Module 1 Patho Term Sheet PDF

Term Sheet: Module 1 Patho 1.1 (G1) Functional Organization of the Human Body o​ Nuclear pores ​ Homeostasis o​ Nucleolus ​ Nutrients Extracellular vs intracellular ​ Diffusion vs active transport ​ ECF vs ICF...

Term Sheet: Module 1 Patho 1.1 (G1) Functional Organization of the Human Body o​ Nuclear pores ​ Homeostasis o​ Nucleolus ​ Nutrients Extracellular vs intracellular ​ Diffusion vs active transport ​ ECF vs ICF ​ Endocytosis ​ Nutrients & Metabolic Byproduct for: o​ Pinocytosis o​ Respiratory system o​ Phagocytosis ▪​ Alveolar membrane (thickness?) ​ ATP vs ADP o​ GI ​ Glycolysis o​ Liver ​ Krebs cycle ▪​ Bile ​ Electron transport chain In o​ Kidney o​ Oxidative phosphorylation ▪​ Plasma ​ ATP uses ex: ​ Nervous System (3) ​ Amoeboid Motion ​ Hormones regulation in fxn: o​ Pseudopodia o​ feedback mechanisms and ex. o​ Chemotaxis ​ Protection of Body: ​ Ciliary motion (rate?) o​ Immune system o​ Non-motile ▪​ Phagocytosis 1.3 (G4) Transport of Substances through cell ▪​ Antibodies membranes o​ Integumentary - thickest layer? ​ Hydrophilic vs Hydrophobic sides of cell membranes o​ Reproductive system ​ Simple diffusion (ex) ​ Negative vs Positive Feedback ​ Facilitated diffusion o​ Vmax 1.2 (G2) The Cell & its Functions ​ Rate of Lipid Soluble substances (ex) ​ Cell composition: water, ions, proteins, lipids, carbs ​ Pores ​ Structural vs functional proteins o​ Aquaporins o​ Integral vs peripheral proteins ​ Protein channels o​ Channels, active transport carriers, receptors o​ Ligand gated vs voltage gated ▪​ Ligand o​ Characteristics ​ Cell membrane (thickness?) o​ Ex w/ K o​ Amphipathic ​ Gating of Protein channels ​ Glycoproteins, proteoglycan, glycocalyx o​ Controlled by voltage, ligand (chemical) ​ Endoplasmic Reticulum ​ Factors the effect net diffusion rate (3) o​ Smooth (lipids, glycogen- for energy, detox) vs ​ Osmosis rough (protein synthesis, processing) ​ Osmotic pressure ​ Golgi apparatus o​ Molar concentration, osmole o​ Hyaluronic acid & Chondroitin sulfate ​ Osmolality vs osmolarity ​ Lysosomes o​ Normal osmolality o​ Autolysis & autophagy ​ Primary active transport vs secondary ​ Peroxisomes ​ Na/K pump ​ Mitochondria ​ Calcium primary active transport o​ Cristae ​ H Ion primary active transport ​ Cytoskeleton ​ Co-transport (symport) ex o​ Intermediate filaments ​ Counter-transport (antiport) ex o​ Actin filaments ​ Cellular sheets o​ Microtubules 1.4 (G5) Membrane Potentials ​ Nucleus ​ Resting Membrane Potential o​ Nuclear envelope o​ K vs Na roles ​ Nernst Potential o​ Effusion ​ Goldmans equation ​ Cardiac Pacemaker cells 1.7 (G31) Proteins as Intracellular Buffers o​ Oscilloscope : measures changes in membrane ​ Hydrogen ions influence: potential ( AP). how they got RMP (-70mV), ​ Acids vs bases threshold, etc. o​ Strong vs weak o​ Spontaneous depolarization ​ Dissociation constant ​ Nerve signals ​ pH & norm values o​ Resting, depolarization & repolarization ​ Buffer o​ Voltage-gated Na & K behaviors o​ Le Chatelier’s Principle o​ Conductance ​ 3 primary pH regulator systems o​ Threshold of activation o​ Chemical acid-base buffer system ​ Hyperpolarization o​ Resp ​ Axon o​ Renal system (kidneys) ​ Schwann cells ▪​ Filtration, reabsorption, secretion o​ Myelin ​ Bicarbonate buffer system ​ Nodes of Ranvier o​ Carbonic anhydrase o​ Saltatory Conduction (jumps) ​ Protein Buffers 1.5 (G6) The Microcirculation & Lymphatic System ​ Bicarbonate vs Hydrogen secretion ​ Branching of arteries into capillaries (size) ​ Resp Acidosis vs alkalosis ​ Capillary Diffusion ​ Metabolic acidosis vs alkalosis o​ Intracellular clefts ​ Anion gap o​ Special organs: brain, liver, GI & kidney ​ Bases excess vs deficit ​ Intermittent blood flow ​ Interstitial fluid (size) o​ Contains o​ Edema ​ Starling forces o​ PC #17, Pif #3, πC #28, πif #8 o​ NFP + vs – ​ Fluid Filtration & Reabsorption o​ Arterial end (+ NFP) o​ Venous end (- NFP) ​ Lymphatic system (size & flow) o​ Regulation of lymph flow ▪​ what increases lymph flow? 1.6 (G25) Regulation of Body Fluid Compartment ​ Daily water intake & loss o​ Output ex ​ TBF compartments o​ ICF, ECF, Interstitial fluid & Plasma ​ Tonicity o​ Isotonic, hypotonic & hypertonic solutions o​ Time for H2O absorption to equilibrate ​ Hypernatremia ​ Types of edema (2) o​ HF o​ Mechanism against edema ​ Potential spaces Mod 2 term sheet: (Guyton chapter 3, McCance 4,5,6) ​ Cell differentiation: changes in the physical and functional properties of the cell as they proliferate in the embryo to form diff body structures and organs ​ Apoptosis: programmed cell death ​ Phagocytosis: large molecules are engulfed by the plasma membrane and enter the cell so that they can isolated and destroyed by lysosomal enzyme ​ cancer/ mutation ○​ Proto-oncogenes: normal genes that code for various proteins that control cell adhesion, growth, division ○​ Oncogenes: