This document discusses acid-base disorders. It begins by explaining that the human body maintains a slightly basic pH through various buffering mechanisms. It then describes the bicarbonate buffer system and how the lungs, kidneys, and buffers work to regulate pH. It discusses the causes, classifications, and clinical features of metabolic acidosis and alkalosis. Key points include how to interpret arterial blood gases, calculate anion and urine gaps, and determine compensations and mixed disorders. The document provides an in-depth overview of acid-base physiology and pathophysiology.
Short Review regarding Metabolic Acidosis
The Causes, anion gap,urine osmolal gap, Renal Tubular Acidosis, approach to Metabolic Acidosis in Final Slide
Short Review regarding Metabolic Acidosis
The Causes, anion gap,urine osmolal gap, Renal Tubular Acidosis, approach to Metabolic Acidosis in Final Slide
Metabolic acidosis is a significant electrolyte disease defined by an acid-base imbalance in the body. Metabolic acidosis is caused by three major factors: increased acid production, bicarbonate loss, and a decreased ability of the kidneys to eliminate excess acids.
HEMODYNAMICS MONITORING IN CRITICALLY ILL PATIENTS: ASSESSMENT OF FLUID STATU...Bassel Ericsoussi, MD
Invasive methods are well accepted, but there is increasing evidence that these methods are neither accurate nor effective in guiding therapy
An accurate and non-invasive measurement of CO is the best method of cardiovascular assessment
Metabolic acidosis is a significant electrolyte disease defined by an acid-base imbalance in the body. Metabolic acidosis is caused by three major factors: increased acid production, bicarbonate loss, and a decreased ability of the kidneys to eliminate excess acids.
HEMODYNAMICS MONITORING IN CRITICALLY ILL PATIENTS: ASSESSMENT OF FLUID STATU...Bassel Ericsoussi, MD
Invasive methods are well accepted, but there is increasing evidence that these methods are neither accurate nor effective in guiding therapy
An accurate and non-invasive measurement of CO is the best method of cardiovascular assessment
This presentation discuss about acid-base-gas normal ratio and its indication in relation to varying abnormal level and how to manage it. This includes clinical analysis practice.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
- 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
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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
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
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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.
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.
2. ACID BASE BALANCE PHYSIOLOGY
• Human body is always pro acidic as every living cell needs energy
molecule i.e. ATP molecules.
• During ATP production in cell , acid is generated .
• But, the normal blood pH is 7.35-7.45 ( slightly basic ) and the urine pH is
6.5-7.0 (slightly acidic).
• Mechanisms of Acid Base Balance Regulating pH
1. Buffering ( Tissue level)
Extracellular: HCO3- (most imp), albumin
Intracellular: PO42-(bones), Haemoglobin
2. Respiratory Regulation ( minor role )
3. Renal regulation (most potent) by acidification of urine.
3. BUFFERS
• Buffers are substances that attenuate the change in pH that occurs when acids
or bases are added to the body.
• Extracellular buffers accomplish buffering of metabolic causes and intracellular
buffers to that of respiratory causes.
• The pH at which a buffer is 50% dissociated is its pKa ( ionization constant
of acid).
• The best physiologic buffers have a pKa close to 7.40 .When a pH is lower
than pKa of a buffer ,there is more acid than base and vice versa.
• pH of body fluids is calculated using the Henderson-Hasselbach equation
which expresses the relationship among pH , pKa and the concentrations of an
acid and its conjugate base. This relationship is valid for any buffer.
• Equation: pH = 6.1 + 𝑙𝑜𝑔
[𝐻𝐶𝑂3
−]
[𝐶𝑂2]
4. BICARBONATE BUFFER SYSTEM
• It is based on the relationship between CO2 and HCO3¯
• CO2+H2O H+ + HCO3¯
• CO2 acts as an acid which after combining with water releases H+, bicarbonate
acts as its conjugate base in that it accepts an H+.
• The pKa of this reaction is 6.1 .
• The bicarbonate buffer system is very effective because of the high
concentration in the body (24 meq/l) and because it is an open system. The
remaining body buffers are in closed system.
• As the lungs increase CO2 excretion when the blood CO2 concentration
increases.
