PPP Flashcards
1
Q
What is nebulin?
A
Molecule that extends from Z band along the length of one thin actin filament
2
Q
What is titin?
A
Associated with myosin filaments extending from Z disk to M line
3
Q
What is concentric contraction?
A
Contraction stage with an increase in the interdigitation of the filaments
4
Q
What is eccentric contraction?
A
Stretched stage where I and H bands are wide. Thick and thin filaments do not interact
5
Q
How is contraction of skeletal muscle initiated?
A
ACh binds to nicotinic receptor at motor end plate; depolarisation spreads into T-tubules –> DHP is activated –> RyR are linked and activated –> release of Ca2+ from sarcoplasmic reticulum; Ca2+ binds to troponin –> change in tropomyosin allowing myosin heads to attach –> contraction
6
Q
How is extracellular space defined?
A
Plasma + interstitial space
7
Q
How is total body water distributed?
A
Plasma space (5% bw; 3.5 L) Interstitial space (15% bw; 10.5 L) Intracellular space (40% bw; 28 L)
8
Q
What is the amount of CSF in the body?
A
Around 150 ml
9
Q
What substances are used to measure fluid compartments?
A
Plasma volume: albumin, evans blue, labeled inulin
ECS: 24Na, sucrose
TBW: 3H20
10
Q
What is the difference between osmolarity and osmolality?
A
Osmolarity: 1 osmole per liter
Osmolality: 1 osmole per kg
11
Q
What is the osmolarity of plasma?
A
290 mosmol/l
12
Q
What is crystalloid osmotic pressure?
A
Due to small diffusible ions
13
Q
What is the ionic composition of plasma and intracellular compartment?
A
Na+: 140 mM and 10 mM K+: 4 mM and 120/140 mM Ca2+: 2 mM and around 100 nM Cl-: 110 mM bicarbonate: 24 mM
14
Q
Which are the plasma proteins?
A
Albumin: oncotic pressure of around 25 mmHg
Alpha, beta and gamma globulins
Fibrinogen
15
Q
What is the count of RBCs and Hb?
A
RBCs: 5.5/4.8 x 10^12 per litre
Hb: 160/140 g per litre
16
Q
What is the total WBCC?
A
4-11 x 10^9 per litre
Lymphocytes (20-40%)
Monocytes (2-8%)
Granulocytes: neutrophils (50-70%), eosinophils, basophils
17
Q
What is the total number of platelets?
A
150-400 x 10^9 per litre
18
Q
What is the normal MCV?
A
85 fL
19
Q
What are the average pressures in the pulmonary and systemic circulation?
A
Pulmonary: 16 mmHg
Systemic: 92 mmHg
20
Q
What is Fick’s law?
A
Rate of diffusion depends on: 1. Area 2. Difference in concentrations 3. Distance over which it has to travel How easily it diffuses depends on: 1. Temperature 2. Solubility 3. Square root of molecular weight
21
Q
What is Darcy’s law?
A
Flow = (P1-P2)/R
22
Q
What is Poiseuille’s law?
A
R = 8VL/pir^4
23
Q
What is the Fahraeus-Lindqvist effect?
A
Axial streaming due to laminar flow reduces viscosity of blood
24
Q
How is Rtotal calculated in series and in parallel?
A
Series: Rtotal = R1 + R2 +…
Parallel: 1/Rtotal = 1/R1 + 1/R2 +…
25
How do you calculate MABP?
MABP = CO*TPR
26
What is the definition of voltage?
A measure of the electrical work done to separate charges across the membrane
27
What is the equilibrium potential?
When the force of the concentration gradient of K+ out of the cell is matched by the electrical force pulling K+ back into the cell
28
What is the Nerst equation for monovalent ions?
E = 58 (mV) x log [Cout]/[Cin]
29
What are the equilibrium potentials of sodium and postassium?
Sodium: +50 mV
Potassium: -90 mV
30
How do you calculate the driving force on the ion out of the cell?
Vm - Eeq
31
What is the Goldman Hodgkin Katz equation?
Calculates membrane potential taking into account permeabilities of ions
32
Where are cardiac t-tubules absent?
Atria, neonatal and avian hearts
33
How long is the cardiac AP?
200-400 ms
34
Why is the cardiac AP so long?
Prevents tetany, protects against re-entering arrhythmias
35
What does cardiac muscle require to initiate contraction?
Calcium influx
36
What is the difference in the mechanisms of calcium release in skeletal, cardiac and smooth muscle?
Skeletal: depolarization-induced calcium release (L-type calcium channels/DHP act as plug on RyR)
Cardiac: Ca-induced Ca-release
Smooth: IP3
37
How is calcium removed from the sarcoplasm in cardiac muscle cells?
