferating phase

Answer 105

Surge of LH stimulates ovulation release of oocyte

Answer 106

Empty follicle converts to corpus luteum and corpus albicans

Answer 107

cyclical phase progesterone is high

Answer 108

GnRH- starts Stimulates pituitary to produce FSH FSH affects oestrogen Oestrogen increases eggs and uterus

Answer 109

LH surge stimulates ovulation corpus luteum progesterone produced

Answer 110

menstruation

Answer 111

Lining of womb thickens in preparation for the egg

Answer 112

If fertilisation has not taken place the corpus luteum fades away

Answer 113

The uterine lining detaches leading to menstruation

Answer 114

Spermatozoa being produced in the testis

Answer 115

-Ejaculate is a mixture of spermatozoa and seminal plasm

Answer 116

Oval organ, 4 cm long x 2.5 cm in diameter * Covered anteriorly by a saclike extension of the peritoneum (tunica vaginalis) that descended into the scrotum with the testes * Tunica albuginea = white fibrous capsule

Answer 117

septa divide the organ into compartments containing seminiferous tubules where sperm are produced

Answer 118

clusters of cells between the seminiferous tubules and source of testosterone AKA interstitial cells produce sperm

Answer 119

s promote sperm cell development * blood-testis barrier is formed by tight junctions between sertoli cells; separating sperm from immune system

Answer 120

eminiferous tubules drain into network called rete testi

Answer 121

*Pendulous pouch holding the testes divided into 2 compartments by median septum *Testicular thermoregulation is necessary since sperm are not produced at core body temperature - need to be 35 not 37

Answer 122

Mitosis produces 2 genetically identical daughter cells (occurs in tissue repair & embryonic growth)

Answer 123

Meiosis produces gametes haploid cells required for sexual reproduction – 2 cell divisions (after only one replication of DNA) – meiosis keeps chromosome number constant from generation to generation after fertilization – meiosis occurs in seminiferous tubules of males

Answer 124

Meiosis produces gametes haploid cells required for sexual reproduction – 2 cell divisions (after only one replication of DNA) * meiosis I separates homologous chromosome pairs2 haploid cells * meiosis II separates duplicated sister chromatids4 haploid cells – meiosis keeps chromosome number constant from generation to generation after fertilization – meiosis occurs in seminiferous tubules of males

Answer 125

Type A Type B

Answer 126

Type A remain outside blood-testis barrier & produce more daughter cells until death

Answer 127

type B differentiate into primary spermatocytes * cells must pass through BTB to move inward toward lumen - new tight junctions form behind these cells * meiosis I  2 secondary spermatocytes * meiosis II  4 spermatids

Answer 128

Spermiogenesis is transformation of spermatids into spermatozoa – sprouts tail and discards cytoplasm to become lighter

Answer 129

-300 to 600 sperm are made per gram of testis per second. -50g x 50 min x 60 sec x 500 sperm = 75,000,000 spermatozoa

Answer 130

GnRH- ptuitary produces FSH and LH FSH induces surge if spermatogenesis LH acts on leydig cells leydig cells produces testosterone inhibits gnrh

Answer 131

Head is pear-shaped front end – 4 to 5 microns long structure containing the nucleus, acrosome and basal body of the tail flagellum * nucleus contains haploid set of chromosomes * acrosome contains enzymes that penetrate the egg * basal body

Answer 132

Tail is divided into 3 regions – midpiece contains mitochondria around axoneme of the flagellum (produce ATP for flagellar movement) – principal piece is axoneme surrounded by fibers – endpiece is axoneme only and is very narrow tip of flagellum

Answer 133

– 12 small ciliated ducts collecting sperm from the rete testes and transporting it to the epididymis

Answer 134

– 6 m long coiled duct adhering to the posterior of testis – site of sperm maturation & storage (fertile for 40 to 60 days)

Answer 135

– muscular tube 45 cm long passing up from scrotum through inguinal canal to posterior surface of bladder – widens into a terminal ampulla

Answer 136

– 2 cm duct formed from ductus deferens & seminal vesicle & passing through prostate to empty into urethra

Answer 137

Seminal vesicles Prostate gland Bulbourethral gland

Answer 138

-2-5 mL of fluid expelled during orgasm – 60% seminal vesicle fluid, 30% prostatic & 10% sperm and trace of bulbourethral fluid * normal sperm count is 50-120 million/mL (< 25 million/mL is associated with infertility) * sperm serve to digest path through cervical mucus and to fertilize egg

Answer 139

– fructose provide energy for sperm motility – fibrinogen – clotting enzymes convert fibrinogen to fibrin causing semen to clot – fibrinolysin liquefies semen within 30 minutes – prostaglandins stimulate female peristaltic contractions – spermine is a base stabilizing sperm pH at 7.2 to 7.6

Answer 140

* Our cells contain 23 pairs of chromosomes – 22 pairs of autosomes – 1 pair of sex chromosomes (XY males: XX females) * males produce 50% Y carrying sperm and 50% X carrying * all eggs carry the X chromosome * Sex of the child is determined by the type of sperm that fertilizes the mother’s egg

Answer 141

*A small number of spermatozoa reach to the upper part of female reproductive tract *Both Sperm motility and female reproductive tract movement are responsible for sperm transport *Cervical mucus Penetration test

Answer 142

*Capacitation was first discovered by Chang and Austin independently (1950). *The final maturational stage of spermatozoa that takes place in the female genital tract, before spermatozoa gain the ability to fertilize oocyte. *It is one of the most investigated areas of andrology and one of the least understood areas of andrology.

Answer 143

Happens when sperm is in contact with the zona pellucida zp3 starts then zp2

Answer 144

The morula is a globular solid mass of 16-32 blastomeres formed by cleavage of the zygote that precedes the blastocyst

Answer 145

*Artificial Insemination (AI) *Embryo Transfer (ET) *In Vitro Fertilization (IVF) *Intra-Cytoplasmic Sperm Injection (ICSI) *Somatic Nuclear Transfer (Cloning) *Stem Cell Therapy (Regenerative Medicine) *IPS Cells (Induced pluripotent Stem Cells)

Answer 146

Oocyte activation is key and is triggered by a sperm protein called Phospholipase C zeta (PLCz). This ‘activates’ the egg to release calcium from internal stores and this rise in calcium facilitates fertilisation. Oocyte activation is essential for the transformation of the decondensed sperm nucleus in to pronucleus. 4-7 hours after gamete fusion the two sets of haploid chromosomes form the female and male pronucleus (23 chromosomes each) Pronuclei are equal size and contain nucleoli In IVF multinucleate oocytes can be identified - polyspermic

Answer 147

- Male and Female pronucleus migrate to centre (cytoskeletal system plays important role) - Haploid chromosomes pair and replicate DNA in preparation for the first mitotic division - The pronuclear membranes breakdown - The mitotic metaphase spindle forms - 46 Chromosomes organise at the spindle equator

Answer 148

Approx 24 hours after fertilisation the ooplasm divides in to two equal halves If one or more of the PN fail to decondense and move in to one of the blastomeres, diploid or triploid mosaics may occur

Answer 149

Cleavages are timed from sperm entry by an oocyte program that also regulates ‘house keeping’ activities in embryos. Successive cleavages result in an increase in cell number – essential to provide sufficient cells for differentiation.

Answer 150

Prior to 4-8 cell stage the developmental control depends on maternally-derived stores of RNA laid down during oogenesis. Activation of the embryonic genome and start of embryonic transcription occurs in a 4-8 cell embryo. Developmental arrest can occur.

Answer 151

Early cleavage stage embryos are ‘totipotent’ – the nuclei of individual blastomeres are each capable of forming an entire foetus.

Answer 152

- Cells flatten - Maximise intracellular contacts - Tight junctions form - Polarisation of outer cells - Morula – 16 cells

Answer 153

- Tight junctions occur between outer cells – forms the trophectoderm - Fluid filled cavity expands - Sodium pumped in which pulls water in by osmosis Now >80 cells 50-66% comprise trophectoderm, rest is ICM Pluripotent

Answer 154

Trophectoderm cells pump fluid in to the embryo to form the blastocoel cavity

Answer 155

- Cavity expands - Diameter increases - ZP thins

Answer 156

- Blastocyst expansion and enzymatic factors cause the embryo to hatch from the ZP. Essential for implantation - TE – extraembyronic - ICM - embryonic

Answer 157

ATP turnover low ATP / ADP ratio is high Energy metabolism characterised by consumption of pyruvate Glucose uptake and utilisation is low

Answer 158

Metabolic activity rises sharply ATP / ADP ratio falls, reflecting an increase demand for energy e.g for protein biosyntheses and ion pumping associated with blastocoel cavity. Glucose is the predominant exogenous energy substrate

Answer 159

early cleavage- maternal blastocyst- embryonic

Answer 160

Cumulus cells Fallopian Tube secretions e.g. calcium, sodium, chloride, glucose, proteins. Uterine secretions e.g. iron, fat soluble vitamins, glucose

Answer 161

Concentrations of nutrients vary along the tract to provide the embryo requirements at the right time