mutated or excessively activated proto-oncogenes. Abnormally functioning- capable of causing cancer ○​ Antioncogenes: Tumor suppressor genes- suppress the activation of specific oncogenes ​ Chromosomes ○​ Gametes: sperm and egg. Haploid cells (1 member of each chromosome pair) 23 chromosomes ○​ Germline:a gene in a reproductive cell (egg or sperm) that is passed on to offspring ○​ Somatic: includes all cells other than gametes- diploid cells ( one chromosome from mom and one from dad) 46 chromosomes ​ Histone: Histones are vital proteins responsible for DNA packaging and provide structural support for chromosomes. DNA wraps around complexes of histone proteins, which helps give the chromosome a more compact shape. The histones are used as proteins for the DNA to be coiled around. ○​ Mccance: proteins that facilitate the compaction of genomic DNA by coiling into the nucleus of a cell. ​ Gene: a specific segment of DNA that contains the instructions for making a particular protein ​ Allele: genes at a particular locus can have diff. Forms (composed of diff. Nucleotide sequences) ​ Locus: each gene occupies a position along a chromosome ​ Polymorphic: locus that has two or more alleles that each occurs with an appreciable frequency in a population ​ Genotype: composition of genes at a given locus ​ Phenotype: outward appearance of an individual (result of genotype and environment) ​ Dominant: allele whose effects are observable ​ Recessive: allele whose effects are hidden ​ Carrier ​ Homologous: when two alleles are identical (homo at that locus) ​ Heterozygous: when two alleles are not identical ( hetero at that locus) ​ Polyploidy: when a euploid cell has more than the diploid # of chromosomes ○​ Triploidy:: a zygote that has three copies of each chromosome, rather than two (extra set of chromosomes) ​ Zygote: fertilized cell from male and female gamete ​ Aneuploidy: a cell that does not contain a multiple of 23 chromosomes ○​ Trisomy: cell containing three copies of 1 chromosome ( 1 extra chromosome) ​ Abnormalities of chromosome structure ○​ Deletions ​ Cri du chat: deletion short arm of chromosome 5 ○​ Duplications ○​ Inversions: two breaks take place on a chromosome, followed by the reinsertion of the missing fragment at its original site but in inverted order ○​ Translocations: interchange of genetic material between nonhomologous chromosomes ​ Robertsonian translocation: long arms of two nonhomologous chromosomes fuse at the centromere, forming a single chromosome ​ Reciprocal translocation ○​ Fragile sites: (breaks /gaps on chromosomes) ​ Fragile x- syndrome ​ Down syndrome: trisomy of chromosome 21 ​ Turner syndrome: (45, X) monosomy of X chromosome ​ Klinefelter syndrome: (47, XXY) XXY condition ​ Transmission of genetic dx ○​ Mendelian trait/gene: traits caused by a single gene ○​ autosomal dominant ​ Penetrance: % of individuals with a specific genotype who also exhibit the expected phenotype ​ Expressivity: extent of variation in phenotype associated with a particular genotype ​ Obligate carrier: those who have affected parents and affected children and, therefore, themselves must carry mutation ○​ Autosomal recessive ​ Consanguinity: marriage between related individuals ○​ X-linked dominant ○​ X-linked recessive ​ Relative risk (equation): increased rate of the dx among individuals exposed to a risk factor/ incidence rate of the dx among individuals not exposed to a risk factor ​ Multifactorial inheritance ○​ Polygenic: traits in which variation is thought to be caused by a combined effect of multiple genes ○​ Multifactorial trait: when environmental factors are also believed to cause variation in the trait ​ Recurrence risk ○​ Threshold of liability: refers to a hypothetical point on a continuous scale of genetic and environmental factors where, if an individual's combined liability exceeds that point, they will develop a particular disease or trait ○​ Twin studies ​ MZ: monozygotic ( identical)  ​ DZ Dizygotic (fraternal) ​ Concordant: if both members share a trait ​ Discordant: if both twins do not share a trait ○​ Epigenetics: DNA sequence can produce dramatically diff. Phenotypes b/c of chemical modifications altering the expression of genes ​ DNA methylation: the attachment of a methyl group to a cytosine base followed by a guanine base in the DNA sequence ​ Somatic mosaicism ○​ Histone modification ​ Heterochromatic: DNA is tightly bound into a condensed state and is not actively transcribed (dense methylation) ​ Heterchromatin: closed state, transcriptionally inactive ​ Euchromatic: rich in genes, open state and is genetically active ​ Histone modifications​ ​ Acetylation: Histone acetylation leads to relaxation of the chromatin and hence greater transcription. ​ Methylation: the modification of specific amino acids in a histone protein by adding one, two, or three methyl groups ( suppress the function