SUGER Flashcards
1
Q
What are the 7 functions of the kidney?
A
- Waste product removal
- Excess fluid removal
- Balance salt, water, pH
- Control blood pressure
- Red blood cell production
- Healthy bone maintenance
- Removal of drugs
2
Q
A
3
Q
A
4
Q
A
5
Q
What is total cardiac output, renal blood flow and urine flow rate?
A
Cardiac output - 5L/min
Renal blood flow - 1L/min
Urine flow - 1mL/min
6
Q
A
7
Q
Label the blood flow of the kidneys up to efferent arteriole:
A
8
Q
Label the blood flow in the kidney after glomerular capillary:
A
9
Q
A
10
Q
A
11
Q
A
12
Q
What makes up the juxtaglomerular apparatus and where is it?
A
-Juxtoglomerular cells + macula densa
-It is a modified muscular layer of afferent arteriole in hillum of every glomerulus
13
Q
What is there an increased number of in the juxtaglomerular apparatus and what is special about them?
A
-Increased number of smooth muscle cells
-Thicker cells
-Less actin/mysoin but many granules containing renin
14
Q
What do juxtaglomerular cells and macula densa do?
A
-Act as barometers to changes in BP
-LOW BP = LESS DISTENDED WALLS = RENIN RELEASE
15
Q
A
16
Q
What kind of regulation is seen by the kidney in terms of its rate of processes?
A
-Autoregulation = intrinsic
-Maintains constant GFR (Glomerular Filtrate Rate) and excretion of water and waste products
17
Q
What two mechanisms are involved in the auto regulation of the kidney?
A
-Tubuloglomerular feedback
-Myogenic mechanism
18
Q
Label the tuboglomerular regulation in the kidney:
A
19
Q
What system does renal perfusion from the tuboglomerular autoregulation afffect?
A
RAAS system
20
Q
Describe the myogenic autoregulation in the kidneys:
A
-Decrease in BP does opposite
-ONLY PRE_GLOMERULAR RESISTANCE VESSELS
21
Q
What happens at the filtration barrier at the glomerulus?
A
Passage of fluid from the blood into Bowman space to form filtrate
22
Q
What is the distal part of the nephron responsible for?
A
Secretion and reabsorption
23
Q
Label this diagram of the renal filtration barrier:
A
24
Q
What are the 3 components of the renal filtration barrier?
A
25
Label this bit of the kidney:
26
What 5 factors determine filtration in the kidney?
-Pressure
-Size of molecule
-Charge
-Rate of blood flow
-Protein binding
27
What forces favour and oppose filtration in the kidney?
28
How does size affect filtration in the kidney?
-Small molecules and ions up to 10kDa can pass freely e.g. glucose, uric acid, potassium, creatinine
-Large molecules increasingly restricted e.b. plasma proteins
29
How does charge affect filtration in the kidneys?
-Fixed negative charge in GBM (glomerular basement membrane) (glycoproteins) repel negatively charged anions
30
How does rate of blood flow affect kidney filtration?
31
How does protein binding affect filtration in the kidney?
-Albumin has molecular weight of around 66kDa but is -ve so cannot easily pass through
-Filtered fluid is essentially protein free
-Tamm Horsfall protein in urine produced by tubule
-Affects drugs, calcium, thyroxine
32
What can damage to the kidney filtration barrier cause?
-Protein leak called nephrotic syndrome
-Immune conditions/genetic abnormalities
-Diabetes damages filtration barrier
33
What is the basic glomerular filtration rate equation?
34
What is the more complicated glomerular filtration rate equation?
35
What is glomerular filtration rate determined by (3)?
-Net filtration pressure
-Permeability of the filtration barrier
-Surface area available for filtration (approx 1.2-1.5m2 total
36
What two external things regulate the glomerular filtration rate?
-Sympathetic nervous system
-Hormones/autocoids
37
What is the innervation to afferent and efferent arterioles and their consequence?
38
What 6 hormones affect GFR?
39
how do each of these hormones affect GFR?
40
What two changes to afferent and efferent arterioles can increase GFR?
41
What two changes to afferent and efferent arterioles can decrease GFR?
42
Is GFR measured directly?
-NO
-Calculated using excretion marker (M)
-Usually creatinine (muscle metabolite and constantly produced)
43
What is the GFR indirect equation?
44
Properties of a good urine marker?
-Freely filtered
-Not secreted or absorbed
-Not metabolised
-ALL M FILTERED WILL END UP IN THE URINE, NO MORE AND NO LESS AS IT ISN'T SECRETED OR REABSORBED
45
Normal GFR?
125mL/min
46
What things can affect creatinine?
47
What is the gold standard marker for measuring GFR?
-Inulin
-Not very easily carried out
48
What terms are used for high and low blood pH?
Acidemia = low blood pH
Alkalemia = High blood pH
49
Label the main pH balance systems:
50
What are pH and HCo3- governed by?
pH and HCO3- are dependant variables governed by:
-pCO2
-Conc of weak acids(ATOT)
-Strong ion difference (SID)
51
What is the general Henderson-Hasselbach equation?
52
What is the Henderson-Hasselbach equation relating to acidosis?
53
What 6 things do we measure in relation to acidosis (ABG)?
54
What is the standard bicarbonate?
-Bicarbonate concentration standardised pCO2 5.3kPa and temp 37
-Measure of metabolic component of any acid-base disturbance
-“What would the bicarbonate be if the CO2 was normal?”
55
What is absolute bicarbonate affected by?
Respiratory and metabolic components
56
What is base excess?