Through SERCA and sarcolemma Na/Ca exchanger
38
What is the explanation of the length-tension relationship in cardiac muscle?
1. Overlap of thick and thin filaments (only accounts for 20%)
2. Increased calcium affinity to troponin C upon increased sarcomere length
39
What is the Frank Starling law of the heart?
CO is directly related to filling pressure; peak systolic pressure is directly related to resting fibre length
40
How is the force-frequency relationship in a failing heart?
Negative: force decreases with increasing frequency; due to decreased action of SERCA and increased action of Na/Ca exchanger
41
Which are the smooth muscle containing organs?
Blood vessels, GI tract, bladder, ureters, urethra, uterus, respiratory system, vas deferens and corpus cavernosum, iris and ciliary body
42
What are dense bodies?
Structures in SMCs that anchor actin filaments
43
Which are the vasoconstrictors of vascular smooth muscle?
Noradrenaline (from symp nerves)
Histamine (locally released from veins), PGF, TXA2
Adrenaline, angiotensin II, vasopressin (hormones)
Pressure, moderate cold
44
Which are the vasodilators of vascular smooth muscle?
VIP, substance P, CGRP, ACh (ANS nerves)
PGE2, PGI2, NO, EDHF, histamine (arterioles)
Adrenaline (some organs), ANP
Flow, heat
45
How is vascular smooth muscle contraction mediated?
Adrenaline/angiotensin II or other vasoconstrictors --> activate alpha 1 receptors:
1. Phospholipase C --> IP3 and DAG --> calcium release from SR + Ca and Na influx through receptor gated channel
2. Rho kinase --> calcium sensitisation
Stretch --> stretch activated channel --> sodium influx --> membrane depolarisation --> opening of voltage gated calcium channels (VGCC)
46
How does NO-mediated vasodilation occur?
Endothelial cells secrete NO --> activation of guanylate cyclase --> cGMP:
1. Stimulation of SERCA and PMCA (plasma membrane Ca ATPase)
2. Calcium desensitisation
3. Opening of K+ channels --> membrane hyperpolarisation --> closing of VGCC
47
How does cAMP-mediated vasodilation occur?
Adrenaline, adenosine or prostacyclin --> beta1 activation --> increase in cAMP:
1. stimulates SERCA and PMCA
2. Opening of K+ channels --> membrane hyperpolarisation --> closing of VGCC
48
What are the mechanisms of the crossbridge cycle in SM and its regulation?
Myosin light chain kinase + calmodulin + calcium --> active complex:
1. myosin --> phosphorylated myosin --> crossbridge cycle
Regulation by myosin phosphatase:
1. Inhibited by agonists via rho kinase --> Ca sensitisation
2. Activated by NO via cGMP --> Ca desensitisation
49
What are latch bridges?
Form when myosin is dephosphorylated while still bound to actin --> cycle very slowly and thus maintain force
50
What is the AP upstroke and repolarisation in smooth muscle due to?
Upstroke: voltage gated calcium channels influx
Repolarisation: K+ outflow
51
What is the difference between unitary and multi-unit smooth muscle?
Unitary: not all cells have synaptic input, excitation is spread through gap junctions
Multi-unit: each muscle cell has synaptic input (iris, ciliary body, piloerector muscles)
52
Which receptors are present in the sympathetic and parasympathetic pathways?
Preganglionic onto postganglionic: ACh onto nicotinic
Postganglionic onto effector:
1. Sympathetic: NA onto alpha or beta (except sweat glands --> ACh onto muscarinic)
2. Parasympathetic: ACh onto muscarinic
53
What are NA and Adrenaline derived from?
Tyrosine + tyrosine hydroxulase --> DOPA
DOPA + DOPA decarboxylase --> dopamine
dopamine + dopamine beta-hydroxylase --> noradrenaline
54
How and why is NA stored?
Unprotected monoamines (NA, serotonin, dopamine) are metabolised by monoamine oxidase (MAO); thus, NA is taken into vesicles via vesicular monoamine transporter (VMAT)
55
What is the action of reserpine?
Blocks VMAT
56
What is the function of alpha 2 receptors in NA signalling?
Located on the presynaptic membrane and provide negative feedback mechanism to prevent further release of NA
57
What is the action of cocaine?
Blocks uptake 1 channels preventing NA reuptake --> more NA is available for signalling
58
What is the action of clonidine and its uses?
alpha2 receptor agonist --> inhibits NA release
| Uses: hypertension and tachycardia
59
How is NA inactivated?
