Physio Reinforcing Concepts Pt3 PDF

Urinary overview Kidney has 3 major functions: Excretatory: filtering blood, removing wastes and toxins Secretory: maintaining homeostasis of body fluids Endocrine: secretes hormones like calcitriol, erythropoietin, renin, renalase ● Calcitriol: active form of Vitamin D, increases calcium and phospha...

Urinary overview Kidney has 3 major functions: Excretatory: filtering blood, removing wastes and toxins Secretory: maintaining homeostasis of body fluids Endocrine: secretes hormones like calcitriol, erythropoietin, renin, renalase ● Calcitriol: active form of Vitamin D, increases calcium and phosphate absorption in gut, increases calcium reabsorption in kidney ● Erythropoietin: stimulates bone marrow to increase red blood cell synthesis, stimulated by low PO2 ● Renin: released due to low afferent arteriole blood pressure, activates the RAAS system to increase BP Grossly the kidney is divided superficially to deep into a capsule, cortex and medulla. The medulla is the inner portion of the kidney with very high salt concentration to aid in water reabsorption. The nephron is the functional unit of the kidney, descending into and ascending out of the renal medulla by the Loop of Henle Filtrate goes from afferent arteriole to glomerulus, into bowman's capsule, to proximal convoluted tubule, to thin descending limb of loop of henle(LoH), to thin ascending limb of LoH, thick ascending limb of LoH, distal convoluted tubule, to collecting duct Urine formation is the culmination of filtration, reabsorption, and secretion. Urine is what is excreted. Filtration only happens at the glomerulus Reabsorption goes from the renal tubule lumen, back into the blood Secretion is from the blood into the lumen, not from filtration Secretion and reabsorption occur throughout the tubule system if filtration > excretion, reabsorption occurred, if filtration < excretion, secretion occurred Fluids and Lab Tests Capillary membranes separate the plasma volumes from the interstitial volumes, these volumes will have very similar ion concentrations, but the plasma has proteins, the interstitium is low in protein concentration Intracellular fluid will be high in K+, phosphate, proteins, Mg Extracellular fluid will be high in Na+, Ca+, Cl-, bicarb Urine analysis: Color: Colorless if output is high and osmolarity is low Cloudy is a sign of infection, leukocyte and bacteria concentrations high Red-brown without RBCs is either hemoglobin or myoglobin Rhabdomyolysis is a muscle wasting condition that releases myoglobin into the blood leading to kidney damage and often “coca-cola urine.” Urine dipstick will be positive for blood because it senses the heme, even though there are no RBCs, the urine needs further analysis with microscopy. Myoglobinuria and elevated plasma creatinine kinase confirms rhabdomyolysis As muscle cells lyse, their intracellular contents are released into the blood Intravascular hemolysis(destruction of RBCs) can cause hemoglobinuria, especially if there is so much hemoglobin released that haptoglobin becomes saturated. Haptoglobin is a protein that binds free hemoglobin, salvaging it, and preventing damage. Protein analysis: Elevated creatinine indicates less clearance of muscle metabolism products, this suggests decreased GFR, meaning decreased kidney function Elevated BUN indicates less urea clearance, like creatinine this suggests decreased GFR, meaning decreased kidney function Glomerulus and GFR As blood come in through the afferent arteriole, it is filtered by the glomerulus. Filtrate passes from capillary through endothelial cells, through the negatively charged basement membrane, and between podocyte foot processes, into Bowman’s Capsule. ● The basement membrane being negatively charged is a protective mechanism to not filter out albumin Mesangial cells are present in the glomerulus, they are modified smooth muscle cells that respond to vasoactive substances. They can proliferate to the point they impede blood flow and filtration, this is seen in diabetic nephropathy Granular cells are juxtaglomerular cells that release renin to increase BP, granular cells are in close relationship to the afferent arteriole, sensing flow incoming toward the kidney. Sympathetic input is targeted at the granular cells Macula densa is a part of the juxtaglomerular apparatus that senses filtrate flow, it can stimulate granular cells as well Diseases: Nephritic Syndrome: characterized by blood(hematuria) HTN, oliguria, slightly elevated proteinuria Nephrotic Syndrome: characterized by protein (profound proteinuria), edema, hypoalbuminemia, hyperlipidemia ● An example of nephrotic disease is Minimal Change disease, where there is effacement of podocytes on electron microscopy. There is no obvious