5. BICARBONATE BUFFER SYSTEM
• When acid is added to the body, following reaction occurs:
H+ + HCO3¯ CO2 + H2O
• In closed system, the CO2 would increase. The higher CO2 concentration
would lead to an increase in the reverse reaction
CO2 + H2O H+ + HCO3¯
This will increase H+, limiting the buffering capacity of bicarbonate.
As the lungs excrete excess CO2 , the reverse reaction doesn’t occur thus
enhancing the buffering capacity of bicarbonate.
Same mechanism holds with addition of base.
6. NON BICARBONATE BUFFERS
1. Phosphate
• Can bind upto 3 hydrogen molecules so it can exist as PO4 3¯, HPO4 2¯,
H2PO4¯, H3PO4 . However, at a physiological pH most phosphate exists either
as HPO4 2¯ or H2PO4
-
• H2PO4¯ = H+ + HPO4¯
• The pKa of this reaction is 6.8, making it an effective buffer.
2. Protein
• Large numbers of histidine in the Hb makes it an effective buffer. pKa of this
reaction is 6.8.
• Plasma proteins have lesser number of histidine residues than hemoglobin
and hence they are not very effective. pKa of this reaction is 6.8.
7. ENDOGENOUS ACID PRODUCTION
• Normally when food is metabolized, 2 types of acids are added to ECF
1. Volatile acid in the form of carbonic acid ( H2co3), which determines the
level of CO2 in the blood ( PaCO2) and is excreted by lung.
2. Non volatile acids like sulphuric acid and phosphoric acids are produced
by dietary and endogenous protein catabolism. They are excreted by the
kidney.
8. RESPIRATORY REGULATION
• The respiratory compensation begins almost immediately within minutes and
is fully established by 24 hr.
• The lungs participate in regulating pH by increasing or decreasing the
elimination of CO2.
• With acidosis, pH changes around the brainstem stimulate hyperventilation
and the reverse is observed with alkalosis.
• However, the respiratory compensation is not completely effective in restoring
pH as only volatile acids i.e CO2 is taken care by the lungs.
• Failure of respiratory regulation results in respiratory acidosis or
alkalosis.
9. RENAL REGULATION
• It is the most powerful buffering system, which starts within hours and takes
5-6 days for peak effect.
• Involved in the removal of non volatile acids or bases through several active
transport mechanism.
• In response to acidosis-
1. Renal tubules reabsorb bicarbonate that is filtered at the glomerulus
2. Tubular secretion of H+ mostly in the collecting duct, with a small role in
distal tubule.
• Adequate excretion of endogenous acids requires presence of 2 urinary
buffers – Phosphate and ammonia.
10. BICARBONATE REABSORPTION IN PROXIMAL TUBULE
• The reabsorption of filtered bicarbonate is
first step in renal regulation of acid base
balance.
• The proximal tubule reclaims approximately
85% of the filtered bicarbonate.
• Remaining 15% is reclaimed mostly in the
ascending limb of the loop of Henle.
11. BICARBONATE REABSORPTION IN PROXIMAL TUBULE
• Increased HCO3- reabsorption
occurs in
1. Volume depletion
2. Hypokalemia
3. Increased PCO2 (Respiratory
Acidosis)
• Decreased HCO3- reabsorption
occurs in
1. Decreased PCO2 ( Respiratory
Alkalosis)
2. Hyperparathyroidsm ( PTH decreases
HCO3- reabsorption).
3. Carbonic anhydrase inhibitors such as
as acetazolamide
4. Disorders that can cause proximal
RTA.
12. DISTAL TUBULE ACIDIFIACTION
• Distal tubule acidification requires 2
urinary buffers- Phosphate and ammonia.
• Almost 15% of the filtered HCO3- is
absorbed in TAL via apical Na/H
exchanger.
• Type A IC cells in the distal tubule
secretes H+ via H-ATPase and H+/K+
ATPase present in the apical membrane.
• The secreted H+ combines with HPO42- to
form H2PO4- , a titrable acid which is
excreted.
• H+ ATPase is stimulated by aldosterone
13. AMMONIUM EXCRETION
• In the proximal tubule, NH3 is
produced from glutamine in the
renal cells.
