SUGER Flashcards
What is the equation for pH? What is the normal range?
- pH = -log10[H+]
- Normal range of pH = 7.35-7.45
What do these terms mean:
- Base
- Acid
- Base excess
- Standard base excess
- Acidosis
- Alkalosis
- Acidemia
- Alkalemia
- Base = accepts H+ ions
- Acid = donates H+ ions
- Base excess = quantity of acid required to return plasma pH back to normal
- Standard base excess = quantity of acid required to return ECF back to normal
- Acidosis = blood more acidic than normal
- Alkalosis = blood more alkaline than normal
- Acidemia = low blood pH
- Alkalemia = high blood pH
What is the anion gap? What does a wide anion gap mean? What does a narrow anion gap mean?
- Anion gap = the difference between measured anions (negative) and cations (positive)
- Anion gap = [Na+] + [K+] - [Cl-] - [HCO3-]
- Normal = 10-16
- Wide anion gap (low anions) = acidosis
- Narrow anion gap (high anions) = loss of GI HCO3- leading to compensatory Cl- reabsorption = high Cl-
What is the aim of urinary buffers? What are the two types? Where do these take place?
- Urinary buffers aim to add alkalinity to the blood
- 2 types = phosphate and ammonium
- Take place in proximal tubule
What does the urinary phosphate buffer do?
- Tissues are constantly respiring, dumping CO2 into the blood to make it acidic
- Alkaline phosphate (HPO4 2-) = commonest urinary buffer
- When all the carbonate reabsorption has finished ( HCO3- + H+ = H2CO3), H+ needs to bind to something else to be excreted
- Another source of alkaline to enter the blood needs to be established - this is HPO4 2-
- H+ excreted from dissociation of H2CO3 combines with HPO4 2- to form H2PO4 2-, which is then excreted in urine
What does the ammonium urinary buffer do?
- Tubular cells, mainly those of the proximal tubule, take up glutamine both from the glomerular filtrate + peritubular plasma and metabolise it to form NH3 (ammonia) and HCO3- (bicarbonate)
- HCO3- moves into blood, alkalising the blood plasma
- NH3 reacts with H+ and is excreted into the lumen and then excreted as waste
What is respiratory acidosis? What are the causes?
- Respiratory acidosis = buildup of CO2 = decreased blood pH
- Causes:
- Hypoventilation
- COPD
- Respiratory failure (type 1, e.g. pulmonary embolism and type 2, e.g. hypoventilation)
What is respiratory alkalosis? What are the causes?
- Respiratory alkalosis = excess loss of CO2 = increases blood pH
- Causes:
- Hyperventilation
- Hypoxia (no O2 going in then no CO2 being made)
- Respiratory failure (type 1, e.g. pulmonary embolism)
What is metabolic acidosis? What are the causes?
- Metabolic acidosis = excess H+ production
- Causes:
- Renal failure
- Diarrhoea (carbonate loss)
- Low aldosterone (Addison’s disease) = less Na+/H+ pump activity. Respiratory compensation = increasing respiration = lower CO2 = less acid
What is metabolic alkalosis? What are the causes?
- Metabolic alkalosis = increase in blood pH
- Causes:
- Vomiting (loss of H+)
- High aldosterone. Respiratory compensation = reducing respiration = CO2 retention = more acidity
What happens to pH, HCO3- and pCO2 levels in respiratory and metabolic acidosis/alkalosis?
Which part of the mesoderm develops into the genito-urinary system?
Intermediate mesoderm (smaller orange circle)
What are the three overlapping kidney systems that develop from the intermediate mesoderm? Where are they found?
- Pronephros = cervical region
- Mesonephros = thoracic and lumbar
- Metanephros = permanent kidney (one we are born with), develops in pelvis
What happens to the pronephros, mesonephros and metanephros?
- Pronephros = non-functioning, lasts from weeks 4-5
- Mesonephros = may function for short period, develops in week 4 and has duct connecting it to cloaca in males
- Metanephros = permanent kidney
What does the mesonephros comprise? What does the duct form? Is this different in females?
- Comprises a ridge and a duct
- Mesonephric duct (Wolffian duct) will form the vas deferens in males - this disappears in females
- Mesonephric duct ends in cloaca
- Bladder forms from the cloaca
What is the ureteric bud a protrusion from? What does it form?
- Ureteric bud is a protrusion from the mesonephric bud
- Ureteric bud forms the collecting ducts and ureter
Which two sources does the metanephros develop from?
- Metanephric blastema = develops from blastema and gives rise to excretory units
- Ureteric bud
What happens when the ureteric bud enters the blastema?
It divides and dilates, forming the primitive renal pelvis. It repeatedly divides to form the minor and major calyces
Why does the kidney shift to a more cranial position in the abdomen?
- Diminution of body curvature and growth of lumbar + sacral regions
Where are the bladder and urethra ultimately derived from? What is this structure divided into?
- Bladder and urethra ultimately derived from cloaca - a hindgut structure that is a common chamber for gastrointestinal and urinary waste
- In the 4th-7th weeks of development, the cloaca is divided into two parts by the uro-rectal septum:
- Urogenital sinus (anterior)
- Anal canal (posterior)
What are the three parts of the urogenital sinus? What do these form?
