Hope this will help you in studying! :) because you used this, you are obliged to do the same, to upload publicly so that others will have an easy way on researching for their school works! keep up the good work studes! Goodluck!
Reabsorption In Renal Tubule (The Guyton and Hall physiology)Maryam Fida
Features of PCTPCT have high capacity of active & passive re-absorption.
This is due to special cellular features of epithelial cells.
They have increased no. of mitochondria due to high metabolic activity.
brush border on luminal (apical) side.
Brush border contains protein carrier molecules to transport Na+ by co-transport mechanism with other substances (a.acids, glucose etc).
Additional sodium is transported by COUNTER-TRANSPORT that reabsorb sodium while secreting hydrogen.
About 65 % of filtered load of Na+ & water is reabsorbed in PCT.
A lower % age of Cl- is also absorbed.
In 1st half of PC tubules, Na+ is re-absorbed by co-transport along with glucose, a.acids and other solutes.
In 2nd half of PC tubules, mainly Na+ is reabsorbed with Cl- and some of glucose + a.acids remain un-absorbed.
2nd half of PCT has high conc of Cl- (140 mEq/L) as compared to 1st half (105 mEq/L).
Hope this will help you in studying! :) because you used this, you are obliged to do the same, to upload publicly so that others will have an easy way on researching for their school works! keep up the good work studes! Goodluck!
Reabsorption In Renal Tubule (The Guyton and Hall physiology)Maryam Fida
Features of PCTPCT have high capacity of active & passive re-absorption.
This is due to special cellular features of epithelial cells.
They have increased no. of mitochondria due to high metabolic activity.
brush border on luminal (apical) side.
Brush border contains protein carrier molecules to transport Na+ by co-transport mechanism with other substances (a.acids, glucose etc).
Additional sodium is transported by COUNTER-TRANSPORT that reabsorb sodium while secreting hydrogen.
About 65 % of filtered load of Na+ & water is reabsorbed in PCT.
A lower % age of Cl- is also absorbed.
In 1st half of PC tubules, Na+ is re-absorbed by co-transport along with glucose, a.acids and other solutes.
In 2nd half of PC tubules, mainly Na+ is reabsorbed with Cl- and some of glucose + a.acids remain un-absorbed.
2nd half of PCT has high conc of Cl- (140 mEq/L) as compared to 1st half (105 mEq/L).
this presentation comprises of everything about the process of defecation and the defecation reflex and the nerve supply involved.
also discusses about the types of defecation reflexes and deals about them seperately in detail.
Dr. Prabin Kumar Bam, MBBS
Anatomy of urinary bladder, introduction, gross features, histology, relations, interior of the bladder, trigone of bladder, uvula vesicae, ligaments of urinary bladder, histology of urinary bladder,
Prabin Kumar Bam
Defecation..( the guyton and hall physiology)Maryam Fida
Definition:
“Voiding of feces is known as defecation”.
Feces is formed in the large intestine and stored in sigmoid colon.
internal sphincter
Composed of circular smooth muscle
Lies immediately inside the anus
external sphincter
Composed of striated voluntary muscle
Controlled by pudendal nerve. therefore, it is under voluntary, conscious.
reflex pathway
When feces enter rectum
|
Distension of rectal wall
|
Impulses from the nerve endings are transmitted via afferent fibers of pelvic nerve to the defecation center, situated in sacral segments (center) of spinal cord.
|
The center in turn, sends motor impulses to the descending colon, sigmoid colon and rectum via efferent nerve fibers of pelvic nerve.
|
Motor impulses cause strong contraction of descending colon, sigmoid colon and rectum and relaxation of internal sphincter.
Simultaneously, voluntary relaxation of external sphincter occurs. It is due to the inhibition of pudendal nerve.
VOMITING
Definition:
“Vomiting or emesis is the abnormal emptying of stomach and upper part of intestine through esophagus and mouth “.
I am a medical student. I have one friend who is persuing his MBBS degree in Taishan Medical UNiversity. I got these notes from him.
These notes are by Dr. Bikesh, He is a famous lecturer of TMU.
These notes have helped me a lot and i also watch his lecture videos , which are great; highly simple and huge content.
I am uploading with Renal physiology. If you want some other topics i would upload for you.
"Let the Knowledge be spread" Dr. Bikesh
I am a medical student. I have one friend who is persuing his MBBS degree in Taishan Medical UNiversity. I got these notes from him.
These notes are by Dr. Bikesh, He is a famous lecturer of TMU.
These notes have helped me a lot and i also watch his lecture videos , which are great; highly simple and huge content.
I am uploading with Renal physiology. If you want some other topics i would upload for you.
"Let the Knowledge be spread" Dr. Bikesh
this presentation comprises of everything about the process of defecation and the defecation reflex and the nerve supply involved.
also discusses about the types of defecation reflexes and deals about them seperately in detail.
Dr. Prabin Kumar Bam, MBBS
Anatomy of urinary bladder, introduction, gross features, histology, relations, interior of the bladder, trigone of bladder, uvula vesicae, ligaments of urinary bladder, histology of urinary bladder,
Prabin Kumar Bam
Defecation..( the guyton and hall physiology)Maryam Fida
Definition:
“Voiding of feces is known as defecation”.
Feces is formed in the large intestine and stored in sigmoid colon.
internal sphincter
Composed of circular smooth muscle
Lies immediately inside the anus
external sphincter
Composed of striated voluntary muscle
Controlled by pudendal nerve. therefore, it is under voluntary, conscious.
reflex pathway
When feces enter rectum
|
Distension of rectal wall
|
Impulses from the nerve endings are transmitted via afferent fibers of pelvic nerve to the defecation center, situated in sacral segments (center) of spinal cord.
|
The center in turn, sends motor impulses to the descending colon, sigmoid colon and rectum via efferent nerve fibers of pelvic nerve.
|
Motor impulses cause strong contraction of descending colon, sigmoid colon and rectum and relaxation of internal sphincter.
Simultaneously, voluntary relaxation of external sphincter occurs. It is due to the inhibition of pudendal nerve.
VOMITING
Definition:
“Vomiting or emesis is the abnormal emptying of stomach and upper part of intestine through esophagus and mouth “.
I am a medical student. I have one friend who is persuing his MBBS degree in Taishan Medical UNiversity. I got these notes from him.
These notes are by Dr. Bikesh, He is a famous lecturer of TMU.
These notes have helped me a lot and i also watch his lecture videos , which are great; highly simple and huge content.
I am uploading with Renal physiology. If you want some other topics i would upload for you.
"Let the Knowledge be spread" Dr. Bikesh
I am a medical student. I have one friend who is persuing his MBBS degree in Taishan Medical UNiversity. I got these notes from him.