• H+ is secreted by Na+-H+ exchanger
and NH3 diffuses into the lumen.
• NH4
+ is reabsorbed by Na+-K+-
2Cl− cotransporter in the TALH and
deposited in the medullary
interstitial fluid.
• In the collecting ducts, NH3 diffuses
from the medullary interstitium into
the lumen, combines with secreted
H+ in the lumen, and is excreted as
NH4
+.
14. AMMONIUM EXCRETION
• Acid excretion by the
collecting duct increases in
1. Primary
hyperaldosteronism and
secondary
hyperaldosteronism due
to volume depletion
2. Hypokalemia ( stimulates
NH3 production in
proximal tubule and
increases H+ secretion in
the collecting duct).
15. INDICATION OF ABG
• Severe respiratory or metabolic disorders
• Clinical features of hypoxia or hypercarbia
• Shock
• Sepsis
• Decreased urine output
• Renal failure
• Monitoring of babies in ventilator
16. ALGORITHM FOR SIMPLE ACID BASE DISORDER
Blood
pH
Acidemi
a
(↓pH)
Alkalemi
a
(↑pH)
Respiratory
Acidosis
Metaboli
c
Acidosis
Respiratory
Acidosis with
compensatory
metabolic
alkalosis
Metabolic
Acidosis with
compensatory
respiratory
alkalosis
Respiratory
Alkalosis
Metaboli
c
Alkalosis
Respiratory
Alkalosis with
compensatory
metabolic
acidosis
Metabolic
Alkalosis with
compensatory
respiratory
acidosis
↑pCO2
↑pCO2
↓pCO2
↓HCO3
¯ ↑HCO3
¯
↑HCO3
¯ ↓pCO2 ↓HCO3
¯
17. STEPS OF ABG INTERPRETATION
1. Is there an acid base disorder?- Look at the PaCO2 and HCO3 to
determine whether they are in the normal range.
Normal values- pH-7.35-7.45(7.40) , HCO3 – 22-26 meq/l (24), PaCO2-
35-45mm of Hg(40)
2. Is there acidosis or alkalosis?
pH<7.35 -Acidosis
pH>7.45 -Alkalosis
18. 3. What is the primary acid base disorder?
Determine the primary defect from the pH, HCO3 and PaCO2
If pH <7.35 – acidosis , may be either
• Metabolic acidosis- Low HCO3
• Respiratory acidosis- High PaCO2
If pH >7.45- alkalosis , may be either
• Metabolic alkalosis – High HCO3
• Respiratory alkalosis- Low PaCO2
STEPS OF ABG INTERPRETATION
20. 4. Calculate the expected compensation
Metabolic Acidosis
WINTER’S formula-Expected CO2= (1.5xHCO3)+ 8 ±2
Metabolic Alkalosis
Expected CO2= (HCO3 + 15 )
Respiratory Acidosis
• Acute- For every 10 mm increase in pCO2 , HCO3 increases by 1.
• Chronic- For every 10 mm increase in pC02, HCO3 increases by 3.5.
Respiratory Alkalosis
• Acute- For every 10 mm decrease in pCO2, HCO3 decreases by 2.
• Chronic- For every 10 mm decrease in pC02, HCO3 decreases by 4.
STEPS OF ABG INTERPRETATION
21. 5 . Determine the presence of mixed acid base disorder
• If either of the pH or PaCO2 is normal and the other abnormal, then there
is a mixed metabolic and respiratory disorder.
• If the pH is normal in a setting of acid base disorder , there is always a
mixed acid base disorder in the opposite direction.
• In metabolic acidosis, there may be mixed HAGMA and NAGMA or a mixed
HAGMA + metabolic alkalosis ( or pre existing compensated respiratory
acidosis )
• Delta Ratio is measured in high anion gap metabolic acidosis.
6. Clinical correlation and to establish the etiological diagnosis
STEPS OF ABG INTERPRETATION
22. SAME MIXED DISORDERS
Same Mixed Disorders – Which came first?
• If the trend of change in PaCO2 and HCO3 is the same, check the percent
difference. The one , with greater % difference between the two is the one
that is the dominant disorder.