1. Taken up presynaptically by uptake 1 channels --> MAO
| 2. Diffuses away and is taken up by extrasynaptic uptake (uptake 2) --> COMT --> MAO in liver and gut --> VMA in urine
60
What are the actions of salbutamol and salmeterol?
beta2 agonists --> bronchodilation (asthma) and uterine relaxation
61
What are the actions and uses of propanolol?
non-selective beta antagonist; used for hypertension, angina
62
What are the actions and uses of prazosin and tamsulosin?
Alpha adrenoreceptor antagonist --> benign prostatic hypertrophy
63
What are the effects of alpha1 stimulation on the following:
1. Vascular smooth muscle
2. Longitudinal muscle of GI tract
3. Anal sphincter
4. Urinary sphincter
5. Uterine muscle
6. Radial muscle
7. Salivary glands
8. Glycogen metabolism
9. Vas deferens
1. Vascular smooth muscle: contraction
2. Longitudinal muscle of GI tract: relaxation
3. Anal sphincter: contraction
4. Urinary sphincter: contraction
5. Uterine muscle: contraction
6. Radial muscle: contraction
7. Salivary glands: increased secretion
8. Glycogen metabolism: increase
9. Vas deferens: contraction
64
What are the effects of beta1 stimulation?
Increased heart rate and force of contraction
65
What are the effects of beta2 stimulation?
Relaxation of bronchial smooth muscle and vascular smooth muscle
Skeletal muscle, coronary and hepatic arteriole vasodilation
Uterine smooth muscle relaxation
Glycogen mobilisation in the liver
66
How do adrenaline and noradrenaline sympathomimetics differ in their action?
Noradrenaline: more potent on alpha receptors, least on beta2
Adrenaline: more potent on beta receptors, used also for anaphylactic shock (im or sc)
Both used for acute hypotension and cardiac arrest (iv)
67
Which are alpha-selective sympathomimetics?
phenylephrine (alpha1): acute hypotension
| clonidine (alpha2): hypertension, migraine
68
Which are beta-selective sympathomimetics?
Isoprenaline (beta): heart block
Salbutamol: asthma, premature labor
Dobutamine: cardiogenic shock
69
What are labetalol and carvedilol?
non-selective adrenergic receptor antagonists
70
What are propanolol and timolol?
beta-selective antagonists
71
What are metaprolol and atenolol?
beta1-subtype selective antagonists
72
What are the structures of muscarinic and nicotinic receptors?
Muscarinic:
-GPCR
-5 subtypes: M2 (cardiac) --> Galphai/o leads to decrease in cAMP; M3 (smooth muscle, glandular) --> increase in IP3 and DAG
Nicotinic: nonselective cation channel, causes rapid cell depolarisation --> 5 subunits and 2 subtypes
73
How does the baroreceptor reflex work?
Arterial stretch sensed by afferent nerves of vagus nerve (aortic arch) and glossopharyngeal nerve (carotids) --> signal to the NTS in brain stem:
1. increase PNS drive to heart --> decrease heart rate and CO
2. decrease SNS --> decreased TPR
since BP = CO*TPR --> BP decreases
74
What are the parasympathetic effects on the eye?
Accommodation for near vision --> contraction of ciliary muscle allows lens to relax
Pupil constriction --> contraction of sphincter pupillae muscle in the iris (pupil constriction)
Mediated by CN III (oculomotor nerve)
75
What are the mechanisms of cholinergic neurotransmission?
```
Choline acetyltransferase:
Acetyl CoA + choline --> acetylcholine
Storage in vesicles
Acetylcholinesterase:
ACh --> choline + acetate --> reuptake mechanism
```
76
Why is ecothiopate given for closed angle glaucoma?
long-lasting cholinesterase inhibitor:
| pupillary constriction increases outflow of acqueous humour --> decreased intraocular pressure
77
What is the action of botulinum toxin?
Binds to and degrades SNAP-25 --> prevents exocytosis of ACh and other NTs
78
How is salivary secretion controlled?
Afferents from smell, higher brain centres to hypothalamus and from trigeminal nerve (tongue) to brain stem:
1. Parasympathetic efferents: CN IX to parotid and VII to sublingual and submandibular
2. Sympathetic: through thoracic nerves I and II
79
Where is innervation to the GI tract located?
Submucosa: Messner's plexus
| Between inner circular and outer longitudinal: Auberbach's plexus
80
How do parietal cells work?
Activated H+/K+ ATPase by increase in cAMP --> canaliculi formation --> Cl- follows H+ through facilitated diffusion
Cl- enters cell at basolateral membrane through Cl-/HCO3- antiporter
81
How does the gastric phase of gastric acid secretion work?