of the gene) ○​ Non-coding RNAs ​ miRNAs: a class of non-coding RNAs that play important roles in regulating gene expression. ​ Oncomirs: miRNAs regulate diverse signaling pathways, those that stimulate cancer development and progression are called oncomirs ○​ Genetic imprinting: A process where one parent’s allele is silenced, and the other is active ​ Biallelic: Both maternal and paternal alleles are active and expressed. ​ Monoallelic: Only one allele (from either the mother or the father) is active, while the other is silenced (imprinted). ​ Imprinting: The silencing of one allele of a gene due to epigenetic modifications ○​ Prader willi syndrome: deletion of the long arm of chromosome 15, inherited from father ( short stature, obesity, hypogonadism) ○​ Angelman syndrome: same deletion (deletion of the long arm of chromosome 15) inherited from mother (intellectual disability, seizures, ataxic gait) ○​ Beckwith-Wiedemann syndrome (imprinting- two copies of a chromosome from mom and none from dad (uniparental disomy, chromosome 11) ○​ Tx of epigenetic dx ​ DNA methylating agents: 5-azacytidine ​ Histone deacetylase inhibitors increase chromatic compaction- decreasing transcriptional activity M2 Genetics Practice Questions 1.​ What is the difference between a proto-oncogene and an oncogene? 2.​ What is the function of an antioncogene? 3.​ What are the two main types of cells found in the human body? 4.​ What is the function of histones? 5.​ Describe the difference between an allele and a locus. 6.​ What is the difference between a genotype and a phenotype? 7.​ Explain the difference between a dominant and a recessive allele. 8.​ What is meant by homologous chromosomes? 9.​ What is polyploidy? 10.​ What is the difference between triploidy and aneuploidy? 11.​Describe the difference between a duplication and an inversion. 12.​What is a translocation in the context of chromosomes? 13.​Explain the difference between a Robertsonian translocation and a reciprocal translocation. 14.​What is the difference between a concordant and discordant trait in twin studies? 15.​ What is epigenetics? 16.​What are the key differences between euchromatin and heterochromatin? 17.​What are the two primary histone modifications discussed in the text? 18.​Describe the role of non-coding RNAs in gene regulation. 19.​What is genetic imprinting? 20.​What is the difference between biallelic and monoallelic expression? 21.​Describe the characteristics of Prader-Willi Syndrome. 22.​What is the difference between Angelman Syndrome and Beckwith-Wiedemann Syndrome? 23.​How can epigenetic disorders be treated? 24.​Which of the following is NOT a characteristic of aneuploidy? a.​ A) A cell with an extra chromosome b.​ B) A cell lacking a complete set of chromosomes c.​ C) A cell containing three copies of one chromosome d.​ D) A cell containing a multiple of 23 chromosomes 25.​What is the term for a gene that is expressed only if two copies of the recessive allele are present? a.​ A) Dominant allele b.​ B) Recessive allele c.​ C) Carrier allele d.​ D) Polymorphic allele 26.​Which of the following is a type of genetic imprinting? a.​ A) Biallelic expression  b.​ B) Polygenic inheritance c.​ C) Monoallelic expression d.​ D) Multifactorial inheritance 27.​ A concordant trait in twin studies suggests a strong environmental influence. a.​ True b.​ False 28.​Histone acetylation generally leads to increased chromatin compaction and decreased transcription. a.​ True b.​ False 29.​ Non-coding RNAs play a role in regulating gene expression. a.​ True b.​ False 30.​ Genetic imprinting is a phenomenon where the expression of a gene is determined by its parental origin. a.​ True b.​ False 31.​ Prader-Willi Syndrome is caused by a deletion on chromosome 15 inherited from the mother. a.​ True b.​ False 32.​Beckwith-Wiedemann Syndrome is characterized by uniparental disomy of chromosome 11. a.​ True b.​ False Answers: 1.​ A proto-oncogene is a normal gene that controls cell growth and division. An oncogene is a mutated or excessively activated proto-oncogene that can cause cancer. 2.​ Antioncogenes suppress the activation of specific oncogenes. 3.​ somatic (body with 46 chromosomes) and gremlin (sex cells with haploid - or half 23 chromosomes) cells 4.​ Histones are proteins that facilitate the compaction of genomic DNA by coiling it into the nucleus of a cell, providing structural support for chromosomes. 5.​ An allele is a specific form of a gene, while a locus is the specific position of a gene on a chromosome. 6.​ A genotype refers to the genetic makeup of an individual, while a phenotype refers to the observable physical characteristics of an individual, influenced by both genotype and environmental factors. 7.​ A dominant allele exerts its effect regardless of the other allele present, while a recessive allele's effect is only observable if two copies of the recessive allele are present. 