These notes are by Dr. Bikesh, He is a famous lecturer of TMU.
These notes have helped me a lot and i also watch his lecture videos , which are great; highly simple and huge content.
I am uploading with Renal physiology. If you want some other topics i would upload for you.
"Let the Knowledge be spread" Dr. Bikesh
I am a medical student. I have one friend who is persuing his MBBS degree in Taishan Medical UNiversity. I got these notes from him.
These notes are by Dr. Bikesh, He is a famous lecturer of TMU.
These notes have helped me a lot and i also watch his lecture videos , which are great; highly simple and huge content.
I am uploading with Renal physiology. If you want some other topics i would upload for you.
"Let the Knowledge be spread" Dr. Bikesh
Demand Pressure: The Balance Between Candidate Supply & Hiring DemandWANTED Technologies
Demand Pressure is a ratio of the number of job candidates in the workforce for every job posted online, showing the market pressure Recruiters are likely to experience when trying to fill any job. Here's a look at the jobs with the most and least balanced talent pools.
A 7 years old boy had increasing lethargy for a week. On physical examination, he had periorbital and pitting edema at the ankles, but is normotensive and afebrile. Laboratory studies smarked albuminuria. He was given a thiazide diuretic and his urine output increases and his edema resolves
INTRODUCTION
The term urogenital refers to something that has both urinary and genital origins. The word urogenital is used because the urinary and reproductive systems in males merge.
These are grouped together because of their proximity to each other, their common embryological origin and the use of common pathways (ex. urethra).
Kidneys and urinary ducts form the urinary system.
The Urinary system performs two important homeostatic processes like excretion and osmoregulation. This system is intimately associated both anatomically, and in terms of embryonic origin with the genital system.
The genital system includes the gonads which generate gametes and the genital ducts that serve as passages for the gametes.
Though functionally different the two organ systems the urinary and the genital system are treated together as the urino- genital system, since both develop from the same segmental blocks of trunk mesoderm or adjacent tissues and share many of the ducts.
Thus although the two systems have nothing common functionally they are closely associated in their use of common ducts and are studied under the broad heading of urinogenital system.
The function of the excretory system is crucial in considering the possible environment of the ‘vertebrate life ’. Several main functions can be attributed to all vertebrate excretory systems:
Excretion of nitrogenous waste products.
Maintaining homeostasis with regard to ions (i.e. salt balance).
Regaining valuable substances (glucose, salts, amino acids, etc.)
Maintaining a physiological osmotic value (i.e. water balance).
The excretory system is formed by a series of paired, segmental nephrons that begin with a nephrostome opening into the coelomic cavity.
A pair of glomeruli per segment, supplied by branches from the aorta, projects into the coelomic cavity close to these nephrostomes.
At a later stage of development, the glomerulus/nephrostome area becomes separated from the rest of the coelomic cavity by an epithelial fold.
The nephrons connect to a duct that is formed by caudal growth of the most anterior nephric tubules. These paired urinary ducts open near the anal region.
Urinary system overview, it's functional histology and it's congenital diseasesAttique Hassan
This assignment is all about urinary system of animals.
It covers overview of urinary system with perfect pictures of different animal's kidney.
General histology of each part of system and each part of nephron.
At last a brief overview of important congenital diseases with pics....
Urinary.pptx knowledge about tracts and inauguration of the dayakshayamritanshuru40
The urinary tract is the system in the body that is responsible for producing, storing, and eliminating urine. It includes the kidneys, ureters, bladder, and urethra. The kidneys filter waste products from the blood to produce urine, which then travels through the ureters to the bladder for storage. When the bladder is full, urine is expelled from the body through the urethra. The urinary tract plays a crucial role in maintaining the body's fluid balance and removing waste products from the bloodstream.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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1. Renal physiology- Dr. Kh.
Pourkhalili
1
Renal physiology
Presented by:
Dr. Khalil Pourkhalili
Bushehr University of Medical Sciences
(BPUMS)
Faculty of medicine
Bushehr University of Medical Sciences
2. Renal physiology- Dr. Kh.
Pourkhalili
2
B.P.U.M.S
Regulation of water and electrolyte balance
Excretion of metabolic waste
Excretion of bioactive substances (Hormones and many
foreign substances, specifically drugs)
Regulation of arterial blood pressure
Regulation of red blood cell production
Regulation of vitamin D production
Gluconeogenesis
Acid-base balance
Renal functions
3. Renal physiology- Dr. Kh.
Pourkhalili
3
B.P.U.M.S
Position: the kidneys are paired organs that lie on the posterior wall
of the abdomen behind the peritoneum
Weight: 115-170 g (Mean 150 g)
Size: 11 cm long, 6 cm wide, and 3 cm thick
Anatomy of the kidneys and urinary system
4. Renal physiology- Dr. Kh.
Pourkhalili
4
B.P.U.M.S
Major parts:
Cortex
Medulla
Outer medulla
Inner medulla
Minor calyx
Major calyx
Pelvis
8. Renal physiology- Dr. Kh.
Pourkhalili
8
B.P.U.M.S
Number of nephrons in each human kidney:
1-1.2 million nephrons, which are hollow tubes composed of a single cell
layer.
The nephron consists of two parts
1. Renal corpuscle (glomerular capillaries and Bowman's capsule)
2. A long tubule which consists of:
Proximal tubule
Loop of Henle (DTL, ATL & TAL)
Distal tubule
Collecting duct system.
Nephron as functional unit in the kidney
9. Renal physiology- Dr. Kh.
Pourkhalili
9
B.P.U.M.S
Macula densa
Near the end of the thick ascending limb, the nephron passes between the
afferent and efferent arterioles of the same nephron. This short segment of
the thick ascending limb is called the macula densa.
Nephron as functional unit in the kidney
10. Renal physiology- Dr. Kh.
Pourkhalili
10
B.P.U.M.S
Nephron as functional unit in the kidney
Distal tubule
Cortical collecting tubule
Medullary collecting tubule
Collecting duct
12. Renal physiology- Dr. Kh.
Pourkhalili
12
B.P.U.M.S
Cortical nephrones (70-80 %)
Juxtamedullary nephrons (20-30 %) (longer loop of Henle and
the efferent arteriole forms not only a network of peritubular
capillaries but also a series of vascular loops called the vasa
recta).
The juxtamedullary nephrons are important for urine concentration.
Types of nephrons
15. Renal physiology- Dr. Kh.
Pourkhalili
15
B.P.U.M.S
Less than 0.7% of the renal blood flow (RBF) enters the
vasa recta
Functions of vasa recta:
Conveying oxygen and important nutrients to nephron segments
Delivering substances to the nephron for secretion
Serving as a pathway for the return of reabsorbed water and solutes to the
circulatory system
Concentrating and diluting the urine
Role of vasa recta
17. Renal physiology- Dr. Kh.
Pourkhalili
17
B.P.U.M.S
Proximal tubule cells: have an extensively amplified apical
membrane called the brush border (due to the presence of
many microvilli) , which is present only in the proximal tubule.