Distension of the stomach:
1. ENS --> ACh --> stimulation of antral G cells, ECL cells and parietal cells
2. Vagovagal reflex --> ACh release + GRP (gastrin releasing peptide) --> stimulation of antral G cells --> gastrin --> ECL cells --> histamine --> parietal cells)
Digestion of protein:
1. peptides and amino acids stimulate antral G cells
82
What enzymes are present in the pancreatic juice?
Proteolytic: trypsinogen, chymotrypsinogen, procarboxypolypeptidase, ribonuclease, deoxyribonuclease
Amylase
Lipase
83
How are trypsinogen and chymotrypsinogen activated in the intestinal lumen?
Enterokinase: trypsinogen --> trypsin
Trypsin: chymotrypsinogen --> chymotrypsin
84
How are carbohydrates digested?
Pancreas and salivary glands secrete alpha-amylase: starch --> maltose + glucose
Small intestine secretes 1,6-glucosidase
Small intestine contains maltase, lactase and sucrase
85
How are proteins digested?
Stomach: HCl activates pepsinogen --> pepsins
Pancreatic juices: carboxypeptidases, trypsin, chymotrypsin
Small intestine: breakdown tri and dipeptides with aminopeptidases and dipeptidases; absorption through Na+ and H+ (tri and dipeptide) co-transport
86
How is bile secretion regulated?
PNS through vagus nerve --> production of bile in liver
Acidic chyme sensed by enteroendocrine cells of duodenum:
1. Secretion of secretin in the blood --> flow of bile rich in HCO3- and pancreatic juices
Fatty acids and amino acids in chyme:
2. Secretion of CCK --> contraction of gall bladder
87
What is bile flow dependent on?
partial pressure of O2
88
What is the structure of the biliary tree?
Apical membranes of hepatocytes form canaliculi --> terminal bile ductules (canals of Hering) --> perilobular ducts --> interlobular ducts --> septal ducts --> lobular ducts --> left and right hepatic ducts --> common hepatic duct + cystic duct --> common bile duct
89
How does the gallbladder concentrate bile acids?
Apical membrane:
1. Na-H and Cl-HCO3- exchangers --> reabsorption of NaCl
Basolateral membrane:
1. Na/K+ pump --> Na+ exits
2. Cl- leaves through channels
Additional:
1. H2O and HCO3- move through leaky junctions from lumen into blood
Result: isotonic bile with higher concentration of bile acids
90
How is bilirubin excreted?
85% from breakdown of red blood cells; fat soluble and toxic; bound to albumin in blood; free form taken up by the liver --> formation of bilirubin glucuronide --> secretion into bile canaliculi
15% reabsorbed in the intestine
91
How are lipids absorbed?
Glycerol, short-chain and medium-chain FAs: pass through enterocyte and enter capillaries
Cholesterol, lysophospholipids, long-chain FAs and monoglycerides: present in lumen as mixed micelles with bile salts --> allows absorption of fatty acids at brush border (low pH) --> SER, combine with apoproteins from RER to form chylomicrons (apo B48, C-II, E) or VLDLs --> Golgi --> lacteals
92
What is the function of cholesterol ester transfer protein?
Transfer cholesterol esters from HDL to VLDLs, IDLs or LDLs
| Cholesterol esters in HDL are formed by LCAT
93
How does the breakdown of fat work?
Lingual lipase
Breakdown in stomach (10-30%): gastric lipase + emulsification by gastric contractions
Breakdown and micelle formation in duodenum and jejunum (70-90%): pancreatic lipase
Absorption in small intestine
Excretion as Ca2+ soaps (5%)
94
What is the enterohepatic circulation of bile acids?
Bile acids are primarily conjugated to taurine or glycine to form bile salts --> secreted into the duodenum and then:
1. Reabsorbed passively as conjugated bile salts or through Na+-coupled transporters in terminal ileum
2. Bacteria in terminal ileum and colon deconjugate --> passively absorbed by nonionic diffusion
3. Bacteria in terminal ileum and colon dehydroxylate --> secondary bile salts --> passively reabsorbed or excreted in faeces
95
What are the causes of gallstones?
1. too much absorption of water from bile
2. too much absorption of bile acids
3. too much cholesterol in bile
4. inflammation of epithelium
96
What are the effects of vagal and splanchnic nerve stimulation on bile secretion?
Vagus: increase production and secretion
| Splanchnic nerve: vasoconstriction and reduced flow of bile
97
What is function of VIP on bile secretion?
Inhibits net fluid and electrolyte absorption in gallbladder
| alpha adrenergic blockage of neural VIP increases fluid absorption
98
What is the role of GIP?
inhibition of gastric acid secretion + stimulation of insulin secretion; produced by K cells of the duodenum and jejunum
99
What is the function of the chorda lingual nerve?
Parasympathetic innervation evokes marked fluid secretion accompanied by increased blood flow and oxygen consumption
100
What is the function of atropine on salivary excretions?