8.​ Homologous chromosomes are pairs of chromosomes that contain the same genes at the same loci, one chromosome inherited from the mother and the other from the father. 9.​ Polyploidy is a condition in which a euploid cell has more than the diploid number of chromosomes. 10.​triploidy is a condition where a zygote has three copies of each chromosome, while aneuploidy is a condition where a cell does not contain a multiple of 23 chromosomes, often due to the gain or loss of a single chromosome 11.​ duplication involves the duplication of a segment of a chromosome, while an inversion involves the reversal of a segment of a chromosome. 12.​A translocation involves the exchange of genetic material between nonhomologous chromosomes. 13.​A Robertsonian translocation involves the fusion of the long arms of two nonhomologous chromosomes, forming a single chromosome, while a reciprocal translocation involves an exchange of segments between two nonhomologous chromosomes, without any loss of genetic material 14.​ A concordant trait is one that is shared by both members of a twin pair, while a discordant trait is one that is present in one twin but not the other. 15.​ Epigenetics refers to changes in gene expression that do not involve alterations to the underlying DNA sequence, but rather involve modifications to the DNA or the proteins associated with it. 16.​Euchromatin is a less condensed form of DNA (when DNA is wound loosely around histones) that is transcriptionally active, while heterochromatin is a more condensed form of DNA ( DNA is tightly wrapped around histones) that is transcriptionally inactive. 17.​Histone acetylation which diminished the positive charge of histone, reducing the binding strength to DNA. This leads to the relaxation of chromatin and increased  transcription. Histone methylation which can either increase or decrease bonding strength between DNA and histones (depends on location). 18.​Non-coding RNAs, particularly microRNAs (miRNAs), play a significant role in gene regulation by controlling the expression of messenger RNA (mRNA) molecules, which are responsible for protein synthesis. 19.​Genetic imprinting is a phenomenon where the expression of a gene is determined by its parental origin, meaning that only one of the two alleles is active, depending on whether it was inherited from the mother or the father. 20.​Biallelic expression occurs when both maternal and paternal alleles are active and expressed, while monoallelic expression occurs when only one allele is active and the other is silenced. 21.​Prader-Willi Syndrome is a genetic disorder characterized by short stature, obesity, hypogonadism, and intellectual disability, typically caused by a deletion of the long arm of chromosome 15 inherited from the father. 22.​Both Angelman Syndrome and Beckwith-Wiedemann Syndrome are genetic disorders, but they are caused by different genetic mechanisms. Angelman Syndrome is often caused by a deletion of the long arm of chromosome 15 inherited from the mother resulting in intellectual disability, seizures, and ataxic gait. Beckwith-Wiedemann Syndrome is characterized by overgrowth, organomegaly, and an increased risk of tumors, often caused by uniparental disomy of chromosome 11. 23.​ Epigenetic disorders can be treated with DNA methylating agents, such as 5-azacytidine, and histone deacetylase inhibitors, which increase chromatic compaction and decrease transcriptional activity. Also, microRNA encoding loci can be up or down regulated. 24.​D 25.​B 26.​C Monoallelic expression is a hallmark of genetic imprinting, where only one allele from either the mother or the father is active. 27.​B Concordant traits in twin studies suggest a strong genetic influence. A concordant trait indicates that both twins share the same trait, which is more likely due to shared genetic makeup than environmental factors. 28.​B Histone acetylation generally leads to relaxation of chromatin, making DNA more accessible to transcription factors, ultimately increasing transcription. 29.​A Non-coding RNAs, such as microRNAs (miRNAs), play a crucial role in gene regulation primarily by controlling the expression of mRNA molecules, which are responsible for protein synthesis. 30.​A 31.​B - inherited from the father 32.​A 33.