The basolateral membrane (the blood side of the cell) is
highly invaginated. These invaginations contain many
mitochondria.
Cells of descending and ascending thin limbs of Henle's
loop: have poorly developed apical and basolateral surfaces
and few mitochondria.
Cells of the thick ascending limb and the distal tubule:
have abundant mitochondria and extensive infoldings of the
basolateral membrane.
The collecting duct cells: principal cells (P cells)and
intercalated cells (I cells).
Nephron cells
18. Renal physiology- Dr. Kh.
Pourkhalili
18
B.P.U.M.S
Principal cells have a moderately invaginated basolateral
membrane and contain few mitochondria. Principal cells play an
important role in reabsorption of NaCl and secretion of K+.
Intercalated cells, which play an important role in regulating acid-
base balance, have a high density of mitochondria.
- One population of intercalated cells secretes H+ (i.e., reabsorbs
HCO3-), and a second population secretes HCO3- .
Inner medullary collecting duct cells: Cells of the inner
medullary collecting duct have poorly developed apical and
basolateral surfaces and few mitochondria.
21. Renal physiology- Dr. Kh.
Pourkhalili
21
B.P.U.M.S
Ultrastructure of the renal corpuscle
The renal corpuscle consists of:
1- Glomerulus or glomerular capillaries
2- Bowman's capsule
22. Renal physiology- Dr. Kh.
Pourkhalili
22
B.P.U.M.S
Juxtaglomerular apparatus consists of:
The macula densa of the thick ascending limb
Extraglomerular mesangial cells
Renin producing granular cells of the afferent arteriole
The juxtaglomerular apparatus is one component of the tubuloglomerular
feedback mechanism that is involved in the autoregulation of RBF and GFR.
23. Renal physiology- Dr. Kh.
Pourkhalili
23
B.P.U.M.S
1. The capillary endothelium of the glomerular capillaries
2. Basement membrane (The total area of glomerular capillary
endothelium across which filtration occurs in humans is about 0.8 m2)
3. A single-celled layer of epithelial cells (podocytes)
Filtration barrier
26. Renal physiology- Dr. Kh.
Pourkhalili
26
B.P.U.M.S
The endothelium is fenestrated (contains 700-Å holes) and
freely permeable to water, small solutes (such as Na+, urea, and
glucose), and most proteins but is not permeable to red blood
cells, white blood cells, or platelets.
Because endothelial cells express negatively charged
glycoproteins on their surface, they may retard the filtration of
very large anionic proteins into Bowman's space.
In addition to their role as a barrier to filtration, the endothelial
cells synthesize a number of vasoactive substances (e.g., nitric
oxide [NO], a vasodilator, and endothelin-1 [ET-1], a
vasoconstrictor) that are important in controlling renal plasma
flow (RPF).
Role of endothelial cells
27. Renal physiology- Dr. Kh.
Pourkhalili
27
B.P.U.M.S
The basement membrane, which is a porous matrix of
negatively charged proteins, including type IV collagen,
laminin, proteoglycans and fibronectin, is an important
filtration barrier to plasma proteins.
The basement membrane is thought to function primarily
as a charge-selective filter in which the ability of proteins
to cross the filter is based on charge.*
Role of basement membrane
28. Renal physiology- Dr. Kh.
Pourkhalili
28
B.P.U.M.S
The podocytes, have long finger-like processes that
completely encircle the outer surface of the capillaries.
The processes of the podocytes interdigitate to cover the
basement membrane and are separated by apparent gaps
called filtration slits (slit pores).
Each filtration slit is bridged by a thin diaphragm that contains
pores with a dimension of 40 × 140 Å.
Filtration slits, which function primarily as a size-selective
filter, keep the proteins and macromolecules that cross the
basement membrane from entering Bowman's space.
Role of podocytes
31. Renal physiology- Dr. Kh.
Pourkhalili
31
B.P.U.M.S
Nephrotic syndrome: is produced by a variety of disorders and is
characterized by an increase in permeability of the glomerular capillaries
to proteins
Proteinuria
Hypoalbuminemia
Generalized edema
IN THE CLINIC
32. Renal physiology- Dr. Kh.
Pourkhalili
32
Filterability through the filtration barrier
Effect of size
Filterability of solutes is inversely related to their size
Effect of charge
Negatively charged large molecules are filtered less easily than positively
charged molecules of equal molecular size
B.P.U.M.S
35. Renal physiology- Dr. Kh.
Pourkhalili
35
B.P.U.M.S
Filtration, is the process by which water and solutes in the blood
leave the vascular system through the filtration barrier and enter
Bowman's space.
Secretion, is the process of moving substances into the tubular
lumen from the cytosol of epithelial cells that form the walls of the
nephron.
Reabsorption, is the process of moving substances from the
lumen across the epithelial layer into the surrounding interstitium.
Excretion, means exit of the substance from the body (ie, the
substance is present in the final urine produced by the kidneys).
Excreted= Filtered – Reabsorbed + Secreted
Basic renal processes
38. Renal physiology- Dr. Kh.
Pourkhalili
38
Glomerular filtration-the first step in urine formation
Composition of the glomerular filtrate
Filtrate is essentially protein-free and devoid of cellular elements,
including red blood cells.
Most salts and organic molecules, are similar to the concentrations
in the plasma.
Exceptions include calcium and fatty acids, that are not freely filtered
because they are partially bound to the plasma proteins.
B.P.U.M.S
39. Renal physiology- Dr. Kh.
Pourkhalili
39
GFR is about 20 % of RPF
RBF → 1100 - 1200 ml/min
About 5–10% of RBF, flows down into the medulla
RPF → 650 ml/min
GFR → 125 ml/min (180 L/day)
Filtration fraction = GFR/RPF (20 %)
B.P.U.M.S
40. Renal physiology- Dr. Kh.
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40
Determinants of GFR
Ultrafiltration occurs because the starling forces
Rate of filtration = Kf x NFP
Rate of filtration = Kf x (PGC – ΠGC) – (PBC – ΠBC)
Kf = hydraulic permeability x surface area
NFP = (PGC – ΠGC) – (PBC – ΠBC)
The portion of filtered plasma is termed the filtration fraction and is
determined as: FF=GFR/RPF
B.P.U.M.S
42. Renal physiology- Dr. Kh.
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42
1. Increased PBS decreases GFR
2. Increased glomerular capillary Kf increases GFR
3. Increased ΠGC decreases GFR
Two factors that influence the glomerular capillary colloid osmotic
pressure:
The arterial plasma colloid osmotic pressure
The filtration fraction
B.P.U.M.S
Determinants of GFR
43. Renal physiology- Dr. Kh.
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43
4. Increased glomerular capillary hydrostatic pressure increases
GFR (PGC is the primary regulator of GFR)
PGC is determined by three variables, each of which is under
physiologic control:
Arterial pressure
Afferent arteriolar resistance
Efferent arteriolar resistance
B.P.U.M.S
Determinants of GFR
44. Renal physiology- Dr. Kh.
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44
B.P.U.M.S
In normal individuals, the GFR is regulated by alterations in PGC that are
mediated mainly by changes in afferent or efferent arteriolar resistance.