Answer 162

important in embryonic growth and differentiation Insulin-like growth factor - IGF–I and IGF–II increase cell numbers in blastocyst Leukaemia inhibitory factor (LIF) enhances embryo-endo interaction

Answer 163

Cellular differentiation – 10 days After implantation embryogenesis continues with the next stage of gastrulation when the three germ layers of the embryo form in a process called histogenesis The 3 germ layers form: ectoderm, mesoderm and endoderm (three overlapping flat discs) It is from these three layers that all the structures and organs of the body will be derived

Answer 164

- Endometrial cell changes to help absorption of uterine fluid – bring the blastocyst nearer to the endometrium and immobilises it. - Changes in thickness of endometrium and its blood supply development - Formation of the decidua Implantation window = 4 days (6-10 days postovulation)

Answer 165

Well defined starting point Gradual process over several weeks No universal agreement when process is completed

Answer 166

small size of implantation site compared to thickness of endometrium

Answer 167

After embryo hatched the embryonic and maternal cells enter into a complex dialogue High degree of preparation and coordination required Controlled cascade of trophoblast proliferation, differentiation, migration and invasion

Answer 168

The cross talk between endometrium and the developing embryo is mediated by substances including: Hormones (sex steroids) Cell adhesion molecules Proteases Cytokines, Growth Factors Also genetics 5 genes up regulated during implantation window (Haouzi et al 2009)

Answer 169

Apposition Attachment Invasion

Answer 170

Unstable adhesion of the blastocyst to the uterine lining Synchronisation of embryo and endometrium (decidua) Hatched blastocyst orientates via embryonic pole (always attaches at the area above the ICM) Receptive endometrium (implantation window day 19 – 22)

Answer 171

Stable/stronger adhesion penetrate with protrusions of the trophoblast cells (microvilli) Massive communication between the blastocyst and endometrium conveyed by receptor-ligand interactions Apical surfaces of the endometrial epithelial cells express variety of adhesion molecules (integrin subunits) Trophoblastic cells also express integrins Attachment occurs through the mediation of bridging ligands that connect with integrins on their surfaces

Answer 172

Trophoblast protrusions continue to proliferate and penetrate the endometrium cells differentiate to become syncytiotrophoblast The trophoblast surrounding the ICM = cytotrophoblasts. Highly invasive - trophoblast quickly expands and erodes into endometrial stroma. Invasion is enzymatically mediated Syncytiotrophoblast erodes endometrial blood vessels Eventually syncytiotrophoblast comes into contact with maternal blood and form chorionic villi – in initiation of the formation of the placenta Blood filled lacunae form (spaces filled with maternal blood). Exchange nutrients and waste products.

Answer 173

After first few days of implantation, the trophoblast changes character to become less invasive killer cells don't attack it

Answer 174

Promotes placental formation stromal cells adjacent to the blastocyst differentiate into metabolically active, secretory cells or Decidual Cells (under influence of progesterone) Secretions include growth factors/proteins to support growth of implanting blastocyst in the initial stages before the placenta is fully developed. Endometrial glands enlarge and local uterine wall becomes highly vascularised. The decidual reaction is not required for implantation e.g. ectopic implantation can occur anywhere in the abdominal cavity.

Answer 175

These changes include swelling of stromal cells due to accumulation of glycogen and other nutrients. These nutrients help the embryo survive the initial days before the placenta is fully developed, which then establishes a channel for fetus nutrient exchange.

Answer 176

The decidual reaction is seen in very early pregnancy in the generalized area where the blastocyst contacts the endometrial decidua. It consists of an increase in secretory functions of the endometrium at the area of implantation, as well as a surrounding stroma that becomes edematous.[1]

Answer 177

- Modifies the distribution of oestrogen receptors - Stimulates secretory activity - Stimulates stromal oedema - Increases volume of blood vessels - Primes decidual cells - Stabilises lysosomes - Might be an immunosuppresent - May stimulate growth factors and binding proteins - May regulate the formation of reactive oxygen species (reducing oxidative stress)

Answer 178

Embryo is antigenically different from the mother At the same time as the decidual reaction, leukocytes in the endometrial stroma secrete interleukin-2 which prevents maternal recognition of the embryo as a foreign body during the early stages of implantation uterine natural killer cells

Answer 179

produced in the human placenta by the syncytiotrophoblast hCG-a Synthesised in cytotrophoblast cells hCG-b synthesised in syncytiotrophoblast cells of placenta Rising hCG-b levels from day 7-8 signify onset of implantation

Answer 180

Essential to sustain early pregnancy ensures the corpus luteum continues to produce progesterone throughout the first trimester of pregnancy (prevents menstruation). Interacts with the endometrium via specific receptors Immunosuppressive – has highly negative charge, may repel the immune cells of the mother & protect the foetus.

Answer 181

hCG to double every 1.3 days in the first 10-12 days of a normal singleton pregnancy A short doubling time signifies a healthy pregnancy

Answer 182

Early abortion Ectopic pregnancy Delayed implantation Inadequate trophoblast

Answer 183

Embryos are highly sensitive to the environment – essential to optimise conditions to enable successful program

Answer 184

Use a sequential culture medium – different composition at different stages

Answer 185

Day 1-3 Water, salts &ions Pyruvate, lactate, protein and No/low Glucose Non essential amino acids

Answer 186

Day 3+ Water, salts &ions Pyruvate, lactate, protein and Glucose Essential and non essential amino acids Vitamins

Answer 187

Culture day 1-6 in same media one media Let the embryo choose principal useful in uninterrupted systems like time lapse Why? Reduce stress, less disturbance, Increase embryo viability

Answer 188

maternal factors embryonic factors lab conditions

Answer 189

Follicle environment Oocyte maturity (hCG trigger 36hours before egg collection)

Answer 190

Cleavage rate, size of blastomeres, degree of fragmentation Gross chromosome imbalance Variations in embryo metabolism Failure or abnormal formation of the blastocoel cavity

Answer 191

Exposure to light Exposure to high oxygen concentrations Changes in pH or osmolarity Culture medium Volatile organic compounds

Answer 192

Select morphologically (and developmentally) best embryo(s) to transfer on day 5. If any remaining embryos - cryopreserve. Need to be of good quality and correct stage of development to be frozen.

Answer 193

Enable better selection (embryonic genome activated) Promotes synchronization with the endometrium. Higher pregnancy and live birth rates for selected patient populations. Recent systematic review and meta-analysis demonstrated a much improved live birth rate compared to the early cleavage stage when equal numbers of embryos were replaced

Answer 194

Implantation failure is mainly related to either maternal factors or embryonic causes. Problem with the embryo - high proportion of embryos fail to implant Aneuploidy (40% IVF fertilised eggs abnormal) Interaction between embryo and uterus - insufficient trophoblast invasion miscarriage Insufficient invasion of maternal blood vessels Pre-eclampsia, poor foetal growth, hypertension Sperm problem – DNA fragmentation (abnormal genetic material). Increase miscarriage. Nutrition & lifestyle.

Answer 195

Failure to achieve a clinical pregnancy after transfer of at least 4 good quality embryos in at least 3 cycles Under the age of 40

Answer 196

Poor ovarian function Increased sperm DNA fragmentation Uterine pathologies Polyps/fibroids Congenital anomalies Intrauterine adhesions Hydrosalpinges shown to significantly reduce implantation and preg rates - fluid toxic to embryos and affects endometrial receptivity. Immunological factor (NK cells)

Answer 197

Lifestyle changes (smoking, BMI) Sperm DNA fragmentation test Improve embryo selection e.g. PGT-A Hysteroscopy – remove anomalies Fibroid / Polyps /Hydrosalpinges removal Immunotherapy (intravenous immunoglobulin) – maybe only subgroup of women benefit.

Answer 198

- Forms a ridge of issue on the posterior abdominal wall - Both the renal and genital systems develop from it

Answer 199

Three overlapping kidney systems develop from intermediate mesoderm - Pronephros - Mesonephros - Metanephros

Answer 200

Develops in week - 4/40 (disappears by 5/40) Function/ role- Non-functional, rudimentary

Answer 201

Develops in week- 4/40 Function/role- Part of it persists in males. Excretory tubules develop with a group of capillaries Capillaries > glomerulus Tubules > Bowman’s capsule Collecting duct called the mesonephric duct forms Gonad starts to develop

Answer 202

Develops in week- 5/40; starts to function at 12/40 Function/ role- Definitive kidney Definitive kidney Develops in the pelvic region Collecting system and excretory system develop differently Starts to function in week 12 of gestation

Answer 203

Females: Tubules and mesonephric duct degenerate Males: A few tubules and the mesonephric ducts remain: mesonephric duct = vas deferens tubules = ducts of testis

Answer 204

Develops from the ureteric bud The ureteric bud grows out from the mesonephric duct Covered over by a ‘cap’ of metanephric tissue Bud grows into the cap = renal pelvis

Answer 205

Bud splits into two parts = major calyces Continued subdivision and formation of tubules = ureter, renal pelvis, major and minor calyces, collecting tubules

Answer 206

Develops from metanephric cap Development promoted by the developing collecting tubules Development of each is dependent on the other Metanephric tissue forms renal vesicles Vesicles become tubular and capillaries develop = glomerulus Form nephrons

Answer 207

Ureter Renal pelvis Major and minor calyces Collecting tubules

Answer 208

Our systemic pH is maintained within a narrow range (7.35 – 7.45) Normal diet generates non-volatile acid such as sulphuric and phosphoric acid from Protein metabolism, lactate from anaerobic metabolism of Glucose and volatile acid co2 primarily from carbohydrate metabolism. Kidneys excrete the acid load and also reclaim filtered bicarbonate. Lungs mediate excretion of co2.