Atropine blocks secretion but not blood flow (VIP or substance P co-release)
101
How is salivation controlled?
Production of watery saliva is elicited by cholinergic, adrenergic and peptidergic stimulation
Sympathetic innervation: initial vasoconstriction (then vasodilation) with a viscous, protein-rich secretion via beta-adrenergic stimulation
102
What is the structure of the salivary tree?
Acinar cells --> ductule-striated or intercalated ducts --> larger ducts --> main excretory duct into the mouth
103
Through which pathways do sympathetic and parasympathetic nerves operate on salivary glands?
```
Sympathetic:
1. Beta1 --> increased cAMP and NO
2. Alpha1 --> increased Ca2+
Parasympathetic:
1. VIP --> increased cAMP and NO
2. ACh --> muscarinic 1, 3 receptors --> increased cAMP
```
104
How are primary and secondary saliva different?
Primary: isotonic to plasma
Secondary: hypotonic to plasma (reabsorption of NaCl + K+ and HCO3- secretion)
105
How is primary saliva produced?
NTs and hormones --> increase in intracellular Ca2+ in acinar cells:
1. Activation of K+ channels on basolateral membrane and Cl- channels on luminal
2. Reuptake via Na+-K+-2Cl- cotransporter dependent on Na+/K+ ATPase
Result: Cl- leaves through channels in luminal membrane and draws water and Na+ through paracellular space
106
What are the two phases of swallowing?
Voluntary phase: bolus and tongue movements
| Involuntary phase: reflex response stimulated by mechanoreceptors (CN IX and X)
107
How do gastric secretions vary between cardia, pyloric and oxyntic glands?
Cardiac glands: mucous primarily, few or no peptic or oxyntic cells
Pyloric glands: alkaline mucous juice and some electrolytes (Ca phosphate, NaCl, KCl and bicarbonates)
Oxyntic glands: key site of gastric HCl secretion
108
What are the different types of cells in gastric pits and what is their function?
Superficial epithelial cells
Mucous neck cells: HCO3- rich mucous secretion
Stem/regenerative cells
Parietal/oxyntic cells: HCl secretion
Chief cells: pepsinogen production and secretion
Endocrine G cells: gastrin secretion
109
What is the Dimaline model as opposed to the Soll's three receptor model?
Gastrin activates CCK2 on ECL-cell --> histamine is released and acts on H2 receptors on parietal cells --> cAMP increase
Other pathways:
1. Direct activation of parietal cells by gastrin (CCK2 receptors)
2. ACh activation by M3 receptors --> increase in Ca2+
110
What are the functions of famotidine and omeprazole?
Famotidine: H2 antagonist
Omeprazole: proton pump inhibitor
111
How is gastrin secretion regulated?
D-cells sense acid in stomach and release somatostatin which inhibits G-cells
112
What is the intestinal phase of gastric secretion?
Protein digestion products stimulate acid secretion:
1. Intestinal G cells --> gastrin
2. Intestinal endocrine cells --> entero-oxyntin --> G-cell stimulation
3. Absorbed amino acids --> G cell stimulation
Intestinal acid, fat and hyperosmolar solutions inhibit acid secretions:
1. receptors for H+, osmolarity and neutral amino acids --> sympathetic inhibition
2. fat --> secretion of SIH, GIP and secretin --> endocrine inhibition
113
What are the characteristics of pancreatic juice and how is it secreted?
HCO3- and NaCl-rich isotonic fluid
1. Basolateral uptake of Cl- through NKCC
2. Basolateral exit of Na+ through Na+/K+ ATPase and exit of K+ through channels (stimulated by Ca2+)
3. Cl- diffuses down electrochemical gradient at apical membrane
4. Na+ follows paracellularly
5. HCO3- produced by carbonic anhydrase --> diffusion and/or HCO3/Cl- exchanger
114
Is the GI tract single or multi-unit smooth muscle?
Single (gap junctions are present)
115
What are the interstitial cells of Cajal?
Act as pacemakers in the GI tract
116
What is the effect of vagal stimulation, CCK, GIP and secretin on gastric motility?
Vagal stimulation: increases
CCK: decreases
GIP: decreases
secretin: decreases
117
Which has the fastest spontaneous activity: stomach, duodenum, ileum or colon?
Duodenum
118
What is the function of motilin?
Regulates migrating motor complex from stomach to intestines
119
Which mechanisms regulate gastric emptying?