-Quantity of acid required to return pH to normal under standard conditions
-Can be used to calculate bicarbonate dose to correct acidosis
57
What value does base excess have in what conditions?
Negative in acidosis, can be referred to as base deficit
58
What can acid-base disorders be classed into?
-Acidoses and alkaloses
-Respiratory (CO2 excretion change) or metabolic (changes in acid load, excretion or bicarbonate recycling)
-Can co-exist
59
What are clinical features of metabolic acidosis?
60
What is the anion gap?
-Difference between measured anions and cations
61
What three things can cause metabolic alkalosis?
62
What is the compensatory mechanism for metabolic alkalosis?
63
What is the mechanism of respiratory acidosis?
CO2 retention, leading to increased carbonic acid dissociation
64
What causes respiratory acidosis?
-Any cause of respiratory failure
-Comp mech – increased renal H+ excretion and bicarbonate retention
65
What is the mechanism of respiratory alkalosis?
CO2 depletion due to hyperventilation
66
What are the causes and compensation for respiratory alkalosis?
67
What questions are asked in a ABG interpretation?
68
Describe the proximal tubule cells and their processes:
-Active reabsorption of multiple solutes
-Metabolically active cells – lots of mitochondria
-Sodium gradient generated by Na/K ATPase
-Vulnerabe to hypoxia and toxicity
69
What is glycosuria?
-Defect in sodium glucose transporter 2 (SGLT2)
-Mechanism – failure of glucose reabsorption
70
What is cystinuria?
-Defect in renal basic amino acid transporter (rBAT)
-Mechanism – failure of cystine reabsorption, increased urinary cystine conc (stone formation)
71
Label this diagram of bicarbonate reabsorption:
72
What is proximal renal tubular acidosis?
Defect in Na/H antiporter
Mechanism – failure of bicarbonate reabsorption
73
What does the Loop of Henle do?
-Generates medullary concentration gradient
-Active Na reabsorption in thick ascending limb
74
What are the basic ion movements in the ascending limb?
75
What do the distal tubule and collecting duct do?
-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
76
77
78
79
What is the action of aldosterone?
-Steroid hormone
-Increases expression of ENaC and Na/K ATPase
80
What is distal (Type 1) renal tubular acidosis?
Defect in luminal H+ ATPase or H+/k+ ATPase
Mechanism – faliure of H+ excretion and urinary acidification
81
What is distal (Type 1) renal tubular acidosis?
Defect in luminal H+ ATPase or H+/k+ ATPase
Mechanism – faliure of H+ excretion and urinary acidification
82
What does excessive aldosterone activity produce?
-Sodium retention
-Hypertension
-Hypokalaemic alkalosis
-Can be primary or secondary
83
What is the basic embryology of the endocrine pancreas?
-Junction of foregut and midgut 2 pancreatic buds generated and fuse to form pancreas
-Exocrine functions begin after birth
-Endocrine function from 10-15 weeks
84
Describe the basic anatomy of the pancreas:
-Retroperitoneal and post to greater curvature of stomach
-12-15cm long, head near C of duodenum
-Secretions pass into small ducts then larger ducts
85
What cells is the pancreas formed of?
-Formed of small clusters of glandular epithelial cells
-98-99% clusters called acini
86
What cells carry out exocrine and endocrine functions of the pancreas?
-Exocrine - acinar cells:
-Manufacture and secrete fluid and digestive enzymes (pancreatic juice) released into gut
-Endocrine - islet cells:
-Manufacture and release several peptide hormones into portal vein
87
88
What happens in the islets of langerhans?
-Site of insulin and glucagon secretion of the endocrine pancreas
-2-3% of total pancreas volume
89
What islet cells produce what?
What term is used to describe them?
-Heterogeneous
90
Label these cells to their functions:
91
Label the functions of each of these cells:
92
What peptide hormones are produced by the islets and describe them?
Insulin
-Polypeptide
-Reduced glucose output by liver
-Increases storage of glucose, FA, AA
Glucagon
-Polypeptide
-Mobilises glucose, FA, AA from stores
Somatostatin
-Inhibitor
93
How can you describe the actions of insulin and glucagon to each other?
Reciprocal actions
94
What are the 3 key functions of insulin?
Suppresses hepatic glucose output
- Decrease glycogenolysis and gluconeogenesis
Increase glucose uptake into insulin sensitive tissues
-Muscle - glycogen + protein synth
-Fat - FA synthesis
Supresses
-Lipolysis
-Breakdown of muscle (decreased ketogenesis)
95
What are the 3 key functions of glucagon?
It is counter-regulatory to insulin
Increases hepatic glucose output
-Increase glycogenolysis and gluconeogenesis
Reduced peripheral glucose uptake
Stimulates peripheral release of gluconeogenetic precursors (glycerol, AA)
-Lipolysis
-Muscle, glycogenolysis and breakdown
96
What other things have similar effects to glucagon?
-Other counterregulatory hormones
(adrenaline, cortisol, growth hormone
-Become relevant in certain disease states
97
How should glucose levels remain and what is a short term buffer of this?
-Should remain constant
-Liver glycogen is a short term glucose buffer
98
What are the short and long term responses to high blood glucose?
Short term - Make glycogen (glycogenesis)
Long term - Make triglyceride (lipogenesis)
99
What are the short and long term responses to low blood glucose?
Short term - Split glycogen (glycogenolysis)
Long term - Make glucose from amino acids/lactate (gluconeogenesis)
100
How is glucose sensed?
-Primary glucose sensors in pancreatic islets
-Also in medulla, hypothalamus and carotid bodies
-Inputs from eyes, taste buds, gut all involved in regulating food
-Sensory cells in gut wall also stimulate insulin release from pancreas - incretins
101
Is insulin response greater following oral or IV glucose and why?