Answer 209

Role of kidneys in Acid-Base metabolism Reclaim the filtered HCO3- Regenerate HCO3- Excretion of H ions buffered by phosphate or ammonia

Answer 210

pH pO2 pCO2 Std HCO3- Std Base excess May include other measures (eg lactate, Na+, K+)

Answer 211

It is defined as low arterial pH with in conjunction with a reduced serum HCO3- concentration What are the causes? Ketoacidosis, shock, severe diarrhoea, impaired kidney function, ingested toxins H + HCO3 = H2CO3 = H2O + CO2

Answer 212

pH and bicarbonate is high Causes: - Alkali ingestion - Gastrointestinal acid loss: Vomiting - Renal acid loss: Hyperaldosteronism, hypokalaemia (use of diuretics) Compensatory mechanism: Hypoventilation (but limited by hypoxic drive), renal bicarbonate excretion

Answer 213

CO2 retention, leading to increased carbonic acid dissociation Causes: Any cause of respiratory failure e.g hypo- over sedation, brain trauma, immobility, resp muscle paralysis hyper- pneumonia, pulmonary oedema, emphysema, bronchitis Compensatory mechanism: Increased renal H+ excretion and bicarbonate retention (but only if chronic)

Answer 214

CO2 depletion due to hyperventilation Causes: Type 1 respiratory failure, anxiety/panic Compensation: Increased renal bicarbonate loss (if chronic)

Answer 215

A hormone is a substance secreted directly into the blood by specialised cells Hormones are present in only minute concentrations in the blood and bind specific receptors in target cells to influence cellular reactions

Answer 216

Insulin Cortisol Testosterone Oestrogen Thyroxine Adrenaline Aldosterone Progesterone Glucagon VIP

Answer 217

Hypothalamus Pituitary Thyroid Parathyroids Adrenals Pancreas Ovary Testes

Answer 218

-Steroids- e.g cortisol -Peptides- e.g insulin -Thyroid hormones- e.g thyroxine

Answer 219

All steroid hormones are synthesised from cholesterol

Answer 220

Catecholamines synthesised from tyrosine

Answer 221

Storage Secretion Binding protein 1/2 life Time to action

Answer 222

Storage Secretion Binding protein 1/2 life Time to action

Answer 223

Storage Secretion Binding protein 1/2 life Time to action

Answer 224

Storage Secretion Binding protein 1/2 life Time to action

Answer 225

Cascade function in the cell hormone binds to cell surface and can't go thru the membrane G-protein coupl Insulin receptors

Answer 226

Takes a while as it has to travel thru cell membrane and cell nucleus Affects gene transcription in the cell

Answer 227

- Pre-menstrual tension - Pregnancy – post natal depression - Puberty - High dose steroids – psychosis - Hypogonadism – poor libido - Insulinoma - behaviour

Answer 228

Basal metabolic rate, growth (esp. of the brain) Low thyroid hormone means low bmr and lethargy

Answer 229

Ca2+ regulation

Answer 230

Glucose regulation, inflammation, cardiovascular system Too little- addison's disease (low BP and insufficiently raised heart rate)

Answer 231

BP, Na+ regulation

Answer 232

BP, stress

Answer 233

Menstruation and femininity

Answer 234

Sexual function, masculinity

Answer 235

Glucose regulation

Answer 236

Na+ regulation

Answer 237

Ca2+ regulation

Answer 238

Bioassays Immunoassays Mass spectrometry

Answer 239

Controls the release of other hormones Hormones of the anterior pituitary: ACTH, TSH, GH, LH/FSH, PRL Hormones of the anterior pituitary: ADH, Oxytocin

Answer 240

ACTH - Regulation of adrenal cortex TSH- Thyroid hormone regulation GH- Growth (+), metabolism LH/FSH- Reproductive control PRL- Breast milk production

Answer 241

ADH- reduces urine output Oxytocin- breast milk expression

Answer 242

Hypothalamus releases TRH TRH receptor in pituitary stimulates TSH release This stimulates the TSH receptor in the thyroid which releases thyroxine This thyroxine acts on cells but also stimulates the pituitary gland and hypothalamus to stop it

Answer 243

Thyrotoxicosis Cushing's disease/syndrome- disease bc of pituitary tumour, syndrome bc of a collection of symptoms Acromegaly

Answer 244

- Destruction of thyroid tissue using radioiodine - Antithyroid drugs to block hormone synthesis - Partial surgical ablation of thyroid

Answer 245

Somatostatin analogues Dopamine agonists GH receptor antagonists

Answer 246

Severe hypothyroidism Iodine deficiency- goitre Addison's disease

Answer 247

Underactive thyroid – thyroxine Underactive adrenals – hydrocortisone(cortisol) + fludrocortisone (synthetic aldosterone analogue) (Premature) menopause – oestrogen replacement Underactive testes - testosterone

Answer 248

Carcinoid disease Small cell lung cancer Liver secondaries - Flushing - Wheezing - Diarrhoea - Valvular heart disease

Answer 249

Pea-sized Weighs ca. 0.5 g Secretes hormones in response to signals from hypothalamus

Answer 250

The anterior pituitary has no arterial blood supply but receives blood through a portal venous circulation from the hypothalamus

Answer 251

Pit. hormone Hormone type Action

Answer 252

Collection of brain ‘nuclei’ Connections to almost all other areas of the brain Important for homeostasis primitive functions appetite, thirst, sleep, temperature regulation Control of autonomic function via brainstem autonomic centres Control of endocrine function via pituitary gland

Answer 253

Hormone released Releasing hormone TSH TRH ACTH CRH FSH GnRH or LHRH LH GH GHNRG Prolactin Dopamine

Answer 254

Effect of deficiency is small adrenal gland Effect of excess is large adrenal gland

Answer 255

- Acutely stimulates cortisol release - Stimulates corticosteroid synthesis (and capacity) - CRH stimulates ACTH release - Negative feedback of cortisol on CRH and ACTH production

Answer 256

Increase from 3-6 am getting you ready for the day then decreases thru the day with a small peal at 3-4pm

Answer 257

Released throughout life Pulsatile Stimulated by low glucose, exercise, sleep Suppressed by hyperglycaemia Effects mediated by GH and IGF1

Answer 258

Linear growth in children Acquisition of bone mass Stimulates: -protein synthesis -lipolysis (fat breakdown) -glucose metabolism Regulation of body composition Psychological well-being

Answer 259

Negative feedback loop between TSH and thyroxine In pituitary failure both TSH and thyroxine are low (in a case of underactive thyroid, where thyroid and not pituitary is problem, thyroxine is low and TSH rises to stimulate thyroid)

Answer 260

Essential for reproductive cycle LH stimulates sex hormone secretion FSH stimulates development of follicles Absence leads to infertility and hypogonadism

Answer 261

E2 (and others) stimulate the hypothalamus to produce GnRH This stimulates the pituitary to convert the FSH beta and LH beta to be converted to FSH and LH and then be released Inhibitin

Answer 262

- Synthesised in lactotrophs Regulation of PRL different to other anterior pituitary hormones - Negative regulation by tonic release in inhibiting factor - dopamine

Answer 263

Essential for lactation Levels increase dramatically in pregnancy and during breast-feeding – do not test at these times Inhibits gonadal activity through central suppression of GnRH (and thus decreased LH/FSH) Mainly causes disease when present in excess

Answer 264

- Physical or psychological stress - Post seizure - Greater in women - Rarely exceeds 850 – 1000 mU/L - PRL has circadian rhythm with peak during sleep

Answer 265

- Usually easy to recognise in pre-menopausal women - Less apparent in men & post-menopausal women - Pre-menopausal women -Hypogonadism -Oligo/amennorrhoea -Oestrogen deficiency - Galactorrhoea – spontaneous/ expressible - Post-menopausal women - Due to hypogonadal status – none of the above

Answer 266

-PRL-secreting pituitary tumours – prolactinomas -Microadenoma (< 1 cm diameter) -Macroadenoma (≥1 cm diameter) -Loss of inhibitory effect hypothalamic DA -Pituitary stalk compression/ pituitary disconection -Drugs – DA antagonists -Phenothiazines, metoclopramide, TCAs, verapamil -Hypothyrodism

Answer 267

- Benign pituitary adenoma - Craniopharygioma - Trauma - Apoplexy / Sheehans - Sarcoid / TB

Answer 268

1. Pressure on local structure e.g. optic nerves Bitemporal hemianopia 2. Pressure on normal pituitary hypopituitarism 3. Functioning tumour: Prolactinoma Acromegaly Cushing’s disease

Answer 269

Posterior pituitary comes from the neural ectoderm and anterior pituitary comes from oral ectoderm

Answer 270

Chiasmatic compression Cranial nerve damage Hypothalamic damage Bony invasion: pain, CSF leaks

Answer 271

Visual field loss due to damage to optic chiasm Patient can adjust for this by moving head more from side to side to compensate, may not be aware of deficit

Answer 272

ACTH – Leads to increased cortisol levels (Cushing’s disease) GH – Leads to increased GH and IGF-1 levels (Acromegaly) LH or FSH – Very rare! Might stop periods (Gonadotrophinoma) TSH – Leads to thyrotoxicosis. Very rare cause! Prolactin – Leads to galactorrhoea and amenorrhoea (Prolactinoma)

Answer 273

- More common in women - Present with galactorrhoea / amenorrhoea / infertility - Loss of libido - Visual field defect - Treatment dopamine agonist eg Cabergoline or bromocriptine.

