This document provides an overview of renal tubular acidosis (RTA). It defines RTA as a condition where the kidneys are unable to appropriately acidify the urine, resulting in acid accumulation in the body. There are four main types of RTA - type 1 involves a defect in the distal tubule, type 2 involves a defect in the proximal tubule, type 3 is a combined defect, and type 4 involves hyperkalemia. The document outlines the pathophysiology, clinical features, diagnostic testing and management considerations for each type of RTA.
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
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Title: Sense of Taste
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 structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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!
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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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.
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.
3. INTRODUCTION
Metabolic acidosis is a clinical disturbance characterized by an increase in
plasma acidity, low blood pH (<7.35)
It occurs when the body produces excessive quantities of acid or when the
kidneys are not removing enough acid from the body (increased
production of hydrogen ions or the inability of the body to form
bicarbonate (HCO3) in the kidney
If unchecked, leads to acidemia with varying consequences
3
4. INTRODUCTION
Usually, is a sign of an underlying disease process and identification of this
underlying condition is essential to initiate appropriate therapy
Causes are diverse
Consequences can be serious including coma and death
Understanding the regulation of acid-base balance requires appreciation
of the fundamental definitions
4
5. DEFINITION OF TERMS
An acid is a substance that can donate hydrogen ions (H+)
A base is a substance that can accept H+
Buffers
Prevent sudden and large swings in pH , resist pH changes
Consist of a weak base and acid
Chemical buffers- Phosphate buffer, bicarbonate buffer, ammonia buffer
Acidemia refers to a pH < 7.35 (normal range 7.35-7.45)
5
6. RENAL PHYSIOLOGY
Kidneys regulate plasma osmolarity by modulating the amount of water,
solutes, and electrolytes in the blood
They ensure long term acid-base balance
Normally the kidneys secrete H+ into the urine which are lost from the body
during urination
If blood is too acidic, more H+ are lost and vice versa if too basic
Mechanism of urine formation- Glomerular filtration, tubular reabsorption and
tubular secretion
6
7. ACIDIFICATION OF URINE
Urine acidification and bicarbonate reabsorption take place in several
segments of the nephron; proximal tubule, loop of Henle, distal tubule,
and collecting ducts where most acidification occurs
Kidneys normally maintain acid-base balance by excreting the acid ions
and reabsorbing the bicarbonate ions (base) which serves to neutralize the
acid produced by the body
During the elaboration of an acid urine, the distal nephron (DCT and
Collecting duct) reabsorb that portion of the filtered HCO3 escaping
proximal reabsorption, titrtate luminal buffers and lower urine pH
The secretion of H+ occurs by a primary active mechanism which involves
the extrusion of H+ across the luminal cell membrane by an electrogenic
H+ pump driven by the hydrolysis of ATP
7
9. ANION GAP
Na + Unmeasured cations = Cl + HCO3 + Unmeasured anions
Anion gap is the quantity of anions not balanced by cations
Usually due to negatively charged plasma proteins as the charges of the
other unmeasured cations and anions tend to balance out
9
10. CAUSES OF METABOLIC ACIDOSIS
4 main causes;
Increase in the generation of H+ from endogenous and exogenous acids
(Lactate, ketones) or exogenous acids (salicylate, methanol, ethylene glycol)