• Eg : pH=7.25, HCO3=16, PaCO2=60
• Here, the pH is acidotic and both PaCO2 and HCO3 explain its acidosis, so
look at the % difference
• HCO3 % difference= (24-16)/24 = 0.33
• PaCO2 % difference= (60-40)/40= 0.5
• So, respiratory acidosis is the dominant disorder
23. PLASMA ANION GAP
• Plasma Anion gap is the difference between measured cations (Na+) and the
measured anions (Cl-+ HCO3
-). It is also the difference between unmeasured
cations (K , Mg , Ca) and the unmeasured anions ( albumin, phosphate, urate,
sulfate).
• Formula : Na – (Cl – HCO3)
• Normal value 8-12 meq/l or 12±2meq/l
• A 1g/dl decrease in albumin concentration decreases anion gap by 2.5 meq/l. So,
anion gap corrected for albumin is
[Na]-[Cl+HCO3]+2.5(4-albumin)
• High anion gap metabolic acidosis(HAGMA)-AG is high as HCO3 gets
overconsumed to neutralise accumulated acids and increase in unmeasured
anions.
• Normal anion gap metabolic acidosis(NAGMA)- AG is normal as HCO3 loss is
accompanied by Cl reabsorption ( hyperchloremic metabolic acidosis)
24.
25. IMPORTANCE OF ANION GAP
• Useful to establish the etiological diagnosis of metabolic acidosis.
• Useful in diagnosis of mixed disorder.
26. DELTA RATIO
• If there is high anion gap metabolic acidosis then calculate the delta ratio or delta
gap to determine additional hidden metabolic acidosis or metabolic alkalosis.
• Formula : (AG-12)/(24-HCO3)
• <0.4 –Pure NAGMA
• 0.4-0.8- Mixed NAGMA+HAGMA
• 0.8-2- Pure HAGMA
• >2- Mixed HAGMA + metabolic alkalosis
27. METABOLIC ACIDOSIS
• It is characterized by fall in plasma HCO3- and fall in pH (<7.35). The PaCO2 is
reduced secondarily by hyperventilation , which minimizes fall in pH.
• 3 basic mechanisms-
1. Loss of bicarbonate from the body
2. Impaired ability to excrete acid by the kidney
3. Addition of acid to the body ( endogenous or exogenous)
28. CLASSIFICATION AND CAUSES OF METABOLIC ACIDOSIS
I. Overproduction of H+
1. Toxins and drugs –methanol ,
ethylene glycol, salicylate etc
2. Ketoacidosis- DKA, starvation
3. Lactic acidosis-
• Type A – shock, anaemia, CO
poisoning
• Type B- Liver failure, renal failure ,
metformin , zidovudine, INH
II. Underexcretion of H+
Renal failure- uraemic acidosis(
GFR<15ml/1.73m2/min)
III. Excess loss of HCO3
1. GIT causes- diarrhea, pancreatic
fistula, ureterosigmoidostomy
2. Renal causes- RTA , drugs such
as ACEi, aldosterone antagonist,
CA inhibitors
I, II- HAGMA
III- NAGMA
29. URINARY ANION GAP
• It helps in differentiating the causes of normal anion gap metabolic acidosis.
• Urinary anion gap reflects the ability of the kidney to excrete NH4Cl
• Formula – Urinary (Na+K-Cl) =80 –NH4
• Normally UAG is zero or has a positive value around 30-35meq/l, due to the
presence of dissolved anions.
• UAG is negative in GIT causes of metabolic acidosis due to intact mechanism
of renal acidification resulting in enhanced NH4Cl excretion.
• UAG is positive in all forms of RTA due to low renal NH4+ excretion.
30. CLINICAL FEATURES OF METABOLIC ACIDOSIS
I. Manifestations of underlying disorder
II. Manifestations of metabolic acidosis
• Pulmonary changes- Kussmauls breathing
• Cardiovascular changes- In severe acidemia (pH <7.2), there is increased
susceptibility for arrythmias, decreased response to inotropes, secondary
hypotension due to depressed myocardial contractility and arterial vasodilation.
• Neurological changes- Ranges from headache, confusion, lethargy, drowsiness
to coma.
• Chronic acidemia as with renal failure can cause rickets.
