SUGER Flashcards
Rare disease in Europe defined as…
Affecting 1/2000 or less
Kidney roles
Maintain balance of salt, water, pH
Excrete waste products
Endocrine function
Control BP
RBC production
Maintenance of bones
Removal of drugs from body
Components of nephron in cortex
Bowman’s Capsule
Proximal tubule
Distal Tubule
Components of nephron in medulla
Loop of Henle
Collecting Duct
Renal cardiac output
~5 L/min
Renal blood flow
~1 L/min
Renal blood pathway
Abdominal aorta
Renal artery
Interlobar artery
Arcuate artery
Interlobular artery
Afferent arteriole
(nephron) Glomerular capillary
Efferent arteriole
Peritubular capillaries
Vasa recta
Interlobular veins
Arcuate veins
Interlobar veins
Renal veins
IVC
Renal urine flow
1 ml/min
The Tubuloglomerular Feedback Loop
Increased arterial BP
= Increased blood flow and BP in glomerulus
=Increased GFR
= Increased delivery of NaCl to macula densa (this triggers afferent arteriolar constriction)
= Decreased blood flow and BP in glomerulus
Myogenic mechanism for kidney autoregulation
Increased BP
= Stretch in vessel walls
= Opens stretch-activated cation channels
= Membrane depolarisation
= Opens voltage-dependent Ca channels
= Increased intracellular Ca
= Smooth muscle contraction
= Increased vascular resistance
= Minimised change in GFR
(decreased BP does the opposite)
Autoregulation of the kidney comes with 2 mechanisms:
-Tubuloglomerular feedback
-Myogenic mechanism
Which maintain GFR and control water/waste excretion
3 components of kidney filtration barrier
Fenestrated capillary endothelium
Glomerular basement membrane
Podocytes (foot processes)
5 factors affecting glomerular filtration
Pressure
Molecule size
Charge of molecule
Rate of blood flow
Binding to plasma proteins
Small molecules and ions up to …. can pass freely through filtration barrier
10kDa (glucose, uric acid, K)
Why can’t negatively charged ions cross filtration barrier?
Fixed negative charge of glomerular BM repels negatively charged anions
GFR is…
Glomerular filtration rate (filtration volume per unit time)
Embryology of pancreas
At junction of foregut and midgut, 2 pancreatic buds (dorsal and ventral) are generated which fuse to form pancreas
When does exocrine function of the pancreas begin?
After birth
When does endocrine function of the pancreas begin?
Weeks 10-15
Size of pancreas
12-15cm
Anatomical position of pancreas
Retroperitoneal, posterior to greater curvature of stomach
Ejaculate is a mixture of…
Spermatozoa and Seminal Plasma
Anterior covering of testes
Saclike extension of peritoneum (tunica vaginalis)
Tunica albuginea
White fibrous capsule
Septa dividing the testis into compartments containing seminiferous tubules
Where in the testes are spermatozoa produced?
Seminiferous tubules (where meiosis occurs)
What are the Leydig cells?
Cluster of cells between the seminiferous tubules and source of testosterone
Blood-testis barrier
Formed by tight junctions between sertoli cells (separates sperm from immune system)
And basement membrane beneath sertoli cells
Sertoli cell role
Promote sperm development (through testosterone production)
What do the seminiferous tubules drain into?
