CBLG600 Lecture 9ish

Respiratory/ Renal: acid-bases: lungs eliminate volatile carbonic acid by [blank_start]eliminating CO2[blank_end] -Kidneys eliminate other fixed metabolic acids (phosphoric, uric, and lactic acids and ketones) and prevent [blank_start]metabolic acidosis[blank_end]

Metabolic Acidosis and Alkalosis: Causes of metabolic acidosis: - Ingestion of too much [blank_start]alcohol[blank_end] (--> acetic acid) -excessive loss of [blank_start]HCO3-[blank_end] (eg. persistent diarrhea) - accumulation of [blank_start]lactic acid[blank_end], shock, [blank_start]ketosis[blank_end] in diabetic crisis, starvation and [blank_start]kidney[blank_end] failure

Metabolic Alkalosis: much less common than [blank_start]metabolic acidosis[blank_end] - indicated by [blank_start]rising blood pH[blank_end] and [blank_start]HCO3-[blank_end] -caused by [blank_start]vomiting[blank_end] of the acid contents of the stomach or by intake of excess [blank_start]base[blank_end] (eg. antacids)

Effects of Acidosis and Alkalosis: -blood pH below [blank_start]7[blank_end] --> depression of [blank_start]CNS[blank_end] ---> coma ---> death -blood pH above [blank_start]7.8[blank_end] --> [blank_start]excitation[blank_end] of nervous system---> muscle [blank_start]tetany[blank_end], extreme nervousness, convulsions, respiratory arrest

Urinary System Overview • Kidneys are one of the major [blank_start]excretory[blank_end] organs • Urinary bladder is the temporary [blank_start]storage reservoir[blank_end] for urine • [blank_start]Ureters[blank_end] transport urine from the kidneys to the bladder • [blank_start]Urethra[blank_end] transports urine out of the body

What are the functions of kidneys? • Removal of [blank_start]toxins[blank_end], metabolic wastes, and excess ions from the [blank_start]blood[blank_end] • Regulation of blood [blank_start]volume[blank_end], chemical composition, and [blank_start]pH[blank_end]

Schematic of Renal Blood Vessels: Aorta -->[blank_start]Renal[blank_end] artery-->segmental artery-->[blank_start]interlobar[blank_end] artery-->arcuate artery-->cortical radiate atery-->[blank_start]afferent[blank_end] arteriole-->[blank_start]glomerulus[blank_end] (capillaries)-->[blank_start]efferent[blank_end] arteriole --> [blank_start]peritubular[blank_end] capillaries and [blank_start]vasa recta[blank_end] --> cortical radiate vein --> [blank_start]arcuate[blank_end] vein-->interlobar vein-->renal vein--> inferior vena cava

Nephrons These are the structural and functional units that form urine ~[blank_start]1 million[blank_end] per kidney Two main parts: 1. [blank_start]Glomerulus[blank_end]: a tuft of capillaries 2. [blank_start]Renal tubule[blank_end]: begins as cup-shaped glomerular (Bowman’s) capsule surrounding the glomerulus

Nephron Overview

Nephrons • Renal corpuscle – Glomerulus + its [blank_start]glomerular capsule[blank_end] • [blank_start]Fenestrated[blank_end] (windows) glomerular endothelium – Allows filtrate to pass from [blank_start]plasma[blank_end] into the glomerular capsule

Renal Tubule • Glomerular capsule • [blank_start]Parietal[blank_end] layer: simple squamous epithelium • [blank_start]Visceral[blank_end] layer: branching epithelial [blank_start]podocytes[blank_end] – Extensions from the epithelial cells terminate in foot processes that cling to [blank_start]basement membrane[blank_end] – Filtration slits allow filtrate to pass into the [blank_start]capsular[blank_end] space

Filtration Membrane Porous membrane between the [blank_start]blood[blank_end] and the capsular space Consists of 1. [blank_start]Fenestrated endothelium[blank_end] of the glomerular capillaries 2. [blank_start]Visceral[blank_end] membrane of the glomerular capsule (podocytes with foot processes and filtration slits) 3. Gel-like [blank_start]basement membrane[blank_end] (fused basal laminae of the two other layers)

Filtration Membrane • Allows passage of [blank_start]water[blank_end] and solutes smaller than most plasma proteins – Fenestrations prevent filtration of [blank_start]blood cells[blank_end] – Negatively charged basement membrane repels large anions such as [blank_start]plasma proteins[blank_end] – Slit diaphragms also help to repel [blank_start]macromolecules[blank_end]