Answer 274

- GH excess - Leads to increased Insulin-like Growth Factor-1 production in the liver - Both GH and IGF1 increase growth of a range of soft and hard tissues - >98% due to a pituitary tumour, often large

Answer 275

Fat tissue: Central obesity, moon face, ‘buffalo hump” Collagen/protein: Thin skin, striae, easy bruising, myopathy, osteoporosis Androgen excess: Acne, hirsutism, amenorrhoea Other: Hypertension, depression, diabetes, immunosuppression

Answer 276

Diagnosed by: high cortisol production loss diurnal rhythm of cortisol loss of negative feedback of glucocorticoids on the pituitary With pituitary origin ACTH levels will be high or inappropriately normal for the high cortisol levels ACTH levels will be high in the blood draining from the pituitary Treatment is by transsphenoidal surgery

Answer 277

- GH deficiency causes reduced linear growth in childhood. Symptoms less obvious in adulthood - LH/FSH deficiency causes hypogonadism - ACTH deficiency causes adrenal insufficiency - TSH deficiency causes hypothyroidism - Associated with increased morbidity & mortality

Answer 278

Pituitary tumour + Ectopic tumour both produce too much ACTH Synthetic ACTH-> Biggest cause

Answer 279

Common causes: Pituitary tumours (often non-functioning) Pituitary surgery / radiotherapy / infarction Congenital Moderate-severe Head injuries Clinical Features: Depend on hormones deficient Usual sequence of failure: GH, LH/FSH, ACTH, TSH +/- AVP

Answer 280

Proximal = bulk absorption = leaky Distal = fine tuning = impermeable

Answer 281

Cortex- PCT, proximal straight tubule, part of thick ascending limb, DCT and part of collecting duct Medulla- Thin descending limb, loop of Henle, thin ascending limb, part of thick ascending limb and collecting duct

Answer 282

bulk reabsorption: Na, Cl, glucose, amino acids, HCO3; secretion of organic ions

Answer 283

more Na reabsorption, urinary dilution and generation of medullary hypertonicity

Answer 284

Fine regulation of Na, K, Ca, Pi, separation of Na from H2O

Answer 285

similar to distal tubule, + acid secretion, regulated H2O reabsorption concentrating urine

Answer 286

Tubular defect in uptake of amino acids Defect; mutations in the SLC3A1 and SCL7A( genes Genetic test available but not routinely used in clinical practice Failure of cytokine reabsorption - urinary crystal

Answer 287

to generate a hypertonic medullary interstitium so that H2O can be sucked out of the tubule in impermeable distal segments, thus concentrating the urine

Answer 288

Descending limb simple squamous flat cells sparse organelles simple cuboidal/low collumnar

Answer 289

1. Solute reabsorption in the impermeable ascending limb lowers the lumenal osmolality and increases the medullary interstitial osmolarity 2. Increased interstitial osmolarity draws H2O out of the permeable thin descending limb, increasing the lumenal osmolality. 3. The continuous flow of fluid pushes the hyperosmotic fluid from end of the thin limb in to the ascending limb.

Answer 290

- Increases transcription (steroid receptor) of ENaC (and NaKATPase) - This increases apical Na influx - This charge movement facilitates K efflux - Thus aldosterone drives both Na reabsorption and K secretion

Answer 291

principal cells adenylyl-cyclase coupled vasopressin receptor (V2R) kinase actions culminate in insertion of vesicles containing aquaporin 2 into the apical membrane increases water permeability

Answer 292

Site- Loop of Henle Molecules- NKCC2, ROMK or basolateral K/Cl efflux Diuretic equivalent- Loop diuretic Features-HypoK, alkalosis, secondary aldosteronism, lowish BP

Answer 293

Site- DCT Molecule- NCC Diuretic equivalent- Thiazide Features- HypoK, HypoMg, lowish BP

Answer 294

Site- Collecting duct Molecule- ENaC- constitutively active Diuretic equivalent- n/a Features- Hypertension, hypokalaemia

Answer 295

Waterproof barrier Physical barrier Vitamin D synthesis Endocrine organ UV barrier Barrier to infection Immune organ Sensory organ Thermoregulation Energy store / Shock absorber

Answer 296

Largest organ of the body 3.6 Kg 2 m2 3 layers Epidermis Dermis Subcutis Not just a wrapper for the interesting bits!

Answer 297

Waterproofing Physical barrier Immune function Vitamin D synthesis (Endocrine) UV protection Thermoregulation

Answer 298

Thermoregulation Vitamin D synthesis (Endocrine) Sensory organ

Answer 299

Thermoregulation Energy reserve Vitamin D storage Endocrine organ Shock absorber

Answer 300

Tight junctions between cells in stratum granulosum, epidermal lipids and keratin in stratum corneum form both an inside-out and outside-in barrier to water Prevents transepidermal water loss

Answer 301

Skin on fingers and toes wrinkles if immersed for approx. 5 mins. Mediated by sympathetic nervous system Due to vasoconstriction in dermis Improves grip

Answer 302

Structure of skin helps resist trauma Stratified epithelium helps resist abrasive forces Fat in subcutis acts as shock absorber

Answer 303

Medical term for a graze Stripping away of the epidermis Secretions but not blood

Answer 304

7-dehydrocholesterol in plasma membranes of epidermal keratinocytes and dermal fibroblasts converted to previtamin D3 by UVB 15-25 mins whole body exposure produces up to 10,000 IU Vitamin D Serum concentrations peak 24-48 hours after exposure Lipid soluble – can be stored in subcutis adipocytes

Answer 305

Site of hormone action Androgens act on follicles and sebaceous glands Thyroid hormones act on keratinocytes, follicles, dermal fibroblasts, sebaceous glands, eccrine glands

Answer 306

Epidermal changes Coarsened thin scaly skin Dermal changes Myxoedema Hair and Nail changes Dry brittle coarse hair Alopecia Thin brittle nails Sweat gland changes Dry skin Decreased sweating

Answer 307

Vitamin D3 – unique site for cholecalciferol synthesis 17β-hydroxysteroid dehydrogenase in sebocytes and 5α-reductase in dermal adipocytes convert dehydroepiandrosterone (DHEA) and androstenedione to 5α-dihydrotestosterone Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) synthesised by dermal fibroblasts

Answer 308

Both UV-A and UV-B damage skin - Burns - Suppress action of Langerhans cells - Photo-aging - DNA damage (skin cancers) Skin colour depends on: - Melanin - Carotenoids - Oxy/deoxyhaemoglobin

Answer 309

Synthesised in melanosomes within melanocytes from tyrosine Transported via dendrites to adjacent keratinocytes Pheomelanin (red/yellow) Eumelanin (brown/black) Photoprotective – scatters/filters UV light

Answer 310

Melanocyte density varies between body sites Red hair contains more pheomelanin All skin types contain more eumelanin than pheomelanin.

Answer 311

Prone to photodegradation – may generate reactive oxygen species! Pheomelanin increases release of histamine Lots of melanin = less able to utilize UV light to make vitamin D

Answer 312

photooxidation of existing melanin redistribution of melanosomes occurs within minutes and lasts hours-days.