Inability of the kidneys to excrete the hydrogen from dietary protein intake
(type 1 and 4 Renal tubular acidosis)
The loss of bicarbonate due to wasting through the kidneys (type 2 RTA) or
through the GIT (diarrhoea)
The kidneys response to alkalosis
10
11. HIGH ANION GAP
High AG if over 12mEq/L
Causes;
Lactic acidosis
Ketoacidosis
CKD
Ingestions; Salicylte, methanol, ethylene glycol, propylene, paraldehyde, metformin,
phenformin
Massive rhabdomyolysis
11
12. NORMAL ANION GAP
The number of bicarbonate ions decrease
To compensate the amount of lost bicarbonate ions, the body absorbs
chloride ions
As a result, the anion gap remains normal but the amount of chloride ions
increases
Also known as hyperchloremic acidosis
Hyperchloremic acidosis occurs basically due to these conditions;
Severe diarrhoea
Renal tubular acidosis
Rarer causes; uterosigmoid or pancreatic fistulas, acetazolamide use, Addison‘s
disease
12
13. URINE ANION GAP
In severe diarrhoea, bicarbonate is lost in the stool, reducing the amount of
anions, resulting in acidity
GI and renal losses can be distinguished via urinary anion gap analysis;
Urine AG = Urine Na + Urine K – Urine Cl
A positive value suggests a low urinary NH4+, and indicates renal bicarbonate
loss (RTA)
Negative values suggests a high urinary NH4+, found with GI causes
(diarrhoea)
13
14. HYPERCHLOREMIC ACIDOSIS
Loss of bicarbonate stores through diarrhoea or renal tubular wasting
leads to a metabolic acidosis state characterized by increased plasma
chloride concentration and decreased plasma bicarbonate concentration
14
15. RENAL TUBULAR ACIDOSIS
RTA is a condition that results from the kidneys being unable to appropriately
acidify the urine resulting in the accumulation of acid in the body
A metabolic acidosis occuring secondary to decreased renal acid secretion in
the absence of marked decreases in GFR, and characterized by a normal AG are
collectively referred to as Renal Tubular Acidoses
Results in growth retardation, kidney stones, bone disease, CKD
Types;
RTA type 1- Distal RTA
RTA type 2- Proximal RTA
RTA type 3- Combined Proximal and Distal RTA
RTA type 4- Hyperkalemic
15
16. TYPE 1 (DISTAL RTA)
In the distal nephron, primarily the collecting duct, the urine pH reaches its
lowest values
Distal tubule is responsible for generating new bicarbonate under influence of
aldosterone
Damage to alpha-intercalated cells of distal tubule causes no new generation
of bicarbonate and thus, no hydrogen ions
This raises the urine pH due to inadequate acid secretion
It is associated with hypokalaemia due to failure of H+/ATPase
Also known as the classic type
The deficiency is secondary to 2 main pathophysiologic mechanisms;
A secretory defect
A permeability defect
When secretory defect predominates, the decreased secretion of protons (H+)
fails to maximally decrease the urinary pH
16
17. TYPE 1
Other mechanisms include decreased functioning of H+/ATPase, increased
leak of protons from the tubules back into the lumen as seen in
amphotericin B toxicity
Causes (Inherited);
Autosomal dominant; mutations of SLC4A1 gene
Autosomal recessive with deafness; mutations in the gene ATP6V1B expressed
in alpha=intercalated cells of distal tubule and cochlear, having distal RTA and
sensorineural deafness
Autosomal recessive without deafness; mutations in ATP6V0A4
17
18. TYPE 1(Causes-Acquired)
Autoimmune diseases are the commonest cause in adults; SLE, Sjogren
syndrome, RA, SSc, thyroiditis, hepatitis and PBC
Genetic association; Marfan‘s syndrome, Ehler Danlos syndrome, sickle cell
disease, congenital obstruction of the urinry tract
Nephrocalcinosis; chronic hypercalcemia, medullary sponge kidney
Tubulointerstitial diseases; chronic pyelonephritis, chronic interstitial nephritis,