- Upper part = forms bladder
- Pelvic part = forms entire urethra, some of the reproductive tract in females, and prostatic and membranous urethra in males
- Phallic forms part of the female reproductive, and the spongy urethra in males
How are the glands of the prostate formed?
Epithelium of prostatic urethra proliferate and form a number of outgrowths that penetrate the mesenchyme and form the glands of the prostate
Where do both the male and female gonads derive from embryologically? Are the primordial gonads differentiated at 6 weeks?
- Male and female gonads derive embryologically from the UROGENITAL RIDGE
- Up until the 6th week of uterine life, primordial gonads are UNDIFFERENTIATED
Before the functioning of the fetal gonads, the undifferentiated reproductive tract includes a double genital duct system comprised of what?
- Wolffian ducts
- Müllerian ducts
In a genetic male, what happens at 7 weeks?
- Males = XY
- A gene on Y chromosome called SRY gene is expressed in the urogenital ridge cells
- Promotes testis-determining factor
- Genital ridge develops into testis
- Leydig cells secrete testosterone
- Wolffian (mesonephric) duct development = epididymis, vas deferens, seminal vesicles, ejaculatory duct
- Sertoli cells secrete Müllerian-inhibiting factor
- Degeneration of Müllerian duct
In a genetic female, what happens at 7 weeks?
- Female = XX = absence of Y chromosome
- No gonadal hormone influence
- Genital ridge develops into ovarian tissue by default
- Absence of testosterone
- Wolffian ducts degenerates
- Absence of Müllerian-inhibiting factor
- Müllerian glands develop
What are the three layers of the skin?
- Epidermis
- Dermis
- Subcutaneous tissue
What are the functions of the skin?
- Barrier to infection, e.g. mast cells in dermis
- Thermoregulation, e.g. subcutaneous fat = insulation, eccrine sweat glands = heat loss
- Protection against trauma, e.g. stratified epithelium helps resist abrasive forces, fat in subcutis acts as a shock absorber
- Protection against UV light, e.g. melanin (same amount of melanocytes in black people, more melanin)
- Vitamin D synthesis, e.g. 7-dihydrocholesterol converted to previtamin D3 by UVB
- Regulate H2O loss
Where does normal proliferation of the skin occur? Where is the basal layer found?
- Basal layer
- Epidermis (outermost layer)
What are the 5 layers of the epidermis? What are their functions?
- Corneum = dead keratinised cells
- Lucidum = dead cells containing keratohyalin
- Granulosum = keratohyalin + protein envelope, cells begin dying
- Spinosum = keratin fibres and lamellar bodies
- Basale = mitotic cells migrate up to spinosum
What is the outermost layer of the epidermis? What is the stratum corneum made up of? What are the functions of these cells? What happens if we see a decreased number of these cells?
- Outermost layer = stratum corneum
- Made up of corneo-desmosomes and desmosomes
- Corneo-desmosomes keep the corneocytes together
- Increased numbers of corneo-desmosomes seen in psoriasis = thickening of stratum corneum
- Decreased numbers of corneo-desmosomes seen in atopic eczema = thinning of stratum corneum = increased risk of inflammation
What does healthy skin contain? What is desquamation?
- Filaggrin produces natural moisturising factor (NMF)
- Corneocytes filled with NMF, this helps maintain skin’s hydration
- NMF also maintains acidic environment at stratum corneum
- In order to balance the introduction of new cells in basal layer, mature corneocytes are shed from the surface of the stratum corneum = desquamation
What is the brick wall model of the skin?
- Skin barrier can be explained by brick wall model, whereby corneocytes are bricks, the corner desmosomes are the iron rods and lipid lamellae is the cement
- Lipid lamellae:
- Keeps water inside the cells
- Irritants and allergens bounce off surface of skin
- Stratum corneum:
- Barrier to penetrating allergens and irritants
- Prevents water loss
- Vitamin D:
- Produces anti-microbial peptides for defending skin from bacteria and viruses
What are irritants and allergens? What happens when allergens penetrate the skin?
- Irritants = break down healthy skin
- Allergens = trigger skin flare ups by penetrating the skin and causing skin to react
1. Allergens penetrate through the skin
2. Meet lymphocytes
3. Lymphocytes release chemicals
4. Chemicals induce inflammation
What are the three signs of inflammation? What are the reasons for these?
- Red skin = lymphocyte activity causing dilation of blood vessels
- Itchy skin = stimulation of nerves
- Dry skin = skin cells leaking, no H2O retention (due to lymphocyte activity)
What is the normal skin pH and why? What happens if pH is increased?
- Normal skin pH = 5.5, allows proteases to remain on skin hence enabling balance of new cells from basal layer = desquamation
- Affect of increased pH:
- Profilaggrin and filaggrin not present = lack of NMF = less H2O retention in corneocytes
- This means pH will increase = damages corneodesmosomes = damages skin barrier = breakdown of skin barrier = increased risk of infection
How does acne form?
- Hypercornification of stratum corneum occurs = corneodesmosomes block entrance to hair follicles
- Results in increased sebum production from sebaceous glands = greasy skin
- Some sebum trapped in narrow hair follicles
- Sebum stagnates in pit of hair follicle where there is NO OXYGEN
- Provides anaerobic conditions = perfect for bacterial growth (p. acnes)
- P. acnes breaks down triglycerides in sebum into free fatty acids resulting in irritation, inflammation and attraction of neutrophils = pus formation and further inflammation as hair follicle gets filled with attracted neutrophils
What are some triggers for acne?