Neural enterogastric reflex:
1. Short reflexes operate via ENS
2. Long reflexes via CNS (increase symp and inhibit parasymp)
Hormonal mechanisms:
1. Secretin (stimulates HCO3- secretion and inhibits stomach activity)
2. CCK (gallbladder contraction and inhibits stomach activity)
3. GIP (inhibits gastric contractions)
4. Motilin (increases gastric and intestinal motility)
120
What are the crypts of Lieberkuhn?
Opening of intestinal glands
121
Which cells are present in the villous epithelium?
Goblet cells and absorptive cells
122
What is the function of Paneth cells?
Key effectors of innate mucosal defense of intestinal crypts
123
How is absorption of monosaccharides driven?
Basolateral Na+/K+ ATPase generates sodium gradient --> allows SGLUT to work
124
How is the absorption of oligopeptides through H+ cotransporter driven?
Apical Na+/H+ exchanger pumps H+ outside --> creates gradient
Basolateral Na+/K+ ATPase pumps Na+ outside --> creates gradient
125
What are hartnup disease and cystinuria?
Hartnup disease: autosomal-recessive --> reduced absorption of neutral amino acid phenylalanine
Cystinuria: autosomal recessive --> reduced absorption of L-cystine and cationic amino acids (L-arginine)
126
What are the differences between alpha and gamma tocopherol?
Alpha: resecreted as component of hepatically derived HDL and VLDLs
Gamma: metabolised and excreted by the liver
127
How are vitamins B and C absorbed?
B1, 2: sodium cotransporter in jejunum
| C: sodium cotransporter in ileum
128
How is calcium absorbed across intestinal epithelium?
Facilitated diffusion from lumen --> bound to calbindin intracellularly --> exits basolateral membrane via:
1. Ca2+/3Na+ exchanger
2. Ca2+/H+ ATPase
129
What are Brunner glands?
Situated in the duodenum --> secrete alkaline or neutral mucous
130
Which hormones act on the kidneys?
ADH, aldosterone, natriuretic peptides, parathyroid hormones, fibroblast growth factor 23 (FGF23)
131
Which hormones are produced by the kidneys?
Renin, vitamin D, erythropoietin, alphaKlotho, prostaglandins
132
What is the filtration interface of the renal corpuscle composed of?
```
Fenestrated capillary endothelium
Basement membrane (fixed polyanions)
Tubular epithelium (podocytes)
```
133
What are the types of nephrons and their prevalence?
Cortical (85%), juxtamedullary (15%)
134
What constitutes the juxtaglomerular apparatus?
Macula densa (end of ascending loop of Henle)
Mesangial cells in between the afferent and efferent arteriole
Juxtaglomerular cells on afferent arteriole (innervated by sympathetic fibers)
135
How much of the plasma that enters the glomerulus is filtered?
20%
136
What is a substance that is filtered and secreted but not reabsorbed?
PAH
137
What are substances that are filtered and some of it are reabsorbed?
Water and electrolytes
138
What is a substance that is filtered and completely reabsorbed?
Glucose
139
What is the maximal size for glomerular filtration?
7 kDa
140
What are the differences between ultrafiltrate and plasma?
Ultrafiltrate does not contain proteins and molecules that can bind to proteins (Ca2+ and some drugs)
Albumin binds acidic drugs, alpha1-acid glycoprotein binds basic drugs
141
What is the definition of GFR?
Volume of fluid filtered from the glomeruli per minute
142
What is the net glomerular filtration pressure?
(60-15)-(29-0)= 16 mmHg
143
What are the typical GFR and urine output?
GFR: 180 l/day
| urine output: 1.5 l/day
144
How is filtered glucose reabsorbed and where?
PT;
1. SGLT
2. GLUT facilitated transporters
3. Na+/K+ ATPase keeps gradient
145
How are amino acids reabsorbed and where?
PT;
at least 8 aa transporters, 6 Na+-dependent
Proteins: reabsorbed through endocytosis
146
How are phosphate and sulphate reabsorbed in PCT?
Na+ coupled transporters
147
Which compounds are passively reabsorbed in PCT?
urea, chloride, potassium, calcium
| bicarbonate (linked to H+ secretion)
148
Which compounds are secreted in PCT?
Organic acids (anions): enter basolateral through dicarboxylate exchange (OAT1,3; Na+ coupled transport with DC-), exit via ATP-dependent transporters
1. Drugs (penicillin)
2. Endogenous molecules (bile salts, fatty acids, prostaglandins)
3. diagnostic agent (PAH)
Organic bases (cations): enter via facilitated organic cation transporter (OCT2), exit through MATEs antiporter in exchange for H+ or OCTN
1. Endogenous molecules (creatinine, dopamine, choline, guanidine, histamine, serotonin, adrenaline)
2. Drugs (morphine, atropine)
149
What is the definition of clearance?
Volume of plasma that is cleared of a substance in a given time (uv/p)
150
Which substances are used to measure GFR?