45. Renal physiology- Dr. Kh.
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45
B.P.U.M.S
Determinants of GFR
Kf can be altered by the mesangial cells, with contraction of these
cells producing a decrease in Kf that is largely due to a reduction in the
area available for filtration.
47. Renal physiology- Dr. Kh.
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47
B.P.U.M.S
The following pressure measurements were obtained from within the
glomerulus of an experimental animal:
Glomerular capillary hydrostatic pressure = 50 mm Hg
Glomerular capillary oncotic pressure = 26 mm Hg
Bowman’s space hydrostatic pressure = 8 mm Hg
Bowman’s space oncotic pressure = 0 mm Hg
Calculate the glomerular net ultrafiltration pressure (positive
pressure favors filtration; negative pressure opposes filtration).
A. +16 mm Hg B. +68 mm Hg C. +84 mm Hg
D. 0 mm Hg E. −16 mm Hg F. −68 mm Hg
G. −84 mm Hg
Question
48. Renal physiology- Dr. Kh.
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48
B.P.U.M.S
RBF: 22-25% of the cardiac output or near 1100-1200 ml/min, 4 ml/min/gr
Blood flow is higher in the renal cortex and lower in the renal medulla.
About 5–10% of RBF, flows from efferent arterioles down into the medulla.
Renal blood flow
(ml/min/gr)
49. Renal physiology- Dr. Kh.
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49
B.P.U.M.S
1. Pressure difference across renal vasculature
2. Total renal vascular resistance
RBF=
Like most other organs, the kidneys regulate their blood flow by
adjusting vascular resistance in response to changes in arterial
pressure.
The afferent arteriole, efferent arteriole, and interlobular artery are
the major resistance vessels in the kidneys and thereby determine
renal vascular resistance
Determinants of renal blood flow
51. Renal physiology- Dr. Kh.
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51
Physiologic control of GFR and RBF
The determinants of GFR that are most variable and
subject to physiologic control include:
PGC
ΠGC
These variables, in turn, are influenced by:
Sympathetic nervous system
Hormones and autacoids
Feedback controls that are intrinsic to the kidneys
B.P.U.M.S
52. Renal physiology- Dr. Kh.
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52
Sympathetic nervous system activation decreases GFR
Strong activation of the renal sympathetic nerves
can constrict the renal arterioles (α1) and decrease
renal blood flow and GFR.
Severe hemorrhage
Brain ischemia
Moderate or mild sympathetic stimulation has little
influence on renal blood flow and GFR.
Reflex activation of the sympathetic nervous system resulting from
moderate decreases in pressure
B.P.U.M.S
53. Renal physiology- Dr. Kh.
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53
Hormonal and autacoid control of renal circulation
1. Norepinephrine, epinephrine (a1 receptors) and
endothelin constrict renal blood vessels and decrease
GFR.
2. Angiotensin II preferentially constricts efferent arterioles,
thus:
Increased angiotensin II levels raise glomerular hydrostatic pressure while
reducing renal blood flow.
It should be kept in mind that increased angiotensin II formation usually
occurs in circumstances associated with decreased arterial pressure or
volume depletion, which tend to decrease GFR.
In these circumstances, the increased level of angiotensin II, by constricting
efferent arterioles, helps prevent decreases in glomerular hydrostatic
pressure and GFR
At the same time, though, the reduction in renal blood flow caused by
efferent arteriolar constriction contributes to decreased flow through the
peritubular capillaries, which in turn increases reabsorption of sodium and
water
B.P.U.M.S
54. Renal physiology- Dr. Kh.
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54
3. Endothelial-derived nitric oxide decreases renal
vascular resistance and increases GFR.
4. Prostaglandins and bradykinin tend to increase
GFR.
Under stressful conditions, such as volume depletion or after surgery, the
administration of nonsteroidal anti-inflammatory drugs (NSAIDS), such as
aspirin, that inhibit prostaglandin synthesis may cause significant
reductions in GFR.
B.P.U.M.S
Hormonal and autacoid control of renal circulation
56. Renal physiology- Dr. Kh.
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56
B.P.U.M.S
The phenomenon whereby RBF and GFR are maintained relatively constant
(despite blood pressure changes), named autoregulation, to allow precise control
of renal excretion of water and solutes.
Autoregulation, is achieved by changes in vascular resistance, mainly through
the afferent arterioles of the kidneys.
Importance of GFR autoregulation in preventing extreme changes in renal
excretion
Autoregulation of GFR and RBF
57. Renal physiology- Dr. Kh.
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57
B.P.U.M.S
1. Tubuloglomerular feedback (role of adenosine and ATP)
ATP and adenosine constricts the afferent arteriole, thereby returning GFR to
normal levels.
ATP and adenosine also inhibit renin release by granular cells in the afferent
arteriole
2. Myogenic mechanism (role of pressure and stretch
activated cationic channels)
Importance of autoregulation
Autoregulation of GFR and RBF provides an effective means for uncoupling renal
function from arterial pressure, and it ensures that fluid and solute excretion remain
constant.
Mechanisms for autoregulation of RBF and GFR
60. Renal physiology- Dr. Kh.
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60
B.P.U.M.S
Autoregulation is absent when arterial pressure is less
than 80 mm Hg.
Autoregulation is not perfect; RBF and GFR do change
slightly as arterial blood pressure varies.
Despite autoregulation, RBF and GFR can be changed
by certain hormones and by changes in sympathetic
nerve activity.
Three points concerning autoregulation
62. Renal physiology- Dr. Kh.
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62
B.P.U.M.S
A novel drug aimed at treating heart failure was tested in experimental
animals. The drug was rejected for testing in humans because it caused
an unacceptable decrease in the glomerular filtration rate (GFR). Further
analysis showed that the drug caused no change in mean arterial blood
pressure but renal blood flow (RBF) was increased. The filtration fraction
was decreased.
What mechanism is most likely to explain the observed decrease in GFR?