​ M3: Renal Term Sheet o​ NFP of glomerulus #s o​ Glomerular capillary colloid osmotic pressure ​ Renal Homeostasis Mechanisms (7) influence by (2) ​ Kidneys o​ Glomerular hydrostatic pressure influence by o​ Cortex (3) o​ Medulla ​ Renal Blood flow equation o​ Hilum o​ Factors controlling vascular o​ Renal Pyramids o​ Papilla resistance o​ Minor to Major calyces o​ SNS vs hormones o​ Renal pelvis o​ Endothelin o​ Ureter o​ Urethra ​ Autoregulation ​ Renal artery vs vein ​ Nitric Oxide (NO)-induced vasodilation o​ Segmental arteries ​ Juxtaglomerular feedback mechanism o​ Interlobular arteries o​ Arcuate arteries & Veins 3.3 Renal tubular reabsorption and secretion ​ Renal Blood flow o​ Leading to nephron ​ Pinocytosis ​ Nephron anatomy ​ PT reabsorption o​ Glomerulus o​ Transcellular vs paracellular pathway o​ Bowman’s Capsule o​ Primary active & secondary active o​ Proximal Tubules (PT) o​ Loope of Henle (LOH) transport (ex) o​ Distal tubules (DT) ​ SGLT 1 vs 2; GLUT 1 vs 2 o​ Collecting ducts (CT) ​ Secondary active co-transport vs ​ Juxtamedullary apparatus counter-transport (ex) o​ Macula densa ​ Transport maximum (ex) vs no TM ​ Cortical vs Juxtamedullary Nephrons ​ Passive water reabsorption throughout o​ Vesta Recta the nephron ​ Bladder Anatomy ​ Chloride reabsorption o​ Body vs neck o​ Detrusor muscles ​ Proximal Tubule reabsorption o​ Internal sphincter ​ Loop of Henle (LOH) reabsorption o​ Urethra o​ Thin D, thin A, thick A o​ External sphincter ​ DT reabsorption ​ Bladder innervation o​ Principle vs intercalated cells o​ Micturition reflex vs detrusor muscle ​ CD reabsorption o​ Pudendal nerve o​ Type A vs B intercalated cells ​ Bladder flow o​ Cortical vs medullary CD ​ Filtration only (ex) vs filtration w/ partial ​ Ex Diuretics MOA & locations of effect reabsorption (ex) vs filtration w/ ​ Glomerulotubular balance (%?) complete reabsorption (ex) vs filtration ​ Filtration coefficient w/ secretion (ex) ​ Reabsorption into peritubular capillaries ​ Urine excretion equation ​ Hormones that control tubular 3.2 Glomerular filtration, renal BF, & their reabsorption control o​ Aldosterone ▪​ Addisons disease vs Khan syndrome ​ Glomerular filtration (L/day?) o​ Angiotensin II o​ Filtration fraction equation (average?) o​ ADH ▪​ AQP-2 o​ Capillary membrane anatomy o​ ANP o​ Fenestrae vs podocytes (pore size) o​ PTH ​ GFR equation ​ Renal clearance o​ Normal filtration coefficient (Kf) o​ Inulin  o​ Creatinine ​ Thirst center 3.4 Urine concentration & Dilution 3.5 Renal Regulation of K, Ca, Phos, Mg ​ Osmolarity ​ Potassium regulation o​ Dilute vs concentration urine o​ Insulin o​ Changes in osmolarity throughout o​ Aldosterone nephron o​ Secretion vs reabsorption ​ Osmolarity gradient ​ Calcium regulation o​ Hyperosmolarity o​ Alkalosis ​ Counter current multiplier o​ PTH ​ Urea ​ Phosphate Regulation o​ ADH impact on urea reabsorption o​ PTH o​ Transporter protein? ​ SNS ​ Medullary Blood flow o​ ADH o​ Vasa recta o​ ANP ​ Obligatory urine volume o​ CHF ​ ADH synthesis, secretion and sensitivity Questions: 1.​ What type of feedback loop does the micturition reflex use? 2.​ The external sphincter of the bladder is controlled by which nerve fibers? 3.​ What is the difference between the micturition reflex and detrusor muscle in facilitating urinary bladder emptying? 4.​ What are the short and long-term arterial pressure regulations performed by the kidneys? 5.​ What are the 5 main anatomical structures that pass through the kidney’s hilum? 6.​ Which part of the kidney does the vasa recta located and why? 7.​ What is the average filtration fraction and what does that mean? 8.​ What charge is the podocyte cells and why is this important? 9.​ What is the normal glomerulus versus Bowmen’s capsule (BC) colloid osmotic pressure? 10.​What does increasing vs decreasing arterial plasma colloid osmotic pressure have on glomerular filtration and GFR? 11.​Increasing afferent arteriolar resistance would ______ hydrostatic pressure and GFR; whereas, slight increase in efferent arteriolar resistance would ______ hydrostatic pressure and GFR. 12.​Severe increase in efferent arteriolar resistance would ______ GFR. Why? 13.​What is a circulating hormone and locally produced by autocoid in kidneys and system circulation, AND preglomerular vessels are generally protected from its effects? 14.​Explain how patients with atherosclerosis may have impaired Nitric oxide (NO) production and how that impacts the renal function. What important ion is needed for NO-induced vasodilation? 15.​What is the importance of autoregulation of GFR? 16.​What electrolytes do the juxta-glomerular feedback mechanism depend on and why? 17.​How do sodium and glucose get moved from the tubular fluid lumen into the PT tubular cells and then into the peritubular capillaries? What kind of transport and pathway is this example? 18.​Does Na mostly move through the paracellular or transcellular pathway? 19.​What forces drive the passive passage of solutes and water from the interstitial fluid into the peritubular capillaries? 20.​What is the NHE protein and what does it do? 21.​What is glucose transport maximum? 22.​What 3 factors influence the rate of transport if there is no transport maximum? 23.​What areas of the nephron are permeable to water? What areas are dependent on ADH to determine water reabsorption? 24.​Why does chloride passively diffuse from the tubular lumen after sodium? 25.​In PT, how does Na concentration remain the same in tubular lumen when 65% of Na and water are reabsorbed here? 26.