Answer 313

UVA >> UVB oxidation of melanin occurs within hours, lasts 3-5 days

Answer 314

increased melanin synthesis Occurs 2-3 days after UV exposure, maximal at 10-28 days

Answer 315

- Skin presents a large surface area to environment - The properties that render the skin a barrier to water also help prevent infection - A range of peptides synthesised by granular layer keratinocytes have antimicrobial properties - Cathelicidin-related antimicrobial peptide (Cramp – called LL37 in humans) - β defensins - S100A7 and S100A8

Answer 316

- Innate and acquired immune functions - Epidermis -Langerhans cells - Dermis - Regulatory T cells - Natural killer cells - Dendritic cells - Macrophages - Mast cells

Answer 317

Keratinocytes secrete cytokines and chemokines that maintain populations of leucocytes in skin Langerhans cells are antigen-presenting cells and secrete cytokines

Answer 318

- LC migrate to dermis and lymph nodes and activate a T-cell response - Keratinocytes proliferate & secrete cytokines - Leucocytes enter skin from blood

Answer 319

- Merkle cells - basal epidermis (Light touch) - Encapsulated mechanoreceptors in dermis - Pacinian corpuscles (Pressure/Vibration) - Meissner corpuscles (Touch) - Myelinated and unmyelinated sensory nerve endings in dermis (Pain, Itch, Temperature)

Answer 320

Insulation - Subcutaneous fat Heat loss - Cutaneous blood flow - Deep vascular plexus (lower reticular dermis) - Superficial vascular plexus (upper reticular dermis) - Loops of blood vessels from superficial plexus extend to reticular dermis - Eccrine sweating - Hair [What might be other functions of human hair?]

Answer 321

Humans are endothermic homeotherms Heat generated through metabolism Evaporation depends on: Surface area exposed to environment Temp and relative humidity of ambient air Convective air currents Radiation, conduction and convection can add or remove heat

Answer 322

Heat storage = metabolism – work – evaporation +/- radiation +/- conduction +/- convection

Answer 323

- Autonomic regulation of blood flow in dermal vascular plexuses - Sympathetic alpha-noradrenergic: vasoconstriction - Sympathetic cholinergic: vasodilation - (Both in hairy skin. Hairless skin only has cholinergic innervation) - Sympathetic cholinergic nerves that govern sweating may be the same as those controlling active vasodilation - Nitric oxide may play a role in active vasodilation

Answer 324

- 1.6-4 million eccrine sweat glands - 1-3 L sweat per hour - Availability of water is major limiting factor

Answer 325

- Arrector pili muscles innervated by sympathetic α1-adrenergic fibres - Contraction raises cutaneous hairs - Likely little significant impact on heat conservation

Answer 326

-Subcutaneous fat acts as an insulator, a shock absorber and as an energy store - White adipose connective tissue

Answer 327

Driven by hormonal changes- include * Weight gain * Maternal * Fetoplacental * Protein synthesis * Lipid synthesis * Insulin resistance

Answer 328

* Human chorionic gonadotrophin * Oestrogen * Progesterone * Prolactin * Relaxin * Oxytocin * Prostaglandins

Answer 329

* Stimulates oestrogen/progesterone production by ovary * Pregnancy test hormone * Diminishes once placenta mature enough to take over oestrogen/progesterone production

Answer 330

* Produced throughout pregnancy * Regulates levels of progesterone * Prepares uterus for baby, breasts for lactation

Answer 331

* Prevents miscarriage, builds up endometrium for support of placenta * Prevents uterine contractions

Answer 332

* Produced by pituitary gland * Increases cells that produce milk. * After birth levels of P and oestrogen drop dramatically, allowing prolactin to stimulate production of milk, also controlled by suckling. * Prevents ovulation, unreliably

Answer 333

* High early in pregnancy * Limits uterine activity, softens the cervix – cervical ripening in preparation for delivery

Answer 334

* Triggers "caring" reproductive behaviour. * Responsible for uterine contractions during pregnancy and labour. * Cause of contractions felt during breast feeding. * Drug used to induce labour

Answer 335

* Tissue hormones, role in initiation of labour * Synthetic prostaglandins used to induce labour

Answer 336

hCG highest in 1st few weeks then drops as the placenta develops Progesterone increases a bit then plateaus before increasing exponentially from week 20 with the other hormones The other hormones start to increase exponentially at the 10th week

Answer 337

* Increasing cardiac output (CO) * Reduced systemic blood pressure * Reduced total peripheral resistance (TPR) BP= CO x TPR * Increased uterine blood flow Increased blood volume * Increased red cell mass * Increased alveolar ventilation

Answer 338

Varicose veins- because of relaxation of smooth muscles Striae gravidarum + Linea nigra - because of rapid increase in stomach size

Answer 339

Compression of the organs so gastric acid reflux Lumbar lordosis because of relaxation of ligaments

Answer 340

* Biological factors * Poor weight gain/undernutrition * Extremes of maternal age * Medical conditions * Drug misuse: cigarettes, heroin etc * Haemorrhage

Answer 341

* Miscarriage * Abnormal development * Disordered fetal growth * Too big * Too small * Premature birth and consequences

Answer 342

*Uterine growth - cell division and hypertrophy of individual myometrial cells *Myometrium *Smooth muscle cells in bundles, contract and relax

Answer 343

* Protects fetus during development * Mainly collagen and ground substance with glycosaminoglycans * Collagen has cross-links which increase tensile strength

Answer 344

* Growth and remodelling of the cervix prior to labour * Occurs under influence of placental hormones and relaxin throughout gestation * Process accelerates last 3 m due to oestrogens and dehydroepiandrosterone. * Promoted by release of PGE from cervical mucosa, relaxin and placental oestrogens. * Effacement and dilatation due to muscular action of cervix and uterus

Answer 345

* All uterine tissues able to synthesize PG * PGE2 about 10 times as potent as PGF2a in human uterus. * PGF2a - main prostaglandin released during labor

Answer 346

Phase 0 - myometrial repression Phase 1 - Myometrial activation Phase 2 - Biochemical activation Phase 3 - Permanent changes

Answer 347

* Enhanced prostaglandin production * The initiation of labor * maternal signal oxytocin * fetal signals oxytocin, vasopressin, & cytokines * PGF2a enhance action of oxytocin. * With pressure on cervix, release of PG from decidua and chorioamnion.

Answer 348

3 Ps * Passenger the baby * Passages the pelvis * Powers the uterus

Answer 349

Foetal skull bones not yet fused Joined at sutures Can overlap as they are squeezed thru the birth canal

Answer 350

* Braxton-Hicks contraction * Co-ordinate- fundal dominant -push baby down * Inco-ordinate- not associated with good labour progress

Answer 351

*Increased PGF2a enhancing action of oxytocin. * Increased pressure on cervix, release of PGs from decidua and chorioamnion. * The contractile protein actomyosin, formed from actin and myosin. * Myosin can react with actin only when phorphorylated by MLCK. * MLCK functionally dependent on ca+ ions and calmodulin, inactivated by its own phosphorylation

Answer 352

Inlet- oval shapes - foetal head transverse Main bit- circular- left occipital-anterior position Outlet- Oval shaped but the other way- occipital anterior

Answer 353

First stage- start of regular contraction and dilatation of the cervix Second stage- cervix dilated baby travels through vaginal canal Delivery- Baby comes out Third stage- placenta is delivered

Answer 354

* Too narrow * Too wide * Damaged

Answer 355

* Too large or too small * Abnormal lie or presentation eg breech * Tumours * Too poorly

Answer 356

* Too strong * Too weak * Disorganised * Cervix too rigid * Cervix weak * Postpartum bleeding

Answer 357

* Prolonged latent phase * Failure to progress in labour * Delayed 2nd stage – instrumental delivery * Delayed 3rd stage – manual removal of the placenta

Answer 358

* Maternal-foetal organ * Begins developing at blastocyst implantation. * Delivered after the foetus at birth. * Provides for the developing foetus: * Nutrition * gas exchange * waste removal * endocrine and immune support

Answer 359

Fetal surface Maternal surface

Answer 360

* Umbilical cord attachment * Covered with amnion attached to chorionic plate * Umbilical vessels branch into anastomosing chorionic vessels

Answer 361

* Cotyledons * Cobblestone appearance * Covered with maternal decidua basalis

Answer 362

1st stage in dev of placenta * Adhesion/attachment of embryonic trophoblast and endometrial epithelial cells

Answer 363

*Metabolism *Transport *Endocrine

Answer 364

*Synthesizes *Glycogen *Cholesterol *Fatty acids *Provides nutrient and energy

Answer 365

* Gases and nutrition * Oxygen, carbon dioxide, CO * Water, glucose, vitamins * Hormones, mainly steroid not protein * Electrolytes * Maternal antibodies – IgG not IgM * Waste products * Urea, uric acid, bilirubin * Drugs and their metabolites * Fetal drug addiction * Infectious agents * Cytomegalovirus, rubella, measles, microorganisms

Answer 366

* Human chorionic gonadotrophin (hCG) like leutenizing hormone, supports corpus luteum * Human chorionic somatommotropin (hCS) or placental lactogen stimulate mammary development * Human chorionic thyrotropin (hCT) * Human chorionic corticotropin (hCACTH) * Progesterone and Oestrogens support maternal endometrium * Relaxin

Answer 367

* placenta accreta * abnormal adherence, with absence of decidua basalis * placenta percreta * villi penetrate myometrium * placenta praevia * placenta overlies internal os of uterus * abnormal bleeding * usually require caesarean delivery

Answer 368

* Fetus Rh+ /maternal Rh- * Fetus causes anti rh antibodies *Dangerous for 2nd child

Answer 369

* Maternal hypertension: pre-eclampsia * Foetal growth restriction * Tumours * Intra-uterine foetal death