A. Afferent arteriole constriction B. Afferent arteriole dilation
C. Efferent arteriole constriction D. Efferent arteriole dilation
Question
63. Renal physiology- Dr. Kh.
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63
Urine formation by the kidneys
tubular processing of the
glomerular filtrate
B.P.U.M.S
64. Renal physiology- Dr. Kh.
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64
Reabsorption and secretion by the renal tubules
Urinary excretion = Glomerular filtration - Tubular
reabsorption + Tubular secretion
Tubular reabsorption is selective and quantitatively large
B.P.U.M.S
65. Renal physiology- Dr. Kh.
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65
Reabsorption of filtered water and solutes from the tubular
lumen across the tubular epithelial cells, through the renal
interstitium, and back into the blood
Transcellular route
Paracellular rute
B.P.U.M.S
66. Renal physiology- Dr. Kh.
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66
Transport
Passive transport
Simple diffusion
Facilitated diffusion (glucose in
basolateral membrane)
Active transport
Active reabsorption
Primary active transport
(sodium-potassium ATPase pump)
Secondary active transport
Secondary active reabsorption
(glucose by sodium in PT)
Active secretion
Primary active secretion
Secondary active secretion
(H+ by sodium in PT)
Osmosis
Pinocytosis
B.P.U.M.S
67. Renal physiology- Dr. Kh.
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67
Basic mechanisms of transmembrane transport
B.P.U.M.S
68. Renal physiology- Dr. Kh.
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68
Transport maximum
Transport maximum for substances that are actively
reabsorbed
B.P.U.M.S
375 mg/min
250
375 mg
69. Renal physiology- Dr. Kh.
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69
• The renal threshold for glucose is the plasma level at which the
glucose first appears in the urine in more than the normal minute
amounts. One would predict that the renal threshold would be about
300 mg/dL, that is, 375 mg/min (TmG) divided by 125 mL/min
(GFR). However, the actual renal threshold is about 200 mg/dL of
arterial plasma, which corresponds to a venous level of about 180
mg/dL. Figure 38–10 shows why the actual renal threshold is less
than the predicted threshold. The "ideal" curve shown in this
diagram would be obtained if the TmG in all the tubules was
identical and if all the glucose were removed from each tubule when
the amount filtered was below the TmG. This is not the case, and in
humans, for example, the actual curve is rounded and deviates
considerably from the "ideal" curve. This deviation is called splay.
The magnitude of the splay is inversely proportionate to the avidity
with which the transport mechanism binds the substance it
transports.
70. Renal physiology- Dr. Kh.
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70
Transport maximum
Transport maximum for substances that are actively
secreted
B.P.U.M.S
71. Renal physiology- Dr. Kh.
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71
Reabsorption and secretion along nephron
Proximal tubular reabsorption
Normally, about 65 per cent of the filtered load of sodium and water and a
slightly lower percentage of filtered chloride are reabsorbed by the proximal
tubule
Cells of the proximal tubule also secrete organic cations and organic anions
B.P.U.M.S
72. Renal physiology- Dr. Kh.
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72
In the first half of the proximal tubule, Na+ uptake into the cell is
coupled with either H+ (HCO3-) or organic solutes (glucose and AA)
B.P.U.M.S
First half of the proximal tubule
73. Renal physiology- Dr. Kh.
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73
In the second half of the proximal tubule, sodium is reabsorbed
mainly with chloride ions (para and transcellular) because of higher
chloride concentration (around 140 mEq/L compared to 105 in first
half)
B.P.U.M.S
Oxalate
HCO3-
Sulfate
Second half of the proximal tubule
74. Renal physiology- Dr. Kh.
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Osmotic reabsorption of water across the PT
B.P.U.M.S
An important consequence of osmotic water flow across the proximal tubule
is that some solutes, especially K+ and Ca++, are entrained in the
reabsorbed fluid and thereby reabsorbed by the process of solvent drag.
75. Renal physiology- Dr. Kh.
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75
B.P.U.M.S
Concentrations of solutes along the PT
76. Renal physiology- Dr. Kh.
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Reabsorption and secretion along nephron
Solute and water transport in loop of henle
Henle's loop reabsorbs approximately 25% of the filtered NaCl and 15-20 % of
the filtered water
B.P.U.M.S
77. Renal physiology- Dr. Kh.
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77
Distal Tubule
The very first portion of the distal tubule forms part of the juxtaglomerular
complex
The next part of the distal tubule referred to as the diluting segment
because it also dilutes the tubular fluid. It is virtually impermeable to water
and urea.
Approximately 5 percent of the filtered load of sodium chloride is
reabsorbed in the early distal tubule.
B.P.U.M.S
Reabsorption and secretion along nephron
78. Renal physiology- Dr. Kh.
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78
Late distal tubule and cortical collecting tubule
Principal cells
Reabsorb sodium and water from the lumen and secrete potassium ions
into the lumen (sites of action of the potassium-sparing diuretics)
Reabsorption of Na+ generates a negative luminal voltage, which provides
the driving force for reabsorption of Cl- across the paracellular pathway
B.P.U.M.S
79. Renal physiology- Dr. Kh.
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79
Reabsorb potassium ions and secrete H+ ions into the
tubular lumen
Reabsorption of K+ is mediated by an H+,K+-ATPase
located in the apical cell membrane.
B.P.U.M.S
Intercalated cells
80. Renal physiology- Dr. Kh.
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80
Medullary collecting duct
Medullary collecting ducts reabsorb less than 10 % of the filtered water and
sodium
They are the final site for processing the urine and, therefore, play an extremely
important role in determining the final urine output of water and solutes.
Special characteristics MCD:
The permeability of the medullary collecting duct to water is controlled by the
level of ADH.
Unlike the cortical collecting tubule, the medullary collecting duct is permeable to
urea.
The medullary collecting duct is capable of secreting H+ against a large
concentration gradient, as also occurs in the cortical collecting tubule. Thus, the
medullary collecting duct also plays a key role in regulating acid-base balance.
B.P.U.M.S
Reabsorption and secretion along nephron
83. Renal physiology- Dr. Kh.
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83
Summary of concentrations of solutes in the tubular segments
B.P.U.M.S
84. Renal physiology- Dr. Kh.
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84
Regulation of tubular reabsorption
Glomerulotubular balance
The ability of the tubules to increase reabsorption rate in response to
increased tubular load
If GFR increases from 125 ml/min to 150 ml/min, the absolute rate of
proximal tubular reabsorption also increases from about 81 ml/min (65 per
cent of GFR) to about 97.5 ml/min (65 percent of GFR).
Some degree of glomerulotubular balance also occurs in other tubular
segments, especially the loop of Henle.
The importance of glomerulotubular balance:
It helps to prevent overloading of the distal tubular segments when GFR
increases. And acts as a second line of defense to buffer the effects of
spontaneous changes in GFR on urine output. (The first line of defense,
tubuloglomerular feedback, which help prevent changes in GFR.)