​What is the think ascending segment important for making urine? 27.​Explain what 2 protein transporters on the apical side of the TALH side play a key role in the? What is the essential protein transporter on the basal lateral side? 28.​What site of action does loop diuretics, like Lasix, work on? 29.​What diuretic inhibits sodium chloride co-transporter located in the DT? 30.​Where is the site of action for K-sparing diuretics? 31.​What is the difference between the principle cell and intercalated cells of the late DT and cortical collecting tubules? 32.​Which intercalated cells type is usually increased with chronic alkalosis vs chronic acidosis? 33.​What do Type A and B intercalated cells have in common that are important for acid base regulation? 34.​Which part of the collecting ducts is impermeable to urea and which part is permeable? 35.​What does Kf measure and what would decreasing Kf impact reabsorption into peritubular capillaries? 36.​What happens when peritubular capillaries reabsorption is reduced? 37.​What are the 2 most important stimuli for aldosterone? 38.​How does ADH stimulate placement of aquaporins _______? 39.​What does ANP directly inhibit when stimulated by increased atrial blood pressure? 40.​ How does PTH impact calcium and phosphate reabsorption when released? 41.​What is the difference between using inulin and creatinine to determine GFR? 42.​ What is the lowest urine osmolarity can be when hydrated vs the highest urine osmolarity when dehydrated? 43.​Where is ADH synthesized and secreted from? 44.​Does the presence of ADH effect excretion of solutes? 45.​What is the osmolarity of filtrate as it enters the PT? Does it change while in the PT? 46.​Why does the osmolarity at the bottom of descending LOH get as high as 1200? 47.​What is the osmolarity difference in concentration gradient between the ascending limb and the renal interstitium? 48.​Why is the fluid leaving the distal convoluted tubule have such a low osmolarity of 100-140? 49.​Where does ADH have an effect on the nephrons tubules? 50.​Where is urea reabsorbed and why is it important? 51.​Which urea transporter is used for small amounts of urea secretion INTO the tubular fluid? 52.​Why is the vesta recta important carrier of blood into the renal medulla? What does the osmotic gradient mirror? 53.​What are the 2 major regulatory systems for sodium and osmolarity in the body? 54.​Is ADH secretion more sensitive to osmolarity changes or changes in blood pressure? 55.​Where is the thirst mechanism located and how is it stimulated? 56.​Which 2 hormones impact the reuptake of K? 57.​What are most important sites for K regulation? What 2 channels are found at these sites needed for K diffusion? 58.​What type of feedback controls aldosterone secretion? 59.​What percentage of calcium is ionized and biologically active at the cell membranes? What percentage is bound to plasma proteins? How does pH impact these Ca percentages? 60.​ When PTH is stimulated, how does this impact calcium and phosphate regulation? 61.​Explain how CHF leads to a positive feedback loop of the RAAS and the development of circulatory congestion. Answers: 1.​ Positive Feedback 2.​ Skeletal motor fibers – for voluntary control 3.​ The detrusor muscle is a smooth muscle that contracts to enable emptying the bladder, whereas the micturition reflex is an autonomic spinal cord reflex that triggers the sensation or desire to urinate. 4.​ Short term arterial pressure regulation is when the kidneys secrete hormones, such as renin, and long-term BP regulation is done by regulating the sodium and water balance. 5.​ The renal artery, vein, lymphatics, nerves, and ureter. 6.​ Located in the juxtamedullary nephrons, because this specialized vascular structure helps concentration of urine by maintaining hyperosmolar concentration needed in the renal medulla. 7.​ 0.2, which means 20% of the plasma flowing through the glomerulus is filtered into the renal tubules. 8.​ They are negatively charged cells and are important in repelling negatively charged proteins from entering the filtrate fluid. Helps maintain the selective permeability of the glomerulus membrane. 9.​ Glomerular Colloid osmotic pressure is usually 32mmHg and the BC is zero because there are no proteins in the BG. 10.​Increasing would arterial plasma colloid pressure would cause more colloid proteins to “keep the fluid in” the glomerular capillary space reducing filtration and GFR. In contrast, having less colloid proteins would decrease the pressure “keeping the fluid” in the capillary space filtration would increase along with GFR, BUT raised filtration rate causes concentration of plasma proteins and increases capillary osmotic pressure leading to reduction on GFR. 11.​ Decrease and increase 12.