Experimentally: inulin (filtered, not secreted, not reabsorbed)
Clinically: creatinine
151
How do you measure renal plasma flow?
renal plasma flow = PAH clearance (around 600 ml/min)
152
How do you calculate blood flow from plasma flow?
Blood flow = plasma flow/ (1-hematocrit)
153
What are the normal osmolalities for plasma and urine?
Plasma: 285-295 mosom/kg
Urine: 50-1400 mosm/kg
154
Where is the majority of sodium reabsorbed?
Proximal (65%) and thick (25%) ascending
| Hormonal control: distal (2-5%) and collecting (5%)
155
How is sodium reabsorbed in proximal tubule?
```
Apical:
1. Na/H exchanger
2. Na-nutrient symporter
Basolateral:
Na+/K+ ATPase
Others: Cl- follows paracellularly
```
156
How is sodium reabsorbed in the thick ascending limb?
```
Apical:
1. NKCC
2. K+ channels --> pump K+ out to create gradient
Basolateral:
1. Na/K+ ATPase
2. KCl cotransporter
3. Cl- channels
```
157
How is sodium reabsorbed in the distal tubule?
```
Apical:
1. NaCl cotransporter
Basolateral:
1. Na/K+ ATPase
2. Cl- channels
3. K+ channels
```
158
How is sodium reabsorbed in the collecting duct?
Principal cells (Na+ transport), intercalated cells (H+ transport)
Apical: eNaC
Basolateral: Na+/K+ ATPase
159
How does the loop of henle work?
Countercurrent multiplier
Descending limb: picks up salt and loses water (AQP1) --> progressively more concentrated
Ascending limb: solute pump, water-impermeable --> dilute urine (100 mosm/kg)
Vasa recta: countercurrent exchange mechanism
160
How does urea recycling by the kidney occur?
1. PT: passive reabsorption of urea (50%)
2. Loop of henle: apical secretion via urea transporters (UT-A2) --> 60% secreted
3. Inner medullary collecting duct (apical reabsorption via UT-A1 + UT-A3) --> 70% reabsorbed
40% of that filtrated is excreted
161
What is the action of ADH on collecting duct?
ADH stimulates GPCR --> increase cAMP --> activated PKA --> AQP2 expression on apical side
AQP3 and 4 on basolateral
162
What is the definition of oliguria?
Output below 0.428 l/day
163
What are the definitions of concentrated and dilute urine?
Dilute: <300 mosm/kg
Concentrated: >300 mosm/kg
164
How is osmolar clearance calculated?
Cosm = (Uosm*V)/Posm
165
What is the free water clearance?
```
Reflects the ability of the kidneys to excrete concentrated or dilute urine
Ch2o = V- Cosm
>0 --> hypo-osmotic
=0 --> isosmotic
<0 --> hyperosmotic
```
166
What are the regions involved in ADH release?
Osmoreceptors in OVLT, MPN, SFO signal to supraoptic nuclei (SON) and paraventricular nuclei (PVN) in hypothalamus --> ADH release from posterior pituitary
167
Which molecules increase/decrease ADH secretion?
Angiotensin II increases; natriuretic peptides decreases
Alcohol --> inhibits ADH
Nicotine --> stimulates ADH
168
What is diabetes insipidus?
1. urination (polyuria --> >2l/day)
2. thirst (polydipsia)
3. nocturia
Neurogenic: no ADH secreted
Nephrogenic: inherited mutation in channel or acquired
169
What is osmotic diuresis?
Increased urination due to small molecules in renal tubule lumen
170
What are the elements involved in the maintenance of potassium balance?
Renal excretion, GI losses, cellular shifts
171
How much potassium is ingested daily?
40-120 mmoles
172
How is potassium filtered, reabsorbed and secreted in urine?
800 mmoles/day is filtered
| 95% passively reabsorbed (65% passively in PT, 30% in thick ascending limb, 5% in distal tubule via K+/H+ exchanger)
173
How do collecting ducts influence K+ reabsorption and secretion?
Intercalated cells: K+ reabsorbed through K+/H+ exchanger
| Principal cells: K+ is secreted by ROMK, Ca2+ activated big-conductance K+ channels (BK) and KCl cotransporter
174
Which factors affect K+ secretion by principal cells?
1. Factors affecting Na+ entry through ENaC
2. Aldosterone stimulates K+ channels
3. Tubular flow rate: high flow favours secretion
4. Acid-base balance: acidosis inhibits, alkalosis enhances
175
What is hypokalemia and what are its causes?