B.P.U.M.S
85. Renal physiology- Dr. Kh.
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85
Regulation of tubular reabsorption
Hormonal control of reabsorption
Aldosterone
AII
ADH
ANP
PTH
Sympathetic stimulation (E, NE)
B.P.U.M.S
86. Dilates the AA, constricts the EA and relaxes the mesangial cells,
Thus this increases pressure in the glomerular capillaries, thus
increasing the glomerular filtration rate (GFR), resulting in greater
excretion of sodium and water.
Increases blood flow through the vasa recta which will wash the
solutes (NaCl and urea) out of the medullary interstitium.
Decreases sodium reabsorption in the distal convoluted tubule
(interaction with Na-Cl cotransporter) and cortical collecting duct of the
nephron via cGMP dependent phosphorylation of Na channels.
Inhibits renin secretion
Reduces aldosterone secretion
Relaxes vascular wall by elevation of cGMP
Renal physiology- Dr. Kh.
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86
Regulation of tubular reabsorption- role of ANP
B.P.U.M.S
87. Renal physiology- Dr. Kh.
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87
Peritubular capillary and renal interstitial fluid physical forces
Reabsorption =Kf x Net reabsorptive force
B.P.U.M.S
89. Renal physiology- Dr. Kh.
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89
Regulation of peritubular capillary physical forces
The determinants of peritubular capillary reabsorption
1. Hydrostatic pressure of the peritubular capillaries which is
influenced by arterial pressure and resistances of the afferent and
efferent arterioles.
↑ Arterial pressure tend to raise peritubular capillary hydrostatic pressure
and decrease reabsorption rate.
Increase in resistance of either the afferent or the efferent arterioles reduces
peritubular capillary hydrostatic pressure and tends to increase reabsorption
rate.
2. Colloid osmotic pressure of the plasma in peritubular capillaries
↑ Colloid osmotic pressure increases peritubular capillary reabsorption.
The colloid osmotic pressure of peritubular capillaries is determined by:
Systemic plasma colloid osmotic pressure
Filtration fraction
3. Kf (Increases in Kf raise reabsorption)
4. Hormones (Aldosterone, AII, ADH, ANP, PTH)
B.P.U.M.S
90. Renal physiology- Dr. Kh.
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90
B.P.U.M.S
Regulation of peritubular capillary physical forces
91. Renal physiology- Dr. Kh.
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91
Renal interstitial hydrostatic and colloid osmotic
pressures
B.P.U.M.S
92. Renal physiology- Dr. Kh.
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B.P.U.M.S
The amount of substance that is filtered per unit time.
For freely filtered substances, the filtered load is just the product of
GFR and plasma concentration.
Sodium filtered load: 0.14 mEq/mL x 125 mL/min = 17.5 mEq/min.
Filtered load
93. Renal physiology- Dr. Kh.
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93
B.P.U.M.S
The volume of plasma from which that substance has been removed
and excreted into urine per unit time (volume/time).
If a substance is present in urine at a concentration of 100 mg/mL and
the urine flow rate is 1 mL/min, the excretion rate for this substance is
calculated as follows:
If this substance is present in plasma at a concentration of 1 mg/mL,
its clearance is as follows:
Clearance
94. Renal physiology- Dr. Kh.
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94
B.P.U.M.S
A healthy 25-year-old woman was a subject in an approved research
study. Her average urinary urea excretion rate was 12 mg/min, measured
over a 24-hour period. Her average plasma urea concentration during
the same period was 0.25 mg/mL.
What is her calculated urea clearance?
A. 0.25 mL/min B. 3 mL/min
C. 48 mL/min D. 288 mL/min
Question
95. Renal physiology- Dr. Kh.
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95
B.P.U.M.S
GFR is an index of kidney function. Knowledge of the patient's
GFR is essential in evaluating the severity of kidney disease.
The substance used for measuring GFR must:
Be freely filtered across the glomerulus into Bowman's space
Not be reabsorbed or secreted by the nephron
Not be metabolized or produced by the kidney
Not alter the GFR
Inulin and creatinine can be used to measure GFR.
Using clearance to estimate GFR
96. Renal physiology- Dr. Kh.
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96
B.P.U.M.S
Using clearance to estimate GFR
Inulin clearance can be used to estimate GFR
Other substances that have been used clinically to estimate GFR include
radioactive iothalamate and creatinine.
99. Renal physiology- Dr. Kh.
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99
B.P.U.M.S
Correlation between plasma creatinine concentration and GFR
100. Renal physiology- Dr. Kh.
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100
B.P.U.M.S
If we know the GFR (as assessed from inulin clearance) and the
clearance of a given substance, then any difference between
clearance and GFR represents net secretion or reabsorption
(or, in a few rare cases, renal synthesis).
If the clearance of a substance exactly equals the GFR (inulin
clearance), then there has been no net reabsorption or secretion.
If the clearance is greater than the GFR, there must have been net
secretion.
Finally, if the clearance is less than the GFR, there must have been
net reabsorption.
What can the clearance of a substance tell us?
101. Renal physiology- Dr. Kh.
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101
B.P.U.M.S
If a substance is completely cleared from the plasma, the clearance
rate of that substance is equal to the total renal plasma flow thus:
Amount of the substance delivered to the kidneys by RPF equals to
amount of the substance excreted in the urine
RPF x Ps = Us x V
PAH clearance can be used to estimate RPF
The characteristics of the substance used for measuring RPF:
Its concentration in arterial and renal venous plasma should be measureable.
It is not metabolized, stored, or produced by the kidney
Does not itself affect blood flow
Using clearance to estimate RPF
102. Renal physiology- Dr. Kh.
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102
PAH clearance can be used to estimate RPF
B.P.U.M.S
104. Renal physiology- Dr. Kh.
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104
Effective renal plasma flow (ERPF)
ERPF= Clearance of PAH (CPAH)
Example
UPAH: 14 mg/mL
V urine: 0.9 mL/min
PPAH: 0.02 mg/mL
ERPF=?
B.P.U.M.S
PAH
PAH
P
VU
ERPF
.
Estimating renal plasma flow by PAH clearance
min/630
02.0
9.014
mlERPF
105. Renal physiology- Dr. Kh.
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105
ERPF can be converted to actual renal plasma flow (RPF)
Average PAH extraction ratio: 0.9
Actual RPF=ERPF/extraction ratio=630/0.9=700 ml/min
RBF = RPF ÷ (1 − Hct) = 700 ÷ (1-0.45)= 700 ÷ 0.55 = 1273
B.P.U.M.S
PAH
PAHPAH
PAH
P
VP
E
Conversion of ERPF to actual RPF
Extraction
ERPF
ActualRPF
%
106. Renal physiology- Dr. Kh.
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106
Regulation of extracellular fluid
osmolarity and sodium
concentration
B.P.U.M.S
107. Renal physiology- Dr. Kh.
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107
Importance of osmolarity regulation
Extracellular fluid sodium concentration and
osmolarity are regulated by the amount of
extracellular water.