- Cosmetics
- Oily hair gel
- They plug hair follicles and trigger acne process = cosmetically induced acne
What is the SRY gene important for? What happens when we do/do not have it?
- SRY gene provides instruction for making a Y protein, involved in male sexual development
- Presence of SRY gene causes the bipotential gonad to differentiate into the male reproductive organs
- SRY +ve = Müllerian duct regresses, Wolffian duct forms male genitals
- SRY -ve = Wolffian duct regresses, Müllerian duct forms female genitals
What happens when we have the SRY gene on the Y chromosome?
- Testis-determining factor –> testes –> Leydig cell –> testosterone
- Sertoli cell –> Müllerian inhibiting factor –> degeneration of Paramesonephric (Müllerian) duct –> Wolffian duct forms male genitals
What happens in each stage of meiosis?
- Prophase I = chromosomes condense, nuclear envelope breaks down, homologous chromosomes pair up, crossing over occurs
- Metaphase I = pairs of homologous chromosomes, move to the equator of the cell
- Anaphase I = homologous chromosomes move to the opposite poles of the cell
- Telophase I = chromosomes gather at the poles of the cells
- Cytokinesis = cytoplasm divides
- Prophase II = a new spindle forms around the chromosomes
- Metaphase II = chromosomes line up at the equator
- Anaphase II = centromeres divide, chromatids move to the opposite poles of the cells
- Telophase II = nuclear envelope forms around each set of chromosomes
- Cytokinesis = cytoplasm divides
What are germ cells?
Germ cells = specialised, develop into gametes
What is oogenesis? What are the stages of oogenesis?
- Oogenesis = differentiation of the ovum (egg cell) into a cell component to further develop when fertilised
- In early foetal development, primitive germ cells (oogonia) undergo numerous mitosis divisions. At around month 7, foetal oogonia stop dividing. During foetal life, all oogonia differentiate to primary oocytes, before entering meiosis arrest at metaphase 1 - differentiation resumes after puberty
- Oogonia –> 2x primary oocytes (meiosis I begins in utero, before 12 weeks, and arrests at metaphase I until puberty) –> secondary oocytes –> ovum (each primary oocytes produces one ovum and one non-functional polar body)
What is micturition? What is incontinence?
- Micturition (urination) is the process of urine excretion from the urinary bladder
- Incontinence = complaint of any loss of urine
What is needed for normal lower urinalysis tract function?
- Urine storage = low pressure, with perfect continence
- Urine emptying = periodic complete urine expulsion, at low pressure, when socially convenient
Where is urine stored? What is the stress-relaxation phenomenon?
- Urine stored in bladder (detrusor muscle)
- Stress-relaxation phenomenon = as the bladder fills, the rugae distend + constant pressure in the bladder (intra-vesicular pressure) is maintained
Is the passing of urine under sympathetic or parasympathetic control? How does mictuition work?
- Passing of urine is under parasympathetic control
- Bladder fills with urine, stretch receptors activated
- Afferent neurones from these receptors enter the spinal cord and stimulate the parasympathetic neurones (pelvic splanchnic nerve S2-S4) which then cause detrusor muscles to contract via pontine micturition centre
- This change in bladder shape pulls open the internal urethral sphincter
- The afferent input also inhibits sympathetic neurones (hypogastric nerve T1-L2) to the internal urethral sphincter. It also inhibits somatic motor neurones (peudendal nerve S2-S4) to the external urethral sphincter causing CONSCIOUS REDUCTION in voluntary contraction
- Results in opening of both sphincters + contraction of detrusor muscles is able to produce URINATION
In what structure are the spermatozoa produced? What is ejaculate a mixture of?
- Spermatozoa are produced in the testis
- Ejaculate is a mixture of spermatozoa and seminal fluid
What are spermatogonia? What are the three types?
- Spermatogonia = undifferentiated germ cells that begin to divide mitotically at puberty. Type A + Type B
- Type A:
- Dark (Ad) = stem cells that stay outside blood-testis barrier + produce more daughter cells until death
- Pale (Ap) = mature into type B cells
- Type B = differentiating progenitor cells with spherical nuclei + densely stained masses of chromatin - these differentiate into primary spermatocytes
What are the three nerves involved in micturition? At which vertebral level are they found?
- Oel
What is the pathway of spermatogonia to spermatozoa?
- Type B spermatogonia –> primary spermatocytes –> pass through blood-testis barrier (through tight junctions of Sertoli cells, which open in front of them and form new tight junctions behind them) –> enter central compartment –> meiosis I –< 2x secondary spermatocytes –> meiosis II –> 4x spermatids –> spermiogenesis + differentiation –> spermatozoa
What is spermiogenesis?
Spermiogenesis is the final stage of spermatogenesis, involving the maturation of spermatids into mature spermatozoa
What happens to the spermatids in spermiogenesis to become spermatozoa?
- Grow a tail (flagellum; contractile filaments that have whip-like movements to propel the sperm at velocity) and midpiece (many mitochondria to provide energy for movement)
- Discard excess cytoplasm to become lighter
- Acrosomal vesicle becomes acrosome; a protein-filled vesicle containing enzymes to penetrate the oocyte, allowing fertilisation to occur
What is the pathway of sperm? What is the acronym for this?