-Higher after oral despite similar plasma glucose concentrations
-Gut hormones stimulate insulin release are called incretins - glucagon-like peptide (GLP-1) and glucose-dependant insulinotrophic peptide (GIP)
102
103
What are 2 features of GLP-1?
-Glucose dependant
-Short half life (1-2 mins) - DPP-IV cleaves GLP-1 to prevent hypoglycaemia
104
Describe CHO metabolism in a fasting state:
-All glucose comes from liver:
-Glycogenolysis
-Gluconeogenesis (3 carbon precursors such as lactate, alanine, glycerol)
-Glucose delivered to insulin dependant tissues - brain + RBC
-Insulin levels low
-Muscle uses FFA for fuel
-Some processes are very sensitive to insulin, low insulin levels prevent unrestrained breakdown of fat
105
What is the first stage of insulin secretion by the beta cell?
-Glucose equilibrates across the plasma membrane via GLUT2 transporters - varies on conc
-Intracellular conc tracks extracellular
-Phosphorylated by glucokinase to G6P
-Glycolysis increases and ATP in generated
106
What is the second stage of insulin secretion by beta cells?
-ATP closes KATP channel and stops the efflux of K+
-Depolarises membrane allowing opening of voltage-dependant Ca2+ channels
-Rapid influx of Ca2+
-Triggers insulin exocytosis from primed secretory granules
107
Describe CHO metabolism after feeding:
-Physiological need to dispose of nutrient load
-Rising glucose stimulates 5-10 fold increase in insulin secretion + suppress glucagon
-40% to liver, 60% periphery (muscle)
-Replenished glycogen stores
-Excess converted to fats
-Suppress lipolysis
108
What does proinsulin contain?
-A and B chains joined by the C peptide
-Disulfide links A + B
-Presence of C peptide implies endogenous insulin production
109
What kind of release is insulin and what does this mean?
-Biphasic
-B-cells sense rising glucose and aim to metabolise it
-First phase response = rapid release of stored product
-Second phase response is slower and is release of newly synthesised hormone
110
What is the insulin action in muscle and fat cells?
-GLUT4 insulin receptor is a high affinity large transmembrane glycoprotein
-Mechanism not fully understood
-Causes exocytosis of GLUT4 vesicles, increasing glucose transporters in the cell membrane and rapid uptake of glucose
111
Describe normal puberty:
-Centrally driven
-Depends on intact HPG axis
-Influenced by many other factors
-Trigger is not well understood
112
What 5 other factors influence normal puberty?
-Nutrition
-Leptin and insulin
-Socio-cultural
-Genetic
-Exercise
113
What are 3 causes of precocious puberty?
-Gonadotrophin dependant (true or central)
-Intracranial lesions, infections, hypothyroidism
-Gonadotrophin independant
-CAH, sec hormone secreting tumours
-Other variants
-Premature thelarche
114
What is the treatment for precocious puberty?
-Exclude cause
-Do nothing
-Inhibit puberty with GnRH
115
What are the 3 groups of causes of delayed puberty?
-General
-Constitutional delay
-Malabsorption
-Chronic disease
-Gonadal failure
-Turner syndrome
-Gonadotrophin deficiency
-Hypothalamic/pituitary lesions
116
What can be some treatment options for delayed puberty?
-Exclude physical causes
-Sex hormone treatment
-Growth hormone therapy (occasional)
-Treatment of associated infertility
117
What is the genetic determinant of sex and its mechanism in males?
-SRY gene switches testicular development
-Testes produce MIF
-Prevents Mullerian duct development
118
What is the genetic determinant of sex and its mechanism in females?
-Absence of Y chromosome
-Ovaries and Mullerian ducts form
-Uterus and fallopian tubes form
-Two X chromosomes required
119
What are the general features of germ cells?
-Specialised cells – develop into gametes
-Migration to genital ridge by amoeboid movement
-Rapid mitotic division until about 20 weeks
120
Describe the replication and numbers of oocytes over what timescale?
-5-10 million primary oocytes at 20 weeks
-Meiosis starts before 12 weeks
-Rapid oocyte death at 20 weeks
-1 million left at birth
121
What is the importance of meiosis (4)?
-Two meiotic divisions prevent polyploidy
-Key step in germ-cell differentiation
-Increases chromosomal combinations and genetic variability
-Variability contributes to genetic or bio-diversity
122
Describe meiosis 1 in females:
-Reduction division
-46XX = 23X + 23X
-In-utero before 12 weeks
-Homologous recombination & crossover
-Arrested at metaphase 1 until puberty
-Resumption triggered by LH surge
123
Describe meiosis 2 in females:
-Equational division
-23X = 23X + 23X
-Arrested at metaphase 2 until fertilisation
124
125
126
Summarise primitive gonads before 6th week:
Identical
127
Summarise primitive gonads after 6 weeks:
-If Y chromosome (SRY gene) present:
-Testes form
-Mullerian development inhibited
-If Y chromosome absent:
-Ovaries form
-Mullerian development occurs
128
Describe the basic embryology of the female genital tract:
-Paramesonephric (Mullerian) duct develops:
-Fallopian tubes
-Uterus
-Upper 2/3 of vagina
-Mesonephric regresses
-Lower vagina
-Clitoris, labial majora and minora
129
Describe the hypothalamic-pituitary-gonadal axis:
130
When does positive and negative feedback occur during the hypothalamic-pituitary-gonadal axis during the menstrual cycle?