The body water in turn is controlled by:
Fluid intake (thirst)
Renal excretion of water
In this chapter, we discuss specifically:
Mechanisms that cause the kidneys to eliminate excess water by excreting
a dilute urine
Mechanisms that cause the kidneys to conserve water by excreting a
concentrated urine
Renal feedback mechanisms that control the extracellular fluid sodium
concentration and osmolarity
Thirst and salt appetite mechanisms
B.P.U.M.S
108. Renal physiology- Dr. Kh.
Pourkhalili
108
Kidneys excrete excess water by forming a dilute urine
B.P.U.M.S
109. Renal physiology- Dr. Kh.
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109
Tubular fluid remains isosmotic in the proximal tubule
Tubular fluid becomes dilute in the ascending loop of henle
Tubular fluid in distal and collecting tubules is further diluted in the absence
of ADH.
B.P.U.M.S
Renal mechanisms for excreting a dilute urine
110. Renal physiology- Dr. Kh.
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110
Kidneys conserve water by excreting a concentrated urine
The human kidney can produce a maximal urine
concentration of 1200 to 1400 mOsm/L.
Some desert animals, such as the Australian hopping
mouse, can concentrate urine to as high as 10,000
mOsm/L
This allows the mouse to survive in the desert without
drinking water; sufficient water can be obtained through
the food ingested and metabolism.
B.P.U.M.S
111. Renal physiology- Dr. Kh.
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111
B.P.U.M.S
The fact that the large amounts of water are reabsorbed into the cortex, rather
than into the renal medulla, helps to preserve the high medullary interstitial fluid
osmolarity.
Renal mechanisms for excreting a concentrated urine
112. Renal physiology- Dr. Kh.
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112
Requirements for excreting a concentrated urine
1. High ADH Levels
Osmoreceptors and ADH secretion
B.P.U.M.S
113. Renal physiology- Dr. Kh.
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113
Requirements for excreting a concentrated urine
1. High ADH Levels
Osmoreceptors and ADH secretion
B.P.U.M.S
114. Renal physiology- Dr. Kh.
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114
Requirements for excreting a concentrated urine
2. Hyperosmotic renal medulla
The process by which renal medullary interstitial fluid becomes
hyperosmotic:
a. Countercurrent mechanism (50 %)
The countercurrent mechanism depends on the special anatomical arrangement of
the loops of Henle and the vasa recta
b. Urea recycling (40-50 %)
B.P.U.M.S
115. Renal physiology- Dr. Kh.
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115
a. Countercurrent mechanism
Countercurrent mechanism produces a hyperosmotic renal medullary
interstitium
The major factors that contribute to the buildup of solute concentration
into the renal medulla are as follows:
1. Active transport of sodium ions and co-transport of potassium, chloride, and
other ions out of the thick portion of the ascending limb of the loop of Henle
into the medullary interstitium
2. Active transport of ions from the collecting ducts into the medullary interstitium
3. Facilitated diffusion of large amounts of urea from the inner medullary
collecting ducts into the medullary interstitium
4. Diffusion of only small amounts of water from the medullary tubules into the
medullary interstitium, far less than the reabsorption of solutes into the
medullary interstitium
B.P.U.M.S
116. Renal physiology- Dr. Kh.
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116
Steps involved in causing hyperosmotic renal medula
B.P.U.M.S
Countercurrent multiplier system in the loop of Henle for producing
a hyperosmotic renal medulla
117. Renal physiology- Dr. Kh.
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117
Role of distal tubule and collecting ducts in excreting a
concentrated urine
B.P.U.M.S
The fact that the large amounts of water are reabsorbed into the cortex, rather
than into the renal medulla, helps to preserve the high medullary interstitial fluid
osmolarity.
118. Renal physiology- Dr. Kh.
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118
Recirculation of urea from collecting duct to loop of henle
contributes to hyperosmotic renal medulla
B.P.U.M.S
b. Role of urea recycling
119. Renal physiology- Dr. Kh.
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119
Countercurrent exchange in the vasa recta preserves
hyperosmolarity of the renal medulla
There are two special features of the renal medullary blood
flow that contribute to the preservation of the high solute
concentrations:
1. The medullary blood flow is low, accounting for less than 5 per cent of the
total renal blood flow. This sluggish blood flow is sufficient to supply the
metabolic needs of the tissues but helps to minimize solute loss from the
medullary interstitium.
2. The vasa recta serve as countercurrent exchangers, minimizing washout of
solutes from the medullary interstitium
B.P.U.M.S
Countercurrent exchange in the vasa recta
120. 120
Countercurrent exchange in the vasa recta
B.P.U.M.S
Increased medullary blood flow can reduce urine concentrating ability
122. Renal physiology- Dr. Kh.
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122
Summary of urine concentrating mechanism and changes in osmolarity
in different segments of the tubules
B.P.U.M.S
123. Renal physiology- Dr. Kh.
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123
Obligatory urine volume
A normal 70-kilogram human must excrete about 600 milliosmoles
of solute each day.
Maximal urine concentrating ability is 1200 mOsm/L
Drinking 1 liter of seawater with a concentration of 1200 mOsm/L
would provide a total sodium chloride intake of 1200 milliosmoles.
If maximal urine concentrating ability is 1200 mOsm/L, the amount
of urine volume needed to excrete 1200 milliosmoles would be 1200
milliosmoles divided by 1200 mOsm/L, or 1.0 liter.
Why then does drinking seawater cause dehydration?
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Osmolar clearances
When the urine is dilute, water is excreted in excess of solutes.
Conversely, when the urine is concentrated, solutes are excreted in
excess of water.
Osmolar clearance (Cosm):
The volume of plasma cleared of solutes each minute.
For example:
If Posm= 300 mosm/L, Uosm= 600 mosm/L, urine flow rate is 1 ml/min
(0.001 L/min)
Osmolar clearance is 0.6 mosm/min divided by 300 mosm/L, or
0.002 L/min (2.0 ml/min).
This means that 2 milliliters of plasma are being cleared of solute
each minute.
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Free-water clearance (CH20) is calculated as the difference between water
excretion (urine flow rate) and osmolar clearance:
Thus, the rate of free-water clearance represents the rate at which solute-
free water is excreted by the kidneys.
When free-water clearance is positive, excess water is being excreted by
the kidneys
When free-water clearance is negative, excess solutes are being removed
from the blood by the kidneys and water is being conserved.