Nephrons: 2 types 1. [blank_start]Cortical[blank_end] nephrons—85% of nephrons; almost entirely in the cortex. Make urine (not as concentrated) 2. [blank_start]Juxtamedullary[blank_end] nephrons – Really Long loops of Henle deeply invade the [blank_start]medulla[blank_end] – Extensive thin segments (on the loop of henle) – Important in the production of [blank_start]concentrated[blank_end] urine

Nephron Capillary Beds 1. Glomerulus -[blank_start]Afferent[blank_end] arteriole -> glomerulus -> [blank_start]efferent[blank_end] arteriole -Specialized for [blank_start]filtration[blank_end] -Blood pressure is [blank_start]high[blank_end] because -Efferent arterioles are smaller in diameter than afferent arterioles -Arterioles are [blank_start]high-resistance[blank_end] vessels

Nephron Capillary Beds 2. Peritubular capillaries -[blank_start]Low[blank_end]-pressure, porous capillaries adapted for [blank_start]absorption[blank_end] -Arise from [blank_start]efferent[blank_end] arterioles -Cling to adjacent [blank_start]renal[blank_end] tubules in cortex -Empty into [blank_start]venules[blank_end]

Nephron Capillary Beds 3. Vasa recta -Long vessels parallel to long loops of Henle -Arise from [blank_start]efferent[blank_end] arterioles of [blank_start]juxtamedullary[blank_end] nephrons -Function formation of [blank_start]concentrated urine[blank_end]

Mechanisms of Urine Formation • The kidneys filter the body’s entire [blank_start]plasma[blank_end] volume 60 times each day • Filtrate – Blood plasma minus [blank_start]proteins[blank_end] • Urine – <1% of total filtrate – Contains metabolic [blank_start]wastes[blank_end] and unneeded substances

Mechanisms of Urine Formation 1. [blank_start]Glomerular[blank_end] filtration 2. Tubular [blank_start]reabsorption[blank_end] -Returns all glucose and amino acids, 99% of water, salt, and other components to the [blank_start]blood[blank_end] 3. Tubular [blank_start]secretion[blank_end] -Reverse of reabsoprtion: selective addition to [blank_start]urine[blank_end]

1. Filtration Net Filtration Pressure (NFP) The pressure responsible for [blank_start]filtrate formation[blank_end] (10 mm Hg)

Pressure associated behind it and pressure within it. [blank_start]Colloid[blank_end] is proteins in the blood vessel drawing fluid back into the blood vessel This capsule is sitting in fluid which has [blank_start]hydrostatic[blank_end] pressure is about 15 mm Hg If you add all these up this is 10 net mmHg filtration pressure We calculate it by subtration of the bottom two factors from the top one.

Glomerular Filtration Rate (GFR) • [blank_start]Volume of filtrate[blank_end] formed per minute by the kidneys (120–125 ml/min) • This rate is controlled by (and directly proportional to) – Total [blank_start]surface area[blank_end] available for filtration – Filtration membrane [blank_start]permeability[blank_end] – [blank_start]NFP[blank_end]

Renal Tubules/Collecting Ducts • Proximal [blank_start]CT[blank_end] – Site of most [blank_start]reabsorption[blank_end] • 65% of Na+ and water • All nutrients • Ions • Small proteins

•Loop of Henle • Descending limb: [blank_start]H2O[blank_end] • Ascending limb: Na+, K+, Cl-

Distal Collecting Tubules • DCT and collecting duct – Reabsorption is [blank_start]hormonally[blank_end] regulated • Ca2+ (PTH) • Water ([blank_start]ADH[blank_end]) • Na+ ([blank_start]aldosterone[blank_end] and [blank_start]ANP[blank_end])

Tubular Secretion • Can basically be considered as reabsorption in [blank_start]reverse[blank_end] – What types of substances? • K+, H+, NH4+, [blank_start]creatinine[blank_end], and [blank_start]organic acids[blank_end] move from [blank_start]peritubular[blank_end] capillaries or tubule cells into filtrate • Disposes of substances that are bound to [blank_start]plasma proteins[blank_end]

Why is tubular secretion important? Eliminates undesirable substances that have been passively [blank_start]reabsorbed[blank_end] (e.g., urea and uric acid) – Rids the body of excess [blank_start]K+[blank_end] – Controls [blank_start]blood pH[blank_end] by altering amounts of H+ or HCO3– in urine

1. Osmolality – what is it? – Number of [blank_start]solute[blank_end] particles in 1 kg of H2O A. Why is osmolality important? – This value reflects the ability of a fluid to cause [blank_start]osmosis[blank_end] 2. Osmolality of body fluids – Expressed in [blank_start]milliosmols[blank_end] (mOsm) – The kidneys maintain osmolality of plasma at ~300 mOsm, using what is known as countercurrent mechanisms

Countercurrent Mechanisms • Occurs when fluid flows in [blank_start]opposite[blank_end] directions in two adjacent segments of the same tube