​Decrease because fluid would be unable to flow forward, out of the glomerulus creating a high concentration of plasma proteins inc. colloid osmotic pressure decrease filtration & GFR 13.​Angiotensin II 14.​ Patients with atherosclerosis may have impaired NO production due to vascular endothelial cell damage, which inhibits the NO (a vasodilator) increasing vascular resistance in the kidneys. Arginine simulates NO production, where NO converts GTP to cyclic GMP that interacts with phosphodiester, reducing intracellular Calcium levels. This causes relaxation of the vascular smooth muscle. 15.​GFR autoregulation is critical for maintaining constant GFR despite changes in BP, preventing large shifts in water and Na while maintaining a constant flow to kidneys (preventing renal damage). 16.​Juxtaglomerular feedback mechanism depends on NaCl concentrations in the DT where the macula densa is located. The macula dense cells with golgi apparatus that face the afferent and efferent arterioles, detect if NaCL levels are low and secrete renin to prevent low GFR and stabilized renal blood flow. 17.​In the PT, Na easily goes down the concentration gradients from tubular lumen into epithelial cells via the transcellular pathway. This concentration gradients is maintained by the Na/K ATPase pump, keeping intracellular Na levels low to maintain this ion movement. Glucose is co-transported with the Na ions into the cell through secondary active transport by the SGLT (mostly the SGLT 2) transporter protein. Once in the cell, glucose diffuses out via the GLUT (1 & 2) on the basal lateral side, but is considered secondary active transport because the GLUT depends upon the Na/K ATPase pump to maintain a favorable concentration gradient. 18.​Transcellular pathway 19.​Hydrostatic and colloid osmotic pressure gradients 20.​NHE = Na-hydrogen exchanger protein that facilitates counter-transport of Na into the cell (via diffusion) and Hydrogen out of the cell. 21.​TM for glucose = 375mg/min 22.​Electrochemical gradient, permeability of the membrane, and time that the substances remain in the tubules. 23.​PT and thin descending loop of Henle are permeable to water through aquaporins-1 channels & tight junctions (via paracellular pathways). ADH influences aquaporin-2 channel placement in the late DT and collecting ducts, increasing water permeability. 24.​As Na and water are reabsorbed from the tubular lumen, Chloride ions are concentrated, creating a concentration gradient for Cl to passive diffuse through the paracellular pathway. 25.​Na concentration remains the same within the tubular lumen of the PT despite the large amount of reabsorption of Na, because 1) water is being reabsorbed at the same rate, leading to stable Na osmolality 2) decreased amount of water allows for non-permeable solutes (like creatinine) to increase concentration and making osmolarity remain the same. 26.​Thin ascending LOH is impermeable to water and very permeable to solutes, so it helps dilute urine. 27.​The NKCC-2 and Na/H counter-transporter on the apical membrane of TALH play a key roll in facilitating secondary active transport of Na, K and 2Cl out of the tubular lumen. The Na/K ATPase pump is the essential active transport pump on basal lateral membrane that maintains the negative intracellular membrane potential so both NKCC-2 and Na/H counter pumps can function. This allows the large reabsorption of solutes. 28.​Inhibits the NKCC-2 transporter in the TALH. 29.​Thiazide diuretics 30.​In the late DT where they inhibit the Na/K ATPase transporter, this will inhibit K excretion because the concentration gradients that favors K from leaving the inside of the cell will be blocked. 31.​The principle cells reabsorb water and Na while secreting K into tubular lumen, while intercalated cells reabsorb K and secrete hydrogen into the tubular lumen. 32.​For chronic alkalosis, type B intercalated cells are increased b/c they secrete HCO3 and reabsorb H through Pendrin protein (which is Cl/HCO3 counter-transporter). For chronic acidosis, type A cells would increase b/c they secrete H through H-ATP pump and H/K ATP counter-transporter. 33.​Both A & B intercalated cells us carbonic anhydrase inside their cells to buffer H and bicarb into water and carbon dioxide, so both acid and bases can be transported. 34.​The cortical collecting ducts is impermeable to urea and the medullary collect is permeable to urea, helping kidneys concentrate urine. 35.​The Kf (filtration coefficient) measures the permeability and surface area of the capillaries, so decreasing kf would lower reabsorption. 36.​Increase in peritubular capillaries hydrostatic pressure, which pushes solutes back into the interstitium and leaks back into the tubular lumen. 37.​Increased extracellular K and increased angiotensin II levels. 38.​AHD stimulates the placement of AQP-2 by binding to V2 receptors of GPCR that increases cAMP that consequently activates protein kinases. This stimulates protein phosphorylation and exocytosis of AQP-2 along the luminal side allowing water to diffuse out of the tubular lumen. 