deformity on light microscopy, in a child presenting with nephrotic signs Glomerulonephritis: characterized by casts, RBC casts, hematuria, mesangial contraction and proliferation, WBCs in glomerulus ADH and Water balance When water intake is high, large volumes of dilute urine is produced, this is called diuresis When water intake is low, urine is concentrated into a small volume, this is called antidiuresis Urine volume depends on plasma ADH level Urea is not 100% excreted when it is filtered, about 50% of the urea filtered is reabsorbed by the proximal convoluted tubule. This is urea recycling, and used to maintain the high osmolarity in the inner medulla. When ADH levels are high, additional urea is reabsorbed in the collecting duct. ADH:ADH has its largest effect in the collecting duct of the nephron, where is binds V2 receptors on the basolateral membrane and increases apical aquaporin channels. Water is reabsorbed through aquaporin channels. V2 is a Gs protein, so cAMP is created. Other actions include acting on Na/K/Cl channels in the thick ascending LoH, increasing Na reabsorption, and adding apical urea transporters in the collecting duct, increasing urea reabsorption. Reabsorbing these solutes increases the corticomedullary gradient, aiding in water reabsorption Increased plasma osmolarity is the most sensitive, major stimulus for ADH secretion ADH will increase when there is a drop in blood pressure, in response to angiotensin 2, in pain, heat, stress, nausea, vomiting ADH decreases in response to ANP, cold temperatures, alcohol Diabetes insipidus=ADH deficiency, constant diuresis leading to polydipsia, polyuria, hypovolemia. Patient will be losing water but have high plasma osmolarity ● Central DI=lack of production of ADH, plasma ADH will be low. Treat with desmopressin which is an ADH analog ● Nephrogenic DI=problem at the kidney, ADH receptors are either nonfunctional or absent, therefore desmopressin will not help SIADH: inappropriate excess of ADH. This will lead to water retention and hyponatremia. H2O being pulled out of the filtrate will create very high urine osmolarity, low plasma osmolarity Ecstasy: can cause intense thirst leading to hyponatremia, cerebral edema, brain herniation. Female gender is the only risk factor RAAS and aldosterone Renin is released from juxtaglomerular cells, angiotensinogen is made in the liver, ACE enzyme is in the lungs and blood vessels, aldosterone is made in the adrenal cortex, ADH is made in the hypothalamus 1. Renin is released when there is low afferent arteriole pressure, when there is low filtrate flow(sensed by macula densa), or sympathetic input. Renin can be falsely elevated leading to secondary HTN(ex. Renal artery stenosis). Secretion of renin is rate limiting step in RAAS 2. Renin cleaves angiotensinogen into angiotensin 1(inactive) 3. Angiotensin 1 is converted to angiotensin 2(active) by the ACE enzyme. 4. Angiotensin 2 does many things including vasoconstriction, Na reabsorption in proximal convoluted tubule(influencing Na/H antiport), stimulates aldosterone production, stimulates ADH production. 5. Aldosterone is a mineralocorticoid that acts on the distal and collecting tubules, increases basolateral Na/K ATPase activity driving sodium reabsorption RAAS increases BP and promotes positive sodium balance Aldosterone: Major stimuli for release are : angiotensin 2, and high plasma K+ Stimulates basolateral Na/K ATPase at the collecting duct. Stimulates production of apical Na channels(ENaC), and extra Na/K ATPases Aldosterone increases Na reabsorption, H secretion, K secretion Amiloride is a potassium sparing diuretic that targets ENaC Channels Spironolactone is a potassium sparing diuretic that targets the mineralocorticoid receptor aldosterone binds to Fludrocortisone is the injectable mimic of aldosterone for a patient with hypoaldosteronism Conn’s syndrome: primary hyperaldosteronism. tumor of the adrenal gland causing hypersecretion of aldosterone. High plasma aldosterone, low plasma renin, HTN, hypernatremia, hypokalemia, metabolic alkalosis Renal artery stenosis: secondary hyperaldosteronism. Activation of RAAS due to low kidney perfusion, prerenal azotemia. Decreased Fraction of excreted sodium. Increasing BP even though BP is already high. Genitourinary Male Hypogonadism:When assessing male hypogonadism check testosterone and FSH levels, both stimulate sertoli cells for spermatogenesis Symptoms include decreased sexual function, decreased bone mass, anemia. Treat hypogonadism with testosterone replacement therapy patches, side effects of this therapy can include increased hematocrit, balding and acne Micturition: Urine is stored in the bladder, when it accumulates it stretches the detrusor muscle, stimulating the pelvic nerve(S2-S4) to