-Positive feedback – days 12-14
-Negative feedback – most of cycle
131
What is the hormonal control of puberty before puberty?
-Low pulsatility amplitude of GnRH and GnRH secretion from hypothalamus
-Low levels of (pituitary) FSH, LH and (gonadal) sex steroids
132
What is the hormonal control of puberty at pubertal age?
-Increased amplitude of GnRH and GHRH
-Increased levels of FSH, LH and sex steroid
-Increased levels of growth hormone (GH)
133
134
What are the testes covered by anteriorly?
-Covered anteriorly by a saclike extension of the peritoneum (tunica vaginalis)
-Descended into the scrotum with the testes
135
What is the tunica albuginea?
White fibrous capsule
136
What do the septa divide in the testes?
What is produced by these structures?
Divide organ into compartments containing seminiferous tubules where the sperm are produced
137
What are Leydig cells?
Clusters of cells between the seminiferous tubules and source of testosterone
138
What do Sertoli cells do?
Promote sperm cell development
Blood-testis barrier is formed by tight junctions between Sertoli cells
Seperating sperm from immune system
139
What do seminiferous tubules drain into?
Drain into network called rete testis
140
Describe the histology of the testis:
141
142
143
What does this show?
Heat exchange at the pampiniform plexus
144
Describe the stages of meiosis:
-Production of gametes haploid cells required for sexual reproduction
-2 cell divisions
-Meiosis 1 = separation of homologous chromosome pairs = 2 haploid cells
-Meisos 2 – separation of sister chromatids = 4 haploid cells
145
Where does meiosis occur in males?
Seminiferous tubules of males
146
What does spermatogenesis produce?
-2 kinds of daughter cells (spermatogonium)
-Type A remain outside blood-testis barrier & produce more daughter cells until death
-Type B differentiate into primary spermatocytes
147
Describe the movement of type B spermatogonium:
-Must pass through BTB to move inward toward lumen – new tight junctions form behind these cells
-Meisosi I -> 2 secondary spernatocytes
-Meiosis II -> 4 spermatids
148
What transformation occurs in spermiogenesis?
-Transformation of spermatids into spermatozoa
-Sprouts tail and discards cytoplasm to become lighter
149
150
What is the rate of production of sperm?
300 to 600 sperm are made per gram of testis per second
151
What forms the blood-testis barrier?
Tight junctions between and basement membrane under Sertoli cells
152
153
What occurs during spermiogenesis?
-Changes that transform spermatids into spermatozoa
-Discarding excess cytoplasm and growing tails
154
Label this diagram:
What is the process?
Spermiogenesis
155
Label this diagram:
What process does it show?
Feedback control of the hypothalamus-pituitary-testicular axis
156
Describe the head of the spermatazoon:
-Head is pear-shaped front end
-Contains nucleus, acrosome and basal body of the tail flagellum
-Nucleus = haploid chromosomes
-Acrosome = enzymes to penetrate egg
-Basal body
157
Label:
What is it?
Spermatazoon
158
Describe the tail of the spermatazoon:
Divided into 3 regions:
-Midpiece contains mitochondria around axoneme of flagellum (ATP for movement)
-Principal piece is axoneme surrounded by fibres
-Endpiece is axoneme only and is very narrow tip of flagellum
159
What are the 4 spermatic ducts?
-Efferent ductules
-Epididymis
-Ductus (vas) deferens
-Ejaculatory duct
160
Describe the efferent ductules and epididymis:
Efferent ductules:
-12 small ciliated ducts collecting sperm from rete testes and transporting to epididymis
Epididymis:
-Coiled duct adhering to posterior testis
-Site of sperm maturation and storage
161
Describe the ductus (vas) deferens and ejaculatory duct:
Ductus (vas deferens):
-Muscular tube passing up from scrotum through inguinal canal to posterior bladder surface
-Widens into terminal ampulla
Ejaculatory duct:
-Forms from vas deferens & seminal vesicles passing through prostate to empty into urethra
162
163
What are the three accessory glands of sperm production?
-Seminal vesicles
-Prostate gland
-Bulbourethral glands
164
What volume os seminal fluid is expelled during orgasm and what is it made of?
-2-5mL of fluid expelled
-60% seminal vesicle fluid
-30% prostatic
-10% sperm
-Trace of bulbourethral fluid
165
What is normal sperm count and what are sperm's main function?
-50-120 million/mL
-Serve to digest path through cervical mucus and to fertilize egg
166
What are some other components of semen?
-Fructose for energy for sperm motility
-Fibrinogen
167
What happens to the fibrin in the semen?
-Clotting enzymes convert fibrinogen to fibrin causing semen to clot
-Fibrinolysis liquefies semen within 30 mins
-Prostaglandins stimulate female peristaltic contractions
168
Describe oocyte activation (Day 1):
-First stage
-Sperm protein called Phospholipase C zeta (PLCz)
-Activates the egg to release calcium from internal stores
-Activation is essential for the transformation of the decondensed sperm nucleus in to pronucleus
169
What happens 4-7 hours after gamete fusion?
-Two sets of haploid chromosomes form the female and male pronucleus (23 chromosomes each)
-Pronuclei are equal in size and contain nucleoli
-In IVF multinucleate oocytes can be identified - polyspermic
170
Describe syngamy:
-Male and female pronucleus migrate to centre (cytoskeleton role)
-Haploid chromosomes pair and replicate DNA prepping for first mitosis
-Pronuclear membranes break down
-Mitotic metaphase spindle forms
-46 chromosomes organise at spindle equator
171
Describe day 2 of embryo development:
-Cleavage
-Approx 24 hours post-fertilisation ooplasm divides into two equal halves
-If one or more of the PN fail to decondense and move in to one of blastomeres, diploid or triploid mosaics may occur
172
173
What are cleavages during embryonic development controlled by?