Answer 370

Originates from Neuro tissue – large numbers of Glial-type cells 2 Hormones vasopressin Oxytocin

Answer 371

Antidiuretic hormone – controls water secretion into urine) Primarily from supraoptic nuclei

Answer 372

expression of milk from the glands of the breasts to the nipples; promotes onset of labour. Primarily from paraventricular nuclei

Answer 373

1. Binds to membrane receptor 2. Receptor activates cAMP second messenger system 3. Cell inserts AQP2 water pores into the apical membrane 4. Water is absorbed by osmosis into the blood

Answer 374

Baroreceptors- changes in BP- signal to produce ADH Osmoreceptors- changes in conc.- signal to produce ADH

Answer 375

- Concentration of particles per kilo of fluid - size of particle not important, number is important - i.e one molecule of larger protein albumin same effect as Na+ - sodium, potassium, chloride, bicarbonate, urea and glucose present at high enough concentrations to affect osmolality - alcohol, methanol, polyethylene glycol or mannitol - exogenous solutes that may affect osmolality

Answer 376

Sodium Glucose Urea

Answer 377

0-10 mOsmo/kg gap between measured and calculated - higher usually due to alcohol

Answer 378

282 - 295 mOsmol/kg

Answer 379

- Drinking rapidly suppresses vasopressin release and thirst. - In pregnancy osmotic threshold for VP release and thirst is decreased. - Plasma VP concentrations increase with age (also thirst blunting, decreased renal concentrating ability, decreased fluid intake).

Answer 380

- Vasopressin Deficiency, Vasopressin Resistance - Syndrome of inappropriate antidiuretic hormone secretion - SIADH

Answer 381

Large volumes of urine

Answer 382

Large volumes of drinking

Answer 383

polyuria polydypsia no glycosuria or hypercalcaemia or hypokalaemia

Answer 384

measure urine volume - DI unlikely if urine volume <3L/day biochemistry inappropriately dilute urine (<300 mOsm/kg) for plasma osmolality (>290 mOsm/kg) normonatraemia or hypernatraemia water deprivation test

Answer 385

Vasopressin Deficiency – Cranial lack of vasopressin (ADH) Vasopressin Resistance – Nephrogenic resistance to vasopressin

Answer 386

Destruction of hypothalamus Interruption of the connection of hypothalamus to pituitary Acquired Idiopathic Tumours - craniopharyngioma, germinoma, metastases Trauma Infections - TB Vascular - neurosarcoidosis, Langerhans’s histiocytosis Granuloma Familial - very rare - mutations in the neurophysin part of pro-AVP Autosomal dominant Rarely autosomal recessive

Answer 387

Aquired- Osmotic diuresis (diabetes mellitus) Drugs (lithium, Demeclocycline tetracycline) Chronic renal failure Familial-

Answer 388

Hypertonic Saline Stimulation Test measure random copeptin then if iver 21.4 pmol/L give

Answer 389

treat any underlying condition desmopressin

Answer 390

try and avoid precipitating drugs congenital DI - very difficult free access to water very high dose desmopressin hydrochlorothiazide or indomethacin

Answer 391

Common in clinical practice Too much AVP, when it should not be being secreted Causes low blood concentration - low osmolality Urine is inappropriately concentrated Plasma sodium is low Euvolaemia

Answer 392

Hyponatraemia < 135 mmol/L Plasma hypo-osmolality < 275 mOsm/Kg Urine osmolality > 100 mOsm/Kg Clinical euvolaemia No clinical signs of hypovolaemia (orthostatic decreases in blood pressure, tachycardia, decreased skin turgor, dry mucous membranes) No clinical signs of hypervolaemia (oedema, ascites) Increased urinary sodium excretion > 30 mmol/L with normal salt and water intake Exclude recent diuretic use, renal disease, hypothyroidism, and hypocortisolism

Answer 393

treat underlying condition fluid restriction <1L/24 hour sometimes demeclocycline ‘Vaptans’ – V2 receptor antagonists if Na+ low AND fitting hypertonic N/Saline on ITU <12mmol/l increase in Na+ per 24 hour Potential risk of central pontine myelinolysis

Answer 394

release stimulated by milk suckling Action stimulates milk let down stimulates contraction of myometrium (100X more potent that AVP) 200X less active at the V2 receptor compared to AVP

Answer 395

Hypertonic saline should raise sodium by 1 to 2 mmol/l/hour; monitor sodium every 2 hours Hypertonic saline should be stopped when asymptomatic or serum sodium >120mmol/l One should increase sodium around 8 – 12 mmol/l in 24 hours or 16 – 24 mmol/l in 48 hours to avoid osmotic demyelination Aim for a safe range as opposed to a normal range Hypertonic saline should raise sodium by 1 to 2 mmol/l/hour; monitor sodium every 2 hours Hypertonic saline should be stopped when asymptomatic or serum sodium >120mmol/l One should increase sodium around 8 – 12 mmol/l in 24 hours or 16 – 24 mmol/l in 48 hours to avoid osmotic demyelination Aim for a safe range as opposed to a normal range

Answer 396

Zona glomerulosa zona fasciculata Zona reticularis

Answer 397

Mineralocorticoids- aldosterone for salt

Answer 398

Glucorticoids – Cortisol for sugar and stress

Answer 399

Androgens – DHEA, androstenedione For sex

Answer 400

Biiger than kidney Fetal zone, transitional zone and definitive zone instead of layers of cortex (different thicknesses as well)

Answer 401

Cholesterol precursor for all adrenal steroidogenesis cyclopentanoperhydrophenanthrene structure three cyclohexane rings (A, B, and C) single cyclopentane ring (D)

Answer 402

- Lipid soluble - can pass through biological membranes - Bind to specific intracellular receptors - Alter gene transcription directly or indirectly - Exact action depends on structure, ability to bind specific receptors (and recruit cofactors)

Answer 403

Type carbons hormone pregnane derivatives

Answer 404

Deficiency-> small Excess -> large

Answer 405

- Synthesised in zona fasciculata and reticularis - Essential to life - Have actions on most tissues - Many actions “permissive” (do not directly initiate but allow to occur in presence of other factors), e.g. the effects of catecholamines on vascular tone - “Permissive” actions only apparent with deficiency - Important in homeostasis e.g. conditioning body’s response to stress

Answer 406

Increase glucose mobilisation Augment gluconeogenesis Amino acid generation Increased lipolysis Maintenance of circulation Vascular tone Salt and water balance Immunomodulation Dampen immune response Important during stress

Answer 407

Too little -> depression and psychosis Too much -> The same

Answer 408

In the circulation glucocorticoids are heavily bound to proteins 90% bound to Corticosteroid-Binding Globulin (CBG) 5% bound to albumin 5% “free” Only “free” glucocorticoids bioavailable In clinical practice “total” rather than “free” cortisol levels measured CBG levels - with inflammation thus % free cortisol

Answer 409

Non stressed- most bind to CBG STressed- break CBG most not bound

Answer 410

Acutely stimulates cortisol release Stimulates corticosteroid synthesis (and capacity) CRH stimulates ACTH release Negative feedback of cortisol on CRH and ACTH production

Answer 411

Protein folding & translocation across ER Escorting MC2R to cell surface Stabilising of MC2R at cell surface Ligand specificity

Answer 412

Stress, cytokines and diurnal rhythm, stimulate hypothalamus to produce CRH which stimulates the pituitary to produce ACTH which stimulated the adrenal gland to produce Cortisol and CBG which then acts to reduce output of hypothalamus and pituitary

Answer 413

"The sum of the bodies responses to adverse stimuli” Infection Trauma Haemorrhage Medical illness Psychological Exercise/exhaustion

Answer 414

Huge spike Loss of diurnal variation Returns to normal after a few days

Answer 415

Stress cytokines stimulate hypothalamus Decreased synthesis and breakdown of CBG

Answer 416

Synthesised in zona glomerulosa Aldosterone synthase present in this region Main mineralocorticoids are aldosterone and DOC -DOC has 3% mineralocorticoid activity of aldosterone Essential to life Critical to salt and water balance in Kidney, Colon, Pancreas, Salivary glands Sweat glands

Answer 417

Aldoesterone enters cell and stimulates mineralocorticoid receptors

Answer 418

Primary adrenal insufficiency (AI) CAH -Aldosterone synthase deficiency -Inborn AI Autoimmune AI X-linked adrenoleukodystrophy End organ resistance Mineralocorticoid receptor defects ENaC defects Other deficiencies in the collecting tubule pathway Not in secondary adrenal insufficiency

Answer 419

Plasma: Sodium low, potassium high Urine: Sodium high, potassium low

Answer 420

- Effects on pancreas - Sweat glands - Salivary glands - Colon All this causes sodium resorption and decrease sodium content Non-classical effects: - Myocardial collagen production - Role in cardiac fibrosis/remodelling

Answer 421

Convert cortisol to cortisone

Answer 422

- Weak androgens generated in adrenal gland - Dehydroepiandrosterone (DHEA) most abundant adrenal steroid but very weak androgen - Androstenedione more androgenic but only 1/10th that of testosterone - Major source of androgens in women - Oestrogen precursors in postmenopausal women - Production regulated by ACTH rather than gonadotrophins