Thus:
When urine osmolarity is greater than plasma osmolarity, free-water
clearance will be negative, indicating water conservation
When urine osmolarity is lower than plasma osmolarity, free-water
clearance will be positive, indicating that water is being removed from
plasma.
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Free water clearances
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Disorders of urinary concentrating ability
Inappropriate secretion of ADH (Either too much or too little
ADH secretion)
Impairment of the countercurrent mechanism.
A hyperosmotic medullary interstitium is required for maximal urine
concentrating ability. No matter how much ADH is present, maximal urine
concentration is limited by the degree of hyperosmolarity of the medullary
interstitium.
Inability of the distal tubule, collecting tubule, and collecting
ducts to respond to ADH.
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Failure to Produce ADH (Central diabetes insipidus)
The treatment for central diabetes insipidus is administration of a synthetic
analog of ADH, desmopressin.
Inability of the kidneys to respond to ADH
(Nephrogenic diabetes insipidus)
The treatment for nephrogenic diabetes insipidus is to correct, if possible,
the underlying renal disorder.
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Disorders of urinary concentrating ability
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Control of ECF osmolarity and Na+ concentration
Estimating plasma osmolarity from plasma sodium
concentration
Because sodium and its associated anions (Cl-, HCO3-)
account for about 94 per cent of the solutes in the
extracellular compartment, plasma osmolarity can be
roughly approximated as:
Posm=2.1 x Plasma sodium concentration
Posm=2.1 x 142= 298 mosm/L
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Two primary systems regulating the concentration
of sodium and osmolarity of extracellular fluid:
1. The osmoreceptor-ADH system
2. The thirst mechanism
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CNS centers for thirst
1. Anteroventral wall of the third ventricle (AV3V)
Subfornical organ
OVLT
2. A small area located anterolaterally in the preoptic nucleus
Stimuli for thirst
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2. Role of thirst in controlling ECF osmolarity and Na cocentration
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Integrated responses of osmoreceptor-ADH and thirst mechanisms
in controlling extracellular fluid osmolarity and sodium concentration
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Role of AII and aldosterone in ECF osmolarity and Na concentration
Angiotensin II and aldosterone have little effect on sodium
concentration, because:
Although these hormones increase the amount of sodium in the ECF, they
also increase the ECF volume by increasing reabsorption of water along
with the sodium.
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Regulation of potassium excretion
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Normal K intake, distribution and output from the body
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Regulation of potassium excretion
ECF K concentration: 4.2 ±0.3 mEq/L
This precise control is necessary because many cell
functions are very sensitive to changes in extracellular
fluid potassium concentration.
For instance, an increase in plasma potassium
concentration of only 3 to 4 mEq/L can cause cardiac
arrhythmias, and higher concentrations can lead to
cardiac arrest or fibrillation.
Total ECF K → (14×4.2)→ 59 milliequivalents
Total ICF K → (28×140)→ 3920 milliequivalents
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Effect of adding or removing K to ECF
The potassium in a single meal → as high as 50mEq
Daily intake of K → 50 - 200 mEq/day
Therefore:
Failure to rapidly rid the extracellular fluid of the ingested potassium could
cause life-threatening hyperkalemia.
Likewise, a small loss of potassium from the extracellular fluid could cause
severe hypokalemia.
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Factors that can influence the distribution of K between the
intra- and extracellular compartments
Insulin stimulates k uptake into cells by activating Na-K
ATPases in many cells
Aldosterone increases potassium uptake into cells
↑ K intake → ↑ secretion of aldosterone → ↑ cell potassium uptake.
↑ Aldosterone secretion (Conn's syndrome) → hypokalemia.
↓ Aldosterone secretion (Addison's disease) → hyperkalemia due to
accumulation of potassium in ECF as well as to renal retention of K.
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Factors that can influence the distribution of K
B-adrenergic stimulation increases cellular uptake of
potassium probably by (up-regulating the activity of the
sodium-potassium pump)
Acid-base abnormalities can cause changes in
potassium distribution
Metabolic acidosis increases extracellular potassium concentration, in part
by causing loss of potassium from the cells.
Metabolic alkalosis decreases extracellular fluid potassium concentration.
↑ H+ → ↓ activity Na-K ATPase pump → ↓cellular uptake of K and raises
extracellular K
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Factors that can influence the distribution of K
Cell lysis causes increased extracellular K concentration
As occurs with severe muscle injury or with red blood cell lysis
Strenuous exercise can cause hyperkalembia by
releasing potassium from skeletal muscle.
Increased ECF osmolarity causes redistribution of K
from the cells to ECF.
In diabetes mellitus, large increases in plasma glucose raise
extracellular osmolarity, causing cell dehydration and movement of
potassium from the cells into the extracellular fluid
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Overview of renal potassium excretion
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Overview of renal potassium excretion
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Most of the day-to-day variation of potassium excretion is not due to
changes in reabsorption in the proximal tubule or loop of Henle but:
Most daily variation in potassium excretion is caused by changes in
potassium secretion in distal and collecting tubules
Thus, most of the day-to-day regulation of potassium excretion
occurs in the late distal and cortical collecting tubules, where
potassium can be either reabsorbed or secreted, depending on the
needs of the body.
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Overview of renal potassium excretion
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Potassium secretion by principal cells
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Intercalated cells reabsorb k during potassium depletion
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Factors that regulate k secretion by principal cells
Plasma potassium concentration
Aldosterone
Tubular flow rate
Hydrogen ion concentration
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1. Increased ECF K concentration stimulates potassium
secretion by 3 mechanisms:
a. Increased ECF K concentration stimulates the Na-K ATPase pump,
thereby increasing K uptake across the basolateral membrane.
b. Increased ECF K concentration increases the K gradient from the renal
interstitial fluid to the interior of the epithelial cell; this reduces
backleakage of potassium ions from inside the cells through the
basolateral membrane.
c. Increased K concentration stimulates aldosterone secretion, which further
stimulates potassium secretion
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4. Acute acidosis decreases potassium secretion
The primary mechanism by which increased hydrogen
ion concentration inhibits potassium secretion is:
Decreased activity of the Na-K ATPase pump. This in turn decreases
intracellular potassium concentration and subsequent passive diffusion of
potassium across the luminal membrane into the tubule.
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Chronic acidosis, lasting over a period of several days,
increases urinary potassium excretion.
The mechanism for this effect is:
Chronic acidosis inhibit proximal tubular sodium chloride and water
reabsorption, which increases distal volume delivery, thereby stimulating the
secretion of potassium.
This effect overrides the inhibitory effect of hydrogen
ions on the Na-K ATPase pump. Thus, chronic acidosis
leads to a loss of potassium, whereas acute acidosis
leads to decreased potassium excretion
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