-Timed from sperm entry by oocyte program that also regulates 'house keeping' in embryo
-Successive cleavages result in an increase in cell no. - essential to have enough for differentiation
174
Prior to 4-8 cell stage of embryo development, what does control depend on?
-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
-Arrest can occur
175
How do you describe early cleavage stage embryos?
-Totipotent
-Nuclei of individual blastomeres are each capable of forming an entire foetus
176
describe the 5th day of embryo development:
-Cavitation and differentiation
-Tight junctions between outer cells - trophectoderm
-Fluid-filled cavity expands
- >80 cells
- 55-66% comprise trophectoderm rect is ICM
-Pluripotent
177
178
What do the trophectoderm cells do?
Pump fluid to the embryo to form the blastocoel cavity
179
Describe day 5/6 of embryo development:
-Expansion
-Cavity expands
-Diameter increases
-ZP thins
180
Describe day 6+ of embryo development:
-Hatching
-Blastocyst expansion and enzymatic factors cause the embryo to hatch from the ZP
-Needed for implantation
-TE - extraembryonic
-ICM - embryonic
181
Describe the basics of the first 6 days of embryonic development based on the diagram:
182
What is the energy metabolism of the early preimplantation embryo?
-ATP turnover low
-ATP/ADP high
-Energy metabolism = consumption of pyruvate
-Glucose uptake + utilisation low
183
What are the energy metabolism and requirements at the blastocyst stage?
-Metabolic activity rises sharply
-ATP/ADP falls reflecting an increase in energy demand -> protein synth and ion pumping
-Glucose is predominant exogenous energy substrate
184
Label:
185
186
What is the provision of exogenous nutrients in vivo?
Supplied by:
-Cumulus cells
-Fallopian tube secretions
-Uterine secretions (iron and fat-soluble vitamins)
187
What exogenous nutrients are present in vivo of the embryo and how do they differ?
-Concentrations of nutrients vary along the tract to provide the embryo requirements
-Growth factors and cytokines
188
What happens at 10 days of embryo development?
-Cellular differentiation
-After implantation, embryogenesis continues with the next stage of gastrulation when 3 layers of germ cell develop (histogenesis)
-Three layers formed
-All structures of body are derived from these structures
189
What forms the chorion and placenta?
-Chrorioic ectoderm (trophectoderm)
-Extra embryonic mesoderm (icm)
190
What forms the amnion and yolk sac?
Extra embryonic membrane, mesoderm and endoderm
191
What forms the fetus?
Embryonic ectoderm, mesoderm and endoderm
192
What are 3 statements about the embryo implantation process?
-Well defined starting point
-Gradual process over several weeks
-No agreement of when complete
193
What does this show?
-1 day after initiation of implantation
-Note the small size of implantation compared to the thickness of the endometrium
194
Describe the regulation of the implantation process of the embryo:
-After embryo hatched embryonic and maternal cells enter complex dialogue
-High degree of prep and coordination
-Controlled cascade of trophoblast proliferation, differentiation, migration and invasion
195
What mechanisms are involved in the embryo implantation? (5)
-Hormones (sex steroids)
-Cell adhesion molecules
-Proteases
-Cytokines, growth factors
-Genetic
196
What are the 3 phases of embryo implantation?
-Apposition
-Attachment
-Invasion
197
Describe apposition:
-Unstable adhesion of blastocyst to uterine lining
-Synchronisation of embryo + endometrium
-Hatched blastocyst orientates via embryonic pole
-Receptive endometrium (window day 19-22)
198
Describe attachment (adhesion):
-Stronger adhesion
-Penetrates with protrusions of trophoblast
-Massive communication via ligand-receptor interactions
-Integrin subunits (endometrial)
-integrins (trophoblasts)
-Briding ligands connect integrins
199
Describe invasion (penetration):
-trophoblast protrusions continue to proliferate and penetrate endometrium
-Cells change to syncytiotrophoblast
-highly invasive - expands + erodes endometrial stroma)
-Erodes endometrial blood vessels
-Comes into contact with maternal blood to form chorionic villi - initiation of placenta formation
-Blood filled lacunae form
200
Describe the decidual reaction:
-Progesterone promed endometrial stromal cells next to blastocyst differentiate into metabolically active decidual cells (secratory)
-Endometrial glands enlarge
-Local uterine wall becomes highly vascularised
-Secretions -> growth factors, other nutrients to support growth
201
What are the main roles of progesterone (embryo development)?
-Modifies distribution of oestrogen receptors
-Stimulates secretory activity
-Stimulates stromal oedema
-Increase volume of blood vessels
-Primes decidual cells
202
What is maternal recognition of the embryo?
-Embryo is antigenically different from the mother
-At the same time as the decidual reaction, leucocytes in endometrial stroma secrete interleukin-2
-Prevents maternal recognition of embryo as a foreign body
203
What is the role of hCG?
-Essential to sustain early pregnancy
-Ensures corpus luteum continues to produce progesterone throughout first trimester of pregnancy (prevent menstruation)
-Interacts with endometrium via specific receptors
-immunosuppressive - highly negative charge to repel immune cells from fetus
204
Where is hCG produced?
Produced in the human placenta by the synctiotrophoblast
205
Describe the hCG measurement in early pregnancy:
-Doubling time of hCG is 1.3 days in the first 10-12 days of pregnancy
-Short doubling time signifies healthy pregnancy
206
What things are generated that need to be excreted by the kidney?