Answer 423

- Part of autonomic nervous system - Specialised ganglia supplied by sympathetic preganglionic neurones (ACh as transmitter) - Synthesises catecholamines - Main site for adrenaline synthesis (Phenylethanolamine-N-methyl transferase present) - Not essential for life

Answer 424

Tyrosine -> cortisol introduced and sympathetic stimulation-> DOPA -> Dopamine -> sympathetic stimulation -> Noradrenaline -> cortisol introduction -> adrenaline

Answer 425

Relative production of catecholamines 80% adrenaline, 20% noradrenaline Dopamine in small amounts Normal catecholamine synthesis dependent on high local cortisol levels (permissive effect) Catecholamines released during “flight or fight” gluconeogenesis in liver and muscle lipolysis in adipose tissue Tachycardia and cardiac contractility Redistribution of circulating volume

Answer 426

* Migration of primordial germ cells from dorsal endoderm to urogenital ridge by 6-8 wks gestation * Development of indifferent gonad from urogenital ridge * Presence of SRY gene (on Y chromosome) ® testes differentiated by week 9 * Absence of SRY gene ( on Y chromosome) ® ovaries present by 11-12 weeks

Answer 427

adrenal and gonads derive from same tissue

Answer 428

AMH - anti mullarian hormone Mullerian regression

Answer 429

Produce testosterone and DHT Male sex differentiation

Answer 430

Sex determination -> 4-6 weeks Sex differentiation -> 7-9+ weeks

Answer 431

Androstenedione produces both testosterone and oestrone Oestrone produces oestradiol Testosterone produces oestradiol and 5 alpha -dihydro-testosterone (DHT)

Answer 432

Testis present and Leydig cells making testosterone: Wolffian system develops into - epididymis, - vas deferens, - seminal vesicles - ejaculatory ducts Sertoli cells secret AMH, which leads to regression of Müllerian system

Answer 433

No testis or Leydig cells not making testosterone: Müllerian system develops into - fallopian tubes - uterus - upper third vagina

Answer 434

Common genital tubercle at 8 weeks, with lateral urethral folds, labioscrotal swellings * Tubercle becomes glans penis in male, clitoris in female * Urethral folds become corpus spongiosum enclosing urethra in male, labia minora in female * Labioscrotal folds fuse to form scrotum and ventral penis, or labia majora

Answer 435

Opening on underside of penis

Answer 436

Caused by mutations in the androgen receptor (AR) Xq11-12 => AR not responding to androgens Clinical and biochemical phenotype * Very high testosterone and dihydrotestosterone levels * Internal genitalia male (due to AMH production) * External genitalia and external appearance female * Gender identity female => Diagnosis often because of primary amenorrhoea

Answer 437

* DSD with external genitalia classified – typical female with or without clitoromegaly (21 cases) – ambiguous (12 cases) – typical male with or without micropenis (7 cases) * associated nongenital malformations (7 cases) * Genetic diagnosis in a total of 35% (14 of 40) – 22.5% with a pathogenic finding – 12.5% with likely pathogenic findings – 15% with variants of unknown clinical significance

Answer 438

* Measurements of growth provide a sensitive indication of health in childhood * Growth rates are narrowly defined in healthy children with adequate nutrition and an emotionally supportive environment * Changes in growth rates can provide an early and sensitive pointer to health problems in children

Answer 439

* Newborns: larger head, smaller mandible, short neck, chest rounded, abdomen prominent, limbs short * Adults: relative growth of limbs compared to trunk

Answer 440

– Rapid, but rapidly decelerating growth in first 2-3 yrs – determined by nutrition – long term growth failure, if underfed in infancy

Answer 441

– switch from nutritional to hormonal dependence – height velocity slows 2-3 yrs to puberty

Answer 442

* Puberty component: – growth spurt, height velocity due to GH and – sex hormones oestrogen and testosterone – To age 14-15 girls, 16-17 boys * Growth ends with fusion of epiphyses due to influence of oestrogens in boys and girls * Boys convert testosterone to oestrogens in fatty tissues

Answer 443

* Fastest growth rate in utero and infancy * Gradually decreasing rate to puberty * Pubertal growth spurt * Growth ends with fusion of epiphyses (Oestrogen effect) * Huge inter-individual variability

Answer 444

* Parental phenotype and genotype * Quality and duration of pregnancy * Nutrition * Specific system and organ integrity * Psycho-social environment * Growth promoting hormones and factors

Answer 445

* Growth = Chondrogenesis * All growth disorders originate from, or affect the growth plate * Building material needed every day – direct effect of nutrition and calcium/phosphate supply on growth rate and bone architecture

Answer 446

Endocrine signals Nutrition Inflammatory cytokines Extracellular fluid All apart from endocrine signals are affected by oxygen deficiency, acidosis and toxins

Answer 447

* GHRH cell bodies in arcuate nucleus, project to portal capillaries * Regulated by food, sleep, steroids * Negative feedback: SST, GH, IGF-1 * Neurotransmitters: adrenergic, cholinergic, opioids * Other hypothalamic hormones: TRH, CRH

Answer 448

* Synthesized in somatotroph cells, these account for 40-50% of the anterior pituitary * most abundant hormone * Pulsatile secretion max at night * Growth Hormone Binding Protein GHBP

Answer 449

* Stimulates Insulin like growth factor 1 (IGF-1) * Direct effect on growth plate and cortical bone * decrease glucose use; increase lipolysis; Increase muscle mass

Answer 450

Exercise Stress Hypoglycaemia Fasting High protein meals Perinatal development Puberty

Answer 451

Hypothyroidism Hyperglycaemia High carbohydrate meals Glucocorticoid excess Aging

Answer 452

GH secretion GH receptor Post-receptor GH signalling IGF-I gene expression

Answer 453

* Precocious Puberty * Congenital adrenal hyperplasia * McAlbright syndrome * Hyperthyroidism

Answer 454

* Androgen/ or oestrogen deficiency/ oestrogen resistance * GH excess * Klinefelter syndrome (XXY) * Marfan syndrome * (Homocystinuria)

Answer 455

* Describes the physiological, morphological, and behavioural changes as the gonads switch from infantile to adult forms. * Definitive signs: –Girls - Menarche – first menstrual bleeding. – Boys - first ejaculation, often nocturnal. – These do not signify fertility

Answer 456

* Ovarian oestrogens regulate the growth of breast and female genitalia * Ovarian and adrenal androgens control pubic and axillary hair

Answer 457

* Testicular androgens –External genitalia and pubic hair growth –enlargement of larynx and laryngeal muscles -> voice deepening

Answer 458

* Timing of changes are unique to the individual * Sequence of events is related to specific staging criteria, for example: – Breast development – Pubic hair development – External genitalia development in boys

Answer 459

Precocious puberty: onset of secondary sexual characteristics before 8 yrs (girl), 9 yrs (boy) * Menarche before 9 yrs may lead to short stature

Answer 460

Delayed puberty: absence of secondary sexual characteristics by 14 yrs (girl), 16 yrs (boy) * Delayed puberty leads to reduced peak bone mass and osteoporosis

Answer 461

Hypothalamus, Pituitary- produces LH (binds to theca interna) and FSH (binds to granulosa cells) Gonads (ovaries)

Answer 462

Hypothalamus Pituitary- LH (binds to leydig cells), FSH (binds to sertoli cells) Gonads (testes)

Answer 463

* Physical changes controlled by gonadal and adrenal sex steroids regulated by the gonadotrophins, LH and FSH * Marked by circadian rhythm of FSH and LH secretion: – Sleep-augmented LH secretion – pulse-like – Later puberty LH daytime pulses also

Answer 464

– Puberty only requires hypothalamic GnRH – Emphasises the direct link CNS and pituitary and hypothalamic GnRH neurons – Supporting evidence from the rhesus macaque

Answer 465

Increased stimulatory factors most prominently glutamate and kisspeptin Decreased inhibitory tone mostly through GABAergic neurons secreting γ-aminobutyric acid (GABA) and opioidergic neurons

Answer 466

* Critical body weight important for initiation of reproductive cycle * In domestic species (i.e. cattle) body weight rather than chronological age determines start of puberty * Similar in humans

Answer 467

* Genetics: 50-80% of variation in pubertal timing * Environmental factors e.g. nutritional status * Leptin → regulates appetite and metabolism through hypothalmus. Permissive role in regulation of timing of puberty * Adrenarche: gradual “maturation” of the adrenal gland, development of pubic and axillary hair, body odour and acne

Answer 468

* Incidence 1 in 5,000 to 10,000 * 90% of patients female * Idiopathic CPP – Up to 80% female – Only 30% male

Answer 469

* At birth oedema of dorsa of hands, feet and loose skinfolds at the nape of the neck * Webbing of neck, low posterior hairline, small mandible, prominent ears, epicanthal folds high ached palate, broad cheast, cubitus valgus, hyperconvex fingernails * Hypergonadotrophic hypogonadism, streak gonads * Cardiovascular malformations * Renal malformations (horseshoe kidney) * Recurrent otitis media * Short stature