Network called rete testis
Pendulous pouch holding the testes divided into 2 compartments by…
A median septum
Testicular thermoregulation is necessary because…
Sperm aren’t produced at core body temperature (about 34 degrees)
2 types of daughter cells produced by spermatogonia
Type A Spermatogonia - remain outside blood-testis barrier and produce more daughter cells until death
Type B - Differentiate into primary spermatocytes
In spermatogenesis, meiosis I produces…
2 secondary spermatocytes from 1 primary spermatocyte
In spermatogenesis meiosis II produces…
4 spermatids from 2 secondary spermatocytes
Spermiogenesis is…
Transformation of spermatids to spermatozoa (sprouts tail and discards cytoplasm to become lighter)
3 regions of tail of a spermatozoon
Midpiece - contains mitochondria around axoneme of flagellum
Principal piece - axoneme surrounded by fibres
End piece - axoneme only
Length of cycle of seminiferous epithelium (sperm from spermatogonia)
16 days
Seminal fluid produced together by…
Bulbourethral, prostate and seminal glands
Fluid expelled during orgasm
2-5mL fluid
60% seminal vesicle fluid
30% prostatic
10% sperm
Trace of bulbourethral fluid
Normal sperm count
50-120 million/mL
Menstruation cycle summary
Days 1-7: Menstruation (3-7 days)
Days 8-11: Lining of womb thickens in prep for egg
Day 14: Ovulation
Days 18-25: If fertilisation hasn’t taken place, corpus luteum fades away
Days 26-28: Uterine lining detaches leading to menstruation
2 things responsible for sperm movement in female reproductive tract
Sperm motility
Female reproductive tract movement
2 features of PCTs
Simple cuboidal brush border (cells as deep as hairs are long)
High mitochondrial density
PCT function
Bulk reabsorption of Na, Cl, H2O, glucose, amino acids, bicarbonate, lactate, phosphate
Secreting organic ions
Na+/K+ pump for Na reabsorption
Other molecules taken up by secondary active transport, diffusion or osmosis
Water reabsorption in PCTs
By AQP1 channels
Water can also pass through the leaky tight junctions
Glucose reabsorption in PCTs
Early parts - SGLT2 - 1 Na+ and 1 glucose
Later parts - SGLT1 - 2 Na+ and 1 glucose
Sodium reabsorption in PCTs
Na+ actively transported out of PCTs via K+/Na+ (3Na+ out and 2K+ in)
This decreases Na conc in cell increasing gradient for Na+ to go lumen -> PCT cell
Na+ transported into cell either in exchange for H+ or co-transported
From cell, it’s pumped into the interstitium by Na/K ATPase or co-transported with bicarbonate
Amino acid reabsorption in PCTs
Co-transported with Na+
Chloride reabsorption in PCTs
Exchanged for formate in the NKCC2 channel
Formate then becomes formic acid (can diffuse across membrane and be reused)
Protein endocytosis and degradation in PCTs
Protein shouldn’t be in tubules but a mechanism is present for removing them
Microvilli have sensors which specifically bind any protein
Endocytosis occurs in endosomes and protein degradation by lysosomes producing amino acids
Bicarbonate reabsorption in PCTs
In lumen, H+ combines with HCO3- to form carbonic acid (requires carbonic anhydrase)
H2CO3 then -> H2O + CO2
CO2 diffuses through cell wall
H2O reabsorbed by osmosis
In cell, H2O + CO2 -> H2CO3 -> H+ + HCO3-
H+ recycled with transporting Na+
HCO3- co-transported with Na+ into interstitium (1Na+ with 3HCO3-)
Urachus
Remnant of channel between bladder and umbilicus
Renal plasma flow per minute
700ml/min
GFR
120ml/min
Renal blood flow
1250ml/min
How much bicarbonate water secretion does the pancreas produce per day?
1 litre per day
Role of pancreatic bicarbonate secretion
Protection of duodenal mucosa by neutralising stomach acid
Buffers duodenal content to optimise pH for enzyme digestion
Pancreatic proteases
(Protein digestion is initiated by pepsin in stomach and majority occurs in small intestine)
Trypsinogen and chymotrypsinogen which are transported in secretory vesicles containing a trypsin inhibitor (additional safeguard to prevent cell digestion)
Trypsinogen activated by enterokinase (secreted by small intestine epithelial cells)
Trypsin then activates chymotrypsinogen and additional trypsinogen
At this point the trypsin inhibitor is ineffective
Fat digestion due to 2 secretions
Pancreatic and hepatic secretions
Pancreatic amylase
Major source of amylase (salivary amylase has a small role)
Hydrolyses starch to more soluble sugars
Gastric secretion split into 2 stages
Cephalic stage - vagal innervation stimulates production of salivary amylase in mouth and gastrin in stomach (anticipation of a meal)
Intestinal stage - secretion of:
Cholecystokinin, secretin and gastrin
Cholecystokinin stimulus, produced in and action
Stimulus - HCl, protein, fats entering duodenum
Produced in - I cells of duodenum/jejunum
Action - Triggers pancreatic enzyme and HCO3- secretion, gallbladder contraction (releasing bile), inhibition of gastric secretion, delayed gastric emptying
Secretin stimulus, produced in and action
Stimulus - Low duodenal pH
Produced in - Upper small intestine
Action - Pancreatic water and bicarb secretion (flushing out into duodenum carrying enzymes)
Gastrin stimulus, produced in and action
Stimulus - Gastric distension/irritation
Produced in - G cells in stomach
Action - HCl secretion (parietal cells) enzyme release (acinar cells)
As proteins and fats are digested and absorbed, pH rises. What effect does this have on CCK and secretin secretion?