-Volatile acids from diet (sulphuric)and protein metabolism (phorphoric)
-Lactate from anaerobic metabolism
-Volatile acid co2 from carb metab
207
What do the kidneys excrete and reclaim?
-Excrete the acid load and reclaim filtered bicarboante
208
Describe the excretion of H+ ions in the ascending tubule:
209
Describe the reclaim of filtered bicarbonate in the kidney:
210
Describe metabolic acidosis:
-Low arterial pH
-Conjunction with a reduced serum HCO3- conc
211
Describe metabolic alkalosis:
-Caused by retention of excess alkali and manifested by an increase in venous (total Co2) or arterial HCO2-
212
Describe respiratory acidosis:
Acid-base disturbance initiated by an increase in CO2 tensions of body fluids and whole body CO2
-Secondary increment in plasma bicarbonate observed in acute and chronic hypercapnia is integral part
213
Describe respiratory alkalosis:
-Reduction in CO2 tension of body fluids
-Secondary decrease in HCO3- observed in acute and chronic hypocapnia is integral part
214
Label this diagram of the compensations in acid-base disorders:
215
What 2 basic things are needed for normal lower urinary tract function?
-Urine storgae - low pressure with perfect continence
-Urine emptying - periodic complete urine expulsion at low pressure when convenient
216
Describe the two basic phases of micturition and what occurs during each:
217
Describe the neural control of micturition throughout life:
Non potty trained baby = coordinated voiding + no control of off to on
Neurologically normal adult = coordinated voiding + full control when switches from off to on
Old age = same as non-potty trained
218
What are the 4 nerves of the lower urinary tract?
Motor:
-Pelvic
-Hypogastric
-Pudendal
Sensory:
-Visceral afferents
219
Describe the pelvic nerve:
-Autonomic/Parasympathetic
-S2-S4 intermediolateral horn (sacral micturition centre)
-Bladder contraction
220
Describe the hypogastric nerve:
-Autonomic/Sympathetic
-T10-L2 intermediate horn
-Bladder relaxation/bladder neck contraction
221
Describe the hypogastric nerve:
-Autonomic/Sympathetic
-T10-L2 intermediate horn
-Bladder relaxation/bladder neck contraction
222
Describe the pudendal nerve:
-Somatic (voluntary)
-S2-S4 ventral horn
-Striated external sphincter and pelvic floor contraction
223
Describe the visceral afferents of the urinary tract:
-Sensory autonomic
-S2-S4 intermediolateral horn (sacral micturition centre)
-A-delta bladder stretch, C-fibres pain
224
Label the red:
225
Label the green:
226
Label the green:
Bladder filling control
227
Label the blue:
Bladder filling control
228
Label the blue:
Bladder emptying stage
229
Label the purple:
Bladder emptying stage
230
Describe the bladder storage reflex:
-Distention of the bladder produces low-level bladder afferent firing
-Triggers **guarding reflex**
-sympathetic outflow via hypogastric to bladder outlet
-pudendal outflow to external urethral sphincter
-Sympathetic outflow also inhibits contraction of detrusor muscle
A REGION IN ROSTRAL PONTINE STORAGE CENTRE MIGHT INCREASE STRIATED URETHRAL SPHINCTER ACTIVITY
231
Label this diagram of the bladder storage reflex:
232
Describe the voiding reflex:
-Intense bladder-afferent firing in pelvic nerve
-Triggers spinobulbospinal reflex:
-Afferent signals passed to periacqueductal gray (blue)
-Pontine micturition centre activated
-PMC on/off switch
-para outflow to bladder and urehral smooth muscle (green)
-inhibits symp and pudendal outflow to bladder outlet (red)
233
What are the 4 important central neural control mechanisms of micturition?
-Prefrontal
-PAG
-PMC
-Basal ganglia
234
What are the prefrontal and PAG actions on micturition?
235
What are the PMC and and basal ganglia actions of micturition?
236
What are the two classifications of lower urinary tract dysfunction?
-Failure to store
-Failure to void
237
What 3 situations lead to a loss of relationship between plasma osmolality and vasopressin?
-Drinking rapidly suppresses vasopressin release and thirst
-In pregnancy the osmotic threshold for VP release and thirst is decreased
-Plasma VP concentrations increase with age
238
What are the medical terms for large volumes of urine and drinking?
Large volume of urine - polyurea
Large volumes of drinking - polydypsia
239
What 3 things categorise diabetes insipidus?
-Polyuria
-Polydypsia
-No glycosuria or hypercalcaemia or hypokalaemia
240
What are the two types of diabetes insipidus?
-Cranial - lack of vasopressin
-Nephrogenic - resistance to vasopressin
241
how does the relationship between plasma AVP and plasma osmolality differ with diabetes insipidus?
242
What are the two causes of cranial diabetes insipidus?
-Destruction of hypothalamus
-interruption of the connection of hypothalamus to pituitary
243
What stimulates the release of oxytocin?
Release stimulated by milk suckling
Posterior pituitary
244
What is the action of oxytocin?
-Stimulates milk let down
-Stimulates contraction of myometrium
-200 times less active at the V2 receptor compared to AVP
245
Describe the cycle of the release of oxytocin:
246
Describe the action of AVP:
247
248
249
What does the posterior pituitary originate from?
-Neuro tissue
-Large number of glial-type cells
250
What two hormones are secreted from the posterior pituitary?
-Vasopression (ADH) primarily from supraoptic nuclei – control water secretion into urine
-Oxytocin – expression of milk from the glands of the breasts to the nipples (promotes onset of labour) – primarily paraventricular nuclei
251
252
253
What are the volumes in the body?