- SREEVE UP
- Seminiferous tubules
- Rete testis
- Efferent ducts
- Epididymis
- Vas deferens (+ seminiferous tubules)
- Ejaculatory duct
- Urethra
- Penile urethra
What do the hormones oestrogen, progesterone and hCG do? How do these change throughout pregnancy?
- Oestrogen = regulates levels of progesterone, prepares the uterus for baby (stimulates growth of uterine mass), prepares the breasts for lactation, induces synthesis of receptors for oxytocin. First 2 months = supplied by corpus luteum, then by placenta
- Progesterone = prevents miscarriage, builds up endometrium for support of placenta, inhibits uterine contractility - so foetus is not expelled prematurely. Increases throughout pregnancy, first 2 months = supplied by the corpus luteum
- Human Choroinic Gonadotrophin (hCG) = stimulates oestrogen/progesterone production by ovary, pregnancy test hormone - diminishes once the placenta is mature enough enough to take over oestrogen/progesterone production
What do the hormones prolactin, relaxin, oxytocin and prostaglandin do? What happens to them throughout pregnancy?
- Prolactin = increases cells that produce milk, prevent ovulation. Produced by anterior pituitary gland. After birth, oestrogen and progesterone levels decrease, allowing prolactin to stimulate milk production
- Relaxin = helps limit uterine activity, softens cervix + involved in cervical ripening for delivery. Produced by ovary + placenta. High in early pregnancy
- Oxytocin = triggers ‘caring’ reproductive behaviour, responsible for uterine contractions during pregnancy + labour
- Prostaglandins = tissue hormones - role in initiation of labour. PGF2a = main one (PGE2 is 10x more powerful)
What does the primordial follicle develop into?
Primordial follicle –> small primary follicle –> secondary follicle –> pre-ovulatory (a trial) –> ovulation –> luteinsation –> corpus luteum –> luteolysis/regression of follicle
What is the menstrual cycle? What are the two phases?
- Menstrual cycle = an important physiological process of ovulation (egg released from ovaries to be fertilised) and menstruation (period, bleeding that occurs after ovulation if not pregnant) in women
- Follicular or proliferative phase = occurs after menstruation; follicle maturation into an egg
- Luteal or secretory phase = thickening and subsequent shedding of uterine lining
- Ovulation is the release of an ovum from one of the ovaries, occurs between these phases
What are the three phases of the uterine cycle?
- Menses
- Proliferative
- Secretory
Where does fertilisation occur? What happens at fertilisation?
- Occurs at the ampulla of the Fallopian tube
- 4-7 hours after gamete fusion, the 2 sets of haploid chromosomes form the male and female pronuclei
- These then undergo syngamy (fusion of the male and female pronuclei):
- Male and female pronuclei migrate to centre
- Haploid chromosomes synthesise DNA in preparation for first mitotic divisiom
- Pronuclear membranes break down
- Mitotic metaphase spindles form
- 46 chromosomes organise at the spindle equator
When does implantation occur? When does the embryo reach the uterus?
- Implantation occurs at day 21 of the menstrual cycle
- Embryo reaches the uterus at day 5/6
What are the stages of implantation?
- Apposition (unstable adherence of blastocyst to uterine lining)
- Attachment (endometrial epithelial cells + trophoblast cells connect via integrins, causing a strong adhesion)
- Trophoblast differentiation
- Invasion
- Maternal recognition
C
B
D
D
C
E
C
What are the 7 functions of the kidney? What is the acronym for this?
- AWETBED
- Acid-base balance
- Water removal
- EPO
- Toxins
- BP
- Electrolyte
- Vitamin D activation
What is the basic unit of the kidney? In which parts of the kidney are these found?
- Nephron = basic unit of the kidney
- Millions of nephrons in the cortex + medulla:
- Renal corpuscle (glomerulus within Bowman’s capsule) = filter
- Proximal convoluted tubule = for reabsorbing solutes
- Loop of Henle = for concentrating urine
- Distal convoluted tubule = for reabsorbing more water and solutes
- Collecting duct = for reabsorbing water + controlling acid-base + ion balance
What is the cardiac output in L/min? What is the renal blood flow? How about urine flow?
- Cardiac output = 5L/min
- Renal blood flow = 1L/min
- Urine flow = 1ml/min
What is the pathway of the renal artery to the glomerular and peritubular artery?
Renal artery –> interlobar artery –> arcuate artery –> interlobular artery –> afferent arteriole –> (nephron) glomerular capillary and peritubular capillary
What is glomerular filtration?
Passage of fluid from the blood into Bowman’s space to form the filtrate
What does the filtration barrier of the glomerulus consist of?
- Endothelium - fenestrated
- Glomerular basement membrane - T4 collagen, -ve charge
- Epithelium - podocytes with foot processes
What can and can’t pass through the filtration barrier?
- Small molecules + ions up to 10kDa can pass freely, e.g. glucose, uric acid, potassium, creatinine
- Larger molecules increasingly restricted
- Fixed negative charge in glomerular basement membrane repels negatively charged anions
What is the glomerular filtration rate (GFR)? How is it calculated? What is the average GFR in a 70kg person?
- The volume of fluid filtered from the glomerulus to the Bowman’s Space per unit time
- GFR = Kf (Pgc - Pbs - Pi gc)
- In a 70kg person the average GFR = 125ml/min
What are the factors affecting GFR?