Stimuli for CCK and secretin disappear and pancreatic secretion reduces
Pancreatic endocrine function
Insulin and glucagon secretion
Difference in reabsorption between PCTs and DCTs
PCT - Bulk absorption, leaky
DCT - Fine tuning of filtrate, impermeable
Counter-Current Multiplication Mechanism in Loop of Henle
Generation of hyperosmotic interstitium to aid CT in water reabsorption by features of the thick ascending limb and thin descending limb
Role of thick ascending limb in developing a hyperosmotic interstitium
Driven by Na+/K+ ATPase pump on basolateral membranes of cells which keep intracellular Na low allowing ease of Na re-uptake
NKCC2 uses the gradient and pumps Na+ out lumen
K+ recycled on apical membrane back into lumen through ROMK channels
Cl- leaves cells through CLCK A channels (CLCK B in inner medulla) on basolateral membrane
Process promotes +ve charged lumen repelling Ca,Mg,Na ions which leave lumen
Creates a hyperosmotic interstitium
2 hormones secreted by posterior pituitary gland
Vasopressin (ADH) - controls water secretion into urine (primarily from supraoptic nuclei)
Oxytocin - expression of milk from glands of breasts to nipples, promote onset of labour (myometrium contraction) (primarily paraventricular nuclei). Stimulated by milk suckling.
Origin of posterior pituitary
Neuro tissue - large number of Glial-type cells
Max urine osmolality
1200mOsm/l
(In collecting tubules)
What inhibits ADH release?
Caffeine, alcohol
What stimulates ADH release?
Increased osmolality
Decreased blood volume
Nausea, vomiting, stress, exercise
Osmolality
Concentration of particles per kilo of fluid
Vasopressin mechanism of action of collecting tubules
Vasopressin binds to receptor on collecting duct cell membrane
Receptor activate cAMP second messenger system
Cells into aquaporins into apical membrane
Water reabsorbed by osmosis into blood
Restoration of osmolality by 2 ways
Increased plasma osmolality =
-Increased thirst -> Increased fluid intake -> restored osmolality
- Increased ADH neurone firing -> release of ADH -> ADH at V2R -> Water reabsorption -> restored osmolality
Normal Osmolality
285-295 mOsmol/kg
3 skin layers
Epidermis
Dermis
Subcutis
Skin as a waterproof barrier
Tights junctions between cells in straum granulosum, epidermal lipids and keratin in straum corneum form both an inside-out and outside-in barrier to water
Epidermis functions
Waterproofing
Physical barrier
Immune function
Vit D synthesis (endocrine)
UV protection
Thermoregulation
Dermis functions
Thermoregulation
Vit D synthesis (endocrine)
Sensory organ
Subcutis
Thermoregulation
Energy reserve
Vit D storage
Endocrine organ
Shock absorber
Why does skin wrinkle when wet?
Skin on fingers and toes wrinkles if immersed for approx 5 mins
Mediated by sympathetic NS
Due to vasoconstriction in dermis
Improves grip
Skin as a physical barrier
Stratified epithelium helps resist abrasive forces
Fat in subcutis acts as shock absorber
Structure of skin helps resist trauma
Vitamin D synthesis in skin
7-dehydrocholesterol in plasma membranes of epidermal keratinocytes and dermal fibroblasts converted to previtamin D3 (cholecalciferol) by UV
15-25 min whole body exposure produces up to 10,000 IU Vit D
How is Vitamin D stored?