Total body water = 42L
Intracellular = 28L
Extracellular = 14L – Intravascular =3.5L / Interstitial = 10.5L
254
What is the relationship between plasma osmolality, urine osmolality and plasma vasopressin?
255
What are the urine concentrations in the different parts of the nephron?
256
What is the mechanism of action of vasopressin? (4 steps)
257
258
What two things regulate ADH release?
-Osmoreceptors
-Baroreceptors
259
What three things affect the release of vasopressin?
260
261
What does AVP interplay with?
There is an interplay between AVP and salt and water physiology with other hormones
262
Describe the AVP control of dehydration:
263
What is osmolality?
Concentration of particles per kilo of fluid
264
What isn’t important with osmolality?
-Size of particle
-Number is important
265
What things can affect osmolality at high enough concentrations?
-Sodium
-Potassium
-Chloride
-Bicarbonate
-Urea and glucose
266
What do alcohol, methanol, polyethylene glycol or mannitol do to affect osmolality?
All exogenous solutes that may affect osmolality
267
What is normal osmolality?
282-295 mOsmol/kg
268
What is the general relationship of pAVP and pOsm?
-Past a certain pOsm, pAVP increases directly proportionally
269
What other thing shows a similar relationship to pAVP and pOSm?
Thirst
270
What is the general relationship between plasma AVP concentration and urine concentration?
Urine osmolality increases with pAVP after a small delay
271
What are the 3 layers of the skin?
-Epidermis
-Dermis
-Subcutis
272
What gives skin its waterproof barrier?
-Tight junctions between cells in stratum granulosum
-Epidermal lipids
-Keratin in stratum corneum
Form both an inside-out and outside-in waterproof barrier to water
273
What does the waterproof barrier of the skin do?
Prevents transepidermal water loss
274
275
What are the 6 functions of the epidermis?
-Waterproofing
-Physical barrier
-Immune
-Vitamin D synthesis (endocrine)
-UV protection
-Thermoregulation
276
What are the 3 functions of the dermis?
-Thermoregulation
-Vitamin D synthesis (endocrine)
-Sensory organ
277
Describe the 5 functions of the subcutis:
-Thermoregulation
-Energy reserve
-Vitamin D storage
-Endocrine organ
-Shock absorber
278
Describe skin wrinkling when wet:
-Mediated by sympathetic nervous system
-Vasoconstriction in dermis
-Improves grip
279
Describe the skin’s features as a physical barrier:
-Structure of skin helps resist trauma
-Stratified epithelium helps resist abrasive forces
-Fat in subcutis acts as shock absorber
280
Describe vitamin D synthesis in the skin:
-7-deyhdrocholesterol 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 vit D
281
Can vitamin D be stored?
-Yes
-Lipid soluble so stored in subcutis adipocytes
282
Describe the skin as a site of hormone action:
-Androgens act on follicles and sebaceous glands
-Thyroid hormones act on keratinocytes, follicles, dermal fibroblasts, sebaceous glands, eccrine glands
283
Describe the skin as a site of hormone synthesis:
-Vitamin D3 unique production site
-17beta-hydroxysteroid dehydrogenase in sebocytes and 5alpha reductase in dermal adipocytes convert dehydroepiandrosterone (DHEA) and androstenedione to 5alpha-dihydrotestosterone
-IGF binding to protein-3 (IGFBP-3) synthesised by dermal fibroblasts
284
What rays is the skin a barrier to?
Both UV-A and UV-B as they damage the skin
285
What do UV-A and UV-B do?
-Burns
-Suppress action of Langerhans cells
-Photo-aging
-DNA damage (skin cancers)
286
What does skin colour depend on?
-Melanin
-Carotenoids
-Oxy/deooxyhaemoglobin
287
What is melanin synthesised by?
In melanosomes within melanocytes from tyrosine
288
Where is melanin transported?
Via dendrites to adjacent keratinocytes
289
What are the two types of melanin?
-Pheomelanin (red/yellow)
-Eumelanin (brown/black)
290
What are the deleterious effects of melanin?
-Prone to photodegradation – may generate ROS
-Pheomelnin increases release of histamine
-Lots of melanin = less able to utilise UV light to make vitamin D
291
What are the three stages of response to sunlight?
-Immediate pigment darkening
-Persistent pigment darkening
-Delayed tanning
292
Describe the immediate pigment darkening in response to sunlight:
-Photooxidation of existing melanin
-Redistribution of melanosomes
-Occurs within minutes and lasts hours-days
293
Describe the persistent pigment darkening response to sunlight:
-UVA> UVB
-Oxidation of melanin
-Occurs within hours, lasts 3-5 days
294
Describe the delayed tanning response to sunlight:
-Increased melanin synthesis
-Occurs 2-3 days after UV exposure, maximal at 10-28 days
295
How do different skin types respond to sunlight?
296
Describe the skins function as a barrier to infection:
-Properties that render the skin a barrier to water also helps prevent infection
-A range of peptides synthesised by granular layer keratinocytes have antimicrobial properties (cathelicidin-related antimicrobial peptide, b defensins
297
What immune functions does the skin have?
-Innate and acquired immune functions
Epidermis:
-Langerhans cells
Dermis:
-Regulatory T cells
-Natural killer cells
-Dendritic cells
-Macrophages
-Mast cells
298
Describe the immune properties of the epidermis:
-Keratinocytes secrete cytokines and chemokines that maintain populations of leucocytes in skin
-Langerhans cells are antigen-presenting cells and secrete cytokines
299
What do langerhan cells do in the epidermis?