31. APPROACH TO METABOLIC ACIDOSIS
I. History
II. Investigations
III. Management
History- Kussmaul’s breathing is the
most important diagnostic
presentation. H/o diabetes, toxin
ingestion, diarrhoea, FTT, rickets, bone
pains, recurrent episode of
dehydration, vomiting etc
Investigations-
• ABG- Low HCO3, low pH,
compensatory fall in PaCO2.
• Plasma AG
• Delta Gap
• Urinary AG
Management
• Specific management of underlying
disorder
• Correct volume and electrolyte
deficits
• Alkali therapy with NaHCO3 and
Tromethamine
• Amount of IV NaHCO3 required is
calculated as –
B.W x base deficit x0.3
32. ALKALI THERAPY IN METABOLIC ACIDOSIS
Indication of bicarbonate therapy
• Serum pH <7.10 and/or plasma HCO3 <10 meq/l in conditions of
normal anion gap metabolic acidosis.
Disadvantages of bicarbonate therapy
• Hypernatremia and volume overload especially in CHF or renal
failure.
• Increased PaCO2. Therefore, patients ventilatory status should be
assessed before administration.
• Hypokalemia and hypocalcemia
• Overshoot or rebound alkalosis in organic acidosis (i.e
ketoacidosis , lactic acidosis ) due to conversion of accumulated
organic anions into bicarbonate .
34. APPROACH TO METABOLIC ACIDOSIS
NAGMA
UAG POSITIVE
N / ↓K+ ↑K+
Urine pH Urine pH
pH < 5.3 pH > 5.3 pH < 5.3
pH > 5.3
PRTA Distal RTA RTA
Type IV
Hyper K+
Distal RTA
35. CAUSES AND CLASSIFICATION OF METABOLIC ALKALOSIS
Metabolic
Alkalosis
Urine
Chloride
Diuretics
Persistant vomiting, NG
suction
Villous adenoma
Cystic fibrosis
Post hypercapnia
Chloride diarrhea
Blood
pressure
Plasma renin,
aldosterone
Bartter syndrome
Gitelman
syndrome
High renin
High
aldosterone
Low renin
High
aldosterone
Low renin
Low
aldosterone
Renovascular
stenosis
Renin secreting
tumor
Adrenal hyperplasia,
adenoma, carcinoma
GRA
Liddle syndrome
AME, Cushing
syndrome
Exogenous steroids
CAH (11β- or 17α-
Chloride Responsive
Low (<20mEq/L)
Chloride
Unresponsive
High (>20mEq/L)
High Normal
36.
37.
38. APPROACH TO METABOLIC ALKALOSIS
I. History
II. Investigations
III. Management
History-H/o vomiting, swelling of
the body, recurrent respiratory
infections , polyuria, dehydration
urine output, diarrhoea in newborn,
FTT, shock, HTN etc.
Investigations
• ABG- High HCO3, high pH,
compensatory increase in
PaCO2
• Urine Cl levels
• Serum renin and aldosterone
levels
• BP
39. CAUSES AND CLASSIFICATION OF METABOLIC ALKALOSIS
Management of metabolic alkalosis
Cl responsive
• Administration of
sufficient NaCl,KCl.
Replacement of NG
suction.
• Diuretics usage-
potassium
supplementation or
potassium sparing
diuretics is used
• Rarely acetazolamide can
be helpful in severe
metabolic alkalosis
Cl resistant
With HTN
• Volume repletion is C/I
• Adrenal adenomas- resected
• Renovascular dis- can be repaired
• Glucocorticoid remediable aldosteronism,
CAH- glucocorticoid administration
• Cushing syndrome- spironolactone
• Liddle syndrome- Triamterene, amiloride
Without HTN
• Barter and Gitelman syndrome- includes
oral potassium and sodium supplements
42. TREATMENT OF RESPIRATORY ACIDOSIS
Respiratory acidosis is best managed by treatment of underlying etiology.
All patients with acute respiratory acidosis are hypoxic and need
supplemental oxygen or mechanical ventilation ( PaCO2 >60).
• Respiratory acidosis caused by CNS disease require mechanical ventilation
as hypercarbia causes cerebral vasodilation and raised ICT. This is
dangerous for the child.