obstructive uropathy, renal transplant ejection
Hypergammaglobulinemic states; monoclonal gammopathy, multiple
myeloma, amyloidosis, crryoglobulinemia, CLD
Drugs; lithium, amphotericin B, NSAIDs, lead, antiviirals
Miscellaneous; diopathic, familial hypercalciuria, glue sniffing (inhalation of
recreation drug)
18
19. TYPE 2 (PROXIMAL)
Normally, 85% to 95% of bicarbonate is reabsorbed at the proximal tubule
and only 10% absorbed at the distal tubule
Due to a bicarbonate leak, impaired proximal HCO3 reabsorption in
proximal tubule results in excess HCO3 in urine leading to metabolic
acidosis
Often associated with Fanconi syndrome and is rarer than type 1
Hypokalaemia is common due to osmotic diuresis because of decreased
HCO3 reabsorption causing increased flow rate to the tubules and causing
increased K+ excretions
Carbonic anhydrase inhibitors impair proximal bicarbonate reabsorption,
tenofovir, ifosfamide can cause Fanconi syndrome
Genetic causes; autosomal recessive, autosomal dominant
19
21. TYPE 3 (MIXED)
Rare
Mostly affects children from Arabic, North African and Middle Eastern
descent
Due to mutations of CA II resulting in carbonic anhydrase II deficiency
21
22. TYPE 4 (HYPERKALEMIC)
Ammonium excretion requires the renal synthesis of ammonia and the
secretion of hydrogen ions from the collecting tubular cells into the
tubular lumen where they are trapped as ammonium (NH4+)
Hypoaldesteronism causes hyperkalemia and metabolic acidosis
Hyperkalaemia impairs ammonia genesis in the proximal tubule and
reduces the availability of NH3 to buffer urinary hydrogen ions and
decreases hydrogen ion excretion in urine
The failure to acidify urine is due to inadequate amount rather than
complete absence of NH3 available for buffering of protons
Even if only a few protons are secreted distally, urine pH would fall and this
is why these patients have a urine pH < 5.5
22
23. TYPE 4
Deficiency of or resistance to aldosterone is the most common cause of
hyperkalaemic dRTA
Most common cause of type 4 RTA in adults is hyporeninemic
hypoaldosteronism which is frequently observed among patients with mild to
moderate CKD, especially if due to diabetic nephropathy
Resistance to the action of aldosterone is observed in patients with a chronic
tubulointerstitial disease, those on potassium-sparing diuretics and rare
congenital disorder called pseudohypoaldosteronism
Addison disease, bilateral adrenalectomy, certain enzymatic defects, NSAID
use, HIV, Renal transplant
23
24. CLINICAL FEATURES
Symptoms of metabolic acidosis are not specific
The respiratory centre in the brainstem is stimulated and hyperventilation
develops in an effort to compensate for the acidosis
As a result; varying degrees of dyspnoea
Chest pain, headache, confusion, generalized weakness, and bone pain
Nausea, vomiting and loss of appetite
24
25. Important points in the history..
Age of onset, family history may point toward inherited disorders which
usually start in childhood
Visual symptoms, including dimming, photophobia, scotomata- methanol
ingestion
Renal stones- RTA or chronic diarrhoea
Tinnitus, blurred vision, and vertigo- Salicylate poisoning
25
26. Important points in the history..
Diarrhoea- GI losses of HCO
History of DM, alcoholism, starvation- accumulation of ketoacids
Polyuria, increased thirst, epigastric pain, vomiting- DKA
Nocturia, pruritus, polyuria, anorexia, decline in urine output- Renal failure
Ingestion of toxins or drugs- Salicylates, acetazolamide,cyclosporine,
ethylene glycol, methanol, metformin, topiramate
26
27. SIGNS
The best recognized sign of metabolic acidosis is kussmaul respirations, a
form of hyperventilation that serves to increase minute ventilatory volume.
Characterized by an increase in tidal volume rather than respiratory rate.