-Migrate to dermis and lymph nodes and activate a T-cell response
-Keratinocytes proliferate and secrete cytokines
-Leucocytes enter skin from blood
300
What three structures give the skin its sensory functions?
-Merkle cells – basal epidermis (light touch)
-Encapsulated mechanoreceptors in dermis
-Myelinated and unmyelinated sensory nerve endings in dermis (pain, itch, temperature)
301
What three structures give the skin its sensory functions?
-Merkle cells – basal epidermis (light touch)
-Encapsulated mechanoreceptors in dermis
-Myelinated and unmyelinated sensory nerve endings in dermis (pain, itch, temperature)
302
What are the two types of encapsulated mechanoreceptors in the dermis?
-Pacinian corpuscles (pressure/vibrations)
-Meissner corpuscles (touch)
303
What 4 things does the skin have to regulate body temperature?
-Insulation: (subcutaneous fat)
-Heat loss:
-Cutaneous blood flow
-Eccrine sweating
-Hair
304
Describe the cutaneous blood flow and its role in regulating body temperature:
-Deep vascular plexus (lower reticular dermis0
-Superficial vascular plexus (upper reticular dermis
-Loops of blood vessels from superficial plexus extend to reticular dermis
305
What is the equation for heat storage?
306
What does evaporation from the skin depend on and what can add or remove heat?
-Surface area exposed to environment
-Temp and relative humidity of ambient air
-Convective air currents
-Radiation, conduction and convection can add or remove heat
307
What is the nervous control of the blood flow in dermal vascular plexuses?
-Autonomic regulation of blood flow
-Sympathetic alpha-noradrenergic – vasoconstriction
-Sympathetic cholinergic – vasodilation
Both in hairy skin, hairless skin only has adrenergic innervation
308
What is a dual function of sympathetic cholinergic nerves?
Sympathetic cholinergic nerves that govern sweating may be the same as those controlling active vasodilation
309
What non-neuronal factor may act on active vasodilation?
Nitric oxide may play a role in active vasodilation
310
Describe the sweat release of the skin?
-1.6-4 million eccrine sweat glands
-1-3L sweat per hour
-Availability of water is major limiting factor
311
What are goosebumps called?
Piloerection
312
Describe piloerection:
-Arrector pili muscles innervated by sympathetic alpha1 adrenergic fibres
-Contraction raises cutaneous hairs
-Likely little significant impact on heat conservation
313
What are the functions of subcutaneous fat?
-Acts as an insulatpor, shock absorber and energy store
-White adipose connective tissue
314
What are the5 main types of incontinence?
-Stress - loss of urine with exertion,sneezing, coughing
-Urgency - leakage accompanied or preceded by urinary urgency
-Moxed - loss associated with urgency and exertion, effort, sneezing or coughing
Not standardised:
-Overflow - leakage associated with retention
-Total - continuous leakage
315
How many nephrons are there in a kidney?
-200,000 - 1.8 million
316
What is the blood flow to the kidneys?
-1200ml/min
-20-25% cardiac output
317
What is taken from blood to make plasma?
-Haematocrit
-Only plasma can cross glomeruli structures
318
What are normal GFR and UO?
-GFR = 120ml/min
-Uo = 1.5L/day
319
What are each of these structures?
320
Describe the proximal convuluted tubules:
-Confined to renal cortex
-Active reabsorption of multiple things - amino acids, glucose, bicarboante, phosphate, salt and water, potassium, chloride, urea
-Metabolically active cells
321
describe renal glycosuria:
322
Label reabsorption of glucose in the PCT:
323
Describe cystinuria:
-AR inherited
-Tubular defect in uptake of amino acid
-Failure of cysteine reabsorption, increased urinary cysteine conc
324
What causes hypophosphataemic rickets?
unable to reabsorb potassium
325
What causes proximal renal tubular acidosis?
-Na/H antiporter defect
-Failure of bicarbonate reabsorption
326
Describe bicarbonate reabsorption?
327
What is fanconi syndrome?
-Generalised proximal tubular dysfunction possible due to failure of sodium gradient generation by Na/K ATPase
328
What does the loop of henle do and how?
-Generates medullary concentration gradient via countercurrent system
-Active Na reabsorption in thick ascending limb
-Development of a hypertonic interstitium in medullary regions of kidney
-Production of a dilute filtrate entering the distal tubule
329
Describe. theprocess of the ascending limb function:
Drawing a diagram might help
330
What does the distal convuluted tubule do?
Distal tubule and cortical collecting ducts allow fine tuning of sodium reabsorption, potassium and acid-base balance
331
describe the distal convoluted tubule and how it does its function:
-Impermeable to movement of water and sodium
-Uses NCCT co transporter to reabsorb 5% of sodium
-Specific epithelial channel absorbs calcium, paracellular route CA Mg
-Hypokalemia due to increased delivery of sodium to collecting duct
332
Draw the diagram of salt and water transport in the distal convoluted tubule:
333
What causes distal renal tubule acidosis (type 1)?
na channel defect or H-ATPase so failure to secrete acid
334
What does the collecting duct do?
Mediates water reabsorption and maintains acid base homeostasis
335
What are the two cell types in the collecting ducts?
-Principal cells - Na and water reabsorption and K excretion
-Intercalated cells (alfa and beta) - secrete H or HCO3
336
What are the main functions of the two cells types of the collecting duct?
Principal:
-ENaC - specific Na transporter and main site of Na regulation
-Aldosterone increases the number. ofopen ENaC channels
Intercalated:
-Essential for acid-base homeostasis