39.​ANP inhibits renin secretion and reabsorption of Na and water in renal tubules. 40.​PTH increased calcium and magnesium reabsorption and inhibits phosphorate reabsorption, promoting phos secretion. 41.​Inulin has to be injected but is a great tool for determining GFR because it is not reabsorbed, but creatinine is more commonly used because it is entirely filtered by glomerular filtration and only minimal amount is secretion. So GFR us approximately equal to creatinine clearance = urine conc. of creatinine X urine flow rate divided by plasma conc. of creatinine. 42.​ Urine osmolarity can be as low as 50 mOsm/L and high as 1400 mOsm/L. 43.​From the supraoptic and paraventricular nuclei of the hypothalamus, where ADH hormone is transported via axonal extension to the posterior pituitary where it is stored. ADH is stimulated by increased osmolarity where a nerve impulse to the poster pituitary releases calcium ions, allowing ADH to be released into the bloodstream. 44.​No, ADH impacts water reabsorption in late DT and CD without changing the excretion of solutes. However, ADH does facilitate the diffusion of urea in CD by activating urea transporter (UT-A1 and UT-A3). 45.​The osmolarity in the PT is ~300 and it does NOT change because the solute and water reabsorption are happening in equal proportions, so the filtrate remains isosmotic. 46.​The filtrate as it descending the LOH is only permeable to water, so water leaves the tubule lumen via osmosis. The hypertonic environment of the renal medulla pulls the water from the filtrate, concentrating the tubular fluid. 47.​200 mOsm/L gradient, which helps facilitate the countercurrent flow. 48.​Because the TALH is reabsorbing solutes via secondary active transport, diluting the fluid. 49.​ADH effects the permeability of water reabsorption on the cortical collecting tubules and major collecting ducts, making urine highly concentrated. 50.​Urea contributes to about 50% of the osmolarity of the renal medullary interstitium, helping create the hyperosmotic gradient in the renal medulla needed for water reabsorption. 51.​UT-A2 transporter located on the thin LOH. 52.​ The vasa recta acts as a countercurrent exchanger as it prevents the loss of solutes from the renal medullary interstitial fluid. The vasa recta mirrors the osmolarity of the LOH, preventing the dissipation of the medullary osmotic gradient. 53.​Osmoreceptor-ADH system and thirst mechanism 54.​Osmolarity changes, only few % change in plasma osmolarity can significantly increase ADH levels, whereas, ADH secretion does not substantially increase until blood volume decreases by 10%. 55.​Thirst center is located anterior ventral wall of the third ventricle of the brain. It is stimulated by intracellular dehydration that can be causes by increased osmolarity; while decreased extracellular fluid/volume or decreased arterial pressure independently stimulates thirst. Angiotensin II (acts on a region outside the BBB), mouth/mucus membrane dryness, and GI and pharyngeal stimulation can also stimulates thirst center. 56.​Insulin stimulates Na/K ATPase to pump K into cells. Aldosterone stimulates B-adrenergic receptors to increased K reuptake into the cell, which then passively diffuses from inside the principal cell out into tubular fluid for excretion via K channels. This is facilitated by the Na/K ATPase pump absorbing Na and secreting K. *PT on beta blockers risk for HyperK. 57.​Late DT and cortical CD are main sites for K regulation b/c they can EITHER reabsorb or secret K based on body’s needs. The ROMK and BK channels are located here for K to diffuse out for excretion. 58.​Aldosterone negative feedback is controlled by extracellular K concentration, so increase plasma K will stimulate aldosterone secretion. 59.​50% is ionized with 40% bound to plasma protein & 10% unionized. Having a high pH (alkalosis) can increased plasma protein binding to Ca, leading to hypocalcemia (ex: tetany). 60.​ PTH is stimulate in response to low plasma Ca promoting Ca reabsorption in DT by increasing luminal Ca channels and basolateral Ca ATPase pump and Na/Ca exchangers. PTH is also stimulated in response to high plasma phosphate promoting reduced Phos reabsorption by decreasing the luminal Na/P cotransporters increased phos excretion. 61.​In heart failure, the heart is poorly pumping blood leading to the activation of the RAAS to increase the reduced arterial pressures. The arterial pressure is still too low, so the body continues to release renin stimulating angiotensin II increasing water and Na reabsorption. The heart is still unable to pump well, leading to a back flow fluid into the lungs, but the RAAS is still stimulated because of poor arterial pressures and the cycle continues as circulatory congestion develops.