- Blood pressure = increase in BP –> increased hydrostatic pressure –> increase in GFR
- Size of substance = albumin + all that is attached (lipophilic molecules) to it is unable to cross
- Charge of substance = BM is negatively charged, repels other -vela charged substances, e.g. albumin
- Attachment to protein = albumin
- Capillary permeability
- Surface area
What do we use to measure GFR and why? Which substance do we use clinically?
- Use of a marker substance: free filtered (not attached to large proteins), not metabolised + not secreted/reabsorbed
- Amount excreted per minute = amount filtered per minute
- GFR = Um (concentration of marker substance in urine) x urine flow rate / Pm (concentration of marker substance in plasma)
- Clinically: CREATININE (muscle metabolite)
How do we calculate filtration fraction?
Filtration fraction = GFR / renal plasma flow
What is renal clearance? How is this calculated?
- Volume of plasma from which a substance is completely removed by the kidney per unit time
- Marker substance is freely filtered at the glomerulus + is neither reabsorbed nor secreted in the tubule, so all the marker substance that is filtered will end up in the urine, no more (as it is not secreted) and no less (as it is not reabsorbed)
- Clearance = urine concentration x urine volume / plasma concentration
What happens in the proximal convoluted tubule? What are the cells lined by?
- 2/3 of all filtrate reabsorbed = the cells have lots of mitochondria as they actively transport ions from the glomerular filtrate
- BULK reabsorption of NaCl, proteins, polypeptides, amino acids + glucose
- Longest of all the tubules, has microvilli
- Composed of cuboidal epithelium
What happens in the loop of Henle? In which nephrons are these found? What are the two cell types lined by?
- 2 parts: descending and ascending
- Descending: H2O reabsorption (impermeable to ions)
- Ascending: Na+, K+ and Cl- reabsorption, has thin (simple squamous epithelium) + thick (low cuboidal) part
- Found only on juxtamedullary (15%) nephrons (cortical (85%) nephrons do not extend into medulla
What happens in the distal convoluted tubule? What is the macula densa? What shape are its cells?
- Fine tuning, absorption of solutes - beginning to concentrate the urine. Acidified the urine by secreting H+ ions into it
- Exchanges urinary Na+ for body K+, this effect is mediated by aldosterone
- Macula densa = detects Na+ concentration. If low (indicator of low GFR) –> sends signals to release renin –> RAAS –> increase in BP –> increase GFR
- Cells are cuboidal and contain mitochondria
What happens in the collecting duct? What are the two cell types and what do they do? What are the cells lined by?
- Acid secretion and concentration of urine, hormones such as aldosterone and ADH act here
- 2 cells:
- Principal cells (respond to aldosterone = exchanging Na+ for K+ and ADH = increasing water reabsorption)
- Intercalated cells (responsible for exchanging acid for base). Alpha intercalated cells secrete acid, beta intercalated cells secrete bicarbonate
What are the endocrine glands?
- Hypothalamus
- Pituitary
- Thyroid
- Parathyroids
- Adrenals
- Pancreas
- Ovary
- Testes
What are the functions of:
- Thyroid
- Parathyroid
- Cortisol
- Aldosterone
- Catecholamines
- Oestradiol
- Testosterone
- Insulin
- ANP
- Vitamin D
- Basal metabolic rate, growth
- Ca2+ regulation
- Glucose regulation, inflammation
- BP, Na+ regulation
- BP, stress
- Menstruation, femininity
- Sexual function, masculinity
- Glucose regulation
- Na+ regulation
- Ca2+ regulation
What are the anterior pituitary hormones? What are their actions?
- Remember FLAGTOP:
- FSH = follicle stimulating hormone, reproductive control
- LH = luteinizing hormone, reproductive control
- ACTH = adrenocorticotropic hormone, regulation of adrenal cortex
- GH = growth hormone, growth and metabolism
- TSH = thyroid stimulating hormone, thyroid hormone regulation
- Melanocyte stimulating hormone
- Prolactin
What are the posterior pituitary hormones? What do they do?
- ADH = anti diuretic hormone, water regulation
- Oxytocin = breast milk expression
Which of the anterior and posterior pituitary produces its own hormones?
- The anterior pituitary produces and releases its own hormones, under the regulation of hormones made by the hypothalamus
- The posterior pituitary stores and releases hormones produced by the hypothalamus
What is homeostasis? What is the difference between a positive feedback loop and a negative feedback loop?
- Homeostasis = the maintenance of a constant internal environment, in response to changes in external environment
- Positive feedback loops = feedback mechanism resulting in the growth/amplification of the output signal, e.g. oxytocin in children, clotting cascade
- Negative feedback loops = feedback mechanism resulting in the inhibition/slowing down of a process - how to the body maintains homeostasis, e.g. thermoregulation, blood pressure regulation (RAAS)
Diagram of the thyroid gland and its surrounding blood vessels.
Where is the thyroid gland located? How many lobes does it have? Which cells does it consist of? Which 3 hormones does it secrete?
- Located in neck
- Consists of two lobes connected by isthmus
- Consists of follicular and parafollicular cells
- Secretes T4 (thyroxine), T3 (triiodothyronine) and calcitonin
What does the thyroid gland regulate?