Answer 470

Follicular- around colloid C-cells

Answer 471

- Control of metabolism: energy generation and use - Regulation of growth - Multiple roles in development

Answer 472

1. TSH binds to TSHR on the basolateral membrane of follicular cells 2. I- uptake by NIS (Na/I symporter 3. Iodination of Thyroglobulin tyrosyl residues by TPO (thyro- peroxidase) 4. Coupling of iodotyrosyl residues by TPO on apical membrane 5. Export of mature Tg (thyroglobulin) to colliid where it is stored

Answer 473

- T3 is biologically active hormone - Produced by mono-deiodination of T4 which most abundant - Deiodinase (D1, D2, D3) enzymes in peripheral tissues

Answer 474

Produced by follicular thyroid cells Synthesised from the thyroglobulin precursor Iodine is absorbed from bloodstream and concentrated in follicles Thyroperoxidase binds iodine to tyrosine residues in thyroglobulin molecules to form MIT + DIT - MIT + DIT = T3 - DIT + DIT = T4

Answer 475

T4 and T3- TBG, transthyretin, albumin

Answer 476

Different to other types of hormones Like steroid hormones as act on DNA but have to have a transporter protein

Answer 477

Decrease in Serum TSH Increase in Serum free T4 Increase in Serum free T3

Answer 478

Increase in Serum TSH Decrease in Serum free T4 Decrease in Serum free T3

Answer 479

Prevalence: ♀: 20/1000 ♂: 2/1000 Aetiology: - Graves’ hyperthyroidism - Toxic nodular goitre (single or multinodular) - Thyroiditis (silent, subacute): inflammation - Exogenous iodine - Factitious (taking excess thyroid hormone) - TSH secreting pituitary adenoma - Neonatal hyperthyroidism

Answer 480

Cardiovascular - Tachycardia (rapid heart rate) - AF (atrial fibrillation) - Shortness of breath - Ankle swelling Neurological - Tremor - Myopathy (muscle weakness) - Anxiety Gastrointestinal Weight loss Diarrhoea Increased appetite Eyes/skin Sore, gritty eyes Double vision Staring eyes Pruritus (itching)

Answer 481

Prevalence 40/1000 females 5% of over 60’s Aetiology: - Autoimmune – Hashimoto’s thyroiditis (TPO and Tg antibodies - genetic predisposition) - After treatment for hyperthyroidism - Subacute/silent thyroiditis - Iodine deficiency - Congenital (thyroid agenesis/enzyme defects)

Answer 482

Cardiovascular Bradycardia (slow heart rate) Heart failure Pericardial effusion Gastrointestinal Weight gain Constipation Skin Myxoedema Erythema ab igne Vitiligo Neurological Depression Psychosis Carpal tunnel syndrome

Answer 483

Regulate calcium and phosphate levels Secrete parathyroid hormone (PTH) in response to: Low calcium or High phosphate Actions of PTH: Increases calcium reabsorption in renal distal tubule Increases intestinal calcium absorption (via activation of vitamin D) Increases calcium release from bone (stimulates osteoclast activity) Decrease phosphate reabsorption

Answer 484

For: 1. Excitable Tissue 2. Muscle/Nerves 3. Cell Adhesion Stored and released by bone

Answer 485

Parathyroid hormone Vitamin D Calcitonin, FGF23

Answer 486

Mineral phase (Calcium/phosphate) Protein phase (Collagen and non-collagenous proteins) Bone cells Bone ‘turnover’ and remodelling units

Answer 487

Hyperparathyroidism Osteomalacia andosteoporosis

Answer 488

GI tract - releases via vitamin D Kidney - releases via PTH, vitD and FG23 Bone - releases via PTH Vit D 50% of serum calcium ‘free’ (ionised) 50% bound to albumin (so cannot diffuse into cells)

Answer 489

It will lead to kidney stones

Answer 490

84 amino acid peptide but biological activity in first 34 amino acids (PTH 1-34), half-life 8 mins Cleaved to smaller peptides Assayed by two site assay (to avoid detecting fragments) Still detects some inactive fragments e.g. in renal failure Normal adult reference range = 1.6 - 6.9 pmol/L Binds to G protein coupled receptors mainly in kidney and osteoblasts

Answer 491

PTH increases distal tubular reabsorption of calcium (+ inhibition of PO4 reabsorption) PTH also stimulates production of the active form of vitamin D, 1,25(OH)2D PTH enhances bone resorption by stimulating osteoclasts

Answer 492

PTH transcription (mRNA production) is inhibited by 1,25D3 PTH translation (mRNA to protein synthesis) is inhibited by increased serum calcium

Answer 493

parathyroid tumour (usually benign adenoma) Causes hypercalcaemia and low serum phosphate Loss of negative feedback from hypercalcaemia (Treatment is surgery)

Answer 494

renal disease (increased phosphate, decreased activation of vitamin D) (Treatment with phosphate binders or vitamin D analogues)

Answer 495

long-standing secondary HPT leads to irreversible parathyroid hyperplasia. Usually seen when renal disease corrected e.g. by transplantation (Treatment is surgery)

Answer 496

- Produced by thyroid c-cells (parafollicular) - Calcitonin released in hypercalcaemia, inhibits bone resorption (by direct effect on osteoclasts) - Not essential to life (post thyroidectomy no calcium problems) - Two calcitonin genes products from a single gene and primary RNA transcript

Answer 497

Menopause: cessation of menstruation

Answer 498

the period around the menopause and at least the first year after it.

Answer 499

12 months of no period

Answer 500

Average age: 51 in the UK. Range: 48-52. Premature: before 40 (1%).

Answer 501

Age: Depletion of primordial follicles. Premature menopause: Idiopathic. Iatrogenic. Chromosomal (fragile X syndrome, FMR1) Autoimmune. Others.

Answer 502

Only the follicles that reach the right size at the right stage to respond to FSH The other cells undergo atresia

Answer 503

Ovaries depleted of follicles. Decline of oestrogen production. Gradual decline with fluctuation over a few years. Gradual rise of FSH and LH (lack of negative feedback mechanism). Age of menopause decided by the size of the primordial pool.

Answer 504

Increased risk of mortality. Risk of cognitive dysfunction. Heart disease. Mood and sexual disorders. Bone mineral density. Autoimmune and thyroid disease. UK Guidelines on management.

Answer 505

Above 45 years: symptoms are usually enough 40 y - 45 y : Symptoms +/- Tests (incl. antral follicle count, anti-mullerian hormone) < 40 Years: careful !

Answer 506

80% for 4 years, 10% up to 12 years! Short term - Symptoms: -Vasomotor. -Psychological. -Urogenital. -Skin. Long term - Risks: -Osteoporosis. -Cardiovascular disease.

Answer 507

Hot flushes. Sweats: mainly night. Palpitations. Headaches.

Answer 508

Irritability. Lethargy. Emotional lability. Forgetfulness. Loss of libido. Loss of concentration

Answer 509

Urogenital: Vaginal dryness. Dyspareunia: due to dryness. Urethral syndrome: mainly later on in the absence of HRT. Skin: Dryness of skin and hair. Brittle nails.

Answer 510

Decreased amount of bony tissue per unit volume of bone. Wrist, femoral neck and vertebrae. Bone remodelling is uncoupled. Exact aetiology not known. 5% loss of trabecular bone per year.

Answer 511

Race: European and Asian women. Nulliparity. Low body weight. Poor diet in childhood. Alcohol abuse. Heavy smoking. Steroids, thyrotoxicosis, hyperparatyhroidsm, Cushing disease etc.

Answer 512

Protected before menopause but risk is equal to men by age 70 Cause unknown. Family history is a determinant factor. Other variables: obesity, diabetes etc

Answer 513

HRT (ERT) Women's Health Initiative (2002) and Million Women Study (2003) Sedatives and tranquilisers. Clonidine. Beta blockers. Maintaining pre-menopausal sexual activities. Calcium, vitamin D, calcitonin. Symptomatic treatment

Answer 514

Oestrogen Progestogen if uterus intact: to reduce risk of endometrial cancer. Different formats. Different doses. Risks. Contraindications. Preparations- Oral, Skin patches, Vaginal cream, Skin cream, Nasal spray, Vaginal ring., Implants.

Answer 515

Cardiovascular (E): - Slight increase in CVS (oral vs transdermal) - IHD no increased risk but no benefit Breast cancer (E + P vs E): Increased by 2 per 1000 if taken for >5 years. 6/1000 for 10 years use. 12/1000 for 15 years use. VTE: 1-3 in 10,000 women in the first year. Cancer: Slight increase in ovarian cancer (seq. HRT). Endometrial Cancer: if unopposed E2.

Answer 516

Abnormal liver function. Obstetric cholestasis. Thromboemblic disease. Congenital dist. of lipid metabolism. Hormone dependent tumours. Sickle cell anaemia

SUGER 🍦🍧🍨🍩🍪🎂🍭🍬🍫 Flashcards

(552 cards)