It’s lipid soluble so can be stored in subcutis adipocytes
Dietary Vitamin D intake
Vitamin D2 - Fish, meat Vitamin D3 - supplements
Skin as a site of hormone action
Androgens act on follicles and sebaceous glands
Thyroid hormones act of keratinocytes, follicles, dermal fibroblasts, sebaceous glands, endocrine glands
Skin as a site of hormone synthesis
Vit D unique site for cholecalciferol synthesis
17beta-hydroxysteroid dehydrogenase in sebocytes and 5alpha-reductase in dermal adipocytes convert dehydroepiandrosterone (DHEA) and androstenedione to 5alpha-dihydrotestosterone
Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) synthesised by dermal fibroblasts)
What rays is skin a barrier to?
UV-A and UV-B which damage skin (burns, photo-aging, DNA damage)
Skin colour depends on…
Melanin
Carotenoids
Oxy/deoxyhaemoglobin
Melanin synthesis and transport
Synthesised in melanosomes within melanocytes from tyrosine
Transported by dendrites to adjacent keratinocytes
Colour of melanin
Pheomelanin - red/yellow
Eumelanin - brown/black
The more eumelanin your skin contains…
The darker your skin (we all have the same number of melanocytes but different amount of melanin)
Which type of melanin do we have most of in the skin?
Eumelanin
Deleterious effects of melanin
Prone to photodegradation (may generate ROS)
Pheomelanin increases release of histamine
Lots of melanin = less able to utilize UV light to make Vit D
3 stages of response to sunlight
Immediate pigment darkening
Persistent pigment darkening (tanning)
Delayed tanning
Immediate pigment darkening in response to sunlight
Photooxidation of existing melanin
Redistribution of melanosomes
Occurs within minutes and lasts hours/days
Persistent pigment darkening
Oxidation of melanin
Occurs within hours lasting 3-5 days
Delayed tanning
Increased melanin synthesis
Occurs 2-3 days after UV exposure (maximal at 10-28 days)
Skin as a barrier to infection
Properties that render skin a barrier to water also help prevent infection
Range of peptides synthesised by granular layer keratinocytes have antimicrobial properties
Skin as a sensory organ
Merkle cells - basal epididymis (light touch)
Encapsulated mechanoreceptors in dermis
Myelinated and unmyelinated sensory nerve endings in dermis (pain, itch temperature)
What connects seminiferous tubule to epididymis?
Seminiferous tubules -> Straight tubules -> rete testis -> Epididymis
How many primordial follicles in ovary at birth?
400,000 (approx 400 will mature and ovulate)
Insulating role of skin
Insulation by subcutaneous fat
Cutaneous blood flow in heat loss
Deep vascular plexus (lower reticular dermis)
Superficial vascular plexus (upper reticular dermis)
Autonomic regulation of blood flow in dermal vascular plexuses
Sympathetic alpha-noradrenergic: vasoconstriction
Sympathetic cholinergic: vasodilation
(both in hairy skin, hairless skin only has adrenergic innervation)
Eccrine sweat glands
1.6-4 million in skin
1-3 L sweat per hour
Water availability major limiting factor
Piloerection (goosebumps)
Arrector pili muscles innervated by sympathetic alpha1-adrenergic fibres
Contraction raises cutaneous hairs
Epidermis immunity role
Keratinocytes secrete cytokines and chemokines to maintain leucocyte populations in skin
Langerhans cells are antigen-presenting cells and secrete cytokines
Immune cells in dermis
Regulatory T cells
Natural killer cells
Dendritic cells
Macrophages
Mast cells
98-99% of pancreatic cells are…
Glandular epithelial cells forming clusters called acini
What is pancreas exocrine function?
Which cells carry it out?
Secrete pancreatic juice (enzymes an fluid released into gut)
Performed by acinar cells
What is pancreas endocrine function?
Which cells carry it out?
Several peptide hormones (insulin, glucagon) released into portal vein
Performed by islet cells (Islets of Langerhans)
Delta cells of pancreas secrete…
Somatostatin (acts as an inhibitor across a lot of systems)
Alpha cells of pancreas secrete…
Glucagon
Beta cells of pancreas secrete…
Insulin