- Breathing
- Heart rate
- Central and peripheral nervous system
- Body weight
- Muscle strength
- Menstrual cycles
- Body temperature
- Cholesterol levels
Draw out the control of thyroid hormone secretion.
Explain thyroid hormone synthesis.
- TSH binds to TSHR
- Iodide uptake in thyrocytes by the sodium-iodide symporter (NIS)
- Transported at the apical membrane into the follicular lumen, and oxidised by thyroperoxidase (TPO)
- Results in formation of mono- and diiodotyrosines
- Iodotyrosines are subsequently coupled by TPO to form thyroxine (T4) and triiodothyronine (T3). MIT + DIT = T3, DIT + DIT = T4
- Hydrolysed in lysosomes and T4, T3 are released into the bloodstream
What happens to thyroid hormone in the blood?
- T3 + T4 bind to thyroxine-binding globulin (TBG); not soluble in plasma
- The active form of hormone is the free form - needs to dissociate from TBG
- T3 is about 10x more active than T4
- T4 converted to T3 in peripheral tissues by 5’-deiodinase
- Roles: increases BMR, body temperature, appetite, promotes metabolism of nutrients, neural/muscular development, female reproductive system
What are the signs and symptoms of hyperthyroidism?
What are the signs and symptoms of hypothyroidism?
What is the role of the parathyroid glands? What do they secrete?
- Regulate calcium and phosphate levels
- Secrete parathyroid hormone (PTH) in response to low calcium or high phosphate
What is calcitonin produced by? What is it released in response to?
- Produced by thyroid c-cells (parafollicular)
- Calcitonin released in hypercalcaemia, inhibits bone resorption
What is the HPA axis?
HPA axis is the hypothalamo-pituitary-adrenal gland axis. It demonstrates the process leading up to the release of cortisol from the adrenal gland
In the HPA axis, what do the hypothalamus, anterior pituitary and adrenal gland secrete?
- Hypothalamus = CRH (corticotropin releasing hormone)
- Anterior pituitary = ACTH (adrenocorticotropic hormone)
- Adrenal gland = cortisol (stimulates gluconeogenesis, activates anti-inflammatory pathways)
Which layer of the adrenal cortex is responsible for the secretion of cortisol?
- Zona fasciculata
- Outermost zona glomerulosa secretes mineralocorticoids, e.g. aldosterone, and innermost later zona reticularis secretes androgens (sex hormones), e.g. dehydroepiandrosterone (DHEA)
What principle do other hormonal axes share?
Share the same principle as HPA axis. Learn this
Draw out the hypothalamo-pituitary-testes axis.
Draw out the hypothalamo-pituitary-ovarian axis.
What is testosterone? What is dihydrotestosterone?
- Testosterone is the primary male androgen, involved in sexual development, fertility, muscle formation, body composition, bone health and cognitive function
- Dihydrotestosterone is an androgen hormone that stimulates the development of male characteristics, it is formed from testosterone via 5-alpha-reductase
Which androgen is more potent?
Dihydrotestosterone is more potent than testosterone and is involved in hair follicles, prostate, development, sebum production (skin) and development of external genitalia
What are some important determinants of growth?
- Parental phenotype and genotype
- Quality and duration of pregnancy
- Nutrition
- Specific system and organ integrity
- Psycho-social environment
- Growth promoting hormones and factors
Draw out the hormone axis for GH secretion.
What influences GH secretion?
Which factors influence puberty?
What are the physiological changes associated with periods as age increases?
- Menarche = first menstrual period
- Pre-menopause = increasing irregularity in frequency and flow rate of menstrual cycle
- Peri-menopause = onset of symptoms: hot flushes, mood swings, anxiety, vaginal dryness, night sweats, breast tenderness, insomnia, fatigue
- Menopause = last menstrual period
- Post-menopause = hot flushes, mood swings, anxiety, night sweats, breast tenderness, insomnia and fatigue generally cease. Vaginal dryness remains. Risk of osteoporosis and heart disease
Why does the risk of osteoporosis and heart disease increase post-menopause?
Due to a lack of protective oestrogen
Are adrenal glands intraperitoneal or retroperitoneal? What are the three arteries supplying them? What are the two veins draining them? What is their innervation?
- Retroperitoneal
- Arterial supply:
- Superior adrenal artery
- Middle adrenal artery
- Inferior adrenal artery
- Venous drainage:
- Right adrenal vein –> IVC
- Left adrenal vein –> left renal vein
- Innervation = splanchnic nerve
What are the two parts of the adrenal glands?
- Cortex
- Medulla
What are the five main hormones secreted by the adrenal cortex?
- Aldosterone
- Cortisol
- Corticosterone (mineralocorticoids and glucocorticoids are types of corticosteroids)
- DHEA (dehydroepiandrosterone)
- Androstenedione
What are the three layers of the adrenal cortex? What do they secrete?
- Zona glomerulosa –> mineralocorticoids
- Zona fasciculata –> cortisol and small amounts of androgens
- Zona reticularis –> androgens and small amounts of cortisol
What does the adrenal medulla secrete?
Catecholamines:
- Adrenaline
- Noradrenaline
What is the precursor to all corticosteroids?
Cholesterol
What do the hormones secreted by the medulla further stimulate? What are they controlled by? What is the response to stress?