Countercurrent Mechanism • Role of countercurrent mechanisms – why do we need this? – Establish and maintain an [blank_start]osmotic gradient[blank_end] (300 mOsm to 1200 mOsm) from [blank_start]renal cortex[blank_end] through the medulla – Allow the kidneys to vary urine [blank_start]concentration[blank_end]

- Proximal convoluted tubule: • 65% of filtrate volume [blank_start]reabsorbed[blank_end] • Na+, glucose, amino acids, and other nutrients actively transported; H2O and many ions follow [blank_start]passively[blank_end] • H+ and NH4+ secretion and HCO3– reabsorption to maintain [blank_start]blood pH[blank_end] (see Chapter 26) • Some drugs are secreted

Descending limb of loop of Henle • Freely permeable to [blank_start]H2O[blank_end] • Not permeable to [blank_start]NaCl[blank_end] • Filtrate becomes increasingly concentrated as H2O leaves by [blank_start]osmosis[blank_end]

Ascending limb of loop of Henle • Impermeable to [blank_start]H2O[blank_end] • Permeable to [blank_start]NaCl[blank_end] • Filtrate becomes increasingly dilute as [blank_start]salt[blank_end] is reabsorbed

Collecting duct • H2O reabsorption through aquaporins regulated by [blank_start]ADH[blank_end] • Na+ reabsorption and [blank_start]K+[blank_end] secretion regulated by [blank_start]aldosterone[blank_end] • H+ and HCO3– reabsorption or secretion to maintain [blank_start]blood pH[blank_end] (see Chapter 26) • Urea reabsorption increased by [blank_start]ADH[blank_end]

Physical Characteristics • Color and transparency – Clear, pale to deep [blank_start]yellow[blank_end] – Drugs, vitamin supplements, and diet can alter the color – Cloudy urine may indicate a urinary tract infection

Physical Composition of Urine • 95% water and 5% solutes • [blank_start]Nitrogenous[blank_end] wastes: urea, uric acid, and creatinine • Other normal solutes – Na+, K+, PO43–, and SO42–, – Ca2+, Mg2+ and HCO3– • Abnormally high concentrations of any constituent may indicate [blank_start]pathology[blank_end]

Juxtaglomerular Apparatus (JGA) • [blank_start]One[blank_end] per nephron • Important in regulation of [blank_start]filtrate formation[blank_end] and blood pressure • Involves modified portions of the – Distal portion of the [blank_start]ascending[blank_end] limb of the loop of Henle (DCT) – [blank_start]Afferent[blank_end] (sometimes [blank_start]efferent[blank_end]) arteriole

Juxtaglomerular Apparatus (JGA) • [blank_start]Granular[blank_end] cells (juxtaglomerular, or JG cells) – Enlarged, [blank_start]smooth[blank_end] muscle cells of arteriole – Secretory granules contain [blank_start]renin[blank_end] – Act as [blank_start]mechanoreceptors[blank_end] that sense blood pressure • Macula densa – Tall, closely packed cells of the [blank_start]ascending[blank_end] limb – Act as [blank_start]chemoreceptors[blank_end] that sense NaCl content of filtrate

Renin-Angiotensin System: Triggered when the granular cells of the JGA release [blank_start]renin[blank_end]. [blank_start]Angiotensinogen[blank_end] (plasma globulin)-->-->[blank_start]renin[blank_end]---> angiotensin 1-->[blank_start]angiotensin converting enzyme[blank_end] (ACE) --->--> angiotensin 2

Effects of Angiotensin II 1. Constricts arteriolar [blank_start]smooth[blank_end] muscle, causing [blank_start]MAP[blank_end] to rise 2. Stimulates the reabsorption of [blank_start]Na+[blank_end] -Acts directly on the renal tubules -Triggers adrenal cortex to release [blank_start]aldosterone[blank_end] 3. Stimulates the hypothalamus to release [blank_start]ADH[blank_end] and activates the [blank_start]thirst center[blank_end] 4. Constricts [blank_start]efferent[blank_end] arterioles, decreasing peritubular capillary [blank_start]hydrostatic[blank_end] pressure and increasing fluid [blank_start]reabsorption[blank_end]

Diuretics • Chemicals that enhance the [blank_start]urinary output[blank_end] • There are different classes – [blank_start]Osmotic[blank_end] diuretics: substances not reabsorbed, (e.g., high glucose in a diabetic patient) – [blank_start]ADH[blank_end] inhibitors such as alcohol (why the TTC smells on Monday morning) – Substances that inhibit [blank_start]Na+[blank_end] reabsorption and obligatory [blank_start]H2O[blank_end] reabsorption such as caffeine and many drugs