Patients with chronic respiratory acidosis, oxygen should be used
cautiously as it blunts the respiratory drive and further increases PaCO2.
• It is best to avoid mechanical ventilation in chronic respiratory acidosis as
extubation is difficult.
• When intubation is necessary , the PaCO2 should be lowered only to the
patients normal baseline.
44. EXAMPLES
1. A child with DKA has the following ABG
pH-7.1, HCO3- 8 mEq/l , PaCO2- 20 mm of Hg , Na 140 mEq/l , Cl- 106
mEq/l and urinary ketones 3+
• pH is low- so acidosis
• Low HCO3 – suggestive of metabolic acidosis and low PaCO2 – suggestive
of compensation ( same direction rule).
• Expected PaCO2 is (1.5x8)+8±2 = 20±2 which matches with the expected
PaCO2.
• AG is 140-106-8 =26
• Delta gap: 26-12/24-8 =0.8 s/o pure HAGMA
• So, this patient has HAGMA with respiratory compensation.
45. 2. A 12 yr old girl K/c/o Type 1 DM presented with fever , nausea, vomiting
and abdominal pain for 1 day. Lab inv suggests pH- 7.28, PaCO2-27, HCO3-
12, Na- 140 , Cl – 98 , BSL – 400.
• Low pH – so acidosis
• Low HCO3- s/o metabolic acidosis
• Expected PaCO2 – (1.5x12)+8±2=26±2
• AG- 140-98-12 =30 s/o HAGMA
• Delta ratio- 30-12/24-12= 1.5 s/o mixed HAGMA+ metabolic alkalosis
• This girl has HAGMA( DKA) + met alkalosis (vomiting) with respiratory
alkalosis.
EXAMPLES
46. 3. ABG of patient with CHF on furosemide is pH-7.48, HCO3- 34 , PaCO2-49.
• pH is high – so alkalosis
• High HCO3 s/o metabolic alkalosis and high PaCO2 s/o respiratory
compensation (same direction rule)
• Expected PaCO2 = 34+15=49 which matches with the given PaCO2 s/o
simple acid base disorder.
• So, this patient has metabolic alkalosis with respiratory compensation.
EXAMPLES
47. 4. A 11 yr old boy was admitted with high grade fever and hypotension after
a prolonged course of diarrhoea. Lab values showed pH-7.32 , HCO3-6,
PCO2- 20, Na- 139, Cl- 106.
• pH is low- so acidosis
• HCO3 is low – primary defect metabolic acidosis
• Expected PaCO2- (1.5x6)+8 ±2= 17±2 s/o respiratory compensation.
• AG : 139-106-6=27 . So , HAGMA.
• Delta gap 27-12/24-6= 0.8 s/o mixed HAGMA + NAGMA
• So this boy has HAGMA( lactic acidosis) + NAGMA ( diarrhoea) with
respiratory alkalosis
EXAMPLES
48. 5. A 3 yr old comatose child with h/o accidental ingestion of several tablets
of phenobarbitone is intubated and ventilation started with 30% oxygen.
ABG after 6 hr showed pH-7.28 , PaCO2- 56 mm of Hg, HCO3 -26
• Low pH- so acidosis
• High PaCO2 – primary defect is respiratory acidosis and high HCO3 s/o
metabolic compensation(Opposite direction rule)
• It is acute. Increase in CO2 = (56-40)=16
Increase in HCO3 =(24+1.6)=25.6
• So, the patient has respiratory acidosis with metabolic compensation.
EXAMPLES
49. EXAMPLES
6. K/c/o chronic lung disease develops severe vomiting . pH -7.4 , HCO3- 36 ,
PaCO2 – 60.
• pH is normal so patient has either no disorder or has mixed acid base
disorder.
• However, abnormal value of HCO3 and PaCO2 is s/o mixed disorders.
• High HCO3 suggests metabolic alkalosis ( due to vomiting). High PaCO2 is
s/o respiratory acidosis (due to CLD).
• Metabolic alkalosis is expected to increase the pH, while respiratory acidosis
is expected to decrease the pH.
• Normal pH can be explained as an end result of opposite changes caused by
both primary disorders.