- Hormones secreted by medulla
- Controlled by sympathetic nervous system
- Response to stress:
- Increased HR
- Inhibit insulin release
- Increased glycogenolysis
- Increased lipolysis
- Dilates pupil
- Increased sweating
Where are mineralocorticoids secreted from? What is their role? What is the most predominant mineralocorticoid produced?
- Secreted from zona glomerulosa
- Role is to regulate electrocytes
- Aldosterone = most predominant one, due to the presence of aldosterone synthase
What are the functions of aldosterone?
- Maintains salt balance
- Blood pressure –> RAAS
- Afferent arterioles of kidney containing juxtaglomerular cells –> renin release –> triggers aldosterone release
Will problems with the pituitary or hypothalamus affect aldosterone release?
No, but problems with the kidney will
Where are glucocorticoids secreted from? What is their role? What is the predominant glucocorticoid? What is stress?
- Glucocorticoids = important effects on glucose metabolism
- Secretes cortisol in response to stress and low blood glucose levels
- Cortisol is the predominant glucocorticoid in humans
- Stress = threat to homeostasis
What is the function of cortisol under normal circumstances? What happens in the absence of cortisol?
- Maintaining homeostasis in the absence of external stress:
- Maintaining normal BP
- Maintain blood glucose levels (HbA1c)
- Inhibit inflammation
- Controls cell damage
- Decreases capillary permeability, suppresses growth and function of immune cells
- In the absence of cortisol, the immune system may overreact to minor infections
What is the function of cortisol in foetal/neonatal life?
- Acts as a developmental hormone:
- Essential for surfactant production (reduce lung inflation making it easier for lungs to inflate)
- Responsible for proper differentiation of tissues and glands inc. adrenal medulla, intestines, lungs, brain
What is the stress function of cortisol?
- Increases organic metabolism and uses these energy sources to increase plasma concentrations of amino acids, glucose, glycerol, and free fatty acids
- Amino acids: provide source of glucose via hepatic gluconeogenesis, and a source for tissue repair if injury occurs
- Increases vasoconstriction in response to adrenaline to improve cardiovascular function
- Reduces inflammatory response to injury/infection: increased cortisol –> dampens effect on body’s immune responses –> protecting against possible damage as a result of inflammation
- Inhibits non-essential functions - reproduction, growth
What becomes decreased during chronic stress? What is this a result of?
- Severe decreases in bone density
- Severe decreases in immune function
- Severe decreases in reproductive fertility
- Due to increased catabolism elicited by increased cortisol
What stimulates cortisol release during stress?
ACTH
Draw out the process for cortisol release during stress.
What is the majority of cortisol bound to? How about the rest?
- Majority bound to CBG (corticosteroid binding globulin) - 90%
- 5% - bound to albumin
- 5% free - only free cortisol is bioavailable
What is produced in the zona reticularis? What type of androgens do these androgens classify as?
- Dehydroepiandosterone (DHEA)
- Andosterone
- These are the adrenal androgens
Is DHEA a strong or weak androgen? What is function of androstenedione?
- DHEA: most abundant adrenal steroid, but weak androgen
- Androstenedione: major source of androgen in women
What is the role of adrenal androgens? What is the production of androgens in adrenal glands mediated by?
- Adrenal androgens = much less potent effect than testosterone, play less of a role in adult male but more of a role in females, can be converted to testosterone in peripheral tissue
- Production of androgens in adrenal glands are regulated by actions of ACTH secreted by the anterior pituitary
What are the receptors for mineralocorticoids, glucocorticoids, and androgens?
Where are catecholamines released from? What type of hormones are they? What are their functions? What are the three types of beta receptors used for?
- Catecholamines released from adrenal medulla
- Peptide hormones
- Functions:
- Gluconeogenesis
- Lipolysis
- Increased heart rate
- Alpha receptors in smooth muscle - vasoconstriction/dilation
- Beta receptors:
- Beta 1: amylase secretion
- Beta 2: bronchodilation
- Beta 3: lipolysis in adipocytes
What shape is the pancreas? What hormones does it secrete and from which cells?
- Pancreas is a long, slender organ
- Islets of Langerhans secrete glucagon (alpha cells = 20% of islet), insulin (beta cells = 75% of islet), somatostatin (delta cell = 4% of islet), and pancreatic polypeptide (PP cells)
What is the mechanism of insulin secretion?
What is the action of insulin at cells?
Mobilisation of GLUT-4
What is the physiological response to raised/lowered glucose?
What are the 3 ways that the kidney controls water and blood pressure?
- Regulation of osmolality - ADH
- RAAS system
- Atrial Natriuretic Peptide (ANP)
What is the action of ADH/vasopressin when there is a decrease in plasma volume? How about when their is excess H2O ingested?
- Where is ADH made?
- Which receptor does ADH bind to?
- Which segment of the nephron does ADH act on?
- Where are osmoreceptors located?
- ADH releases in response to?
- Hypothalamus
- V2R
- Principal cells in the collecting duct
- Hypothalamus
- Low plasma volume (high osmolality, lots of solutes)
Draw out the RAAS system.
Where is renin released from in response to what?
Renin released by juxtaglomerular cells in response to low renal perfusion (low BP)
Where is aldosterone released from?
Zona glomerulosa
What are the effects of angiotensin II?