Appreciated as deliberate, slow and deep breathing
Chronic metabolic acidosis in children stunted growth and rickets
Coma and hypotension in acute severe metabolic acidosis
27
28. SIGNS
Non specific; and depend on the underlying cause
Some examples; xerosis, scratch marks, pallor, drowsiness, fetor, asterixis,
pericardial rub for renal failure, dry mucous membranes and fruity smell
for DKA
28
29. HISTORY AND PHYSICAL FOR THE
RTAs
Type 1 Distal;
rickets, growth failure, osteomalacia
Hypercalciuria, hypocitaturia (citrate is reabsorbed as a buffer for hydrogen
ions)
Alkaline urine
Nephrocalcinosis (calcium phosphate stones)
Recurrent UTIs
ESRD
Muscle weakness, arrhythmia from hypokalaemia
29
30. HISTORY AND PHYSICAL FOR THE
RTAs
Type 2 Proximal
Osteomalacia
Hypokalaemia
Hypophosphatemic rickets
Loss of glucose, urate, and amino acids in the urine
Type 3 Mixed
Guibaud-Vainsel syndrome
Osteopetrosis
Cerebral calcification, Mental retardation
Facial dysmorphism, conductive hearing loss, blindness due to nerve compression
Type 4 Hyperkalemic
Hyperkalaemia, metabolic acidosis
30
32. Calculations
Anion gap
Osmolar gap
Appropriate PCO2 change based on serum bicarbonate
32
33. INTERPRETATION STEPS
Determine the main acid-base problem
1. Determine the acid-base status (pH lower than 7.35)
Metabolic or Respiratory
2. Bicarbonate < 20mEq/L
Metabolic acidosis
3. Calculate anion gap
Normal AG; 8 – 16mEq/L (5 -7 using newer lab analyzers)
4. Assess if respiratory compensation is adequate
5. Determine if patients history and physical fits the proposed diagnosis of type
and causes of metabolic acidosis
33
34. URINE pH and AG
dRTA – urinary pH > 5.5, urinary AG positive
pRTA – urinary pH < 5.5, urinary AG positive
Type 4 RTA - urinary pH < 5.5, urinary AG positive
Diarrhoea – urinary pH variable, urinary AG negative
34
35. WORK UP
1st clue to metabolic acidosis is a decreased serum bicarbonate
concentration observed from an EUCr
Remember that a decreased serum bicarbonate can be observed as a
compensatory response to respiratory alkalosis
Bicarbonate of less than 15mEq/L almost always is due to at least in part,
metabolic acidosis
Only definitive way to diagnose metabolic acidosis is by simultaneous
measurement of serum electrolytes and arterial blood gases, whcih shows
pH and PaCO to be low
35
36. A low serum HCO3 and pH of less than 7.40 upon ABG analysis confirms
metabolic acidosis
Calculate the anion gap (AG) to help with the differential diagnosis and
diagnose mixed disorders
In general, a high-AG acidosis is present if AG is greater than 10-12mEq/L
and a non-AG acidosis is present if the AG is less than or equal to 10-12
mEq/L.
The AG decreases by 2.5mEq for every 1g/dl decrease in serum albumin
36
37. Osmolar gap (OG) = Measured serum osmolality - Calculated serum osmolality
Normal is about 10-15mOsm/kg
Calculated plasma osmolality (P) = {2 X Na}+{Glucose in mg/dl}/18+{BUN in mg/dl}/2.8
If AG is elevated, calculate osmolar gap
OG > 15mOsm/kg indicates the presence of abnormal unmeasured os motically active
molecules
Most common causes; ethanol, methanol, ethylene glycol, isopropanolol
37
38. EVALUATION OF RTAs
(General)
Consider RTAs in any patient with an otherwise unexplained normal anion
gap (hyperchloremic) metabolic acidosis
Measure blood pH
Plasma potassium; low in type 1 and type 2 and high in type 4
BUN/Cr; normal or near normal (rules out renal failure as the cause of
acidosis)
Urine anion gap (Na + K) – Cl (positive gap signifies low NH4Cl excretion
which causes a decrease inchloride in urine along with hyperchloemic
metabolic acidosis suggesting RTA
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39. EVALUATION OF RTAs
(Specific)
Acid load test confirms diagnosis of distal RTA
Bicarbonate infusion test
Urine Na; type 4 RTA presents with persistently high urine Na despite
restricted Na diet because of aldosterone deficiency or resistance
39
40. TREATMENT
Treatment of GI causes of hyperchloremic acidosis is aimed at;
Administration of saline solutions to repair volume losses
Early administration of potassium
Treatment of acidosis with bicarbonate-containing solutions is