K+ < 3.5 mM
1. Increased external losses (diuretics, hyperaldosteronism, alkalosis, vomiting, diarrhoea, burns, intense sweating)
2. redistribution into cells (metabolic alkalosis, insulin excess)
3. Inadequate K+ intake
176
What is hyperkalemia and what are its causes?
K+ > 5.5 mM
1. Decreased external losses (renal failure, hypoaldosteronism, action of drugs)
2. Redistribution out of cells (acidosis, lack of insulin, tissue destruction)
Treatment: Ca2+ iv, insulin administration, long-term diuretics
177
What is the lateral preoptic area responsible during water deprivation?
Osmoreceptors --> signal thirst
178
What are the intrinsic and extrinsic controls of GFR?
Extrinsic: maintains arterial BP by controlling GFR (sympathetic NS baroreceptor reflex)
Intrinsic: protects renal capillaries from hypertensive damage (tubuloglomerular feedback)
179
How does the tubuloglomerular feedback work?
Increased flow of Na through macula densa --> increased production of adenosine --> increased Ca2+ in granular juxtaglomerular and VSM cells --> constriction and inhibition of renin release
180
What stimuli lead to renin release?
1. low sodium delivery to macula densa
2. decreased wall tension in afferent arteriole (intrarenal baroreceptor)
3. sympathetic activity
4. low blood volume (hypovolemia)
181
What are the effects of renin?
```
Plasma angiotensinogen --> Angiotensin I
Angiotensin I + ACE --> angiotensin II:
1. Stimulates PT Na+ reabsorption
2. ADH release
3. Aldosterone secretion
4. Thirst
5. Vasoconstriction of small arterioles
```
182
What stimuli lead to aldosterone secretion?
Angiotensin II; increased K+ concentration
183
What are natriuretic peptides?
Released when the heart is stretched; A type from atrial myocardium and B type from ventricular myocardium
Actions:
1. Inhibit Na+ entry through ENaC in principal cells and Na/K ATPase in proximal tubule
2. inhibit renin release and aldosterone production
3. Inhibit ADH release
4. Systemic vasodilation --> decreased BP
5. Afferent arteriole dilation --> increased GFR
184
What are the buffers in blood, extracellular, intracellular fluid and urine?
Blood: hemoglobin, bicarbonate and plasma proteins
Extracellular fluid: bicarbonates, very little proteins
Intracellular fluid: intracellular proteins, phosphates, a little bicarbonate
Urine: ammonia, phosphates
185
How does the kidney control pH?
1. Absorb HCO3-
| 2. Excrete H+
186
Where does bicarbonate reabsorption occur?
PT, ascending loop of Henle, intercalated cells type A
H2O + CO2 + carbonic anhydrase --> H+ + HCO3-:
bicarbonate goes to blood
H+ secreted into filtrate --> not excreted if HCO3- is available in the lumen
187
How does H+ excretion happen?
In combination with nonbicarbonate buffer (monohydrogen phosphate)
Result: addition of new HCO3- to plasma
188
Apart from H+ excretion, what is another mechanism that produces new HCO3-?
Glutamine absorbed through Na+ symport into tubular epithelium
Glutamine metabolised in tubule epithelium --> ammonium ions + bicarbonate
Ammonium ions secreted through Na+ exchanger
189
What is the difference between respiratory and metabolic acidosis and alkalosis?
Respiratory acidosis: high pCO2
Respiratory alkalosis: low pCO2
Metabolic acidosis: low HCO3-
Metabolic alkalosis: high HCO3-
190
How is acidosis compensated?
1. Chemical: CO2 --> HCO3-
2. Brainstem: adjust ventilation
3. Renal mechanisms: increase plasma HCO3-
191
How is metabolic alkalosis compensated in the kidneys?
Type B intercalated cells secrete HCO3- through HCO3-/Cl- exchanger
192
How does glutamine production by the liver change in alkalosis and acidosis?
Acidosis: increases
Alkalosis: decreases
193
How is the epithelium of the colon?
Flat with deep crypts
194
What is the percentage of water in normal stool?
65-85%
195
How does intestinal Na+ reabsorption vary throughout the GI tract?
Proximal bowel: Na/H exchanger
Jejunum: SGLUT, Na-aa cotransport
Ileum: NaCl cotransport
Colon: Na+ ion channels + HCO3-/Cl- antiporter
196
What types of diarrhoea are there?
Congenital: deficiency of normal ion transport system (Cl-/HCO3- exchanger lacking)
Bacterial infection: cholera toxin --> permanently activates AC --> increased cAMP --> Cl- secretion
Osmotic (>350 mosm)
197
Which bacteria are present in the colon?
Bacteroides: gram-negative, anaerobic, non spore forming
Bifidobacteria: "good bacteria", gram-positive, non-sporeforming, lactic acid bacteria