- Aldosterone release
- ADH release
- Vasoconstriction
- Increased sympathetic activity
- Thirst
What does ANP do?
- Has the opposite function of aldosterone (aldosterone reabsorbed Na+, water follows resulting in an increase in BP)
- ANP is released when the atrial wall stretches too much (signifying the BP is way too high)
- ANP acts by:
- Blocking sodium channels in the collecting ducts
- Directly inhibiting aldosterone release via renin inhibition
- Vasodilation of the afferent arteriole increases GFR –> more sodium excretion
What happens happens to these hormones during pregnancy:
a) human chorionic gonadotropin (hCG)
b) oestrogen
c) progesterone?
a) peaks at 2 months then decreases
b) increases until delivery
c) increases until delivery but lower levels than oestrogen
What are the cardiovascular and respiratory changes that occur during pregnancy?
- Cardiovascular changes:
- Increased CO
- Decreased systemic blood pressure
- Decreased total peripheral resistance
- Increased uterine blood flow
- Increased blood volume
- Increased plasma and blood cell mass
- Varicose veins
- Respiratory changes:
- Increased alveolar ventilation
What are the gastrointestinal and skin changes that occur during pregnancy?
- Gastrointestinal changes:
- Increased acid reflux and gastroparesis (delayed emptying)
- Skin changes:
- Linea nigra
- Striae gravidarium
- Darkened areola of breasts
What are the biochemical changes that occur during pregnancy?
- Biochemical changes:
- Weight gain - maternal and fetoplacental. Obese women do not put on much weight during pregnancy since they have fat stores that can be mobilised to supply energy. Slim women do not have these fat stores, so put on more weight
- Increased protein and lipid synthesis, insulin resistance
How long does normal pregnancy last? What is parturition? What do smooth muscle cells synthesise throughout most of pregnancy?
- Normal pregnancy lasts 40 weeks
- Birth process = parturition
- Smooth muscle cells synthesise connexins (proteins that form gap junctions between cells) to allow coordinated contractions
What happens in prelabour?
- Maternal sign = oxytocin
- Foetal sign = oxytocin, vasopressin + cytokines
- Increased pressure on the cervix stimulates the release of prostaglandins (e.g. PGFa enhances action of oxytocin)
What is labour initiated by? What does this cause?
Initiated by PGFa –> increased action of oxytocin –> myometrial contraction –> increased pressure on cervix –> promotes further contraction –> continues (positive feedback mechanism)
What happens at the onset of labour? What happens to uterine contractions when labour begins?
- At onset, the amniotic sac ruptures, and the amniotic fluid flows through the vagina = ‘water breaking’
- When labour begins, uterine contractions become stronger and occur approximately 10-15 minute intervals, they begin in the upper portion and sweep downwards
- As contraction increases in intensity and frequency, cervix is gradually forced open (dilation) to a maximum diameter of 10cm
What are the stages of labour?
- Latent phase = little cervical dilation, lasts around 8 hours
- Active phase = organised uterine contractions and dilation, around 5 hours:
- Stronger, increased frequency, contractions + dilation, around 5 hours
- Full dilation = foetal expulsion (birth)
- Placental expulsion
- Poostpartum phase
What is cervical ripening? What happens to this process during the last 3 months of pregnancy and why? What is the uterus sealed by? What happens to the cervix during the last few weeks of pregnancy?
- Growth and remodelling of the cervix prior to labour
- Process accelerated during last 3 months of pregnancy due to presence of oestrogen
- During pregnancy uterus is sealed at outlet by firm, inflexible collagen fibres (cervix) - this is maintained by progesterone
- In the last few weeks of pregnancy - at the same time as the connexins form, the cervix becomes soft and flexible due to enzymatically mediated breakdown of collagen fibres
What are the three layers of the uterine wall?
- Perineurium = outermost serous layer; the visceral peritoneum
- Myometrium = the middle layer; interlacing layers of smooth muscle
- Endometrium = mucosal lining of the uterine cavity changes in thickness during menstrual cycle
What does the placenta take over from? What does it provide? How is it attached to the umbilical cord?
- Takes over from endometrial cells, which provide the first few weeks of nutrition
- Placenta provides nutrition, gas exchange, water removal, and endocrine and immune support
- Umbilical cord attachment = villus chorion –> umbilical vessels branch into chorionic vessels –> these anastomose
Which 5 hormones are released by the placenta? What do they do?
- hCG (human chorionic gonadotrophin) - supports corpus luteum
- hCS (somatotropin) - stimulates mammary development
- Progesterone + oestrogen - supports maternal endometrium
- Relaxin
How does the placenta develop?
- Morula –> blastocyst. Outer layer = primary trophoblastic cell mass (TCM) –> TCM invades endometrium which degenerates –> trophoblast contracts stroma –> implantation complete by 11th day post-ovulation
- By 5th week post-implantation, the placenta is well established
Where does the final stage of vitamin D activation occur? What is the active form of vitamin D?
- Kidneys
- 1,25 dihydroxyvitamin D is the active form of vitamin D
What is erythropoeitin produced by? What is it important for? What is an immature erythrocyte called? What happens if we have too mmany or too little erythrocytes?
- Produced by kidneys
- Essential for the maturation of erythrocytes in the bone marrow
- Immature RBC = reticulocyte
- Too little = anaemia, too many = viscous blood (polycythemia)