accompanied by potassium replacement to avoid severe hypokalemia
Generally, identify underlying disease entity, give specific therapy
However therapy for hyperchloremic RTA still needed
Goals of therapy; reduce rate of progression to CKD, neutralize metabolic
bone disease and in children, improve growth
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41. TREATMENT/ MANAGEMENT OF THE
RTAs (Hypokalaemic dRTA)
Treatment consists of long-term alkali administrationin amounts sufficient to
counterbalance endogenous acid productionand any bicarbonaturia that may
be present
Oral bicarbonate replacement at 1-2 mEq/kg per day by sodium bicarbonate
or potassium citrate
Potassium citrate necessary for patients with hypokalaemia, nephrolithiasis or
nephrocalcinosis
Sought and treat underlying conditions
Most bicarbonate is absorbed in the proximal tubule so distal RTA is relatively
easy to correct
Spironolactone can be used to maintain normokalaemia
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42. TREATMENT/ MANAGEMENT OF THE
RTAs (Proximal RTA)
High doses of bicarbonate greater than 5 to 15 mEq/kg per day are required to
treat type 2 RTA
Raising the serum bicarbonate concentration will increase the filtered
bicarbonate load above the proximal tubule‘s reduced absorptive capacity,
resulting in a marked bicarbonate diuresis so a larger amount of alkali is
required to account for these urine losses
Increased bicarbonate concentration in urine induced by alkali therapy also
increases urinary potassium losses
Administration of potassium salts must accompany or precede as it minimizes
the degree of hypokalemia associated with alkali therapy
Can be dificult to treat because alkali administration results in prompt and
marked bicarbonaturia and potassium wasting
Thiazide diuretics cause extracellular volume depletion which will enhance
bicarbonate reabsorption in type 2 RTA
42
43. TREATMENT/ MANAGEMENT OF THE
RTAs (Hyperkalaemic dRTA)
Identify entities amenable to intervention such as obstructive uropathy
Most patients can be managed with a limitation of dietary potassium to 40 to
60 mEq per day
Avoid foods and drugs that may contain high potassium content
Cation exchange resins may be helpful in hyperkalaemia
Distal sodium delivery is increased if patients increase ingestion of dietary salt
Fludrocortisone 0.1mg per day is effective in managing hyperkalaemia
associated with aldosterone deficiency. However it is not usually used due to
hypertension, heart failure and oedema exacerbated in patients with renal
insufficiency
43
44. Hypophosphatemia due to decreased proximal phosphate reabsorption
and reduced activation of vitamin D also occurs in some patients and may
be a major contributor to the development of bone disease
Thus phosphate and vitamin D supplementation may be required to
normalize the serum phosphate and reverse metabolic bone disease
44
45. PROGNOSIS
Morbidity and mortality in metabolic acidosis are primarily related to the
underlying condition and the acid-base derangement
Prognosis is poor if the derangements are large and vitals are unstable
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46. CONCLUSION
Metabolic acidosis is a clinical disturbance characterized by an increase in
plasma acidity (pH < 7.35 and a low HCO3 level)
It is usually a sign of an underlying disease process
Identify underlying and initiate appropriate therapy
Treatment is case dependent and lab tests include; arterial blood gas,
electrolytes, toxin levels
The overall prevalence in the population is uncertain
46
47. REFERENCES
Roth KS, Chan JC. Renal tubular acidosis; a new look at an old problem.
Clin Pediatr (Phila). 2001 Oct;40(10):533-43 (Pub Med)
Trepiccione F, Prosperi F, Hubner CA, Chambrey R. New findings on the
Pathogenesis of Distal Renal Tubular Acidosis. Kidney Dis (Basel). 2017
Dec;3(3):98-105 (Pub Med)
Johnson RJ, Feehally J, Floege J, Marcello T. Comprehensive Clinical
Nephrology. 5e. Philadelphia, PA; Elsevier/Saunders 2015
Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds.
Harrison‘s Principles of Internal Medicine, 18e. New York; McGraw Hill;
2012.
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