trigger the micturition reflex Detrusor muscle has 2 receptors, M3 and B3. M3 is parasympathetic causing contraction of the detrusor muscle. B3 is sympathetic causing relaxation of the muscle. Sympathetic innervation comes from the hypogastric nerve. There are two urethral sphincters, inner and outer. The inner urethral sphincter has sympathetic innervation using alpha 1 receptors. Sympathetic stimulation via the hypogastric nerve will cause contraction of the internal sphincter preventing urination The outer urethral sphincter is under voluntary control via the pudendal nerve. If stimulated it decreases sphincter tone promoting urination. The ability to control the outer urethral sphincter occurs between ages 2-3, until then there is a simplified micturition reflex Incontinence: Overflow: due to hypoactive detrusor, bladder completely fills to the point bladder pressure > sphincter pressure, constant dribbling leakage. Example is following spinal cord injury. Give cholinergic to enhance detrusor contraction Urge: due to hyperactive detrusor, spastic contraction of detrusor gives constant sensation of needing to void. Example is parkinson’s. Give antimuscarinic to reduce the contractions ● Benign prostatic hyperplasia: proliferation of cells in the transitional and periurethral zones of the prostate, leading to incomplete voiding and increased urgency. Increased exposure to testosterone increases hyperplasia. Treat with 5 alpha reductase inhibitors (finasteride, dustaride) or alpha 1 antagonists(tamsulosin) Stress: due to weak pelvic floor muscles unable to handle increases in abdominal pressure, incontinence when sneezing, coughing, lifting objects. Example is pregnancy. Prescribe kegel exercises. Various Applications: Multiple sclerosis: autoimmune disorder leading to degradation of oligodendrocytes, loss of myelination in CNS, difficulty walking ensues when the process affects the basal ganglia or cerebellum Duchenne Muscular Dystrophy: lack of or abnormal mutation in the dystrophin protein that anchors actin to the cell membrane. Contracting the muscle will lead to cell membrane damage, progressively worsening weakness Pericardial tamponade: accumulation of fluid in the pericardial space that inhibits ventricular filling, will be present with muffled heart sounds, JVD and hypotension. Treat with pericardiocentesis to increase preload Myocardial infarction: occlusion of a coronary artery leading to ischemia and necrosis of the myocardium, inhibiting its function Kidney stones: consequence of dehydration, jagged stones can lodge in the ureter and damage epithelial cells causing extreme pain. May cause microscopic hematuria Diabetic nephropathy: glucose will be found in the urine. Glycosylation of basement membrane and increased HBA1c make the glomerulus more permeable to glucose and albumin Asthma: type of obstructive lung disease characterized by bronchospasm and mucus production. Bronchospasm is triggered by allergens and irritants and excess exercise. Bronchospasm increases the airway resistance, making exhalation more difficult, and wheezing noticeable. There will be decrease in FEV1/FVC ratio Carbon monoxide poisoning: carbon monoxide binds hemoglobin at higher affinity than oxygen. Lack of oxygen binding sites lead to decreases in arterial PO2, and hypoxia Acute mountain sickness: arterial hypoxia leads to increases ventilation, dropping arterial CO2 creating cerebral vasodilation, leading to headache. Hypoxia also disrupts sleep Parkinson’s: progressive degenerative motor disease caused by damage to the substantia nigra. Low dopamine causes increased inhibition of movement. Symptoms are bradykinesia(slow movements) postural instability, impaired balance Alzheimer's: neurodegenerative disorder leading to impaired memory, progressing to dementia and cognitive decline Epilepsy: excessive activity in a cluster of neurons, symptoms are determined by which area of the brain is hyperactive. Seizures can be brought on by trauma, fever, neurotransmitter imbalances, abnormal brain development Grave’s disease: autoimmune disorder stimulating the thyroid gland to increase production of T3/T4. Enlargement of the thyroid gland and elevated thyroid hormone will be observed. Exophthalmos is a common symptom, protrusion of the eyeballs Hashimoto’s: autoimmune disease against the thyroid gland reducing the production of thyroid hormone. Destruction of thyroid follicles Hyperparathyroidism: mostly from adenoma, excessive production of PTH increases bone resorption, disrupting calcium regulation and reducing bone strength. Pheochromocytoma: tumor of the adrenal medulla leading to excess catecholamine production(epi, norepi). Stimulates sympathetic nervous system increasing blood pressure, increasing heart rate